Editing Urinary Tract Infections (section)

== Bladder Infections ==

=== Risk Factors ===
* '''Reduced urine flow'''
** '''Outflow obstruction (BPH, prostate cancer, urethral stricture, foreign body (calculus)''')
** '''Neurogenic bladder'''
** '''Inadequate fluid uptake''' (dehydration)
* '''Promote colonization'''
** '''Sexual activity'''—increased inoculation
** '''Spermicide'''—increased binding
** '''Estrogen depletion'''—increased binding
** '''Antibiotic use'''—decreased indigenous flora
* '''Facilitate ascent'''
** '''Catheterization'''
** '''Urinary incontinence'''
** '''Fecal incontinence'''
** Residual urine with ischemia of bladder wall

=== Uncomplicated Acute Bacterial Cystitis ===

==== Definition ====

* '''<span style="color:#ff0000">Diagnosis of acute bacterial cystitis requires (2):'''
*# '''<span style="color:#ff0000">Laboratory confirmation of significant bacteriuria AND'''
*# '''<span style="color:#ff0000">Acute-onset symptoms (lower urinary tract symptoms)'''

==== Pathophysiology ====
* '''Pathogens'''
** '''<span style="color:#ff0000">E. coli is the causative organism in 75-90% of cases of acute cystitis in young women.'''
** '''<span style="color:#ff0000">S. saprophyticus, a commensal organism of the skin, is the second most common cause of acute cystitis in young women, accounting for 10-20% of these infections. Other organisms less commonly involved include Klebsiella and Proteus species and Enterococcus.'''
** '''<span style="color:#ff0000">In men, E. coli and other Enterobacteriaceae are the most commonly identified organisms.'''
* '''Sexual transmission of uropathogens has been suggested''' by demonstrating identical E. coli in the bowel and urinary flora of sex partners

==== Diagnosis and Evaluation ====

* '''<span style="color:#ff0000">Differential Diagnosis (11):</span>'''
#'''<span style="color:#ff0000">Interstitial cystitis/bladder pain syndrome</span>'''
#'''<span style="color:#ff0000">Overactive Bladder</span>'''
#'''<span style="color:#ff0000">Urinary calculi</span>'''
#'''<span style="color:#ff0000">Infectious bacterial or fungal vaginitis</span>'''
#'''<span style="color:#ff0000">Urethral infections caused by sexually transmitted pathogens</span>'''
#'''<span style="color:#ff0000">Vulvar dermatitis</span>'''
#'''<span style="color:#ff0000">Non-infectious vulvovestibulitis</span>'''
#'''<span style="color:#ff0000">Vulvodynia</span>'''
#'''<span style="color:#ff0000">Hypertonic pelvic floor muscle dysfunction</span>'''
#'''<span style="color:#ff0000">Genitourinary syndrome of menopause</span>'''
# '''<span style="color:#ff0000">CIS of the bladder</span>''' (less commonly)
===== History and Physical Exam =====
* '''<span style="color:#ff0000">History'''
** '''<span style="color:#ff0000">Signs and Symptoms'''
***Variable presenting symptoms of cystitis 
***'''<span style="color:#ff0000">Usually include dysuria, frequency, and/or urgency'''
***'''<span style="color:#ff0000">Suprapubic pain, incontinence, hematuria, or foul-smelling urine may develop'''
*** '''In older adults, the symptoms of UTI may be less clear'''
**** Given the subjective nature of these symptoms, '''careful evaluation of their chronicity becomes an important consideration.'''
***** Older females frequently have nonspecific symptoms that may be perceived as a UTI, such as dysuria, cloudy urine, vaginal dryness, vaginal/perineal burning, bladder or pelvic discomfort, urinary frequency and urgency, or urinary incontinence, but these tend to be more chronic
***** '''Acute-onset dysuria, particularly when associated with new or worsening storage symptoms, remains a reliable diagnostic criterion in older females''' living both in the community and in long-term care facilities.
*** '''By definition, acute cystitis is a superficial infection of the bladder mucosa, so <span style="color:#ff0000">fever, chills, and other signs of dissemination are not present.'''
* '''<span style="color:#ff0000">Physical Exam'''
** '''Most have no diagnostic physical findings'''
**'''<span style="color:#ff0000">Abdomen'''
***Some patients may experience suprapubic tenderness
** '''<span style="color:#ff0000">Pelvis'''
***'''<span style="color:#ff0000">Prolapse, urethral tenderness, urethral diverticulum'''
***'''<span style="color:#ff0000">Skene’s gland cyst, or other enlarged or infected vulvar or vaginal cysts'''
***'''<span style="color:#ff0000">Any other infectious and inflammatory conditions (vaginitis, vulvar dermatitis, herpes, and vaginal atrophy</span>''' (genitourinary syndrome of menopause)
***'''Pelvic floor musculature''' for tone, tenderness, and trigger points

===== Laboratory =====
* '''<span style="color:#ff0000">Urinalysis'''
** '''<span style="color:#ff0000">The presumptive laboratory diagnosis of acute cystitis is based on microscopic urinalysis, which indicates microscopic pyuria, bacteriuria, and occasionally hematuria.'''
* '''<span style="color:#ff0000">Urine culture'''
** '''<span style="color:#ff0000">Remains the definitive test'''
***'''Clinical judgment is needed to determine when a culture result represents clinically significant bacteriuria considering the patient presentation, urine collection method, and the presence of other suggestive factors such as pyuria.'''
****'''<span style="color:#ff0000">The definition for clinically significant bacteriuria of >10<sup>5</sup> colony forming units (CFU)/mL represents an arbitrary cut-off.</span>'''
****'''Although > 10<sup>5</sup> CFU/mL for bacterial growth on midstream voided urine may help distinguish bladder bacteriuria from contamination in asymptomatic, pre-menopausal women, <span style="color:#ff0000">a lower 10<sup>2</sup> CFU/mL threshold may be appropriate in symptomatic individuals</span>'''
**'''Obtain repeat urine studies when an initial urine specimen is suspect for contamination, with consideration for obtaining a catheterized specimen'''
***'''Urine culture contamination should be suspected when (3):'''
***#'''Mixed cultures containing ≥2 organisms'''
***#'''Low quantities (<103 CFU/mL) of a pathogenic organism in an asymptomatic patient'''
***#'''Specimen exhibits growth of normal vaginal flora (e.g. Lactobacilli, Group B Streptococci, Corynebacteria, or non-saprophyticus coagulase-negative Staphylococci)'''
***#*'''Growth of these organisms are thought to be contaminant and generally do not require treatment'''
***'''Concomitant urinalysis can also be useful (presence of epithelial cells or mucus on microscopic urinalysis may also suggest contaminant).'''
***'''When there is high suspicion for contamination, consider obtaining a catheterized specimen for further evaluation prior to treatment.'''
***'''Urine specimens should not sit at room temperature for > 30 minutes to facilitate lab diagnosis of UTI.'''

==== Management ====
* '''<span style="color:#ff0000">Antibiotic regimen'''
**'''<span style="color:#ff0000">Preferred (3)'''
**# '''<span style="color:#ff0000">Fosfomycin 3 gram PO x single dose'''
**# '''<span style="color:#ff0000">Nitrofurantoin 100 mg PO BID x 5 days'''
**# '''<span style="color:#ff0000">Trimethoprim-sulfamethoxazole DS 1 pill PO BID x 3 days'''
**'''<span style="color:#ff0000">Alternative when bacteria are resistant to the preferred antibiotics: ciprofloxacin, 250 mg BID x 3 days'''
***'''<span style="color:#ff0000">Fluoroquinolone antibiotics should not be the first line treatment of uncomplicated cystitis.'''
*'''≈90% of women are asymptomatic within 72 hours after initiating antibiotics'''
* '''A follow-up visit or culture is not required in young women who are asymptomatic after therapy.'''
** A follow-up visit, urinalysis, and urine culture are recommended in older women or those with potential risk factors and in men.
** '''Urologic evaluation is unnecessary in women and is usually unnecessary in young men who respond to therapy.  However, UTIs in most men should be considered complicated until proven otherwise.'''
* '''If a patient does not respond to therapy, appropriate microbiologic and urologic evaluations should be undertaken for the causes of unresolved and complicated UTIs.'''

=== Complicated Cystitis in Females ===
* '''Complicated UTIs requires either (5):'''
*# '''Anatomic or functional abnormality of urinary tract (outlet obstruction, stone disease, diverticulum, neurogenic bladder, VUR etc.)'''
*# '''Urinary instrumentation or foreign bodies in the urinary tract (i.e. catheters, stents, nephrostomy tubes)'''
*# '''Systemic disease (renal insufficiency, diabetes, immunodeficiency, organ transplantation)'''
*# '''Pregnancy'''
*# '''Multi–drug resistant bacteria'''
* '''Diagnosis and Evaluation'''
**'''Labs'''
***'''Urine cultures'''
****'''Mandatory to identify the bacteria and its antibiotic susceptibility'''
****Prior cultures should be reviewed and empiric selection of those results
* '''Management'''
** '''Patients who are candidates for outpatient therapy:'''
*** '''Oral ciprofloxacin 500 mg BID x 7 days'''
*** Once daily oral fluoroquinolone (ciprofloxacin 1000 mg ER x 7 days or levofloxacin 750 mg x 5 days)
*** Oral TMP-SMX DS BID x 14 days (not for Enterococcus or Pseudomonas)

=== Cystitis in Males ===

* '''Diagnosis and Evaluation'''
** '''Labs'''
*** '''Urine cultures'''
**** '''Mandatory to identify the bacteria and its antibiotic susceptibility'''
** '''Imaging'''
*** '''Complicated UTI in an older male warrants urologic evaluation such as CT urogram and cystoscopy due to the high incidence of associated urologic abnormalities such as obstruction from either urethral or ureteral strictures, tumor, or stones'''
**** ≈50% of males with UTIs have a significant abnormality
*** '''Uncomplicated cystitis in a young sexually active male may not require investigation beyond a follow-up urine culture.'''

*'''Management'''
** '''Preferred:'''
*** '''Trimethoprim/sulfamethoxazole DS (160/800 mg) 1 pill PO BID'''
*** Levofloxacin 500 mg po daily
*** Ciprofloxacin 500 mg po BID
*** Ciprofloxacin ER 1000 mg po daily
** '''Treatment is generally for 7-14 days, optimal duration is not known'''
=== Unresolved UTIs ===
* Indicates that initial therapy has been inadequate in eliminating symptoms and/or bacterial growth in the urinary tract.
* '''If the symptoms of UTI do not resolve by the end of treatment or if symptoms recur shortly after therapy, urinalysis and urine culture with susceptibility testing should be obtained.'''
** If the patient’s symptoms are significant, empirical therapy with a fluoroquinolone is appropriate, pending results of the culture and susceptibility testing.
* '''Causes of Unresolved Bacteriuria, in Descending Order of Importance'''
*# '''Pre-existing bacterial resistance''' to the drug selected for treatment
*# '''Development of resistance from initially susceptible bacteria'''
*# '''Bacteriuria caused by 2 different bacterial species with mutually exclusive susceptibilities'''
*# '''Rapid re-infection with a new, resistant species''' during initial therapy for the original susceptible organism
*# '''Renal failure''' (inability to deliver an adequate concentration of antibiotics into the urinary tract)
*# '''Papillary necrosis from analgesic abuse''' (defects in the medullary concentrating ability dilutes the antibiotic)
*# '''Staghorn calculi''' (large mass of bacteria)
*# '''Self-inflicted infections or deception in taking antimicrobial drugs''' (a variant of Munchausen syndrome)
* '''The first 4 causes that are associated with resistant bacteria require no further evaluation. However, if re-culture shows that the bacteria are sensitive to the antimicrobial agent the patient is taking, renal function and radiologic evaluation should be performed to identify renal or urinary tract abnormalities.'''
* '''Management'''
** '''Initial empirical antimicrobial selection for unresolved UTI should be based on the assumption that the bacteria are resistant and an''' antibiotic different from the original agent should be selected.
*** Fluoroquinolones offer excellent coverage in most cases and should be given for 7 days.
** When the bacterial susceptibilities are available, adjustments can be made if necessary.
** Urine cultures should be performed during and 7 days after therapy to ensure microbiologic efficacy.

=== Recurrent UTI ===
* '''See [[AUA & CUA Recurrent UTI (2019)|AUA/CUA Guideline Notes]]'''
* '''Recurrent UTIs are caused by either re-emergence of bacteria from a site within the urinary tract (bacterial persistence) or new infections from bacteria outside the urinary tract (re-infection).'''
** Clinical identification of these two types of recurrence is based on the pattern of recurrent infections. Bacterial persistence must be caused by the same organism in each instance, and infections that occur at close intervals are characteristic. Conversely, reinfections usually occur at varying and sometimes long intervals and often are caused by different species.
** The distinction between bacterial persistence and reinfection is important in management because '''patients with bacterial persistence can usually be cured of the recurrent infections by identification and surgical removal or correction of the focus of infection. Conversely, women with reinfection usually do not have an alterable urologic abnormality and require long-term medical management.'''
** '''The probability of recurrent UTIs'''
*** '''Increases with the number of previous infections'''
*** '''Decreases in inverse proportion to the elapsed time between the first and the second infections'''
* '''Bacterial persistence'''
** Once the bacteriuria has resolved (i.e., the urine shows no growth for several days after the antimicrobial agent has been stopped), recurrence with the same organism can arise from a site within the urinary tract that was excluded from the high urine concentrations of the antimicrobial agent.
** '''Correctable urologic abnormalities that cause bacteria to persist within the urinary tract between episodes of recurrent bacteriuria:'''
**# '''Infection stones'''
**# '''Chronic bacterial prostatitis'''
**# '''Foreign bodies'''
**# '''Urethral diverticula and infected periurethral glands'''
**# '''Unilateral infected atrophic kidney'''
**# '''Ureteral duplication and ectopic ureters'''
**# '''Unilateral medullary sponge kidney'''
**# '''Non-refluxing, normal-appearing, infected ureteral stumps after nephrectomy'''
**# '''Infected urachal cysts'''
**# '''Infected communicating cysts of the renal calyces'''
**# '''Papillary necrosis'''
**# '''Perivesical abscess with fistula to bladder'''
* '''Re-infections'''
** Patients with recurrent infections caused by different species or occurring at long intervals almost invariably have reinfections. These reinfections most often occur in females and are associated with ascending colonization from the bowel flora. Reinfections in men are often associated with a urinary tract abnormality.
** '''The possibility of a vesicoenteric or vesicovaginal fistula should be considered when the patient has any history of pneumaturia, fecaluria, diverticulitis, obstipation, previous pelvic surgery, or radiation therapy.'''
** Evaluation for presumed reinfections must be individualized.

=== Asymptomatic Bacteriuria ===
*'''<span style="color:#ff0000">Definition: bacteriuria of any magnitude without symptoms</span>'''
*'''<span style="color:#ff0000">Management</span>'''
**'''<span style="color:#ff0000">DO NOT routinely treat or screen for asymptomatic bacteriuria</span>'''
***No evidence that treatment of asymptomatic bacteriuria improves outcomes
**'''<span style="color:#ff0000">Indications for screening/treatment of asymptomatic bacteriuria (2):</span>'''**#'''<span style="color:#ff0000">Pregnant females</span>'''
**#'''<span style="color:#ff0000">Patients undergoing elective urologic surgery</span>'''
**#'''Neonatal candiduria, not technically bacteruria but should be treated even if asymptomatic'''
**#*'''Treat candiduria in neonates with parenteral fluconazole'''
** '''Asymptomatic bacteriuria and struvite stones'''
***'''Routine treatment of urease-producing bacteriuria in the absence of UTI symptoms or documented urinary tract stones is not recommended'''
***There is no clear evidence that identification and treatment of asymptomatic bacteriuria caused by urease-producing organisms (recall that urease-producing organisms include proteus, pseudomonas, klebsiella, mycoplasma, and staphylococcus) prevents struvite stone formation. However, '''in certain patients with recurrent struvite stones, screening for and treating urease-producing bacteriuria may be indicated if other measures have not been able to prevent stone formation.'''

=== Pyocystis ===
* '''Occurs in ≈20% of patients who undergo supravesical diversion'''
* Patients typically have a malodorous discharge and may develop sepsis
* '''Management'''
** '''Conservative: routine bladder irrigations'''
** '''If conservative measures fail, vaginal vesicostomy (creation of a large vesico-vaginal fistula), is an effective method of preventing pyocystis in females.'''

=== Urachal cyst infection ===
* '''The cyst material consists of desquamated epithelial cells. These cells can become infected'''
* '''Staphylococcus aureus has been identified as the most common organism.'''