From the Guidelines
Carbapenems, particularly meropenem or ertapenem, are not the best option for this patient due to the need for dose adjustments in renal impairment, and instead, intravenous fosfomycin is a suitable alternative for treating ESBL-producing E. coli in patients with impaired renal function, as shown in the ZEUS and FOREST trials 1.
Key Considerations
- The patient's culture preliminary report shows resistance to penicillins and cephalosporins, but sensitivity to ceftriaxone, ciprofloxacin, levofloxacin, gentamicin, ertapenem, and meropenem.
- The patient has impaired renal function, which requires careful consideration of antibiotic dose adjustments to avoid nephrotoxicity.
- Intravenous fosfomycin has been shown to be effective in treating complicated urinary tract infections (cUTI) caused by ESBL-producing Enterobacterales, including E. coli, with no significant differences in clinical or microbiological cure compared to piperacillin-tazobactam or meropenem 1.
Antibiotic Options
- Intravenous fosfomycin: a suitable alternative for treating ESBL-producing E. coli in patients with impaired renal function, with a lower risk of nephrotoxicity compared to aminoglycosides.
- Aminoglycosides (e.g., gentamicin): may be considered as an alternative, but with careful monitoring of renal function and dose adjustments to avoid nephrotoxicity 1.
- Carbapenems (e.g., meropenem or ertapenem): require dose adjustments in renal impairment, which may increase the risk of nephrotoxicity 1.
Dose Adjustments
- Intravenous fosfomycin: no dose adjustment is necessary in renal impairment.
- Aminoglycosides: dose adjustments are necessary based on renal function, with careful monitoring to avoid nephrotoxicity 1.
- Carbapenems: dose adjustments are necessary in renal impairment, with a reduced dose of 500 mg every 12 hours for moderate impairment (CrCl 25-50 mL/min) and 500 mg every 24 hours for severe impairment (CrCl 10-25 mL/min) 1.
From the Research
Antibiotic Resistance and Sensitivity
- The culture preliminary report shows resistance to penicillins and cephalosporins, but sensitivity to ceftriaxone, ciprofloxacin, levofloxacin, gentamicin, ertapenem, and meropenem 2, 3, 4, 5, 6.
- ESBL-producing E. coli is a significant concern, and the choice of antibiotic is crucial in treating such infections.
Ertapenem as a Treatment Option
- Ertapenem is a carbapenem antibiotic that has shown effectiveness against ESBL-producing E. coli 3, 4, 5, 6.
- Studies have demonstrated that ertapenem has a high susceptibility rate against ESBL-producing E. coli, with MIC90 values ranging from 0.03 to 1 mg/L 4, 5, 6.
- However, the pharmacokinetics of ertapenem in patients with impaired renal function needs to be considered, as the AUC of ertapenem can increase significantly in patients with renal impairment 2.
Considerations for Patients with Impaired Renal Function
- The study by 2 suggests that the doses of ertapenem may need to be adjusted in patients with impaired renal function to avoid toxicity.
- The probability of achieving 40%T > MIC (MIC ≤ 4 μg/mL) was nearly 100% throughout the recommended dosing interval, indicating that ertapenem can still be effective in patients with impaired renal function, but with careful dose adjustment 2.
Comparison with Other Antibiotics
- Other antibiotics such as ciprofloxacin, levofloxacin, and gentamicin may also be effective against ESBL-producing E. coli, but their use should be guided by susceptibility testing and consideration of potential side effects 6.
- Carbapenems such as imipenem and meropenem may also be effective, but resistance rates are increasing, and their use should be reserved for severe infections 5, 6.