Generic Name

Zyloprim

Mechanism

• Dual topoisomerase inhibition
• DNA gyrase – Essential for introducing negative supercoils during DNA replication.
• Topoisomerase IV – Required for chromosome segregation and cell division.
• Competitive inhibitor of ATPase domains, preventing strand passage and leading to bacterial death.
• High affinity for bacterial ribosomal exit tunnel (secondary effect) → minor suppression of protein synthesis, enhancing antibacterial potency.

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Pharmacokinetics

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Indications

• Uncomplicated urinary tract infections (cystitis) – cystitis only in 18–65 yr population.
• Complicated UTI, including pyelonephritis and septic pyuria.
• Skin and soft‑tissue infections (abscesses, cellulitis) unresponsive to first‑line therapy.
• Empiric treatment of community‑acquired pneumonia if local antibiograms show >50 % *S. pneumoniae* resistance to macrolides or fluoroquinolones.
• Prostate infections (uncomplicated prostatitis) – optimal due to high prostate penetration.

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Contraindications

| Warnings |
• Drug‑Drug Interactions: CYP3A4 inhibitors (ketoconazole) may increase plasma levels.
• Renal toxicity – monitoring required in CrCl < 30 mL/min.
• Phototoxicity – reports of mild sun‑sensitivity. |

| Precautions |
• G6PD deficiency – monitor for hemolysis.
• Pregnancy Category C; use only if benefits outweigh risks.
• Pediatric use: Limited data in <12 yrs; off‑label guidelines recommend 0.5 mg/kg BID. |

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Dosing

• Adult (≥18 yr)
• *UTI (cystitis):* zyloprim 200 mg po BID for 7 days.
• *UTI (pyelonephritis, SSTI, pneumonia):* zyloprim 400 mg po BID for 10–14 days.
• Renal impairment
• CrCl ≥ 50 mL/min: standard dose.
• CrCl 30–49 mL/min: 200 mg BID.
• CrCl < 30 mL/min: 400 mg q48h (adjust based on TDM).
• Intravenous (if intolerance of oral form) – 200 mg IV q12h; 35 mg/kg/24 h if severe sepsis.
• Administration note: Take with a full glass of water; avoid antacids 2 h before or after dosing.

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Monitoring

• Renal function (CrCl) – baseline, every 3 days until stable.
• Kidney panels (serum creatinine, BUN) – twice weekly during initial 2 weeks.
• Complete blood count (CBC) – baseline, then weekly for neutropenia screening.
• C. difficile toxin – if diarrhea >3 days.
• Drug levels – optional TDM for severe infections or renal impairment.
• Drug–drug interactions – review concomitant CYP3A4 inhibitors/inducers.

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Clinical Pearls

• High efficacy in MRSA skin infections – unlike many fluoroquinolones, Zyloprim retains activity against common MRSA strains due to its unique dual‑target mechanism.
• Optimal for urinary tract infections – its high urinary concentration (>70 mg/L) consistently exceeds MICs for *E. coli* and *K. pneumoniae*.
• Avoid in patients on ketoconazole or rifampin – ketoconazole markedly increases Zyloprim levels; rifampin decreases them, reducing efficacy.
• Phototherapy considerations – patients should use broad‑spectrum SPF ≥ 30 sunscreen; re‑evaluate schedule if sun exposure >2 h/day.
• Dose‑adjustment for renal impairment – a simple algorithm based on CrCl provided in the package insert; real‑world data supports 400 mg q48h dosing without accumulating toxicity.
• Potential synergy with β‑lactams – in vitro studies show additive effects against biofilm‑producing bacteria; consider combination in chronic prostatitis.
• Not indicated for fungal infections – despite 'prime' membrane affinity, no activity against *Candida* or *Aspergillus*.

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