Which antibiotics are appropriate and how should they be dose‑adjusted for a patient with severe chronic kidney disease (stage 4‑5, estimated glomerular filtration rate < 30 mL/min/1.73 m²), and which agents should be avoided?

Antibiotic Selection and Dose Adjustment in Severe Chronic Kidney Disease (eGFR < 30 mL/min/1.73 m²)

Penicillins

Penicillins remain usable in severe CKD but require dose reduction and careful monitoring to prevent neurotoxicity and crystalluria. 1

• Benzylpenicillin (Penicillin G): Reduce dose by 50% when eGFR < 30 mL/min/1.73 m² and limit maximum daily dose to 6 g/day to prevent neurotoxicity 1
• High-dose penicillins carry risk of crystalluria when eGFR < 15 mL/min/1.73 m² 1
• Monitor for neurological symptoms (confusion, seizures, myoclonus) which indicate drug accumulation 1

Aminoglycosides

Aminoglycosides should be avoided whenever possible in severe CKD due to nephrotoxicity and ototoxicity, but if essential, require aggressive dose reduction and therapeutic drug monitoring. 1

• Reduce dose and/or increase dosage interval when eGFR < 60 mL/min/1.73 m² 1
• Mandatory monitoring: Measure both trough and peak serum levels to prevent accumulation 1
• Avoid concomitant ototoxic agents such as furosemide 1
• Consider once-daily dosing strategies with extended intervals (e.g., every 48–72 hours) in severe CKD 1

Macrolides

Macrolides are relatively safe in severe CKD with moderate dose adjustment. 1

• Reduce dose by 50% when eGFR < 30 mL/min/1.73 m² 1
• Azithromycin and clarithromycin are preferred over erythromycin due to better tolerability 1

Fluoroquinolones

Fluoroquinolones require dose reduction only in very severe renal impairment. 1

• Reduce dose by 50% when eGFR < 15 mL/min/1.73 m² 1
• Levofloxacin and ciprofloxacin are commonly used; moxifloxacin requires no renal dose adjustment 1

Tetracyclines

Tetracyclines should be avoided in severe CKD as they can exacerbate uremia. 1

• Reduce dose when eGFR < 45 mL/min/1.73 m² 1
• Doxycycline is the safest tetracycline in CKD as it undergoes primarily hepatic elimination, but prolonged use should still be avoided 1

Antifungals

Antifungal selection in severe CKD requires careful consideration of nephrotoxicity and dose adjustment. 1

• Amphotericin B: Avoid unless no alternative exists when eGFR < 60 mL/min/1.73 m² due to severe nephrotoxicity 1
• Fluconazole: Reduce maintenance dose by 50% when eGFR < 45 mL/min/1.73 m² 1
• Flucytosine: Reduce dose when eGFR < 60 mL/min/1.73 m² and monitor serum levels 1

Critical Nephrotoxins to Avoid

NSAIDs are contraindicated in severe CKD (eGFR < 30 mL/min/1.73 m²) and should be avoided entirely. 1, 2

• NSAIDs cause acute kidney injury, hyperkalemia, and accelerate CKD progression 1
• Prolonged NSAID therapy is not recommended even when eGFR is 30–60 mL/min/1.73 m² 1
• Avoid the "triple whammy" combination of NSAIDs + ACE inhibitor/ARB + diuretic 1

Monitoring Requirements

All patients with severe CKD receiving antibiotics require close monitoring of renal function and drug levels where applicable. 1, 2

• Check eGFR and serum creatinine before starting antibiotics and 1–2 weeks after initiation 1
• Monitor serum potassium every 3–6 months, especially with drugs that impair potassium excretion 1
• Obtain therapeutic drug monitoring for aminoglycosides, vancomycin, and other narrow-therapeutic-index antibiotics 1

Common Pitfalls to Avoid

• Do not use standard doses of renally cleared antibiotics without adjustment—this leads to drug accumulation and toxicity 1
• Do not combine nephrotoxic antibiotics (e.g., aminoglycosides) with other nephrotoxins (e.g., NSAIDs, contrast agents)—this markedly increases acute kidney injury risk 1, 2
• Do not assume all antibiotics in the same class have identical renal dosing—individual agents differ in renal clearance 1
• Do not forget to reassess antibiotic dosing if renal function changes during treatment—eGFR can fluctuate in acute illness 2