In an adult patient with chronic kidney disease (CKD) and a confirmed or suspected Enterobacter species or Klebsiella aerogenes infection, what empiric antibiotic options should be used and how should the doses be adjusted based on estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl)?

Antibiotic Selection for Enterobacter and Klebsiella aerogenes in CKD

For Enterobacter species or Klebsiella aerogenes infections in CKD patients, use fluoroquinolones (ciprofloxacin or levofloxacin) as first-line empiric therapy with dose adjustment based on creatinine clearance, or cefepime 1-2g IV every 12-24 hours depending on infection severity and renal function. 1, 2

Empiric Antibiotic Selection Algorithm

First-Line Options for Uncomplicated Infections

• Ciprofloxacin 500 mg PO every 12 hours if CrCl >50 mL/min, or 500 mg every 24 hours if CrCl 30-50 mL/min, for 7-10 days 1, 3
• Levofloxacin 750 mg loading dose, then 250 mg every 48 hours if CrCl <50 mL/min 4, 1
• Fluoroquinolones maintain excellent urinary and tissue concentrations even with renal impairment and require only interval extension rather than dose reduction 1

Second-Line Options for Severe or Complicated Infections

• Cefepime 1-2g IV every 12 hours for moderate to severe infections if CrCl >60 mL/min 2
• Cefepime 1g IV every 24 hours if CrCl 30-60 mL/min 2
• Cefepime 0.5-1g IV every 24 hours if CrCl 11-29 mL/min 2
• Cefepime provides excellent coverage for Enterobacter and Klebsiella aerogenes, including many ESBL-producing strains 2

For Suspected Multidrug-Resistant Organisms

• Ceftazidime-avibactam 2.5g IV every 8 hours with dose adjustment based on renal function for carbapenem-resistant Enterobacterales 1, 3
• Meropenem-vaborbactam 4g IV every 8 hours with dose adjustment for CRE 3
• Obtain culture and susceptibility testing immediately to guide targeted therapy 3

Critical Dosing Principles in CKD

Interval Extension vs. Dose Reduction

• Use interval extension rather than dose reduction for concentration-dependent antibiotics like fluoroquinolones to maintain peak bactericidal activity 1
• Smaller doses significantly reduce efficacy of concentration-dependent antibiotics 1

Renal Function Assessment

• Calculate creatinine clearance using the Cockcroft-Gault equation for antibiotic dosing, as this was used in pivotal clinical trials 5
• Do not rely on CKD-EPI eGFR alone, as it can differ significantly from creatinine clearance and lead to inappropriate dosing 5, 6
• Reassess renal function and electrolytes within 1 week of starting any renally-cleared antibiotic 4

Antibiotics to ABSOLUTELY AVOID in CKD

• Aminoglycosides (gentamicin, tobramycin, amikacin) should be avoided due to extreme nephrotoxicity risk, except for single-dose therapy in simple cystitis 4, 1
• Tetracyclines can exacerbate uremia and require dose reduction even at eGFR <45 mL/min 4
• Nitrofurantoin causes peripheral neuritis in CKD patients and has insufficient efficacy data in renal impairment 3

Specific Dose Adjustments by Creatinine Clearance

CrCl 30-50 mL/min

• Ciprofloxacin: 500 mg every 24 hours 1
• Levofloxacin: 750 mg loading, then 500 mg every 48 hours 4
• Trimethoprim-sulfamethoxazole: Reduce to half dose (1 single-strength tablet daily) 1
• Cefepime: 1g IV every 24 hours 2

CrCl <30 mL/min or Hemodialysis

• Ciprofloxacin: 50% dose reduction 4
• Levofloxacin: 250 mg every 48 hours 4
• Trimethoprim-sulfamethoxazole: Use half dose or alternative agent 4, 1
• Cefepime: 0.5-1g IV every 24 hours 2
• Administer antibiotics after hemodialysis to prevent drug removal during dialysis 1

Critical Management Considerations

Drug Stewardship in CKD

• Establish collaborative relationships with pharmacists to ensure proper drug stewardship and dose adjustments 7
• Educate patients about expected benefits and risks of antibiotics so they can identify and report adverse events 7
• Monitor for drug accumulation even with hepatically-metabolized drugs, as renal failure increases toxicity risk through altered metabolism 1

Temporary Medication Adjustments

• Temporarily discontinue ACE inhibitors, ARBs, NSAIDs, and diuretics during acute infection to prevent acute kidney injury 4
• Ensure adequate hydration (minimum 1.5 liters daily) when using fluoroquinolones to prevent crystalluria and acute kidney injury 4
• Restart nephroprotective medications (ACE inhibitors, ARBs) after infection resolves to prevent unintentional harm 7

Common Pitfalls to Avoid

• Do not use CKD-EPI eGFR for antibiotic dosing—use Cockcroft-Gault creatinine clearance instead, as this is what clinical trials and FDA recommendations are based on 5
• Do not assume all cephalosporins are safe in CKD—cefepime specifically requires dose adjustment and can cause neurotoxicity if dosed inappropriately 2
• Do not continue empiric broad-spectrum therapy once culture results are available—narrow to targeted therapy to preserve antibiotic utility 3
• Patients with CKD have 19-41% higher odds of infections by multidrug-resistant organisms, making culture-guided therapy essential 8

Resistance Considerations

• Local antibiogram data should guide empiric choices, as fluoroquinolone resistance varies significantly by region 3
• Consider ESBL-producing organisms in patients with prior antibiotic exposure or healthcare contact 3
• Shorter treatment durations (5-7 days) are appropriate for uncomplicated infections with fluoroquinolones 3