Antimicrobial Stewardship
Antimicrobial Stewardship
Antimicrobial Stewardship
March 2013
Clinical guidelines are made available to the public for informational purposes only. The
Federal Bureau of Prisons (BOP) does not warrant these guidelines for any other purpose, and
assumes no responsibility for any injury or damage resulting from the reliance thereof. Proper
medical practice necessitates that all cases are evaluated on an individual basis and that treatment
decisions are patient-specific. Consult the BOP Clinical Practice Guidelines Web page to
determine the date of the most recent update to this document:
http://www.bop.gov/news/medresources.jsp
Federal Bureau of Prisons Antimicrobial Stewardship Guidance
Clinical Practice Guidelines March 2013
Table of Contents
1. Purpose ............................................................................................................................................. 3
2. Introduction ...................................................................................................................................... 3
3. Antimicrobial Stewardship in the BOP............................................................................................ 4
4. General Guidance for Diagnosis and Identifying Infection ............................................................. 5
Diagnosis of Specific Infections ........................................................................................................ 6
Upper Respiratory Infections (not otherwise specified) ............................................................................... 6
Rhinosinusitis ............................................................................................................................................. 6
Pharyngitis................................................................................................................................................. 6
Bronchitis .................................................................................................................................................. 6
Osteomyelitis.............................................................................................................................................. 7
Clostridium Difficile Infection (CDI) .......................................................................................................... 7
5. Culture and Sensitivity ..................................................................................................................... 8
Urinalysis.......................................................................................................................................... 8
Urine Culture .................................................................................................................................... 8
Respiratory Cultures.......................................................................................................................... 9
6. Therapy Selection ............................................................................................................................. 9
Specific Diagnoses .......................................................................................................................... 10
Upper Respiratory Infections (URIs) – Not Otherwise Specified ................................................................ 10
Rhinosinusitis ........................................................................................................................................... 10
Acute Pharyngitis ..................................................................................................................................... 11
Bronchitis ................................................................................................................................................ 11
Pneumonia ............................................................................................................................................... 11
Deep Tissue Infections .............................................................................................................................. 12
Immunocompromised ............................................................................................................................... 12
Osteomyelitis............................................................................................................................................ 12
Cellulitis .................................................................................................................................................. 13
Acne ......................................................................................................................................................... 14
Clostridium Difficile Infection (CDI) ........................................................................................................ 14
Dental Prophylaxis................................................................................................................................... 14
7. Intravenous to Oral Conversion Guidelines .................................................................................. 16
Three Types of IV to PO Therapy Conversions ............................................................................... 16
General IV to PO Conversion Considerations .................................................................................. 17
Major Criteria to Consider When Selecting Patients for IV to PO Conversion .................................. 18
Considerations for Converting Specific Medications from IV to PO ................................................ 19
IV to PO Conversion Myths ............................................................................................................ 20
8. Multi-Drug Resistant Organisms – Specific Diagnoses ................................................................. 20
9. Communication Strategies ............................................................................................................. 21
10. Competencies and Training .......................................................................................................... 22
National Guidelines ............................................................................................................................. 24
References ............................................................................................................................................ 26
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Tables:
Table 1. Common Methods to Confirm the Presence of Infection and Identify the Cause ................ 5
Table 2. Common Diagnoses NOT Recommended for Treatment with Antibiotics ......................... 10
Table 3. Dental Prophylaxis for Bacterial Endocarditis Prevention (Adult Patients Only) ............. 15
Table 4. Examples of Medications That Can Be Converted with the Sequential
or Switch Methods ................................................................................................................ 16
Table 5. Step-Down Therapy Conversion Medication Pairs ............................................................. 17
Table 6. Considerations Concerning the GI Tract and Conversion from IV to PO Therapy .......... 18
Table 7. Signs That Clinical Status is Improving .............................................................................. 18
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1. Purpose
The purpose of this document is to provide guidance on the appropriate use of antimicrobials, to
provide recommendations and standards for the medical management of inmates receiving
antimicrobial therapy, and to outline the Federal Bureau of Prisons (BOP) Antimicrobial
Stewardship Program.
This document should be utilized in tandem with the BOP Technical Guidance for the Use of
Injectable Medications, as applicable.
2. Introduction
Antimicrobial resistance is a growing problem in the healthcare and community settings—
leading to increased morbidity, mortality, and healthcare costs. The Centers for Disease Control
and Prevention (CDC) states that antibiotic resistance is one of the world’s most pressing public
health problems. Inappropriate antimicrobial prescribing practices are largely responsible for the
growth of resistant microbes. Studies have shown antibiotic use is unnecessary or inappropriate
in as many as 50% of the cases in the United States. According to one study, antibiotics were
prescribed in 68% of acute respiratory tract visits; of those, 80% were unnecessary, according to
CDC guidelines. Common prescribing concerns include unnecessary antimicrobials, overuse of
broad spectrum antibiotics, ineffective agents, wrong doses, and extended durations of therapy.
All of these contribute to the growing resistance problem.
To combat bacterial resistance and minimize adverse effects related to treatment, many
institutions and organizations have developed antimicrobial stewardship programs. Such
programs provide healthcare providers with guidance on pathogen identification and selection of
appropriate antimicrobial agents, dosage, and the route and duration of therapy. When
implemented appropriately, antimicrobial stewardship programs in conjunction with infection
control can lead to decreased antimicrobial resistance and reduced healthcare costs.
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(2) Formulary Management: The BOP utilizes a formulary with varying degrees of
restrictions. Medications are either unrestricted (e.g., amoxicillin) or restricted
(e.g., clarithromycin as a second-line agent requiring physician co-sign). Additionally, some
medications may be restricted to use for certain diagnoses only.
Depending upon local circumstances, the pharmacy and therapeutics committees in some
institutions may choose to place additional restrictions on medications on the BOP National
Formulary or to remove certain items from their local formularies.
(3) Prior Approval Programs: All medications not listed on the BOP National Formulary
require prior approval via the non-formulary request process. The BOP does not require
prior-approval for medications listed on the National Formulary, so long as their use
complies with any applicable formulary restrictions.
Similar to the formulary management option described above, the pharmacy and therapeutics
committees in some institutions require additional approval for the use of certain formulary
medications. This approval may include the institution’s clinical director or pharmacist, or
both. This type of local prior approval is often applied to second-line therapy and may
require culture and sensitivity data.
(4) Streamlining: Streamlining refers to the practice of converting a patient from broad-
spectrum to narrow-spectrum therapy. If a provider starts a patient on empiric treatment with
broad-spectrum antimicrobials, he or she should narrow the treatment selection to better meet
the patient’s specific needs once culture and sensitivity data are available. This may involve
changing antibiotics, reducing the number of medications, or discontinuing treatment.
Benefits associated with streamlining include:
• Reduced secondary infections
• Decreased morbidity and mortality
• Minimized antimicrobial resistance
• Minimized toxicity and adverse effects
• Reduced healthcare expenses
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Pharyngitis
The large majority of adults with acute pharyngitis have a self-limiting illness that should be
treated with supportive care only. The benefits of antibiotic treatment of adult pharyngitis are
limited to those patients with group A streptococcal (GAS) infection. GAS is the etiologic agent
in approximately 5–15% of adult cases of pharyngitis.
Clinical features alone are unreliable in differentiating between GAS and viral pharyngitis,
except where overt viral features are present (e.g., rhinorrhea, cough, oral ulcers, and/or
hoarseness). Because the signs and symptoms of streptococcal and non-streptococcal (usually
viral) pharyngitis overlap, diagnosis should be accomplished through laboratory testing with
either a throat culture or a rapid antigen detection test (RADT).
Throat cultures are not recommended for confirming negative RADT results in adults. Throat
cultures may be indicated when investigating outbreaks of GAS infection, as a means of
monitoring the development and spread of antibiotic resistance, or when pathogens such as
gonococcus are being considered.
Bronchitis
When evaluating adults who have an illness with an acute cough, or with a presumptive
diagnosis of uncomplicated acute bronchitis, the provider should focus on ruling out pneumonia.
In healthy, non-elderly adult patients, pneumonia is uncommon in the absence of vital sign
abnormalities or findings of consolidation on lung auscultation. Chest radiographs are not
warranted when these objective signs of pneumonia are not present in the patient presenting with
acute nasopharyngeal symptoms and cough.
Chest radiography is only warranted for patients with a cough lasting three weeks or longer, in
the absence of other known causes.
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Osteomyelitis
The diagnosis of osteomyelitis is often accomplished using x-ray; however, it is important to
note that changes may not appear on x-ray for 10–14 days following an infection. Clinical
features include fever, leukocytosis, and erythema/pain/swelling in the area of infection. Bone
scans are of limited benefit, since they are non-specific for infection and will show any
inflammation that is present. Erythrocyte sedimentation rate and C-reactive protein may be
beneficial, but again are non-specific. CT/MRI may also be useful in diagnosis. It is important
to follow cultures and sensitivities for the source of infection (i.e., blood, bone biopsy, or aspirate
cultures).
Acute osteomyelitis cases have an approximate 80% cure rate; however, chronic osteomyelitis is
more difficult to treat due to necrotic bone being a site for continued infection.
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Urinalysis
Urine will often grow organisms when cultured because it passes through tissue that is typically
colonized with bacteria. Therefore, a urinary infection should be confirmed by the presence of
bacteria and elevated white blood cells in the urinalysis, and by systemic signs of infection.
Indicators of infection on a urinalysis:
• Turbid/cloudy urine.
• Positive leukocyte esterase, which indicates the presence of white blood cells in the urine.
• Presence of >10 WBCs. Upon microscopy, the presence of 10 WBCs per high-power field is
equivalent to 100 cells/mm3 of urine, which is considered the upper limit of normal.
• Positive nitrite test, which indicates the presence of a nitrate-reducing microorganism, such
as Escherichia coli or any other member of the Enterobacteriaceae family.
• Elevated pH (6.5–8). This may indicate the presence of organisms that produce the enzyme
urease, which catalyzes the hydrolysis of urea into ammonia and carbon dioxide. Some of
these organisms include Staphylococcus saprophyticus, Klebsiella pneumonia, and Proteus
species.
• Presence of ≥105 colony forming units (CFU) of bacteria per milliliter of urine.
Approximately one-third to one-half of young women with symptomatic lower urinary
tract infections have less than 105 CFU/ml of urine. Thus, the presence of ≥102 CFU/ml
should be considered in the context of the patient characteristics and the signs and
symptoms.
Urine Culture
A urine culture must always be interpreted in the context of a urinalysis and patient
symptoms.
A urine culture is not required for the treatment of women with symptomatic cystitis unless the
patient has recurrent urinary tract infections, is immunocompromised, or has other co-morbid
complications. A urine culture is always warranted for the evaluation of men presenting with
symptoms of cystitis.
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Asymptomatic patients with positive urine cultures have either asymptomatic bacteriuria or a
contaminated urine specimen. Typically, catheterized patients will become colonized within
48 hours of catheterization. Asymptomatic bacteriuria is generally not treated, with two
important exceptions: pregnant women and patients scheduled for genitourinary surgical
procedures
Respiratory Cultures
• Lower Respiratory Tract: Appropriate specimens for use in identifying pathogens that
cause disease of the lower respiratory tract (tracheitis, bronchitis, pneumonia, lung abscess,
and empyema) include expectorated and induced sputum, endotracheal tube aspirations,
bronchial brushings, washes or alveolar lavages collected during bronchoscopy, and pleural
fluid.
• Upper Respiratory Tract: Appropriate specimens for use in identifying pathogens that
cause upper respiratory tract infections include samples from the nasopharynx, throat, oral
ulcerations, and inflammatory material from the nasal sinuses.
All specimens should be stored under refrigeration until delivered to the laboratory (to inhibit
growth of normal flora). Neisseria gonorrhea is particularly susceptible to dehydration, so
swabs must be inoculated directly to plate media or put into an appropriate transport medium.
Rapid antigen detection (RADT) tests for GAS can be utilized to direct treatment of pharyngitis.
If an RADT test is utilized, ensure that the test is a CLIA waived variety. RADT tests should only
be performed under structured waived testing programs, and each site must have their own CLIA
waiver.
6. Therapy Selection
When selecting therapy, providers should consider: the severity and acuity of the disease, host
factors, factors related to the medications used, and the necessity for multiple agents. Depending
on severity and acuity, therapy is often begun empirically—directed at organisms that are
frequently known to cause the infection in question.
When selecting empiric antibiotic therapy, it is necessary to select an antimicrobial with the
following characteristics:
• Spectrum is broad enough to target organisms that are reasonably suspected of causing the
infection, yet narrowed to cover only the suspected families of organisms.
Example: If a patient is suspected of having an infection caused by a gram-positive organism,
empiric therapy should be selected for gram-positive organisms. The therapy should not
cover both gram-positive and gram-negative organisms.
• Least potential for adverse effects
• Greatest ease of administration
• Most cost-effective
Local susceptibility data should always be considered to direct and narrow the therapy. If/when
a particular pathogen is isolated as the causative pathogen of the infection, the antibiotic should
be switched to the most narrow-spectrum antibiotic that has activity against that pathogen, as
defined by the criteria listed above.
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Specific Diagnoses
Upper Respiratory Infections (URIs) – Not Otherwise Specified
Antibiotic treatment of nonspecific upper respiratory infections in adults does not enhance
illness resolution nor prevent complications, and is therefore not recommended.
Purulent secretions in the nares and throat (commonly reported and seen in patients with an
uncomplicated, upper respiratory tract infection) neither predict bacterial infection nor benefit
from antibiotic treatment.
Rhinosinusitis
Most cases of acute rhinosinusitis are viral in nature and therefore antibiotic treatment is not
indicated. Symptomatic treatment and reassurance is the preferred, initial management
strategy for these patients.
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Acute Pharyngitis
Since antibiotic therapy is only beneficial in the 5–15% of pharyngitis cases with GAS infection,
antibiotic prescriptions should be limited to those patients who have confirmed acute GAS
pharyngitis. The preferred antibiotic for treatment of acute GAS pharyngitis is penicillin or
amoxicillin, with sufficient treatment duration to eradicate infection (usually 10 days). First-
generation cephalosporins are preferred for penicillin-allergic patients whose allergy is not
associated with anaphylaxis. Clindamycin or clarithromycin for 10 days, or azithromycin for 5
days, is recommended in penicillin-allergic patients with anaphylaxis.
See the algorithm in Appendix 1, Treatment of Pharyngitis.
All patients with pharyngitis should be offered, or be referred to the commissary for, appropriate
doses of analgesics, antipyretics, and other supportive care, in accordance with the BOP National
Formulary Part I, Over the Counter Prescribing Criteria Matrix.
Bronchitis
Routine antibiotic treatment of uncomplicated bronchitis is not recommended, regardless of
duration of the cough.
In the unusual circumstance when pertussis infection is suspected, consult the current CDC
guidelines. Patient satisfaction with the care for acute bronchitis is largely reliant on provider-
patient communication, rather than on the use or non-use of antibiotics.
Pneumonia
Pneumonia treatment is divided into several basic types:
• Community-acquired pneumonia (CAP).
See the algorithm in Appendix 2, Treatment of Community Acquired Pneumonia.
• Hospital-acquired pneumonia (HAP). Occurs at least 48 hours or more after admission,
but was not incubating at the time of admission. HAP patients who are intubated should be
managed in the same way as those with ventilator-associated pneumonia.
• Ventilator-associated pneumonia (VAP). Refers to pneumonia that arises more than 48–72
hours after endotracheal intubation.
• Healthcare-associated pneumonia (HCAP). Includes any patient who was hospitalized in
an acute care hospital for two or more days within 90 days of the infection; who resided in a
nursing home or long-term care facility; who received recent intravenous antibiotic therapy,
chemotherapy, or wound care within 30 days of the current infection; or who attended a
hospital or hemodialysis clinic.
The initial treatment of HAP, VAP, and HCAP is consolidated within this guidance—with the
assumption that providers will narrow therapy, based on local bacteriologic variability and
culture and sensitivity reports.
See the algorithm in Appendix 3, Treatment of Hospital, Ventilator, and Healthcare
Pneumonia.
See also Appendix 4, Antibiotics Used in the Treatment of Pneumonia.
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Immunocompromised
Special attention is warranted in patients with suboptimal immune defenses, including:
• Patients without a spleen
• HIV infection
• Patients with cancer or those undergoing therapy for cancer
• Dialysis patients
• Those undergoing stem cell or organ transplantation
• Those with congenital immunodeficiency
• Immunosuppressive medications (e.g., chronic steroid therapy)
Patients who have undergone splenectomy have a reduced ability to fight infections caused by
encapsulated organisms (e.g., S. pneumoniae). Appropriate antimicrobial therapy and close
follow-up may be appropriate because a simple URI may quickly progress to a systemic illness
in immunocompromised patients. Although the threshold for hospitalization is lowered for these
patients, their risks of nosocomial infections must be weighed against the benefits of close
monitoring in the inpatient setting.
Osteomyelitis
Osteomyelitis is an infection of the bone, and can be divided into three major categories based on
the source of the infection. Infections can be hematogenous, contiguous, or related to a diabetic
ulcer or vascular insufficiency.
• Hematogenous infections originate in the blood and usually affect the long bones. They are
more common in children <16 years old, males, and IV drug users. Risk factors include
prematurity, respiratory distress syndrome, puncture wounds, and sickle cell disease.
Common pathogens include S. aureus, Streptococci species, Salmonella in sickle cell
patients, and Pseudomonas following nail puncture injury.
• Contiguous osteomyelitis infections occur when the organisms spread directly from a
localized area, such as surgery or bone injury. Common pathogens include various
Staphylococci and gram-negative rods (including Pseudomonas).
• Osteomyelitis associated with diabetic ulcers or vascular insufficiency could be
considered a subcategory of contiguous osteomyelitis. Usual pathogens include anaerobes,
Staphylococci, Streptococci species, and gram-negative rods. These infections are almost
always polymicrobial in nature.
Antibiotic treatment of osteomyelitis is usually 4–6 weeks in duration, and surgery often plays an
important role in the treatment.
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Cellulitis
Non-Purulent Cellulitis Infections – Methicillin-Sensitive Staphylococcus aureus (MSSA)
Non-purulent cellulitis infections—at institutions that have surveillance cultures indicating
that a Methicillin-Resistant Staphylococcus aureus (MRSA) infection is unlikely—can be
managed with empiric therapy, as follows:
• Dicloxacillin 500 mg po q6h
• Cephalexin 500 mg po q6h
• Clindamycin 300–450 mg po q6-8h
• Cefazolin 1–2 g IV q8h
• Oxacillin or nafcillin 2 g IV q4h
• Clindamycin 600–900 mg IV q8h
Follow-up after starting empiric therapy should be done after 48–72 hours to assess for
clinical improvement. If there is no improvement, resistance or an alternative diagnosis
should be considered. If there is clinical improvement, treatment should be continued for
5–10 days.
Moderate: Moderate cellulitis extends > 2 cm around a diabetic ulcer, and usually affects
deeper tissues. Coverage for these infections begins to cover gram-negative rods and
anaerobes. Treatment for moderate cellulitis includes:
• SMX-TMP DS 2 tabs po q12h and amoxicillin-clavulanate 875/125mg po q12h
• Clindamycin 300-450 mg po q 6-8h and
► Ciprofloxacin 750 mg po q12h or
► Levofloxacin 750 mg po q24h or
► Moxifloxacin 400 mg po q24h
Severe: Cellulitis associated with signs of systemic toxicity is considered severe cellulitis.
Usual treatment is with IV vancomycin, in addition to another agent (refer to Appendix 7 for
specific dosing guidance). The second agent should include imipenem 500 mg IV q6h,
ertapenum 1 g IV daily, or meropenem 1 g IV q8h if the organism is suspected to be an
Extended Spectrum Beta-Lactamase producer.
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Acne
Acne is a very common condition, affecting 45 million people in the United States, and carries a
lifetime prevalence of 85%. In the BOP, treatment of acne is classified as “Limited Medical
Value.” Treatment of conditions in this category is usually excluded from the scope of services
provided. Patients who have cystic acne and who show evidence of, or are at high risk for,
permanent scarring may be considered for treatment on a case by case basis. All other patients
should be referred to the commissary to purchase appropriate over-the-counter products.
While scarring can be a common clinical manifestation of acne, permanent scarring is
characterized by either excessive tissue formation (hypertrophic scars and keloids) or atrophic
scars, both of which can be brought about by dermal damage and the longstanding presence of
cysts.
Patients who are candidates for acne treatment (have evidence of, or are at high risk for
permanent scarring) should be reviewed by the Institution Utilization Review Committee prior to
the initiation of therapy.
Oral antibiotic therapy should be limited to 12–18 weeks when medically indicated.
Antibiotics used to treat acne can contribute to the development of antibiotic resistance.
Dental Prophylaxis
Infective Endocarditis
Currently, the American Dental Association (ADA) and the American Heart Association
(AHA) recommend the use of preventive antibiotics prior to dental procedures that involve
manipulation of gingival tissue or the periapical region of the teeth, or perforation of the oral
mucosa, for patients with the following conditions:
• Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
• History of infective endocarditis
• Cardiac transplant that develops cardiac valvulopathy
(list of conditions continues on next page)
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The current prophylactic regimens for prevention of bacterial endocarditis are listed in
Table 3 below. All providers are encouraged to access the AHA and ADA websites for the
latest premedication recommendations, including the links found at:
http://www.gmda.org/resources/premedication/2007premed.htm.
Table 3. Dental Prophylaxis for Bacterial Endocarditis Prevention (Adult Patients Only)
Prophylactic Regimen
Scenario Route (Administer ONE of the following medications
30–60 minutes before the procedure.)
NOT Allergic Oral Amoxicillin 2 grams
to Penicillins or
Ampicillin IM* Ampicillin 2 grams
Cephalexin 2 grams
Oral Clindamycin 600 milligrams
Allergic to
Penicillins or Azithromycin or clarithromycin 500 milligrams
Ampicillin
Cefazolin or ceftriaxone** 1 gram
IM*
Clindamycin 600 milligrams
* IM = Intramuscular (use if patient is unable to take oral medication)
** Cephalosporins should not be used in a person with a history of anaphylaxis, angioedema, or urticaria
from using penicillins or ampicillin
Adapted from: Table 2 in Wilson W, Taubert KA, Gewitz M, et al. Prevention of infective endocarditis:
guidelines from the American Heart Association. JADA. 2008;139:3s–24s. Available at
http://jada.ada.org/content/139/suppl_1/3S.full.pdf
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The IV to PO conversion promotes many positive clinical outcomes, including: increased quality
of life, decreased risk of the adverse events associated with IV infusions, decreased
administration errors due to the ease of PO administration, and decreased risk of the secondary
infections related to IV catheters. Often times, if a patient is in an inpatient bed, conversion of
IV medications to PO can hasten their discharge.
In addition to the clinical advantages of switching patients from IV to PO routes, institutions can
realize several other benefits, including: decreased costs related to medications (PO formulations
are generally less expensive), decreased equipment and supply needs (PO does not require IV
sets/pumps), decreased laboratory monitoring, and decreased personnel time for preparation and
administration.
The ease of use, safety profile, and ability to achieve therapeutic concentrations makes the oral
formulation the ideal route of administration, whenever possible.
Antibiotics Antifungals/Antivirals
Azithromycin Ciprofloxacin Fluconazole
Cefuroxime Levofloxacin Itraconazole
Clindamycin Moxifloxacin Voriconazole
Doxycycline Metronidazole Acyclovir
Linezolid Sulfamethoxazole/Trimethoprim Gancyclovir
Note: This list is not exhaustive.
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(2) Clinical status must be improving: The clinical signs and symptoms of the condition for
which the antibiotic is being prescribed should be improving or resolving in patients before
being switched to PO therapy (see Table 7 below). The patient should be clinically stable,
and clinical deterioration should not be anticipated.
Table 7. Signs That Clinical Status is Improving
In patients with active infections, a febrile or maximum temperature < 100.4 F in past 24 hours,
White blood cell (WBC) count trending downward1,2,3.
In cases where GI bleeding was present, confirmed and documented stoppage of bleeding.
1
Normalization of WBC indicates the patient’s inflammatory response to the infection is waning.
2
If clinical status is improving, but leukocytosis remains, evaluate the patient’s medication profile for
other medications that may be causing an increase or sustained high WBC, such as steroids. In this
case, a safe conversion to PO therapy can still be made for patients who meet all other criteria for IV to
PO conversion.
3
Neutropenic patients (absolute WBC < 500 cell/mm 3) are usually excluded from IV to PO conversion,
although this varies between institutions.
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(3) The patient’s condition must not require IV therapy: Oral therapy can be used
effectively to treat many different infections; however, certain infections require IV therapy
due to the severity or location of the infection. These include:
• Infective endocarditis
• Bacterial meningitis
• Brain abscess
• Orbital cellulitis
• Other CNS infections
• Endophthalmitis
• Patients with numerous antibiotic allergies
Triazole Antifungals:
• Fluconazole has high bioavailability and is well-absorbed. It is not affected by food or
alteration in gastric pH.
• Itraconazole requires an acidic environment for absorption; therefore, antacids,
H2 antagonists, proton-pump inhibitors, and sucralfate can significantly decrease
itraconazole’s bioavailability. Manufacturer labeling provides directions for avoiding
absorption issues.
► Itraconazole solution is better absorbed on an empty stomach.
► Contrary to the solution, itraconazole capsules are better absorbed with food.
• Voriconazole is best absorbed if given 1 hour before or 1 hour after meals.
Both voriconazole and itraconazole IV solutions are contraindicated in renal dysfunction
due to possible toxic accumulation of cyclodextran, which is found in both of the IV
formulations.
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Vancomycin:
• IV use: For treatment of gram-positive bacterial infections
• PO use: The oral formulation is poorly absorbed and therefore should only be used to treat
Clostridium difficile colitis.
Do not use vancomycin in IV to PO conversion programs. The IV and PO formulations
have different indications.
Linezolid:
• Linezolid exhibits a weak, non-selective, reversible inhibition of monoamine oxidase
(MAO).
• Patients should avoid foods high in tyramine due to an increased risk of serotonin syndrome,
leading to a hypertensive emergency. Examples of foods high in tyramine include aged
cheeses; cured meats, such as sausage, pepperoni, or salami; soy sauce; and sauerkraut.
Improperly stored or spoiled food can also contain tyramine.
IV to PO Conversion Myths
There are many myths associated with IV to PO conversions. New information and studies have
disproved many of these myths, such as:
Myth: Infectious diseases need IV treatment. Convert to PO sparingly.
Truth: Newer antimicrobials are available with equivalent IV and oral bioavailability.
Literature has shown IV to PO conversion is efficacious, convenient, cost-effective, and
safe.
Myth: PO antimicrobial must be the same medication or in the same class as the IV
treatment.
Truth: PO needs to cover the same or similar spectrum of activity, have similar tissue
penetration, and be effective against the same isolated or suspected organism(s) as the
IV. It does not need to be the same medication or in the same class.
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9. Communication Strategies
Literature suggests that patient satisfaction is influenced more by communication, than by
whether or not the patient receives an antibiotic. The following strategies can be used to validate
a patient’s illness, and help justify not prescribing antibiotics when they are not clinically
indicated.
• Choosing terminology such as “viral bronchitis,” instead of referring to “just a virus” can
validate the patient’s symptoms. In addition, sharing normal findings of an exam, such as
clear lung sounds, reassures patients that the illness may not be as severe as they first thought
and helps them be more open to the idea of not receiving an antibiotic.
• Offering symptomatic relief is another important strategy. Many patients want an antibiotic
because they believe it will make them feel better. By suggesting effective symptomatic
therapies, providers can offer patients the relief they are seeking.
• Providers should discuss side effects of antibiotics, including adverse events and resistance,
and describe what to expect in the days after the initial evaluation. It is important for patients
to be aware of what to expect when symptoms change or become more severe, including
when it might be appropriate to return for re-evaluation and further treatment.
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For Physicians/Dentists/MLPs
• Ordering and interpreting culture and sensitivity reports
• Familiarity with BOP Clinical Practice Guidelines, Management of MRSA Infections
• Understanding and interpreting antibiograms
• Review of decision flowcharts (algorithms) for various infectious states
• Appropriate dosing of IV antibiotics
• Knowledge of formulary PO antibiotic agents
• Knowledge of formulary IV antibiotic agents
• Timeline for de-escalation of antibiotic therapy
• Awareness of Antibiotic Therapy Guideline Updates
• Understanding the principles of Antibiotic Stewardship
• Knowing the common side effects and adverse events associated with antimicrobials
For Nurses
• Understanding of C&S reports
• Understanding common IV antibiotic dosing frequencies and regimens
• Knowing the signs of improving clinical status that facilitate de-escalation
• Understand the timing of medication dosing and blood sample collection
• Knowing the signs/symptoms of common allergic reactions to frequently used medications
• Awareness of Antibiotic Therapy Guideline Updates
• Understanding the principles of Antibiotic Stewardship
• Knowing the common side effects and adverse events associated with antimicrobials
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Clinical Practice Guidelines March 2013
For Pharmacists
• Interpreting and utilizing C&S reports in evaluating appropriate antibiotic selection
• Understanding and interpreting antibiograms
• Understanding appropriate therapies/flowcharts (algorithms) for locally treatable conditions
• Calculating accurate dosage adjustments based on abnormal renal and liver function tests
• Therapeutic drug monitoring, to include appropriate frequency of lab value collection and
understanding of target values
• Appropriate IV to PO dose conversion, to include dose timing and frequency
• Familiarity with BOP Clinical Practice Guidelines, Management of MRSA Infections
• Awareness of Antibiotic Therapy Guideline Updates
• Understanding the Principles of Antibiotic Stewardship
• Knowledge of antibiotic pharmacokinetics
• Knowing the common side effects and adverse events associated with antimicrobials
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
Clinical Practice Guidelines March 2013
National Guidelines
Asymptomatic Bacteremia
Nicolle LE, Bradley S, Colgan R, et al. Infectious Diseases Society of America guidelines for the
diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis. 2005;40:643–654.
Available at: http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-
Patient_Care/PDF_Library/Asymptomatic%20Bacteriuria.pdf
Clostridium difficile
Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection
in adults: 2010 Update by the Society for Healthcare Epidemiology of America (SHEA) and the
Infectious Diseases Society of America (IDSA). Infect Control Hosp Epidemiol. 2010;31(5):431–455.
Available at: http://www.cdc.gov/HAI/pdfs/cdiff/Cohen-IDSA-SHEA-CDI-guidelines-2010.pdf
Pneumonia
Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-
associated pneumonia. Am J Respir Crit Care Med. 2005;171(4):388–416. Available at:
http://ajrccm.atsjournals.org/content/171/4/388.full. Accessed August 14, 2011.
Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American
Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.
Clin Infect Dis. 2007;44(Suppl 2):S27–72. Available at:
http://www.thoracic.org/statements/resources/mtpi/idsaats-cap.pdf. Accessed August 14, 2011.
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
Clinical Practice Guidelines March 2013
Osmon DR, Berbari EF, Berendt AR, et al. Diagnosis and management of prosthetic joint infection:
clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis.
2013;56(1):e1–25. Accessed at: http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-
Patient_Care/PDF_Library/IDSA%20PJI%20Guideline%20CID%2012%202012.pdf
Vancomycin
Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a
consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society
of America, and the Society of Infectious Diseases Pharmacists. American Journal of Health-System
Pharmacy. 2009;66(1):82–98. Available at: http://www.ajhp.org/content/66/1/82.full
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
Clinical Practice Guidelines March 2013
References
American Dental Association and American Academy of Orthopaedic Surgeons. Antibiotic
prophylaxis for dental patients with total joint replacements. JADA. 2003;134:895–899.
Available at http://jada.ada.org/content/134/7/895.full.pdf+html
Antibiotic Prophylaxis for Patients after Total Joint Replacement: Information Statement from
the American Academy of Orthopaedic Surgeons, 2009. Available at:
http://orthodoc.aaos.org/davidgrimmmd/Antibiotic%20Prophylaxis%20for%20Patients%20after
%20Total%20Joint%20Replacement.pdf. Accessed November 27, 2012.
Armbrust, A, Capraro GA, Fey PD, et al. Antimicrobial and Clinical Microbiology Guidebook.
2nd ed. Omaha, NE: Nebraska Medical Center; 2010. Available at:
http://www.nebraskamed.com/careers/education-programs/asp. Accessed September 15, 2011.
Baddour LM. Cellulitis and erysipelas. In: Sexton DJ, Kaplan SL, eds. UpToDate. Waltham,
MA: UpToDate; 2008. Available at: http://www.uptodate.com/contents/cellulitis-and-erysipelas
Centers for Disease Control and Prevention. Get smart: know when antibiotics work. CDC Web
site. Available at: http://www.cdc.gov/getsmart/antibiotic-use/fast-facts.html. Accessed
September 14, 2011.
Gilbert DN, Moellering RC Jr , Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial
Therapy, 40th ed. Sperryville, VA; 2010.
Hall-Flavin, DK. Depression (Major Depression): MAOIs and Diet. Mayo Clinic Web site.
Available at: http://www.mayoclinic.com/health/maois/HQ01575. Accessed February 9, 2011.
Kelly CP, LaMont JT. Treatment of Clostridium difficile infection in adults. In: Calderwood
SB, ed. UpToDate. Waltham, MA: UpToDate; 2012. Available at
http://www.uptodate.com/contents/treatment-of-clostridium-difficile-infection-in-adults
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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References (continued)
Kuti JL, Le TN, Nightingale CH, Nicolau DP, R Quintiliani. Pharmacoeconomics of a
pharmacist-managed program for automatically converting levofloxacin route from IV to oral.
Am J Health Sys Pharm. 2002;59:2209–2215. Available at:
http://www.ajhp.org/content/59/22/2209.full.pdf+html
Lacy CF, Armstrong LL, Goldman MP, et al., eds. Drug Information Handbook, 15th ed.
Hudson, OH: Lexi-Comp; 2007.
Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections.
Clin Infect Dis. 2004;39:885–910.
Murdaugh LB. Competence Assessment Tools for Health-System Pharmacies. 4th ed. Bethesda,
MD: American Society of Health-System Pharmacists, Inc.; 2008.
Rehm SJ, Sekeres JK, Neuner E, et al. Guidelines for antimicrobial usage, index of tables.
Cleveland Clinic Continuing Medical Education (CME). Cleveland Clinic Center for Continuing
Education; 2009. Available at:
http://www.clevelandclinicmeded.com/medicalpubs/antimicrobial-guidelines
Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management
of group A streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin
Infect Dis. 2012;55(10):e86–e102. Available at:
http://cid.oxfordjournals.org/content/55/10/e86.full.pdf+html
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References (continued)
Weintrob AC, Sexton DJ. Overview of diabetic infections of the lower extremities.
In: Sexton DJ, ed. UpToDate. Waltham, MA: UpToDate; 2008. Available at:
http://www.uptodate.com/contents/overview-of-diabetic-infections-of-the-lower-extremities
Weller, PF. Vancomycin hypersensitivity. In: Adkinson NF Jr, ed. UpToDate. Waltham, MA:
UpToDate; 2011. Available at: http://www.uptodate.com/contents/vancomycin-hypersensitivity.
Wynn RL, Meiller TF, Crossley HL. Drug Information Handbook for Dentistry, 17th ed.
Hudson, OH: Lexi-Comp, Inc.; 2011:1914–1915.
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
Clinical Practice Guidelines March 2013
Clinical Features
Clinically screen all patients suspected of pharyngitis for epidemiologic and clinical
features suggestive of group A streptococcal (GAS) and viral pharyngitis.
References:
Shulman ST, Bisno AL, Clegg HW, et al. Clinical practice guideline for the diagnosis and management of group A
streptococcal pharyngitis: 2012 update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86–e102.
Available at: http://cid.oxfordjournals.org/content/55/10/e86.full.pdf+html
Pichichero M. Treatment and prevention of streptococcal tonsilliopharyngitis. In: Sexton DJ, Edwards MS, eds. UpToDate,
2010. Available at: http://www.uptodate.com/contents/treatment-and-prevention-of-streptococcal-tonsillopharyngitis
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Labs: CXR, ABG/O2Sat, blood culture x 2, sputum cultures, gram stain (prior to antibiotic tx)
Pathogen identified: Initiate therapy based on C & S.
Pathogen not known: Start empiric therapy and streamline once C&S data available. Likely pathogens
include Pneumococcus, Mycoplasma, Legionella, Chlamydia pneumonia, H. influenza, viruses.
No organism isolated in 40–60% of cases.
CURB-65 score: 0–1 (mild) CURB-65 score: 0–2 (moderate) CURB-65 score: > 3
Consider outpatient care. Consider inpatient management Consider ICU.
(non-ICU).
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Labs: CXR, ABG/O2Sat, blood culture x 2, sputum cultures, gram stain (prior to antibiotic tx)
YES NO
Ceftriaxone
TMP-SMX
For patients with severe penicillin For patients with severe kidney
allergy, consider substituting disease, kidney transplant, or
aztreonam/levofloxacin for concurrent nephrotoxic therapy,
piperacillin-tazobactam. substitute levofloxacin for
aminoglycoside.
Notes:
1
Early onset (<5 days): Pathogens include S. pneumoniae, H. influenza, gram-negative bacilli (E. coli, Enterobacter,
Serratia, Klebsiella), MSSA, Legionella.
2
Late onset (≥5 days): Pathogens include Pseudomonas, MRSA, resistant gram-negative bacilli, Acinetobacter (use
amikacin in combination).
3
If rare gentamicin resistance occurs, substitute with tobramycin and then amikacin.
4
Consider linezolid for confirmed MRSA resistant to vancomycin.
Immunocompromised patients, e.g. HIV, transplant; patients who are recipients of steroids (>15mg of prednisone qd) or
other immunosuppressants may have pneumonia due to PCP, CMV, Aspergillus, Nocardia, etc.
Treatment duration is usually 7–14 days, but if no improvement or slow response, further treatment may be required.
Anaerobic pleuropulmonary infections may require 6 weeks of therapy.
For aspiration pneumonia, consider ampicillin-sulbactam + clindamycin.
For extended-spectrum beta-lactamases (ESBL) positive pathogens, consider imipenem-cilastin.
Reference:
Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
Am J Respir Crit Care Med. 2005;171(4):388–416. Available at: http://ajrccm.atsjournals.org/content/171/4/388.full.
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Aminoglycosides :
1 care facility
Gentamicin/ tobramycin Home infusion therapy (including
5-7 mg/kg IV per day (once daily dosing) antibiotics)
1-1.7 mg/kg q 8 hours (conventional dosing)
Chronic dialysis within 30 days
Amikacin
Home wound care
15-18 mg/kg IV per day (once daily dosing)
5–7.5 mg/kg IV q 8–12 hours (conventional dosing) Family member with multidrug-resistant
pathogen
Antipseudomonal quinolones:
Levofloxacin 500–750 mg IV/PO q day Immunosuppressive disease and/or therapy
Ciprofloxacin 250–750 mg q 12 hours suggesting a variable outcome impact,
according to the severity
MRSA Agents:
2
Vancomycin 1 gm IV q 12 hours
Linezolid 600 mg IV/PO q 12 hours
Miscellaneous:
Aztreonam 1–2 gm IV/IM q 8–12 hours
Azithromycin 500 mg IV/PO q day
Amoxicillin 500–875 mg PO q 12 hours
Doxycycline 100 mg PO/IV q 12 hours
SMX-TMP 1–2 DS tablets q 12 hours
References:
Gilbert DN, Moellering RC Jr , Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial Therapy, 40th ed. Sperryville,
VA; 2010.
Martin C, Hoven A. University Guide to Empiric Antimicrobial Therapy. Lexington, KY: University of Kentucky; 2004. Available at:
http://www.hosp.uky.edu/pharmacy/formulary/criteria/UK_Antimicrobial_Manual.pdf
Rehm SJ, Sekeres JK, Neuner E, et al. Guidelines for antimicrobial usage, index of tables. Cleveland Clinic Continuing Medical
Education (CME). Cleveland Clinic Center for Continuing Education, 2009. Available at:
http://www.clevelandclinicmeded.com/medicalpubs/antimicrobial-guidelines
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Labs: Bone biopsy and pus sample for gram stain and cultures (before antibiotic tx),
CBC, ESR, blood culture in acute cases, X-ray/MRI/bone scan if indicated
Notes:
1
Usual pathogens include S. aureus, Streptococci species, Salmonella in sickle cell patients, Pseudomonas
following nail puncture injury.
2
Usual pathogens include various forms of Staphylococci, gram-negative rods (including Pseudomonas).
3
Usually polymicrobial, including anaerobes, Staphylococci, Streptococci species, GNR.
Therapy should start with IV therapy. Conversion to oral antibiotics can be considered if the patient has a
confirmed case of osteomyelitis, the organism is identified, antibiotic susceptibility determined, oral agent(s)
with good bioavailability is selected, and the patient demonstrates good compliance.
References:
Gilbert DN, Moellering RC Jr , Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial Therapy, 40th ed. Sperryville,
VA; 2010.
Martin C, Hoven A. University Guide to Empiric Antimicrobial Therapy. Lexington, KY: University of Kentucky; 2004. Available
at: http://www.hosp.uky.edu/pharmacy/formulary/criteria/UK_Antimicrobial_Manual.pdf
Rehm SJ, Sekeres JK, Neuner E, et al. Guidelines for antimicrobial usage, index of tables. Cleveland Clinic Continuing
Medical Education (CME). Cleveland Clinic Center for Continuing Education, 2009. Available at:
http://www.clevelandclinicmeded.com/medicalpubs/antimicrobial-guidelines
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Risk Factors for MRSA: Incarceration, IV drug use, HIV, sharing sporting
equipment, recent antibiotic use, hemodialysis, recent hospitalization
Culture blood/pus (prior to antibiotic tx): If patient has systemic toxicity, extensive skin
1
involvement, underlying comorbidities , animal/ human bite, or recurrent/persistent cellulitis
If NO: If YES:
Change therapy, Continue therapy for 7–14 days for mild to
based on C&S. moderate infections, and 2–4 weeks for severe.
Notes:
Dosages assume normal renal/hepatic function.
Usual pathogens: Staphylococci & beta hemolytic Streptococci. For diabetic ulcers, may include gram-negative bacilli & anaerobes.
1
Comorbidities: diabetes, lymphedema, malignancy, neutropenia, immunodeficiency, splenectomy
2 nd
If known clindamycin resistance is high, consider adding 2 agent.
3
If mild infections are unresponsive to therapy, change to moderate treatment to cover gram-negative bacilli and anaerobes.
References:
Baddour LM. Cellulitis and erysipelas. In: Sexton DJ, Kaplan SL, eds. UpToDate. Waltham, MA: UpToDate; 2008.
Gilbert DN, Moellering RC Jr, Eliopoulos GM, et al, eds. The Sanford Guide to Antimicrobial Therapy, 40th ed. Sperryville, VA; 2010.
Lipsky BA, Berendt AR, Deery HG, et al. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2004;39:885–910.
Weintrob AC, Sexton DJ. Overview of diabetic infections of the lower extremities. In: Sexton DJ, ed. UpToDate. Waltham, MA: UpToDate; 2008.
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Studies have shown that the strongest predictor of vancomycin nephrotoxicity is the concomitant
use of nephrotoxins. There are limited data suggesting a direct causal relationship with specific
serum vancomycin concentrations. Therefore, routinely obtaining more than a single trough
concentration is NOT recommended for treatment courses less than 3 to 5 days, or for doses
targeting a trough below 15 µg/mL.
Trough levels should be obtained just prior to the fourth dose, so that the drug has adequate time
to reach steady state concentration. Once the trough is drawn—unless the results are
immediately known and a provider is available to review and make necessary dosing
adjustments—the scheduled dose should be given without delay.
The chart on the following page, “IDSA Vancomycin Drug Monitoring Summary,” contains
some of the current recommendations for monitoring vancomycin therapy.
Note: “Red Man Syndrome” (RMS) is a reaction that has been associated with the infusion rate
of vancomycin. RMS differs from an allergic reaction in that it is not mediated by drug-
specific antibodies and it can occur as early as the first dose. To prevent RMS, infusion
rates of vancomycin should be given at no higher than 10 mg/min. Patients who have
experienced RMS may continue to receive vancomycin; however, the rate of infusion
must be decreased.
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Federal Bureau of Prisons Antimicrobial Stewardship Guidance
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Frequency of monitoring Frequent monitoring (more than one trough before the fourth dose) for
short courses or for uncomplicated infections is not recommended.
All patients on prolonged courses of vancomycin should have at least
one steady-state trough concentration obtained no earlier than at
steady state (just before the 4th dose) and repeated as clinically
appropriate.
Once-weekly monitoring is recommended for hemodynamically stable
patients on long-term therapy.
More frequent or daily trough monitoring is advisable in patients who
are hemodynamically unstable.
Optimal trough concentration for Minimum trough concentrations should always be maintained
uncomplicated infections above 10 µg/mL to avoid development of resistance.
Optimal trough concentration for Trough concentrations of 15–20 µg/mL are recommended to improve
complicated infections penetration, increase the probability of obtaining optimal target serum
(bacteremia, endocarditis, concentrations, and improve clinical outcomes.
osteomyelitis, meningitis,
hospital-acquired pneumonia
caused by S. aureus)
Dosing
Dosing to achieve optimal trough Doses of 15–20 mg/kg (ABW) given every 8–12 hr are recommended
concentrations for most patients with normal renal function to achieve the suggested
serum concentrations, with adjustments as necessary after the trough
is obtained.
Loading doses for complicated In seriously ill patients, a loading dose of 25–30 mg/kg (ABW) can be
infections used to facilitate rapid attainment of target trough concentrations
Adverse Events
36