Core Curriculum in Nephrology

Urinary Tract Infections: Core Curriculum

2024
Hawra Al Lawati, Barbra M. Blair, and Jeffrey Larnard

Urinary tract infections (UTIs) are some of the most commonly encountered infections in clinical Complete author and article
practice. Accurate diagnosis and evidence-based treatment of UTIs will lead to better clinical care for information provided at end
of article.
many patients and limit unnecessary antibiotic use. Urinalysis and urine cultures are helpful tools in the
diagnosis of UTIs; however, it is important to recognize their limitations. Differentiating between Am J Kidney Dis. 83(1):90-
asymptomatic bacteriuria (ASB) and true UTI is important because antibiotics are unnecessary in most 100. Published online
October 30, 2023.
nonpregnant patients with ASB and can even potentially cause harm if prescribed. Choice and
duration of antibiotics varies across the spectrum of UTI syndromes such as acute uncomplicated doi: 10.1053/
cystitis, pyelonephritis, prostatitis, and catheter-associated UTIs. The treatment approach also de- j.ajkd.2023.08.009
pends on patients’ degree of immunosuppression and their genitourinary anatomy. Therefore, patients © 2023 by the National
with urological obstruction or kidney transplants may require a specialized and multidisciplinary Kidney Foundation, Inc.
management approach. For individuals prone to frequent UTIs, some preventative measures can be
utilized, yet there is often not a “one size fits all” approach.

sensation during urination with urinary fre- FEATURE EDITOR

Introduction Melanie Hoenig
quency and discomfort in her lower abdomen.
Urinary tract infection (UTI) is a broad term She recalls having the same symptoms a year
that encompasses a spectrum of infectious ago, which was the only other time she was ADVISORY BOARD
syndromes that affect the urinary tract any- treated for a UTI. She is otherwise healthy and Ursula C. Brewster
where from the urethra to the kidneys. UTIs takes no medications. Her last menstrual period Michael J. Choi
was 2 weeks ago. Biff F. Palmer
are some of the most common infections, and Bessie Young
it is reported that 50%-60% of women have at
least 1 UTI in their lifetime. The usual Question 1: What is the best next step in The Core Curriculum
mechanism of infection is bacteria colonizing the management of this patient? aims to give trainees
the urethra or periurethral space migrating (a) Ask her to submit a urine sample for uri- in nephrology a
into the bladder and causing an inflammatory nalysis and urine culture and recommend strong knowledge
antibiotics pending culture results. base in core topics in
response. The bacteria that typically cause this the specialty by
are from the gastrointestinal (GI) tract and are (b) Prescribe ciprofloxacin 500 mg twice daily
providing an over-
collectively called Enterobacterales; examples for 7 days. view of the topic and
(c) Prescribe nitrofurantoin 100 mg twice daily citing key references,
include Escherichia coli, Klebsiella pneumoniae, and
for 5 days. including the founda-
Proteus mirabilis. Another possible way of (d) Prescribe amoxicillin 875 mg twice daily for tional literature that
developing UTIs is bacteria in the bloodstream 5 days. led to current clinical
migrating to the kidneys or bladder, but this is (e) Prescribe cefpodoxime 100 mg twice daily approaches.
very rare. The risk factors for UTIs include for 5 days.
female sex, recent sexual intercourse, diabetes
mellitus, and structural or functional uro- For the answer to this question, see the
following text.
logical abnormalities. Diagnosis and manage-
ment depend on patient factors and the extent
of disease. In this installment of AJKD’s Core
Curriculum in Nephrology, we provide a re- Diagnosis and Testing
view of the clinical presentation, diagnosis, Acute uncomplicated cystitis (also known as
and evidence-based management of common “simple cystitis”) is a type of UTI, specif-
and important UTI syndromes such as cystitis, ically an infection of the bladder in an
pyelonephritis, asymptomatic bacteriuria, otherwise immunocompetent host with
prostatitis, catheter associated UTIs, and normal urinary tract anatomy. The classic
recurrent UTIs. symptoms are dysuria, urinary frequency,
urinary urgency, or suprapubic pain in the
Acute Uncomplicated Cystitis absence of systemic illness (eg, fever, rigors, or
vomiting) or upper urinary tract involve-
Case 1: A 27-year-old woman calls her phy- ment (eg, flank pain or costovertebral angle
sician’s office reporting 3 days of a burning tenderness). “Complicated UTI” is a broad

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Al Lawati et al

term that has been traditionally used to lump the UTI

Box 1. Clinical Features of Acute Uncomplicated Cystitis
syndromes that do not meet the aforementioned
description of simple cystitis as well as UTIs that occur History
in patients with severe immunosuppression or with Key method of diagnosis
significant anatomical abnormalities. Because compli- Possible symptoms
cated UTIs encompass a wide spectrum of syndromes, • Dysuria
there is no singular approach to managing them. • Urinary frequency
• Urinary urgency
Therefore, rather than using the binary of uncompli-
• Suprapubic pain
cated versus complicated UTIs, this text discusses an • “Feels like prior treated UTI”
approach to the individual syndromes that fall under the • Absence of vaginal symptoms
umbrella of “complicated” UTI such as pyelonephritis, • Absence of systemic symptoms (shaking chills, rigors)
prostatitis, or catheter-associated UTIs. • Absence of upper tract symptoms
Diagnosis of UTIs is primarily made by the presence of Other Diagnosticsa
typical symptoms and can be confirmed by 2 main labo- Not required for all patients
ratory tests: urinalysis and urine cultures. Urinalysis can • Urinalysis: pyuria (approximately >10 WBC/HPF), pres-
help with diagnosis of UTIs. There are 2 main urinalysis ence of “many” bacteria
tests: urine microscopy and urine dipstick. Urine micro- • Urine dipstick: + nitrite, + leukocyte esterase
scopy can identify the presence of white blood cells • Urine culture with >105 CFU growth of a pathogenic
(WBCs) in urine, which is termed pyuria. Having ≥10 organism
WBCs/μL in urine is suggestive but not diagnostic of a Abbreviations: CFU, colony-forming units; HPF, high-power field; UTI, urinary
tract infection; WBC, white blood cells.
UTI. The greatest value of checking for pyuria lies in its a
These tests can increase likelihood of a cystitis diagnosis but are not diagnostic
negative predictive value, which is reported to be more on their own. Clinical context is necessary to interpret results.
than 85%. Therefore, without pyuria it is unlikely that a
patient has a UTI.
The advantage of a urine dipstick is that it is usually case 1, can be sufficient to make a clinical diagnosis (Box 1)
more readily available than microscopy or culture. The and recommend empiric treatment. An example would be
2 main tests in a urine dipstick that can aid with UTI the combination of dysuria and urinary frequency without
diagnosis are leukocyte esterase and nitrite. Leukocyte vaginal discharge or irritation, which has a reported positive
esterase, an enzyme released by lysed WBCs, acts as a likelihood ratio of 24 for the diagnosis of a UTI. Patients,
surrogate marker for pyuria. Nitrites in the urine are especially if they have had prior UTIs like this patient, often
attributed to the ability of some Gram-negative bac- recognize the symptoms and identify when they have a UTI.
teria like E coli (the most common cause of UTIs) to One study found that self-diagnosis has a positive likelihood
convert urine nitrate to nitrite. Positive nitrite on a ratio of 4.
urine dipstick can therefore be an indicator for the The following are examples of situations where a uri-
presence of bacteria in the urine (bacteriuria) and nalysis and urine culture should be sent when evaluating a
specifically Gram-negative bacteria. One of the limi- patient for a UTI:
tations of this test is that it would not detect bacteri-
• Signs or symptoms of upper tract disease or systemic
uria with organisms that do not have the biochemical
illness.
ability to create nitrite such as Enterococci and Pseudomonas
• Atypical symptoms, such as a patient who has dysuria
species. Additionally, a false-positive nitrite can be
and vaginal symptoms that are also suggestive of
seen in patients who use phenazopyridine, which is a
vaginitis.
common over-the-counter urinary analgesic in the
• Patients at high risk of developing complications, such as
United States. The reported sensitivity of both leuko-
those who are immunocompromised or have urological
cyte esterase and nitrite for detecting bacteriuria
abnormalities.
was variable, but the specificity was found to be more
• Patients at risk of infection with multidrug-resistant or-
than 90%.
ganisms (MDRO), such as those with a history of in-
Midstream voided urine cultures are a more direct
fections with MDROs or who have had recent courses of
way to assess the presence of pathogenic bacteria in the
antibiotics or a recent hospitalization.
urine. Bacteriuria in some cases represent contamina-
• Lack of improvement or progression of symptoms after
tion; however, in symptomatic patients this could
about 48-72 hours of initial empiric antibiotics.
help confirm the diagnosis of a UTI. The classic cutoff
for a positive urine culture to reflect the presence of Another important test to consider is a pregnancy
bladder bacteriuria has been >105 colony-forming test in women of childbearing age. Pregnancy can affect
units (CFU)/mL. the threshold to treat UTIs and the type of antibiotics
Testing with urinalysis or urine culture up front is not used; therefore, it is important to obtain a pregnancy
indicated in most cases of uncomplicated cystitis. Having test if it is challenging to ascertain the likelihood of
classic symptoms of acute uncomplicated cystitis, as in pregnancy with history alone. See Table 1 for a brief

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Table 1. Safety of Oral Antibiotics in Pregnancy

FDA Pregnancy
Antibiotic Risk Categorya Comment
Nitrofurantoin B Can be used during the first and second trimester. Avoid use
in the last trimester due to the risk of hemolytic anemia in the
newborn.
Trimethoprim-sulfamethoxazole D Avoid use if there are alternatives. Use in the first trimester is
(TMP-SMX) associated with an increased risk of fetal neural tube
defects. In the third trimester there is an increased risk of
hyperbilirubinemia and kernicterus. If necessary for use, the
second trimester would be the safest window.
Fosfomycin B Can be used.
Oral β-lactams (eg, amoxicillin- B Recommended for use in pregnancy.
clavulanic acid or cefpodoxime)
Fluoroquinolones (eg, C Avoid use if there are alternatives.
ciprofloxacin)
The risk–benefit balance needs to be assessed with use of any medication in individual patients. Consider involving their obstetrician if there are any concerns.
a
FDA Pregnancy Risk Categories:
• Category A: No risk in human studies.
• Category B: No risk in animal studies.
• Category C: Risk cannot be ruled out. There are no satisfactory studies in pregnant women, but animal studies
demonstrated a risk to the fetus; potential benefits of the drug may outweigh the risks.
• Category D: Evidence of risk. Studies in pregnant women have demonstrated a risk to the fetus; potential benefits of the
drug may outweigh the risks.
• Category X: Contraindicated. Studies in pregnant women have demonstrated a risk to the fetus; and/or human or animal
studies have shown fetal abnormalities. Risks of the drug outweigh the potential benefits.

overview of the safety of common oral antimicrobials Review of Question 1

in pregnancy. This patient had symptoms that would be classic for simple
cystitis (burning, frequency, suprapubic pain), so she can be
started on treatment without confirmatory laboratory testing.
Empiric Treatment
Of the treatment options listed, nitrofurantoin is the only
One of the main first-line agents for the treatment of acute first-line agent. Ciprofloxacin should be reserved for pyelo-
uncomplicated cystitis is oral nitrofurantoin for 5 days nephritis or more complicated infections, and β-lactams such
(Table 2). Fosfomycin is an acceptable alternative if as amoxicillin are second-line agents. Thus, the answer is (c),
nitrofurantoin cannot be used. It is important to note that prescribe nitrofurantoin 100 mg twice daily for 5 days.
both nitrofurantoin and fosfomycin should be avoided if
early pyelonephritis is suspected because they have poor Pyelonephritis
drug penetration to renal parenchyma. Trimethoprim-
sulfamethoxazole can also be used empirically as a first- Case 1, continued: The patient then developed subjective
line agent except in cases where local resistance rates to fevers and right lower back pain despite having taken the
Enterobacteriales (like E coli) exceed 20% or in patients who nitrofurantoin prescribed empirically by urgent care for 3 days.
The diagnosis is pyelonephritis, and the urine cultures
have used trimethoprim-sulfamethoxazole for an infection
grew > 100,000 CFU/mL E coli which was resistant to nitro-
in the past 3 months. furantoin and trimethoprim-sulfamethoxazole but susceptible to
Oral β-lactams such as amoxicillin-clavulanate or cefpo- ciprofloxacin. She was switched to ciprofloxacin 500 mg twice
doxime are effective second-line agents in treating UTIs. a day. She showed improvement in her symptoms by day 2 of
They are considered second-line agents because there are treatment and resolution of all symptoms by day 3.
limited data suggesting their inferior efficacy and a longer
duration of administration is needed compared with other Question 2: How many total days of ciprofloxacin
medications. They should only be used if the previously listed would be recommended for this patient?
first-line options are not feasible due to allergy, availability, (a) Treat for a total 3 days
or resistance. Fluoroquinolones like ciprofloxacin are often (b) Treat for a total 7 days
effective in treating UTIs but are not recommended as first- (c) Treat for a total 14 days
line agents for uncomplicated cystitis if there are other oral (d) Treat for a total 21 days
(e) Determine treatment based on repeat urine culture re-
alternatives. This is due to their side-effect profile and to
sults at day 7
mitigate the increasing rates of quinolone resistance. They are
reserved for more serious infections such as pyelonephritis. For the answer to this question, see the following text.

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Table 2. Oral Antibiotics for the Management of Cystitis and Pyelonephritis

Antibiotic Acute Uncomplicated Cystitis Pyelonephritis
Nitrofurantoin • First-line agent • Avoid due to suboptimal concentrations in
• 100 mg twice daily for 5 daysa renal parenchyma
Trimethoprim- • First-line agent • Can be used if bacteria are identified to be
sulfamethoxazole • 1 DS tablet twice daily for 3 daysa susceptible.
• Avoid if used in the past 3 months or if • 1 DS tablet twice daily
prevalence of local resistance is known to • Note: The Infectious Diseases Society of
exceed 20%. (Rates of TMP-SMX America (IDSA) recommends 14 days, but
resistance in E coli isolates in most of the more recent data indicate that 7 days
United States exceed 20%.) would be adequate provided the patient is
improving clinically.
Fosfomycin • First-line agent. • Avoid due to suboptimal concentrations in
• 3 g as 1 dose renal parenchyma
Oral β-lactams (eg, • Use only if the above first-line agents • Not recommended as an initial agent.
amoxicillin-clavulanic acid cannot be used • Can consider using oral β-lactam agent if
or cefpodoxime) • Example (not comprehensive list): pathogen known to be susceptible and
> Amoxicillin, clavulanic acid 500/125 mg after the patient receives an initial intrave-
twice daily for 5-7 daysa nous dose of a long-acting parenteral
> Cefpodoxime, 100 mg twice daily for 5- antimicrobial, such as 1 g of ceftriaxone.
7 daysa
Fluoroquinolones (eg, • Effective but use only if alternative oral • Ciprofloxacin 500 mg twice daily for 7
ciprofloxacin) antimicrobials for acute cystitis are not days
available or possible
• Example: Ciprofloxacin 250 mg twice daily
for 3 daysa
Doses listed in this table are for creatinine clearance > 60. Abbreviations: DS, double strength; TMP-SMX, trimethoprim-sulfamethoxazole.
a
Duration of therapy for cystitis are based on guideline recommendations for women. For uncomplicated cystitis in men, consider duration of w7 days provided there is no
evidence of prostatitis.

Pyelonephritis is a UTI that extends to the kidneys. The pyelonephritis because of their suboptimal penetration to
typical symptoms include flank pain, fevers, rigors, nausea, renal parenchyma (Table 2). With regard to the duration
or vomiting. In contrast to cystitis, obtaining urinalysis and of treatment, there have been multiple randomized clinical
urine cultures is recommended for all cases of suspected trials showing that 7 days of antibiotic therapy was non-
pyelonephritis. inferior to longer courses for treatment of pyelonephritis
The diagnosis of pyelonephritis should be made by in most patients.
clinical assessment and laboratory testing (urinalysis and
urine culture). Imaging is not required for all comers and
can be reserved for cases where the patient is critically ill, Review of Question 2
not improving on initial therapy, or suspected to have an The patient’s fever and flank pain indicated that she
obstruction or a complication. Complications of pyelo- had progressed to pyelonephritis. The recommended
nephritis include but are not limited to sepsis, acute renal duration for treatment of pyelonephritis with ciprofloxacin
failure, renal or perinephric abscess, kidney stones (eg, is 7 days, provided the patient is clinically improving as in
staghorn calculi), and emphysematous pyelonephritis (a this case. Tests of the cure with repeat urine cultures is not
serious necrotizing infection). Computed tomography recommended. Thus, the answer is (b), 7 days.
(CT) scan of the abdomen with intravenous (IV) contrast Case 2: A 53-year-old man with diabetes mellitus, incom-
is typically the primary mode of imaging in the majority plete bladder emptying, and a deceased donor renal trans-
of these cases. Renal ultrasound is less sensitive than a CT plant 2 years ago who is taking mycophenolate mofetil and
scan but is a reasonable alternative for patients where tacrolimus presents to the emergency department (ED) with
exposure to radiation or contrast is of concern. Manage- 5 days of dysuria, urinary frequency, and fatigue. On the fifth
ment of these complications may require drainage of day, he developed fever with rigors, so he presented to the
ED. In the ED he is hemodynamically stable with WBC of
collections and a multidisciplinary approach involving
15,000 with urinalysis showing >182 WBC, 2 red blood
specialties such as urology, interventional radiology, or
cells (RBC), + leukocyte esterase, and 4+ bacteria. Within
infectious diseases. 24 hours, his urine and a single blood culture bottle grow E
In patients who are clinically stable and can tolerate oral coli that is multidrug resistant (see the table below). His renal
medications, the treatment can be via a highly bioavailable transplant ultrasound is normal. The patient has an estimated
drug such as oral ciprofloxacin. Note that some of glomerular filtration rate (eGFR) of 48 (creatinine clearance
the agents typically used for cystitis (nitrofurantoin and of 50) and normal electrolytes; he clinically responds within
fosfomycin) are not recommended for use with 24 hours of appropriate antibiotic therapy.

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E coli (Urine) > 105 CFU this drug class, where the concentration in the urine usually
exceeds the intermediate MIC. The pharmacokinetics are not
MIC Interpretation
comparable for the bloodstream where the concentration is
Ampicillin-Sulbactam ≥32 Resistant
unlikely to exceed the intermediate MIC, thus, this strategy
Ceftriaxone ≥4 Resistant
should be avoided in bacteremia. Finally, although the use of
Meropenem <0.25 Susceptible
trimethoprim-sulfamethoxazole in this case is reasonable
Ertapenem <1 Susceptible
based on the favorable eGFR of 48 (creatinine clear-
Ciprofloxacin 0.5 Intermediate
Nitrofurantoin ≥128 Resistant
ance > 30), many transplant recipients may not fit this
Trimethoprim- <1 Susceptible
description. In those cases, eGFR should factor into the
sulfamethoxazole antimicrobial selection and dosing, which are complex and
Fosfomycin ≥256 Resistant not generalizable to a case-based review. Thus, in this case
Abbreviations: CFU, colony-forming unit; MIC, minimum inhibitory concentration. with the caveats as described, the best answer listed to this
question is (c).

Question 3: With which antibiotic and for what dura- Additional Readings
tion would you treat this patient? ➢ Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S.
(a) 3 days of ertapenem Does this woman have an acute uncomplicated urinary
(b) 7 days of nitrofurantoin tract infection? JAMA. 2002;287(20):2701-2710.
(c) 9 days of trimethoprim-sulfamethoxazole after 5 days of https://doi.org/10.1001/jama.287.20.2701
ertapenem
➢ Drekonja DM, Trautner B, Amundson C, Kuskowski M,
(d) 21 days of trimethoprim-sulfamethoxazole
(e) 14 days of ciprofloxacin
Johnson JR. Effect of 7 vs 14 days of antibiotic therapy
on resolution of symptoms among afebrile men with
For the answer to this question, see the following text. urinary tract infection: a randomized clinical trial.
JAMA. 2021;326(4):324-331. https://doi.org/10.1
001/jama.2021.9899
Comparable to the second part of case 1, this is a case ➢ Eliakim-Raz N, Yahav D, Paul M, Leibovici L. Duration
of pyelonephritis but in a renal transplant recipient and of antibiotic treatment for acute pyelonephritis and
has an associated bloodstream infection. In this case, septic urinary tract infection—7 days or less versus
imaging of the genitourinary tract is performed to longer treatment: systematic review and meta-analysis
exclude an abscess or other transplant complication of randomized controlled trials. J Antimicrob Chemother.
because these will likely impact management if found. 2013;68(10):2183-2191. https://doi.org/10.1093/
The choice and duration of antibiotic in this case involves jac/dkt177x
consideration of the host, the pathogen’s susceptibility ➢ Expert Panel on Urological Imaging; Smith AD, Niko-
profile, and the associated bloodstream infection. The laidis P, Khatri G, et al. ACR appropriateness criteria
Infectious Disease (ID) Committee of Practice for the acute pyelonephritis: 2022 update. J Am Coll Radiol.
American Society of Transplantation recommends 14 days 2022;19(11S):S224-S239. https://doi.org/10.1016/j.
of treatment for complicated UTI/pyelonephritis. Yet in jacr.2022.09.017
practice there is variability, as published by authors who ➢ Flores-Mireles AL, Walker JN, Caparon M, Hultgren SJ.
surveyed the ID committee’s providers and transplant Urinary tract infections: epidemiology, mechanisms of
nephrologists. infection and treatment options. Nat Rev Microbiol.
2015;13(5):269-284. https://doi.org/10.1038/
Review of Question 3 nrmicro3432
In general, 14 days of treatment is favored, but shorter du- ➢ Goldman JD, Julian K. Urinary tract infections in
rations are sometimes utilized based on newer data. Further, solid organ transplant recipients: guidelines from
when acceptably bioavailable oral options exist, the total the American Society of Transplantation Infectious
duration of treatment does not need to be parenteral. For that Diseases Community of Practice. Clin Transplant.
reason, answer (a) is incorrect; 3 days of ertapenem only is 2019;33(9):e13507. https://doi.org/10.1111/
an insufficient course for pyelonephritis in general. Answer ctr.13507
(b) is incorrect as well; nitrofurantoin should only be used ➢ Gupta K, Hooton TM, Naber KG, et al. International
for cystitis and never for upper tract disease or bacteremia. clinical practice guidelines for the treatment of acute
Although treatment with trimethoprim-sulfamethoxazole uncomplicated cystitis and pyelonephritis in women: a
alone is reasonable, a 21-day course is excessive without 2010 update by the Infectious Diseases Society of
abscess and raises the risk of complications, thus making America and the European Society for Microbiology
answer (d) incorrect. Answer (e) is also incorrect, while and Infectious Diseases. Clin Infect Dis.
some providers might choose to use a quinolone with an 2011;52(5):e103-120. https://doi.org/10.1093/cid/
intermediate MIC for cystitis, given the pharmacokinetics of ciq257 +ESSENTIAL READING

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➢ Kumar R, Pereira M, Taimur S, True K, Detwiler R, van difficile infection. One study by Rotjanapan and colleagues
Duin D. Duration of antibiotic treatment for acute graft showed that the 3-month risk of C difficile was 8.5 times
pyelonephritis: what’s the standard of care? Transpl Infect higher in patients who were treated for ASB. Therefore,
Dis. 2023;25(1):e13996. https://doi.org/10.1111/ screening or treatment for ASB should be avoided in most
tid.13996 patients.
➢ McAteer J, Lee JH, Cosgrove SE, et al. Defining the The main exceptions to this are the following 2 pop-
optimal duration of therapy for hospitalized patients ulations (Box 2). The first is pregnant women because
with complicated urinary tract infections and associated treatment decreases the risk of pyelonephritis and negative
bacteremia. Clin Infect Dis. 2023;76(9):1604-1612. fetal outcomes. The second population that may benefit
https://doi.org/10.1093/cid/ciad009 from a course of antibiotics are patients who will undergo
➢ Medina M, Castillo-Pino E. An introduction to the urologic procedures associated with significant mucosal
epidemiology and burden of urinary tract infections. bleeding and trauma (eg, transurethral surgery of the
Ther Adv Urol. 2019;11:1756287219832172. https:// prostate or the bladder, or percutaneous stone surgery).
doi.org/10.1177/1756287219832172 Relatedly, most of the data available do not support
➢ Voora S, Adey DB. Management of kidney transplant treatment of ASB in renal transplant patients. This, how-
recipients by general nephrologists: core curriculum ever, continues to be studied; currently, because of the lack
2019. Am J Kidney Dis. 2019;73(6):866-879. https:// of data on the immediate transplant period (1-2 months
doi.org/10.1053/j.ajkd.2019.01.031 after transplant), many centers will treat ASB if found
➢ Yahav D, Franceschini E, Koppel F, et al. Seven versus coincidently during this time, but they do not routinely
14 days of antibiotic therapy for uncomplicated Gram- screen for such.
negative bacteremia: a noninferiority randomized
controlled trial. Clin Infect Dis. 2019;69(7):1091-1098. Review of Question 4
https://doi.org/10.1093/cid/ciy1054 Pregnancy is an indication for the treatment of ASB, so the
answer is (a). Uncomplicated diagnostic cystoscopy or
Foley catheter placement have a low risk of infection.
Asymptomatic Bacteriuria Although urine culture results can help guide the standard
Case 3: A 33-year-old woman with diabetes mellitus pre-
1-2 doses of perioperative prophylaxis for cystoscopy, a
sents to her primary care doctor’s office for a routine follow- UTI treatment course with multiple days of antibiotics is
up visit. She feels well and has no acute complaints. The considered unnecessary. Patients with solid organ trans-
urine sample she submitted for annual screening for albu- plants, other than early renal transplant, do not require
minuria was also sent for urine microscopy and urine culture treatment for ASB.
due to a processing error. The urine microscopy was notable
for 5-10 WBC/high-power field (HPF), and the urine cul- Additional Readings
tures grew more than 105 CFU/mL of pan-susceptible ➢ Goldman JD, Julian K. Urinary tract infections in solid
Klebsiella oxytoca. organ transplant recipients: guidelines from the
American Society of Transplantation Infectious Diseases
Question 4: In which of the following scenarios would Community of Practice. Clin Transplant. 2019;33(9):e13507.
antibiotic treatment targeted at urine culture results
https://doi.org/10.1111/ctr.13507
be indicated for this patient?
(a) Pregnancy
➢ Nicolle LE, Gupta K, Bradley SF, et al. Clinical practice
(b) Elective hernia repair scheduled in the next 48 hours guideline for the management of asymptomatic
(c) Elective cystoscopy in the next 48 hours bacteriuria: 2019 update by the Infectious Diseases
(d) Placement of a Foley catheter Society of America. Clin Infect Dis. 2019;68(10):e83-
(e) Liver transplant in the past year e110. https://doi.org/10.1093/cid/ciy1121 +ESSENTIAL
READING
For the answer to this question, see the following text.
➢ Rotjanapan P, Dosa D, Thomas KS. Potentially inap-
propriate treatment of urinary tract infections in two
Asymptomatic bacteriuria (ASB) is defined as ≥105 Rhode Island nursing homes. Arch Intern Med.
CFU/mL in a voided urine specimen without signs or 2011;171(5):438-443. https://doi.org/10.1001/
symptoms attributable to UTI. This is regardless of archinternmed.2011.13
whether pyuria is present. ASB is a common benign
finding in many populations including healthy women,
residents in long-term care facilities, and patients with Box 2. Main Indications to Treat Asymptomatic Bacteriuria
urinary tract abnormalities. Studies have shown that anti-
microbial treatment for the majority of patient populations • Pregnancy
• Urologic procedures associated with mucosal bleeding or
with ASB does not confer significant benefit but can in-
trauma
crease the risk of antimicrobial resistance or Clostridioides

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Catheter-associated Urinary Tract Infection Review of Question 5

The CDC surveillance definition of CAUTI includes the 3
Case 4: You are seeing a 64-year-old man with diabetes mel- criteria detailed previously. Of the answer choices, only
litus and heart failure with reduced ejection fraction who was (b) is consistent with 1 of the criteria: urine culture with
admitted to the cardiac intensive care unit with acute decom-
1 organism with a bacterium of >105 CFU/mL. Note that
pensated heart failure. He did not have a fever or leukocytosis
indwelling catheters only need to be in place for 2
on presentation. An indwelling urinary catheter was placed on
hospital day 1 to assist with intravenous diuresis. On hospital consecutive days in an inpatient location to meet the
day 4, the patient was noted to have a fever to 38.5 C. Blood surveillance definition. Also, although CAUTI often are
cultures were drawn and are pending. The urinalysis revealed caused by Gram-negative organisms, Enterococcus spp,
moderate leukocyte esterase and >182 WBC/HPF. The urine Staphylococcus spp, and Candida spp are also possible causa-
culture grew >100,000 CFU/mL of Klebsiella pneumoniae. tive pathogens.

Question 5: Which of the following is consistent with

the Centers for Disease Control and Prevention (CDC) Additional Readings
surveillance definition of a catheter-associated urinary ➢ Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis,
tract infection (CAUTI)? prevention, and treatment of catheter-associated uri-
(a) Indwelling catheter in place for at least 2 weeks nary tract infection in adults: 2009 international clin-
(b) Urine culture with 1 organism with bacterium of >105 ical practice guidelines from the Infectious Diseases
CFU/mL Society of America. Clin Infect Dis. 2010;50(5):625-663.
(c) Hemodynamic instability (ie, hypotension, tachycardia)
https://doi.org/10.1086/650482 +ESSENTIAL READING
(d) Presence of E coli or other Gram-negative rod isolated in
urine culture
➢ Raz R, Schiller D, Nicolle LE. Chronic indwelling
(e) Admission to a hospital for less than 48 hours catheter replacement before antimicrobial therapy for
symptomatic urinary tract infection. J Urol.
For the answer to this question, see the following text. 2000;164(4):1254-1258. https://doi.org/10.1016/
S0022-5347(0567150-9)
The CDC surveillance definition of a CAUTI necessitates ➢ National Healthcare Safety Network. Urinary tract in-
that patients meet the following 3 criteria: fections (catheter-associated urinary tract infection
[CAUTI] and non-catheter-associated urinary tract
1. Indwelling catheter in place for more than 2 consecu- infection [UTI]) events. US Centers for Disease Control
tive days in an inpatient location. and Prevention, updated January 2023. https://www.
2. Urine culture with no more than 2 organisms present cdc.gov/nhsn/pdfs/pscmanual/7psccauticurrent.pdf
and 1 organism with bacterium of >105 CFU/mL. ➢ Weiner LM, Webb AK, Limbago B, et al. Antimicrobial-
3. Presence of at least 1 of the following: fever (38 C), resistant pathogens associated with healthcare-
suprapubic tenderness, costovertebral angle pain or associated infections: summary of data reported to
tenderness, urinary urgency, urinary frequency, or dysuria. the National Healthcare Safety Network at the Centers
The patient in case 4 above meets each of the 3 CAUTI for Disease Control and Prevention, 2011-2014. Infect
criteria. CAUTI is the most frequent health care–related Control Hosp Epidemiol. 2016;37(11):1288-1301. https://
infection worldwide, and it has been associated with the doi.org/10.1017/ice.2016.174
development of bacteremia and increased mortality. The
diagnosis of CAUTI can be difficult because pyuria is an
Acute Bacterial Prostatitis
expected finding in patients, and the symptoms are often
nonspecific if the catheter is still present. Case 4, continued: After CAUTI was diagnosed in the
The treatment for CAUTI includes first discontinuing the previous patient, he was started on intravenous ceftriaxone.
indwelling catheter or replacing the catheter (if still needed) However, he continued to have temperatures above 38.0 C
if it has been in place for more than 2 weeks. Because urine over the next 2 hospital days. A digital rectal examination
cultures from long-term indwelling catheters may reflect the revealed that the patient’s prostate was tender and swollen.
microbiology of the catheter’s biofilm instead of the infection A CT scan of his abdomen and pelvis showed a
in the bladder, obtaining a urine culture from a newly placed heterogeneous-appearing prostate without abscesses or
other intra-abdominal pathology. The patient slowly begins to
catheter is recommended to guide antimicrobial therapy.
show clinical improvement, and you plan a treatment course
Antimicrobial therapy should be initiated in patients for acute bacterial prostatitis (ABP).
with suspected CAUTI and tailored to the urine culture
results. Common bacterial causes of CAUTI include E coli, Question 6: If ABP is diagnosed, as with the patient in
Klebsiella spp, Pseudomonas aeruginosa, and Enterococcus spp. A case 4, how long should the patient receive antibiotics,
duration of 7 days of antimicrobial therapy is likely suf- assuming continued clinical improvement?
ficient, provided that the patient improves clinically after (a) 3-5 days
starting antimicrobials. (b) 7 days

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Al Lawati et al

(c) 7-14 days

➢ Lipsky BA, Byren I, Hoey CT. Treatment of bacterial
(d) 14-28 days prostatitis. Clin Infect Dis. 2010;50(12):1641-1652.
(e) 42 days or longer https://doi.org/10.1086/652861 +ESSENTIAL READING
➢ Millan-Rodrı́guez F, Palou J, Bujons-Tur A, et al. Acute
For the answer to this question, see the following text. bacterial prostatitis: two different sub-categories ac-
cording to a previous manipulation of the lower uri-
ABP is typically characterized by the abrupt onset of nary tract. World J Urol. 2006;24(1):45-50. https://doi.
voiding symptoms and is also often accompanied by systemic org/10.1007/s00345-005-0040-4
symptoms, though it can be difficult to diagnose because
helpful diagnostics are limited. As in this case, an indwelling Case 4, continued: The patient clinically improves while on
urinary catheter or urinary manipulation is a risk factor for parenteral ceftriaxone, and his discharge to home is planned.
development of ABP in men. On digital prostate palpation He is transitioned to oral levofloxacin to complete a 21-day
antimicrobial course. On review of his discharge medications,
(which should be done gently to avoid risk of bacteremia),
you notice that the patient is currently taking the sodium/glucose
the prostate is often tender, swollen, and warm. In one cotransporter 2 (SGLT2) inhibitor empagliflozin for his heart
retrospective, multicenter study of patients with an acute failure.
prostatitis diagnosis, 63% had pain with palpation of the
prostate, and 83% had an “abnormal digital rectal exami- Question 7: The above patient asks whether he should
nation.” Prostatic abscess is a rare complication of ABP in continue the empagliflozin because as he has read it
general, but it may be more common in patients with ABP in they can predispose individuals to infection. You
the setting of recent urinary tract manipulation. Imaging to recommend:
assess for prostatic abscess should be pursued if clinical (a) Continue the empagliflozin at same dose
(b) Continue the empagliflozin but decrease the dose
improvement is not seen with antimicrobial therapy. Imag-
(c) Stop empagliflozin
ing modalities to diagnose prostatic abscess include prostate (d) Stop empagliflozin and start an alternative medication for
ultrasonography, CT, and magnetic resonance imaging. the patient’s diabetes
The management of ABP typically requires 2-4 weeks of (e) Switch to a different SGLT2 inhibitor
antimicrobial therapy, ideally tailored to the results of the
urine culture if available. ABP is most commonly caused by For the answer to this question, see the following text.
E coli, P aeruginosa, Klebsiella spp, and Enterococcus spp; in sexually
active men, Neisseria gonorrhoeae and Chlamydia trachomatis should Though SGLT2 inhibitors (eg, empagliflozin, dapagli-
also be evaluated with urine nucleic acid amplification flozin, canagliflozin) have been associated with genital
testing. Though most antibiotics will penetrate acutely infections, the literature regarding their association with
inflamed prostate tissue as these patients improve clinically, UTI is conflicting. In a large, recent population-based
care should be taken to ensure antimicrobial agents are cohort study, SGLT2 inhibitor use was not associated
chosen that achieve adequate concentration in prostate tis- with serious and nonserious UTI. If SGLT2 inhibitors are
sue such as fluoroquinolones or trimethoprim- otherwise indicated for management of diabetes or heart
sulfamethoxazole. failure, providers should generally not discontinue the
medications in the setting of UTI.
Review of Question 6 Review of Question 7
Though there is a relative paucity of data regarding optimal Because SGLT2 inhibitors are not clearly associated with
treatment duration of ABP, most guidance recommends 2- UTI, they can generally be continued if patients have UTI,
4 weeks of therapy. Therefore, the correct answer is (c), especially if there are other clear risk factors for the
14-28 days. development of UTI as was the case with this patient (the
presence of indwelling urinary catheter). The correct
Additional Readings
answer is (a) because no change is necessary.
➢ Brehm TJ, Trautner BW, Kulkarni PA. Acute and
chronic infectious prostatitis in older adults. Infect Dis Additional Reading
Clin North Am. 2023;37(1):175-194. https://doi.org/1 ➢ Dave CV, Schneeweiss S, Kim D, Fralick M, Tong A,
0.1016/j.idc.2022.09.004 Patorno E. Sodium-glucose cotransporter-2 inhibitors and
➢ Coker TJ, Dierfeldt DM. Acute bacterial prostatitis: the risk for severe urinary tract infections: a population-
diagnosis and management. Am Fam Physician. based cohort study. Ann Intern Med. 2019;171(4):248-
2016;93(2):114-120. +ESSENTIAL READING 256. https://doi.org/10.7326/M18-3136
➢ Etienne M, Chavanet P, Sibert L, et al. Acute bacterial
prostatitis: heterogeneity in diagnostic criteria and
Nephrostomy Tube
management. Retrospective multicentric analysis of 371
patients diagnosed with acute prostatitis. BMC Infect Dis. Case 5: A 43-year-old woman with metastatic ovarian can-
2008;8:12. https://doi.org/10.1186/1471-2334-8-12 cer is admitted to the hospital for fever, nausea, vomiting, and

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 Al Lawati et al

back and abdominal pain. She has bilateral nephrostomies

Ciprofloxacin is highly bioavailable, and the patient can
placed 3 months ago for tumor-related ureteral obstruction. be switched to this to complete her course because she can
They were last exchanged 3 weeks ago. Fresh urine tolerate an oral medication. As a reminder, nitrofurantoin
collected from the tube (not the urine collecting in the bag) does not achieve adequate concentrations in the upper
grew a pan-susceptible E coli. Her blood cultures are without urinary tract. Therefore, the correct answer is (d), switch
growth, and the CT scan shows that the left tube is malpo- to oral ciprofloxacin for a total of 7-10 days of antibiotics.
sitioned and the left kidney had perinephric stranding with no
abscess. She was started on IV ceftriaxone. After 72 hours Additional Readings
she had resolution of her fever and tolerated a full diet. Her ➢ Bahu R, Chaftari AM, Hachem RY, Ahrar K, Shomali W,
nephrostomy tube was exchanged, and the next one is
El Zakhem A, et al. Nephrostomy tube related pyelo-
scheduled in 4 weeks.
nephritis in patients with cancer: epidemiology,
Question 8: What is the most appropriate next step in
infection rate and risk factors. J Urol. 2013;189(1):130-
management? 135. https://doi.org/10.1016/j.juro.2012.08.094
(a) Continue IV ceftriaxone for a total of 4 weeks (until next ➢ Kar M, Dubey A, Patel SS, Siddiqui T, Ghoshal U, Sahu
exchange) C. Characteristics of bacterial colonization and urinary
(b) Continue IV ceftriaxone for 10 days followed by oral tract infection after indwelling of Double-J ureteral
ciprofloxacin until next exchange stent and percutaneous nephrostomy tube. J Glob Infect
(c) Switch to oral ciprofloxacin for a total of 4 weeks (until Dis. 2022;14(2):75-80. https://doi.org/10.4103/jgid.
next exchange) jgid_276_21
(d) Switch to oral ciprofloxacin for a total of 7-10 days of
antibiotics
(e) Switch to oral nitrofurantoin for a total of 7-10 days of Approaching Candiduria
antibiotics
Case 6: A 64-year-old man is admitted to the intensive care
For the answer to this question, see the following text. unit after a coronary artery bypass graft procedure. A Foley
catheter was placed during the procedure. On postoperative
day 3, the patient has a fever of 38.3 C. Blood cultures are
Obstruction is a common indication for placement of obtained and are pending. His urinalysis is notable for the
percutaneous nephrostomy tubes. It is important to note presence of leukocyte esterase and >50 WBC/HPF. The
that the urine in a nephrostomy bag is not sterile and urine culture ultimately grows >100,000 CFU/mL Candida
therefore not appropriate for conducting microbiological albicans.
testing. If there is a clinical suspicion for UTI, testing
should only be performed on fresh urine draining directly Question 9: What is the most appropriate next step in
management?
from the tube. If the patient is undergoing an invasive
(a) Initiate antifungal treatment with fluconazole.
procedure, urine can also be sampled directly from the
(b) Replace the indwelling urinary catheter and repeat the
renal pelvis. However, even when sampling directly from urine culture.
the tube it is important to only test the urine if there are (c) Obtain a renal ultrasound.
clinical signs or symptoms of an infection because patients (d) Replace the indwelling urinary catheter and start treat-
with nephrostomy tubes can have ASB. This does not ment with fluconazole.
require treatment and was reported at a rate of w7.5% in a (e) Initiate antifungal treatment with micafungin.
study involving patients with cancer.
For the answer to this question, see the following text.

Review of Question 8
There are limited data and no guideline recommendations The task of clinicians when approaching patients with
on duration of therapy for pyelonephritis in patients with candiduria is to determine whether the isolated Candida
percutaneous nephrostomies. However, extrapolating indicates contamination, colonization, or infection. For
from the pyelonephritis and CAUTI approaches, 7-10 days patients with indwelling catheters and Candida isolated from
of treatment would likely be adequate provided there is urine culture, the catheter should be discontinued (if
clinical improvement and no abscess or other foreign possible) and a repeat urine culture obtained to investigate
body. Treating patients routinely for a longer period of whether Candida is still present. If an indwelling catheter is
time can lead to these patients being colonized with still required, the catheter should be exchanged and a new
resistant organisms and can expose them to preventable culture obtained to again assess for persistence of
drug toxicities. If a case is more complicated and does not candiduria.
meet the conditions described, then we would recommend If Candida is again isolated, the clinician must then
a multidisciplinary approach including involvement of an determine whether the patient has continued colonization
infectious diseases team to decide on an appropriate versus cystitis or upper tract infection. Note that pyuria is
duration of therapy. an expected finding in patients who have indwelling

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catheters and is not helpful in delineating colonization Question 10: What advice would you give as an initial
versus infection. Treatment of Candida UTI is only indicated intervention to this patient?
in cases of persistent candiduria in patients who have (a) Prescribe continuous antibiotic prophylaxis with
symptoms consistent with UTI without an alternative eti- ciprofloxacin
ology (ie, concurrent bacteriuria). Imaging such as renal (b) Start vaginal estrogen
ultrasound or CT abdomen/pelvis should also be obtained (c) Recommend cranberry juice supplementation
in the setting of persistent candiduria to assess for (d) Initiate episodic antibiotic prophylaxis with intercourse
obstruction and need for urology consultation. (e) Explain to her that there are no evidence-based methods to
For candiduria in patients without indwelling catheters, reduce the frequency of UTIs in postmenopausal women
the management approach is similar. First, a repeat clean- For the answer to this question, see the following text.
catch urine sample should be obtained (or a specimen
from the catheter if clean catch is not feasible) to see if Recurrent UTIs take many different forms. They can be
Candida is again isolated. If applicable, patients should also precipitated by sexual intercourse most frequently in pre-
be assessed for the presence of concurrent vaginitis. For menopausal women but also in postmenopausal women.
patients who reisolate Candida in urine, imaging is indicated Postmenopausal women are especially prone to recurrent
to assess for obstruction; however, as with catheterized UTIs due to the increased incidence of atrophic vaginitis
patients, treatment of candiduria is only indicated when and changes in the vaginal microbiome precipitated by lack
patients have signs/symptoms consistent with UTI. Ex- of estrogenization of the tissues in the vaginal and lower
ceptions to this management approach include patients urinary tracts. A detailed review of this pathophysiology is
undergoing urologic procedures and neutropenic patients included in the recommended reading.
for which asymptomatic candiduria should be treated. In general, recurrent UTIs in men are often associated
with underlying structural issues leading to urinary
Review of Question 9 retention or the presence of an indwelling catheter.
The patient in case 6 has evidence of a possible UTI with When undertaking the care of a patient with recurrent
fever and a urine culture from an indwelling urinary catheter UTI, there is frequently no single intervention that “heals
growing C. albicans. Though this could be consistent with all.” There are associations with recurrent UTIs related to
fungal CAUTI causing fever, the isolation of C. albicans may sexual activity related to spermicidal contraceptives; if a
also represent colonization of the catheter. Empiric treatment woman is using this form of contraception, changing to a
is not warranted at this stage. Replacement of the urinary different agent may provide benefit. It is not clear that other
catheter (if the catheter cannot be removed all together) behavior modifications such as early voiding after sexual
followed by repeating the urine culture should be pursued. intercourse or increased hydration to precipitate more
Unless Candida is reisolated or there is clinical evidence of an frequent urination are effective in isolation, but certainly
upper urinary tract obstruction, renal ultrasound is not these are low-risk interventions that are easy to do.
necessary at this juncture. The answer is (b), replace the For postmenopausal women, especially those in whom
indwelling urinary catheter and repeat the urine culture. there may be associated incontinence, a pelvic examination
to exclude pelvic floor dysfunction or prolapse is advised. If
Additional Reading there is no correctable anatomic issue, then vaginal estro-
➢ Kauffman CA. Diagnosis and management of fungal gens are a well-tolerated, low-risk intervention to under-
urinary tract infection. Infect Dis Clin North Am. take. Vaginal estrogens can be applied in many forms
2014;28(1):61-74. https://doi.org/10.1016/j.idc.2 including vaginal rings, creams, and tablets and may take
013.09.004 +ESSENTIAL READING some careful feedback from the patient about her experi-
ences to find the most favorable preparation. Utilization of
supplements such as cranberry extracts and D-mannose have
Recurrent UTI been tried, and some individuals may find benefit, but the
data are mixed (as presented in a recent Cochrane review).
Case 7: A 78-year-old woman comes to see her primary Investigators are studying the use of vaginal probiotics,
care doctor after her third episode of cystitis in the last 9 which may have efficacy in combination with estrogens.
months. She notes that each episode was heralded by uri- For those who are unable to derive benefit from these
nary frequency, urgency, and dysuria. She has no known
interventions, antibiotic prophylaxis is often tried. Post-
other medical conditions except for well-controlled hyper-
tension on a single medication and osteoarthritis of her
coital antibiotics can be effective in decreasing the inci-
knees. Her pelvic examination does not reveal a prolapse but dence of UTI and the most well-studied agent is
does show changes consistent with atrophic vaginitis. Her trimethoprim/sulfamethoxazole. Continuous prophylaxis
laboratory results reveal normal kidney function and no evi- has been shown to be effective in clinical trials, but the
dence of diabetes. Her urinalysis on evaluation when she is efficacy is lost once prophylaxis is stopped. Further, pro-
asymptomatic is normal, without any cells in sediment. She phylaxis is not usually 100% effective, so UTIs will likely
asks for something to prevent further infections. be less frequent but still present, and when they occur, the

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 Al Lawati et al

organisms present are likely to have antimicrobial resis- Conclusion

tance to the class of prophylactic drug.
Urinary tract infections are common and diverse, as
Review of Question 10 reviewed here. When approaching a patient with lower
urinary tract symptoms, not all patients require evaluation
The patient described in case 7 does not appear to have an
with urinalysis and urine culture. Not infrequently, how-
anatomic issue to which her recurrent UTIs can be ascribed.
ever, given the complexity of patients and the increasing
Further, she has changes on examination that are consistent
incidence of drug-resistant bacteria, urinalysis and urine
with atrophic vaginitis. Based on the sentinel randomized
culture can be an invaluable tool for management. Relat-
controlled trial of vaginal estrogens versus placebo per-
edly, isolation of bacteria or Candida from urine is not al-
formed by Raz and Stamm and published in 1993, this
ways pathogenic, necessitating careful consideration of the
patient will likely derive benefit from vaginal estrogens. This
reason for testing, the host, and any extenuating circum-
study not only demonstrated decreased antimicrobial use for
stances such as upcoming urologic procedures or preg-
UTI in the estrogen group over the follow-up period but
nancy. Like urine testing, imaging to exclude upper tract
also demonstrated other benefits such as decreased vaginal
involvement is not always necessary but in certain situa-
colonization with Enterobacterales with lower vaginal pH
tions, as outlined previously, is essential to guide treatment
and recolonization with Lactobacillus spp (normal vaginal
decisions. Finally, UTIs may be recurrent. In these situa-
flora). Thus, the correct answer is (b), start vaginal estrogen
tions, careful evaluation for potential modifiable risk fac-
as an initial intervention.
tors is beneficial. A number of pharmacologic
interventions have been studied, some less rigorously than
Additional Readings
others, and a standard approach to treating such recurrent
➢ Albert X, Huertas I, Pereiro I, Sanfelix J, Gosalbes V, infections does not currently exist. As the world’s popu-
Perrotta C. Antibiotics for preventing recurrent urinary lation ages and as medical advancements continue to in-
tract infection in non-pregnant women. Cochrane Database crease, additional study into better approaches to prevent
Syst Rev. 2004;(3):CD001209. https://doi.org/10.1 UTIs is needed.
002/14651858.CD001209.pub2
➢ Cooper TE, Teng C, Howell M, Teixeira-Pinto A, Jaure A,
Wong G. D-Mannose for preventing and treating urinary tract Article Information
infections. Cochrane Database Syst Rev. 2022;(8):CD013608. Authors’ Full Names and Academic Degrees: Hawra Al Lawati,
https://doi.org/10.1002/14651858.CD013608.pub2 MD, Barbra M. Blair, MD, and Jeffrey Larnard, MD.
➢ Goldstein I, Dicks B, Kim NN, Hartzell R. Multidisci- Authors’ Affiliations: Beth Israel Deaconess Medical Center,
plinary overview of vaginal atrophy and associated Harvard University, Boston, Massachusetts.
genitourinary symptoms in postmenopausal women. Sex Address for Correspondence: Barbra M. Blair, MD, Beth Israel
Med. 2013;1(2):44-53. https://doi.org/10.1002/sm2.17 Deaconess Medical Center, 110 Francis St, Lowry GB, Boston,
MA 02215-5501. Email: bblair@bidmc.harvard.edu
➢ Raz R, Stamm WE. A controlled trial of intravaginal
estriol in postmenopausal women with recurrent uri- Support: None.
nary tract infections. New Engl J Med. 1993;329(11):753- Financial Disclosure: The authors declare that they have no
relevant financial interests.
756. +ESSENTIAL READING
➢ Sihra N, Goodman A, Zakri R, Sahai A and Malde S. Peer Review: Received March 24, 2023 in response to an invitation
from the journal. Evaluated by 2 external peer reviewers and a
Nonantibiotic prevention and management of recurrent member of the Feature Advisory Board, with direct editorial input
urinary tract infections. Nature Rev Urol. 2018;15:750- from the Feature Editor and a Deputy Editor. Accepted in revised
776. https://doi.org/10.1038/s41585-018-0106-x form August 7, 2023.

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