# 19 - 140 Urinary Tract Infections- Cystitis, Prostatitis, and Pyelonephritis

### 140 Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis

colectomy should be performed before the serum lactate level 
reaches 5 mmol/L. However, mortality and morbidity associated 
with colectomy may be reduced by performing instead a laparo­
scopic ileostomy followed by colon lavage with polyethylene glycol 
and vancomycin infusion into the colon via the ileostomy.

■
■PROGNOSIS
The mortality rate attributed to CDI, previously found to be 0.6–3.5%, 
has reached 6.9% in recent outbreaks and is progressively higher with 
increasing age. Most patients recover, but recurrences are common.
■
■PREVENTION AND CONTROL
Strategies for the prevention of CDI are of two types: those aimed 
at preventing transmission of the organism to the patient and those 
aimed at reducing the risk of CDI if the organism is transmitted. 
Transmission of C. difficile in clinical practice has been prevented by 
gloving of personnel, elimination of the use of contaminated electronic 
thermometers, and use of hypochlorite (bleach) solution for environ­
mental decontamination of patients’ rooms. Hand hygiene is critical; 
hand washing is recommended in CDI outbreaks because alcohol hand 
gels are not sporicidal. CDI outbreaks have been best controlled by 
restricting the use of specific antibiotics, such as clindamycin, second- 
and third-generation cephalosporins, and fluoroquinolones. Outbreaks 
of CDI due to antibiotic-resistant strains have resolved promptly when 
specific antibiotic use is restricted. Future primary prevention strate­
gies include use of monoclonal antibodies, as well as biotherapeutics 
with live organisms to prevent colonization. Vaccines have to date been 
unsuccessful.
PART 5
Infectious Diseases
■
■FURTHER READING
Dingle KE et al: Effects of control interventions on Clostridium 
difficile infection in England: An observational study. Lancet Infect 
Dis 17:411, 2017.
Feuerstadt P et al: SER-109, an oral microbiome therapy for recur­
rent Clostridioides difficile infection. N Engl J Med 386:220, 2022.
Guh AY et al: Trends in U.S. burden of Clostridioides difficile infection 
and outcomes. N Engl J Med 382:1320, 2020.
Guh AY et al: Potential underreporting of treated patients using a 
Clostridioides difficile testing algorithm that screens with a nucleic 
acid amplification test. Infect Cont Hosp Epidemiol 2024. Online 
ahead of print.
He M et al: Emergence and global spread of epidemic healthcareassociated Clostridium difficile. Nat Genet 45:109, 2013.
Johnson S et al: Vancomycin, metronidazole, or tolevamer for 
Clostridium difficile infection: Results from two multinational, 
randomized, controlled trials. Clin Infect Dis 59:345, 2014.
Johnson S et al: Clinical practice guideline by the Infectious Diseases 
Society of America (IDSA) and Society for Healthcare Epidemiology of 
America (SHEA): 2021 Focused update guidelines on management of 
Clostridioides difficile infection in adults. Clin Infect Dis 73:755, 2021.
Khanna S et al: Efficacy and safety of RBX2660 in PUNCH CD3, a 
phase III, randomized, double‑blind, placebo‑controlled trial with a 
Bayesian primary analysis for the prevention of recurrent Clostridioi­
des difficile infection. Drugs 82:1527, 2022.
Kociolek LK et al: Natural Clostridioides difficile toxin immunization 
in colonized infants. Clin Infect Dis 70:2095, 2020.
Louie TJ et al: Fidaxomicin versus vancomycin for Clostridium difficile 
infection. N Engl J Med 364:422, 2011.
McDonald LC et al: Clinical practice guidelines for Clostridium 
difficile infection in adults and children: 2017 update by the Infec­
tious Diseases Society of America (IDSA) and the Society for Health­
care Epidemiology of America (SHEA). Clin Infect Dis 66:987, 2018.
Polage CR et al: Overdiagnosis of Clostridium difficile infection in the 
molecular test era. JAMA Intern Med 175:1792, 2015.
See I et al: NAP1 strain type predicts outcomes from Clostridium dif­
ficile infection. Clin Infect Dis 58:1394, 2014.
Wilcox MH et al: Bezlotoxumab for prevention of Clostridium difficile 
infection recurrence. N Engl J Med 376:305, 2017.

Urinary Tract Infections: 

Cystitis, Prostatitis, and 
Pyelonephritis
Barbara W. Trautner, Prathit A. Kulkarni, 

Nicolás W. Cortés-Penfield, Kalpana Gupta
In the preantibiotic era, urinary tract infection (UTI) caused significant 
morbidity. Hippocrates described acute cystitis as sometimes lasting 
for a year before either resolving or worsening to involve the kidneys. 
Early twentieth-century chemotherapeutics for UTI were ineffective, 
and persistent infection was common. Nitrofurantoin, which became 
available during the 1950s, was the first tolerable and effective agent for 
UTI treatment. Today, UTI remains common, being one of the leading 
reasons for which antibiotics are used within and outside the hospital. 
Patients typically favorably and quickly to appropriately chosen mod­
ern antimicrobials.
Since the most common manifestation of UTI is acute cystitis, which 
is far more prevalent among women than among men, most clinical 
research on UTI has involved healthy young adult women recruited 
from college campuses or large U.S. health maintenance organizations. 
Therefore, clinicians must understand that UTI remains relatively under­
studied in other patient populations, and they must use expert judgment 
to decide when and to what extent UTI clinical trial data and treatment 
guidelines can be generalized to other groups of patients.
■
■DEFINITIONS
The term urinary tract infection refers to an infection somewhere along 
the urinary tract that produces clinical symptoms. Infection can be 
caused either by bladder invasion by a new urinary pathogen or by a 
shift in the existing urinary bacteria’s dynamic equilibrium with the 
host; both causes result in local tissue injury and inflammation. Thus, 
while UTI encompasses a broad range of clinical presentations, from 
acute simple cystitis to bacteremic emphysematous pyelonephritis, 
importantly, the presence alone of bacteria in the urinary tract in a 
patient without related symptoms does not constitute UTI. The pres­
ence of bacteria in the urine without associated symptoms is instead 
termed asymptomatic bacteriuria (ASB).
This distinction between UTI and ASB has major clinical impli­
cations. Both UTI and ASB connote the presence of bacteria in the 
urinary tract and are usually accompanied by white blood cells in the 
urine (termed pyuria). However, while antibiotic treatment of UTI is 
almost always indicated to relieve the symptoms attributable to urinary 
bacterial infection and to prevent progression of the infection, ASB 
typically poses no threat for most patients and usually does not require 
treatment. Limited data suggest inappropriate treatment of ASB might 
in fact increase risk for future UTI, perhaps by facilitating bladder colo­
nization with more virulent and potentially more resistant pathogens. 
Two exceptions to the general rule that ASB should not be treated are 
patients who are pregnant or who are about to undergo certain urologic 
procedures. In pregnant patients, untreated ASB is associated with 
pyelonephritis, preterm delivery, and low birth weight, which justifies 
use of routine ASB screening and treatment. In patients undergoing 
procedures that cause urologic mucosal injury (e.g., lithotripsy or 
transurethral resection of the prostate), bacterial translocation from 
urine to blood can occur; therefore, screening for, and periprocedural 
treatment of, ASB is recommended in this setting.
In this chapter, the term urinary tract infection denotes symptom­
atic disease; cystitis, symptomatic infection of the bladder; prostatitis, 
symptomatic infection of the prostate; and pyelonephritis, symptomatic 
infection of the kidneys. Uncomplicated urinary tract infection refers 
to an infection confined to the bladder in a woman or man without a 
urinary catheter, whereas complicated urinary tract infection refers to 
infection that extends beyond the bladder (e.g., prostatitis, pyelone­
phritis, bacteremia, or UTI in the setting of intermittent or indwelling

urinary catheterization, termed catheter-associated UTI [CAUTI]). 
Recurrent urinary tract infection is not necessarily complicated; indi­
vidual episodes can be uncomplicated and treated as such. This 
approach to UTI categorization differs from the classic approach, in 
which UTI in men and other populations perceived to be at higher risk 
for poor outcome (e.g., patients with diabetes, anatomic abnormali­
ties of the urinary tract, or immunocompromise) was automatically 
considered complicated. The new updated approach more closely 
reflects actual clinical practice. For the frontline clinician, the key con­
siderations in diagnostic workup and therapy for UTI include whether 
the patient is stable for outpatient management, whether a source of 
recalcitrant and/or recurrent infection (e.g., obstructing renal calculi) 
needs to be identified, and whether the prescribed antimicrobial agents 
must achieve adequate levels in the blood and renal tissue in addition 
to the urine.
Prostatitis, usually categorized as either acute bacterial prostatitis 
(ABP) or chronic bacterial prostatitis (CBP), can complicate cystitis 
or arise hematogenously (e.g., as a metastatic focus of Staphylococcus 
aureus bacteremia) in men and transgender women. While prostatitis 
is certainly an infection of the genitourinary tract, it is largely unrepre­
sented in UTI clinical trial data, and earlier ABP literature suggests that 
prolonged therapy with antimicrobials penetrating the prostate might 
be required. Therefore, clinical practice guidelines for complicated 
UTI cannot be assumed to be generalizable to patients with prostatitis. 
Urethritis is occasionally caused by Escherichia coli and other urinary 
pathogens but is predominantly due to Neisseria gonorrhea, Chlamydia 
trachomatis, and Mycoplasma genitalium. Hence, symptoms such as 
urethral pain, pruritus, or discharge should prompt evaluation for 
sexually transmitted infections (STIs), which are covered in Chap. 141.
■
■EPIDEMIOLOGY AND RISK FACTORS
During the neonatal period, the incidence of UTI is slightly higher 
among males than among females because male infants more com­
monly have congenital urinary tract anomalies. After 50 years of age, 
obstruction from prostatic hypertrophy becomes common in men, 
and incidence of UTI is almost as high among men as among women. 
Between 1 year and ~50 years of age, however, UTI and recurrent 
UTI are predominantly conditions of females, with most true male 
UTI occurring in the context of urinary catheterization or anatomic 
abnormalities. The prevalence of ASB is ~5% among women between 
ages 20 and 40 and might be as high as 40–50% among elderly women 
and men. Up to 80% of women develop at least one UTI during their 
lifetime, predominantly acute simple cystitis. The lifetime prevalence 
of UTI in men in the United States is estimated to be 14%.
About 20–30% of women who have had one episode of UTI will 
have recurrent episodes. Early recurrence (within 2 weeks) is usually 
regarded as relapse rather than reinfection and might indicate the need 
to evaluate the patient for a sequestered focus of ongoing infection. 
The rate of UTI recurrence ranges from 0.3 to 7.6 infections per patient 
per year, with an average of 2.6 reinfections per year. It is not uncom­
mon for multiple recurrences to follow an initial infection, resulting 
in clustering of episodes. Clustering may be related to the presence of 
a new risk factor, sloughing of the protective outer bladder epithelial 
layer in response to bacterial attachment during acute cystitis, or possibly 

antibiotic-related alteration of the normal bacterial flora. The likelihood 
of recurrence decreases with increasing time since the last infection. 
Risk factors for recurrent UTI include frequent sexual intercourse, use 
of spermicide, a new sexual partner, first UTI before 15 years of age, and 
maternal history of UTI; of these, frequent sexual intercourse and sper­
micide use are the most consistently documented risk factors.
Some component of UTI susceptibility is likely hereditary, as family 
and maternal history of UTI has been identified as a risk factor for cys­
titis, pyelonephritis, and recurrent UTI. In addition, colonization with 
specific bacterial strains predisposed to cause infection might also be an 
important factor, as suggested by studies indicating that new sexual part­
ners are a risk factor for UTI in women and that uropathogenic E. coli 
are shared between partners via vaginal and oral sex. Beyond this, risk 
factors for UTI can be grouped broadly into three categories: (1) factors 
that impede the normal outflow of urine, (2) factors that introduce new 

bacteria into the genitourinary tract or serve as a nidus of infection, and 
(3) factors that disrupt or impair local mucosal defenses.

The flushing action of normal urination is a key mechanism by 
which the host controls urinary bacterial populations and mitigates 
bacterial ascent from the urethra to the bladder and kidneys. Ana­
tomic factors that result in urinary obstruction or retention have been 
associated with cystitis, pyelonephritis, and recurrent UTI. These risk 
factors include congenital urinary tract abnormalities, cystoceles, 
pelvic-organ prolapse, bladder dysfunction leading to overflow urinary 
incontinence, and benign prostatic hypertrophy. Importantly, not all 
men with UTI have detectable urinary tract abnormalities; this point is 
particularly relevant for men ≤45 years of age.
Factors that promote bacterial entry into the urinary tract predis­
pose to UTI. Sexual activity is likely the most common among these 
and is temporally associated with cystitis, with an increased relative 
risk in one study ranging from 1.4 with weekly intercourse to 4.8 with 
intercourse five times weekly. For men, insertive rectal intercourse 
and lack of circumcision are associated with increased UTI risk, the 
latter likely because E. coli is tends to colonize the glans and prepuce 
and subsequently migrate into the urinary tract. For men and women, 
urinary instrumentation (e.g., intermittent or chronic catheterization 
or existence of a draining nephrostomy tube) dramatically increases 
bacterial entry into the urinary tract and risk of UTI. In addition, for­
eign bodies in the urinary tract (e.g., stents and kidney stones) also can 
become colonized with bacteria and serve as niduses for recurrent UTI.
Factors that disrupt or impair local mucosal defenses, usually 
either by irritating the urogenital mucosa or by disrupting the normal 
female urogenital microbiome (i.e., symbiotic lactobacilli), predispose 
to UTI. Such factors include recent use of diaphragms or spermicide 
and menopause. Women with diabetes have two- to threefold higher 
rates of ASB and UTI than women without diabetes, and this risk 
increases further with a longer duration of having had diabetes and 
with the need for insulin rather than oral medications. The specific 
mechanisms for this risk are not clear, although impaired cytokine 
secretion or diabetes complications leading to bladder dysfunction 
likely contribute. Whether glycosuria is major contributor to UTI risk 
remains controversial. The U.S. Food and Drug Administration has 
issued a drug-safety warning for the observed association between use 
sodium–glucose cotransporter 2 (SGLT-2) inhibitors for treatment 
of diabetes and UTI. The postulated mechanism is that these drugs 
increase excretion of glucose in the urine.
CHAPTER 140
Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis 
■
■ETIOLOGY
E. coli is the predominant pathogen across the spectra of UTI clinical 
syndromes and patient populations. In cases of acute cystitis in the 
United States, E. coli accounts for 75–90% of isolates, Staphylococcus 
saprophyticus for 5–15% (with more frequent isolation from younger 
women), and other Enterobacterales species (i.e., Klebsiella, Proteus, 
Enterobacter, and Citrobacter) for the majority of the remainder. The 
microbiology of pyelonephritis is similar to that of acute cystitis, as 
would be expected since pyelonephritis usually develops as ascend­
ing infection from the bladder. The microbiology of CAUTI is more 
diverse, but E. coli remains the predominant organism. Other impor­
tant pathogens in CAUTI are Pseudomonas aeruginosa, enterococci, 
Staphylococcus aureus, and Candida. Genetic sequencing of the bladder 
microbiome has consistently demonstrated that more bacterial spe­
cies are present than can be identified by routine culture methods, in 
both symptomatic and asymptomatic states. The clinical significance 
of these noncultivable organisms is unknown, but such work demon­
strates that the healthy bladder is often not a sterile site.
Antimicrobial resistance among Enterobacterales species that cause 
UTI is increasing. One recent surveillance study of isolates from the 
United States demonstrated resistance rates of >20% to trimethoprimsulfamethoxazole (TMP-SMX), fluroquinolones, and nitrofurantoin 
among ambulatory patients in many regions of the country. In addi­
tion, approximately 6% of isolates were resistant to three or more 
antibiotic classes, and approximately 9% of isolates had production 
of extended-spectrum β-lactamase. Surveillance studies conducted in 
South America and Europe have yielded similar findings. The increased

prevalence of multidrug-resistant uropathogens has left few oral 
options for therapy in some cases and no single agent or agents that 
can confidently be recommended for empirical ambulatory treatment 
of UTI without regard to geographic region. Since resistance rates vary 
in different areas, local antibiogram data can help inform which drugs 
should be used as preferred empirical therapy in UTI, with the caveat 
that organisms are identified only in cases in which urine is sent for 
culture—typically, when complicated or recurrent UTI is suspected—
and so may overestimate antimicrobial resistance in healthy ambula­
tory patients with a primary episode of UTI.

■
■PATHOGENESIS
The urinary tract can be viewed as an anatomic unit linked by a con­
tinuous column of urine extending from the kidneys to the urethra. In 
the majority of UTIs, bacteria establish infection by ascending from the 
urethra to the bladder. Continuing ascent up the ureter to the kidney 
is the pathway for most renal parenchymal infections. The other main 
route of entry into the genitourinary tract is hematogenous in cases 
where bacteremia precedes UTI. Importantly, introduction of bacteria 
into the bladder does not inevitably lead to sustained and symptomatic 
infection. The interplay of host, pathogen, and environmental factors 
determines whether tissue invasion and symptomatic infection will 
ensue (Fig. 140-1). For example, bacteria often enter the bladder after 
sexual intercourse, but normal voiding and innate host defense mecha­
nisms in the bladder eliminate these organisms. Any foreign body in 
the urinary tract, such as a urinary catheter or stone, provides an inert 
surface for bacterial colonization. Additionally, abnormal micturition 
and/or significant residual urine volume promotes infection. In the 
simplest terms, anything that increases the likelihood of bacteria enter­
ing the bladder and staying there increases risk of developing UTI. 
Intracellular bacterial communities of infecting organisms within the 
bladder epithelium have been demonstrated in animal models of UTI 
and in exfoliated human urothelial cells, but the clinical impact of this 
phenomenon in humans is not yet clear.
PART 5
Infectious Diseases
Bacteria can also gain access to the urinary tract through the blood­
stream. However, hematogenous spread only accounts for less than 2% 
of documented UTIs and usually results from bacteremia caused by 
relatively virulent organisms, such as S. aureus and Salmonella. The 
isolation of either of these pathogens from a urine culture warrants 
consideration of concomitant bacteremia. Hematogenous infections 
can also produce focal renal abscesses or pyelonephritis.
The pathogenesis of candiduria in particular is distinct because the 
hematogenous route is more common in that situation. The presence 
of Candida in the urine of a non-instrumented immunocompetent 
patient implies either genital contamination or potentially widespread 
visceral dissemination. By contrast, candiduria is common in catheter­
ized patients, particularly following antimicrobial therapy for CAUTI 
or inappropriate treatment of ASB.
Host
 
Genetic background
 
Behavioral factors
 
Underlying disease
 
Tissue-specific receptors
Organism
 
Type of organism
 
Presence of virulence factors
 
Expression of virulence factors
Organism
Host
Infection,
colonization, or
elimination
Environment
Environment
 
Vaginal ecology
 
Anatomy/urinary retention
 
Medical devices
FIGURE 140-1  Pathogenesis of urinary tract infection. The relationship among 
specific host, pathogen, and environmental factors determines the clinical outcome.

Environmental Factors 
• 
VAGINAL ECOLOGY  Vaginal ecology 
is an important environmental factor affecting risk of UTI in women. 
Colonization of the vaginal introitus and periurethral area with organ­
isms from the intestinal flora (usually E. coli) is the critical initial step 
in the pathogenesis of UTI. Sexual intercourse is associated with an 
increased risk of vaginal colonization with E. coli and thereby increases 
risk of UTI. Nonoxynol-9 in spermicide is toxic to normal vaginal 
lactobacilli and thus is likewise associated with an increased risk of 
vaginal colonization and bacteriuria due to E. coli. In postmenopausal 
women, the previously predominant vaginal lactobacilli are replaced 
with colonizing Gram-negative bacteria because of vaginal atrophy. 
Topical estrogens have been demonstrated to reduce frequency of 
recurrent UTIs in postmenopausal women without altering systemic 
hormone levels. Given the side effects of systemic hormone replace­
ment, oral estrogens should not be used to prevent UTI.
ANATOMIC AND FUNCTIONAL ABNORMALITIES  Any condition that 
permits urinary stasis or obstruction predisposes the patient to devel­
opment of UTI. Foreign bodies such as stones or urinary catheters 
provide an inert surface for bacterial colonization and formation of 
a persistent biofilm. Thus, vesicoureteral reflux, ureteral obstruction 
secondary to prostatic hypertrophy, neurogenic bladder, and urinarydiversion surgery all create an environment that can lead to UTI. 
Inhibition of ureteral peristalsis and decreased ureteral tone leading to 
vesicoureteral reflux are important in the pathogenesis of pyelonephri­
tis in pregnant patients. Anatomic factors—in particular, the length 
of the urethra—are considered to be the primary reason why UTI is 
predominantly an illness of young women rather than of young men.
Host Factors 
 The genetic background of the host influences 
the individual’s susceptibility to recurrent UTI. In women, famil­
ial disposition to UTI is well documented. Additionally, women 
with recurrent UTI are more likely to have had their first UTI before 
the age of 15 years and to have a maternal history of UTI. A component 
of the underlying pathogenesis of this familial predisposition to recur­
rent UTI might be persistent vaginal colonization with E. coli, even 
during asymptomatic periods. Vaginal and periurethral mucosal cells 
from women with recurrent UTI bind uropathogenic bacteria three­
fold more than do mucosal cells from women without recurrent infec­
tion. This difference appears to be at least partly mediated by not 
expressing certain blood group antigens, facilitating adherence of E. coli to 
the urothelium. Mutations in host innate immune response genes (e.g., 
those coding for Toll-like receptors and the interleukin 8 receptor) also 
have been linked to recurrent UTI and pyelonephritis.
Microbial Factors 
 Strains of E. coli that cause invasive symp­
tomatic infection of the urinary tract in otherwise normal hosts 
often possess and express genetic virulence factors, including 
bacterial-surface adhesins that mediate microbial binding to specific 
receptors on the surface of uroepithelial cells. The best-studied adhes­
ins are the P fimbriae, hairlike protein structures that interact with a 
specific receptor on renal epithelial cells. (The letter P denotes the abil­
ity of these fimbriae to bind to blood-group antigen P, which contains 
a d-galactose-d-galactose residue.) P fimbriae are important in the 
pathogenesis of pyelonephritis and subsequent bloodstream invasion 
from the kidney. Another adhesin is the type 1 pilus (fimbria), which 
all E. coli strains possess but which is not always expressed. Type 1 pili 
are thought to play a key role in initiating E. coli bladder infection; they 
mediate binding to mannose on the luminal surface of bladder uroepi­
thelial cells. Toxins, metal (iron)-acquisition systems, biofilm forma­
tion, and bacterial capsules also can contribute to the ability of 
pathogenic E. coli to thrive in the bladder.
APPROACH TO THE PATIENT
Clinical Syndromes and Diagnostic Approaches
The key questions to be addressed when UTI is suspected are:
•  Does the patient actually have UTI (rather than ASB or uri­
nary symptoms not related to infection)?

•  If the patient does have UTI, is it confined to the bladder 
(cystitis), or is there evidence that infection might be present 
beyond the bladder?
•  If the diagnosis is uncertain, would it be safe to delay empiri­
cal antimicrobial therapy while attempting to achieve more 
diagnostic certainty?
The answers to these immediate clinical questions will shape the 
diagnostic and therapeutic approach. 
ASYMPTOMATIC BACTERIURIA
A diagnosis of ASB should be strongly suspected when a patient 
with a positive urine culture does not have either localizing urinary 
symptoms or systemic symptoms that are unexplained. The clinical 
presentation is typically bacteriuria that is detected incidentally 
when a patient undergoes a screening urine culture. Accordingly, 
diagnostic stewardship (i.e., not sending urine cultures in patients 
who lack clinical signs and symptoms that suggest UTI except when 
screening patients who are pregnant or about to undergo urologic 
procedures) is the key intervention in reducing misdiagnosis of UTI 
and inappropriate treatment of ASB.
In the setting of pyuria (presence of white blood cells in the 
urine) and bacteriuria in a patient without symptoms localizing 
to the urinary tract, systemic symptoms and signs such as fever, 
altered mental status, and leukocytosis could be features of UTI but 
do not on their own merit a diagnosis of UTI unless other potential 
etiologic causes for such findings have been adequately explored 
and ruled out. Critically, the degree of pyuria in an asymptomatic 
patient should not influence the diagnosis of ASB versus true UTI. 
Very high levels of pyuria are common in urinary stasis, such as in 
patients with end-stage renal disease or obstructed urinary catheters.
In practice, one of the most challenging clinical scenarios to dif­
ferentiate ASB from true UTI occurs when an older patient presents 
with isolated altered mentation, often superimposed on chronic 
cognitive deficits and potentially with little prior documentation. 
Accurately diagnosing the cause of such a patient’s acute encepha­
lopathy is challenging both because the patient might not be able to 
reliably report localizing urinary symptoms and because true UTI 
is an important diagnostic consideration on a long list of possible 
causes of the patient’s symptoms. In such a patient, the treating 
clinician should first establish whether there is evidence of sepsis. If 
not, the next consideration is whether empirical therapy for poten­
tially serious bacterial infection can be safely withheld while the 
diagnostic process is ongoing and symptomatic treatment for other 
noninfectious causes of delirium is given. The clinician should seek 
out collateral history, such as by calling the patient’s caregivers if 
none are present at the bedside, to elicit information about what 
occurred prior to the patient’s development of acute encephalopa­
thy. A history of prior recurrent UTIs is might not be accurate and 
instead reflects a history of persistent ASB. The clinician must be 
vigilant to avoid premature diagnostic closure. Specifically, the 
clinician should rule out other potential causes of delirium, particu­
larly those whose treatment is time-sensitive or that may worsen 
with if the diagnosis is not considered and addressed. 
CYSTITIS
The typical symptoms of cystitis are dysuria, urinary frequency, 
and urinary urgency. Other common symptoms include supra­
pubic discomfort or tenderness and new nocturia, hesitancy, or 
gross hematuria. Fever, rigors, and unilateral back or flank pain 
are all inconsistent with uncomplicated cystitis and should provoke 
investigation for infection beyond the bladder (i.e., involving the 
kidneys, prostate, or bloodstream).
Cystitis in women can be treated on the basis of history alone. 
However, if the symptoms are not specific or if a reliable history 
cannot be obtained, then a urine dipstick (or, if rapidly available, 
urine microscopy) should be performed. In the scenario of a 
woman with symptoms potentially suggestive of cystitis, a negative 
dipstick result does not fully rule out UTI, and appropriate next 

steps would include formal urine microscopy with reflex to culture, 
possibly a pelvic examination or STI testing, and close clinical 
follow-up. In pregnant patients, in patients suspected to have a 
resistant organism, or in cases of recurrent UTI, a urine culture is 
specifically warranted to guide appropriate therapy. Urine dipstick 
and/or urine microscopy alone are not sufficient.
The signs and symptoms of cystitis in men are similar to those in 
women, but this diagnosis should be approached cautiously, as cys­
titis in men is less common, except in the setting of urinary cathe­
terization/instrumentation or obstructive uropathy due to prostatic 
hypertrophy. Urine cultures should be obtained for all cases of male 
UTI, as the documentation of bacteriuria can differentiate the less 
common syndromes of acute and chronic bacterial prostatitis from 
the more common entity of chronic pelvic pain syndrome, which 
is not associated with bacteriuria and not improved by antibiotics. 
PROSTATITIS
Prostatitis includes both infectious and noninfectious abnormali­
ties of the prostate gland. Infections can be acute or chronic, are 
almost always bacterial in nature, and are far less common than the 
noninfectious entity chronic pelvic pain syndrome (formerly known 
as chronic prostatitis). ABP presents as dysuria, frequency, and pain 
in the prostatic pelvic or perineal area. It is typically a severe illness 
that can be accompanied by fever, rigors, and/or bladder outlet 
obstruction. CBP presents more insidiously as recurrent episodes 
of cystitis, sometimes with associated pelvic and perineal pain. 
Systemic signs of infection are typically absent, and many patients 
are evaluated for CBP in the ambulatory setting. Males with recur­
rent cystitis should be evaluated for a prostatic focus as well as for 
urinary retention.
CHAPTER 140
Men with febrile UTI can have an elevated serum level of 
prostate-specific antigen and an enlarged prostate and enlarged 
seminal vesicles on ultrasound—findings suggestive of prostate 
involvement. In a study of 85 men with febrile UTI, symptoms of 
urinary retention, early recurrence of UTI, hematuria at follow-up, 
and voiding difficulties were predictive of surgically correctable 
disorders. Men with none of these symptoms had normal upper 
and lower urinary tracts on urologic workup. In general, men with 
febrile UTI, including at the first episode, should have imaging 
performed (CT or ultrasound) if it has not been performed previ­
ously. The purpose of such investigation is specifically to evaluate 
for urinary tract abnormalities or obstruction. If the diagnosis of 
UTI is unclear or if UTI is recurrent, referral for urologic consulta­
tion is appropriate. 
Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis 
PYELONEPHRITIS
Fever is one of the main features distinguishing cystitis from pyelo­
nephritis, and while “febrile UTI” is sometimes used as a diagnos­
tic category in UTI research, practically speaking, many of these 
patients have pyelonephritis or other infection that has extended 
beyond the bladder (hence the inclusion of fever as a criterion for 
complicated UTI).
Mild pyelonephritis can present with low-grade fever with or 
without lower back or costovertebral angle pain, whereas severe 
pyelonephritis often manifests with high fever, rigors, nausea, vom­
iting, and flank pain. Symptoms are generally acute in onset and 
may or may not be preceded by symptomatic cystitis. Obstructive 
uropathy related to acute papillary necrosis (i.e., when the sloughed 
papillae obstruct the ureter) can complicate pyelonephritis. Acute 
papillary necrosis can also occur in sickle cell disease and analge­
sic nephropathy. In the rare cases of bilateral papillary necrosis, a 
rapid rise in the serum creatinine level might be the first indication 
of the condition. Emphysematous pyelonephritis is a particularly 
severe form of pyelonephritis associated with production of gas in 
the renal and perinephric tissues. It occurs almost exclusively in 
patients with poorly controlled diabetes (Fig. 140-2). Xanthogranu­
lomatous pyelonephritis occurs when chronic urinary obstruction 
(often by staghorn calculi), together with chronic infection, leads to 
suppurative destruction of renal tissue (Fig. 140-3). On pathologic

FIGURE 140-2  Emphysematous pyelonephritis. Infection of the right kidney of a 
diabetic man by Escherichia coli, a gas-forming, facultative anaerobic uropathogen, 
has led to destruction of the renal parenchyma (arrow) and tracking of gas through 
the retroperitoneal space (arrowhead).
PART 5
Infectious Diseases
examination, the residual renal tissue frequently has a yellow color­
ation, with infiltration by lipid-laden macrophages (hence the term 
xanthogranulomatous). Pyelonephritis can also be complicated by 
intraparenchymal abscess formation; this development should be 
suspected when a patient has continued fever and/or bacteremia 
despite antibacterial therapy. 
CATHETER-ASSOCIATED URINARY TRACT INFECTION (CAUTI)
Clinically, CAUTI can be defined by the presence of symptoms 
along with presence of bacteriuria and pyuria. CAUTI may cause 
localizing urinary symptoms or otherwise unexplained systemic 
manifestations, such as fever. The accepted threshold for bacteriuria 
to meet the definition of CAUTI is ≥103 colony-forming units per 
milliliter of urine.
The central diagnostic difficulty of CAUTI is that, because cathe­
ters provide a conduit for bacteria to enter the bladder, bacteriuria is 
inevitable with urinary catheterization. The typical signs and symp­
toms of UTI, including pain, urgency, dysuria, fever, and peripheral 
leukocytosis, also have less predictive value for diagnosis of UTI in 
catheterized patients. Since bacteriuria and pyuria are expected in 
this population, the diagnostic evaluation of a febrile patient with 
a urinary catheter should not end with an abnormal urinalysis. 
To make a diagnosis of CAUTI, first, signs and symptoms of UTI 
(localizing and/or systemic) should be present along with pyuria 
and bacteriuria. Additionally, other infectious and noninfectious 
causes of the patient’s symptoms should be systematically ruled out 
before settling on the diagnosis of CAUTI.
■
■DIAGNOSTIC TOOLS
History 
The diagnosis of any of the UTI syndromes or ASB begins 
with a detailed history (Fig. 140-4). Patient-reported symptoms have 
high positive predictive value in uncomplicated cystitis, at least among 
adult women; data are lacking for other populations. Self-diagnoses 
among women with recurrent UTI are particularly accurate and 
account for the success of patient-initiated treatment for recurrent 
cystitis. A meta-analysis of the diagnostic utility of history and physical 
findings for UTI concluded that, in women presenting with at least one 
localizing urinary symptom (dysuria, frequency, hematuria, or back 

A
B
FIGURE 140-3  Xanthogranulomatous pyelonephritis. A. This photograph shows 
extensive destruction of renal parenchyma due to long-standing suppurative 
inflammation. The precipitating factor was obstruction by a staghorn calculus, 
which has been removed, leaving a depression (arrow). The mass effect of 
xanthogranulomatous pyelonephritis can mimic renal malignancy. B. A large 
staghorn calculus (arrow) is seen obstructing the renal pelvis and calyceal system. 
The lower pole of the kidney shows areas of hemorrhage and necrosis with collapse 
of cortical areas. (Images courtesy of Dharam M. Ramnani, MD, Virginia Urology 
Pathology Laboratory, Richmond, VA.)
pain) and no complicating factors, the probability of acute cystitis or 
pyelonephritis is 50%. If vaginal discharge and complicating factors are 
absent and risk factors for UTI are present, then the probability of UTI 
is close to 90%. Further laboratory evaluation with dipstick testing or 
urine culture prior to antimicrobial treatment is not necessary in such 
patients unless there is concern for resistant pathogens (e.g., in patients 
presenting with recurrent UTI, prior treatment failure, known coloni­
zation with extensively resistant pathogens, or high local prevalence of 
resistance to the empirical antibiotic being given).
In applying the patient’s history as a diagnostic tool, one significant con­
cern is that STIs—caused by C. trachomatis in particular—might be inap­
propriately treated as UTI. Importantly, women with multiple sexual 
partners and inconsistent use of condoms are at increased risk for both 
UTI and STIs, and symptoms alone do not always distinguish between 
these conditions. Dysuria might instead be due to cervicitis (C. trachomatis, 
N. gonorrhoeae), vaginitis (Candida albicans, Trichomonas vaginalis), 
herpetic urethritis, interstitial cystitis, or noninfectious vaginal or vul­
var irritation. Vaginal discharge in particular should prompt consider­
ation of STI. In this particular patient population, consideration should

Clinical Presentation
Patient Characteristics
Diagnostic and Management Considerations
Otherwise healthy woman who
is not pregnant, low risk for
multidrug resistance
Woman with a history of or risk
factors for STI
Acute onset of urinary
symptoms
Dysuria
Frequency
Urgency
Male with perineal, pelvic, or
prostatic pain
Patient with indwelling urinary
catheter
All other patients
Otherwise healthy woman
who is not pregnant
Acute onset of back pain,
nausea/vomiting, or fever
with or without cystitis
symptoms
All other patients
Systemic symptoms
Elderly patients; patients with
spinal cord injury,
immunocompromise, no
alternate diagnosis
Fever
Altered mental status
Leukocytosis
Consider complicated UTI
Consider other etiologies
Urine culture
Blood cultures
Positive urine culture in patient
who is pregnant, or patient
undergoing invasive urologic
procedure
No urinary symptoms
Positive urine culture in all other
patients
Positive urine culture in patient
with indwelling catheter
Otherwise healthy woman who
is not pregnant
Recurrent acute urinary
symptoms
Male patient
FIGURE 140-4  Diagnostic approach to urinary tract infection (UTI). NTF, nitrofurantoin; TMP-SMX, trimethoprim-sulfamethoxazole; UTI, urinary tract infection.
be given to STI screening either at the time of empirical treatment for 
UTI or if symptoms do not resolve with treatment.
Urine Dipstick Test, Urinalysis, and Urine Culture 
Useful 
tools in the diagnosis of UTI include the urine dipstick test (for nitrite 
and leukocyte esterase) and microscopic urinalysis (for counts of red 
and white blood cells), both of which provide point-of-care informa­
tion that can primarily be used for ruling out UTI in patients who do 
not have a clear clinical diagnosis. Urine culture, another diagnostic 
tool, can retrospectively provide proof that bacteria were present in 
the urinary tract and can provide information on susceptibilities of the 

Consider uncomplicated cystitis
No urine culture needed
Consider telephone management
Consider uncomplicated cystitis or STI
Urinalysis, culture
STI evaluation, pelvic exam
Consider acute prostatitis
Urinalysis and culture
Consider urology evaluation
Consider CAUTI
Exchange or remove catheter
Urinalysis and culture
Blood cultures if fever
Consider complicated UTI
Urinalysis and culture
Address any modifiable anatomic or
functional abnormalities
Consider pyelonephritis
Urinalysis and culture
Consider outpatient management
Consider pyelonephritis or acute prostatitis
(male)
CHAPTER 140
Urine culture
Blood cultures
Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis 
Consider ASB
Screening and treatment warranted
Consider ASB
No additional workup or treatment
needed
Consider CA-ASB
No additional workup or treatment
needed
Remove unnecessary catheters
Consider recurrent cystitis
Urine culture to establish diagnosis
Consider prophylaxis or patient-initiated
management (see text)
Consider chronic bacterial prostatitis
Consider urology consult
isolated organism(s). A key point is that patients with urinary catheter­
ization will almost always have both pyuria and bacteriuria. Therefore, 
presence of pyuria and bacteriuria alone in the absence of symptoms do 
not indicate a diagnosis of UTI.
Understanding the parameters of the dipstick test is important in 
interpreting its results. Only members of the Enterobacterales family 
convert nitrate to nitrite, and enough nitrite must accumulate in the 
urine to reach the threshold of detection. This poses three problems 
limiting nitrites’ sensitivity and specificity. First, nitrites could be posi­
tive in a patient with Enterobacterales ASB. Second, nitrites would be 
negative in a patient with UTI due to non-Enterobacterales organisms.

Third, nitrites might also be falsely negative in a woman with acute cys­
titis who is voiding frequently because of significant oral fluid intake.

The leukocyte esterase test detects this enzyme in neutrophils 
present in the host’s urine, whether the cells are intact or lysed. Practi­
cally speaking, it is a less sensitive and specific surrogate for pyuria 
as measured by urine microscopy. Many reviews have attempted to 
describe the diagnostic accuracy of dipstick testing for UTI. The most 
important point for practicing clinicians is that a dipstick test negative 
for both nitrite and leukocyte esterase should prompt consideration of 
diagnoses other than UTI to explain the patient’s symptoms, keeping 
in mind that the dipstick results can be falsely negative in a small per­
centage of cases. Importantly, a negative urine dipstick test is not suf­
ficiently sensitive to rule out bacteriuria in pregnant women, for whom 
ASB screening should be performed via urine culture.
Urine microscopy reveals pyuria in nearly all cases of cystitis and 
hematuria in approximately 30% of cases. Pyuria has historically been 
defined as >10 leukocytes per high-powered microscopy field (HPF). 
Modern data indicate that, at least for older women, median urine 
white blood cells (WBCs) per HPF are far higher in UTI. As such, the 
cutoff of >10 WBCs/HPF has poor specificity (36%) for UTI, and a 
cutoff closer to 250 WBCs/HPF might better correlate with presence of 
urinary symptoms. However, at present, >10 WBCs/HPF remains the 
generally accepted standard for what defines presence of pyuria.
Detection of bacteria in a urine culture from a patient with symptoms 
of cystitis can confirm the diagnosis of UTI. However, culture results 
often do not become available until at least 24 h after a patient presents 
for care, with identification of individual organisms and their suscepti­
bilities usually requiring an additional 24–48 h. Furthermore, identify­
ing the presence of bacteria in the urine does not necessarily imply the 
presence of symptoms; therefore, a positive urine culture is consistent 
with both UTI and ASB. This issue is a perennial source of inaccuracy 
for retrospective studies of UTI, which are often flawed by defining UTI 
as the combination of pyuria and bacteriuria without requiring clinical 
documentation of symptoms. Studies of women with symptoms of cysti­
tis have found that a colony count threshold of >102 bacteria/mL is more 
sensitive (95%) than a threshold of 105/mL for the diagnosis of acute 
cystitis in women. Fewer data are available in men about the threshold 
of bacteriuria to establish cystitis. When interpreting urine culture 
results, the clinician should consider that contamination with the normal 
microbial flora of the distal urethra, vagina, or skin is common and that 
these contaminants can grow to high numbers when the collected urine 
is allowed to stand at room temperature. In most instances, a culture 
that yields mixed bacterial species is contaminated except in settings of 
long-term catheterization, chronic urinary retention, or the presence of a 
fistula between the urinary tract and the gastrointestinal or genital tract.
PART 5
Infectious Diseases
TREATMENT
Urinary Tract Infections
The approach to diagnosis and treatment is influenced by which of 
the UTI clinical syndromes is suspected and presence of risk factors 
for resistant pathogens (Fig. 140-4).
GENERAL CONSIDERATIONS FOR ANTIMICROBIAL THERAPY
Studies indicate that treatment of UTI is usually the first or second 
most common indication for antimicrobials in ambulatory, inpa­
tient, and long-term-care settings. Responsible use of antimicrobi­
als for this common infection has broad implications for preserving 
antibiotic effectiveness into the future.
Importantly, antimicrobial therapy is warranted for any true 
(symptomatic) UTI. Studies of nonantibiotic treatment for UTI 
(e.g., with nonsteroidal anti-inflammatory drugs alone) suggest 
that this approach delays clinical response and predisposes patients 
to more invasive infections. Delayed therapy, in which a patient 
receives a prescription for antibiotics but fills it only if symptoms 
fail to resolve in a day or two, has the potential advantage of 
avoiding antibiotic use in those patients who do not have cysti­
tis to begin with; however, this approach has the downsides of 

prolonging discomfort and a small increased risk of progression to 
pyelonephritis in patients who do have true UTI. Potentially higheryield antimicrobial stewardship interventions in UTI management 
include encouraging clinicians to avoid unnecessary treatment of 
ASB, to avoid ordering urine cultures in patients who lack urinary 
or systemic symptoms suggestive of UTI, and to avoid prescribing 
overly long antibiotic durations for UTI.
In 1999, trimethoprim-sulfamethoxazole (TMP-SMX) was rec­
ommended as the treatment of choice for uncomplicated cystitis 
in the first published UTI guidelines of the Infectious Diseases 
Society of America. However, local uropathogen resistance patterns 
and national differences in the availability of certain antimicrobial 
agents are such that providing a global or even national recom­
mendation for a single preferred empirical antibiotic for UTI is 
challenging. Instead, clinicians must use their knowledge of local 
resistance patterns and individual patient factors (e.g., allergies 
and potential for drug–drug interactions) to select from groups of 
antimicrobials based on their efficacy, toxicity risks, and potential 
for collateral damage (defined below). The choice of antimicrobial 
agent, the dose, and the duration of therapy also depend on the 
clinical syndrome (that is, which type of UTI specifically is being 
treated) and the rapidity of clinical improvement.
Collateral damage refers to the adverse ecologic effects of anti­
microbial therapy, including killing of the patient’s normal flora 
(predisposing to Clostridioides difficile infection) and selection of 
drug-resistant organisms. The implication of collateral damage for 
UTI management is that a drug that is highly efficacious for treat­
ment of UTI is not necessarily the optimal first-line agent if it also 
has pronounced secondary effects on the normal flora or is likely 
to significantly adversely affect resistance patterns. Drugs used for 
UTI that have a minimal effect on fecal flora include pivmecil­
linam, fosfomycin, and nitrofurantoin. In contrast, TMP-SMX, 
quinolones, and β-lactams (particularly the late-generation cepha­
losporins) affect the fecal flora more significantly and are notably 
the agents for which rising resistance has been documented.
Choosing judiciously whether to initiate antibiotic therapy and 
then selecting the agent with the least potential for collateral dam­
age to be given for the shortest effective duration are important 
factors in global efforts to stem the rise of antimicrobial-resistant 
organisms. Common risk factors for resistance to specific anti­
microbials in UTI include prior urine or blood cultures with an 
organism resistant to that antimicrobial, recent exposure to that 
antimicrobial, or travel to an area where resistance to that antimi­
crobial is especially prevalent. For each of these factors, the magni­
tude of risk is greater with more recent exposures in the preceding 
year; the greatest increase in risk occurs with fluoroquinolones. 
More data is available documenting this risk of resistance with 
prior exposure to the antibiotic for fluoroquinolones than for other 
antibiotics. Other general risk factors for antimicrobial resistance in 
UTI include urinary catheterization, prior exposure to antibiotics of 
any class, and residence in a healthcare facility.
ASYMPTOMATIC BACTERIURIA
Critically, treatment of ASB does not decrease frequency of subse­
quent true UTIs. Clinical trial data from renal transplant recipients 
suggest that ASB treatment might even increase future risk of infec­
tion. Importantly, though, treatment of ASB in pregnant patients 
and patients undergoing high-risk urologic procedures is recom­
mended to reduce risk of complications (see discussion above) and 
should be guided by urine culture results. In all other populations, 
screening for and treating ASB are discouraged. Specifically, a urine 
culture does not need to be obtained at the time of placement or 
removal of a urinary catheter if the patient is asymptomatic. The 
majority of cases of catheter-associated bacteriuria are asymptom­
atic and do not warrant antimicrobial therapy.
CYSTITIS
Many episodes of uncomplicated cystitis in women (i.e., cystitis 
without systemic symptoms, symptoms of pyelonephritis, or urinary

TABLE 140-1  Treatment Strategies for Acute Uncomplicated Cystitis
DRUG
DOSE
DURATION
COMMON SIDE EFFECTS
Nitrofurantoin
100 mg bid
Women or men: 5–7 days
Nausea, headache
TMP-SMX
1 DS tablet bid
Women: 3 days Men: 7 days
Rash, urticaria, nausea, vomiting, hematologic abnormalities
Fosfomycin
3-g sachet
Women: 1 day
Men: qod × 3 doses
Pivmecillinam
400 mg bid
Women: 3–7 days
Nausea, vomiting, diarrhea
Fluoroquinolones
Dose varies by agent
Women: 3 days
Men: 7 days
β-Lactams
Dose varies by agent
Women or men: 5–7 days
Diarrhea, nausea, vomiting, rash, urticaria
Abbreviations: DS, double-strength; TMP-SMX, trimethoprim-sulfamethoxazole; bid, twice a day; qod every other day.
catheterization) can be managed remotely (Fig. 140-4). Studies of 
telephone-management algorithms for UTI indicate low risk of 
serious complications, with the important caveat that such algo­
rithms have generally involved otherwise healthy women who are 
at low risk of complications of UTI; thus, patients with other UTI 
syndromes or more complicated prior histories require further diag­
nostic evaluation and might not be as adequately managed remotely.
As described above, cystitis in men is unusual except in the 
setting of urinary catheterization or obstructive uropathy. Before 
settling on this diagnosis in men, however, the clinician should be 
confident that ABP, CBP, and pyelonephritis with or without uri­
nary obstruction have been excluded. True uncomplicated cystitis 
in afebrile men can be treated with only 7 days of antimicrobial 
therapy; the durations shorter than 7 days used for uncomplicated 
cystitis in women have not been adequately studied in men.
Several effective therapeutic regimens are available for acute 
uncomplicated cystitis in women; data are very limited on therapy 
for cystitis in men (Table 140-1). Preferred agents for treatment 
of acute uncomplicated cystitis include TMP-SMX, nitrofuran­
toin, fosfomycin, and pivmecillinam. Fosfomycin is somewhat less 
studied than TMP-SMX and nitrofurantoin, but it is also effective 
and is preferred in cystitis because of its selective concentration in 
urine, low risk for collateral damage, and potential to retain efficacy 
against MDR E. coli. Pivmecillinam was approved for treatment of 
cystitis in the United States in 2024. It also often retains activity 
against MDR E. coli, including some expressing extended-spectrum 
β-lactamases.
Alternative agents for treatment of cystitis include fluoroquino­
lones and β-lactams. β-lactams require longer durations of therapy 
(5–7 days) even in uncomplicated cystitis and are associated with 
higher clinical failure rates (compared with either fluoroquinolones 
or TMP-SMX) in some randomized controlled trials. Despite these 
limitations, β-lactams are favored over fluoroquinolones as an 
alternative agent for treatment of uncomplicated cystitis because of 
the bacterial resistance and side effects associated with fluoroqui­
nolones. Fluoroquinolones are highly effective for treating UTI but 
cause high collateral damage as well as numerous rare but serious 
drug toxicities (e.g., collagen vascular pathology such as tendon 
rupture, retinal detachment, and aortic aneurysm), leading the 
U.S. Food and Drug Administration (FDA) to advise against using 
fluoroquinolones for uncomplicated cystitis in women unless no 
alternatives are available. Importantly, in men, if there is concern 
for prostatic involvement, fluoroquinolones or TMP-SMX are pre­
ferred over β-lactams because fluoroquinolones have superior pen­
etration into the prostate. The pros and cons of each specific agent 
are discussed in more detail below.
TMP-SMX remains an excellent option for treatment of cys­
titis in areas where local uropathogen antibiogram data do not 
clearly favor other preferred agents or when the patient has recent 
microbiology demonstrating a TMP-SMX–susceptible uropatho­
gen. Otherwise, the optimal setting for empirical use of TMP-SMX 
is uncomplicated cystitis in a patient who has an established rela­
tionship with the practitioner and has no barriers to seeking further 
care if their symptoms do not respond promptly.

Diarrhea, nausea, headache
Nausea, vomiting, diarrhea, headache, drowsiness, insomnia
Resistance to nitrofurantoin remains low despite >70 years of 
use, probably because several mutational steps are required for 
bacterial resistance to this drug. Nitrofurantoin remains highly 
active against E. coli. However, importantly, most Proteus, Provi­
dencia, Morganella, Pseudomonas, and Serratia and some Klebsiella 
and Enterobacter strains are intrinsically resistant to this drug. A 
5-day course of nitrofurantoin is as effective as a 3-day course of 
TMP-SMX for treatment of acute uncomplicated cystitis in women. 
Nitrofurantoin should not be used in patients with a creatinine 
clearance <30 mL/min. It does not reach significant levels in tissue 
and so cannot be used to treat pyelonephritis or prostatitis. Addi­
tionally, we advise against long-term (i.e., multiple years) prescrip­
tion of nitrofurantoin as prophylaxis for recurrent UTIs because of 
the risk of sometimes irreversible pulmonary toxicities.
CHAPTER 140
Guidelines also recommend fosfomycin, which interferes with 
bacterial cell-wall formation, as an option for uncomplicated cysti­
tis, given its easy dosing and low collateral damage. While fosfomy­
cin is active against E. coli, its activity against other Enterobacterales 
species is less reliable. Moreover, fosfomycin susceptibility testing 
is difficult to perform, and the results of such testing are not typi­
cally included in standard automated microbiologic susceptibility 
reports. Oral fosfomycin is given as a single 3-g dose sachet (pow­
der) that is dissolved in a glass of water and swallowed. Similar to 
nitrofurantoin, renal tissue levels of fosfomycin are low, and a dif­
ferent antibiotic should be used if treating pyelonephritis. While not 
extensively studied for this indication, fosfomycin has been used in 
the treatment of prostatitis to manage pathogens resistant to other 
oral agents.
Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis 
Despite their often high rates of urinary secretion, β-lactams as a 
class have not performed as well as TMP-SMX or fluoroquinolones 
for treatment of acute cystitis. Rates of pathogen eradication are 
lower, and relapse rates are higher with β-lactam drugs compared 
with other agents. The generally accepted explanation for this 
observation is that β-lactams fail to eradicate uropathogens from 
the vaginal reservoir, which is specific to female patients with UTI. 
Supporting this hypothesis are limited indirect data indicating 
that treatment success with cephalexin is as good as or better than 
success with other classes in male UTI. Amoxicillin resistance has 
become widespread in E. coli, and many strains resistant to TMPSMX are also resistant to some or all of the other oral β-lactams. 
Thus, as described for TMP-SMX above, β-lactams such as cef­
podoxime or cefixime are optimally used for patients known to 
have susceptible uropathogens or in areas where local antibiograms 
demonstrate that resistance remains uncommon.
The fluoroquinolones ciprofloxacin and levofloxacin are highly 
effective as short-course therapy for cystitis due to susceptible flora. 
By contrast, moxifloxacin in particular might not reach adequate 
urinary levels. The two main concerns about using fluoroquino­
lones for acute cystitis are the propagation of fluoroquinolone 
resistance, not only among uropathogens but also among other 
organisms causing more serious and difficult-to-treat infections 
at other sites, and fluoroquinolones’ rare but potentially serious 
adverse effects (increased risk of Achilles’ tendon rupture, neuropa­
thy, and aortic dissection). In light of these potential detrimental

effects, the FDA issued an advisory against using fluoroquinolones 
to treat acute cystitis in patients who have other effective therapeu­
tic options.

Urinary analgesics are appropriate in certain situations to help 
the patient with resolution of bladder discomfort in cystitis. The 
urinary tract analgesic phenazopyridine is widely used but can 
cause significant nausea. Combination analgesics containing uri­
nary antiseptics (such as methenamine and methylene blue), a 
urine-acidifying agent (sodium phosphate), and an antispasmodic 
agent (hyoscyamine) also are available. There are no well-established 
criteria for when to use these agents, although as mentioned 
above, multiple clinical trials demonstrate that symptomatic treat­
ments alone are not an adequate substitute for antimicrobials when 
patients have true UTI.
PROSTATITIS
The prostate is involved in the majority of cases of febrile UTI in 
men and can also be a source of recurrent cystitis. ABP should 
specifically be suspected in men presenting with UTI with systemic 
symptoms without another clear anatomic location of UTI, such 
as pyelonephritis. CBP should be suspected when patients have 
recurrent UTI, especially if not in the context of urinary catheter­
ization). Both ABP and CBP should be suspected when patients 
have prostatic symptoms. If ABP is suspected, antimicrobial therapy 
should be promptly initiated after urine and blood cultures are 
obtained. For ABP, at least 2 weeks and potentially up to 4 weeks 
of a fluoroquinolone or TMP-SMX is recommended for susceptible 
uropathogens. Identification of a prostatic abscess should prompt 
consultation to urologic specialists. For CBP, a 4- to 6-week course 
of antibiotics is typically given, and recurrences (not uncommon) 
may warrant up to a 12-week course of therapy. These durations are 
based on older observational studies and historic norms of practice 
and need be to clarified with modern randomized controlled trials.
PART 5
Infectious Diseases
PYELONEPHRITIS
Patients with pyelonephritis have tissue-invasive disease and are 
often systemically ill. Therefore, empirical therapy should be reli­
able and rapidly reach therapeutic levels in both renal parenchyma 
and blood. In years past, increasing TMP-SMX resistance made 
fluoroquinolones the empirical treatment of choice for pyelone­
phritis, and quinolones remain among the best-studied agents for 
acute pyelonephritis. However, quinolone resistance is now also 
increasingly prevalent.
For hospitalized patients, we recommend empirical therapy 
with an IV β-lactam for pyelonephritis, with attention to choosing 
an agent to which the patient has not recently had a resistant uro­
pathogen in urine or blood and appears highly reliable based on the 
local antibiogram. For patients with pyelonephritis who are not and 
do not need to be hospitalized, we recommend empirical therapy 
with TMP-SMX, ciprofloxacin, or levofloxacin based on local anti­
biogram data, along with urine culture collection and short-term 
follow-up. Optimally, an initial dose of IV or IM β-lactam or an 
aminoglycoside to ensure effective empirical therapy can be pre­
scribed, where this is practical and feasible. Ambulatory patients 
with pyelonephritis should be hospitalized if they are unable to 
tolerate oral medications (e.g., due to nausea and vomiting) or are 
unlikely to adhere to short-term follow-up.
For susceptible isolates, clinical trial data indicate that 5–7 days 
of an oral fluroquinolone or 7–14 days of oral TMP-SMX (depend­
ing on rapidity of clinical improvement) are highly effective options 
for pyelonephritis. Oral β-lactam agents are less effective and 
should be used with caution and close follow-up. Nitrofurantoin, 
pivmecillinam, and fosfomycin should not be used for pyelonephri­
tis. Options for parenteral therapy for uncomplicated pyelonephri­
tis include late-generation cephalosporins (such as ceftriaxone or 
cefepime), piperacillin-tazobactam, a carbapenem, or fluoroqui­
nolones (although the high bioavailability of this class makes IV 
administration superfluous for patients with who can tolerate and 
absorb oral medications). Alternative parenteral antibiotics include 

novel β-lactam/β-lactamase inhibitors (e.g., meropenem-vaborbactam) 
and aminoglycosides, which are considered alternative due to cost 
and toxicity profiles, respectively.
In general, the treatment of pyelonephritis should be guided by 
urine culture results and clinical resolution of symptoms. Pyelone­
phritis due to drug-resistant uropathogens requiring nonpreferred 
antibiotics should be treated in consultation with infectious disease 
specialists. Once the patient has responded clinically, oral therapy 
can be substituted for parenteral therapy. Treatment can be con­
cluded at 7 days for patients who have clinically responded (i.e., res­
olution of fever and return to hemodynamic stability with adequate 
source control) within that timeframe and who can be treated with 
a fluoroquinolone or TMP-SMX. Oral β-lactams may necessitate a 
longer course of treatment for pyelonephritis.
Patients with pyelonephritis who have not had a clinical response 
within 72 h should undergo further evaluation for an uncontrolled 
source of infection. Pyelonephritis can be complicated by acute 
papillary necrosis causing urinary obstruction, which requires 
intervention to relieve the obstruction, overcome the infection, and 
preserve renal function. Perinephric and renal cortical abscesses 
may require drainage percutaneous drainage. Percutaneous drain­
age can also be used as the initial therapy in emphysematous pyelo­
nephritis and can be followed by elective nephrectomy as needed 
depending upon the patient’s clinical status in consultation with 
urologic specialists. Xanthogranulomatous pyelonephritis (XGP) is 
treated with close collaboration with urologic colleagues and often 
requires nephrectomy; antibiotic treatment duration should be 
individualized in cases of XGP.
CATHETER-ASSOCIATED UTI
The bacteriology of CAUTI is diverse, and urine culture results 
are essential to guide treatment. The catheter should be exchanged 
(or, if possible, removed entirely) during treatment for CAUTI, the 
purpose of which is to remove biofilm-associated organisms that 
could serve as a nidus for reinfection. When possible, this should 
be done prior to sending urine cultures to ensure that the culture 
results reflect the microbiology of the bladder rather than the cath­
eter walls.
Most clinicians treat CAUTI for 7–14 days based on clinical 
response; the need for longer therapy than is used in uncomplicated 
cystitis is supported by a randomized controlled trial that identified 
more relapses after 3 versus 14 days of antimicrobials. Further stud­
ies on the optimal duration of therapy in CAUTI are needed.
The best strategy for prevention of CAUTI is to avoid insertion 
of unnecessary catheters and to remove catheters once they are no 
longer necessary. Quality-improvement collaboratives that have 
addressed technical aspects of CAUTI prevention (such as avoid­
ance of inappropriate catheterization) and team-communication 
strategies have shown the benefit of such approaches in decreasing 
rates of CAUTI in both acute- and long-term-care settings. Anti­
microbial catheters impregnated with silver or nitrofurazone have 
not been shown to provide significant clinical benefit with regard to 
reducing CAUTI rates and should not be used routinely. Evidence 
is insufficient to systematically recommend suprapubic catheters 
and condom urinary catheters as alternatives to indwelling urinary 
catheters as a way to prevent bacteriuria. Intermittent catheteriza­
tion may be preferable to long-term indwelling urethral catheteriza­
tion in certain populations (e.g., patients with spinal cord injury) to 
prevent both infectious and anatomic complications.
UTI IN PREGNANT PATIENTS
Aminopenicillins (ampicillin and amoxicillin) and cephalosporins 
have been used extensively in pregnancy and are the drugs of choice 
for treatment of ASB or UTI in pregnant patients. Importantly, 
though, widespread resistance to aminopenicillins precludes their 
use for pregnant patients with UTI if urine culture results are not 
already available. One retrospective case-control study suggested 
an association between nitrofurantoin use in the first trimester and 
birth defects, but this association has not been confirmed, and the

American College of Obstetrics and Gynecology (ACOG) suggests 
that nitrofurantoin can be used during all trimesters if β-lactam 
agents are not an option. Sulfonamides (including TMP-SMX) 
should be avoided both in the first trimester (because of possible 
teratogenic effects) and near term (because of a possible role in the 
development of neonatal kernicterus), although ACOG suggests 
TMP-SMX can be used as a potential treatment option at both times 
if no alternatives are available. Fluoroquinolones are avoided dur­
ing pregnancy because of possible adverse effects on fetal cartilage 
development. Pregnant patients with ASB or cystitis are generally 
treated for 5–7 days because of the absence of evidence to support 
shorter durations of therapy in this patient population. For preg­
nant patients with pyelonephritis, guidelines recommend parenteral 
β-lactam therapy with or without aminoglycosides based on limited 
observational data and historic norms of practice.
CANDIDURIA
The appearance of Candida in the urine is an increasingly common 
complication of indwelling catheterization, particularly for patients 
in the intensive-care unit, those taking broad-spectrum antimicro­
bial drugs, and those with underlying diabetes mellitus. In many 
studies, >50% of urinary Candida isolates have been found to be 
non–C. albicans species. The clinical presentation of candiduria 
varies widely—from asymptomatic colonization to pyelonephritis 
and sepsis—thereby making management challenging in some 
instances, particularly for patients with multiple other ongoing 
medical conditions. Removal of the urinary catheter results in reso­
lution of candiduria in more than one-third of asymptomatic cases. 
As with ASB, treatment of asymptomatic patients with candiduria 
has not been found to reduce recurrence of candiduria or subse­
quent infection. Therefore, treatment of asymptomatic patients is 
not routinely recommended for most patients.
By contrast, candiduria should be treated in patients who have 
symptomatic cystitis or pyelonephritis or those who are asymptom­
atic but are at high risk for disseminated disease (e.g., patients with 
neutropenia, patients who will undergo urologic manipulation, 
and low-birth-weight infants). Fluconazole (200–400 mg/d for 
7–14 days) reaches high levels in the urine and is the first-line regi­
men for Candida infections of the urinary tract. Although instances 
of successful eradication of candiduria by some of the newer azoles 
and echinocandins have been reported, these agents are relatively 
unstudied and are not recommended as first-line agents but can be 
considered in certain cases. For Candida isolates with high levels of 
resistance to fluconazole, oral flucytosine and/or parenteral ampho­
tericin B are additional options. Bladder irrigation with amphotericin B 
is generally not recommended.
■
■PREVENTION OF RECURRENT UTI IN WOMEN
Recurrence of uncomplicated cystitis in women is common, and a 
preventive strategy is indicated if recurrent UTIs are interfering with a 
patient’s lifestyle. The threshold of three or more symptomatic episodes 
per year to intervene or develop a specific preventive strategy is not 
absolute; clinicians are recommended to engage in shared decisionmaking with each individual patient to make determinations about a 
UTI preventive strategy.
Initial evaluation of a patient with recurrent cystitis should include 
confirmation of the diagnosis of recurrent UTI, imaging to identify 
renal calculi or another potential nidus of infection, and assessment for 
urinary retention. Referrals to urology, urogynecology, and/or pelvic 
physical therapy might be helpful when the diagnosis is unclear or an 
anatomic abnormality is suspected.
Nonantimicrobial prophylactic approaches to recurrent UTI are 
increasingly being studied. Observational data indicate that increasing 
fluid intake might reduce recurrent UTIs, and such an approach is gen­
erally well tolerated by healthy adults. Two recent clinical trials found 
that methenamine hippurate (converted to the antiseptic formaldehyde 
in the bladder) is well tolerated and might reduce recurrent UTIs as 
much as antibiotic prophylaxis. A recent Cochrane review of random­
ized clinical trials of cranberry products also found a significant benefit 

for adult women and children with recurrent UTI. Less is known about 
which products and what precise dosing are optimal. Lactobacillus 
probiotics are under investigation for UTI prevention, with one recent 
factorial trial suggesting that intravaginal but not oral lactobacilli 
products reduce recurrent UTIs. We advise caution, however, in rec­
ommending probiotics to immunocompromised patients, in whom 
probiotic-associated invasive infections have been described. Studies 
of mannose products for UTI prevention have produced mixed results.

Three antibiotic prophylactic strategies are available: continu­
ous (using daily or thrice-weekly dosing), postcoital (one dose after 
intercourse), and patient-initiated therapy. For the continuous and 
postcoital strategies, low doses of TMP-SMX or nitrofurantoin are typi­
cally utilized. Such approaches are usually highly effective during the 
period of active antibiotic intake. A prophylactic regimen is typically 
prescribed for 6 months and then discontinued. If bothersome infec­
tions recur, the prophylactic program can be reinstituted for the same 
duration or for a longer period.
Selection of resistant strains in the fecal flora has been documented 
in studies of patients taking prophylactic antibiotics. An approach of 
alternating antibiotic prophylaxis with periods of nonantimicrobial 
prevention could hypothetically allow for intermittent recovery of the 
gut microbiome. The choice between methenamine and cranberry 
products should be based on shared decision-making and individual 
patient response. Some studies suggest that although the rate of UTI 
will be decreased when using nonantimicrobial prophylaxis compared 
with no prophylaxis, the rate of UTI might be slightly higher than dur­
ing the antibiotic-suppression period.
Patient-initiated therapy involves supplying the patient with materi­
als for urine culture and with a course of antibiotics for self-medication 
at the first symptoms of infection. The urine culture is refrigerated and 
delivered to the physician’s office for confirmation of the diagnosis. 
When an established and reliable patient–provider relationship exists, 
the urine culture can be omitted as long as the symptomatic episodes 
respond completely to short-course therapy and are not followed by 
relapse.
CHAPTER 140
Urinary Tract Infections: Cystitis, Prostatitis, and Pyelonephritis 
■
■PROGNOSIS
Cystitis is a risk factor for recurrent cystitis and pyelonephritis. ASB is 
common among elderly and catheterized patients but does not in itself 
increase risk of infection or death. The relationships among recurrent 
UTI, chronic pyelonephritis, and renal insufficiency have been widely 
studied. In the absence of anatomic abnormalities such as reflux, recur­
rent infections in children and adults do not lead to chronic pyelone­
phritis or renal failure. Additionally, infection does not play a primary 
role in chronic interstitial nephritis; the primary etiologic factors in 
this condition are analgesic overuse, obstruction, reflux, and toxin 
exposure. By contrast, in the presence of underlying renal abnormali­
ties (particularly obstructing stones), infection as a secondary factor 
can accelerate renal parenchymal damage.
■
■FURTHER READING
Bilsen M et al: Current pyuria cutoffs promote inappropriate urinary 
tract infection diagnosis in older women. Clin Infect Dis 76:2070, 
2023.
Brehm TJ et al: Acute and chronic infectious prostatitis in older adults. 
Infect Dis Clin North Am 37:175, 2023.
Christmas MM et al: Menopause hormone therapy and urinary 
symptoms: A systematic review Menopause 30:672, 2023.
Drekonja DM et al: Effect of 7 vs 14 days of antibiotic therapy on reso­
lution of symptoms among afebrile men with urinary tract infection: 
A randomized clinical trial. JAMA 326:324, 2021.
Gupta V et al: Effectiveness of prophylactic oral and/or vaginal pro­
biotic supplementation in the prevention of recurrent urinary tract 
infections: A randomized, double-blind, placebo-controlled trial. 
Clin Infect Dis 78:1154, 2024.
Hooton TM et al: Asymptomatic bacteriuria and pyuria in premeno­
pausal women. Clin Infect Dis 72:1332, 2021.
Lafaurie M et al: Antimicrobial for 7 or 14 days for febrile urinary 
tract Infection in men: A multicenter noninferiority double-blind,