REVIEW

Top Myths of Diagnosis and Management of

Infectious Diseases in Hospital Medicine
Melissa D. Johnson, PharmD, MHS, Angelina P. Davis, PharmD, MS, April P. Dyer, PharmD, MBA, MSCR,
Travis M. Jones, PharmD, S. Shaefer Spires, MD, Elizabeth Dodds Ashley, PharmD, MHS
Duke Antimicrobial Stewardship Outreach Network (DASON), Duke University Medical Center, Durham, NC.

ABSTRACT

Antimicrobial agents are among the most frequently prescribed medications during hospitalization. How-
ever, approximately 30% to 50% or more of inpatient antimicrobial use is unnecessary or suboptimal.
Herein, we describe 10 common myths of diagnosis and management that often occur in the hospital set-
ting. Further, we discuss supporting data to dispel each of these myths. This analysis will provide hospital-
ists and other clinicians with a foundation for rational decision-making about antimicrobial use and
support antimicrobial stewardship efforts at both the patient and institutional levels.
Ó 2022 Elsevier Inc. All rights reserved.  The American Journal of Medicine (2022) 135:828−835

KEYWORDS: Antibacterial agents; Antibiotics; Antimicrobial stewardship; Decision-making; Drug-related side

effects and adverse reactions; Fluoroquinolones; Hospitalists; Hypersensitivity; Inpatients; Penicillins; Urinary tract
infections

INTRODUCTION patients at hospital discharge despite having no clinical

Antimicrobial agents are among the most frequently pre- indication, an inappropriate spectrum of activity, incorrect
scribed medications during hospitalization. However, dose, or unnecessarily long duration.3-5
approximately 30% to 50% or more of inpatient antimicro- As infectious diseases clinicians and consultants in aca-
bial use is unnecessary or suboptimal.1,2 In addition, antibi- demic and community hospitals, we are uniquely positioned
otics are continued for common infections in a majority of to observe common areas of need for the optimization of
antimicrobial agents. In this paper we review 10 common
myths of infectious diseases diagnosis and management in
Funding: This work was not funded by any commercial entity. adults. Further, we discuss supporting data to dispel each of
Conflicts of Interest: The authors declare that they have no known
these myths. This analysis will provide hospitalists and other
competing financial interests or personal relationships that could have
appeared to influence the work reported in this paper. APD, TMJ, and SSS clinicians with a foundation for rational decision-making
have no conflicts to disclose. APD has received consulting fees from about antimicrobial use and support antimicrobial steward-
Merck. EDA has received personal fees from Joint Commission Resour- ship efforts at both the patient and institutional levels.
ces, Belmont University, and Making a Difference-Infections Diseases,
author royalties from UpToDate, and research grants to her institution
from the Centers for Disease Control and Prevention, and consulting fees Myth 1: Antibiotics Do No Harm
from University of Maryland, University of Chicago, American College of Tackling antibiotic overuse and misuse requires an under-
Clinical Pharmacy, Hospital Association of New York State, and Sarah standing of factors that drive prescriber decisions to use
Moreland Russell Consulting. MDJ has received consulting fees from antibiotics. One of these is the perception that many antibi-
Astellas, Cidara, Merck, Entasis, Paratek, Pfizer, and Theratechnologies,
author royalties from UpToDate, and research grants to her institution
otics carry some potential benefit, but a very low risk of
from Astellas, Scynexis, Charles River Laboratories, and Merck & Co, harm for the individual patient they are treating. In fact, this
outside the submitted work. perceived lack of risk can explain some prescriber variabil-
Authorship: All authors had access to the data and a role in writing ity in antibiotic use; prescribers in an Emergency Depart-
this manuscript. ment setting were 28% more likely to prescribe antibiotics
Requests for reprints should be addressed to Melissa Johnson, PharmD,
MHS, Department of Medicine, Duke University Medical Center, Box
when treatment decisions were framed on an assumption
102359, Durham, NC 27710. that antibiotic therapy is harmless compared with prescrib-
E-mail address: [email protected] ers who perceived that antibiotics may be harmful.6

0002-9343/© 2022 Elsevier Inc. All rights reserved.

https://doi.org/10.1016/j.amjmed.2022.03.019
Johnson et al Top Myths of Infectious Diseases 829

Strategies to dispel this myth may be more successful by risk of developing antimicrobial resistance, and increased
increasing focus on more immediate and individual risks. use of health care resources/costs.
These include the fact that antibiotics are the second most Short therapy durations have not been established for
common cause of adverse drug event-related Emergency all infection types (eg, tuberculosis, meningitis, prosthetic
Department visits.7 Similar results have been found in hos- joint infections, Staphylococcus aureus/Staphylococcus
pitalized patients, with 20% suffering at least one antibi- lugdunensis bacteremia, endocarditis, deeply invasive fun-
otic-related adverse drug event within 90 days of antibiotic gal infections).17 Special consideration should be given to
use, 97% of which resulted in added antibiotic durations in patients with
hospital days, clinic visits, or labo- CLINICAL SIGNIFICANCE deep-seated infections, compro-
ratory testing.8 mised immune systems, and com-
Antibiotic prescriptions increase  At least 30%-50% of inpatient antimi- plicating factors. Patients who do
the risk that an individual patient crobial use has been shown to be not experience resolution of symp-
will develop a subsequent infection. unnecessary or suboptimal. toms should be evaluated and
This may be Clostridioides difficile  Antibiotic overuse is a pervasive prob- treated for new or worsening infec-
infection (CDI) or an infection due lem that contributes to antimicrobial tion.
to antibiotic-resistant bacteria. Each resistance. According to the World
day of antibiotic therapy increases
Health Organization, antibiotic pre- Myth 3: If One Drug is Good,
individual risk of CDI by 9%.9 Sim-
scribing increased in 35 of 56 countries 2 (or More!) Must Be Better
ilarly, in many disease states,
receipt of antibiotics within the pre- during the COVID pandemic. Using multiple antibiotics in combi-
vious 30 to 90 days is one of the  There are several commonly held myths nation is a longstanding practice
strongest independent risk factors in infectious diseases diagnosis and and offers several potential advan-
of multi-drug-resistant infection. 10- management that need to be dispelled. tages, including broadened spec-
13
Published data provide support for evi- trum of activity when resistant or
dence-based decision-making and polymicrobial infections are sus-
Myth 2: Antibiotic rational antibiotic use regarding these pected, potential synergy between
clinical scenarios that are frequently agents, and preventing emerging
Durations of 7, 14, 21 Days resistance. 18
Combination antibiotic
encountered in hospital medicine.
are Typically Necessary use is common in US hospitals, but
Antibiotic duration of 7, 14, 21 days when done unnecessarily, this prac-
are commonly ordered by prescribers despite evidence that tice contributes to excessive antibi-
many common infections can be treated with shorter otic use and cost. A large study suggested that 78% of acute
courses. There are several misconceptions that may lead to care hospitals had evidence of potentially inappropriate
this prescribing: concerns over infection relapse, belief that redundant antibiotic combinations; reducing redundancy
antibiotic resistance can be prevented by treating beyond resulted in a total potential cost avoidance of more than
symptom resolution, and belief that longer antibiotic »$50 million annually for US hospitals.19
courses are more effective. The relapse myth was prompted Some antibiotic combinations are considered so redun-
by an early pneumonia case series indicating that penicillin dant that concomitant use is nearly never warranted. Pri-
durations for pneumonia should continue past symptom res- mary examples of this are combination beta-lactam therapy
olution due to increased relapses in patients who received and regimens that provide duplicative coverage for anaero-
short-course therapies. However, a re-evaluation of the data bic pathogens. There are a limited number of exceptions
disproved this theory when it determined that patients had when these combinations may be warranted. In the case of
new infections with different bacterial serotypes, rather dual anti-anaerobic therapy, this includes treatment of nec-
than relapses.14 Despite studies in pneumonia demonstrat- rotizing fasciitis, CDI, and select biliary tract infections.20
ing that longer antibiotic courses lead to the emergence of Specific beta-lactam combinations that are exceptions to
resistance,15,16 patients have long been instructed to finish this rule include ceftriaxone plus ampicillin for enterococ-
antibiotic courses to prevent resistance, even if they feel cal endocarditis, as well as ampicillin in addition to a ceph-
better sooner. Clinical trials have shown that short-course alosporin when Listeria monocytogenes is suspected, such
therapies for a variety of infections are equivalent to longer as in select patients with meningitis.21,22
durations: 3-5 days of therapy (DOT) for community- More controversial, however, is the practice of double
acquired pneumonia; ≤8 DOT, nosocomial pneumonia; 5-7 coverage for gram-negative pathogens, a common practice
DOT, pyelonephritis; 4 DOT, intra-abdominal infection; that is endorsed in many empiric treatment guidelines.23,24
≤5 DOT, acute exacerbation of chronic obstructive pulmo- This practice is not based on evidence that 2 agents increase
nary disease; 5 DOT, acute bacterial sinusitis; 5-6 DOT, activity or improve clinical outcomes; rather, the evidence
cellulitis.17 As mentioned above, excessive antimicrobial that best supports this practice is that it increases the likeli-
durations have serious implications for patient outcomes, hood that at least one agent will cover the causative patho-
including increased risk of adverse effects (including CDI), gen.25 Therefore, when multiple agents are used to target
830 The American Journal of Medicine, Vol 135, No 7, July 2022

gram-negative pathogens, it is imperative that de-escalation with oral step-down prior to day 3 and low-dose oral step-
occurs once pathogen identification and susceptibility are down therapy in streptococcal bacteremia, which may sig-
known. nal the importance of timing of step-down and optimal dos-
Combination therapy for methicillin-resistant S. aureus ing in the successful oral management of severe infection.
(MRSA) infections has gained recent attention due to per- Although the optimal time to step-down therapy has not
sistent poor outcomes in patients with invasive MRSA been clearly defined, successful step-down therapy has
infections. The most recent addition to this body of litera- been achieved as early as day 3 of IV therapy. Commonly
ture, the CAMERA-2 randomized clinical trial, failed to cited key considerations for IV to oral conversion include:
show a benefit in patients with MRSA bacteremia given clinical stability, absence of fever, and resolving leukocyto-
standard therapy (vancomycin or daptomycin) vs combina- sis. Administration via the IV route is still recommended
tion therapy (anti-staphylococcal beta-lactam plus vanco- for infections where drug levels at the site of infection may
mycin or daptomycin).26 Importantly, acute kidney injury be limited, or the host response is severely compromised
was reported more often and with a higher degree of sever- (ie, meningitis, high-risk neutropenia).
ity compared with mono-therapy regimens, mimicking data
from other combination trials for MRSA infections.27 At Myth 5: Bacteria in the Urine Signifies a UTI
present, duplicative anti-MRSA therapy does not have a
role in the routine treatment of these infections, although
and Should Be Treated; Related Myth: Cloudy or
this area remains one of active investigation. Smelly Urine Indicates Your Patient Has a UTI
Urinary tract infections (UTIs) are one of the most frequent
indications for antimicrobial use in hospitals and must be
Myth 4: Oral Antibiotics Are Not as Good as IV distinguished from their counterpart bacteriuria. Diagnosis
Antibiotics for Hospitalized Patients of UTI should be based on clinical signs/symptoms con-
The administration of intravenous (IV) antibiotics allows firmed by microscopy/culture rather than laboratory find-
for rapid attainment of peak drug levels for optimal treat- ings alone. Bacteria in the urine in the absence of
ment of serious infections. For this reason, IV antibiotics symptoms signifies asymptomatic bacteriuria (ASB) and
are often prescribed for hospitalized patients. However, should generally not be treated with antibiotics.35 Unneces-
routine use is not indicated solely based on hospital admis- sary treatment of ASB is common and increases the risk of
sion. Factors that should be considered when determining adverse events, the risk of drug-resistant organisms in
the preferred route of administration include the bioavail- health care institutions as well as the community, and health
ability of the oral agent, ability to swallow or absorb medi- care costs.36 Treatment of ASB in premenopausal, non-
cations via the oral route, severity of illness, clinical pregnant women does not decrease the frequency of symp-
stability, isolated pathogen, and site of infection.28 The use tomatic UTI or prevent subsequent episodes of ASB, and in
of oral antibiotics can have numerous benefits, including fact, treatment with antibiotics was associated with
promoting readiness for earlier discharge, reduced risk of increased risk of a future UTI.35
IV catheter infection and associated complications, cost, While the vast majority of patients with ASB do not
and workload.29 require treatment with antibiotics (Table),35,36 antibiotics
More recent clinical data show that some serious infec- may be indicated for pregnant women and patients undergo-
tions (ie, chronic osteomyelitis, infective endocarditis, bac- ing endoscopic urologic procedures associated with muco-
teremia from a urinary source) can be successfully sal trauma (such as transurethral resection of the
managed with a step-down to a highly bioavailable oral prostate).35-37
agent.30-32 Additionally, full oral antibiotic therapy has Urinalysis is overused as a diagnostic modality for UTIs
been successful in periprosthetic joint infections and strep- and is frequently performed in those without symptoms
tococcal bacteremia.33,34 Clinical failure has been observed localized to the urinary tract.38 Furthermore, the presence

Table Patient Groups with ASB Who Should Not/Should Be Screened or Treated with Antibiotics35,36
Patient Groups with ASB Who Should NOT Be Routinely Screened/ Patient Groups with ASB Who Should Be Screened/Treated
Prescribed Antibiotics
 Nonpregnant women  Pregnant women
 Women with diabetes mellitus  Patients undergoing select urologic procedures (endoscopic
 Elderly patients living in the community urologic procedures associated with mucosal trauma)
 Patients with spinal cord injury
 Patients with an indwelling catheter in place
 Renal transplant recipients >1 month post-transplant
 Non-renal solid organ transplant recipients
 Patients undergoing elective neurologic surgery

ASB = asymptomatic bacteriuria.

Johnson et al Top Myths of Infectious Diseases 831

of cloudy or foul-smelling urine alone is an unreliable indi- a non-beta-lactam in a patient with a penicillin allergy, it is
cator of UTI.39,40 Pyuria and bacteriuria are expected in critical to engage the patient/caregivers and ask thoughtful
patients with chronic indwelling urinary catheters and do questions about the symptom details, timing, and outcome of
not help distinguish between ASB and asymptomatic their allergic reaction and whether they have successfully tol-
UTI.35 It is important to be aware of common urinalysis erated another beta-lactam in the past. Many hospitals have
findings and possible interpretations.35,38,41 The use of developed and implemented penicillin-allergy de-labeling
more stringent urine testing algorithms and reporting may protocols incorporating allergy history assessment, penicillin
help reduce overprescribing of antibiotics for ASB.38,42 skin testing, or direct oral amoxicillin challenges with the
safe administration of beta-lactams to patients with a previ-
Myth 6: A History of a Penicillin Allergy Means ous penicillin allergy label.49,50
Importantly, patients with a history of delayed reactions
the Patient Can Never Receive a Beta-Lactam (symptoms >2 hours after drug administration) with organ
Antibiotic dysfunction (ie, hemolytic anemia, renal/hepatic failure),
Penicillin allergy is the most common drug allergy, delayed reactions with severe cutaneous manifestations, or
reported by 10% to 15% of hospitalized patients.43 Unfortu- serum sickness are not candidates for de-labeling or re-chal-
nately, patients with a history of penicillin allergy, regard- lenge (Figure 1).51
less of the reaction type, often receive broader-spectrum
antibiotics that may be more toxic and costly.44 In fact,
patients with a history of penicillin allergy have longer hos-
Myth 7: Antibiotics for Surgical Prophylaxis
pital stays, higher costs, and even higher mortality Should Typically Be Continued for at Least 24
rates.45,46 Several myths surrounding penicillin allergy exist Hours
and warrant discussion. A common misconception surrounding antibiotics for surgi-
First, the widely quoted cross-reactivity risk of 10% cal prophylaxis is that they should continue postoperatively
between penicillin and other beta-lactams is a fallacy. These for 24 hours to reduce the patient’s risk of developing a sur-
estimates originated from early studies that were conducted gical site infection (SSI). In 2017, the Centers for Disease
when cephalosporins were often contaminated with penicil- Control and Prevention SSI guidelines were revised to state
lin through manufacturing processes that have since been that clean and clean-contaminated procedures do not
optimized. In patients with confirmed immunoglobulin E- require additional antibiotic prophylaxis doses after the sur-
mediated penicillin allergies, the risk of cross-reaction with gical incision is closed in the operating room, even in the
cephalosporins and carbapenems is actually quite low (<3% presence of drains.52 A review of prospective and random-
and <1%, respectively).47 Many patients with a history of a ized trials supports the position that single-dose antibiotic
non-severe allergy to penicillin can safely tolerate an alter- prophylaxis for major surgery is recommended and multi-
native beta-lactam such as a cephalosporin or carbapenem. ple-dose prophylaxis offers no clear advantage.53 In fact, a
Second, the vast majority (>90%) of patients with a his- 79,000 patient study revealed that increasing durations of
tory of penicillin allergy are not, in fact, allergic at all.48 SSI prophylaxis were associated with higher odds of CDI
Unfortunately, allergy history data in the electronic health and acute kidney injury in a duration-dependent fashion.
record is often inaccurate or incomplete. Prior to prescribing Increased durations did not lead to any reduction in SSI.54

Figure 1 Example of adult penicillin allergy assessment algorithm.51 AGEP = acute generalized exanthematous
pustulosis; DRESS = drug reaction with eosinophilia and systemic symptoms; SJS = Stevens Johnson Syndrome;
SOB = shortness of breath; TEN = toxic epidermal necrolysis.
832 The American Journal of Medicine, Vol 135, No 7, July 2022

Controversy still exists relating to the optimal duration for good mantra to live by in these difficult scenarios is “no cur-
antimicrobial prophylaxis for cardiothoracic surgery and rent intervention, even if suboptimal, should be taken away
ventricular assist devices.55,56 Other notable exceptions to without replacing it with a better one.’ We encourage working
re-dosing of antibiotic prophylaxis include procedures with with proceduralists to define the best infection prevention
durations that exceed 2 half-lives of the prophylactic agent, practices that will avoid extended antibiotic prophylaxis.
procedures with more than 1500 mL of blood loss, and
patient-specific conditions that shorten antimicrobial half-
lives.55 If patients still have an active infection requiring anti- Myth 9: Nitrofurantoin Can Be Used for UTIs
microbials after their surgical procedure, therapy should be Only if Creatinine Clearance Exceeds 60 mL/
managed by the treating physician on a case-by-case basis. Min
Nitrofurantoin is an orally administered nitrofuran antibi-
otic with 40% of the active drug excreted in the urine, and
Myth 8: Antibiotics Are Necessary if Drains Are the remainder excreted as inactive metabolites.62 In an era
in Place of increasingly resistant urinary tract infections, nitrofuran-
Continuation of antibiotics after surgery in patients with toin has retained excellent activity against some bacteria,
postoperative drains is especially common, and not neces- especially Escherichia coli. It is recommended by the Infec-
sarily associated with clear benefits. Three procedures, in tious Diseases Society of America as a first-line treatment
particular, routinely require postoperative drains: cardiotho- for uncomplicated cystitis in females, and emerging data
racic procedures, radical mastectomies, and craniotomies. support its use for cystitis in males.63
A deep postoperative infection in these patients is of high There have been concerns about both the efficacy and
cost to both patient and surgeon; defensive medicine can safety of nitrofurantoin in patients with renal impairment,
play a substantial role in decision-making to continue anti- however, this literature has evolved. More recent studies
biotics for extended durations until all chest tubes and have suggested that the labeled cut-off of 60 mL/min for use
drains are removed.57,58 of nitrofurantoin when treating cystitis may be unwarranted,
However, the Society of Thoracic Surgeons workforce although there is more limited evidence supporting efficacy
on antibiotic prophylaxis published a guideline stating they for those with creatinine clearances of <30 mL/min.62-66 A
“found no scientific evidence that this practice (eg, antimi- few studies have suggested that efficacy may be lower in
crobials until chest tubes removed) provides enhanced pro- those with clearances <60 mL/min, but these were
tection against infectious complications.”59 retrospective.67,68 In addition, chronic (>14 days), rather
Antibiotic prophylaxis following mastectomy with than acute, use of nitrofurantoin was associated with a higher
immediate breast reconstruction remains common despite a risk of pulmonary toxicity in an elderly population.66 The lat-
randomized clinical trial and subsequent meta-analysis ter data led to updated Beers criteria to avoid only if creati-
showing that an extended course (> 24 hours) had no effect nine clearance is <30 mL/min or as chronic suppression.69
on reducing the incidence of surgical site infection.58,60
The Neurocritical Care Society, as well as the Infectious
Diseases Society of America, state that only one perioperative
Myth 10: Fluoroquinolones Remain an
dose of antibiotics should be administered prior to external Excellent First-Line Option for Most Common
ventricular drain placement; however, there is still not a con- Infections
sistent practice across the subspecialty.21,61 The fluoroquinolones (FQ) are broad-spectrum antimicro-
While the evidence seems to be lacking in demonstrating bials with favorable pharmacokinetic properties that are
benefit, there is still not a clear and definitive consensus that is generally available in oral and intravenous formulations.
broad enough to change everyday practice in these cases. A These characteristics make them attractive agents to treat

Figure 2 Timeline of US Food and Drug Administration (FDA) announcements related to FQ adverse drug
events.70-74 FDA = Food and Drug Administration; FQ = fluoroquinolone.
Johnson et al Top Myths of Infectious Diseases 833

Figure 3 Ten truths in diagnosis and management of infectious diseases.

many community- and hospital-onset infections. However, these agents are no longer considered first-line agents for
the FQs have been linked to several serious and potentially many community-onset infections when safer alternatives
disabling adverse drug events such as hypoglycemia, ten- are available.
don rupture and tendonitis, mental health effects, and most
recently, aortic rupture or dissection (Figure 2).70-74 In addi-
tion to these adverse events, the FQs are well known to be CONCLUSIONS
associated with QTc interval prolongation, C. difficile-asso- In summary, there are many common myths involving the
ciated diarrhea, and drug−drug interactions. As a result, diagnosis and management of infectious diseases that
834 The American Journal of Medicine, Vol 135, No 7, July 2022

continue to contribute to the overuse and misuse of antimi- 18. SJ Johnson, Ernst EJ, Moores KG. Is double coverage of gram-nega-
crobials in both hospital and outpatient settings. By review- tive organisms necessary? Am J Health Syst Pharm 2011;68(2):119–
ing the evidence herein, we have shed light on these 24.
19. Schultz L, Lowe TJ, Srinivasan A, Neilson D, Pugliese G. Economic
misconceptions, stated truths (Figure 3), and provided impact of redundant antimicrobial therapy in US hospitals. Infect Con-
examples of tools that will support antimicrobial steward- trol Hosp Epidemiol 2014;35(10):1229–35.
ship efforts through rational decision-making and partner- 20. Huttner B, Jones M, Rubin MA, et al. Double trouble: how big a prob-
ship with both prescribers and patients. lem is redundant anaerobic antibiotic coverage in Veterans Affairs
medical centres? J Antimicrob Chemother 2012;67(6):1537–9.
21. Tunkel AR, Hasbun R, Bhimraj A, et al. 2017 Infectious Diseases
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