45.1 Uncomplicated UTI, Pyelonephritis & Acute Urethritis

Epidemiology, Pathogenesis & Classification of Lower Urinary Tract Infections

Urinary tract infections (UTIs) represent one of the most common bacterial infections encountered in outpatient family medicine, accounting for over 10 million ambulatory visits annually in the United States. Nearly 50% to 60% of adult women will experience at least one symptomatic UTI during their lifetime, with 20% to 30% suffering a recurrence within 6 months.

Pathogenesis

The overwhelming majority of urinary tract infections occur via the ascending transurethral route. The female anatomical predisposition is primarily driven by a short urethra (~4 cm compared to ~20 cm in males) situated in close proximity to the warm, moist, bacterial reservoirs of the vagina, perineum, and perianal region.

1. Uropathogen Colonization: Normal vaginal flora, dominated by hydrogen peroxide-producing Lactobacillus species, maintains an acidic vaginal pH (3.8 to 4.5) that inhibits Enterobacteriaceae colonization. Depletion of lactobacilli—triggered by sexual intercourse, spermicide use (nonoxynol-9), systemic antibiotics, or estrogen deficiency in postmenopausal women—permits uropathogenic Escherichia coli (UPEC) to colonize the introitus and periurethral area.
2. Urothelial Adherence: UPEC strains possess specialized virulence factors, most notably Type 1 fimbriae (mannose-sensitive adhesins that bind uroplakin receptors on superficial bladder umbrella cells) and P fimbriae (pyelonephritis-associated pilus, which binds glycosphingolipids on renal tubular epithelial cells). Adherence triggers bacterial internalization into bladder epithelial cells, forming intracellular bacterial communities (IBCs) that evade host immune surveillance and antibiotic penetration.
3. Host Inflammatory Response: Bacterial lipopolysaccharide (LPS) activates urothelial Toll-like receptor 4 (TLR4), triggering an intense local release of interleukin-6 (IL-6) and interleukin-8 (IL-8). IL-8 recruits neutrophils into the urinary space, producing the hallmark microscopic pyuria and sensory symptoms of bladder irritation.

Microbial Etiology

• Uropathogenic Escherichia coli (UPEC): Responsible for 75% to 95% of all acute uncomplicated cystitis cases and >80% of outpatient pyelonephritis.
• Staphylococcus saprophyticus: Coagulase-negative, novobiocin-resistant staphylococcus accounting for 5% to 15% of uncomplicated UTIs in sexually active young women; characteristically displays seasonal summertime peaks.
• Klebsiella pneumoniae & Proteus mirabilis: Account for 3% to 8% each. Proteus mirabilis produces bacterial urease, predisposing to alkaline urine and struvite calculi.
• Enterococcus faecalis & Group B Streptococcus (Streptococcus agalactiae): Account for <5% of uncomplicated cystitis; more commonly isolated in older adults, diabetics, and pregnant patients.

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Uncomplicated vs. Complicated Urinary Tract Infection

Accurate clinical triage into uncomplicated versus complicated infection dictates the necessity of diagnostic urine cultures, the selection and duration of antimicrobial therapy, and the threshold for urological imaging.

                  CLINICAL CLASSIFICATION OF URINARY TRACT INFECTIONS

   Category          Patient Population                    Diagnostic & Management Mandate
   ═══════════════════════════════════════════════════════════════════════════════════════════
   Acute             • Non-pregnant, immunocompetent       • Clinical diagnosis; dipstick suffices
   Uncomplicated       premenopausal female                • Routine urine culture NOT required
   Cystitis          • Anatomically normal urinary tract   • 3-5 days of first-line oral agents
                     • No systemic signs of infection      • No imaging indicated

   Complicated       • All male patients                   • Urine culture & susceptibility MANDATORY
   UTI               • Pregnant females                    • Minimum 7 to 14 days of therapy
                     • Uncontrolled diabetes mellitus      • Broadened empiric antimicrobial coverage
                     • Immunocompromise (HIV, transplant)  • Low threshold for renal ultrasound / CT
                     • Indwelling catheter, stent, or PVR  • Rule out obstruction, abscess, or stone
                     • Anatomical defects (strictures, VUR)
                     • Renal insufficiency / CKD
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Clinical Presentation of Acute Uncomplicated Cystitis

Patients present with a constellation of classic lower urinary tract symptoms (LUTS):

• Dysuria: Sharp, burning urethral pain during or immediately following micturition.
• Frequency & Urgency: Compelling, uncontrollable urge to void small volumes of urine.
• Suprapubic Pain: Dull, aching pressure or discomfort over the urinary bladder.
• Gross Hematuria: Present in up to 30% of acute uncomplicated cystitis presentations ("hemorrhagic cystitis"); does not alter classification or portend worse outcomes in acute young women.
• CRITICAL EXAM PEARL: The presence of classic dysuria and frequency in the absence of vaginal discharge or vaginal irritation carries a positive predictive value >90% for acute uncomplicated cystitis. Physical examination reveals suprapubic tenderness to palpation, but normal vital signs, absence of fever, and absence of costovertebral angle (CVA) tenderness.

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Urinalysis Interpretation: Leukocyte Esterase, Nitrites & Microscopy

Urinalysis is the primary diagnostic adjunct in ambulatory family medicine. A properly collected clean-catch midstream urine specimen is essential to avoid perineal contamination.

                        URINALYSIS INTERPRETATION IN UTI

   Component          Diagnostic Mechanism                  Clinical Pearls & Pitfalls
   ═══════════════════════════════════════════════════════════════════════════════════════════
   Leukocyte          • Detects esterase enzyme released    • Sensitivity: 75% to 95%; Specificity: 95%
   Esterase             by lysed polymorphonuclear cells   • Correlates with pyuria (>=10 WBC/mm3)
                        (neutrophils) in urine             • False negative: concentrated urine,
                                                              glucosuria, high-dose cephalosporins

   Nitrites           • Detects conversion of dietary       • Highly specific (>95%), moderate sensitivity
                        nitrates to nitrites by bacterial    • Positive indicates Enterobacteriaceae
                        nitrate reductase enzyme            • False negatives: Enterococcus, S. sapro-
                                                              phyticus, Pseudomonas (lack reductase);
                                                              bladder dwell time <4 hours; low dietary
                                                              vegetables; high vitamin C (ascorbate)

   Microscopy         • Identifies intact WBCs, RBCs,       • Significant pyuria: >5 WBCs/HPF
                        bacteria, and epithelial cells     • Squamous epithelial cells >5/HPF indicate
                                                              perineal contamination (invalid sample)
   ═══════════════════════════════════════════════════════════════════════════════════════════

When is a Urine Culture Indicated?

In an otherwise healthy, non-pregnant woman presenting with classic symptoms of uncomplicated cystitis, routine urine culture and antimicrobial susceptibility testing are NOT cost-effective and are NOT recommended by IDSA guidelines. Empiric therapy is initiated immediately based on clinical presentation and dipstick confirmation.

Urine culture and susceptibility testing ARE mandatory in the following clinical scenarios:

1. Suspected acute pyelonephritis or systemic toxicity
2. Complicated UTI (males, pregnancy, diabetes, immunosuppression, indwelling hardware)
3. Recurrent UTIs (defined as >=2 distinct episodes in 6 months or >=3 episodes in 12 months)
4. Symptoms that fail to resolve or recur within 2 to 4 weeks following antimicrobial completion
5. Atypical clinical symptoms or diagnostic ambiguity
6. Suspected multi-drug resistant organisms (MDROs) or recent hospitalization/international travel

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IDSA Guideline First-Line Antimicrobial Regimens for Uncomplicated Cystitis

The Infectious Diseases Society of America (IDSA) and European Society of Microbiology and Infectious Diseases (ESCMID) establish three primary first-line empiric antimicrobial regimens for acute uncomplicated cystitis. These agents were explicitly selected for their high clinical efficacy, minimal collateral damage to normal gastrointestinal and vaginal microbiomes, and low rates of resistance.

          FIRST-LINE EMPIRIC REGIMENS FOR ACUTE UNCOMPLICATED CYSTITIS

   Antimicrobial Agent       Dosage & Schedule             Duration   Key Clinical Considerations
   ═══════════════════════════════════════════════════════════════════════════════════════════
   1. Nitrofurantoin         100 mg PO BID with meals      5 Days     • High bladder concentration;
      monohydrate/                                                      negligible tissue penetration
      macrocrystals                                                   • CONTRAINDICATED if eGFR <30 mL/min
      (Macrobid)                                                      • Ineffective for pyelonephritis/prostate
                                                                      • Safe in 2nd/3rd trimester (avoid at term)

   2. Trimethoprim-          1 Double-Strength (DS) tab    3 Days     • Dose: 160 mg TMP / 800 mg SMX
      sulfamethoxazole       (160/800 mg) PO BID                      • Avoid if local E. coli resistance >20%
      (TMP-SMX; Bactrim DS)                                           • Avoid in sulfa allergy, G6PD defect
                                                                      • Risk of hyperkalemia and SJS

   3. Fosfomycin             3 g PO single-dose sachet     1 Dose     • Dissolve powder in 3-4 oz cold water
      trometamol             dissolved in cold water                  • Excellent compliance; ESBL active
                                                                      • Lower clinical cure (~75-80%) vs Macrobid
   ═══════════════════════════════════════════════════════════════════════════════════════════

Detailed Pharmacotherapy Review

1. Nitrofurantoin (Macrobid)

• Mechanism: Reduced by bacterial flavoproteins to highly reactive electrophilic intermediates that non-specifically attack ribosomal proteins, DNA, RNA, and metabolic enzymes.
• Clinical Strengths: Minimal resistance (<3% to 5% among UPEC despite 60 years of clinical use) and negligible impact on bowel flora.
• Crucial Pharmacokinetic Limitation: Rapidly cleared and concentrated exclusively in the urinary bladder lumen. It fails to achieve therapeutic parenchymal tissue levels in the renal parenchyma or prostate gland. Consequently, nitrofurantoin is STRICTLY INEFFECTIVE for acute pyelonephritis, renal abscess, or acute bacterial prostatitis.
• Renal Cutoff: Historically contraindicated at CrCl <60 mL/min, the 2015 updated Beers Criteria and American Geriatrics Society revised the threshold down to eGFR <30 mL/min. At eGFR <30 mL/min, urinary drug excretion is insufficient to clear bladder bacteriuria, while systemic accumulation increases the risk of peripheral neuropathy and pulmonary toxicity.

2. Trimethoprim-Sulfamethoxazole (TMP-SMX)

• Mechanism: Sequential inhibition of bacterial folic acid synthesis (sulfamethoxazole inhibits dihydropteroate synthase; trimethoprim inhibits dihydrofolate reductase).
• Resistance Threshold: TMP-SMX remains an outstanding 3-day regimen only if the local community prevalence of E. coli resistance is known to be <20% and the patient has not received TMP-SMX within the preceding 3 months. If local resistance exceeds 20%, an alternative first-line agent must be chosen.
• Adverse Effects: Trimethoprim chemically blocks the epithelial sodium channel (ENaC) in the cortical collecting duct (identical to the potassium-sparing diuretic amiloride), frequently causing hyperkalemia, especially in patients taking ACE inhibitors, ARBs, or spironolactone.

3. Fosfomycin Trometamol

• Mechanism: Inactivates bacterial enolpyruvate transferase (MurA), permanently blocking the initial committed step in peptidoglycan cell wall biosynthesis.
• Indications: Single 3-gram oral sachet. Retains activity against multidrug-resistant pathogens, including extended-spectrum beta-lactamase (ESBL)-producing E. coli. Although single-dose adherence is 100%, randomized trials (e.g., JAMA 2018) demonstrate that clinical and microbiologic cure rates for fosfomycin (75% to 80%) are modestly inferior to 5 days of nitrofurantoin (84% to 90%).

Second-Line Alternative Regimens: Oral Beta-Lactams

When first-line agents cannot be utilized due to allergy, intolerance, or local resistance, oral beta-lactams are appropriate second-line alternatives:

• Cephalexin: 500 mg PO BID to QID for 5 to 7 days.
• Cefpodoxime: 100 mg PO BID for 5 to 7 days.
• Amoxicillin-Clavulanate: 500/125 mg PO BID for 5 to 7 days.
• Caution: Beta-lactams demonstrate lower microbiologic eradication rates and higher recurrence rates compared to nitrofurantoin or TMP-SMX, and are associated with a greater incidence of gastrointestinal adverse effects and vaginal candidiasis. Ampicillin or amoxicillin alone should NEVER be used empirically due to worldwide E. coli resistance exceeding 30% to 50%.

Why Fluoroquinolones are AVOIDED for Uncomplicated Cystitis

Historically, ciprofloxacin (250-500 mg BID x 3 days) was heavily prescribed for uncomplicated cystitis. Today, the FDA, IDSA, and AAFP explicitly state that fluoroquinolones should NOT be used as first-line therapy for acute uncomplicated cystitis.

[!WARNING] FDA BLACK BOX WARNING & ANTIMICROBIAL STEWARDSHIP Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) carry severe, potentially irreversible and disabling black box warnings:

1. Tendinopathy & Tendon Rupture: Primarily involving the Achilles tendon; risk is amplified in patients aged >60 years and those taking concurrent systemic corticosteroids.
2. Peripheral Neuropathy: Axonal polyneuropathy that may become permanent.
3. Central Nervous System Toxicities: Seizures, hallucinations, psychosis, severe anxiety, and delirium.
4. Aortic Aneurysm & Dissection: Accelerated collagen degradation in the aortic wall.
5. QT Prolongation & Torsades de Pointes: Cardiac conduction delays.
6. Clostridioides difficile Colitis: High propensity to disrupt intestinal microbiome.

Fluoroquinolones must be conserved for serious, invasive infections—specifically acute pyelonephritis and complicated prostatitis—where oral alternatives are severely limited.

Symptomatic Relief: Phenazopyridine (Pyridium)

Phenazopyridine is an azo dye that exerts a topical analgesic effect on the urinary tract mucosa (100 to 200 mg PO TID after meals). It provides symptomatic relief of severe dysuria during the initial 24 to 48 hours while antibiotics take effect.

• Duration: Restrict to a maximum of 48 hours; longer therapy masks persistent infection and increases toxicity.
• Patient Counseling: Clinicians must proactively warn patients that phenazopyridine causes harmless, bright orange-to-red discoloration of urine that permanently stains clothing and contact lenses.
• Adverse Effects: Prolonged use or accumulation in renal impairment can induce hemolytic anemia and methemoglobinemia.

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Asymptomatic Bacteriuria (ASB): Strict Evidence-Based Indications

Asymptomatic bacteriuria (ASB) is defined as the presence of >=10^5 colony-forming units (CFU)/mL of a single bacterial species in a clean-catch voided urine specimen in a patient without any signs or symptoms of a urinary tract infection (two consecutive specimens in females, single specimen in males).

               EVIDENCE-BASED INDICATIONS FOR SCREENING & TREATING ASB

   Clinical Indication                   Rationale & Recommended Regimen
   ═══════════════════════════════════════════════════════════════════════════════════════════
   1. Pregnant Individuals               • Progesterone-induced ureteral dilation and mechanical
      (Screen at 12-16 weeks)               uterine compression cause urinary stasis.
                                         • Untreated ASB progresses to acute pyelonephritis in
                                           20% to 30% of pregnancies.
                                         • High risk of preterm labor, low birth weight, sepsis.
                                         • Treat 4-7 days: cephalexin, amox-clav, nitrofurantoin
                                           (avoid nitrofurantoin in 1st trimester & at term).
                                         • Test-of-cure urine culture 1 to 2 weeks post-treatment.

   2. Urologic Procedures with           • Endoscopic instrumentation (e.g., TURP, ureteroscopy)
      Anticipated Mucosal Bleeding         disrupts mucosal barrier, causing direct bacteremic
                                           seeding and high rates of life-threatening urosepsis.
                                         • Screen and treat 24 to 48 hours prior to procedure.
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Clinical Populations in Whom ASB MUST NOT Be Treated

In nearly all other populations, asymptomatic bacteriuria represents benign commensal colonization rather than invasive infection. Extensive clinical trials prove that antibiotic eradication in these groups does not decrease symptomatic UTI episodes, does not reduce mortality, does not improve incontinence, but directly triggers C. difficile infection and promotes multidrug-resistant uropathogens.

Do NOT screen or treat ASB in:

• Non-pregnant premenopausal women
• Well-controlled or poorly controlled diabetic patients
• Elderly community-dwelling or nursing home residents (ASB prevalence 25% to 50%)
• Patients with spinal cord injury or neurogenic bladder
• Patients with indwelling Foley catheters or chronic suprapubic tubes (bacteriuria is universal within 30 days)
• Preoperative non-urologic surgical candidates (e.g., prior to total hip or knee arthroplasty)

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Acute Pyelonephritis: Clinical Presentation, Triage & Management

Acute pyelonephritis is an invasive bacterial infection of the renal parenchyma and pelvicalyceal system, typically arising from transurethral ascent of uropathogens from the bladder.

Clinical Presentation & Diagnostic Triad

Patients present with a systemic, toxic illness characterized by:

1. Flank Pain & Costovertebral Angle (CVA) Tenderness: Unilateral or bilateral dull, throbbing pain elicited by gentle fist percussion over the 12th rib posteriorly.
2. High Fever & Shaking Chills / Rigors: Temperature characteristically exceeds 38.0°C (100.4°F), often accompanied by tachycardia and diaphoresis.
3. Systemic Symptoms: Severe nausea, vomiting, anorexia, headache, and general prostration.
4. Lower Urinary Tract Symptoms: Dysuria, frequency, and urgency are present in 60% to 70% of patients, but may be absent.

Laboratory & Diagnostic Evaluation

• Urinalysis & Microscopy: Marked pyuria, positive leukocyte esterase, and nitrites. The presence of White Blood Cell (WBC) Casts on microscopic examination is pathognomonic for renal parenchymal inflammation, confirming upper tract involvement.
• Urine Culture & Susceptibility: Mandatory in 100% of suspected pyelonephritis cases.
• Blood Cultures: Indicated in all hospitalized patients, immunocompromised hosts, or when hemodynamic instability/sepsis is suspected. Blood cultures are positive in 15% to 20% of pyelonephritis admissions.
• Serum Chemistries & CBC: Leukocytosis with significant left shift (neutrophilic bandemia); elevated serum BUN and creatinine reflecting dehydration or acute parenchymal injury.

Outpatient vs. Inpatient Admission Decision-Making

                    ACUTE PYELONEPHRITIS ADMISSION CRITERIA

   Hemodynamic Instability     • Septic shock, hypotension (SBP <90 mmHg), sustained tachycardia
   Severe Clinical Toxicity    • High persistent fevers (>39°C), rigors, severe prostration
   Intractable Vomiting        • Inability to maintain oral hydration or tolerate oral medications
   Obstruction / Calculi       • Known or suspected nephrolithiasis, ureteral stricture, hydronephrosis
   Pregnancy                   • ALL pregnant women with pyelonephritis mandate inpatient IV therapy
   Severe Comorbidities        • Immunocompromise (solid organ transplant, neutropenia, advanced HIV)
                               • Advanced chronic kidney disease (CKD stage 4 or 5)
                               • Poorly controlled brittle diabetes mellitus
   Social Vulnerability        • Lack of home support, cognitive impairment, inability to follow up
   Outpatient Failure          • Persistent fevers or clinical deterioration after 48-72 hours of oral therapy

Outpatient Empiric Antimicrobial Protocols

Outpatient therapy is appropriate for mild-to-moderate pyelonephritis in stable, reliable patients who can tolerate oral fluids.

1. Oral Fluoroquinolones (First-Line if Community Resistance <10%):
   • Ciprofloxacin: 500 mg PO BID for 7 days (or Ciprofloxacin Extended-Release 1000 mg PO daily x 7 days).
   • Levofloxacin: 750 mg PO daily for 5 days.
2. If Local Fluoroquinolone Resistance is >=10% or Unknown:
   • Administer an initial, long-acting parenteral dose in the clinic: Ceftriaxone 1 g IV/IM (or a consolidated aminoglycoside dose, e.g., Gentamicin 5-7 mg/kg IV) followed by oral fluoroquinolone therapy.
3. Alternative Oral Regimens (When Fluoroquinolones Cannot Be Used):
   • Administer Ceftriaxone 1 g IV/IM initial dose, followed by:
   • Trimethoprim-Sulfamethoxazole (TMP-SMX DS): 1 tablet PO BID for 14 days (if susceptibility confirmed), OR
   • Oral Beta-Lactam: Cefpodoxime 200 mg PO BID or Amoxicillin-Clavulanate 875/125 mg PO BID for 10 to 14 days.

Inpatient Parenteral Regimens

Patients requiring hospitalization should be initiated on intravenous therapy immediately:

• First-Line IV: Ceftriaxone 1 g to 2 g IV every 24 hours.
• Pseudomonas Coverage / Complicated / Sepsis: Cefepime 2 g IV every 8 to 12 hours, OR Piperacillin-Tazobactam 3.375 g to 4.5 g IV every 6 hours, OR Meropenem 1 g IV every 8 hours (if ESBL risk).
• Step-Down Therapy: Transition to oral agents once the patient is afebrile and clinically improving for 24 to 48 hours, guided by culture susceptibility results, completing a total 10- to 14-day antimicrobial course.

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Acute Urethritis: Gonococcal vs. Non-Gonococcal Urethritis (NGU)

Acute urethritis is an infectious inflammation of the urethral mucosa, predominantly transmitted through sexual contact in adolescents and young adults.

Clinical Distinction: Gonococcal vs. Non-Gonococcal

                     COMPARISON OF ACUTE URETHRITIS ETIOLOGIES

   Feature             Gonococcal Urethritis (GU)           Non-Gonococcal Urethritis (NGU)
   ═══════════════════════════════════════════════════════════════════════════════════════════
   Pathogen            • Neisseria gonorrhoeae              • Chlamydia trachomatis (20-40%)
                         (Gram-negative diplococcus)        • Mycoplasma genitalium (15-25%)
                                                            • Trichomonas vaginalis (2-5%)
                                                            • Ureaplasma urealyticum, HSV

   Incubation Period   • Rapid: 2 to 5 days                 • Indolent: 1 to 3 weeks

   Urethral Discharge  • Copious, thick, frankly PURULENT   • Scant to moderate, watery, thin,
                         (creamy yellow-green)                MUCOPURULENT or clear

   Dysuria             • Severe, sharp, prominent           • Mild to moderate; pruritus/tingling

   Microscopy /        • Intracellular Gram-negative        • Polymorphonuclear leukocytes (>=2-5/OIF)
   Gram Stain            diplococci within neutrophils       without intracellular diplococci
   ═══════════════════════════════════════════════════════════════════════════════════════════

Diagnostic Protocol: Nucleic Acid Amplification Testing (NAAT)

• First-Catch Urine NAAT: The diagnostic standard of care. Instruct the patient NOT to void for at least 1 to 2 hours prior to collection. Collect the first 20 to 30 mL of the initial voided urine stream.
• CRITICAL EXAM PEARL: Do NOT collect a clean-catch midstream urine for urethritis testing! Midstream collection flushes urethral exudate and pathogens into the toilet, generating false-negative NAAT results. The first 20 mL contains the highest concentration of desquamated urethral epithelial cells harboring N. gonorrhoeae and C. trachomatis.
• Gram Stain of Urethral Swab: Point-of-care evaluation demonstrating >=2 to 5 WBCs per oil immersion field with intracellular Gram-negative diplococci provides immediate presumptive confirmation of gonococcal infection.

CDC 2021 Sexually Transmitted Infections Treatment Guidelines

Because co-infection between Neisseria gonorrhoeae and Chlamydia trachomatis occurs in up to 20% to 40% of cases, empiric therapy initiated prior to NAAT confirmation must provide dual coverage:

            CDC 2021 EMPIRIC ANTIMICROBIAL REGIMEN FOR ACUTE URETHRITIS

   Coverage Target           Antimicrobial Regimen & Route
   ═══════════════════════════════════════════════════════════════════════════════════════════
   Gonococcal Coverage       • CEFTRIAXONE 500 mg IM in a single dose
     (N. gonorrhoeae)          (If body weight >=150 kg [300 lbs], administer Ceftriaxone 1 g IM)

          PLUS                     PLUS

   Chlamydial Coverage       • DOXYCYCLINE 100 mg PO BID for 7 days
     (C. trachomatis)          (First-line preferred agent; superior eradication)
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The Shift Away from Azithromycin

In prior CDC guidelines, Azithromycin 1 g single oral dose was co-first-line. The CDC 2021 guidelines downgraded Azithromycin.

• Why Doxycycline is Superior: Doxycycline achieves significantly higher microbiologic cure rates for rectal chlamydia (which frequently coexists asymptomatically in men and women) and prevents selection of macrolide resistance in Mycoplasma genitalium (where resistance rates to azithromycin now exceed 60% to 80%).
• Azithromycin Role: Reserved strictly for patients with documented severe doxycycline allergy or in pregnant patients (Azithromycin 1 g PO single dose).

Comprehensive Management & Partner Notification

1. Sexual Partner Management: All sexual partners within the preceding 60 days must be evaluated and empirically treated. Provide Expedited Partner Therapy (EPT) (prescribing or dispensing therapy directly to the patient to deliver to partners) where legally permitted.
2. Sexual Abstinence: Patients and their partners must completely abstain from oral, anal, and vaginal sexual intercourse for 7 days following completion of single-dose therapy or until completion of the 7-day doxycycline regimen, and until all symptoms have completely resolved.
3. Screening for Co-Infections: All patients diagnosed with an STI must be screened for HIV, syphilis (serology), and Hepatitis B/C.