14.1 Localised & Systemic UTIs, Pyelonephritis, Urosepsis & Specific Infections

Localised & Systemic UTIs, Pyelonephritis, Urosepsis & Specific Infections

Urinary tract infections (UTIs) encompass a wide pathophysiological spectrum ranging from self-limiting acute localized mucosal inflammation to fulminant, life-threatening uroseptic shock and chronic granulomatous destruction. Modern clinical urology per the European Association of Urology (EAU) Guidelines mandates a rigorous, phenotype-driven framework that integrates host vulnerability, antimicrobial stewardship, avoidance of ecological collateral damage, and emergency surgical decompression when urinary tract obstruction supervenes.

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1. Modern EAU Classification: Localised vs. Systemic UTIs

Historically, urological literature categorized UTIs dichotomously into "uncomplicated" and "complicated" infections, often arbitrarily labeling all male infections as complicated. Modern urological science per the current EAU Urological Infections Guidelines has evolved beyond this rigid dichotomy and superseded legacy systems (such as ORENUC) with a clinically driven classification based on anatomical localization, systemic severity, and individual host risk factor profiling.

+------------------------------------------------------------------------------------------------+
|                            CURRENT EAU UTI CLASSIFICATION FRAMEWORK                            |
|                                                                                                |
|  1. LOCALISED UTI (Lower Urinary Tract Symptoms Only):                                         |
|     --> Symptoms confined strictly to the bladder and urethra                                  |
|     --> Local symptoms: Dysuria, urinary frequency, urgency, suprapubic pain / pressure        |
|     --> Absence of systemic signs (no fever, no chills, no flank pain, normal hemodynamics)    |
|     --> Clinical entities: Acute cystitis, recurrent cystitis                                  |
|                                                                                                |
|  2. SYSTEMIC UTI (Systemic Signs of Urinary Infection):                                        |
|     --> Systemic signs, with or without local urinary symptoms                                 |
|     --> Clinical hallmarks: Fever (>38.0°C) or hypothermia (<36.0°C), rigors, flank pain,      |
|         costovertebral angle (CVA) tenderness, systemic malaise, nausea, vomiting              |
|     --> Clinical entities: Acute pyelonephritis, acute bacterial prostatitis, urosepsis        |
|     --> Infection-related organ dysfunction: Sepsis (acute SOFA increase >= 2)                 |
|                                                                                                |
|  CRITICAL EAU PARADIGM: MALE SEX IS NOT AN INDEPENDENT COMPLICATION FACTOR!                    |
|  --> In the current classification, male sex alone does not automatically classify an infection|
|      as complicated. An otherwise healthy, young adult male with an acute localized lower UTI  |
|      without structural, voiding, or prostate abnormalities is managed based on his specific   |
|      clinical presentation and microbiological findings.                                       |
|  --> Host risk factors are assessed individually for each patient.                             |
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Individual Host Risk Factor Profiling

Instead of applying blanket labels, clinicians evaluate each patient for specific anatomical, functional, and systemic risk factors that modulate clinical risk, recurrence, and treatment failure:

• Anatomical / Urological Risk Factors: Obstructive urolithiasis, benign prostatic hyperplasia (BPH) with bladder outlet obstruction, urethral stricture disease, bladder diverticula, pelviureteric junction obstruction, and vesicoureteral reflux (VUR).
• Functional / Neurogenic Risk Factors: Neurogenic lower urinary tract dysfunction (spinal cord injury, multiple sclerosis), detrusor underactivity, incomplete bladder emptying with a clinically significant post-void residual.
• Foreign Bodies / Catheter-Related Factors: Indwelling transurethral or suprapubic catheters, double-J ureteral stents, nephrostomy tubes, and clean intermittent catheterization (CIC).
• Nephropathic Factors: Chronic kidney disease (CKD), solitary functional kidney, renal allograft recipient, and polycystic kidney disease (ADPKD).
• Systemic / Metabolic Host Defenses: Uncontrolled diabetes mellitus, pharmacologic immunosuppression, active chemotherapy, biological agents, advanced liver cirrhosis, and hematological malignancies.
• Pregnancy: Physiological hydroureter, decreased ureteral peristalsis, and altered humoral immunity predisposing to rapid upper tract ascension.

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2. Localised Lower Urinary Tract Infections (Acute & Recurrent Cystitis)

Microbial Etiology

Acute localized cystitis is predominantly caused by bowel-derived enteric uropathogens that ascend through the urethra into the bladder lumen:

• Uropathogenic Escherichia coli (UPEC): Accounts for 75% to 95% of all uncomplicated isolates. UPEC strains express specialized adhesins and toxins, most notably Type 1 fimbriae (bearing the FimH adhesin that binds mannosylated urothelial receptors on apical umbrella cells), P fimbriae (PapG adhesin), alpha-hemolysin, and cytotoxic necrotizing factor 1 (CNF-1).
• Staphylococcus saprophyticus: Accounts for 5% to 10% of cases, predominantly in young, sexually active females (novobiocin-resistant, coagulase-negative gram-positive coccus).
• Klebsiella pneumoniae, Proteus mirabilis, and Enterococcus faecalis: Account for the remaining minority of localized infections.

Evidence-Based Antimicrobial Guidelines

Empirical treatment of localized cystitis must prioritize antimicrobials with high urinary concentration, minimal impact on intestinal and vaginal commensal flora ("minimal collateral damage"), and acceptable local susceptibility. The 20% resistance threshold specifically guides empirical trimethoprim or TMP-SMX use.

Recurrent Urinary Tract Infections (rUTI)

Recurrent UTI is defined by documented symptomatic episodes occurring with a frequency of >= 2 episodes within 6 months OR >= 3 episodes within 12 months. Confirm the initial diagnosis of recurrent cystitis by urine culture. Interpret counts with symptoms and sampling method rather than requiring a universal threshold. Reculture atypical, persistent or early recurrent symptoms; routine surveillance cultures are not needed when asymptomatic.

+--------------------------------------------------------------------------------------------------------+
| STEPWISE PREVENTION OF RECURRENT CYSTITIS IN WOMEN                                                     |
|                                                                                                        |
| 1. BEHAVIOURAL MEASURES                                                                                |
|    Increase water intake in low-volume drinkers; an additional 1.5 L/day reduced episodes in a trial.  |
|    Avoid spermicides. Counsel on voiding and hygiene, acknowledging limited evidence for some measures.|
|                                                                                                        |
| 2. NON-ANTIBIOTIC OPTIONS                                                                              |
|    Vaginal estrogen: postmenopausal women.                                                             |
|    Methenamine hippurate: an antibiotic-sparing option in women without urinary tract abnormalities.   |
|    Immunomodulatory prophylaxis (e.g. OM-89): EAU recommends use within a regulated clinical trial.    |
|    D-mannose: discuss the weak, contradictory evidence; do not promise reliable protection.            |
|    Intravesical hyaluronic acid +/- chondroitin: selected patients after less-invasive options fail.   |
|                                                                                                        |
| 3. ANTIBIOTICS WHEN NON-ANTIBIOTIC PREVENTION FAILS                                                    |
|    Postcoital: a single appropriate dose after intercourse when episodes are clearly coitus-related.   |
|    Continuous examples: nitrofurantoin 50–100 mg daily, trimethoprim 100 mg daily,                     |
|    or fosfomycin trometamol 3 g weekly; choose according to cultures, local resistance and safety.     |
|    Study durations range from 3–12 months; individualize duration and reassess benefit and harms.      |
|    Intermittent fosfomycin schedules are continuous prophylaxis, not postcoital single-dose therapy.   |
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3. Systemic Urinary Tract Infections: Pyelonephritis & Urosepsis

Acute Pyelonephritis

Acute pyelonephritis represents an invasive infectious inflammation of the renal parenchyma, calyces, and renal pelvis. It requires immediate, aggressive bactericidal treatment to prevent parenchymal suppuration, abscess formation, and systemic septic cascades.

• Clinical Hallmarks: Flank pain / CVA tenderness, pyrexia (fever > 38.0°C, rigors, diaphoresis), and systemic toxicity (nausea, vomiting, headache, malaise), with or without concurrent dysuria and frequency.
• Diagnostic Workup: Urinalysis (marked leukocyturia, positive nitrite, leukocyte esterase, WBC casts may support renal inflammation but are not specific for bacterial pyelonephritis), mandatory quantitative urine culture with antimicrobial susceptibility testing, and routine blood tests (CBC showing leukocytosis with left shift, elevated C-reactive protein, serum creatinine, and eGFR).
• Imaging: Assess promptly for obstruction or another urgent urological disorder. Ultrasound is the initial systemic-UTI study, particularly with stone history, renal impairment or high urine pH. Obtain cross-sectional imaging for suspected obstruction/hydronephrosis, severe illness or deterioration, and for failure to improve after 48–72 hours of appropriate treatment. Do not wait for persistent fever when the patient is unstable. Imaging also evaluates renal/perinephric abscess or emphysematous infection.

Outpatient vs. Inpatient Therapeutic Protocols

Urosepsis: Pathophysiology & Sepsis-3 Criteria

Urosepsis is sepsis arising from a urinary source. Important urological precipitants include obstructive pyelonephritis (a calculus, stricture or malignant compression) and infection after instrumentation. The proportion of all sepsis attributable to the urinary tract varies by population.

Under the international Sepsis-3 consensus, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection:

• SOFA Score (Sequential Organ Failure Assessment): Organ dysfunction is formally identified by an acute increase in the total SOFA score of >= 2 points attributable to the infection. SOFA assesses six organ systems: respiration (PaO2/FiO2), coagulation (platelets), liver (bilirubin), cardiovascular (mean arterial pressure, requirement for vasopressors), central nervous system (Glasgow Coma Scale), and renal (creatinine, hourly urine output).
• qSOFA (Quick SOFA): A bedside marker of increased risk outside the ICU, not a diagnostic definition or a rule-out test. SSC 2026 favors NEWS/NEWS2, MEWS or SIRS over qSOFA alone for screening. A score of >=2 of 3 identifies increased risk:
  1. Respiratory Rate: >= 22 breaths/min
  2. Altered Mental Status: Glasgow Coma Scale (GCS) < 15
  3. Systolic Blood Pressure: <= 100 mmHg
• Septic Shock: A subset of sepsis wherein underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Clinically identified by persistent hypotension requiring vasopressors to maintain a Mean Arterial Pressure (MAP) >= 65 mmHg AND a serum lactate > 2.0 mmol/L (18 mg/dL) despite adequate volume resuscitation.

SSC 2026 Emergency Resuscitation & Urinary Source Control

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| UROSEPSIS: START ASSESSMENT, RESUSCITATION AND SOURCE CONTROL TOGETHER                                      |
|                                                                                                             |
| 1. CULTURES AND LACTATE                                                                                     |
|    Obtain blood and urine cultures promptly, ideally before antibiotics, without delaying urgent therapy.   |
|    Measure lactate and follow the clinical response; repeat an elevated lactate in context.                 |
|                                                                                                             |
| 2. PROMPT INTRAVENOUS ANTIBIOTICS                                                                           |
|    Shock or probable/definite sepsis: administer immediately, ideally within 1 hour.                        |
|    Possible sepsis without shock: rapid investigation; give antibiotics within 3 hours if concern persists. |
|    Select empirical coverage by severity, prior cultures/exposure and local resistance; then narrow.        |
|    Critical illness/obstruction or substantial ESBL risk may warrant meropenem; it is not mandatory for all.|
|                                                                                                             |
| 3. CIRCULATION                                                                                              |
|    Hypoperfusion/shock: SSC suggests at least 30 mL/kg IV crystalloid during the first 3 hours.             |
|    Balanced crystalloids are generally preferred; individualize volume and reassess frequently.             |
|    Follow perfusion, blood pressure, urine output and lactate trend; avoid fluid overload.                  |
|    Persistent hypotension: norepinephrine, with an initial MAP target around 65 mmHg.                       |
|    Profound instability may require vasopressors concurrently with initial fluid resuscitation.             |
|                                                                                                             |
| 4. URGENT SOURCE CONTROL                                                                                    |
|    Infected urinary obstruction requires urgent drainage: PCN or retrograde JJ stent.                       |
|    Antibiotics alone do not provide adequate source control; begin resuscitation while arranging drainage.  |
|    Defer definitive stone fragmentation/extraction until sepsis and infection have resolved.                |
+-------------------------------------------------------------------------------------------------------------+

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4. Genitourinary Tuberculosis (TB) (ETR pp. 32-33)

Genitourinary tuberculosis (GUTB) is an important extrapulmonary manifestation of TB; its frequency varies substantially by region and population. Caused by Mycobacterium tuberculosis, it is an insidious, destructive disease that frequently evades early diagnosis, culminating in severe organ deformity, extensive fibrotic stricturing, and non-functioning auto-amputated kidneys.

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|                             GENITOURINARY TUBERCULOSIS PATHOGENESIS                             |
|                                                                                                 |
|  1. Primary Pulmonary Infection:                                                                |
|     --> Inhalation of Mycobacterium tuberculosis droplet nuclei                                 |
|     --> Asymptomatic primary pulmonary focus / Ghon complex                                     |
|                                                                                                 |
|  2. Haematogenous Seeding (Cortical Phase):                                                     |
|     --> Early bacillemia disseminates organisms haematogenously to the rich vascular bed of the |
|         BILATERAL renal cortex (glomerular and peritubular capillary tufts)                     |
|     --> Granuloma formation with caseous necrosis; contained within quiescent cortical nodules  |
|     --> Prolonged latency interval: Clinical disease manifests 10 to 30 YEARS later!            |
|                                                                                                 |
|  3. Reactivation & Medullary Cavitation (Medullary Phase):                                      |
|     --> Breakdown of host cell-mediated immunity activates quiescent cortical bacilli           |
|     --> Bacilli extend into the medulla and renal pyramids, causing papillary necrosis          |
|     --> Cavitation into the pelvicalyceal system: Mycobacterium released into urine (BACILLURIA)|
|                                                                                                 |
|  4. Canalicular Downstream Seeding:                                                             |
|     --> Infected urine seeds the pelvicalyceal collecting system, ureters, bladder, prostate,   |
|         and, via the ejaculatory ducts, the vasa deferentia and epididymides                    |
|     --> Intense submucosal granulomatous inflammation followed by PROFOUND CICATRICIAL FIBROSIS |
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Clinical Presentation

GUTB is notorious for its deceptive, indolent onset:

• "Sterile Pyuria": The classic clinical hallmark of GUTB is persistent, acidic pyuria with negative routine 24- to 48-hour aerobic bacterial cultures. Persistent sterile pyuria with compatible symptoms or epidemiological risk should prompt evaluation for GUTB, while considering other causes of sterile pyuria.
• Painless Hematuria: Microscopic (50%) or gross painless macroscopic hematuria resulting from mucosal ulcerations or capillary rupture in inflamed calyces.
• Intractable Lower Urinary Tract Symptoms: Severe urinary frequency, urgency, and nocturia that fail to improve after standard empirical antibacterial therapy. Intractable daytime frequency and nocturnal voiding are driven by chronic tuberculous cystitis and progressive muscular fibrosis.
• Constitutional Symptoms: Low-grade evening pyrexia, drenching night sweats, anorexia, fatigue, and unexplained weight loss (present in only 20–30% of localized GUTB cases).
• Genital Manifestations in Men: Painless, firm, nodular enlargement of the epididymis (starting at the tail/globus minor); thickened, indurated, beaded vas deferens ("rosary bead" vas); scrotal cutaneous fistulae draining caseous discharge; and chronic indurated prostatitis.

Pathological Features & Structural Deformities

The hallmark of chronic GUTB is extensive fibrosis, scarring, and luminal stenosis as granulomas heal by cicatrization:

• Infundibular Strictures & Calyceal Amputation: Granulomatous ulceration at the infundibulum heals by circular scarring, occluding the calyceal neck and causing hydrocalycosis (isolated dilated calyx) or complete obliteration ("phantom calyx" or "calyceal amputation" on IVU/CT urogram).
• Ureteric Strictures & The "Pipestem" Ureter: Tuberculous ureteritis involves the submucosa and muscular layers. Fibrotic healing leads to multiple segment strictures (most commonly at the ureterovesical junction, pelvic brim, or pelviureteric junction), total muscular destruction, longitudinal retraction, and wall rigidification. The ureter becomes shortened, straightened, and non-peristaltic, producing the classic "pipestem" rigid ureter or "beaded/corkscrew" ureter on contrast imaging.
• The Contracted "Thimble Bladder" (Microcystis): Chronic transmural tuberculous cystitis destroys the detrusor muscle, replacing elastic smooth muscle fibers with dense fibrous scar tissue. The bladder contracts into a rigid, non-compliant, thick-walled sphere with an functional capacity of < 50 to 100 mL. The ureteral orifices become stiff, gaping, and retracted upward into a fixed "golf-hole" appearance, permitting severe, continuous vesicoureteral reflux that rapidly transmits high intravesical pressures to the kidneys, driving bilateral renal destruction.
• Caseocavernous Renal Destruction & The "Putty Kidney": Progressive medullary cavitation coalesces, transforming the renal parenchyma into multiple cavities filled with inspissated caseous, cheese-like material. Dystrophic calcification ensues throughout the necrotic tissue. The entire kidney is converted into an auto-amputated, non-functioning calcified sac, termed a "putty kidney" (cement kidney / tuberculous auto-nephrectomy).

Diagnostic Evaluation

• Urine Mycobacterial Testing: Diagnostic gold standard requires collection of at least 3 consecutive early-morning midstream clean-catch urine specimens (first voided morning urine is concentrated overnight in the bladder):
  • Acid-Fast Bacilli (AFB) Smear: Ziehl-Neelsen stain or auramine-rhodamine fluorochrome staining. Demonstrates acid-fast rods; urine smear sensitivity is low (EAU reports 0–25%), so a negative result does not exclude GUTB.
  • Mycobacterial Culture: Inoculation onto solid media (Lowenstein-Jensen) and liquid automated culture systems (MGIT - Mycobacteria Growth Indicator Tube). Liquid systems detect growth in 1 to 3 weeks; solid media take 6 to 8 weeks. Culture remains the definitive gold standard for species confirmation (M. tuberculosis) and phenotypic drug susceptibility testing (DST).
  • Automated Nucleic Acid Amplification Testing (NAAT / GeneXpert MTB/RIF): Rapid real-time automated PCR assay providing simultaneous detection of M. tuberculosis complex DNA and identification of mutations in the rpoB gene (which confers resistance to rifampicin) within 2 hours. Highly recommended for rapid diagnostic confirmation.
• Imaging Modalities:
  • CT Urography: Helps define disease extent and complications; tailor the protocol to renal function and the clinical question. Identifies cortical scarring, calyceal distortion, phantom calyces, infundibular stenoses, hydronephrosis, ureteral wall thickening/strictures, thimble bladder, and renal parenchymal calcifications.
  • Chest Radiograph: Evaluates associated pulmonary disease; a normal radiograph does not exclude GUTB.
• Cystoscopy: Reveals mucosal hypervascularity, small yellowish-white subepithelial tubercles surrounded by an erythematous halo, patchy velvety red mucosal ulcerations, gaping rigid "golf-hole" ureteral orifices, and profoundly diminished bladder capacity under general anesthesia.

Medical Treatment Protocols

Uncomplicated GUTB is managed primarily with multi-agent antituberculous chemotherapy to ensure rapid bactericidal clearance, prevent emergence of drug resistance, and sterilize quiescent caseous foci.

+------------------------------------------------------------------------------------------------+
|                             STANDARD 6-MONTH SHORT-COURSE CHEMOTHERAPY                         |
|                                                                                                |
|  INTENSIVE INITIAL PHASE (2 Months) -- 4 Drugs (2RHZE):                                        |
|  1. Rifampicin (RIF):     10 mg/kg PO once daily (max 600 mg) [Bactericidal; red-orange urine] |
|  2. Isoniazid (INH):      5 mg/kg PO once daily (max 300 mg) [Potent bactericidal; neuropathy] |
|  3. Pyrazinamide (PZA):   25 mg/kg PO once daily (max 2000 mg) [Sterilizes caseous lesions]    |
|  4. Ethambutol (EMB):     15–20 mg/kg PO once daily (max 1600 mg) [Prevents resistance; optic] |
|                                                                                                |
|  CONTINUATION PHASE (4 Months) -- 2 Drugs (4RH):                                               |
|  1. Rifampicin (RIF):     10 mg/kg PO once daily (max 600 mg)                                  |
|  2. Isoniazid (INH):      5 mg/kg PO once daily (max 300 mg)                                   |
|                                                                                                |
|  *ADJUNCT: Pyridoxine (Vitamin B6) 25 to 50 mg daily co-administered to prevent INH peripheral |
|            neuropathy, especially in diabetics, alcoholics, malnourished, or pregnant patients.|
+------------------------------------------------------------------------------------------------+

• Systemic Corticosteroids: These are not a routine component of GUTB treatment and are not established prophylaxis against urinary strictures. Use effective antituberculous drugs, monitor drainage and renal function, and relieve significant obstruction. Any separate steroid indication requires specialist assessment.

Surgical Management Principles

• Timing of Surgery: Start effective antituberculous treatment and individualize elective reconstruction or nephrectomy according to inflammation, organ damage, drainage and response. EAU finds insufficient evidence for one mandatory waiting interval. Do not defer urgently needed decompression while waiting for 4–6 weeks of treatment or a negative urine culture; reconstructive surgery is generally planned after disease control.
• Indications for Surgical Intervention:
  1. Temporary Drainage: Percutaneous nephrostomy or JJ ureteral stenting during acute chemotherapy for obstructive hydronephrosis.
  2. Nephrectomy: Consider for a non-functioning or poorly functioning tuberculous kidney, especially with persistent pain, infection or hypertension; assess the contralateral kidney and any associated tumor.
  3. Augmentation Enterocystoplasty: Consider for a severely contracted, poorly compliant bladder causing refractory symptoms or upper-tract risk after infection control. Assess renal function, metabolic consequences, bowel suitability and ability to empty the reconstructed reservoir; normal renal function is not a universal prerequisite.

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5. Fungal Infections of the Genitourinary Tract (ETR pp. 32-33)

Fungal urinary tract infections, predominantly candiduria, have experienced a dramatic rise in hospital settings due to widespread use of broad-spectrum antimicrobials, long-term indwelling urethral catheters, immunosuppressive therapies, and prolonged intensive care stays.

Etiological Pathogens & Species Vulnerabilities

• Candida albicans: Accounts for 50% to 70% of all genitourinary fungal isolates. A dimorphic fungus forming yeast cells, pseudohyphae, and true hyphae (invasive form). Generally highly susceptible to fluconazole and amphotericin B.
• Candida glabrata: Accounts for 20% to 30% of isolates. Non-dimorphic yeast with intrinsically reduced susceptibility or high acquired resistance to fluconazole and other triazoles.
• Candida krusei: Accounts for 1% to 3% of isolates. Inherently and universally resistant to fluconazole; susceptible to amphotericin B and voriconazole.
• Candida tropicalis and Candida parapsilosis: Common opportunistic isolates, frequently involved in biofilm formation on foreign materials.

Asymptomatic Candiduria vs. Invasive Candidiasis

• Asymptomatic Candiduria: Candida in an asymptomatic catheterized patient usually represents colonization. Colony counts alone, particularly with a catheter, cannot distinguish colonization from infection.
• Management in Asymptomatic Patients: Routine systemic antifungal pharmacotherapy is NOT indicated for asymptomatic candiduria. Systemic antifungals eradicate the organism only transiently and drive selection of azole-resistant strains. Remove an unnecessary catheter or replace it when continued drainage is required, and correct other predisposing factors. This often clears candiduria, without guaranteeing resolution in every patient.
• Mandatory Indications for Treating Candiduria:
  1. Symptomatic Candida Infection: Symptomatic lower tract cystitis (dysuria, frequency, suprapubic pain) or ascending candidal pyelonephritis.
  2. Neutropenia: A high-risk exception to observation alone; evaluate for invasive candidiasis. Immunosuppression or diabetes by itself does not mandate treatment of every asymptomatic urine isolate.
  3. Low-Birth-Weight Neonates: Very low birth weight (< 1500 g) due to immature immune defenses and high mortality from candidemia.
  4. Planned Urological Instrumentation / Surgery: Patients with candiduria who are scheduled for transurethral surgery, ureteroscopy, or nephrolithotomy. Instrumentation through colonized urine can cause mucosal micro-trauma, leading to fatal candidemia and septic shock. Give an appropriate peri-procedural antifungal for several days before and after manipulation: fluconazole 400 mg daily for a susceptible isolate, or IV amphotericin B deoxycholate 0.3–0.6 mg/kg daily when appropriate. Select by susceptibility, renal function and specialist advice.

Antifungal Pharmacotherapy & Renal Pharmacokinetics

Antimicrobial selection for urinary fungal infections is dictated by the urinary excretion profile of the drug:

+---------------------------------------------------------------------------------------------------------+
| ANTIFUNGALS: SITE, SUSCEPTIBILITY AND FORMULATION MATTER                                                |
|                                                                                                         |
| 1. FLUCONAZOLE FOR SUSCEPTIBLE ISOLATES                                                                 |
|    High active urinary excretion; usual cystitis maintenance dose 200 mg orally daily for 14 days.      |
|    Ascending pyelonephritis: 200–400 mg daily for 14 days; adjust for renal function.                   |
|    EAU uses a double maintenance dose on day 1. Confirm susceptibility before treating C. glabrata.     |
|    C. krusei is fluconazole-resistant.                                                                  |
|                                                                                                         |
| 2. AMPHOTERICIN B DEOXYCHOLATE                                                                          |
|    Selected resistant cystitis: bladder irrigation 50 mg/L sterile water daily for 5 days.              |
|    Irrigation acts locally and does not treat upper-tract or disseminated disease.                      |
|    Resistant ascending infection: IV deoxycholate 0.3–0.6 mg/kg/day for 1–7 days;                       |
|    flucytosine 25 mg/kg orally four times daily may be added for C. glabrata.                           |
|    Monitor renal function, electrolytes and flucytosine toxicity; adjust flucytosine for renal function.|
|                                                                                                         |
| 3. LIPID AMPHOTERICIN FORMULATIONS                                                                      |
|    Liposomal amphotericin achieves poor urinary levels and is unsuitable for ascending luminal UTI.     |
|    It is not interchangeable with deoxycholate for the urinary regimens above.                          |
|    Candidemia or hematogenous renal infection follows an invasive-candidiasis regimen.                  |
|                                                                                                         |
| 4. ECHINOCANDINS                                                                                        |
|    Poor active urinary excretion limits routine use for bladder-lumen infection.                        |
|    Adequate renal tissue levels can support use for renal parenchymal/invasive infection.               |
|    EAU also includes caspofungin among specialist options for resistant Candida UTI;                    |
|    select by site, susceptibility and patient factors rather than claiming universal failure.           |
+---------------------------------------------------------------------------------------------------------+

Endourological Management of Fungal Balls (Bezoars)

Fungal balls (mycetomas or bezoars) are tangled masses of fungal pseudohyphae, necrotic epithelial debris, mucus, and matrix that aggregate within the renal pelvis, calyces, or bladder lumen. They present with acute obstructive uropathy, hydronephrosis, anuria, or progressive sepsis, particularly in poorly controlled diabetics or low-birth-weight neonates.

• Management Algorithm:
  1. Immediate Decompression: Emergency placement of a percutaneous nephrostomy (PCN) tube to drain the obstructed infected kidney.
  2. Endourological Extraction / Fragmentation: Percutaneous nephroscopy or flexible retrograde ureterorenoscopy using basket retrieval, suction, or gentle fragmentation to physically clear the obstructing fungal bezoar.
  3. Local Intracavitary Irrigation: When a nephrostomy is present, IDSA recommends amphotericin B deoxycholate 25–50 mg in 200–500 mL sterile water for local irrigation, alongside systemic treatment and removal of obstructing material. Use a supervised irrigation protocol with reliable drainage.

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6. Parasitic Infestations of the Genitourinary Tract (ETR pp. 32-33)

Urogenital Schistosomiasis (Bilharzia)

Urogenital schistosomiasis is caused by the digenetic blood trematode (fluke) Schistosoma haematobium, endemic across sub-Saharan Africa, the Nile River basin, and parts of the Middle East. It represents one of the major neglected tropical diseases worldwide, with profound long-term urological morbidity.

+-------------------------------------------------------------------------------------------------+
|                             SCHISTOSOMA HAEMATOBIUM LIFE CYCLE                                  |
|                                                                                                 |
|  1. Freshwater Reservoir:                                                                       |
|     --> Infected humans excrete urine containing viable terminal-spined ova into fresh water    |
|     --> Eggs hatch in water, releasing ciliated free-swimming MIRACIDIA                         |
|                                                                                                 |
|  2. Intermediate Host:                                                                          |
|     --> Miracidia penetrate freshwater aquatic snails of the genus BULINUS                      |
|     --> Undergo asexual amplification within the snail, developing into thousands of fork-tailed|
|         free-swimming CERCARIAE, released into water                                            |
|                                                                                                 |
|  3. Human Infection:                                                                            |
|     --> Cercariae penetrate INTACT human skin during bathing, swimming, or agricultural wading  |
|     --> Shed tails, transform into SCHISTOSOMULA, enter cutaneous venules                       |
|     --> Migrate through the heart, pulmonary vasculature, and portal circulation                |
|                                                                                                 |
|  4. Maturation & Perivesical Venous Tropism:                                                    |
|     --> Adult male and female worms mate in the portal veins, then migrate against portal blood |
|         flow via the mesenteric and hemorrhoidal channels into the VESICAL AND PELVIC VENOUS    |
|         PLEXUSES (surrounding the urinary bladder, prostate, and lower ureters)                 |
|                                                                                                 |
|  5. Oviposition & Granulomatous Reaction:                                                       |
|     --> Adult female produces hundreds of TERMINAL-SPINED OVA daily                             |
|     --> Ova breach the venular endothelium and migrate through the bladder wall to enter urine  |
|     --> Trapped ova provoke intense Th2 cell-mediated EOSINOPHILIC GRANULOMATOUS INFLAMMATION,  |
|         leading to pseudotubercles, sandy patches, and progressive transmural fibrosis          |
+-------------------------------------------------------------------------------------------------+

• Clinical Presentation:
  • Terminal Painless Hematuria: Hallmark presenting symptom. As the detrusor contracts at the completion of micturition, inflamed, friable mucosal granulations are squeezed, releasing bright red blood into the final drops of urine.
  • Dysuria, frequency, and suprapubic discomfort.
• Pathological Features & Radiographic Milestones:
  • "Sandy Patches" on Cystoscopy: Submucosal granulomas and calcified, dead ova that produce an irregular, roughened, granular mucosal appearance resembling sand on a beach. Highly pathognomonic for chronic schistosomiasis.
  • Curvilinear Bladder Wall Calcification: Calcified dead ova densely deposited in the submucosa and muscularis create extensive curvilinear, rim-like calcification outlining the bladder perimeter. Seen on plain pelvic radiography (KUB) as the classic "fetal head" sign (calcified circular shell resembling a fetal cranium in the true pelvis) and on non-contrast CT.
  • Ureteral Strictures & Hydronephrosis: Tuberculoid granulomas and fibrosis in the intramural and distal third of the ureter produce strictures, aperistaltic dilatation, and progressive hydroureteronephrosis, often leading to secondary chronic renal failure.
• Malignancy: Bladder Squamous Cell Carcinoma (SCC):
  • Chronic S. haematobium infection is classified by IARC as a Group 1 human carcinogen, strongly predisposing to Squamous Cell Carcinoma (SCC) of the urinary bladder through chronic inflammation and squamous metaplasia. The proportion of bladder tumors that are SCC varies by region and era; this is an association, not a universal endemic-region percentage.
  • Carcinogenic Mechanism: Continuous mechanical irritation by ova, chronic cellular regeneration, squamous metaplasia, and secondary bacterial infections with nitrate-reducing enteric organisms that synthesize potent carcinogenic N-nitrosamines.
• Treatment:
  • Praziquantel: The drug of choice for schistosomiasis, acting most effectively on adult worms; immature parasites are less susceptible. Administered as a single oral dose of 40 mg/kg (or divided into two doses of 20 mg/kg spaced 4 to 6 hours apart). Praziquantel increases cell membrane permeability to calcium in adult worms, causing massive intracellular calcium influx, rapid spastic tetanic paralysis, and disintegration of the parasite tegument, allowing host immune destruction.

Renal Echinococcosis (Hydatid Disease)

Renal hydatid disease is a zoonotic parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus. Humans act as accidental intermediate hosts. The liver and lungs are the commonest sites; renal involvement is uncommon.

• Cyst Wall Architecture:
  1. Pericyst (Adventitia): Outer, dense fibrous layer produced by host tissue reaction and compressed renal parenchyma; vascular and adherent to surrounding renal tissue.
  2. Ectocyst (Laminated Membrane): Middle, acellular, elastic laminated layer that resembles hard-boiled egg white.
  3. Endocyst (Germinative Layer): Inner, cellular layer containing nucleated germinal cells that produce brood capsules, scolices, and internal daughter cysts.
  • Hydatid Sand: The fluid within the cyst cavity contains thousands of microscopic invaginated scolices, hooklets, and detached brood capsules.
• Clinical Presentation:
  • Renal cysts may remain asymptomatic for years; growth is variable.
  • Pathognomonic Sign: Hydatiduria: Sudden onset of severe renal colic followed by the macroscopic passage of grape-like gelatinous membranes, daughter cysts, or grape-skin structures in the urine. Occurs when the hydatid cyst ruptures through the parenchymal barrier into the pelvicalyceal collecting system. Cyst rupture can trigger severe anaphylactic reactions, bronchospasm, and sudden death!
• Diagnosis:
  • Serology: Hydatid ELISA and indirect hemagglutination (IHA) against hydatid fluid antigens.
  • Ultrasonography / CT (Gharbi Classification): Demonstrates well-defined unilocular fluid cysts (Type I), floating detached laminated membranes producing the classic "water lily" sign (Type II), multivesicular cysts containing internal daughter cysts creating a "spoke-wheel" or "honeycomb" pattern (Type III), heterogeneous pseudotumoral solid lesions (Type IV), or heavily calcified inactive cysts (Type V).
• Management Protocols:
  • Albendazole: An adult regimen is 400 mg PO BID (weight-based dosing for smaller patients). It is commonly used around intervention to reduce viable parasite burden and seeding risk; specialist protocols determine timing and duration. Monitor liver enzymes and blood counts.
  • The PAIR Technique (Puncture, Aspiration, Injection, Re-aspiration):
    • An expert-center option for selected renal cysts, particularly simple fluid cysts, without collecting-system communication. Do not treat every daughter-cyst-containing Type III lesion as suitable for simple PAIR.
    • Principle: Image-guided Puncture, Aspiration, Injection of a suitable scolicidal agent, and Re-aspiration. Agent, concentration, dwell time and need for catheter drainage follow an expert protocol after confirming that the cyst does not communicate with the collecting system.
    • Absolute Contraindication to PAIR: Documented communication with the pelvicalyceal collecting system (scolicidal agents entering the renal pelvis cause severe chemical urothelial necrosis and infundibular/ureteral strictures).
  • Surgical Excision: Laparoscopic or open partial pericystectomy or complete cyst enucleation. Preserve functioning renal tissue where feasible, protect the field and avoid cyst-content spillage, which can cause dissemination or anaphylaxis. The team selects safe isolation and scolicidal measures; nephrectomy may be needed for extensive renal destruction.

Summary Reference Tables: UTI Classification & Specific Infections

Table 1: Modern EAU Classification & Clinical Phenotypes of UTIs

Table 2: Specialist Genitourinary Infections: TB, Candidiasis, Schistosomiasis & Hydatid Disease