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Combination antibiotic therapy in pediatrics
Insights
Beta-lactam and amikacin antibiotic combinations are effective for pediatric infections. Amikacin shows satisfactory results and low toxicity, supporting its continued use in pediatric care.
Area of Science:
- Pediatric Infectious Diseases
- Pharmacology
- Antimicrobial Therapy
Background:
- Beta-lactam and aminoglycoside antibiotics are standard for pediatric infections.
- Amikacin has been the exclusive aminoglycoside at this institution for five years.
- These combinations are used empirically and definitively for various serious pediatric conditions.
Purpose of the Study:
- To evaluate the efficacy and safety of amikacin in combination antibiotic regimens for pediatric infections.
- To assess the correlation between in vitro synergy and in vivo outcomes, particularly with amikacin and imipenem.
Main Methods:
- Retrospective review of amikacin usage in pediatric patients.
- Analysis of clinical outcomes in patients receiving amikacin-based combination therapy.
- Evaluation of in vitro synergy data and its correlation with in vivo efficacy.
Main Results:
- Amikacin in combination therapy yielded highly satisfactory clinical results across diverse pediatric infections.
- Aminoglycoside toxicity, specifically with amikacin, was rarely observed.
- Absence of in vitro synergy between amikacin and imipenem did not preclude improved survival in a relevant animal model.
Conclusions:
- Combination antibiotic regimens including amikacin remain crucial in pediatric infectious disease management.
- Amikacin is a safe and effective aminoglycoside for empirical and definitive pediatric therapy.
- In vitro synergy testing may underestimate the clinical benefit of certain antibiotic combinations, like amikacin and imipenem.
Abstract:
Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed.