INFECTIOUS DISEASE

ESSENTIALS

John F. Fisher, MD MACP FIDSA

Table of contents
Diagnosing infectious disease
Taking a complete history 5
Performing a world-class physical exam 8
Interpreting blood test results 12
Deciphering culture results 16

Respiratory infections
Overcoming the common cold 23
Handling pharyngitis 26
Diagnosing upper respiratory infections 30
Coping with bronchitis 34
Determining where to treat community-acquired pneumonia 36
Managing community-acquired pneumonia 38
Treating hospital-acquired pneumonia 42

Gastrointestinal tract and abdominal infections

Differentiating intraabdominal infections 48
Recognizing appendicitis and diverticulitis 52
Managing cholecystitis and colitis 56
Handling food poisoning 60
Coping with diarrhea 65

Urogenital infections
Resolving urinary tract infections 69
Diagnosing urethritis and pelvic inflammatory disease 75
Discerning primary and secondary syphilis 79
Treating tertiary and latent syphilis 82
Bone, joint, and skin infections
Treating osteomyelitis 87
Conquering septic arthritis 92
Recognizing common skin and soft tissue infections 94
Controlling life-threatening skin and soft tissue infections 98

Central nervous system infections

Identifying acute meningitis 105
Managing chronic meningitis 112
Eliminating encephalitis 119

Life-threatening systemic infections

Recognizing sepsis 123
Defeating infective endocarditis 129
Spotting Lyme disease 132
Characterizing primary and post-primary tuberculosis 134
Evaluating latent tuberculosis 137
Managing active tuberculosis 140
Handling multidrug-resistant bacterial infections 142

Appendix
Basic characteristics of common pathogenic bacteria 149
References and recommended reading 152
 Chapter 1

DIAGNOSING
INFECTIOUS DISEASE
Taking a complete history
The key to medical and surgical diagnosis is to have the same orderly
approach to every patient. It is well known that 70% of diagnoses can be
made by excellent history-taking. Physical exam and labs make about
30% of diagnoses.

The three-paragraph approach

The chief complaint, or presenting

complaint, is the key.

Paragraph one
Make the patient decide what is the worst of all symptoms and then
­allow a description in their own words without interrupting. If the patient
strays from describing the chief complaint, get the patient back to it. No
other symptom descriptions are allowed at this point. When the physi-
cian has a thorough understanding of this chief complaint, paragraph
one is complete.

5
Paragraph two
The patient may now describe all remaining symptoms associated with
the chief complaint, in their own words. The physician should now have
a reasonable idea of the organ system causing the trouble.

Paragraph three
The physician inquires about symptoms in the suspected organ system,
which the patient did not complain of.

At this point, the history-taking of present illness is finished. The

­remainder of the history can be considered with the offending organ
system in mind.

6
Remaining history
For infectious diseases, a travel history is very important. If it has
not come up earlier, it should be addressed at this point, along with
other relevant social factors such as occupation, smoking history, and
sexual history. A comprehensive physical exam of the offending organ
system must be carried out, along with at least a cursory exam of other
systems. If you stick to this template with every patient, you will ­compose
a thorough and complete history of the present illness. This will allow
you to be better equipped to make a quick and accurate ­diagnosis for
your patient.

Previously seen patients are evaluated in exactly the same way except
that the medical record should be at least briefly reviewed before
interviewing the patient.

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Performing a world-class
physical exam
It is impossible to examine every body system in detail in most patients
suspected of having an infectious disease. It is possible and essential to
examine the body system which is the suspected source of the infection
in great detail, with at least a cursory exam of other body systems.

For example, if the history of present illness indicated a probable lung

infection, it is important to maintain a systematic approach to the
examination of the thorax. All other organ systems may be considered at
a later time point.

The classic medical school training of inspection, palpation, percussion,

and auscultation remains a great organizational tool, and can be used to
examine many organ systems.

For example, let’s look in more detail at how to perform a thorough phys-
ical examination of the lungs in a person with a suspected r­espiratory
infection.

Inspection

You can observe much about a patient’s condition just by looking.

•• Flaring of the nostrils signifies air hunger.

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•• Intercostal retractions denote increased work of
breathing or stiff lungs from a consolidative process
like some pneumonias.

•• Stridor usually signifies upper airway obstruction

(for example, croup, epiglottitis, or the presence of
a foreign body).

•• A fast respiratory rate is indicative of hypoxia.

Palpation

Palpation involves actually feeling the thorax with your hands.

In some patients with chest pain the origin is a superficial structure

­rather than a deep organ (for example, in a patient with broken ribs);
tender­ness of the sternum at the junction of ribs could be mistaken for
pain of myocardial origin.

Having the patient breathe in, while the hands are

placed on either side of the chest posteriorly, can
show the physician whether each lung is expanding
during breathing.

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Percussion

By using good percussion technique, it is possible to recognize the

presence of a normal amount of air in the lungs, which has a resonant
sound.

A dull sound will be found in patients with a large area of consolidation

underlying the percussing fingers.

The percussion note has almost no resonance (i.e., flat) if a pleural

­effusion or pus in the pleural space is present.

A drum-like tympanitic sound will be present if there’s too much air in the
underlying lung, such as emphysema or, more urgently, a ­pneumothorax.

Auscultation

The entire thorax should be examined for crackles, which may range from
fine (indicating early pneumonia or heart failure) to coarse with a Velcro-
like sound (as present in pneumonia, pulmonary edema, pulmonary
fibrosis) and may occur early to late in inspiration.

Wheezes are musical sounds, usually in expiration, which indicate

bronchial obstruction (asthma, COPD). Overlying a consolidated lobe,
large airway breathing (referred to as bronchial breath sounds) may be
apparent where it is not normally found, indicating pus in most alveoli
under the stethoscope.

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Other consolidative sounds are egophony (a bleating, nasal quality
­imparted to the spoken voice) and whispered pectoriloquy (whispered
words intelligible to the listener when normally whispered words are not
intelligible).

In addition, the vibrations of the sound of the spoken voice are ­increased
over an area of consolidation. This is known as increased vocal fremitus.

Finally, a leathery sound may be apparent over an area of pleuritis

(­pleural friction rub).

Based on the careful physical examination of the chest, findings

suggestive of a particular pathogen or disease process may be found.
However, performing a proper and thorough physical exam will provide you
with important information necessary for making an accurate diagnosis.

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Interpreting blood test results
When presented with the blood test results from a patient, it is important
to know what to look for if you suspect an infectious disease.

Red blood cells

Erythrocytes, or red blood cells (RBCs), are normally

disk-shaped with a diameter of 6.2–8.2 µm. Acute
infections are generally limited in duration and do
not dramatically affect RBC size. However, assessing the number and
morphology of RBCs can help you recognize conditions such as anemia,
dehydration, malnutrition, and leukemia.

Chronic infections
Chronic infections like tuberculosis may cause the anemia of chronic
disease. Cytokines released as a consequence of infection drive this
process by direct bone marrow suppression, by inhibition of erythro-
poietin production, or by disruption of iron metabolism either directly or
indirectly.

Malaria
Malaria due to Plasmodium falciparum can cause massive hemolysis,
disseminated intravascular coagulation (DIC), and microangiopathic
hemolytic anemia (MAHA) because so many RBCs are affected, and
the lining of small blood vessels become roughened by clots and
inflammation. The other types of malaria generally don’t cause massive
hemolysis and cells are normocytic.

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When severe hemolysis is present there is often anisocytosis (variation in
cell size) because of the presence of reticulocytes. This occurs ­because
the bone marrow is turning out young RBCs in response to the ­hemolysis.

Macrocytic anemia
Macrocytic anemia is notoriously caused by the fish tapeworm Diphyl­
lobothrium latum, which absorbs more B12 than the human host and
leads to B12 deficiency.

Microcytic, hypochromic anemia

Microcytic, hypochromic anemia (MHA) is usually due to blood loss
and hookworm infestation could be the cause of it. This is a result of
the worms engulfing and disrupting small intestinal villi causing ­chronic
blood loss. Microscopically reviewing the blood smears of patients
with anemia is an excellent habit for the interested infectious disease
diagnos­tician because it may lead to a direct diagnosis or to suggest
­infectious causes.

White blood cells

Most acute bacterial infections cause a leukocytosis

with a predominance of neutrophils and bands (im-
mature neutrophils), and many viral illnesses present
with leukopenia or no predominance of neutrophils.

Bacterial infections Viral infections

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However, when faced with a sick, febrile patient there are some classic
bacterial infections which can be associated with leukopenia, such as
typhoid fever and brucellosis, which an astute physician would likely
consider.

Some viral illnesses, like infectious mononucleosis, will present with an

atypical lymphocytosis. These are actually mostly activated T cells (95%)
responding to Epstein-Barr virus infection of B cells. The c
­ ytoplasm
tends to be indented by surrounding RBCs. They are frequently found in
the early stages of infectious mononucleosis, but are not ­specific for the
disease.

When thrombocytopenia, petechiae, and hemorrhage are part of the

­clinical picture, some hemorrhagic fevers should be considered and a
careful travel history obtained.

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Other tests

Erythrocyte sedimentation rate

The erythrocyte sedimentation rate (ESR) is a blood test that indirectly
measures the degree of inflammation in the body.

ESR is generally elevated in the presence of acute phase reactants, like

c-reactive protein and fibrinogen, which are produced in high quantities
during inflammation.

≥ 100 mm / h > 20 mm / h normal

C-reactive protein
C-reactive protein (CRP) synthesis rate in the liver increases propor-
tionally with the intensity of the inflammatory process stimulating CRP
­production and vice versa. In one study, an extremely high CRP elevation
of more than 500 mg / L was associated with more than 80% likelihood
of the presence of a bacterial infection.

This summarizes the most common blood tests used to diagnose

infectious diseases. But other tests may be conducted by specialists as
needed.

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Deciphering culture results
The most common cultures used to test for infectious agents
•• Blood
•• Sputum
•• Urine
•• Wound
•• Cerebrospinal fluid
•• Stool

Blood samples
Skin contaminants in blood culture bottles are common,
very costly to the healthcare system, and are frequently
confusing to clinicians. However, with professional phlebo­
tomists the incidence of contamination is lessened.

Blood from at least two venipunctures is ideal to help confirm the ­results.
Common skin contaminants include coagulase-negative s
­ taphylococci,
Bacillus spp, and diphtheroids.

16
When only one of two samples yields such organisms, skin contamina-
tion is probable. However, when virulent organisms are isolated, such as
Staphylococcus aureus or beta-hemolytic streptococci, skin contamina-
tion is unlikely and results should be considered genuine. Isolation of
aerobic gram-negative bacilli should be considered valid results, since
these organisms are not natural residents of human skin.

For suspected endocarditis, at least three separate blood cultures should

be done. This is because an infected heart valve will shed bacteria into
the blood continuously, therefore, all or almost all blood cultures will be
positive.

Sputum samples
The vast majority of microbiology labs perform
Gram stains of sputum specimens to determine
the quality of the sample before processing. Even
before examining under oil immersion, ­technicians
will review the smear under low magnification
(10x) because human cells can be recognized at
this power, whereas most bacteria cannot.

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An adequate sputum sample has innumerable white blood cells
(neutrophils) and little to no other cell types, especially squamous
­epithelial cells.

Many neutrophils Few epithelial cells

The presence of high levels of squamous epithelial cells indicates

­potential contamination with saliva, and necessitates obtaining ­another
sample.

If the sputum sample is reviewed before antibiotic therapy, it will usually

contain the culprit bacteria. Such a sample is worthy of review under oil
immersion and can be used for further culture.

A sample that is contaminated by saliva will contain mixed flora

reflecting the oral microbiome. It should not be cultured and will be
rejected by most labs.

Although many patients are not able to cough up an adequate sputum

sample, the Gram stain of an adequate specimen is generally helpful
in identifying the probable cause of pneumonia, such as the gram­
positive Streptococcus pneumoniae, or the gram-negative Klebsiella
pneumoniae.

A smear which shows many neutrophils but no organisms can also be

valuable because is suggests the cause is an organism which does

18
not stain well with Gram’s method or that the cause of the pulmonary
­process is not infectious at all. Thus a negative Gram stain will lead the
prudent physician to look for another cause like tuberculosis, fungus,
Legionella or another cause of inflammation of the lung.

Urine samples
A urine culture which contains more that 100 000
colony-forming units (cfu) / mL is considered
­indicative of bacteriuria in adult patients.

Less than 100 000 cfu / mL is considered a contaminant unless the

sample comes from a female patient with symptoms of a urinary tract
­infection (UTI). In such a situation even 1000 cfu / mL is considered
significant if the ­culture yields a known uropathogen like E. coli. Note
that many o
­ lder women have asymptomatic bacteriuria which does not
require ­treatment.

Likewise, patients with indwelling urinary catheters acquire bacteriuria at

the rate of about 8% per day. Thus, at the end of two weeks most will have
significant bacteriuria. Catheterized patients should not be treated for UTI
in the absence of symptoms indicating a urinary source of infection.

Wound samples
An open wound will become colonized by multiple
organisms but may not actually be infected. Thus, a
careful evaluation of the patient and the cleaned and
debrided wound is essential. Secondary infections are
often extensions of preexisting lesions like traumatic
or surgical wounds or pressure ulcers, which serve

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as the ­primary portal of entry for microbial pathogens and are often
polymicrobial involving subcutaneous tissue.

Wound cultures should not be done unless infection is suspected.

Signs of infection
•• Increased pain
•• Warmth
•• Erythema
•• Drainage
•• Systemic symptoms

When infection is diagnosed clinically, deep tissue specimens retrieved

via biopsy or needle puncture with semi-quantitative bacterial counts
are preferred to guide antibiotic therapy.

Cerebrospinal fluid samples

During a lumbar puncture, a minimum of
0.5–1 mL of cerebrospinal fluid (CSF) should
be sent immediately after collection to the
microbiology laboratory in a sterile container for
bacterial testing. Larger volumes (5–10 mL) increase the sensitivity of
culture and are required for optimal recovery of mycobacteria and fungi.

> 0.5–1 mL 5–10 mL

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A Gram stain should be done when bacterial meningitis is suspected.
The sensitivity of the Gram stain for the diagnosis of bacterial meningitis
is 60%–80% in patients who have not received antimicrobial therapy
and 40%–60% in patients who have received treatment. For the most
common cause of fungal meningitis, Cryptococcus neoformans, the
sensitivity of CSF culture is > 70%.

Stool samples
The specimen of choice to diagnose diarrheal illness
is the diarrheal stool, not a formed stool or a swab.

Most laboratories will have the ability to culture for

Salmonella, Shigella, and Campylobacter and test for
Shiga toxin-producing E. coli.

In studies of adult patients who submitted more than

one specimen, the enteric pathogen was detected in
the first sample 87%–94% of the time, with the second
specimen bringing the positive rate up to 98%. In
pediatric patients, the first specimen investigated in
the laboratory detects 98% of the enteric pathogens.

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Lesson name Chapter 2

RESPIRATORY
INFECTIONS

22
Overcoming the common cold
Causes
Most upper respiratory infections are caused by viruses.

The most frequent type of infection is the common cold.

Many of these infections are acquired through ­contact
with children from the ages of six months to five years,
who average more than seven colds per year. In ­children,
colds cause eustachian tube dysfunction and ­often are
accompanied by middle ear infections.

Pathogenesis
The symptoms of sinus congestion and runny nose are not due to the
­virus itself but are instead a result of our own immune cytokine response,
with kinins causing much of the congestion.

Virus particles present on the hands of an infected person enter the

­nasal epithelial cells and replicate. Some are able to disrupt and shed
the nasal cells and cilia in the process but with control of the infection,
the ­mucosa normalizes in two weeks or less. This also means that
symptoms can linger for more than a week making some patients seek
anti­biotics unnecessarily.

23
 The common cold is complicated by bacterial
sinusitis in < 10% of people, so antibiotic treatment
is generally unnecessary.

Clinical management
Management of the common cold essentially involves managing
symptoms.

For malaise, myalgias, and arthralgias, acetaminophen or a nonsteroidal

antiinflammatory drug (NSAID) is usually sufficient.

Blowing the nose should be done gently, since forceful blowing can drive
secretions up into the sinuses possibly predisposing to acute ­bacterial
sinusitis.

Patients should be advised to limit the use of nasal sprays, as rebound

vasodilation can occur after just 2–3 days of use, exacerbating the
symptoms.

Aspirin should not be given to children because of concern for Reye

­syndrome, which is characterized by increased intracranial pressure and
acute fatty liver.

Dozens of studies using vitamin C and / or echinacea products have

shown no reduction in severity or duration of disease. In a meta-analysis
of 16 studies, zinc products were shown to reduce the duration of symp-
toms by approximately one day.

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Prevention
Cold victims should refrain from shaking hands with others until symp-
toms have subsided.

The best prevention is thorough hand washing

after potential contact with patients with cold
symptoms.

Soft tissues for gentle nose blowing are far

better than a dirty handkerchief.

When present, coughing should be done properly, by coughing into the

arm / sleeve, rather than into the hands, to decrease spread to others.

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Handling pharyngitis
Pharyngitis is the inflammation of the pharynx, most commonly referred
to as a sore throat. It can be either viral or bacterial in origin. About 70%
of pharyngitis is caused by viruses.

70%

Viral pharyngitis

Pathogenesis
The symptoms and signs of viral pharyngitis are not distinctive unless
there is accompanying conjunctivitis, which is most commonly caused
by adenoviruses.

Common symptoms
•• Oral ulcers
•• Nasal congestion
•• Cough

Herpangina (mouth blisters) is characterized by ulcers and vesicles in

the posterior pharynx and is usually due to a coxsackie virus. The most
common cause of hand-foot-mouth disease is coxsackie A 16. It causes
painful lesions in the mouth and on the hands and feet.

26
Clinical management

Over-the-counter pain relievers, such as acet-

aminophen or a nonsteroidal a
­ntiinflammatory
agent, like ibuprofen or naproxen have been
shown to provide fast and effective relief of sore
throat pain.

Salt-water gargles are an old standby for throat

pain. It is not clear that salt water works to relieve
pain but it is unlikely to be harmful.

Sprays containing topical anesthetics, such as

benzocaine or phenol are available to treat sore
throat. However, such sprays are no more effective
than sucking on hard candy.

A variety of lozenges or cough drops containing

topical anesthetics are available to treat throat
pain or relieve dryness. Lozenges may persist
­longer in the throat than sprays or gargles and
thus may be more effective for symptom relief.

Other treatments that may help with throat pain

include sipping cold or warm beverages, or e
­ ating
cold or frozen desserts, such as ice cream or
­popsicles.

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Bacterial pharyngitis

Bacterial pharyngitis is less common than viral pharyngitis.

Pathogenesis
Except for relatively rare infections like diphtheria or peritonsillar
­abscess, bacterial pharyngitis most commonly results from a group A
streptococcal infection. About 30% of pharyngitis in children and 15% in
adults is due to this organism.

Group A Streptococcus 30% 15%

Common symptoms of group A streptococcal pharyngitis

•• ­Fever
•• Severe sore throat with tonsillar exudates
•• Tender anterior cervical lymphadenopathy
•• Absence of a cough

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Clinical management
Rapid streptococcal antigen testing has a sensitivity of 70–90% and a
specificity of 95%.

This infection is ordinarily treated with ten days of penicillin V or

amoxicillin.

For patients with a beta-lactam allergy, ten days of cephalexin or a

five-day course of azithromycin may be used.

10 days 10 days 5 days

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Diagnosing upper respiratory infections

Acute bacterial sinusitis

Acute bacterial sinusitis is an unusual complication of viral sinusitis

from the common cold. It is more likely to occur in patients with
anatomic abnormalities of the nose and sinuses, for example, a deviated
­nasal septum or obstruction of ostea.

Causes
The principal cause is Streptococcus pneumoniae and less commonly
Haemophilus influenzae, or Moraxella catarrhalis.

Pathogenesis

Patients often present with

•• Fever
•• Focal sinus pain
•• Toothache in maxillary sinusitis (possible)
•• Purulent nasal secretions
•• Opacification of one or more sinuses on CT scan

Clinical management­
In addition to promoting drainage with decongestants for 48 hours,
amoxicillin-clavulanate is a good choice because of the possible ­presence
of beta-lactamase-producing pathogens like Moraxella ­catarrhalis.

30
For patients with a penicillin allergy, an oral third-generation cephalo-
sporin like cefpodoxime is an acceptable choice.

If the patient has a history of anaphylaxis to penicillin, a respiratory

quinolone like levofloxacin will cover most of the common pathogens.

Acute otitis media

Middle ear infections are the most common cause of office visits in
children six months to two years of age. They are a frequent complication
of viral upper respiratory infections. It is an uncommon infection in adults
and when present suggests anatomical obstruction of the eustachian
tube, like allergy or a nasopharyngeal tumor.

Pathogenesis

Common symptoms in children

•• Fever
•• Fussiness
•• Ear pain (indicated by tugging at one or both ears)
•• Cough

On exam, the tympanic membrane is bulging, immobile, and has a

diminished light reflex.

The most common pathogen is again the gram-positive Streptococcus

pneumoniae, followed by gram-negatives Haemophilus influenzae and
Moraxella catarrhalis.

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Clinical management
If patients have not received antibiotics recently, amoxicillin is preferred.
If given recent antibiotics, resistant organisms should be suspected and
amoxicillin-clavulanate is a better choice.

For patients with a penicillin allergy, cefpodoxime is recommended.

Fluoroquinolones are relatively contraindicated in children because of

the effect on growing cartilage and tendons.

Acute epiglottitis

Acute epiglottitis is a life-threatening infection, which can be compli­

cated by sudden asphyxiation. It is most common in children between
two and six years of age.

Pathogenesis
In the past, the most common cause was Haemophilus influenzae
type  b (Hib) but in developed countries most children receive Hib
vaccine making this pathogen rare. However, it is still a problem in the
developing world.

Other causes are group A Streptococcus (GAS), Staphylococcus ­aureus

including methicillin-resistant Staphylococcus aureus (MRSA), and
Streptococcus pneumoniae.

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Common symptoms
•• ­Acutely ill
•• Fever
•• Sitting forward in classic tripod position (to keep airway open)
•• Hoarseness
•• Inspiratory stridor

Clinical management
The oropharynx should be examined with
extreme caution by having the patient open the
mouth and trying to observe a swollen ­epiglottis
without the use of a tongue depressor, which
may cause sudden occlusion of the airway by
the inflamed epiglottis.

When the diagnosis is suspected, emergency consultation with an ear,

nose, and throat specialist should be obtained.

The airway may then be visualized by nasopharyngoscopy and the

­trachea intubated if necessary.

Blood cultures are often positive for the pathogen. Empirical therapy
should be given with ceftriaxone plus vancomycin, adjusting after the
­results of cultures are available.

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Coping with bronchitis
Bronchitis is the inflammation of the bronchi.
It can be either acute or chronic.

90%
Acute bronchitis

Acute bronchitis is frequently treated by physicians with antibiotics

­despite the fact that 90% of cases are viral in etiology.

Most cases of acute bronchitis occur in wintertime.

Common symptoms
•• Cough
•• Low-grade fever
•• Physical findings limited to rhonchi or wheezes

Clinical management
Chest x-ray is usually not helpful in diagnosing acute
bronchitis.

Albuterol has been shown to be helpful in decreasing

the severity and duration of the cough.

If symptoms are unusually severe at the outset, or

bronchitis fails to resolve gradually, a bacterial infec-
tion might be considered. The presence of a cough
that is repetitive and exhausting, followed by an

34
audible inhalation sound, like a whoop, or cough followed by vomiting
(in a child) should make a doctor consider pertussis.

Acute exacerbation of chronic bronchitis

Pathogenesis
The most common cause of acute exacerbation of chronic bronchitis
(AECB) is a viral infection. This is characterized by a period of unstable
lung function with worsening airflow and productive cough.

Continued smoking and air pollution most likely contribute to severe

acute exacerbations. Chlamydophila pneumoniae is responsible for
about 5% of mild or moderate AECB.

Clinical management
For mild exacerbations, a case could be made for increasing use of
broncho­dilators without antibiotics or with amoxicillin or doxycycline.

For severe exacerbations, most authorities recommend a five-day course

of prednisone plus amoxicillin-clavulanate. Azithromycin or levofloxacin
could serve as alternatives, for patients with a beta-lactam allergy.

35
Determining where to treat community-
acquired pneumonia

Tests to consider for optimal evaluation of patients with

community-acquired pneumonia
•• Pulse oximetry
•• Complete blood count with differential white blood cell count
•• Chest x-ray
•• Metabolic panel
•• Sputum Gram stain and culture
•• Blood cultures (for ICU patients)
•• Urine antigen tests (for ICU patients)

For very severe pneumonia, Klebsiella should be considered among the

causes.

Where should I treat my patient with

community-acquired pneumonia?

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CURB-65

Most emergency departments employ the CURB-65 criteria. In this

­scoring system, a point is given for the presence of each of the following
­criteria.

•• Confusion or altered mental status

•• Blood urea nitrogen greater than 20 mg / dL
•• Respiratory rate of over 30 breaths per minute
•• Blood pressure < 90 mmHg systolic or
diastolic blood pressure < 60 mmHg
•• Age 65 years or older

0–1 points: consider management as an outpatient after an observation

period.
1–3 points: can be managed on the medical ward.
> 3 points: should be initially treated in the intensive care unit (ICU).

≤ 1 point 1–3 points ≥ 3 points

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Managing community-acquired
pneumonia

Outpatients

Pathogenesis

Major pathogens to consider

•• Streptococcus pneumoniae
•• Haemophilus influenzae
•• Mycoplasma pneumoniae
•• Chlamydophila pneumoniae
•• Legionella pneumophila

Clinical management
Azithromycin has good efficacy against these organisms. Alternatively,
a respiratory fluoroquinolone, such as levofloxacin should be sufficient.

38
Inpatients

Pathogenesis
Many patients admitted to the medical wards will be able to produce an
adequate sputum specimen for culture and Gram stain. The smear, if
classic for Streptococcus pneumoniae or Staphylococcus aureus, will
dictate more specific antibiotic therapy until culture results are available.

Clinical management
­IV antibiotics are generally necessary for inpatients with
community-acquired pneumonia.

Typically, vancomycin or ceftaroline is used to treat Staphylococcus

­aureus or ceftriaxone for ­
Streptococcus pneumoniae. However, in the
­absence of a good sputum sample, it is necessary to treat ­empirically for
several possible pathogens. Therefore, a cephalosporin like ­ceftaroline,
which covers gram-negative and gram-positive pathogens including
methicillin-resistant Staphylococcus aureus (MRSA), can be given.

In addition, azithromycin should be added to cover atypical patho-

gens like Chlamydophila pneumoniae, Legionella pneumophila, and
­Mycoplasma pneumoniae. Alternatively, a respiratory quinolone should
be sufficient to treat these atypical causes.

39
A patient who has experienced influenza prior to becoming sick again
would be a classic story for a complicating staphylococcal pneumonia
since influenza infection damages the lining of the bronchi and predis-
poses the lung to infection by a virulent organism like S. aureus, which
may colonize the upper respiratory tract. Other virulent organisms may
also be involved in patients with preceding influenza.

Intensive care unit

Patients with severe, lobar pneumonia may be so hypoxic that ­mechanical

ventilation is required. Organisms to consider in such a ­scenario include
Klebsiella pneumoniae. These patients often have bloody sputum, the
Gram stain of which classically shows thick, gram-negative b
­ acilli. Pa-
tients can be treated safely with ceftriaxone for suspected ­Klebsiella
pneumonia.

If the patient is producing no sputum, many pulmonologists would

perform a bronchoalveolar lavage to obtain immediate microbiologic
­samples before treating empirically. Such a strategy would be ­superior to
treating empirically and observing the patient for 24–48 hours ­because if
the patient worsens, bronchoalveolar lavage may then be too ­dangerous
and the results of cultures and smears altered by the e
­ mpirical therapy.

40
Agents which would cover possibly resistant gram-negative bacilli
like Pseudomonas, such as piperacillin-tazobactam, cefepime, or
meropenem, along with a respiratory quinolone like levofloxacin to cover
Legionella could be chosen empirically while awaiting the results of
lavage specimen testing.

Health-care-associated pneumonia
When treating patients with pneumonia who arrive in the clinic or
emergency department, it is important to watch out for patients who
frequent hospitals regularly, either as inpatients or outpatients. When
­pneumonia develops in these persons, we call it health-care-associated
pneumonia (HCAP).

Because of their frequent exposure to the hospital, they may be exposed

to the hospital's bugs. Many of these organisms are multidrug-resistant
(MDR).

With respect to treatment, they are a unique group of patients if they are
diagnosed with pneumonia when they arrive at the hospital. However, the
workup of these patients, including CURB-65 evaluation, would ­generally
be the same as for those with community-acquired ­pneumonia.

41
Treating hospital-acquired pneumonia
As the name suggests, hospital-acquired pneumonia occurs when a
patient develops pneumonia while hospitalized with another illness.

Far and away, the most common type of hospital-acquired pneumonia is

ventilator-associated pneumonia (VAP), which can be defined as pneumo-
nia developing 48 hours or more after mechanical ventilation has begun.

The incidence of getting pneumonia by coming into the hospital is less

than 10% unless the patient requires a ventilator for more than a day, in
which case the incidence rises to greater than 25%.

< 10% > 25%

The overall mortality from VAP is greater than 30%. In most intensive
care units, 10–35% of the patients already have VAP and this increases
with time. More than 50% of patients who have been on a ventilator for
ten days have VAP.

42
Risk factors that increase mortality from VAP
•• Male gender
•• Organ dysfunction
•• Central nervous system (CNS) disorders
•• Emergency surgery

Risk factors for developing VAP

•• Blood transfusion
•• Nasogastric (NG) tube
•• Tracheostomy
•• Required to remain in supine position (e.g., because of low
blood pressure)

Pathogenesis
80% of VAP is caused by the organisms
summarized by the acronym, ESKAPE.

70% are gram-negative bacilli, with Pseu­

domonas being the most common pathogen. Staphylococcus aureus is
the most common organism among the gram-positive causes.

Many of these organisms are more prone to becoming multidrug-­

resistant, which is important to keep in mind, since patients with
­prolonged stays in intensive care units (ICUs), like trauma patients who
might develop VAP more than once, are at an increased risk of develop-
ing infections caused by multidrug-resistant organisms. This severely
limits the choice of antibiotics that can be used to treat these infections.

43
Unusual causes of VAP
•• Legionella
•• Aspergillus
•• Respiratory syncytial virus (RSV) or other viruses

Organisms like these should be suspected when empirical therapy is not

working or when Gram stain and routine cultures haven’t revealed the
cause, and the patient is deteriorating.

For these bugs, special cultures and stains or even wet mounts of
secretions may allow the physician to stumble onto the diagnosis.
­
VAP has such a high mortality that it is important to obtain appropriate
pulmo­nary secretions for culture.

Clinical management
­Most pathogens will be identified by either endotracheal suction,
broncho­
alveolar lavage or, if necessary, video-assisted thorascopic
­surgery to obtain lung tissue for culture.

Since diagnosis is at times difficult, a physician should adopt the

Sherlock Holmes attitude by performing a world-class exam of the lungs,
both anteriorly and posteriorly, reviewing all imaging, and reviewing the
Gram stain of the secretions in the microbiology lab.

If the Gram stain is negative, an acid-fast smear for tuberculosis should

be ordered and reviewed, followed by a Wright’s or Giemsa stain of
­secretions. If still no cause is apparent but evidence for pneumonia is
solid, a wet mount of pulmonary secretions may reveal a fungal cause
long before fungal culture results are available.

44
Since the most common cause of VAP is a gram-negative rod, and Pseu­
domonas is most likely, it is reasonable to begin an empiric antipseudo-
monal beta-lactam plus or minus an aminoglycoside. The beta-lactams
will cover upwards of 90% of Pseudomonas, and the aminoglycosides
should cover as many as possible of the other resistant 10%.

Pseudomonas 90% 10%

Although the aminoglycoside is nephrotoxic, short-term therapy until cul-

ture results are available will likely not affect renal function substantially.

For patients with a beta-lactam allergy, aztreonam or ciprofloxacin

(possibly with an aminoglycoside) is a good option.

When S. aureus is suspected by Gram-stained smears, empirical therapy

should cover MRSA (e.g., vancomycin or linezolid) at least until ­culture
results are available.

45
If the isolate is not MRSA, very narrow-spectrum drugs, such as nafcillin
or oxacillin are preferred. Alternatively, cefazolin or clindamycin may be
used in patients with a penicillin allergy.

At least one study has shown no significant difference in outcome

­between eight or 14 days of antibiotic treatment. Therefore, it is best to
discontinue effective antimicrobial therapy after eight days of treatment
to decrease the likelihood of inducing antibiotic resistance.

46
 Chapter 3

GASTROINTESTINAL
TRACT AND ABDOMINAL
INFECTIONS
Differentiating intraabdominal
infections

Peritonitis

The normal peritoneal cavity contains less than 100 mL of sterile fluid
and contains less than 250 cells / µL, all macrophages and lymphocytes.

Pathogenesis
Spontaneous bacterial peritonitis (SBP) almost always arises without
explanation in patients with ascites due to hepatic dysfunction or
nephrotic syndrome. Bacteria may enter the ascitic fluid from bacteremia
or by translocation across the bowel wall.

Causes of spontaneous bacterial peritonitis

•• Escherichia coli (50%)
•• Streptococcus pneumoniae and other streptococci (15–20%)
•• Klebsiella (10%)
•• Anaerobic bacteria like Clostridium (5%)

Common symptoms
•• Patients may be asymptomatic or have only mild diffuse
­abdominal pain
•• Abdominal tenderness (50% of patients)
•• Fever (80% of patients)

A high index of suspicion for peritonitis is important in a patient with

fever or deterioration in liver or kidney function.

48
The diagnosis of SBP is confirmed by examining the peritoneal fluid for
the presence of more than 250 neutrophils / µL.

> 250 cells / µL

Clinical management
Gram staining is frequently negative, but when positive, the morphology
of the organism can determine appropriate empirical antibiotics.

When Gram staining is negative, antibiotics should be chosen which

cover a mixed microbial flora including anaerobes. This might include
piperacillin-tazobactam or a carbapenem like ertapenem.

49
Intraabdominal abscess

Intraabdominal abscesses are ordinarily complications of other

­processes.

Biliary tract disease is the most common predisposing

factor of liver abscesses.

Bacteremia, especially from infective endocarditis is

the most likely source of a splenic abscess.

Previous acute pancreatitis from alcoholism,

gallstones or trauma can be complicated by
­pancreatic abscess.

Often, the actual cause of the abscess remains unknown.

Common symptoms
•• Fever
•• Chills
•• Right or left upper quadrant pain
•• Pain radiating to the shoulders (usually liver or spleen abscesses)
•• Worsening epigastric pain radiating to the back (pancreatic abscess)
•• Septic-like picture (pancreatic abscess)

Clinical management
The most sensitive imaging for intraabdominal abscess is abdominal
computed tomographic (CT) scan, but ultrasound may be used for the
initial study.

50
Blood cultures should be routinely done and in the case of splenic
­abscess, an echocardiogram might be necessary to rule out e
­ ndocarditis
as the source of the abscess.

CT-guided drainage is required for most abscesses. The fluid should be

processed with Gram stain and aerobic and anaerobic cultures.

Since mixed infections are characteristic of all three types of abscess,

antibiotics like piperacillin-tazobactam or in the case of a life-threaten-
ing pancreatic abscess a carbapenem like meropenem, should cover the
involved aerobic and / or anaerobic organisms.

51
Recognizing appendicitis
and diverticulitis

Acute appendicitis

Acute appendicitis usually begins with vague,

often colicky epigastric or periumbilical pain,
which localizes to the right lower quadrant over
the next 12 hours.

Pathogenesis

Common symptoms
•• Moderate fever
•• Right lower quadrant tenderness
•• Guarding
•• Rebound tenderness
•• Positive obturator sign
•• Moderately elevated white blood cell count

The technique for detecting the obturator sign, called the obturator test,
is carried out on each leg in succession. The patient lies on their back
with the hip and knee both flexed at ninety degrees. The examiner holds
the patient’s ankle with one hand and knee with the other hand. The
examiner internally rotates the hip by moving the patient’s ankle away
from the patient’s body while allowing the knee to move only inward.

When acute appendicitis is suspected, the inflamed and enlarged

appendix may come into physical contact with the obturator internus
52
muscle, which will be stretched when this maneuver is performed on
the right leg. This causes pain and is evidence in support of an ­inflamed
appendix.

Obturator sign

Clinical management
Rectal exam should be done in virtually all patients who present with
abdominal pain, and in the case of appendicitis, tenderness in the high
right rectal region is suggestive of the diagnosis.

The diagnosis can be confirmed with a CT scan

and in uncomplicated cases ­laparoscopic ap-
pendectomy is curative.

Antibiotics play a lesser role, however, and

are only given once the diagnosis is apparent.
Ertapenem, with its long half-life in a single
daily dose, has been shown to be effective.

53
Diverticulitis

Diverticulitis is inflammation of a diverticulum.

Diverticula are small pouches that can develop in
the wall of the intestine.

Pathogenesis

Common symptoms
•• Mild to moderate left lower quadrant abdominal pain (lasting days)
•• Diarrhea
•• Nausea
•• Vomiting
•• Fever
•• Slight increase in white blood cell count
•• Left lower quadrant abdominal tenderness
•• Phlegmon (an inflammatory mass)

Clinical management
For most patients surgical resection of the
­involved sigmoid colon is ultimately required.

However, in order to reduce inflammation and

infection, treating with antibiotics that cover
the mixed flora of the colon prior to surgery is
highly recommended.

54
For mildly ill patients, amoxicillin-clavulanate or a fluoroquinolone plus
metronidazole should be effective.

For sick patients, hospitalization and IV antibiotics, such as piperacillin-

tazobactam or ertapenem are required.

55
Managing cholecystitis and colitis

Cholecystitis

Cholecystitis refers to the inflammation of the gall bladder.

Pathogenesis
Gallstones are present in more than 90% of
patients who develop acute cholecystitis.
The stones slow down the normal flow of
bile in a similar way that sluggish urine
flow predisposes to urinary tract infection.
Bacteria from the gut colonize the partially
obstructed biliary tract and eventually cause
acute cholecystitis.

Common symptoms
•• Abrupt onset of steady right upper quadrant (RUQ) abdominal pain
-- often after a large, fatty meal
•• Pain may radiate to the right shoulder region
•• Nausea and vomiting (70% of cases)
•• Abdominal tenderness
-- often in the RUQ upon inspiration (Murphy’s sign)

Common laboratory findings

•• Elevated white blood cell counts
•• Bilirubin
•• ALT (alanine aminotransferase)
•• Alkaline phosphatase
56
Clinical management
The imaging of choice is ultrasound and when the probe is placed
in the RUQ and the patient inspires, the associated pain / tenderness
constitutes a positive sonographic Murphy’s sign.

For mild to moderate disease, ceftriaxone is recommended. For severe

disease, a carbapenem like meropenem is preferred.

Mild / moderate Severe

For patients with a beta-lactam allergy in severe disease, the combi-

nation of a fluoroquinolone plus metronidazole should cover the mixed
aerobes and anaerobes expected.

After the acute inflammation subsides, an elective

laparoscopic cholecystectomy is recommended in
most patients.

Antibiotic-associated colitis

The vast majority of cases of antibiotic colitis are caused by Clostridium

difficile, an anaerobic gram-positive bacillus, which is resistant to many
antibiotics.

57
Pathogenesis
C. difficile is also a member of the normal colonic flora in many
individuals. Thus, when patients receive antibiotics, the bacteria may
survive or transition to spores, which may later germinate and produce
toxins that injure the bowel and cause diarrhea.

When the injury is severe, the mucosa may be studded with pseudo-
membranes made up of sloughed epithelial cells and inflammatory cells.
The diarrhea may be mild or severe and is rarely bloody, although stools
may test positive for occult blood.

Characteristics of severe disease

•• Fever
•• Abdominal tenderness or distention
•• Hyperactive or hypoactive bowel sounds
•• Hypertension
•• Septic shock

In critically ill patients, the only clue to the colitis may be otherwise
unexplained leukocytosis. Stools are usually positive for leukocytes and
C. difficile toxin. Alternatively, pseudomembranes can be recognized by
colonoscopy if the diagnosis cannot be confirmed by toxin assay.

Clinical management
The initial treatment of choice in a patient who is toxin-positive
and mildly to moderately ill would be oral vancomycin for ten days.
Alternatively, oral fidaxomicin, a macrocyclic lactone antibiotic with
­activity ­versus C. difficile, could also be given for ten days. Fidaxomicin
has a lower rate of recurrence than vancomycin. If neither of these drugs

58
is available, ­metronidazole, which was once considered first-line therapy,
can be used.

For recurrent disease, fecal transplants from uninfected persons

are more effective than vancomycin. If unrecognized and untreated,
C. ­difficile colitis may lead to the development of toxic megacolon, which
sometimes requiring lifesaving colectomy for hope of cure.

59
Handling food poisoning

There are many potential causes of food poisoning or food-borne

illnesses and many different presentations. Most food poisoning is not
caused by the presence of the bacterium itself, but by the presence of
a toxin produced by bacteria which can linger in food. There are two
­basic categories of toxins that cause food poisoning: heat-stable toxins,
which remain active at high temperatures, and heat-labile toxins, which
are inactivated by high temperatures such as through cooking food.

Heat-stable toxins

Staphylococcus aureus
Staphylococcus aureus food poisoning is com-
monly seen at picnics.

Common sources of preformed toxin

•• Sandwich spreads
•• Packaged meats
•• Cream-filled pastries
•• Foods left unrefrigerated for extended periods

The syndrome produced has the fastest onset of any food poisoning.

Common symptoms
•• Abrupt onset of nausea and vomiting (4–8 hours)
•• Usually resolves in 24–48 hours

Management is primarily supportive.

60
Hemolytic uremic syndrome
Enterohemorrhagic Escherichia coli (EHEC) is an organism ­possessing
a toxin originally found in Shigella dysenteriae known as Shiga toxin
2. Shiga toxin 2 causes widespread endothelial damage, which in turn
disrupts and distorts RBCs and results in a microangiopathic hemolytic
anemia.

The endothelial damage includes the renal vasculature and can cause
acute kidney injury. Thus, the process is known as the hemolytic uremic
syndrome (HUS).

The food source most commonly ­associated

with HUS is undercooked hamburger meat.
­Patients are usually infants and toddlers.

Common symptoms
•• Abdominal cramps
•• Nausea and vomiting
•• Non-bloody diarrhea (becomes bloody within 3 days)
•• High fever not typical
•• Elevated blood urea nitrogen and creatinine levels

Ironically, treatment with antibiotics may result in increased toxin levels,

especially with bactericidal antibiotics, which may result in the release of
preformed toxin and worsen the process. Thus, antibiotics are reserved
only for patients with documented bacteremia.

61
Heat-sensitive toxins

Alpha toxin
Clostridium perfringens is a gram-positive
anaerobic organism, which is the second
most common cause of food-borne illness
in the United States and the United Kingdom.
It produces a heat-labile, preformed alpha toxin and can be found in
­undercooked beef. The toxin damages the small intestinal membrane
producing pores in the mucosa.

Common symptoms
•• Abdominal cramps
•• Mild or severe watery diarrhea

The disease is self-limited and only supportive care is required.

Botulinum toxin
Clostridium botulinum produces a ­toxin which
blocks acetylcholine release from the synapses
of neurons at the ­
neuromuscular junction,
resulting in life-threatening flaccid paralysis
when it involves muscles of respiration.

When spores of the organism contaminate canned foods in an ­acidic

environment, the spores germinate and become toxin-producing
gram-positive bacilli.

62
Common symptoms
•• Diplopia (within hours)
•• Difficulty breathing (becomes more obvious later)

Treatment involves antitoxin administration and respiratory support with

mechanical ventilation if necessary.

Before 1950, the fatality rate associated with food-borne botulism was
60–70%, while currently it is 5–10% in developed countries.

Heat-stable and heat-labile toxins

Some bacteria produce both heat-stable and heat-labile toxins, which

contribute to food poisoning.

Bacillus cereus
Like staphylococcal food poisoning, Bacillus cereus makes a heat-stable
toxin in foods (notoriously fried rice), which when reheated and ingested,
causes the abrupt onset of vomiting. The organism also makes a
heat-labile toxin, which causes watery diarrhea lasting one to two days.

Treatment of food poisoning due to B. cereus consists of supportive

care; antibiotics are not indicated.

Enterotoxigenic Escherichia coli

The most common cause of traveler’s diarrhea is Enterotoxigenic
Escherichia coli (ETEC).

63
The infection is transmitted via ­contaminated drinking water sometimes
obvious and at ­other times in unsuspected sources like ­salads and even
salsa in restaurants.

Unlike the E. coli of normal fecal flora, ETEC

produces both a heat-­stable and a heat-labile
toxin. The heat-stable toxin causes cells to
secrete chloride into the intestinal lumen—
water and sodium would follow. The heat-
labile toxin also causes electrolytes and water
to be secreted into the lumen through a similar
mechanism.

Common symptoms (abrupt onset)

•• Cramps
•• Watery diarrhea
•• Sometimes fecal incontinence

Travelers diarrhea can be treated with a single dose of ciprofloxacin or

azithromycin.

64
Coping with diarrhea
Infectious diarrhea can originate in either the large or small bowel, with
distinguishing characteristics typical of each type.

Invasive large bowel diarrhea

Common routes of transmission

•• Food handlers
•• Unpasteurized dairy products
•• Undercooked eggs (potentially carrying Salmonella)
•• Seafood (potentially harboring Vibrio spp)
•• Exposure to wild and domestic animals
•• Consumption of contaminated water (most common)

Invasive diarrhea most often causes colitis. Thus, patients have the
abrupt onset of variable fever, hypogastric cramps, and small-volume
­diarrhea with tenesmus, which describes the severe urgency to defecate
with or without anal discomfort.

Stool exam shows the presence of white and red blood cells indicating
an invasive process. Stool and blood cultures are recommended for sick
patients.

Many infections are self-limited with symptoms resolving within a week.

If symptoms are mild, no antibiotics need to be given unless there is
­danger of exposing others to organisms like Salmonella and Shigella.
However, when in doubt, it’s generally best to treat. It is noteworthy that

65
for severe disease ciprofloxacin is the primary or alternative treatment,
although doxycycline is recommended for Yersinia enterocolitica
infections.

Antidiarrheal agents should not be used

Antidiarrheal
because slowing peristalsis may result in a agents
buildup of the enteric pathogen, leading to
complications like toxic megacolon.

Small bowel diarrhea

Viruses cause 30–40% of infectious ­diarrhea.

Two viruses in particular are notorious—
Rotavirus and Norovirus.

Rotavirus
Rotavirus is the leading worldwide cause of dehydrating, diarrheal illness
in very young children, and causes 400 000 deaths per year. By age five,
virtually all children have been infected.

The onset of disease begins with two to three days of fever and vomiting
followed by watery diarrhea producing up to 20 stools / day.

The disease is ordinarily self-limiting and does not require antibiotic

treatment.

Norovirus
Norovirus is the leading cause of foodborne diarrhea in the United States
and is responsible for 20% of all cases of diarrhea in adults and children.

66
It is often transmitted via food handlers in mass settings like cruise
ships but is also common in daycare centers and classrooms.

Since dehydration can be life-threatening in severe viral diarrhea, it

can be avoided with oral rehydration solutions containing sucrose and
­sodium chloride, or with IV normal saline in sicker patients.

How can we distinguish small

from large bowel diarrhea?

Small bowel diarrhea

•• Usually caused by viruses
•• Watery diarrhea
•• Large-volume diarrhea
•• Sometimes results in fecal incontinence

Large bowel diarrhea

•• Usually caused by non-viral pathogens
•• Colitis
•• Small-volume diarrhea
•• Fecal urgency
•• Tenesmus

67
 Chapter 4

UROGENITAL
INFECTIONS
Resolving urinary tract infections

Acute cystitis

Acute cystitis, or bladder infection, is ordinarily

an infection of women and of girls over two years
of age. Cystitis can occur in newborn boys but is
extremely rare in older boys or men.

Pathogenesis

Common symptoms (acute onset)

•• Dysuria
•• Frequent urination

Urinalysis typically shows

•• Red blood cells
•• White blood cells
•• Positive leukocyte esterase
•• Nitrites

Clinical management
E. coli is the most common cause of bacterial cystitis and ­antibiotic
resist­
ance is increasing owing to the frequent use of trimethoprim-­
sulfamethoxazole and ampicillin over many decades.

Three days of therapy has been shown to be as good as two weeks of

treatment when treating acute cystitis.

69
Single-dose therapy may be considered in women and a ­fluoroquinolone,
such as ciprofloxacin is often the best choice.

In prepubescent girls, however, a third-generation cephalosporin

like cefpodoxime (or cefixime) should be given empirically pending
the results of cultures, and urinary tract ultrasound is recommended
to rule out anatomical abnormalities. Seven to 14 days of therapy is
­recommended.

A negative urine culture in a patient with dysuria should raise the

possibility of chlamydial urethritis, which can be diagnosed with
­nucleic acid amplification tests. This would be treated with seven
days of doxycycline.

70
Acute pyelonephritis

Acute pyelonephritis refers to infection of the kidney.

Pathogenesis

Common symptoms
•• Fever
•• Chills
•• Pyuria
•• Flank pain
•• Costovertebral angle tenderness over the affected kidney

Urinalysis typically shows

•• Numerous white blood cells
•• Gram stain showing neutrophils and gram-negative rods
•• At least 100 000 colonies of E. coli (or other gram-negative bacillus)

Clinical management
If there is a low risk of multidrug-resistant gram-negative bacilli in the
region, seven to 14 days of a fluoroquinolone will likely be effective.

Fluoroquinolone

71
For concern of multidrug-resistant gram-negative bacteria, seven to
14 days of a carbapenem like meropenem is recommended pending
­culture ­results.

Imaging should be used sparingly in young women and is not generally

necessary for a straightforward case. However, if stones or ureteral
obstruction are suspected or for recurrent pyelonephritis, imaging
should be done beginning with ultrasound followed by CT scan.

Acute prostatitis

Acute bacterial prostatitis is typically a disease of men over 35 years of

age and is usually caused by E. coli or more rarely, Enterococcus spp.
When it occurs in men under 35 years of age, Neisseria gonorrhoeae
should be suspected.

Common symptoms
•• Fever
•• Chills
•• Dysuria
•• Increased urinary frequency
•• Lower back or pelvic pain (sometimes)
•• Pyuria

72
Clinical management
Recommended treatment is with a fluoroquinolone or trimethoprim-sulfa-
methoxazole for a minimum of ten to 14 days. However, if necessary, some
authorities recommend four weeks of treatment because of the rela­tively
poor concentrations of most antibiotics achievable in the prostate.

Chronic bacterial prostatitis

Fluoroquinolone

In contrast, chronic bacterial prostatitis is a disease of men with en-

larged prostates.

Common symptoms
•• Patients are not acutely ill
•• Intermittent dysuria
•• Increased urinary frequency
•• Pelvic pain (sometimes)

Clinical management
A bacterial cause can be determined by a comparison of pre- and
post-prostate massage urinalysis and cultures of prostate secretions.

Because the prostate is not inflamed in chronic prostatitis, most anti-

biotics do not penetrate the gland sufficiently to treat the infection.
Fluoro­quinolones and to a lesser extent trimethoprim-sulfamethoxazole

73
(TMP-SMX) treatment does result in adequate tissue levels, but at least
four to six weeks of a fluoroquinolone or up to 12 weeks of TMP-SMX is
generally necessary to fully eradicate the infection.

Fluoroquinolone

A newer antibiotic, fosfomycin, penetrates the prostate gland and was

reportedly successful in the treatment of chronic prostatitis with 12–16
weeks of treatment.

74
Diagnosing urethritis and
pelvic inflammatory disease
Urethritis

Urethritis refers to infections involving the urethra.

Pathogenesis

Common causes
•• Neisseria gonorrhoeae
•• Chlamydia trachomatis

Gonorrhea

Common symptoms of gonorrhea in men

•• Urethral gonnorhea
•• Severe dysuria
•• Urethral discharge
•• Symptoms one to ten days after exposure from sexual ­encounter

Common symptoms of gonorrhea in women

•• More subtle than symptoms in men
•• Vaginal discharge
•• Dysuria
•• Intermenstrual bleeding

A Gram stain of the urethral discharge will show gram-negative, intra-

cellular diplococci. This test is very sensitive in men but not in women.

75
Chlamydia

Most non-gonococcal urethritis is caused by Chlamydia trachomatis.

Common symptoms
•• Urethral (men)
•• Vaginal discharge (women)

In men, Gram stain may be helpful in distinguishing the two pathogens.

In Chlamydia infections, neutrophils are present, but no bacteria are
seen. The Gram stain is not helpful in women because of the mixed
flora in vaginal secretions. PCR tests have very good sensitivity and
specificity for both pathogens.

Clinical management —gonorrhea and chlamydia

The treatment recommended by the Centers for Disease Control and
Prevention (CDC) for urethral or vaginal gonorrhea is dual therapy with a
single dose of ceftriaxone plus azithromycin.

Ceftriaxone Azithromycin

The use of combination therapy involving two antimicrobials with

different mechanisms of action aims at improving treatment efficacy
and potentially slowing the emergence and spread of resistance to
cephalosporins. Use of azithromycin as the second antimicrobial is
preferred to doxycycline because of the convenience and compliance

76
advantages of single-dose therapy and the substantially higher
prevalence of resistance of N. gonorrhoeae isolates to tetracyclines than
to azithromycin. It should be noted that 40–50% of patients with proven
gonorrhea are coinfected with Chlamydia. Accordingly, azithromycin in a
single dose or ten days of doxycycline should be included even if tests
are negative for Chlamydia.

Pelvic inflammatory disease

Pelvic inflammatory disease (PID) is a disease that affects the female

reproductive organs.

Pathogenesis

Common causes
•• Neisseria gonorrhoeae
•• Chlamydia trachomatis

PID can result from previous tubal injury and partial obstruction from one
of these pathogens. In that case, a mixed microbial flora resembling ­fecal
flora can be present with or without N. gonorrhoeae or C. trachomatis. The
disease ordinarily occurs in sexually active young women.

Common symptoms
•• Pelvic pain
•• Vaginal discharge
•• Dyspareunia
•• Fever (often but not always)
•• Uterine or adnexal tenderness
•• Cervical motion tenderness
77
Common laboratory findings
•• Elevated white blood cell count
•• Elevated erythrocyte sedimentation rate (ESR)
•• Increased c-reactive protein

Ultrasound may reveal a dilated fallopian tube or even a pyosalpinx, a

condition in which the fallopian tube fills up and swells with pus.

For patients who require hospitalization, the combination of cefotetan

and doxycycline has been popular for many years.

Unlike cephalosporins of most

generations, cefotetan (a second-
gen­eration cephamycin) has useful
activity against anaerobes which
might be part of the infectious
process.

For patients who can be treated

as outpatients, a single dose of
ceftriaxone plus a 14-day course of
doxy­cycline is usually effective. Single dose 14 days

78
Discerning primary and
secondary syphilis
Syphilis is a sexually transmitted disease
caused by the spirochete, Treponema pallidum.
These spirochetes have a characteristically
­helical shape and are transmitted from a person
with an active syphilitic skin lesion, through
mucosal lesions or microperforations, which
are breaks in the skin or mucosal sites.

Syphilis presents in four stages

•• Primary
•• Secondary
•• Tertiary
•• Latent

Primary syphilis

Ten to 90 days after sexual exposure, the first signs of a primary syphilis
infection appear.

Common symptoms
•• Chancre (circumscribed, painless ulcer with rounded, firm borders
and a clean base)
-- usually asymptomatic
-- easily transmitted to uninfected persons
•• Lymphadenopathy (painless, rubbery)

79
 Serology may be negative in up to
30% of individuals with primary syphilis.

Clinical management
Treatment is a single dose of benzathine
penicillin G (2.4 million units intramus-
cular [IM]) or azithromycin (2 g orally).

Secondary syphilis

Secondary syphilis results when many organisms from the primary lesions
gain access to the bloodstream. This typically occurs two to eight weeks
­after the chancre appears. In some patients the chancre is still present.

Common symptoms
•• ­Diffuse papulosquamous rash on hands and feet
•• Chancre may still be present
•• Mucous membrane lesions in mouth or genitals
•• Exophytic lesions in genital area
•• Aseptic meningitis-like picture with cerebrospinal fluid pleocytosis
•• Fever
•• Malaise
•• Sore throat
•• Myalgias
At this stage, nearly 100% of patients will have a positive serologic test
for syphilis.

80
Clinical management
The treatment for secondary syphilis is the same as for primary syphilis
(single dose of benzathine penicillin G [2.4 million units IM] or azithro-
mycin [2 g orally]).

If not treated, the symptoms of secondary syphilis will eventually sub-

side, but the infection will remain and develop into tertiary or latent
syphilis.

81
Treating tertiary and latent syphilis

Tertiary syphilis

Tertiary syphilis may clinically manifest in many ways and may involve the
cardiovascular system, brain, spinal cord, and any deep organ.

Common presentation
•• Some patients are asymptomatic
•• Cardiovascular syphilis
-- aortitis (70–80% of untreated patients)
-- aortic aneurysms
-- aortic insufficiency
-- narrowing of coronary ostea
•• Tabes dorsalis (classic spinal cord lesion)
-- loss of vibratory and position sense
-- peripheral neuropathy
-- unstable gait
•• Syphilitic gummas (macroscopic or microscopic
granulomatous reactions)
-- can appear in any infected organ (including skin)
•• Neurosyphilis

Neurosyphilis can manifest as a stroke or as gradual ­

deterioration
in cognitive ability. It can manifest as emotional lability, paranoia,
careless­ness in appearance, delusions or hallucinations, confabulation,
­decreased memory, and slurred speech.

82
Neurosyphilis should be considered in patients with unexplained
­dementia, and serology and cerebrospinal fluid (CSF) analysis should be
­carried out in these patients. CSF findings include a pleocytosis, elevated
­protein, and a positive CSF VDRL, which is a non-treponemal test that
detects antibodies to cardiolipin antigen.

Clinical management
­Cardiovascular syphilis and gummas can be treated with benzathine
penicillin G (2.4 million units IM) once a week for three weeks

but neurosyphilis requires two weeks of high-dose, ­intravenous ­penicillin

G (18–24 million units / day).

With treatment, many patients show some improvement in neurological

function and ongoing aortitis may be halted. Patients with ­
aortic
­aneurysms and aortic insufficiency need to be carefully evaluated by
cardiologists and cardiovascular surgeons for definitive therapy.

83
Latent syphilis

Patients with latent syphilis have a positive serology for Treponema

pallidum without manifest disease.

Early latent syphilis

The initial infection occurred within the past 12 months.

Late latent syphilis

The infection occurred more than 12 months previously.

Diagnosing early latent syphilis

•• Positive syphilis serology
and
•• Four-fold increase in non-treponemal titers compared to first sero-
logical measurement
or
•• Experienced symptoms suggestive of primary or secondary syphilis
in past year
or
•• Had sexual partner with primary, secondary, or latent syphilis within
last year

Clinical management
Treatment of early latent syphilis involves a single intramuscular dose of
2.4 million units of benzathine penicillin G.

84
Diagnosing late latent syphilis
All other patients with a positive serology are considered to have late
latent syphilis.

These patients could have occult neurosyphilis and cerebrospinal ­fluid

analysis is recommended. If the cerebrospinal fluid (CSF) does not reveal
white blood cells or increased protein, patients can be treated with 2.4
million units of benzathine penicillin G IM once a week for three weeks.

However, if their CSF contains more than five white blood cells per
microliter (µL) and CSF protein is greater than 45 mg / dL, they should be
assumed to have neurosyphilis and should be treated as such.

85
 Chapter 5

BONE, JOINT, AND

SKIN INFECTIONS
Treating osteomyelitis
Osteomyelitis refers to infection of the bone.

Osteomyelitis can arise from

•• Bacteria circulating in the bloodstream
(hematogenous)
•• Organisms in infections present near bones
(contiguous infections)
•• Traumatic inoculation
•• A complication of joint replacement

Common causes
•• Staphylococcus aureus
-- 80% of cases
•• Kingella kingae
-- children under two
•• Staphylococcal, Salmonella or gram-negative rod bacteremia
-- older persons
-- persons with frequent IV infusions, bladder and
intravascular catheters
•• Pasteurella mulocida
-- dog and cat bites

Acute osteomyelitis

Acute osteomyelitis is most common in infants

and children and is hematogenous in origin.

87
Pathogenesis
Staphylococcus aureus is the most common organism involved but
streptococci or Haemophilus influenzae can cause the disease as well.

In infants the nearby joint is often involved because the joint capsule
surrounds the epiphysis and diaphysis. Concomitant joint infections are
not common in older children and adults because the joint capsule is
outside the epiphysis.

Common symptoms
•• Fever with or without chill
•• Focal pain
•• Redness
•• Tenderness

Laboratory and imaging findings

•• Moderately elevated white blood cell count
-- predominance of neutrophils and bands
•• Rapid erythrocyte sedimentation rate (ESR)
•• Elevated c-reactive protein
•• Radiolucencies and elevated periosteum (occasionally) on x-ray
•• Areas of enhancement in bone marrow on MRI

Vertebral osteomyelitis, like acute osteomyelitis in children, is ­usually

hematogenous in origin and may result from an infected intravenous
access, urosepsis or from dental abscesses. Thus, the ­microbiology
often involves S. aureus, enteric bacteria or mixed mouth flora. Fewer
than half of the patients are febrile but focal pain and tenderness of the
spine is characteristic.

88
Clinical management
Bone infections are difficult to eradicate and antimicrobial therapy is
necessarily prolonged. Therefore, it is crucial to biopsy involved bone to
make an exact microbiologic diagnosis to tailor antimicrobial t­herapy
to the best regimen. Biopsies must be performed prior to antimicrobial
treatment and can be done via needle or open biopsy.

For acute osteomyelitis in infants, empirical therapy with vancomycin to

cover gram-positive organisms including MRSA, plus cefepime to cover
gram-negatives, is preferred.

For older children, the bone biopsy should be sent for cultures and
Gram’s stain. If gram-positive organisms are present, vancomycin
should be commenced empirically.

89
If cultures yield methicillin-susceptible Staphylococcus aureus, intra­
venous nafcillin or oxacillin should be substituted for vancomycin.

In children, three weeks of antibiotic treatment is usually sufficient.

Debridement of bone is rarely necessary unless there is antibiotic
­
­failure. Moreover, once the infection is clearly improved, therapy may be
switched to oral antibiotics.

Chronic osteomyelitis

Chronic osteomyelitis often follows a traumatic wound with fractures

­requiring open reduction and internal fixation.

Pathogenesis
­Symptoms may be subtle since patients are left with residual chronic
symptoms from the original injury. Signs of infection may come and go
with overlying redness, pain, increased warmth, and tenderness over the
underlying bone. Purulent drainage through fistulous tracts may emerge
from the area.

Overall, Staphylococcus aureus is the most common cause in upper or

lower extremities, but gram-negative organisms may be found, especially
in lower extremity infections. Imaging of bone often shows lucencies

90
and periosteal elevation and a frank abscess in bone may occur, called
Brodie’s abscess.

Clinical management
Treatment of chronic osteomyelitis first
involves surgical debridement of all dead bone
and, if the remaining defect is large, covering
of the wound with skin and / or muscle flaps.

Four to six weeks of antibiotic therapy

is usually required and is based upon
the results of cultures from the debrided
tissue. Drugs with long half-lives, such
as ceftriaxone and ertapenem, are often
­chosen because they can often be given
once ­daily as outpatients. However, broad-spectrum agents used for a
long time when not absolutely necessary increase the risk of multidrug-
resist­ant bacteria, so it’s best to de-escalate treatment based on the
culture results when possible.

Many surgeons place antibiotic-impregnated

polymethylmethacrylate beads into the wound
as part of local therapy, especially if the wound
contains large areas of dead space after surgery.
Procedures are mainly a surgical decision and
antibiotics have to be adapted to cultures and to
remaining defects in the infected bone.

91
Conquering septic arthritis
Septic arthritis is usually the result of a hematogenous (blood-borne)
infection.

Pathogenesis

Common causes
•• Staphylococcus aureus (~ 50% of cases)
•• Other streptococci (20% of cases)
-- Streptococcus pneumoniae
-- Streptococcus gallolyticus
-- suggests intestinal lesion like colon cancer
-- consider colonoscopy in these patients
•• Neisseria gonorrhoeae (3% of cases)
-- most common in sexually-active young adults

The knee is the most common joint involved in persons over 15 years
of age and the hip in infants and children. Septic arthritis is also more
­frequent in persons with prosthetic joints and rheumatoid arthritis.

92
The infection can be rather subtle in patients with rheumatoid ­arthritis
because they may have redness and tenderness of joints due to the
underl­ying disease. An infected joint may go unrecognized before major
joint destruction has occurred.

The diagnosis of septic arthritis requires joint aspiration, ­fluid ­analysis,

fluid culture and Gram stain. Infected joint fluid will generally show
increased white blood cell count, increased protein, and has a
decreased viscosity and glucose. Gram stains are positive for the
­
causative  organ­ism in half of the patients and joint fluid culture is
positive in more than 80%. Blood cultures are positive in half the
patients. Because of the possible negative results of these studies,
empirical treatment is ­often needed.

Clinical management
­A good combination for empirical therapy is vancomycin (for s
­ uspected
MRSA) plus cefepime, which would cover the vast majority of pathogens
expected.

Repeat drainage by arthrocentesis is needed until

cultures are negative and WBC counts decrease. The
hip joint is difficult to drain percutaneously and ­usually
requires open drainage. Drainage is urgent because
infection can destroy a joint in a short period of time.

93
Recognizing common skin and
soft tissue infections
There are many common skin and soft tissue infections. None are h
­ ighly
contagious. However, precautions should be taken when changing open
wound dressings with increased attention to regular handwashing and
hygiene as well as the avoidance of direct contact with even small skin
breakdown to help curtail spread.

Impetigo

Impetigo is a vesiculopustular or crusted, superficial

skin infection usually caused by Streptococcus
pyogenes with or without Staphylococcus aureus.

Common symptoms
•• May be slightly itchy
•• Pain and constitutional symptoms absent

The crusts are typically honey-colored and the undersurface contains

abundant gram-positive cocci.

To hasten resolution, the infected crusts should be gently scrubbed

off with a soft cloth or soft brush. For patients with few lesions, topical
mupirocin, fusidic acid or retapamulin antibiotics work well, but if many
lesions are present, systemic therapy with penicillin V or trimethoprim-
sulfamethoxazole for a five-day course is usually sufficient. Healing
­occurs without scarring.

94
Erysipelas

Erysipelas is a spreading infection, which

involves the epidermis and more super­
ficial layers of the skin and is almost
­always caused by Streptococcus pyogenes
but Staphylococcus aureus can mimic it.

The lesions are characteristically sharply demarcated and the skin ­follicles

are easily visible because of the superficial edema giving the surface of
the skin a peau d’orange, or orange peel, appearance. The lesions are
most commonly on the lower extremities and less often the face.

Common symptoms
•• Skin lesion
•• Pain
•• Fever
•• Systemic toxicity

Lymphangitis

Lymphangitis is inflammation of the l­ymphatic

system. Lymphangitis and lymphadenitis are
usually caused by Staphylococcus aureus
or ­
beta-hemolytic streptococci, alone or in
combination. They are generally a complication
of an infected wound, traumatic or otherwise.

95
Common symptoms
•• Characteristic red streak (overlying inflamed lymphatic channels)
•• Tender, engorged lymphatic channels
•• Fever
•• Chills
•• Malaise
•• Infection may progress rapidly to bacteremia and sepsis

After obtaining blood cultures, empirical vancomycin to cover possible

methicillin-resistant Staphylococcus aureus should be given pending
the culture results.

Furuncles and carbuncles

Furuncles, or boils, originate from a staphylo-

coccal folliculitis and are deep-seated infections
involving the entire hair follicle and adjacent soft
tissue.

A carbuncle consists of several furuncles devel-

oping in adjoining hair follicles and coalescing to
form a large, deeply situated mass with multiple
drainage sites.

Because of increased carriage of Staphylococcus aureus, diabetes

mellitus is a risk factor.

96
Patients may or may not have fever and other systemic symptoms but
the lesions are generally very painful. Incision and drainage are the
mainstays of treatment.

Most patients are given antibiotics before manipulation of the abscess.

Because of concern for community-acquired MRSA, outpatients are
generally given trimethoprim-sulfamethoxazole or doxycycline.

Inpatient therapy would begin with intravenous vancomycin prior to

incision.

Hidradenitis suppurativa

Hidradenitis suppurativa is secondarily an

infectious disease but primarily a congenital
­keratinous follicular plugging of apocrine sweat
gland ducts. The obstruction leads to infection
by innate and colonizing skin flora and is thus
usually a mixed infection. S. aureus can be a
part of the pathologic process.

This diagnosis should always be considered in patients with a history of

recurrent boils.

Antibiotics for mixed infection which include anaerobes are most

effective, such as amoxicillin-clavulanate or a fluoroquinolone plus
metronidazole, along with incision and drainage of any obvious abscess.
­Definitive therapy requires excision of areas where apocrine sweat
glands are found, such as axillae or groin.

97
Controlling life-threatening skin and
soft tissue infections
While some skin infections are rather innocuous, there are others you
will need to identify and treat quickly, as they can be life-threatening.

Cellulitis

Staphylococcal or streptococcal causes

Cellulitis is commonly caused by staphylococci or streptococci. It is
mainly superficial but extends into subcutaneous tissue.

Because cellulitis and erysipelas can be

serious infections, blood cultures should be
drawn before antibiotics are given.

Vancomycin is the prudent empirical choice pending susceptibility stud-

ies. Warm soaks and elevation of extremities may hasten recovery by
improving circulation in the involved areas.

Other causes
Cellulitis can also be caused by less common organisms. For example,
Aeromonas hydrophila is a gram-negative rod, which is an ubiquitous
inhabitant of fresh water. Vibrio vulnificus is a curved gram-negative rod,
which is likewise part of normal sea water flora.

98
Both organisms can cause life-threatening cellulitis and bacteremia
with fever, pain, tenderness, erythema, and swelling of skin usually after
traumatic injury and exposure to these bodies of water.

These types of cellulitis are notorious for rapid progression because of

their virulence and can lead to necrotizing fasciitis.

Fluoroquinolones are preferred for Aeromonas hydrophila and the

combin­ation of ceftriaxone and doxycycline for Vibrio vulnificus.

Periorbital cellulitis

Cellulitis can also involve the orbit. The orbital septum is a membranous
sheet forming the anterior boundary of the orbit.

Preorbital cellulitis
Infection of the skin anterior to the septum are
known as preorbital cellulitis.

Common symptoms
•• Fever
•• Swelling, redness, and tenderness of periorbital tissues
•• Orbit itself is not involved
•• Extraocular muscle movements intact

Infections are usually due to respiratory pathogens like Haemophilus

influenzae and Streptococcus pneumoniae.

99
Postseptal cellulitis
Patients with postseptal orbital cellulitis have
deep involvement of the orbit itself.

Common symptoms
•• Extraocular palsy
•• Visual disturbance
•• Redness
•• Tenderness
•• Swelling

The usual pathogen in postseptal orbital cellulitis is Staphylococcus

­aureus.

Emergency debridement and drainage are usually needed for postseptal

cellulitis because of the possibility of multidrug-resistant bacteria.
Vancomycin should be given along with a beta-lactam like ceftriaxone.

Necrotizing fasciitis

Necrotizing fasciitis is a life-threatening

form of deep skin infection, which involves
all layers plus muscle fascia beneath.
Early on, the infection may resemble
cellulitis with fever, erythema, tenderness, and warmth. However,
­
antibiotic ­
therapy would fail, owing to deep collections of purulent
material beneath the skin. The overlying skin is very indurated and feels
hard with little inden­tation of the skin with palpation.

100
Later, cutaneous anesthesia may be present, reflecting involvement of
sensory nerves as they emerge through fascia en route to the skin. In
late stages bullae may form.

Emergency imaging will reveal fasciitis and

an emergent surgical consultation should be
requested. Cure requires wide debridement of
all involved tissue including resection of fascia.

Antibiotic therapy should be based upon Gram

stain of pus and tissue resected at surgery, plus historical clues.

Five types of necrotizing fasciitis have been identified

•• Type I—infection by at least one anaerobe (e.g., Bacteroides or
Pepto­streptococcus and one or more facultative anaerobic species,
e.g., E. coli, Streptococcus spp [not group A])
•• Type II—S. pyogenes + / - other organisms (especially S. aureus)
•• Type III—infection caused by marine organisms (e.g., Vibrio ­vulnificus,
Aeromonas hydrophila)
•• Type IV—community-acquired MRSA
•• Type V—Klebsiella pneumoniae as monomicrobial cause

The evaluation and surgical management are the same for all types, only
the choice of antimicrobial will differ.

Fournier’s gangrene
Fournier’s gangrene is a unique form of Type I necrotizing fasciitis
­involving male genitalia. Found most commonly in diabetics, the in-
fection can also be related to local trauma, paraphimosis, periurethral

101
extra­vasation of urine following urologic surgery or perirectal surgery. It
is a rapidly spreading cellulitis and fasciitis often characterized by cuta-
neous crepitus from gas-producing gastrointestinal flora.

Emergent wide debridement is indicated and broad coverage with

piperacillin-tazobactam or a carbapenem are reasonable choices of
antimicrobial agents.

Gas gangrene

Gas gangrene is a life-threatening, deep infection through fascia down to

muscle, which develops following a traumatic wound or recent surgical
procedure. The infection is caused by toxin-producing Clostridium spp,
usually Clostridium perfringens.

Initially the overlying skin is pale, but rapidly becomes bronze, then
­purplish-red with the formation of bullae on the skin. Within 24 hours, a
rapid development of shock and multi-organ failure occurs.

Widespread debridement may not be sufficient. Rather, amputation of

an extremity may be required to achieve a margin around the process.
At surgery, the dead muscle is brick-red and fails to contract when
stimulated by electrocautery.

102
Antibiotic therapy with high-dose IV penicillin G (to kill the organisms)
plus clindamycin (to shut down toxin production) is only adjunctive to
surgery. Prognosis for patients with gas gangrene is poor.

103
 Chapter 6

CENTRAL NERVOUS
SYSTEM INFECTIONS
Identifying acute meningitis
Meningitis is inflammation of the meninges­
—the
membranes that surround the brain and spinal cord.

Meningitis can be viral or bacterial in origin and can

present acutely or more chronically.

Viral meningitis

Acute viral meningitis typically occurs in warmer months of the year.

Common causes
•• Enteroviruses (46%)
•• Herpes simplex virus (HSV) 1 or 2
•• Varicella zoster virus

Common symptoms (abrupt onset)

•• Headache
•• Nausea
•• Vomiting
•• Neck pain or stiffness
•• Photophobia (< 30% of patients)
-- high predictive value
•• Kernig’s sign
-- strong pain in back (when knee extended and hip flexed)
-- high predictive value

105
•• Brudzinski’s sign
-- involuntary hip flexion (when neck is flexed)
-- high predictive value

Kernig’s sign Brudzinski’s sign

All patients with suspected meningitis should undergo a lumbar puncture

for cerebrospinal fluid (CSF) studies.

Common laboratory findings (CSF)

•• Lymphocytic pleocytosis
•• Normal protein
•• Normal glucose
•• Negative Gram stain and culture

Clinical management
In classic cases when the patient is mildly to
moderately ill with no confounding features,
such as being ­
immunocompromised or
prior antibiotic therapy, a case can be
made for withholding empirical anti­biotic
therapy for bacterial meningitis with close
observation. This includes rest, analgesia, and anti-nausea medication.
However, most authorities recommend administering empirical anti­
biotics until the final results of cultures are available. One common
empirical regimen is the combination of ceftriaxone and vancomycin.

106
Most patients with HSV2 ­meningitis
­receive IV acyclovir when the PCR is
­positive for viral DNA. Whether it r­esults
in faster resolution or prevention of long-
term sequelae is uncertain. Most people with mild viral meningitis
­usually get better on their own within seven to ten days.

Bacterial meningitis

The most common cause of bacterial meningitis is Streptococcus

­
pneumoniae. However, this can differ with the age of the individual. In
newborns, group B Streptococcus is most common because of the high
vaginal colonization rate of pregnant women but Listeria and E.  coli
must also be considered. Neisseria meningitidis become common after
the age of two years and is most common among teens and young
adults, especially those living in dormitories or military barracks. In older
people, Streptococcus pneumoniae and Listeria infections are the most
likely cause of acute bacterial meningitis.

Group B Neisseria S. pneumoniae/

­ treptococcus
S ­meningitidis Listeria

107
Common symptoms

Newborns
•• Listless or fretful
•• Poor feeders with weak sucks
•• Labile temperatures
•• Vomiting
•• Diarrhea

Toddlers
•• Fever
•• Vomiting
•• Stiff neck

Older children / adults

•• Fever
•• Altered mental status (80% of cases)
•• Neck stiffness
•• Kernig’s sign (may be present)
•• Brudzinski’s sign (may be present)
•• Petechial or purpuric rash (when N. meningitidis is the cause)

Clinical management
Since acute bacterial meningitis is among the causes of sudden death,
empirical antibiotics need to be given as soon as possible. Patients
whose picture is suggestive of bacterial meningitis should be quickly
­examined for focal neurologic deficits like cranial nerve palsy because,
if present, there is greater danger of uncal herniation following a lumbar
puncture.

108
If no focal findings are apparent on neurologic exam, an immediate
lumbar puncture should be done, CSF collected, and empirical antibiotics
given. The CSF is then immediately sent to the laboratory for analysis
(cell count, protein, glucose, cultures, and Gram’s stain) to save time and
possibly mortality.

When there are focal neurologic signs, empiric antibiotics should be

­given before the patient is sent off for a brain CT scan, because a delay
in providing antibiotics may affect mortality.

If imaging shows no focal abnormalities, an immediate lumbar puncture

should be done and CSF sent to the lab for analysis.

Common laboratory findings (CSF)

•• High WBC count (> 90% neutrophils)
•• High protein (> 100 mg / dL)
•• High glucose (< 2/3 of corresponding blood glucose
obtained immediately before lumbar puncture)

109
 Normal CSF contains no neutrophils,
so any amount is significant.

Specific therapy can often be guided by Gram stain results, which are
positive in 60–90% of cases, and bacterial antigens in 5
­ 0–100% of
cases. If patients have received antibiotics before CSF was obtained, the
Gram stain will be less often positive. Bacterial antigen testing may still
be useful.

When there is an antecedent history of swimming and especially diving

in fresh water lakes, free-living amoeba can cause a picture identical to
acute bacterial meningitis. Thus, it is prudent to take that history and
consider a wet mount of freshly obtained CSF where the motile amoebae
can usually be seen.

In most patients, the combination of

­ceftriaxone, vancomycin, and dexametha-
sone is given empirically. Ceftriaxone and
vancomycin should cover the vast ma-
jority of pathogens and dexamethasone
has been shown to lower the incidence
of complications from the inflammatory
­reaction in the subarachnoid space.

110
The empirical therapy is directed at the most likely organisms to cause
meningitis in various age groups. However, the Gram stain may reveal a
specific organism, which may make a physician modify treatment.

Ceftriaxone is a mainstay for most types of meningitis in older children

and adults and is usually not de-escalated. Importantly, ceftriaxone is
to be avoided in newborns but ampicillin is added to empirical therapy
in newborn or elderly patients, because of the risk of Listeria infections.

111
Managing chronic meningitis
Chronic meningitis has a slower onset than
the acute forms. Patients have often had
symptoms for one month or longer.

Common causes
•• Typically slower growing pathogens
•• Mycobacterium tuberculosis
•• Cryptococcus spp
•• Histoplasma capsulatum
•• Coccidioides immitis
•• Borrelia burgdorferi

Tuberculous meningitis

Common symptoms (gradual onset)

•• Listlessness
•• Irritability
•• Anorexia
•• Fever
•• Headache
•• Vomiting
•• Seizures
•• Coma
•• Stiff neck
•• Cranial nerve palsies

112
Common laboratory findings (CSF)
•• Yellowish
•• Increased pressure
•• Lymphocytic pleocytosis
•• High protein
•• Low glucose

Cultures are negative in 15–25% of cases and the tuberculin skin test is
usually, but not always, positive.

If a strong clinical case can be made for tuberculous meningitis, four-

drug therapy with a combination of isoniazid, rifampin, ethambutol, and
pyrazinamide should be given, along with tapering doses of prednisone
to diminish inflammation, while awaiting the results of confirmatory
studies.

Cryptococcal meningitis

Cryptococcal meningitis is the most common fungal cause of m

­ eningitis.
It is usually due to Cryptococcus neoformans serogroup A or D, which is
frequently isolated from pigeon and other bird excreta.

113
Common symptoms
•• Slowly progressive headache
•• Confusion
•• Mild-moderate meningismus
•• Visual disturbances

Common laboratory findings (CSF)

•• Elevated opening pressure
•• Low glucose
•• High protein
•• High leukocyte count (> 20 / µL) with lymphocyte predominance

India ink mount is positive about half the time but cryptococcal antigens
are present in CSF and blood in most patients.

Clinical management
Induction treatment with two weeks of liposomal amphotericin B plus
flucytosine is followed by three months of fluconazole (or longer in
patients with HIV infection).

In AIDS patients who have cryptococcal meningitis and have just begun
antiretroviral therapy, symptoms of meningitis may transiently worsen
as their immune function improves. This is referred to as the immune

114
reconstitution inflammatory syndrome (IRIS), which is treated with
tapering corticosteroids while continuing antifungal therapy. Close
­
monitoring of intracranial pressure is indicated if initial pressures were
elevated or borderline. Daily lumbar punctures until pressures have
decreased or symptoms have resolved are indicated, as this can be a
life-threatening complication.

Histoplasma meningitis

Histoplasma meningitis occurs almost exclusively

in immunocompromised patients.

Common symptoms (slow progression)

•• Fever
•• Headache
•• Confusion
•• Cranial nerve defects

Common laboratory findings (CSF)

•• Lymphocytic pleocytosis
•• High protein
•• Low glucose

Clinical management
Diagnosis is made in a patient from an endemic area and since p
­ ositive
cultures are the exception, diagnosis is confirmed by the ­presence of
Histoplasma antigens and anti-Histoplasma IgM antibodies.

115
Treatment is with liposomal amphotericin B for four to six weeks,
followed by itraconazole for 12 months.

Coccidioides meningitis

Coccidioides spp can produce a chronic meningitis much like that of

histoplasmosis.

Common symptoms
•• Headache
•• Vomiting
•• Stiff neck
•• Confusion
•• Diplopia

Common laboratory findings (CSF)

•• Lymphocytic pleocytosis
•• High protein
•• Low glucose

Testing of CSF for anti-Coccidioides antibodies complimented by

cultures and antigen testing yields the diagnosis with high sensitivity
and specificity.

116
 Coccidioides meningitis is presently incurable
because of high relapse rates.

In the 20th century, patients with this infection

had to endure monthly intraventricular
injections of amphotericin B through devices
such as Ommaya reservoirs. The development
of fluconazole revolutionized treatment, since
it has excellent penetration into CSF and has good activity against
Coccidioides spp; however, it still only controls the infection, rather than
curing it, so lifelong therapy has been recommended because relapses
are so common.

Lyme meningitis

Chronic meningitis due to Lyme borreliosis usually begins within

approximately one month of the tick bite.

Common symptoms
•• Headache
•• Stiff neck
•• Photophobia
•• Bell’s palsy (occasionally)
•• Negative Kernig’s sign
•• Negative Brudzinski’s sign

117
Common laboratory findings (CSF)
•• Lymphocytic pleocytosis (< 100 cells / µL)
•• Normal glucose
•• High protein

Serology for Lyme disease will ordinarily be positive for antibodies to

Borrelia burgdorferi at this stage. Immunotesting of CSF will usually
show a positive IgG or IgM.

Clinical management
Treatment with ceftriaxone should be given
for 14–28 days depending upon the response
to therapy.

118
Eliminating encephalitis
Encephalitis is characterized by diffuse inflammation and swelling of
the brain.

Arboviruses

The most common causes of epidemic encephalitis are the arboviruses,

of which West Nile virus is most common in the United States. Most
arboviruses are transferred via mosquito bites.

Common causes

Older adults
•• West Nile Virus
•• St. Louis encephalitis

Infants and young children

•• Western equine encephalitis
•• Eastern equine encephalitis

Common symptoms (appear 5–15 days after mosquito bite)

•• Fever
•• Lethargy
•• Stiff neck
•• Stupor (severe cases)
•• Seizures (severe cases)

119
Common laboratory findings (CSF)
•• Lymphocytic pleocytosis
•• High protein
•• Normal glucose

These infections can be diagnosed by employing PCR to

identify specific viral causes.

Clinical management
These are not chronic infections and the immune system gradually deals
with the virus. Some tend to be more severe than others with mortality
rates ranging from 4–33%. Treatment can only be supportive.

Herpes encephalitis

Herpes encephalitis is the most common cause of sporadic encephalitis.

Common symptoms (abrupt onset)

•• Headache
•• Fever
•• Behavioral and speech changes

Imaging usually reveals abnormalities in the temporal lobe.

120
Clinical management
Without treatment, mortality is 70%. This can be reduced to 10–20% with
intravenous acyclovir for 10–21 days.

121
 Chapter 7

LIFE-THREATENING
SYSTEMIC INFECTIONS
Recognizing sepsis
Sepsis can best be defined as a systemic, deleterious host response to
infection. When severe, it can lead to acute organ dysfunction or septic
shock, which is not easily reversed with fluid resuscitation.

Septic shock carries a mortality of

40–70%. Many cases of sepsis are
­
associated with bacteremia but a focus
of infection outside the bloodstream
can cause the entire process.

Common sources of infection

•• Pulmonary infections (~ 50% of cases)
•• Unspecified source (~ 20% of cases)
•• Genitourinary or gastrointestinal tract infections
(most remaining cases)

Sepsis can be caused by either gram-positive or gram-negative bacterial

infections, although the latter are slightly more common.

The presence of gram-positive or gram-negative organisms stimulates

an immune system cascade, which leads to the production of both pro­
inflammatory and antiinflammatory cytokines. When an over response
occurs in this process, sepsis develops.

123
Common symptoms

Early manifestations
•• Confusion
•• High fever
•• Chills
•• Hypotension

Late manifestations
•• Extreme hypotension
•• Rash or other skin lesions
•• Gangrenous changes in extremities
•• Acute respiratory distress syndrome

In babies
•• Fever or hypothermia
•• Respiratory distress
•• Gastrointestinal problems
•• Poor feeding
•• Weak suck
•• Vomiting
•• Abdominal distension
•• Worsening jaundice

In elderly patients
•• Vomiting
•• Diarrhea
•• General weakness
•• Oliguria

124
The physician must maintain a high index of suspicion for sepsis in
patients who present to emergency facilities or in hospitalized patients
who develop some of the following unexplained signs or symptoms.
•• Hypothermia
•• Tachycardia
•• Tachypnea or hyperpnea
•• Abdominal pain
•• Pelvic pain
•• Vaginal discharge
•• Abnormal blood clotting
•• Altered mental status

The quick Sequential Organ Failure score (qSOFA) was developed to

prompt physicians to look for organ dysfunction, initiate early antibiotic
treatment (within one hour), and refer the patient to an ICU.

Three parameters to quickly assess for sepsis

1. Glasgow coma score < 14
2. Systolic blood pressure < 100
3. Respiratory rate > 21

A qSOFA score of > 2 is highly suggestive of organ dysfunction and a

poor outcome of sepsis.

Sepsis is most common and most dangerous in pregnant women,

older adults, children under one year old, people with chronic health
conditions (e.g., diabetes, kidney disease, lung disease or cancer), and
immunocompromised individuals. So it is important to quickly and
efficiently diagnose sepsis, especially in these patient populations, so
that treatment can be initiated immediately.
125
Clinical management
The management of sepsis can be complicated. Emergently, the ­patient’s
oxygenation and organ perfusion needs treatment. Oxygenation is satis-
factory if the central venous O2 saturation is above 75%.

Fluid resuscitation is necessary to maintain a central venus pressure

(CVP) of 8–13 mmHg and a mean arterial pressure of at least 65 mmHg.
If fluids fail to reach these targets, norepinephrine is the pressor of
choice.

Antimicrobial failure is likely in the presence of a large abscess. Thus,

an abscess must be located and adequately drained. When adequate
­history and physical signs are available, identifying the offending organ
system is crucial to the selection of antimicrobial agents.

In many instances, microscopy and recent culture results will direct

appropriate antibiotic choices but if not, empirical therapy is necessary.

When no history is available and there are no physical signs suggesting

the offending organ system, several blood cultures should be obtained and
very broad antimicrobial coverage (e.g., a carbapenem) should be given.

Empirical treatment should be based

on the suspected source of infection.

126
For pneumonia—a fluoroquinolone or azithromycin plus an anti-
pseudomonal beta-lactam like piperacillin-tazobactam or cefepime
should be given.

For intraabdominal infection—piperacillin-tazobactam or a carbapenem

are excellent choices for mixed aerobic and anaerobic ­infections. For
patients with a beta-lactam allergy a fluoroquinolone plus metronidazole
is a good alternative.

For urosepsis—a fluoroquinolone is a good choice.

127
For sepsis of unknown source—vancomycin plus a carbapenem like
meropenem is warranted.

128
Defeating infective endocarditis
Pathogenesis
The pathogenesis of infective endocarditis begins with damaged heart
valves from congenital heart disease, rheumatic fever, IV drug abuse or
the placement of intracardiac devices, such as implantable defibrillators
and pacemakers.

Valve damage leads to sterile deposits of platelets, red blood cells, white
blood cells, and fibrin called nonbacterial thrombotic endocarditis, or
NBTE (a non-infected vegetation).

If a sufficiently virulent organism is present in the bloodstream in

sufficient amounts it may colonize the damaged valve and its associated
NBTE and now the mass of bacteria and NBTE (an infected vegetation)
becomes infective endocarditis.

Eighty percent of infective endocarditis is caused by gram-positive c

­ occi
of which Staphylococcus aureus is most common.

The HACEK group of organisms consists of fastidious gram-negative

bacteria that are unusual causes of infective endocarditis. They are,
­together with fungal infections, notoriously associated with large, friable,
vegetations, which can easily break off and cause emboli to vital organs.

Enterococcus causes about 10% of infective endocarditis. ­Enterococcus

is a notorious problem if it causes endocarditis because agents that
inter­fere with the organism’s cell wall can inhibit these organisms but

129
cannot kill them. However, bactericidal therapy is essential to prevent
recurrence of endocarditis of any cause. Thus, for enterococcal endo­
carditis, potentially toxic aminoglycosides must be added to cell wall
agents for the entire period of treatment to eradicate the infection.

Diagnosis is confirmed by multiple positive blood cultures and visible

vegetations noted on echocardiography.

Clinical management
Definitive management of patients with infective endo-
carditis is best accomplished by an infectious disease
specialist and the nuances of antimicrobial therapy are
beyond the scope of this lesson.

However, while awaiting culture results, empirical ­therapy

of native valve infective endocarditis with v
­ ancomycin
plus ceftriaxone is recommended.

For prosthetic valve endocarditis, the combination of vancomycin

plus gentamicin plus oral rifampin is recommended because of the
possibility of methicillin-resistant Staphylococcus aureus (MRSA).
­
This combination is also recommended for methicillin-resistant
­Staphylococcus epidermidis (MRSE). Adjustment of antibiotics can be
made by an infectious disease specialist when available.

130
In some cases of endocarditis, valve replacement early in the course of
endocarditis should be considered. It is associated with a ­lower mortality
than elective valve replacement after prolonged ­antimicrobial treatment.

Candidates for urgent valve replacement

•• Congestive heart failure
•• Infections caused by difficult-to-treat organisms
-- Enterococcus (especially on prosthetic valves)
-- S. aureus
-- aerobic gram-negative bacilli
-- fungi
•• Previous cerebral embolism
•• Presence of large vegetations

If surgery is inevitable, early surgery

has a better prognosis than delaying surgery.

An endocarditis team consisting of a cardiologist, a cardiac surgeon,

an infectious disease physician, a microbiologist, and an intensivist
who discuss patients in the hospital with infective endocarditis weekly
and make decisions about surgery has been shown to reduce mortality
substantially. To complete the picture as an outpatient, follow up by a
cardiology and infectious disease specialist at one, three, six, and 12
months after surgery, is optimal.

131
Spotting Lyme disease
Ticks are capable of transmitting many diseases,
from viral to parasitic. There is good treatment for
only bacterial and parasitic diseases. The most
prevalent tick-borne infection in North America,
Asia, and Europe is Lyme disease.

Lyme disease is caused by the spirochete, ­Borrelia

burgdorferi, and usually transmitted by the bite
of the nymphal stage of the hardshell tick Ixodes
scapularis.

The earliest manifestation is an expanding, target-­

like lesion which may be slightly pruritic and ­begins
to appear within a month of the tick bite. The skin
lesion usually precedes fever and other signs of
infection, although myalgias and arthralgias may
­
appear in the early stages, when the skin lesion is
still present.

Early disseminated disease can involve the joints, the heart, or the
central nervous system (CNS). Arthritis that mostly affects the knee joint
may occur when the infection remains untreated. It may be accompanied
by effusion but fever is rarely present. A cranial nerve VII palsy is the
most common central nervous system manifestation but an aseptic
meningitis-like picture can also occur. Varying types of heart block are
indicative of carditis.

132
 Who should be screened
for Lyme disease?

Screening serology is not necessary in patients without any disease

after simply being exposed to a tick. Observation is best in these cases.

Screening is also not necessary in patients who present with the classic
skin lesion—these patients should be treated.

Screening should be carried out in patients with confirmed tick

exposure, who show clinical findings such as facial palsy, meningitis
or frank arthritis.

Clinical management
Oral therapy with doxycycline or amoxi­cillin
for 14–21 days is usually sufficient for early
Lyme ­disease and mild degrees of c
­ ranial
nerve VII palsy, but must be continued for
30–60 days in p
­atients with associated
arthritis.

The more serious manifestations are

managed with intravenous ceftriaxone.

133
Characterizing primary and
post-primary tuberculosis
Mycobacterium tuberculosis has infected almost two billion i­ndividuals
worldwide. There are 7–8 million new infections each year, with two
­million deaths from tuberculosis (TB) worldwide every year, partly due to
the epidemic of HIV infection in sub-Saharan Africa and other ­developing
countries. Globally, TB incidence is falling at about 2% per year and the
World Health Organization (WHO) aims at ending the epidemic by 2030.

If a previously healthy individual is exposed to TB, there is a 5% chance

of developing clinical disease in the first year and another 5% over a life-
time. Patients with HIV infection have a 10% annual risk of developing
active disease.

First year Lifetime Annual risk

An overview of disease progression

1. After the initial infection in the lower lobes, the
organisms circulate to all organs including
other areas of the lung.

134
2. After cell-mediated immunity develops, they
may persist in the upper lobes and eventually
cause a chronic infection, which keeps a
person alive long enough to develop a lung
cavity and chronic cough, that causes them to
transmit the infection to others.

3. The infected patient coughs macroscopic dro-

plets containing Mycobacterium tuberculosis
into the air.

4. These macroscopic droplets evaporate into

micro­
droplets containing one or more orga-
nisms and are small enough to be deposited into
the alveoli of an unaffected individual.

5. In the lower lobes of the lungs where they are

usually inhaled, alveolar macrophages engulf
the organisms, but cannot kill them, resulting
in a low-grade inflammatory response in the
region within the first week after infection. This
is referred to as primary tuberculosis.

6. Organisms can also enter the bloodstream and spread everywhere

during this primary infection. In the first two weeks after infection,
immature granulomas begin to develop wherever organisms have
been carried in the bloodstream to any organ. However, cell-mediated
immunity has yet to develop fully and the patient generally remains
asymptomatic. For this ­reason, this dissemination is referred to as a
period of silent bacillemia.
135
7. At three to nine weeks after the initial infection, the immune ­system
begins to react to the infection. Development of granulomas that
contain activated T cells begins and activated macrophages, which
have settled around foci of Mycobacterium tuberculosis emerge.
If a skin test were done at this point, it would likely be positive,
even though most patients do not show symptoms at this stage.
The mature response to TB antigens wherever they are present is
known as post-primary tuberculosis.

A Ghon complex is a radiographic phenomenon that appears after the

cell-mediated immune response has matured. This represents ­granulomas
in the region where the primary lung infection initially occurred, as well as
in neighboring lymph nodes. Presence of the Ghon complex confirms past
infection with TB but does not indicate an active infection.

136
Evaluating latent tuberculosis
Remember that post-primary tuberculosis (TB) occurs after the develop­
ment of a mature cellular immune response to the TB antigen. At this
stage, the patient is generally still asymptomatic. At this point in time,
TB in most patients will remain latent.

Patients with latent TB have been exposed, developed mature granulomas,

and already have post-primary TB, but they are asymptomatic and likely
don’t know they have the disease.

Diagnosis
Latent TB is diagnosed in most of
the world with a tuberculin skin test,
which involves intradermal injec-
tion of a purified protein derivative
of M. tuberculosis (PPD), then moni­
toring the site for the presence of a
reaction within 48–72 hours after 48–72 h

­injection.

In healthy individuals, a skin test

is considered positive if a 15 mm
­induration (a bump) is present at the
site of injection 48–72 hours later.

Healthcare workers are understandably at greater risk of exposure and

certain others may be predisposed to contracting TB, including children

137
under four years of age, diabetics, prisoners, and IV drug users. Thus,
the skin test in these individuals is considered positive with 10 mm
induration.

≥ 10 mm

Immunosuppressed persons may not have a vigorous response to

­tuberculin, thus they should be assumed to have a positive test if the
­response measures greater than 5 mm.

≥ 5 mm

Recently, newer tests known as interferon-gamma release assays have

become available. They come at a considerably increased cost, but avoid
the necessity of returning to have the skin test read by a ­professional.
The principle behind these tests is to incubate the patient’s own
T cells in the presence of tuberculosis antigens and determine whether
interferon-gamma has been released by the T cells. They are reasonably
sensitive and specific.

138
Clinical management
Patients with latent tuberculosis should have a
screening chest x-ray to rule out active tubercu-
losis.

For persons with a negative chest x-ray but a

­positive TB skin test (or interferon-gamma release
assay), nine months of isoniazid is recommended.

Since hepatitis is a known adverse effect associated with isoniazid, it is

important to also obtain a single alanine aminotransferase (ALT) l­evel
after one month of therapy. Thereafter, if ALT is normal, monitoring for
hepatitis symptoms is sufficient.

For patients with HIV, a combination of pyridoxine plus isoniazid is

­recommended to treat latent TB.

Interestingly, patients with latent TB may not reveal any abnormality on

chest x-ray, but sometimes a Ghon complex or apical scarring is present.

If the skin test or interferon-gamma release assay

is truly positive, the patient has been infected with TB
and should be offered therapy.

139
Managing active tuberculosis
Active or clinical TB can develop in any
­organ system; however, pulmonary TB is the
most common type of clinical TB. Living or-
ganisms in the lungs (usually in the apices)
may cause a caseous pneumonia, which
can cavitate, resulting in what is known as
cavitary disease. The caseous pneumonia
also results in granuloma formation.

Common symptoms of cavitary disease

•• Chronic illness
•• Low-grade fever
•• Fatigue
•• Weight loss
•• Productive cough (may be blood-streaked)
•• Hemoptysis

Common imaging and laboratory findings

•• Apical infiltrates and cavities (chest x-ray)
•• Hypoalbuminemia
•• Anemia of chronic disease
•• Hyponatremia
•• Hypercalcemia
•• High calcium

140
While sputum cultures are usually positive, acid-fast stains are positive
in less than 50% of patients. PCR of body fluids is available in three to
four hours but false-positive test results are frequent.

Clinical management
To treat active tuberculosis a nine-month treatment course is necessary.
Pyrazinamide, ethambutol, isoniazid, and rifampin are given t­ogether
initially. Pyrazinamide is dropped after two months and ethambutol is
dropped after three months. Isoniazid and rifampin are continued for the
full nine months.

2 months 3 months 9 months

141
Handling multidrug-resistant
bacterial infections
Many organ-specific infections can be caused by multidrug-resistant
(MDR) organisms. When this is the case, the arsenal of antibiotics with
which you can potentially treat the infection is generally limited.

It is important to remember that infections acquired in the h

­ ospital
­environment are more likely to be caused by more antibiotic-­resistant
­bacteria. This requires empirical treatment with a broad-spectrum agent.
De-escalation to a more narrow-spectrum agent ­hopefully can be done
after the results of cultures and susceptibility testing become available.

Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) was one of the first

MDRs recognized, and is a common pathogen, particularly in the hos-
pital environment. In addition to methicillin, MRSA is resistant to a host
of beta-lactam antibiotics which were previously staples for treating
S. ­aureus infections.

Risk factors for MRSA

•• ­ Recent hospitalization or surgery
•• Nursing home residence
•• Indwelling vascular catheter

142
The community-acquired MRSA is usually susceptible to trimethoprim-
sulfamethoxazole, clindamycin or doxycycline, but cultures and suscep-
tibility testing of drainage should be done (when possible) to best ­target
the infection.

The hospital-acquired MRSA is susceptible to fewer antibiotics. The

fifth-generation cephalosporin, ceftaroline, does have activity against
MRSA, and provides the safety of a beta-lactam antibiotic, so in hospi­
talized patients, either ceftaroline or a glycopeptide like vancomycin
should be used.

Enterococcus faecium

Enterococcus spp are normal inhabitants of

the gastrointestinal tract that cause about 10%
of cases of infective endocarditis. They are
difficult to treat on native valves and especially
on prosthetic valves because enterococci
are only inhibited but not killed by cell wall
agents. Thus, the relapse rate for enterococcal

143
endocarditis is high. Moreover enterococci, especially E. faecium, have
increasingly developed resistance to antibiotics over many years of
antibiotic use. Vancomycin- and ampicillin-resistant E. faecium are now
commonplace. The susceptibility results for ampicillin and vancomycin
will automatically appear on the lab report along with the culture results.

For infections without bacteremia, alternative therapy for these resistant

bacteria, such as daptomycin, can be used. However, for enterococcal
endocarditis, the organisms must be tested for gentamicin susceptibility.
If the organism is susceptible to ampicillin, then the combination of
ampicillin plus gentamicin may be used.

However, organisms like E. faecium are often resistant to ampicillin, vanco-

mycin, and gentamicin. For native valve endocarditis due to this ­organism,
rather unexpectedly, the combination of ampicillin plus ceftriaxone has
been shown to have some efficacy. Failing that, the valve may need to be
replaced, as it almost always does for infection on a ­prosthetic valve.

Linezolid or daptomycin cannot be used for a resistant enterococcal

endocarditis.

Acinetobacter baumannii

Acinetobacter baumannii is actually a complex of gram-negative coccal

organisms resembling Neisseria, which are environmental contaminants
found in hospitals. Almost 20% of the isolates are multidrug-resistant.

144
Infection with these organisms is often in
the form of ventilator-associated pneumonia
(VAP). Because of antimicrobial resistance
along with serious illness, which prolongs
hospital stays, the mortality from VAP due to
A. baumannii approaches 70%.

Antibiotic therapy for this infection would be the combination

of ampicillin-sulbactam and colistin. Of interest, the sulbactam
component, which ordinarily functions only as a beta-lactamase
­
inhibitor, actually has activity against these organisms adding to the
effect of the ­ampicillin.

Pseudomonas aeruginosa

P. aeruginosa has been a notorious ­hospital

pathogen since the mid-20th century and is
the single most common cause of ventila-
tor-associated pneumonia (VAP).

In addition to the capability of acquiring multidrug resistance genes, the

organism also has several intrinsic properties that allow it to persist in the
presence of many antibiotics. Moreover, unlike many enteric organisms,
it has an arsenal of toxins targeting immune cells in the lung, such as a
phospholipase, which can destroy the cell membrane of white blood cells.

A reasonable treatment choice for proven or suspected multidrug-­

resistant P. aeruginosa VAP would be the combination of meropenem
plus colistin.

145
Enterobacteriaceae

Even enteric organisms can become MDR. Organ-

isms belonging to the family ­Enterobacteriaceae
are residents of the human gastrointesti-
nal tract. As a result, this group is responsible
for ­
infections in many organ systems, such as
wound infections, urinary tract infections, gastro-
intestinal tract infec­tions, and pneumonia (both
­community-acquired and VAP).

Some of these organisms have developed resistance to many

beta-lactam antibiotics, including commonly used extended-spectrum
cephalosporins, such as third-generation compounds like ceftriaxone,
cefotaxime, and the fourth-generation cephalosporin, cefepime.

Risk factors for infection

•• Diabetes mellitus
•• Prior quinolone use
•• Recurrent urinary tract infection
•• Prior hospital admissions
•• Older age

146
Many of these bacteria are susceptible to carbapenems, which are the
drugs of choice for treating infections resulting from these organisms.
However, as might be expected, the high use of these broad-spectrum
drugs has increased the rates of carbapenem resistance among these
­organisms.

If there is resistance to all carbapenems, colistin is one of the last

­options. However, it has major side effects like nephrotoxicity and neuro­
toxicity, and so should only be used as a last resort.

147
APPENDIX
Basic characteristics of common
pathogenic bacteria

Short name Full name Gram stain Shape Characteristics

A. hydrophila Aeromonas Negative Rod

­hydrophila

A. baumannii Acinetobacter Negative Cocco-­ Aerobic

baumannii bacillus

B. cereus Bacillus cereus Positive Rod Anaerobic

B. burgdorferi Borrelia Neither Spirochete Primarily

­burgdorferi ­extracellular

C. trachomatis, Chlamydia Negative Elementary Intracellular

Chlamydia ­trachomatis bodies

C. pneumoniae Chlamydophila Negative Elementary Intracellular

pneumoniae bodies

C. botulinum Clostridium Positive Rod Anaerobic,

­botulinum ­produces botu-
linum toxin

C. difficile Clostridium Positive Rod Anaerobic

­difficile

C. perfringens Clostridium Positive Rod Anaerobic

­perfringens

E. coli Escherichia coli Negative Rod Aerobic

Enterobacter spp Negative Rod Aerobic

E. faecium Enterococcus Positive Coccus Aerobic

faecium

H. influenzae Haemophilus Negative Cocco-­ Aerobic

­influenzae bacillus

149
K. kingae Kingella kingae Negative Cocco-­ Aerobic
bacillus

K. pneumoniae Klebsiella Negative Rod Aerobic

­pneumoniae

L. pneumophila Legionella Negative Rod Aerobic

­pneumophila

M. catarrhalis Moraxella Negative Coccus Aerobic

­catarrhalis

M. tuberculosis Mycobacterium Positive Rod Aerobic,

tuberculosis ­intracellular

N. gonorrhoeae Neisseria Negative Coccus Aerobic

­gonorrhoeae

N. meningitidis Neisseria Negative Coccus Aerobic

­meningitidis

P. multocida Pasteurella Negative Cocco-­ Aerobic

­multocida bacillus

P. aeruginosa Pseudomonas Negative Rod Aerobic

aeruginosa

S. agalactiae Streptococcus Positive Coccus ­Anaerobic,

agalactiae group B strep

S. gallolyticus Streptococcus Positive Coccus Aerobic

gallolyticus

S. pneumoniae Streptococcus Positive Coccus Aerobic

pneumoniae

S. pyogenes Streptococcus Positive Coccus Aerobic,

pyogenes ­group A strep

S. aureus Staphylococcus Positive Coccus Aerobic

aureus

S. saprophyt­ Staphylococcus Positive Coccus Aerobic,

icus saprophyticus coagulase-­
negative

150
 T. pallidum Treponema Neither Spirochete Aerobic
­pallidum

Vibrio spp Negative Rod Aerobic

(comma-­
shaped)

Y. enterocolitica Yersinia Negative Cocco-­ Aerobic

­enterocolitica bacillus

Multidrug-resistant bacteria

Short name Full name Gram stain Shape Characteristics

ESBL-­ Extended-­ Negative Rods Aerobic,

producing spectrum, ­includes ­E.coli,
Enterobacteri­ beta-­lactamase- ­Klebsiella,
aceae producing Entero­ Salmonella,
bacteriaceae ­Shigella, and
Yersinia

MRSA Methicillin-­ Positive Coccus Aerobic

resistant Staphylo­
coccus aureus

MRSE Methicillin-­ Positive Coccus Aerobic

resistant Staphylo­
coccus epidermidis

VRE Vancomycin-­ Positive Coccus Aerobic

resistant Entero­
coccus faecium

151
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