Infections & Inflammation

Antibiotics & Prophylaxis

Antibiotic choice in urology is governed by a principle that does not apply elsewhere in medicine: antimicrobials are excreted in the urine at concentrations far higher than in serum. This makes urinary drug levels — not serum levels — the key driver of cure in uncomplicated infection, while serum levels remain critical whenever the kidney, prostate, or bloodstream is involved.

Principles of Antibiotic Therapy

Selecting empirical therapy depends on whether the infection is complicated or uncomplicated, the drug's spectrum against the probable pathogen, hypersensitivity history, side-effect profile, and cost. Duration depends on the extent and duration of tissue invasion, the bacterial and achievable antimicrobial concentration in urine, and host risk factors that impair natural defences.

Urine versus serum concentration:

• Resolution of infection tracks the susceptibility of the organism to the urinary concentration of the drug, but susceptibility testing is based on serum concentrations.
• Some agents never reach adequate serum levels for bacteraemia yet are effective at their achievable urinary concentration — e.g. E. coli may test resistant to amoxicillin while amoxicillin still clears urinary E. coli because of the high urine concentrations achieved.
• Blood concentration is unimportant in uncomplicated UTI but critical in bacteraemia and febrile infection with renal or prostatic parenchymal involvement.

Renal function:

• Dose modification is required for renally cleared agents: ciprofloxacin, nitrofurantoin, trimethoprim/sulfamethoxazole, trimethoprim, amoxicillin, piperacillin/tazobactam, cephalexin, cefuroxime, levofloxacin, clarithromycin, and tetracycline.
• In renal failure the kidney may fail to concentrate the drug in the urine, making eradication difficult. Urinary tract obstruction can likewise reduce urinary drug concentration.

Bacterial resistance — three mechanisms:

• Inherited chromosomal — the species lacks the target the drug acts on (e.g. Proteus and Pseudomonas are always resistant to nitrofurantoin).
• Acquired chromosomal — induced by exposure to antimicrobial agents.
• Extrachromosomal (plasmid-mediated) — acquired and transferable via plasmids ("R-factor" resistance). It arises in the bowel flora and is far more common than selection of pre-existing mutants in the urinary tract. All classes can produce plasmid-mediated resistance, but it is rare with fluoroquinolones and has never been reported for nitrofurantoin.

Because bowel flora is the major reservoir for uropathogens, infections after antibiotic therapy are commonly multidrug-resistant — yet resistant E. coli from bowel flora almost always remain susceptible to nitrofurantoin or the quinolones. Resistance is also influenced by the duration and amount of antibiotic used.

Mechanism of Action

Drug or class	Mechanism of action	Mechanism of resistance
β-Lactams (penicillins, cephalosporins, carbapenems, aztreonam)	Inhibit bacterial cell-wall synthesis	β-lactamase production; altered penicillin-binding protein; reduced porin size (decreased penetration)
Vancomycin	Inhibits cell-wall synthesis (binds D-Ala-D-Ala)	Enzymatic alteration of peptidoglycan at a point other than the target
Fosfomycin	Inhibits cell-wall synthesis (inactivates MurA/enolpyruvyl transferase)	Novel amino-acid substitutions or loss of transporter function
Aminoglycosides (gentamicin, tobramycin)	Inhibit ribosomal protein synthesis	Downregulated drug uptake; aminoglycoside-modifying enzymes
Clindamycin, macrolides (erythromycin, clarithromycin, azithromycin)	Inhibit ribosomal protein synthesis (50S subunit)	Ribosomal methylation; efflux
Quinolones (ciprofloxacin, levofloxacin)	Inhibit bacterial DNA gyrase	Mutation in the DNA-gyrase binding site; reduced porin size; active efflux
Trimethoprim-sulfamethoxazole	Competitive inhibition of dihydrofolate reductase	Draws folate from the environment (enterococci)
Nitrofurantoin	Inhibits several bacterial enzyme systems	Not fully elucidated; develops slowly with prolonged exposure

Spectrum of Coverage

Agent or class	Gram-positive	Gram-negative
Amoxicillin / ampicillin	Streptococcus, enterococci	Proteus mirabilis
Amoxicillin-clavulanate	Streptococcus, enterococci	Proteus, Klebsiella
Ampicillin-sulbactam	Staphylococcus (not MRSA), enterococci	Proteus, Klebsiella, H. influenzae
Anti-staphylococcal penicillins (methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin)	Streptococcus, Staphylococcus (not MRSA); not enterococci	None
Anti-pseudomonal penicillins (piperacillin, ticarcillin)	Streptococcus, enterococci	Most, including Pseudomonas
1st-gen cephalosporins (cefazolin, cephalexin)	Streptococcus, Staphylococcus (not MRSA)	E. coli, Proteus, Klebsiella
2nd-gen cephalosporins (cefamandole, cefuroxime, cefaclor)	Streptococcus, Staphylococcus (not MRSA)	E. coli, Proteus, Klebsiella, H. influenzae
2nd-gen cephalosporins (cefoxitin, cefotetan)	Streptococcus	E. coli, Proteus (incl. indole-positive), Klebsiella, H. influenzae
3rd-gen cephalosporins (ceftriaxone)	Streptococcus, Staphylococcus (not MRSA)	Most, excluding P. aeruginosa
3rd-gen cephalosporins (ceftazidime)	Streptococcus	Most, including P. aeruginosa
Aztreonam	None	Most, including P. aeruginosa
Aminoglycosides (gentamicin, tobramycin)	Staphylococcus (urine)	Most, including P. aeruginosa
Fluoroquinolones (e.g. ciprofloxacin)	Streptococcus (agent-dependent); not enterococci	Most, including P. aeruginosa
Nitrofurantoin	Staphylococcus (not MRSA), enterococci	Many Enterobacteriaceae (not Klebsiella, Proteus); does not cover P. aeruginosa, Providencia, Serratia, Acinetobacter
Fosfomycin	Enterococci; variable against S. saprophyticus	Most Enterobacteriaceae (variable against Klebsiella, Enterobacter); does not cover P. aeruginosa
Pivmecillinam	None	Most, excluding P. aeruginosa
Trimethoprim-sulfamethoxazole	Streptococcus, Staphylococcus; not enterococci	Most Enterobacteriaceae; does not cover P. aeruginosa
Vancomycin (option in penicillin allergy)	All, including MRSA	None
Clindamycin (option in penicillin allergy)	Streptococcus, Staphylococcus; not enterococci	Anaerobes; not Enterobacteriaceae
Carbapenems (ertapenem, imipenem, meropenem)	Broad	Broad — ertapenem has weak Pseudomonas coverage compared with meropenem

Adverse Reactions and Contraindications

• Aminopenicillins (amoxicillin, ampicillin, ampicillin-sulbactam): hypersensitivity (immediate or delayed), diarrhoea/GI upset, pseudomembranous colitis, a non-allergic maculopapular rash, decreased platelet aggregation. Rash risk rises with concurrent viral illness or allopurinol. Clavulanate adds diarrhoea/GI upset.
• Anti-staphylococcal penicillins: as above, plus acute interstitial nephritis (especially methicillin).
• Anti-pseudomonal penicillins: as above, plus hypernatraemia (sodium-salt load — caution in sodium-sensitive patients) and injection-site reactions.
• Cephalosporins: hypersensitivity (less than penicillins), GI upset, pseudomembranous colitis, positive Coombs test, decreased platelet aggregation (cefotetan, cefamandole, cefoperazone). Avoid with immediate penicillin hypersensitivity; ceftriaxone is contraindicated in neonates.
• Aztreonam: <1% cross-reactivity in penicillin/cephalosporin-allergic patients — usable with caution.
• Aminoglycosides: ototoxicity (vestibular and auditory), nephrotoxicity (non-oliguric azotaemia), neuromuscular blockade at high levels. Avoid in pregnancy except for pyelonephritis; caution in renal impairment, diabetes, hepatic failure, myasthenia gravis, and with other oto-/nephrotoxic drugs.
• Fluoroquinolones: tendon rupture and aortic rupture (each ~20/100,000 — stop at first sign of tendon pain), QT prolongation, photosensitivity, CNS effects (dizziness, tremor, confusion, mood change, hallucinations), and dysglycaemia with anti-diabetic agents.
• Fosfomycin: headache, GI upset, vaginitis.
• Pivmecillinam: rash, GI upset; caution in penicillin hypersensitivity.
• Nitrofurantoin: pulmonary hypersensitivity (acute cough/dyspnoea/fever through to chronic interstitial fibrosis), hepatotoxicity, peripheral neuropathy (worse with renal impairment, anaemia, diabetes, electrolyte imbalance, B-vitamin deficiency), GI upset, and haemolysis in G6PD deficiency. Avoid if renal function is <50 mL/min and avoid concomitant probenecid, magnesium, or quinolones.
• Trimethoprim-sulfamethoxazole: hypersensitivity/rash, GI upset, photosensitivity, haematologic toxicity (higher in AIDS patients and the elderly).

Antibiotics by Class

Aminopenicillins

Resistance now affects 40–60% of common urinary isolates (see Toronto antibiograms), limiting ampicillin/amoxicillin. Their effect on bowel and vaginal flora predisposes to reinfection with resistant strains and to Candida vaginitis. Adding clavulanate improves activity against β-lactamase producers but is costly with frequent GI effects. Extended-spectrum derivatives (pivmecillinam, piperacillin, mezlocillin, azlocillin) keep anti-enterococcal activity and add many ampicillin-resistant gram-negatives. Safe in pregnancy.

Cephalosporins

As a group, activity is high against Enterobacteriaceae and poor against enterococci. First-generation agents favour gram-positives plus E. coli and K. pneumoniae; second-generation adds anaerobe activity; third-generation is the most reliable against community-acquired and nosocomial gram-negatives. Reserve broad-spectrum agents for complicated infections, parenteral need, or likely resistance. Safe in pregnancy; ceftriaxone contraindicated in neonates.

Nitrofurantoin

Effective against common uropathogens but not Pseudomonas or Proteus. Rapidly excreted in urine but does not reach therapeutic tissue levels — so it is not used for upper-tract or complicated infection. It has minimal effect on bowel/vaginal flora (good for prophylaxis), and acquired resistance is exceedingly low.

• Pregnancy (ACOG 2017): in the first trimester, discuss benefits versus the unknown risks; nitrofurantoin or sulfonamides remain appropriate when no suitable alternative exists. In the second and third trimesters they can be first-line. Contraindicated in G6PD deficiency.
• Pregnancy (Campbell's): safe in the first and second trimester in patients without G6PD deficiency; discontinue at 35 weeks because of neonatal haemolytic-anaemia risk.

Trimethoprim-sulfamethoxazole

Effective against most common uropathogens but not Enterococcus or Pseudomonas. TMP alone is as effective as the combination for most uncomplicated infections with fewer side effects, but adding SMX gives synergistic bactericidal activity for upper-tract infection, reaches therapeutic tissue levels, and may slow resistance. It is inexpensive with minimal effect on bowel flora; main downsides are rash and GI upset. TMP blocks tubular secretion of creatinine, so serum creatinine rises while GFR is unchanged. Avoid TMP-SMX in pregnancy (early teratogenicity, late kernicterus); avoid TMP alone in pregnancy (megaloblastic anaemia), though TMP alone is acceptable in neonates.

Fosfomycin

Effective against most uropathogens — including the majority of gram-negatives and vancomycin-resistant Enterococcus — but not Pseudomonas. There is limited cross-resistance with other classes. It is effective as a single-dose empirical treatment for uncomplicated cystitis and is generally well tolerated.

Fluoroquinolones

Broad spectrum, highly effective against Enterobacteriaceae and P. aeruginosa, with good activity against S. aureus and S. saprophyticus but only marginal anti-streptococcal and modest anti-enterococcal coverage. Anaerobes are resistant, so vaginal/bowel flora are spared. Resistance is rising from overuse. Not nephrotoxic, but renal impairment prolongs the half-life — dose-adjust if creatinine clearance <30 mL/min. Contraindicated in children, adolescents, and pregnant/nursing women (cartilage damage). Interactions: may enhance warfarin; antacids (Mg/Al), iron, zinc, and sucralfate markedly reduce oral absorption; enoxacin and ciprofloxacin raise theophylline levels; avoid other QT-prolonging drugs such as amiodarone.

Surgical Prophylaxis

Surgical Wound Classification

• Clean — uninfected, no inflammation, no entry into the genital, urinary, or alimentary tract.
• Clean-contaminated — uninfected, controlled entry into those tracts.
• Contaminated — major break in sterile technique (gross GI spillage or non-purulent inflammation).
• Dirty — pre-existing clinical infection or perforated viscus.

Host Risk Factors for Post-Operative Infection

Advanced age, anatomic anomalies, poor nutritional status, smoking, chronic corticosteroid use, immunodeficiency, chronic indwelling hardware, infected endogenous/exogenous material, distant coexistent infection, and prolonged hospitalisation.

Recommended Regimens

Procedure	Antibiotic	Alternative	Duration
Cystoscopy with minor manipulation	If risk factors: TMP-SMX or amoxicillin/clavulanate	1st/2nd-gen cephalosporin; aminoglycoside ± ampicillin; aztreonam ± ampicillin	Single dose
Transurethral resection	Cefazolin or TMP-SMX	Amoxicillin/clavulanate; aminoglycoside ± ampicillin; aztreonam ± ampicillin	Single dose
Transrectal prostate biopsy	Fluoroquinolone or 1st/2nd-gen cephalosporin ± aminoglycoside or 3rd-gen cephalosporin	Aztreonam (may need ID consult)	Single dose
Percutaneous renal surgery	1st/2nd-gen cephalosporin or aminoglycoside + (clindamycin or metronidazole) or aztreonam + (metronidazole or clindamycin)	Ampicillin/sulbactam	≤24 hours
Ureteroscopy	1st/2nd-gen cephalosporin or TMP-SMX	Aminoglycoside ± ampicillin; aztreonam ± ampicillin; amoxicillin/clavulanate	Single dose
Open/lap/robotic — no urinary-tract entry	Cefazolin	Clindamycin	Single dose
Open/lap/robotic — controlled urinary-tract entry	Cefazolin or TMP-SMX	Ampicillin/sulbactam; aminoglycoside or aztreonam + (metronidazole or clindamycin)	Single dose
Open/lap/robotic — involving small bowel	Cefazolin	Clindamycin + aminoglycoside; cefuroxime; aminopenicillin + β-lactamase inhibitor ± metronidazole	Single dose
Implanted prosthetics (AUS, IPP, sacral neuromodulator)	Aminoglycoside or aztreonam + (1st/2nd-gen cephalosporin or vancomycin)	Aminopenicillin or β-lactamase inhibitor (ampicillin/sulbactam, ticarcillin, tazobactam)	≤24 hours

Typical doses: TMP-SMX 800/160 mg PO ×1; cefazolin (1st-gen) 2 g IV ×1; ceftriaxone (3rd-gen) 2 g IV ×1; clindamycin 600 mg IV ×1; levofloxacin 500 mg PO ×1 or ciprofloxacin 500 mg PO ×1; gentamicin 2 mg/kg IV ×1; vancomycin 1 g IV ×1; metronidazole 500 mg IV ×1. Intraoperative redosing: cefazolin 2 g q4h, clindamycin 600 mg q8h, gentamicin 1 mg/kg q8h, metronidazole 500 mg q6h.

Catheter Removal and Endocarditis Prophylaxis

Antibiotics after catheter removal do not significantly reduce UTI risk after radical prostatectomy or TURP. A 2021 systematic review and meta-analysis (Liu et al.) of 8 RCTs of prophylaxis after removal of a temporary (≤14-day) catheter — including two laparoscopic radical prostatectomy trials and one TURP trial — found only 2 of 8 studies showed benefit, and none of the three urological trials did (the two positive trials were in abdominal-surgery patients or women with bacteriuria). Overall prophylaxis reduced UTIs (RR 0.47, 95% CI 0.28–0.72), and subgroups most likely to benefit were age >60, those given TMP-SMX, and indwelling catheters >5 days.

Endocarditis risk: the risk of infective endocarditis (IE) after urologic procedures is low, and Enterococcus faecalis is the organism most likely to cause IE following GU bacteraemia. Prophylaxis solely to prevent IE is not recommended (a change from earlier AHA guidance). For patients with high-risk cardiac conditions (prosthetic valve, prior IE, congenital heart disease, cardiac transplant) and an active GU infection/colonisation who are to undergo GU manipulation — including elective cystoscopy — antibiotics to sterilise the urine may be reasonable (Class IIb): amoxicillin/ampicillin first-line for enterococci, vancomycin for penicillin allergy.

Indwelling orthopaedic hardware: prophylaxis is generally not indicated for urologic patients with joint replacements, pins, plates, or screws. It is advised only for those at higher risk of prosthetic-joint seeding — recently inserted implants (within 2 years) and/or the host risk factors above.

UTI: Fundamentals

This tab covers the framework that underlies every urinary tract infection — how UTIs are defined and classified, who gets them, how organisms reach and colonise the tract, and how the diagnosis is established. The condition-specific tabs (cystitis, pyelonephritis, special hosts) build on these principles.

Definitions

• Cystitis — a clinical syndrome of dysuria, frequency, urgency, and occasionally suprapubic pain. These symptoms usually indicate bacterial cystitis but may also reflect urethral or vaginal infection, or non-infectious causes (interstitial cystitis, bladder carcinoma, calculi). Conversely, a patient may be asymptomatic yet have bladder — and possibly upper-tract — infection.
• Acute pyelonephritis — a clinical syndrome of chills, fever, and flank pain accompanied by bacteriuria and pyuria. The term should not be used if flank pain is absent. It may have no morphologic or functional correlate on routine imaging, and is difficult to diagnose in spinal-cord-injured and elderly patients who cannot localise discomfort.
• Chronic pyelonephritis — a shrunken, scarred kidney diagnosed by morphologic, radiologic, or functional evidence. It may be post-infectious but is frequently not associated with UTI.

Uncomplicated vs complicated: an uncomplicated infection occurs in a healthy patient with a structurally and functionally normal urinary tract (the majority are women). A complicated UTI requires at least one of the following:

• Anatomic or functional abnormality (outlet obstruction, stone disease, diverticulum, neurogenic bladder, vesicoureteral reflux).
• Urinary instrumentation or foreign bodies (catheters, stents, nephrostomy tubes).
• Systemic disease (renal insufficiency, diabetes, immunodeficiency, organ transplantation).
• Pregnancy.
• Multidrug-resistant bacteria.

"Chronic" is a poor term in the context of UTIs (except chronic pyelonephritis or chronic bacterial prostatitis) because the duration is undefined. UTIs are also defined by their relationship to one another:

• First / isolated — occurs in someone who has never had a UTI, or whose prior infection was remote.
• Unresolved — has not responded to therapy and is documented to be the same organism with a similar resistance profile.
• Recurrent — occurs after documented successful resolution of a prior infection. Two subtypes: bacterial reinfection (re-introduction of bacteria from outside) and bacterial persistence (the same organism re-emerging from a focus within the tract — an infection stone, the prostate, or an infected atrophic kidney). Relapse is often used interchangeably.

The distinction matters because reinfection and persistence drive different evaluations and treatments. Two related terms: antimicrobial prophylaxis (preventing reinfection) and antimicrobial suppression (preventing growth of a persistent focus that cannot be eradicated).

Epidemiology

• UTIs are the most common bacterial infection. About 30% of women have had a symptomatic UTI requiring antimicrobials by age 24, and ~50% experience one in their lifetime.
• Catheter-associated UTIs (CAUTIs) are the most common nosocomial infection; 80% of nosocomial UTIs are due to an indwelling urethral catheter.
• Once a patient has one infection, further infections are likely: the probability of recurrence rises with the number of prior infections and falls in inverse proportion to the interval between the first and second. About 70% of recurrences are reinfection with a different organism, and most occur after 2 weeks but within 5 months.
• Incidence is increased in spinal cord injury, women with diabetes, multiple sclerosis, and HIV/AIDS. Diabetic women have more asymptomatic and symptomatic UTIs (no substantial increase in diabetic men); most diabetic UTIs are asymptomatic but diabetes predisposes to more severe infection. UTIs are 5× more prevalent in HIV-positive individuals. Of all patients with bacteriuria, those with spinal cord injury have the most severe UTIs and morbidity.

Pathogenesis

A UTI results from interaction between uropathogen and host, determined by bacterial virulence factors, inoculum size, and inadequacy of host defences.

Routes of Infection

• Ascending (most common) — bacteria from the bowel ascend the urethra into the bladder; adherence to introital and urothelial mucosa is key, and the route is enhanced by faecal soiling of the perineum, spermicide use, and catheters. Most pyelonephritis arises from retrograde ascent from bladder → ureter → renal pelvis and parenchyma. Reflux is probably not required, but cystitis-related oedema can alter the ureterovesical junction enough to permit it. Ascent is increased by anything that impairs ureteral peristalsis (gram-negative endotoxins, pregnancy, obstruction); bacteria then enter the parenchyma through the collecting ducts at the papillary tips.
• Haematogenous — uncommon in normal individuals; the kidney may be seeded in S. aureus bacteraemia (often oral origin) or Candida fungaemia.
• Lymphatic — direct extension from adjacent organs via lymphatics in unusual circumstances (severe bowel infection, retroperitoneal abscess).

Uropathogens

Most UTIs are caused by facultative anaerobes originating from bowel flora; S. epidermidis and C. albicans come from vaginal/perineal skin. (Recall: staphylococci are gram-positive cocci in clusters, streptococci in chains.) A useful list of common pathogens is KEEPPS — Klebsiella, E. coli, Enterococcus, Proteus, Pseudomonas, S. saprophyticus.

• Gram-negative: Enterobacteriaceae — E. coli is the most common cause (≈85% of community-acquired and 50% of hospital-acquired UTIs); the ST131 (O25b:H4) clone is a rapidly emerging multidrug-resistant strain with common β-lactamase and fluoroquinolone resistance. Also Proteus, Klebsiella, and (Pseudomonadaceae) Pseudomonas.
• Gram-positive (most of the remaining community-acquired infections): Enterococcus faecalis and Staphylococcus saprophyticus.
• Nosocomial: E. coli, Klebsiella, Enterobacter, Citrobacter, Serratia, Pseudomonas, Providencia, E. faecalis, and S. epidermidis.
• Age effects: S. saprophyticus causes ≈10% of symptomatic lower UTIs in young, sexually active women but rarely infects males or the elderly. In neonates and young infants, empirically cover Enterococcus (higher incidence in early infancy).
• Fastidious organisms: symptomatic UTIs growing only obligate anaerobes are rare but these are frequent in suppurative GU infections — usually Bacteroides (incl. B. fragilis), Fusobacterium, anaerobic cocci, and Clostridium perfringens. Suspect them when irritative symptoms plus cocci or gram-negative rods on microscopy coexist with negative routine aerobic cultures. M. tuberculosis and non-TB mycobacteria do not grow aerobically and may surface during a sterile pyuria work-up.
• Uropathogenic E. coli (UPEC): expresses fimbrial and afimbrial adhesins. Type 1 (mannose-sensitive) pili are found on both pathogenic and non-pathogenic E. coli; "P" pili (P for pyelonephritis) are found in most pyelonephritogenic strains.

Host Defences and Susceptibility

• Epithelial receptivity — women susceptible to UTI may have vaginal (and buccal) epithelial cells with increased bacterial adherence, suggesting a genetic trait; blood-group determinants on uroepithelial cells also influence susceptibility. Uropathogens adhere more in menopausal than premenopausal women, and estrogen decreases recurrent-UTI susceptibility. At the bladder, FimH-mediated binding is the initial step and is essential for UPEC invasion.
• Natural defences — the normal flora of the introitus, periurethral area, and urethra (lactobacilli, corynebacteria, coagulase-negative staphylococci, streptococci) form a barrier. The most inhibitory urinary factors are osmolality, urea concentration, organic-acid concentration, and pH; growth is inhibited by very dilute urine or by high osmolality with low pH. Uromodulin (Tamm-Horsfall protein) saturates the mannose-binding sites of type 1 pili, blocking attachment to uroplakin receptors.
• Immune response — pathogen-associated molecular pattern receptors (e.g. Toll-like receptors) link recognition to the innate response (primarily local inflammation; faster than adaptive; PMNs, neutrophils, macrophages, eosinophils, NK cells, mast cells, dendritic cells). Adaptive immunity (T/B lymphocytes, high-affinity antibodies) develops 7–10 days after infection. UPEC modulates TLR signalling to extend a "window of opportunity" for infection.

Altered Host Defences and Renal Papillary Necrosis

• Obstruction is the key factor increasing susceptibility; stasis promotes bacterial growth and adherence.
• Vesicoureteral reflux — children with gross reflux and UTIs typically develop progressive renal damage (scarring, proteinuria, renal failure); lesser reflux usually improves or resolves. In adults, reflux does not reduce renal function unless there is stasis with concurrent UTIs.
• Renal papillary necrosis (RPN) — necrosis of the papillae and inner medulla (which receives 10% of renal blood flow). Associated conditions follow POSTCARDS: Pyelonephritis, Obstruction, Sickle cell disease, Tuberculosis, Cirrhosis, Analgesic abuse, Renal vein thrombosis, Diabetes mellitus (most common), Systemic vasculitis — plus miscellaneous causes (cryoglobulinaemia, renal candidiasis, contrast media, amyloidosis, calyceal arteritis, necrotizing angiitis, rapidly progressive glomerulonephritis, hypotensive shock, acute pancreatitis, transplant rejection, dehydration, hypoxia, neonatal jaundice). The role of infection is controversial. Acute ureteral obstruction from a sloughed papilla with concurrent UTI is a urologic emergency.

Natural History

• Complicated UTIs can cause progressive renal damage; the long-term effects of uncomplicated recurrent UTIs are not fully known, and no association has been established with renal scarring, hypertension, or progressive azotaemia.
• 57–80% of untreated (or placebo-treated) bacteriuric women clear their infection spontaneously.
• The risk of recurrent bacteriuria is the same whether a patient receives no treatment or short-term, long-term, or prophylactic therapy — prophylaxis reduces reinfections but does not change the underlying predisposition. Extended prophylaxis (≥6 months) lowers infection rates during treatment, but the rate returns to baseline once prophylaxis stops.

Diagnosis and Evaluation

History and Physical Exam

• Cystitis — dysuria, frequency, and/or urgency; suprapubic pain and haematuria are less common. Lower-tract symptoms usually precede upper-tract symptoms by several days.
• Pyelonephritis — fever, chills, flank pain; nausea and vomiting may occur.
• Renal or perirenal abscess — indolent fever with a flank mass and tenderness.
• Elderly — symptoms may be subtle (epigastric/abdominal discomfort) or absent.
• Indwelling catheters — often asymptomatic bacteriuria, but fever from bacteraemia can develop rapidly and become life-threatening.

Urine Collection

• Males (voided): circumcised men need no preparation; uncircumcised men should retract the foreskin, wash the glans with soap, and rinse. Collect the first 10 mL (urethral) and a midstream specimen (bladder). Prostatic fluid is obtained by digital massage onto a slide; the first 10 mL voided after massage reflects added prostatic fluid. Catheterisation for culture is not indicated unless the patient cannot urinate.
• Females (voided): midstream contamination with introital bacteria and WBCs is common — instruct the patient to spread the labia, cleanse the periurethral area with moist gauze, then collect midstream. Antiseptic cleansing is not recommended (risk of false-negative culture). A specimen showing vaginal epithelial cells and lactobacilli is contaminated, and a catheterised sample should be obtained.
• Suprapubic aspiration: highly accurate but carries some morbidity; reserved for patients who cannot urinate on command (spinal cord injury, newborns).
• Bag specimens: unreliable and unacceptable in high-risk populations and infants — in a child who is not toilet-trained, only a catheterised or needle-aspirated specimen is diagnostic (bagged specimens have a high false-positive rate). A negative bag or diaper specimen collected after good perineal cleansing and processed promptly can help exclude bacteriuria.

Urinalysis

Urinalysis gives rapid identification of bacteria and WBCs and a presumptive diagnosis (assess bacteria, epithelial cells, pyuria, haematuria, nitrites), but does not replace urine culture, which confirms the diagnosis. Sediment from ≈5–10 mL centrifuged for 5 minutes at 2000 rpm is examined.

• Bacteriuria — bacteria in normally sterile urine; "significant bacteriuria" is a count exceeding contamination. Found in >90% of infections at ≥10⁵ cfu/mL (highly specific); bacteria are usually not seen microscopically at lower counts (10²–10⁴/mL). False-negatives: early infection, dilute urine — a negative result never excludes bacteria. False-positives: contamination (numerous squamous epithelial cells), with risk rising as technique reliability falls from suprapubic aspiration → catheter → voided.
• Pyuria — WBCs in urine, indicating infection or inflammation from bacteria, stones, or a foreign body. Its absence should make you question the UTI diagnosis until culture returns. Bacteriuria without pyuria suggests colonisation rather than infection. Sterile pyuria warrants evaluation for tuberculosis, stones, or cancer (among many causes); almost any urinary-tract injury can elicit PMNs. Leukocyte-esterase tests detect pyuria.
• Nitrites — bacteria convert urinary nitrates to nitrites. Enterobacteriaceae (E. coli, Klebsiella, Proteus, Enterobacter, Serratia, Citrobacter) convert; gram-positives (enterococcus, staphylococcus) generally do not. The important exception is Pseudomonas, a gram-negative that lacks the enzyme.
• Haematuria — an inflammatory marker; microscopic haematuria appears in 40–60% of cystitis and is uncommon in other dysuric syndromes.

Urine Culture

Two techniques: direct surface plating and dip slides. Refrigerate immediately and culture within 24 hours. A cut-off of ≥10⁵ cfu/mL is the traditional definition of significant bacteriuria from a midstream specimen — but 20–40% of women with symptomatic UTIs present with only 10²–10⁴ cfu/mL, so in dysuric patients an appropriate threshold is 10² cfu/mL of a known pathogen. The ≥10⁵ cut-off can also over-diagnose contaminated specimens.

Localisation and Imaging

Fever and flank pain are common in pyelonephritis but can occur with bladder infection; ureteral catheterisation can separate bacterial persistence into upper versus lower tract and identify which kidney is involved.

Imaging is not required in most UTIs, since clinical and laboratory findings suffice. Indications include: risk factors for complicated UTI; febrile infection; failure to respond to appropriate therapy; potential obstruction (stricture, tumour, prior GU surgery, calculi — especially struvite stones); potential papillary necrosis; polycystic kidneys in dialysis/severe renal insufficiency; neurogenic bladder; and unusual organisms (tuberculosis, fungus, or urea-splitting organisms such as Proteus, Pseudomonas, Klebsiella, Staphylococcus, Mycoplasma). Options are ultrasound, CT/MRI, voiding cystourethrogram (VCUG, for reflux), and radionuclide studies.

Cystitis & Lower UTI

Cystitis is infection confined to the bladder mucosa. This tab covers the uncomplicated and complicated forms, cystitis in men, and the special problems of unresolved and recurrent infection, asymptomatic bacteriuria, pyocystis, and infected urachal cysts.

Risk Factors

• Reduced urine flow — outflow obstruction (BPH, prostate cancer, urethral stricture, foreign body/calculus), neurogenic bladder, inadequate fluid intake (dehydration).
• Promote colonisation — sexual activity (increased inoculation), spermicide (increased binding), estrogen depletion (increased binding), antibiotic use (depletes indigenous flora).
• Facilitate ascent — catheterisation, urinary incontinence, faecal incontinence.
• Residual urine with ischaemia of the bladder wall.

Uncomplicated Acute Bacterial Cystitis

Diagnosis requires both laboratory confirmation of significant bacteriuria and acute-onset lower urinary tract symptoms.

Pathogens

• E. coli causes 75–90% of acute cystitis in young women.
• S. saprophyticus (a skin commensal) is second at 10–20%; Klebsiella, Proteus, and Enterococcus are less common.
• In men, E. coli and other Enterobacteriaceae predominate. Sexual transmission of uropathogens is suggested by finding identical E. coli in the bowel and urinary flora of sexual partners.

Diagnosis and Evaluation

The differential diagnosis is broad: interstitial cystitis/bladder pain syndrome, overactive bladder, urinary calculi, bacterial or fungal vaginitis, STI urethritis, vulvar dermatitis, non-infectious vulvovestibulitis, vulvodynia, hypertonic pelvic-floor dysfunction, genitourinary syndrome of menopause, and (less commonly) bladder CIS.

• Symptoms — variable, usually dysuria, frequency, and/or urgency; suprapubic pain, incontinence, haematuria, or foul-smelling urine may develop. In older adults symptoms are less clear, and nonspecific chronic complaints (cloudy urine, vaginal dryness/burning, pelvic discomfort) are often misread as UTI. Acute-onset dysuria with new or worsening storage symptoms remains a reliable criterion in older women, both community-dwelling and in long-term care. By definition acute cystitis is a superficial mucosal infection, so fever, chills, and signs of dissemination are absent.
• Examination — usually no diagnostic findings; some have suprapubic tenderness. The pelvic exam looks for prolapse, urethral tenderness or diverticulum, Skene's-gland or other vulvar/vaginal cysts, vaginitis/dermatitis/herpes/atrophy, and pelvic-floor tone, tenderness, and trigger points.
• Labs — urinalysis gives the presumptive diagnosis (microscopic pyuria, bacteriuria, occasionally haematuria); urine culture is definitive. The >10⁵ CFU/mL threshold is arbitrary — useful to distinguish bacteriuria from contamination in asymptomatic premenopausal women, but a lower 10² CFU/mL threshold is appropriate in symptomatic patients. Suspect contamination when there are mixed cultures (≥2 organisms), low counts (<10³ CFU/mL) of a pathogen in an asymptomatic patient, or growth of normal vaginal flora (lactobacilli, group B streptococci, corynebacteria, non-saprophyticus coagulase-negative staphylococci) — these are not treated. Epithelial cells or mucus on urinalysis also suggest contamination; obtain a catheterised specimen when suspicion is high. Specimens should not sit at room temperature for >30 minutes.

Management

• Preferred first-line: fosfomycin 3 g PO single dose; nitrofurantoin 100 mg PO BID ×5 days; or TMP-SMX DS 1 tab PO BID ×3 days.
• Alternative (when resistant to the above): ciprofloxacin 250 mg BID ×3 days. Fluoroquinolones should not be first-line for uncomplicated cystitis.
• About 90% of women are asymptomatic within 72 hours. No follow-up visit or culture is needed in young women who are asymptomatic after therapy; a follow-up visit, urinalysis, and culture are recommended in older women, those with risk factors, and men.
• Urologic evaluation is unnecessary in women and usually unnecessary in young men who respond — but UTIs in most men should be considered complicated until proven otherwise. If there is no response, pursue the microbiologic and urologic work-up for unresolved/complicated UTI.

Complicated Cystitis in Females

A UTI is complicated if any one of five features is present: an anatomic/functional abnormality, urinary instrumentation or a foreign body, systemic disease (renal insufficiency, diabetes, immunodeficiency, transplant), pregnancy, or multidrug-resistant bacteria.

• Evaluation — urine culture is mandatory to identify the organism and susceptibilities; review prior cultures to guide empiric selection.
• Management (outpatient candidates): oral ciprofloxacin 500 mg BID ×7 days; a once-daily fluoroquinolone (ciprofloxacin 1000 mg ER ×7 days or levofloxacin 750 mg ×5 days); or oral TMP-SMX DS BID ×14 days (not for Enterococcus or Pseudomonas).

Cystitis in Males

• Evaluation — urine culture is mandatory. Complicated UTI in an older male warrants urologic evaluation (CT urogram and cystoscopy) because of the high rate of associated abnormalities — obstruction from urethral or ureteral stricture, tumour, or stones; ≈50% of males with UTIs have a significant abnormality. Uncomplicated cystitis in a young, sexually active male may need nothing beyond a follow-up urine culture.
• Management — preferred: TMP-SMX DS (160/800 mg) 1 tab PO BID; alternatives levofloxacin 500 mg daily, ciprofloxacin 500 mg BID, or ciprofloxacin ER 1000 mg daily. Treat for 7–14 days (optimal duration unknown).

Unresolved UTI

An unresolved UTI means initial therapy failed to clear symptoms and/or bacterial growth. If symptoms do not resolve by the end of treatment or recur shortly after, obtain urinalysis and culture with susceptibilities; if symptoms are significant, start empirical fluoroquinolone pending results.

Causes, in descending order of importance:

• Pre-existing bacterial resistance to the chosen drug.
• Development of resistance from initially susceptible bacteria.
• Bacteriuria from two species with mutually exclusive susceptibilities.
• Rapid reinfection with a new, resistant species during initial therapy.
• Renal failure (cannot deliver adequate antibiotic concentration to the tract).
• Papillary necrosis from analgesic abuse (impaired medullary concentrating ability dilutes the antibiotic).
• Staghorn calculi (large bacterial mass).
• Self-inflicted infection or deception about taking the drug (a Munchausen variant).

The first four (resistance-associated) need no further evaluation. If re-culture shows the bacteria are sensitive to the drug the patient is taking, perform renal-function and radiologic evaluation for a renal or urinary-tract abnormality.

Management: assume resistance and choose an antibiotic different from the original; fluoroquinolones cover most cases — give for 7 days, adjust to susceptibilities, and culture during and 7 days after therapy.

Recurrent UTI

Recurrent UTI is caused by either bacterial persistence (re-emergence from a site within the tract) or reinfection (new bacteria from outside). The pattern distinguishes them: persistence is the same organism at close intervals, whereas reinfection is different species at varying or long intervals. This distinction is critical — persistence is usually curable by finding and surgically removing/correcting the focus, whereas reinfection (typically in women) usually has no alterable abnormality and needs long-term medical management. Recurrence probability rises with the number of prior infections and falls in inverse proportion to the interval between the first and second.

Bacterial persistence — after the urine shows no growth for several days off antibiotics, recurrence with the same organism arises from a focus shielded from high urinary drug concentrations. Correctable causes include:

• 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 calyceal cysts.
• Papillary necrosis; perivesical abscess with fistula to the bladder.

Reinfection — different species or long intervals; most often in females via ascending colonisation from bowel flora, while reinfection in men is often associated with a urinary-tract abnormality. Consider a vesicoenteric or vesicovaginal fistula with any history of pneumaturia, faecaluria, diverticulitis, obstipation, prior pelvic surgery, or radiation. Evaluation is individualised.

Asymptomatic Bacteriuria

Definition: bacteriuria of any magnitude without symptoms.

• Do not routinely screen or treat — there is no evidence that treatment improves outcomes.
• Screen and treat in two settings: pregnant women, and patients undergoing elective urologic surgery.
• Neonatal candiduria (not strictly bacteriuria) should be treated even if asymptomatic — with parenteral fluconazole.
• Struvite stones: routine treatment of urease-producing bacteriuria, absent UTI symptoms or documented stones, is not recommended — there is no clear evidence it prevents struvite stones (urease producers: Proteus, Pseudomonas, Klebsiella, Mycoplasma, Staphylococcus). In selected patients with recurrent struvite stones, however, screening and treating urease-producing bacteriuria may be indicated when other measures have failed.

Pyocystis and Urachal Cyst Infection

Pyocystis occurs in ≈20% of patients after supravesical diversion (the defunctionalised bladder fills with purulent material). Patients have a malodorous discharge and may become septic. Management is conservative with routine bladder irrigations; if that fails, a vaginal vesicostomy (creation of a large vesicovaginal fistula) effectively prevents pyocystis in women.

Urachal cyst infection — the cyst contains desquamated epithelial cells that can become infected; Staphylococcus aureus is the most common organism.

Pyelonephritis & Renal Infections

This tab covers infection of the kidney and its surrounds — from acute pyelonephritis through abscesses, the gas-forming and granulomatous variants, and parasitic disease. A recurring theme: obstruction or granulomatous infection turns a treatable infection into a surgical emergency.

Bacterial Nephritis: Overview

The classic triad of acute fever, chills, and flank pain usually signals renal infection, but the correlation is imperfect in both directions — significant renal infection can present insidiously or be entirely asymptomatic.

• Laboratory findings correlate poorly with renal infection. Bacteriuria and pyuria, the hallmarks of UTI, are not predictive of renal involvement, and a patient with significant renal infection may have sterile urine if the draining ureter is obstructed or the infection lies outside the collecting system. Pathologic and radiologic criteria can also mislead.
• Effect on renal function is variable. Acute or chronic pyelonephritis may alter function transiently or permanently, but non-obstructive pyelonephritis is no longer considered a major cause of renal failure. When combined with obstruction or granulomatous infection, however, it can rapidly cause inflammatory complications, renal failure, or death.

Acute Pyelonephritis

Pathogens

E. coli causes ≈80% of cases (a virulent subgroup). Suspect more resistant species — Proteus, Klebsiella, Pseudomonas, Serratia, Enterobacter, Citrobacter — in patients with recurrent UTIs, hospitalisation, indwelling catheters, or recent instrumentation. Apart from E. faecalis, S. epidermidis, and S. aureus, gram-positive bacteria rarely cause pyelonephritis. The differential includes acute appendicitis, diverticulitis, and pancreatitis (similar pain intensity, different location).

Diagnosis and Evaluation

The clinical spectrum runs from gram-negative sepsis to cystitis with mild flank pain.

• Symptoms — upper-tract signs are abrupt-onset chills, fever, and unilateral or bilateral flank/costovertebral-angle (CVA) pain or tenderness, often with LUTS (dysuria, frequency, urgency). Exam: CVA tenderness to deep palpation.
• Labs — CBC may show leukocytosis with neutrophil predominance. Urinalysis usually shows numerous WBCs (often in clumps) and bacterial rods or chains of cocci; granular or leukocyte casts suggest acute pyelonephritis. Urine cultures are usually positive, though ≈20% have <10⁵ cfu/mL and therefore a negative urine Gram stain. Blood cultures should not be obtained routinely in uncomplicated pyelonephritis in women (positive in ≈25%, mostly replicating the urine culture without changing management) — reserve them for men, anyone with systemic toxicity or needing hospitalisation, and risk factors such as pregnancy.
• Imaging — defer initial imaging in outpatient uncomplicated cases; renal ultrasound can exclude stones/obstruction when there is concern or poor access to follow-up. In known or suspected complicated disease, CT best defines the urinary tract and the severity/extent of infection. Use US/CT for initial complicated evaluation or to re-evaluate patients who fail to respond after 72 hours.

Management

Any substantial obstruction must be relieved expediently by the safest, simplest means — an obstructed kidney cannot concentrate or excrete antibiotics.

• Oral: amoxicillin/clavulanate 625 mg PO TID ×7 days (amoxicillin ± clavulanate if a gram-positive organism is suspected); ciprofloxacin 500 mg PO BID ×7 days; or levofloxacin 500 mg PO daily ×7 days. Many clinicians give a single parenteral dose (ceftriaxone, gentamicin, or a fluoroquinolone) before starting oral therapy.
• IV (for hospitalisation-level illness — high fever, high WBC, vomiting, dehydration, sepsis — complicated disease, or outpatient failure): ceftriaxone 1–2 g IV q24h; ciprofloxacin 400 mg IV TID; or gentamicin 5–7 mg/kg q24h. For gram-positive cocci, ampicillin/sulbactam ± an aminoglycoside.
• Follow-up: repeat urine cultures after 5–7 days of therapy and 10–14 days after stopping it. 10–30% relapse after a 14-day course; relapse is usually cured by a second 14-day course, occasionally requiring 6 weeks.

Focal and Multifocal Bacterial Pyelonephritis (Lobar Nephronia)

An uncommon, severe infection in which a heavy leukocyte infiltrate is confined to one renal lobe (focal) or several (multifocal) — a midpoint between pyelonephritis and renal abscess. Presentation resembles acute pyelonephritis but is usually more severe; ≈50% of patients are diabetic and sepsis is common. Diagnosis is radiologic (US or CT). Management is hydration plus IV antimicrobials for ≥7 days, then 7 days of oral therapy; failure to respond should prompt studies for obstructive uropathy, renal or perirenal abscess, renal carcinoma, or acute renal vein thrombosis.

Renal and Perinephric Abscess

A renal abscess is purulent material confined to the renal parenchyma (mostly gram-negative organisms); the primary pathway is ascending infection with tubular obstruction from prior infection or calculi. A perinephric abscess results from rupture of a cortical abscess into the perinephric space or haematogenous seeding; diabetes is present in ≈1/3.

• Presentation — renal abscess: fever, chills, abdominal/flank pain, occasionally weight loss and malaise, with marked leukocytosis. Perinephric abscess has a more insidious onset (symptoms >5 days in most) — suspect it with a UTI plus a flank mass or persistent fever after 4 days of antibiotics.
• Distinguishing perinephric abscess from acute pyelonephritis: uncomplicated pyelonephritis is symptomatic for <5 days before hospitalisation and defervesces within 4 days of appropriate antibiotics, whereas perinephric abscess is symptomatic for >5 days and stays febrile for ≥5 days (median 7).
• Diagnosis — CT is the procedure of choice; CT- or US-guided aspiration may distinguish abscess from a hypervascular tumour.

Drainage thresholds differ between the two:

	Renal abscess	Perinephric abscess
Antibiotics alone	<3–5 cm in a clinically stable patient	<3 cm in an immunocompetent patient
Drainage	≥5 cm (percutaneous)	>3 cm — early drainage

Follow with serial US/CT until resolution, and once a perinephric abscess is drained, address the underlying cause.

Chronic Pyelonephritis

In patients without underlying renal or urinary-tract disease, chronic pyelonephritis from UTI is rare and an even rarer cause of chronic renal failure; with underlying functional or structural abnormalities, chronic infection can cause significant impairment. There are no symptoms until renal insufficiency develops, after which it resembles any chronic renal failure, and urinary findings correlate poorly. Imaging shows asymmetry and irregularity of the renal outline, blunting and dilation of one or more calyces, and cortical scars at the corresponding sites. Management is directed at treating infection, preventing recurrences, and monitoring and preserving renal function.

Infected Hydronephrosis and Pyonephrosis

Infected hydronephrosis is bacterial infection within a hydronephrotic kidney. Pyonephrosis is infected hydronephrosis with suppurative parenchymal destruction and total or near-total loss of renal function. The patient is usually very ill — high fever, chills, flank pain, and tenderness — and a prior history of calculi, infection, or surgery is common. (This is a drainage emergency.)

Emphysematous Pyelonephritis

An acute necrotising parenchymal and peri-renal infection caused by gas-forming uropathogens. E. coli is the most common cause (also of emphysematous cystitis), and it usually occurs in diabetics. Almost all patients show the classic triad of fever, vomiting, and flank pain.

• Imaging establishes the diagnosis by gas in the parenchyma or collecting system; a crescentic gas collection over the upper pole is distinctive, and gas extends into the perinephric space and retroperitoneum as it progresses. Do not confuse it with emphysematous pyelitis (gas confined to the collecting system) — a less serious, often non-diabetic, gas-forming bacterial UTI that usually responds to antimicrobials.
• Management is urgent. Most patients are septic, so fluid resuscitation and broad-spectrum antimicrobials are essential. Relieve an obstructed kidney with a stent or nephrostomy; a functioning kidney may be managed medically. Nephrectomy is indicated when the affected kidney is non-functioning and not obstructed (medical therapy alone is usually lethal) or when there is failure to improve after a few days of therapy.

Granulomatous Nephritis

Xanthogranulomatous Pyelonephritis (XGP)

A rare chronic infection, more common in women and in diabetics. The pathogenesis is a triad of nephrolithiasis (usually staghorn) → chronic obstruction → infection, producing diffuse destruction of an enlarged, non-functioning kidney; it begins in the pelvis and calyces and extends to destroy the parenchyma and adjacent tissue, and is usually unilateral. Proteus is the most common organism; E. coli is also common.

• Diagnosis — urinalysis shows pus and protein; urine culture is mixed in ≈10% and shows no growth in ≈1/3 (recent/current antibiotics), so the organism may emerge only on intra-operative tissue culture. CT is the most useful modality: unilateral renal enlargement, a large pelvic calculus without pelvic dilatation, and little or no function (low nephrographic enhancement), with the classic triad in 50–80%. CT often cannot distinguish XGP from renal cell carcinoma — it mimics virtually every other inflammatory renal disease and RCC. Pathology: accumulation of lipid-laden foamy macrophages (characteristic — frequently examined).
• Management — antibiotics may stabilise the patient preoperatively and occasionally (long-term) eradicate infection and restore function, but total nephrectomy (radical or simple) is usually performed, since the kidney is often diagnosed preoperatively as a tumour suspicious for cancer or is a source of recurrent infection. A retrospective cohort of 86 nephrectomies for XGP found the midline approach had longer operative time and slower return of oral intake than the flank retroperitoneal approach, with no difference in complications; laparoscopy has relatively high conversion rates and suits experienced surgeons, while open is better for the inexperienced. Localised XGP identified preoperatively or at exploration is amenable to partial nephrectomy.

Malacoplakia

Greek for "soft plaque," it probably arises from abnormal macrophage function in response to bacterial infection — most often E. coli. Consider it when one or more renal masses are seen, especially in women with recurrent E. coli UTIs, altered immune responses, or cystoscopic plaques/filling defects. Biopsy shows von Hansemann cells and Michaelis-Gutmann bodies (pathognomonic). Management is directed at controlling the UTIs, which stabilises the disease; long-term antibiotics (sulfonamides, rifampin, doxycycline, trimethoprim) are effective.

Renal Echinococcosis

A parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus. It behaves like a slowly growing tumour — most patients are asymptomatic or have a flank mass, dull pain, or haematuria — and because the cyst is focal it rarely affects renal function. Rarely it ruptures into the collecting system, causing severe colic and passage of debris resembling grape skins (hydatiduria). Excretory urography shows a thick-walled cystic mass, occasionally calcified. Diagnostic aspiration should not be performed because rupture and spillage of the highly antigenic contents risk fatal anaphylaxis. Surgery is the mainstay of treatment.

Special-Host & Complicated UTI

UTIs behave differently — and are managed differently — depending on the host and the situation. This tab covers urosepsis and the special contexts where the usual "treat the bacteriuria" rules change: the elderly, the catheterised, the spinal-cord-injured, the pregnant, candiduria, and the surgical emergency of periurethral abscess.

Bacteraemia, Sepsis, and Septic Shock

Term	Definition
SIRS	Extremes of body temperature, heart rate, ventilation, and immune response — may follow infection, trauma, thermal injury, or sterile inflammation
Sepsis	SIRS + infection (documented or strongly suspected)
Severe sepsis	Sepsis + organ dysfunction or tissue hypoperfusion (typically SBP <90 mmHg or MAP <70 mmHg)
Septic shock	Sepsis-induced hypotension persisting despite adequate fluid resuscitation (± elevated lactate or oliguria)

• The earliest metabolic change in septicaemia is respiratory alkalosis — bacteraemic patients hyperventilate even before temperature extremes and chills.
• Gram-negative bacteria predominate (30–80% of cases) over gram-positive (5–24%); anaerobes cause bacteraemia when the source is a post-surgical intra-abdominal abscess or transrectal prostate biopsy. The prime initiator of gram-negative septic shock is endotoxin (LPS) from the bacterial outer membrane; exotoxins can also trigger it, but the bacteria and their cell-wall components are primarily responsible.
• A resistant pathogen is more likely with antimicrobial use in the past month, advanced age, and male sex.
• Management principles: resuscitation, supportive care, monitoring, broad-spectrum antimicrobials, and drainage or elimination of the infective source.

Bacteriuria in the Elderly

• Epidemiology — >20% of women and 10% of men over 65 have bacteriuria.
• Pathogenesis — declining cell-mediated immunity, neurogenic bladder dysfunction, perineal soiling from faecal/urinary incontinence, more urethral catheterisation, and (in women) estrogen-depleted vaginal change.
• Pathogens — E. coli causes 75%; S. saprophyticus is not seen in this population.
• Diagnosis is difficult — most are asymptomatic, concomitant disease masks or mimics UTI, and even severe upper-tract infection may lack fever or leukocytosis. Do not screen for asymptomatic bacteriuria in community-dwelling or long-term-care elderly: RCTs of treatment versus no therapy in nursing-home residents showed no fewer symptomatic episodes and no survival benefit, while treatment increased adverse drug effects, resistant reinfection, and cost.
• Management — do not treat asymptomatic bacteriuria (treating it to improve incontinence is not justified). For symptomatic UTI, give 7 days of therapy with the goal of eliminating symptoms, not sterilising the urine. Bacteriuria is clinically significant and needs prompt therapy when there is a structural abnormality (e.g. obstruction with hydronephrosis) or systemic condition (e.g. severe diabetes). Urea-splitting organisms (Proteus, Klebsiella) form infection stones and can cause severe renal damage; the ammonia they generate is absorbed systemically and may cause encephalopathy or coma at high levels, particularly with obstruction.

Catheter-Associated Bacteriuria

The most common nosocomial infection — 80% of nosocomial UTIs follow an indwelling urethral catheter, and closed drainage is the most effective preventive measure. Most patients are asymptomatic. Treat only when symptomatic (e.g. febrile): obtain a urine culture before starting antimicrobials, and stop the agent within 48 hours of resolution. If the catheter has been in for several weeks, encrustation can shelter bacteria from the drug, so the catheter should be changed.

UTIs in Spinal Cord Injury

• Risk factors — impaired voiding, bladder over-distension, elevated intravesical pressure, obstruction, vesicoureteral reflux, instrumentation, stones, low fluid intake, poor hygiene, perineal colonisation, decubiti/local trauma, and reduced host defence from chronic illness.
• Pathogens — short-term catheterisation is usually a single organism; catheterisation beyond a month is usually polymicrobial.
• Presentation — most are asymptomatic (loss of sensation removes frequency/urgency/dysuria); instead they report flank/back/abdominal discomfort, leakage between catheterisations, increased spasticity, malaise, lethargy, or cloudy/malodorous urine. UTI is the most common cause of fever in the SCI patient.
• Management — clean intermittent catheterisation (CIC) lowers lower-tract complications (low intravesical pressure, fewer stones) and reduces UTI, fever, bacteraemia, epididymitis, and prostatitis. Suprapubic and indwelling urethral catheters reach an equivalent infection rate eventually, though bacteriuria onset may be delayed with a suprapubic catheter (this differs from the NLUTD guidelines, which suggest a lower infection rate with suprapubic). In the absence of reflux, asymptomatic bacteriuria in CIC patients is not a significant risk for renal damage and does not need antibiotics. Treat only symptomatic patients — always culture first (diverse flora, high resistance); an oral fluoroquinolone is the agent of choice for afebrile patients, and an indwelling catheter should be changed to maximise drainage. Prophylaxis is not supported for most neurogenic bladders from SCI.

Periurethral Abscess

A life-threatening infection of the male urethra and periurethral tissues, frequently a sequela of gonorrhoea, urethral stricture disease, or catheterisation. Presenting features are scrotal swelling (94%), fever (70%), acute urinary retention (19%), a spontaneously drained abscess (11%), and dysuria or urethral discharge (5–8%). Management is immediate suprapubic urinary drainage and wide debridement.

Candiduria

Common, particularly with indwelling catheters, diabetes, and recent antibiotics; usually asymptomatic and benign.

• Asymptomatic — remove the indwelling catheter if feasible (clears funguria in 75% within 2 weeks); in catheter-dependent patients, change the catheter and repeat the culture (resolves funguria in 20%). Switch from an indwelling catheter to CIC when possible (indwelling carries a 10× higher candiduria risk). Persistent candiduria warrants a work-up for predisposing factors — post-void residual to exclude retention, and renal ultrasound for hydronephrosis, urolithiasis, fungus balls, and abscess; if none are found, observe with repeat culture over 1–3 months. Obtain fungal blood cultures in critically ill ICU patients with persistent funguria. Treat asymptomatic candiduria only in three groups: neutropenic patients, very-low-birth-weight infants (<1500 g), and patients undergoing urologic manipulation.
• Symptomatic — treat. First-line is oral fluconazole 200 mg daily ×14 days. Nearly all C. albicans and most C. glabrata are susceptible; for resistant strains use flucytosine or amphotericin B.

Bacteriuria in Pregnancy

Anatomic and Physiologic Changes

• Renal size increases (~1 cm) from greater vascular and interstitial volume.
• Hydronephrosis from the obstructive effect of the enlarging uterus (likely the main factor) plus progesterone-mediated smooth-muscle relaxation (reduced ureteral peristalsis, ureteral dilatation, increased bladder capacity).
• Bladder is displaced by the uterus, with increased capacity (progesterone) and possible hypertrophy (estrogen).
• Renal function improves — GFR rises 30–50% and protein excretion increases, so values normal in non-pregnant women may indicate insufficiency in pregnancy; urinary protein is not abnormal until >300 mg/24 h.
• Changes that raise UTI risk: reduced bladder tone (oedema, hyperaemia) and increased upper-tract urine volume as physiologic dilation evolves — both predispose to pyelonephritis.

Complications of bacteriuria in pregnancy include pyelonephritis, prematurity and perinatal mortality, and (conflicting evidence) maternal anaemia. Recurrent UTIs are not a contraindication to pregnancy. In women with renal insufficiency, the degree of impairment is the major determinant of outcome — fetal survival is only slightly reduced with mild/moderate disease, but perinatal mortality is ~4× higher with severe disease. Pathogens are similar to non-pregnant women.

Asymptomatic Bacteriuria

One of the most common infections in pregnancy (prevalence 4–7%, similar to the general population), but it is far more likely to progress to pyelonephritis and, unlike in non-pregnant women, rarely resolves spontaneously without treatment. The risk of progression to pyelonephritis is 1% in non-pregnant versus 20–40% in pregnant women — driven by the anatomic/physiologic changes above and a urinary pH more suitable for E. coli growth at all stages. Treating asymptomatic bacteriuria cuts the pyelonephritis risk to 0–5%.

Diagnosis

Obtain an initial screening urine culture in all pregnant women in the first trimester (urinalysis/reagent strips have significant false-negative rates). If there is no growth, repeat cultures are generally unnecessary, since early no-growth predicts low later risk.

Management

Treat bacteriuria with a full 3–7 day course; hospitalise acute pyelonephritis for initial parenteral therapy.

• Safe agents: penicillins (ampicillin 500 mg QID, amoxicillin 250 mg TID, penicillin V 500 mg QID); cephalosporins (cephalexin 500 mg QID, cefaclor 500 mg QID); fosfomycin; and nitrofurantoin (especially with penicillin allergy, 100 mg QID — discontinue at 35 weeks).

Avoid in pregnancy	Reason
Fluoroquinolones	Damage to immature cartilage
Trimethoprim	Megaloblastic anaemia (anti-folate)
TMP-SMX	Early teratogenicity; late kernicterus
Nitrofurantoin (3rd trimester)	Neonatal haemolytic anaemia
Chloramphenicol	"Gray baby" syndrome
Erythromycin	Maternal cholestatic jaundice
Tetracyclines	Maternal liver decompensation; inhibits fetal bone growth

Obtain follow-up cultures to document clearance. A positive follow-up must be classified as unresolved infection (select another drug), bacterial persistence, or reinfection (consider antimicrobial suppression or prophylaxis for the rest of the pregnancy). After a single episode of pyelonephritis or two episodes of cystitis, give daily suppression with nitrofurantoin or cephalexin until delivery.

Fournier's Gangrene

Fournier's gangrene is an acute, rapidly progressive, and potentially fatal necrotising fasciitis of the external genitalia, perineum, or perianal region. It is a urological emergency — survival depends on early recognition and aggressive surgical debridement.

Definition and History

First described in 1764 by Baurienne, the condition is named after Professor Jean-Alfred Fournier (1832–1914), a Parisian venereologist who in 1883 presented a case of perineal gangrene in an otherwise healthy young man.

Relevant Anatomy

Understanding the fascial planes explains both how the infection spreads and which structures it spares.

Layers superficial to deep (above the inguinal ligament):

• Skin.
• Camper's fascia — fat-containing tissue of variable thickness carrying the superficial vessels to the skin.
• Scarpa's fascia — continuous with Colles' fascia (superficial perineal fascia) in the perineum and Dartos fascia in the penis and scrotum.

Superficial perineal space: Colles' fascia attaches to the pubic arch and the base of the perineal membrane (the inferior fascia of the urogenital diaphragm); together they define the superficial perineal space, which contains the membranous urethra, bulbar urethra, and bulbourethral glands and lies adjacent to the anterior anal wall and ischiorectal fossae. Infection of the male urethra, bulbourethral glands, perineal structures, or rectum can drain into this space and extend into the scrotum or up the anterior abdominal wall to the level of the clavicles.

What is involved vs spared: Fournier's involves the superficial and deep fascia (Camper's, Scarpa's/Dartos/Colles') and skin, but often spares the deep muscle and, variably, the overlying skin. The corpora, urethra, testes, and cord structures are usually not involved — the scrotal contents are wrapped by their own fascial layers, distinct from the Dartos:

• External spermatic fascia (most superficial; continuous with the external oblique aponeurosis at the superficial inguinal ring).
• Internal spermatic fascia (continuous with the transversalis fascia).
• Buck's fascia covers the corpora cavernosa and anterior urethra and fuses to the tunica albuginea deep in the pelvis.

These layers are not breached by a superficial perineal-space infection, limiting the depth of destruction.

Routes of spread (and their limits):

• Posteriorly along Dartos → Colles' fascia, but the attachment of Colles' fascia to the perineal body stops it at the anal margin — infection is limited posteriorly by Colles' fascia.
• Up the anterior abdominal wall through the potential space between Scarpa's fascia and the deep fascia (external oblique); superiorly Scarpa's and Camper's coalesce and attach to the clavicles — infection is limited superiorly by the clavicles.

Pathogenesis and Risk Factors

Infection most commonly arises from the skin, urethra, or rectal region and usually begins as cellulitis adjacent to the portal of entry. Risk factors:

• Diabetes mellitus.
• Local trauma.
• Paraphimosis.
• Urethral stricture (often STI-related, causing periurethral urine extravasation).
• Urethrocutaneous fistula.
• Perirectal or perianal infection.
• Instrumentation.
• Surgery such as circumcision or herniorrhaphy.

Diagnosis and Evaluation

• History and exam — early on the area is swollen, erythematous, and tender as the infection reaches the deep fascia; discharge is absent early. Pain is prominent and systemic toxicity is marked. Distinguishing necrotising fasciitis from cellulitis is difficult because the initial signs (pain, oedema, erythema) are non-specific — but marked systemic toxicity and pain out of proportion to the exam should alert the clinician.
• Labs — wound cultures generally yield multiple organisms, reflecting anaerobic-aerobic synergy.
• Imaging — CT pelvis shows signs of necrotising fasciitis and subcutaneous gas.

Management

This is a urological emergency. The three essential interventions are early recognition, aggressive surgical debridement, and broad-spectrum antibiotics.

• Antibiotics — broad-spectrum cover with a β-lactam plus β-lactamase inhibitor, e.g. piperacillin-tazobactam.
• Resuscitation — IV hydration in preparation for debridement.
• Surgery — immediate debridement of skin and the involved Dartos/Scarpa's/Colles' fascia is essential. Make an extensive incision through skin and subcutaneous tissue beyond the involved area until normal fascia is reached; excise necrotic fat and fascia and leave the wound open. (Prep widely with antiseptic — up to the clavicles and down the thighs.)
• Spared structures — the external, cremasteric, and internal spermatic fasciae are spared (embryologically distinct, with their own blood and nerve supplies). Orchiectomy is almost never required, because the testes have an independent blood supply from the compromised scrotal circulation.
• Re-look — a second procedure at 24–48 hours is indicated if there is any doubt about the adequacy of the initial debridement.
• Adjunctive procedures (include in pre-surgical consent) — suprapubic urinary diversion if urethral trauma or extravasation is suspected, and colostomy for colonic or rectal perforation.

Prostatitis & CPPS

Prostatitis is the most common urologic diagnosis in men under 50 and the third most common in men over 50 (after BPH and prostate cancer), with a prevalence of ≈7% in men over 18 and 6–8% of male urology outpatient visits. Most of the clinical challenge lies in category III chronic pelvic pain syndrome (CPPS), where pain — not infection — dominates.

Epidemiology and Histopathology

Histologically, prostatitis is an increased number of inflammatory cells within the prostatic parenchyma — most commonly a lymphocytic infiltrate in the stroma immediately adjacent to the acini. This finding may or may not accompany clinical prostatitis, BPH, or prostate cancer, and is seen at autopsy in up to 44% of prostate samples from men without definitive prostate disease.

NIH Classification

Category	Name	Defining feature
I	Acute bacterial prostatitis	Acute infection
II	Chronic bacterial prostatitis	Recurrent UTIs from a prostatic focus
IIIA	Inflammatory CP/CPPS	Pain, no bacteria, excess leukocytes in EPS / post-massage urine / semen
IIIB	Non-inflammatory CP/CPPS	Pain, no bacteria, no significant leukocytes
IV	Asymptomatic inflammatory prostatitis	Leukocytes ± bacteria, no pain (incidental)

There is no validated WBC/HPF cut-off separating inflammatory from non-inflammatory CPPS; consensus favours 5–10 WBCs/HPF in EPS as the upper limit of normal, which fluctuates over time and with ejaculation frequency.

Microbiology and Pathogenesis

• Gram-negative organisms predominate — Enterobacteriaceae from GI flora (E. coli, Serratia, Klebsiella, Proteus, Pseudomonas), with E. coli the most common (65–80%).
• Gram-positive — enterococci account for 5–10%; the role of other gram-positive urethral commensals is controversial.

Risk factors for bacterial colonisation/infection of the prostate: intraprostatic ductal reflux, phimosis, specific blood groups, unprotected anal intercourse, UTI, acute epididymitis, indwelling urethral or condom-catheter drainage, and transurethral surgery (especially with untreated infected urine).

Nonbacterial prostatitis/CPPS reflects an interrelated cascade of inflammatory, immunologic, endocrine, muscular, neuropathic, and psychological mechanisms triggered in a susceptible man:

• Intraprostatic ductal reflux — reflux of urine ± bacteria into the prostatic ducts. Prostatic calculi are made of substances found only in urine (not prostatic secretions), evidence that reflux occurs; bacteria can hide in biofilms within these calculi, causing recalcitrant infection and recurrent UTIs despite seemingly adequate antibiotics.
• Chemically induced inflammation from noxious refluxed urinary substances.
• Dysfunctional voiding — high-pressure dysfunctional flow from anatomic or neurophysiologic obstruction.
• Pelvic-floor muscle abnormality / neural sensitisation — neural dysregulation with extraprostatic tenderness, and altered autonomic responses driving pain.
• Immunologic — possibly autoimmune; CPPS can persist via immune mechanisms long after bacteria are eradicated.
• Psychosocial factors contribute to development and exacerbation.

Clinical Presentation

• Category I (acute bacterial) — acute pain with storage and voiding LUTS and signs of sepsis (fever, chills, malaise, nausea/vomiting, even hypotensive septicaemia); pain is perineal/suprapubic ± external genitalia. About 5% progress to chronic bacterial prostatitis.
• Category II (chronic bacterial) — documented recurrent UTIs from a focal prostatic reservoir of uropathogens.
• Category III (CPPS) — the predominant symptom is pain (perineum, suprapubic, penis; also testes, groin, low back); pain during or after ejaculation is among the most bothersome features, often with storage/voiding symptoms. IIIA and IIIB are clinically indistinguishable. By definition it is chronic after 3 months; symptoms wax and wane, and ≈1/3 improve over a year (those with shorter duration and fewer symptoms). Quality of life is greatly diminished.
• Category IV (asymptomatic) — incidental (e.g. on prostate biopsy).

Diagnosis and Evaluation

• Mandatory: history and exam including DRE; urinalysis/culture; pelvic-floor assessment.
• Recommended: two-glass lower-tract test; the NIH Chronic Prostatitis Symptom Index (NIH-CPSI); sexual-function questionnaire; flow rate; post-void residual; urine cytology.
• Not recommended routinely: four-glass test, semen analysis/culture, STI/urethral cultures, urodynamics or video-urodynamics, TRUS, pelvic imaging, PSA, cystoscopy, and prostate biopsy. Note that chronic LUTS in young men may be misdiagnosed as non-bacterial prostatitis when they actually have undiagnosed voiding dysfunction; PSA can rise markedly in acute bacterial prostatitis and normalises over 6 weeks to months; cystoscopy is justified only in refractory cases; and seminal vesiculitis (with abscess) can complicate bacterial prostatitis.

Phenotyping — UPOINT classifies CPPS into one or more of six domains and directs individualised therapy: Urinary, Psychosocial, Organ-specific, Infection, Neurologic/systemic, Tenderness (muscle).

Exam findings: in category I the prostate is hot, boggy, and exquisitely tender — expressing prostatic fluid is unnecessary and potentially harmful. Categories II and III are usually unremarkable apart from pain, and the degree of palpation pain does not differentiate the syndromes.

NIH-CPSI has 9 questions across three domains: pain, urinary function, and quality of life.

Lower urinary tract localisation:

• Category I — a urine culture is the only test required.
• Category II/III — the 4-glass test: VB1 (first 10 mL = urethra), VB2 (midstream = bladder), EPS (expressed prostatic secretion collected during massage), and VB3 (first 10 mL after massage). All go for quantitative culture, and centrifuged sediment is examined for leukocytes, macrophages, oval fat bodies, erythrocytes, bacteria, and fungal hyphae.
  • Category II — a 10× increase in bacteria in EPS or VB3 versus VB1/VB2.
  • Category IIIA — no uropathogens but excess leukocytes (>5–10 WBCs/HPF) in EPS or VB3.
  • Category IIIB — no uropathogens and no significant leukocytosis.
• 2-glass test — a simpler, cost-effective alternative (midstream pre-massage urine + first 10 mL post-massage urine) that categorises most patients.

Management

Acute Bacterial Prostatitis

• First-line (AUA): TMP-SMX or a fluoroquinolone (e.g. TMP-SMX 1 DS tab PO BID); second-line a 2nd-generation cephalosporin; third-line a 3rd-generation cephalosporin. (Australian Family Physician options: trimethoprim 300 mg daily, cephalexin 500 mg BID, or amoxicillin-clavulanate 500/125 mg BID — each ×14 days.)
• Duration ≈2 weeks, starting with parenteral therapy (depending on severity) then oral broad-spectrum cover.
• For ESBL or suspected-ESBL organisms (often after transrectal prostate biopsy), use a carbapenem (ertapenem, imipenem, meropenem), amikacin, or colistin for ≥10–14 days.

Chronic Pelvic Pain Syndrome

No therapy shows marked benefit in sham-controlled trials. Moderate benefit (selected trials): α-blockers and pregabalin. Modest benefit: anti-inflammatories, phytotherapies, ESWT, TUMT, and selected neurostimulation.

• Recommended — α-blocker as part of multimodal therapy in newly diagnosed, α-blocker-naive men with voiding symptoms; an antibiotic trial in selected antibiotic-naive, recently diagnosed patients; selected phytotherapies (Cernilton, Quercetin); directed physiotherapy; and multimodal therapy directed at the individual UPOINT phenotype.
• Not recommended — α-blocker monotherapy (especially if previously treated), anti-inflammatory monotherapy, antibiotics as primary therapy (especially after prior failure), 5α-reductase-inhibitor monotherapy (consider only with coexisting BPH), most minimally invasive procedures (TUNA, laser), and invasive surgery (TURP, radical prostatectomy).

Modality specifics:

• Antibiotics — bacteria are cultured in only 5–10% of cases, but antibiotics may help via three mechanisms: a strong placebo effect, eradication/suppression of non-cultured organisms, and an anti-inflammatory effect. For CP caused by E. coli, give a month of fluoroquinolone, continuing only 4–6 weeks if pre-treatment cultures were positive and/or the patient improved. Fluoroquinolones work best against E. coli/Enterobacteriaceae (less so P. aeruginosa or enterococci); TMP-SMX is less effective; macrolides are superior for proven chlamydial infection. Up to 20% of initial failures respond to a second cycle of a different agent. Do not prescribe to previously treated men with long-standing CP/CPPS.
• α-blockers — target the poor bladder-neck relaxation underlying the LUTS, but trials do not support them in recently diagnosed α-blocker-naive men.
• Anti-inflammatories/immune modulators — high-dose, long-duration COX-2 monotherapy is not recommended; an RCT of pentosan polysulfate 900 mg/day (3× the usual dose) showed modest benefit for some men (alopecia is an associated effect); these are adjuncts, not monotherapy.
• Hormonal — finasteride/dutasteride are not recommended as monotherapy except with coexisting BPH. Allopurinol showed no advantage over placebo.
• Prostatic massage / pelvic-floor physiotherapy — massage evidence is "soft" but may be a multimodal adjunct (frequent ejaculation may do the same); pelvic-floor physiotherapy (perineal massage, myofascial trigger-point release) helps selected patients with demonstrable pelvic-floor pathology refractory to other therapy. Acupuncture is reasonable in selected men.
• Lifestyle/conservative — the foundation of care: education (sometimes sufficient alone), avoiding exacerbating foods/drinks/activities, low-impact exercise, local heat, and coping skills.
• Surgery has no role unless a specific indication is found — a prostate abscess that fails rapid antibiotic response is drained (percutaneous is more effective and less morbid than transurethral), and seminal-vesicle abscesses are managed by antibiotics, transrectal aspiration, or excision.

Orchitis & Epididymitis

Inflammation of the testis (orchitis) and the epididymis (epididymitis) frequently coexist as epididymo-orchitis. The single most important step in any acutely painful scrotum — especially in a younger patient — is to rule out testicular torsion before settling on an inflammatory diagnosis.

Orchitis

Orchitis is inflammation of the testis (the term is sometimes misapplied to testicular pain without objective inflammation). Acute orchitis is the sudden onset of pain and swelling with acute inflammation; chronic orchitis is inflammation and pain, usually without swelling, persisting >6 weeks.

Classification:

• Acute bacterial — secondary to UTI or STI.
• Non-bacterial infectious — viral (the most common viral cause is mumps), fungal, parasitic, rickettsial.
• Non-infectious — idiopathic, traumatic, autoimmune.
• Chronic orchitis / chronic orchialgia — often clinically indistinguishable from each other.

Pathogenesis — bacterial orchitis usually accompanies epididymitis (local spread from the ipsilateral epididymis). In boys and elderly men, UTIs (E. coli, Pseudomonas) are the usual source; in young sexually active men, STIs are often responsible. Isolated orchitis without epididymitis is rare and usually viral (haematogenous spread); mycobacterial infection, TB, and BCG therapy can also cause it. It is usually unilateral but may be bilateral, especially when viral.

Diagnosis and evaluation:

• Acute infectious orchitis — recent testicular pain, often with abdominal discomfort, nausea, and vomiting, possibly preceded by parotitis (boys/young men), UTI (boys/elderly), or STI symptoms; the patient may appear toxic and febrile.
• Acute non-infectious orchitis — similar but without the toxic appearance or fever; in a young patient the key differential is testicular torsion.
• Chronic orchitis/orchialgia — often prior episodes; the scrotum is usually non-erythematous but the testis is indurated and tender.
• Labs — urinalysis, microscopy, and culture; a urethral swab if an STI is suspected. Imaging — scrotal ultrasound if the diagnosis is unclear (and to exclude malignancy in chronic orchitis/orchialgia).

Management — general measures are bed rest, scrotal support, hydration, antipyretics, anti-inflammatories, and analgesics; chronic orchitis/orchialgia is managed supportively (anti-inflammatories, analgesics, heat, nerve blocks).

• Infectious orchitis gets targeted antibiotics (for the underlying UTI, prostatitis, or STI); if early tests are negative or unavailable, empirical therapy with a fluoroquinolone is the best choice.
• TB orchitis — antituberculous therapy (rifampin, isoniazid, and pyrazinamide or ethambutol), rarely surgery.
• Mumps orchitis — no specific antiviral; supportive care.
• Abscess is rare and needs percutaneous or open drainage. Spermatic-cord blocks with local anaesthetic may relieve severe pain. Surgery is rarely indicated unless torsion (or, rarely, xanthogranulomatous orchitis) is suspected; orchidectomy is reserved for pain refractory to all else (and may still not relieve it).

Epididymitis

Epididymitis is inflammation of the epididymis. Acute epididymitis is sudden pain and swelling lasting <6 weeks; chronic epididymitis is pain (usually without swelling, but with induration in long-standing cases) persisting >6 weeks. Chronic infectious epididymitis is most commonly tuberculous — from haematogenous spread rather than seeding from the kidneys.

Classification:

• Acute bacterial — secondary to UTI or STI.
• Non-bacterial infectious — viral, fungal, parasitic.
• Non-infectious — idiopathic, traumatic, autoimmune, amiodarone-induced, or syndrome-associated (e.g. Behçet disease).
• Chronic epididymitis / chronic epididymalgia.

Causes — acute epididymitis usually spreads from the bladder, urethra, or prostate along the ejaculatory ducts and vas deferens. The likely pathogen depends on the population:

Population	Common pathogens
Children and elderly men	Uropathogens — E. coli most common (driven by BPH stasis, UTI, catheterisation)
Sexually active men <35 (sex with women)	N. gonorrhoeae and C. trachomatis
Men who have sex with men (anal intercourse)	E. coli and Pseudomonas

Chronic epididymitis arises from inadequately treated or recurrent acute epididymitis, tuberculosis, amiodarone, or Behçet disease. Risk factors for recurrent epididymitis are meatal stenosis, urethral stricture, high-pressure voiding dysfunction, and ectopic ureter.

Diagnosis and evaluation — rule out testicular torsion, especially in younger patients. Examination localises tenderness to the epididymis (often with testicular involvement = epididymo-orchitis), and the spermatic cord is usually tender and swollen. Labs: midstream urine and Gram stain of a urethral smear. Imaging: scrotal ultrasound can help but is not always diagnostic.

Management — start empirical therapy before results return (anti-inflammatories, analgesics, scrotal support, nerve blocks). For acute bacterial epididymitis (EAU Guidelines on Urological Infections):

• Gonorrhoea likely: ceftriaxone 1000 mg IM/IV ×1 + doxycycline 200 mg PO once then 100 mg BID for 10–14 days.
• Gonorrhoea unlikely (no urethral discharge): doxycycline 200 mg then 100 mg BID for 10–14 days plus an agent active against Enterobacterales for 10–14 days.
• Non-sexually active: an oral fluoroquinolone (levofloxacin) daily for 10–14 days.

For chronic epididymitis, a 4–6 week antibiotic trial covering likely pathogens — particularly C. trachomatis — may be appropriate. Epididymectomy is considered only after all conservative measures are exhausted, and only once the patient accepts that it has at best a 50% chance of curing the pain.

Sexually Transmitted Infections

The most common bacterial STIs in the US, in descending order, are chlamydia then gonorrhoea. This tab covers urethritis, the ulcerative and non-ulcerative genital lesions, vaginitis, and the urologic manifestations of HIV/AIDS.

Epidemiology and Screening

Risk factors: number of lifetime partners, unprotected sex (no condom), risky sexual partners, and the effect of alcohol or drugs on sexual decision-making.

CDC screening recommendations:

• Women — annual chlamydia screening for all sexually active women ≤25 and any with new/multiple partners; annual gonorrhoea screening for at-risk women; and syphilis, HIV, and chlamydia for all pregnant women (gonorrhoea for at-risk pregnant women), starting early with repeat testing as needed.
• Men — at least annual syphilis, chlamydia, gonorrhoea, and HIV screening for all sexually active MSM, increasing to every 3–6 months for those with multiple/anonymous partners or drug use.

Reportable in every US state: chlamydia, gonorrhoea, syphilis, chancroid, and HIV/AIDS.

Urethritis

Urethral inflammation is classified as gonococcal or non-gonococcal (NGU).

• Gonococcal — Neisseria gonorrhoeae, a gram-negative diplococcus; an oxidase-positive culture on Thayer-Martin medium is diagnostic. Incubation 3–14 days.
• Non-gonococcal (NGU) — caused by organisms other than N. gonorrhoeae. Chlamydia trachomatis accounts for 15–40%, with less common causes being Mycoplasma genitalium, Trichomonas vaginalis, adenoviruses, and HSV-1.
  • Chlamydia — gram-negative; incubation 3–14 days (same as gonorrhoea).
  • Mycoplasma genitalium — lacks a cell wall (cannot be Gram-stained) and can become intracellular, establishing chronic infection and evading immunity/antibiotics. Risk factors in men: young age, intercourse in the past month, and a partner with recent STI.
  • Ureaplasma — conflicting evidence as a cause.
  • Trichomonas vaginalis — a flagellated parasite of the lower genitourinary tract; a common vaginal pathogen that can also cause male urethritis.

Natural history:

• Gonorrhoea — in women causes PID, tubal scarring, infertility, ectopic pregnancy, and chronic pelvic pain; increases HIV transmission risk; disseminated disease (rare) causes arthritis, dermatitis, meningitis, and endocarditis.
• Chlamydia — the major risk in men is transmission to female partners causing PID; male complications include epididymitis and Reiter syndrome (conjunctivitis, urethritis, reactive arthritis); ascending infection in women causes tubal scarring, PID, ectopic pregnancy, pelvic pain, and infertility.

Diagnosis — symptoms are urethral discharge, pruritus, and dysuria. Gonorrhoea is usually symptomatic in men (urethritis, epididymitis, proctitis, prostatitis) though some sources report frequent asymptomatic infection; women are frequently asymptomatic. Chlamydia causes dysuria, discharge, and epididymitis in men, but up to 42% of men with NGU and up to 75% of women are asymptomatic; ~25% of M. genitalium infections are asymptomatic. NAATs on urine are the test of choice for both gonorrhoea and chlamydia — test for both given frequent co-infection — and have replaced urethral swabs, wet mounts, and culture (including for trichomonas; M. genitalium is diagnosed by NAAT/PCR).

Management — ceftriaxone 250 mg IM single dose plus either azithromycin 1 g PO single dose or doxycycline 100 mg PO BID ×7 days. Dual therapy covers both N. gonorrhoeae and chlamydia because of frequent co-infection, and all patients should be tested for other STIs including syphilis and HIV.

Ulcerative Genital Lesions

Genital ulcers are classified as infectious or non-infectious:

Infectious	Non-infectious
Herpes, syphilis, chancroid, lymphogranuloma venereum, donovanosis/granuloma inguinale	Trauma, malignancy, psoriasis, yeast, aphthae, fixed drug eruption

In sexually active young US men, genital herpes is the most common ulcer, followed by syphilis; chancroid occurs in some areas, LGV is increasing among MSM, and donovanosis is essentially confined to tropical/developing regions. Work-up is history/exam plus targeted labs (HSV culture or NAAT/PCR + serology; syphilis serology ± darkfield; H. ducreyi testing where chancroid is prevalent) and HIV testing. Even after full evaluation, 25% of genital ulcers have no laboratory-confirmed diagnosis; biopsy unusual or non-responding ulcers.

Herpes

The most common cause of genital ulcers, caused by the double-stranded DNA herpes simplex virus. HSV-1 is mainly oral but causes 5–30% of first genital episodes; HSV-2 causes most genital herpes. Women are more susceptible to and more often symptomatic with HSV-2, and most transmission comes from people unaware they are infected; HSV-2 protects against HSV-1, but HSV-1 gives only slight protection against HSV-2.

• Pathophysiology — HSV replicates in epithelial cells at the entry site, then travels up peripheral sensory nerves to lie latent in the nerve cell body; reactivation (triggered by local trauma/surgery/UV light, immunosuppression, or fever) sends virus back to the surface. Incubation 4–7 days.
• Presentation — pain, burning, or itching, with dysuria in 80% of women, plus flu-like symptoms; complications include aseptic meningitis and autonomic dysfunction causing urinary retention. The classic primary lesion is clusters of erythematous papules and vesicles that do NOT follow a neural distribution, with tender inguinal/femoral nodes; over 2–3 weeks 75% develop new lesions that vesiculate, pustulate, coalesce into ulcers, then crust and heal. HSV-1 and HSV-2 cannot be told apart clinically.
• Labs — NAAT (preferred) or cell culture of a lesion; the Tzanck preparation is non-specific and insensitive; with no active lesions, type-specific IgG serology distinguishes HSV-1 from HSV-2.
• Course/management — genital HSV-1 recurs far less than HSV-2, and recurrences decrease after the first year. Treat the first episode on clinical grounds before confirmation; antivirals (acyclovir, valacyclovir, famciclovir — the "-ciclovir" agents) reduce signs/symptoms and new lesions but do not eradicate the virus. Acyclovir is used for neurologic complications, inability to take oral medication, or widespread disease (immunocompromised). Treat 7–10 days (extend if not healed); untreated lesions heal in 5–10 days.

Syphilis

Caused by Treponema pallidum.

• Primary — incubation 2–3 weeks (range 9–90 days); the lesion is a chancre at the inoculation site (glans/corona/perineum in men; labia/perianal in women), usually single and painless (up to 25% painful) with non-tender local lymphadenopathy. Untreated lesions heal in 3–8 weeks.
• Secondary — systemic bacteraemia appearing 3–5 months after infection, with a maculopapular rash involving the palms and soles, condyloma lata, fever, malaise, weight loss, patchy alopecia, and ocular inflammation; ~10% develop a broad vasculitis (hepatitis, iritis, nephritis, cranial-nerve involvement — especially CN VIII). Relapses occur mainly in the first year, then the infection becomes latent (seroreactive, no clinical disease).
• Tertiary/late — ~35% of late-latent patients develop neurosyphilis, cardiovascular syphilis, or gummatous syphilis.
• Diagnosis — culture is not possible; direct darkfield microscopy identifies T. pallidum. Serology has two classes: non-treponemal (RPR, VDRL, TRUST — directed against phospholipids; used to monitor activity but need treponemal confirmation, as they false-positive in viral infection, pregnancy, malignancy, autoimmune disease, and advanced age) and treponemal (FTA-ABS, MHA-TP, TP-HA, TP-PA). Test all patients for HIV.
• Management — benzathine penicillin G for all stages (dose/duration set by stage). The Jarisch-Herxheimer reaction (fever, malaise, nausea, vomiting ± chills and rash flare) is not a penicillin allergy but a reaction to treponeme death, most common in early syphilis — manage with bed rest and NSAIDs.

Chancroid

Caused by H. ducreyi (gram-negative coccobacilli): a papule progresses to painful anogenital ulceration with lymphadenitis and bubo formation; incubation 3–10 days, most often on the prepuce. Definitive diagnosis needs culture on media not routinely available; the CDC allows a probable diagnosis with one or more painful ulcers, no T. pallidum on darkfield/serology ≥7 days after onset, typical ulcers/adenopathy, and negative HSV testing. It is an HIV-transmission risk factor — test for HIV. Treatment: azithromycin 1 g once, ceftriaxone 250 mg IM once, ciprofloxacin 500 mg BID ×3 days, or erythromycin base 500 mg TID ×7 days.

Lymphogranuloma Venereum

Caused by chlamydia: a self-limited (often already-gone) genital ulcer/papule is followed by the common secondary stage — tender, typically unilateral inguinal/femoral lymphadenopathy (more common in men, since cervical/vaginal drainage is retroperitoneal). LGV proctocolitis can mimic IBD, with chronic colorectal fistulas and strictures. Diagnosis: swab/bubo aspirate for culture, direct immunofluorescence, or nucleic acid detection. Treatment: doxycycline 100 mg BID ×21 days.

Donovanosis / Granuloma Inguinale

Caused by Klebsiella granulomatis (intracellular gram-negative); rare in the US. It causes painless, slowly progressive beefy-red, easily bleeding ulcers on the genitals and perineum; despite the name, inguinal involvement is uncommon (10%, tender if present). Diagnosis: Donovan bodies on crush preparation or biopsy. Treatment: doxycycline 100 mg PO BID for at least 3 weeks and until all lesions heal.

Summary of Ulcerative STIs

Disease	Agent	Lesion	Lymphadenopathy	Systemic	Testing	Treatment
Genital herpes	HSV-1/2	Painful shallow vesicles, usually multiple	Tender, bilateral inguinal	During primary infection	NAAT/culture; serology for subtype	"-ciclovir" agents
Primary syphilis	T. pallidum	Painless, indurated, clean base, usually single	Non-tender, rubbery, non-suppurative, bilateral	None	Darkfield, serology	Benzathine penicillin G
Chancroid	H. ducreyi	Painful papule → undermined purulent ulcer	Tender, regional, suppurative	None	Culture (special media)	Azithromycin
LGV	Chlamydia	Small, painless vesicle/papule → ulcer	Tender, matted, with fistulous tracts	After genital lesion heals	NAAT/culture of aspirate	Doxycycline
Donovanosis	Klebsiella	Painless, multiple, slowly progressive	Usually absent	—	Donovan bodies	Doxycycline

Other Genital Lesions

Human Papillomavirus (HPV)

A double-stranded DNA virus. Non-oncogenic types 6 and 11 cause ≈90% of anogenital warts (condyloma acuminata); oncogenic types 16 and 18 cause cervical and other anogenital cancers (penile, vulvar, vaginal, anal) — type 16 is most important for penile cancer.

• Epidemiology/natural history — >50% of sexually active people are infected at least once; ~70% clear within 1 year and 90% within 2 years, with persistence in the rest. Transmission occurs from asymptomatic/subclinical infection. Risk factors: foreskin, more partners, no condom use, smoking. Urethral warts can cause haematuria, dysuria, or voiding difficulty.
• Management — the goal is removal of warts; treatment does not eradicate infection, and is guided by wart size, number, location, and preference.
  • Patient-applied: imiquimod cream 3.75%/5% (8 h daily ×2 weeks; max 8 weeks for 3.75% vs 16 weeks every other day for 5%); podofilox 0.5% (BID ×3 consecutive days/week, up to 4 weeks); sinecatechins 15% ointment (TID up to 16 weeks).
  • Provider-administered: podophyllin, trichloroacetic acid, cryotherapy, and surgery (scissor/shave excision, curettage, CO₂ laser).
• Vaccine — prevents infection but does not clear established infection; recommended for females and males under 26, ideally before sexual debut. Gardasil is quadrivalent (6, 11, 16, 18); Cervarix is bivalent (16, 18).

Scabies

Caused by the mite Sarcoptes scabiei — the female lays eggs in the skin, transmitted by skin-to-skin contact; incubation 2–6 weeks. The main symptom is rash with itching, especially at night; diagnosis is by microscopy of a skin scraping for mites, eggs, or faeces (scybala). Treatment: permethrin cream or oral ivermectin 200 μg/kg.

Pediculosis Pubis (Crab Louse, Phthirus pubis)

An obligate bloodsucking parasite spread by close contact, presenting with pruritus (delayed hypersensitivity) worse at night and after baths. Treatment: permethrin 5% rinse or pyrethrins with piperonyl butoxide, each washed off after 10 minutes.

Molluscum Contagiosum

A poxvirus infection that can be sexually transmitted, with characteristic small, waxy, umbilicated papules 3–5 mm across. Usually self-limited (resolves in 6–12 months, up to 4 years), but more severe and extensive in immunocompromised/HIV patients.

Candidal Balanitis

C. albicans causes burning and pruritus with erythema of the glans/prepuce and subpreputial discharge. Risk factors: diabetes, HIV, iatrogenic immunosuppression, foreskin, and widespread antibiotic use. Treatment is not standardised — topical antifungals (± systemic), usually azoles (clotrimazole, miconazole, econazole, fluconazole, itraconazole).

Vaginitis

Vaginal infections present with discharge, itching, or odour; the three most associated with discharge are bacterial vaginosis, trichomoniasis, and candidiasis, of which bacterial vaginosis is the most common.

Bacterial Vaginosis

A handy mnemonic: "I have no CLUE why there are FISH in my GARDEN." BV is caused by replacement of normal hydrogen-peroxide-producing Lactobacillus with anaerobes (Prevotella, Mobiluncus, Gardnerella vaginalis, Ureaplasma, Mycoplasma, and other fastidious anaerobes). It is not sexually transmitted and the partner is not treated. Most women with BV are asymptomatic; diagnosis rests on clue cells and a fishy odour. Treatment: metronidazole.

Trichomoniasis

Caused by the protozoan T. vaginalis and is sexually transmitted. Discharge is diffuse, malodorous, and yellow-green with vulvar irritation, sometimes with a strawberry cervix. Diagnosis is by microscopy of vaginal secretions. Treatment: metronidazole — the partner must be treated.

Candidiasis

Usually C. albicans. Diagnosis is by wet prep (saline or KOH) or Gram stain showing yeast/hyphae/pseudohyphae, or culture — do wet mounts first for all patients, reserving culture for symptomatic patients with negative wet mounts. Treatment of uncomplicated disease: OTC intravaginal azoles (butoconazole, clotrimazole, miconazole, or tioconazole).

HIV/AIDS

HIV is a single-stranded RNA retrovirus infecting CD4 helper T cells and dendritic cells; its envelope precursor gp160 is cleaved into gp120 and gp41. After a needle-stick, seroconversion risk rises with deep exposure, visible blood on the device, prior placement of the device in an artery/vein, and the source patient dying within 2 months.

Diagnosis — the initial screen is an antibody enzyme immunoassay (EIA) (result in 30 minutes); a reactive screen must be confirmed by a supplemental antibody test (Western blot, IFA) or virologic HIV-1 RNA assay. HIV is detectable in 95% within 3 months; during the "window" period the screen may be negative while the person is infected, so a viral-load assay is the best test in acute infection. AIDS is diagnosed with a CD4 count <200 cells/mm³ or a serious opportunistic infection, neoplasm, or other life-threatening condition.

Urologic manifestations:

• General — test for HIV in anyone with or at risk for an STI; bleeding genital ulcers increase infectiousness.
• Kidney infections — higher risk of clinical TB (renal/extrapulmonary); mycobacterial renal infection is found at autopsy in 6–23% of AIDS patients; also CMV, aspergillus, toxoplasma.
• Prostatitis — may be more common; usually E. coli, but many other organisms occur (S. aureus, K. pneumoniae, P. aeruginosa, S. marcescens, Salmonella Typhi, M. tuberculosis, M. avium intracellulare, CMV, fungi — especially with T cells <200/μL), so culture broadly.
• UTI — bacteriuria incidence tracks CD4 count and viral load; unusual organisms (e.g. CMV) occur.
• Testis/epididymis/seminal vesicles — semen is the main transmission vector (persists despite ART); the most common intrascrotal finding is testicular atrophy; HIV is cytotoxic to germ and Sertoli cells, and testosterone falls with disease progression.
• Erectile dysfunction — more prevalent than in uninfected men; start PDE5 inhibitors at the lowest dose because protease inhibitors and NNRTIs inhibit CYP3A and markedly raise PDE5i levels.
• Renal function — HIV-associated nephropathy (HIVAN): rapidly progressive azotaemia with severe (often nephrotic) proteinuria and little peripheral oedema; APOL1 polymorphism is associated with HIVAN in African-American patients.
• Voiding/haematuria — increased LUTS and microscopic haematuria (evaluate haematuria as in anyone else).
• Stones — protease inhibitors (especially indinavir) cause stones; indinavir stones are typically radiolucent on plain film and CT (but can appear radiopaque if mixed with calcium); newer agents (lopinavir, atazanavir, amprenavir, nelfinavir) less so. Manage protease stones with drug cessation and hydration first; ammonium acid urate stones are also more common (chronic diarrhoea/malnutrition).
• Neoplasms — AIDS-defining cancers are Kaposi sarcoma, non-Hodgkin lymphoma, and invasive cervical cancer. Kaposi sarcoma (caused by HHV-8 in >90%) is most relevant to urology for penile lesions. HIV also raises the risk of testicular tumours (including testicular non-Hodgkin lymphoma), kidney cancer, and penile cancer (though the 2018 EAU guidelines state penile cancer is not linked to HIV/AIDS), but not prostate or bladder cancer. Use caution with intravesical BCG in HIV-positive patients, as its efficacy depends on a functioning immune system.