What antibiotics should be avoided in patients with impaired renal function?

Antibiotics to Avoid in Kidney Disease

Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin) should be avoided or used with extreme caution in patients with impaired renal function due to their high nephrotoxicity and ototoxicity risk, and when absolutely necessary, require dose reduction, extended dosing intervals, and mandatory therapeutic drug monitoring. 1, 2, 3

High-Risk Nephrotoxic Antibiotics Requiring Avoidance or Extreme Caution

Aminoglycosides - Primary Concern

• Aminoglycosides are potentially nephrotoxic with risk greatest in patients with impaired renal function and those receiving high dosage or prolonged therapy 2, 3
• When GFR <60 mL/min/1.73 m², aminoglycosides require dose reduction and/or increased dosing intervals 1
• Mandatory monitoring includes serum trough and peak levels to avoid toxicity 1, 2
• Avoid concomitant ototoxic agents such as furosemide 1
• Neurotoxicity manifested by ototoxicity (both vestibular and auditory) can occur and is usually irreversible 2, 3

Amphotericin B

• Avoid amphotericin unless no alternative exists when GFR <60 mL/min/1.73 m² 1
• This antifungal has known nephrotoxic potential 4

Tetracyclines

• Reduce dose when GFR <45 mL/min/1.73 m² as tetracyclines can exacerbate uremia 1
• However, doxycycline specifically requires no complex dosing calculations based on creatinine clearance and has minimal nephrotoxicity risk 4

Antibiotics Requiring Significant Dose Adjustment

Penicillins

• Risk of crystalluria when GFR <15 mL/min/1.73 m² with high doses 1
• Neurotoxicity with benzylpenicillin when GFR <15 mL/min/1.73 m² with high doses (maximum 6 g/day) 1
• Piperacillin/tazobactam is frequently prescribed without appropriate renal dose adjustment in clinical practice 5

Fluoroquinolones

• Reduce dose by 50% when GFR <15 mL/min/1.73 m² 1
• Contraindicated when CrCl <30 mL/min for most agents 1

Macrolides

• Reduce dose by 50% when GFR <30 mL/min/1.73 m² 1
• Azithromycin specifically requires no therapeutic drug monitoring and has minimal nephrotoxicity risk 4

Carbapenems (Imipenem-cilastatin, Meropenem)

• May reduce dosing frequency in renal impairment 1
• Carbapenems are frequently used without appropriate dose adjustment, increasing toxicity risk 6

Antifungals Beyond Amphotericin

• Reduce maintenance dose of fluconazole by 50% when GFR <45 mL/min/1.73 m² 1
• Reduce dose of flucytosine when GFR <60 mL/min/1.73 m² 1

Antibiotics Safe Without Dose Adjustment

Preferred Options in Renal Impairment

• Doxycycline and azithromycin require no complex dosing calculations based on creatinine clearance and have minimal nephrotoxicity risk 4
• Clindamycin requires no adjustment for renal status, including the standard prophylactic dose of 600 mg 1, 7
• Moxifloxacin requires no change in dosing for renal impairment 1

Critical Clinical Pitfalls

The "Triple Whammy" Risk

• Avoid combining NSAIDs, diuretics, and ACE inhibitors/ARBs in CKD patients, as each additional nephrotoxin increases acute kidney injury odds by 53%, and combining three or more nephrotoxins results in 25% AKI risk 4

Common Prescribing Errors

• Almost one-third of antibiotics used in CKD patients have no dose adjustment in real-world practice, generating significant toxicity risk 6
• Glycopeptides and carbapenems are most frequently prescribed without appropriate dose adjustment 6
• 51.6% of hospitalized CKD patients receive antibiotics without renal dose adjustments 5

High-Risk Patient Populations

• Elderly patients with preexisting chronic renal failure or comorbidities are at greatest risk 8
• Patients with dehydration or those hospitalized in intensive care units require heightened vigilance 8
• Stage 4 and Stage 5 CKD significantly increase the probability of receiving antibiotics without appropriate dose adjustment 6

Monitoring Requirements

For Aminoglycosides When Unavoidable

• Monitor renal function and eighth cranial nerve function closely 2, 3
• Examine urine for decreased specific gravity, increased protein excretion, and presence of cells or casts 2
• Determine BUN, serum creatinine, or creatinine clearance periodically 2
• Obtain serial audiograms when feasible, particularly in high-risk patients 2
• Adjust dosage to avoid prolonged peak levels above 12 mcg/mL and trough levels above 2 mcg/mL 2

General Antibiotic Monitoring in CKD

• Careful assessment of renal function is paramount in patients with acute and chronic infections undergoing antibiotic therapy 9
• Monitor serum concentrations, renal function, serum electrolytes (sodium, magnesium, calcium, phosphate), urine output, and urinalysis 3