From the Guidelines
The combination of meropenem and amikacin is a suitable option for children with serious infections requiring broad-spectrum coverage, particularly for suspected gram-negative infections. For children, meropenem is typically dosed at 60 mg/kg/day every 8 hours, as indicated in the guidelines by the Surgical Infection Society and the Infectious Diseases Society of America 1. Amikacin is generally dosed at 15–22.5 mg/kg/day, with the frequency of dosing ranging from every 8 to 24 hours, depending on the severity of infection and the child's age, as outlined in the same guidelines 1. Some key points to consider when using this combination include:
- The importance of therapeutic drug monitoring for amikacin to minimize the risks of nephrotoxicity and ototoxicity, aiming for peak levels of 20-30 mcg/mL and trough levels below 5-10 mcg/mL.
- The need to adjust dosing intervals for neonates and young infants due to immature renal function.
- The combination provides synergistic activity against many gram-negative pathogens, with meropenem offering excellent beta-lactam coverage and amikacin providing additional bactericidal activity through a different mechanism (protein synthesis inhibition).
- This combination should be reserved for severe infections such as healthcare-associated pneumonia, complicated intra-abdominal infections, febrile neutropenia, or sepsis where multidrug-resistant organisms are suspected, and de-escalation to narrower therapy should occur once culture results are available. It is crucial to note that antibiotic serum concentrations and renal function should be monitored when using amikacin, as recommended in the guidelines 1.
From the Research
Meropenem Amikacin Combination in Children
- The combination of meropenem and amikacin has been studied in children with febrile neutropenia, with one study finding that meropenem monotherapy was as effective and safe as ceftazidime plus amikacin 2.
- Another study compared meropenem plus amikacin with piperacillin-tazobactam plus netilmicin as empiric therapy for high-risk febrile neutropenia in children, finding that both combinations were equally effective and safe 3.
- Meropenem has a broad spectrum of in vitro activity against Gram-positive and Gram-negative pathogens, including extended-spectrum beta-lactamase (ESBL)- and AmpC-producing Enterobacteriaceae 4.
- The pharmacokinetics of meropenem in critically ill pediatric patients have been studied, with modeling and simulation suggesting that a dosing regimen of 20 mg/kg every 8 h with a 3 h infusion may be effective for targeting susceptible pathogens 5.
Efficacy and Safety
- The efficacy and safety of meropenem plus amikacin have been compared with other antibiotic combinations, with one study finding that the combination of vancomycin and piperacillin/tazobactam was associated with a higher risk of acute kidney injury compared with vancomycin and meropenem 6.
- Meropenem has been shown to be well tolerated in children, with a low propensity for inducing seizures, making it suitable for treating bacterial meningitis 4.
- The combination of meropenem and amikacin has been found to be effective and safe in pediatric cancer patients with febrile neutropenia, with a success rate of 52% with initial empiric therapy 3.