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The safety of cefepime and ceftazidime in pediatric oncology patients
James M Hoffman1, Jamie Frediani, Michael Herr
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Insights
Cefepime use in pediatric oncology patients did not increase mortality compared to ceftazidime. Secondary infections, not the antibiotic choice, were linked to mortality, though study numbers were small.
Area of Science:
- Pediatric Oncology
- Infectious Diseases
- Pharmacology
Background:
- Concerns exist regarding cefepime's potential to increase mortality.
- Limited data are available on beta-lactam antibiotic use, particularly cefepime, in pediatric oncology patients.
Purpose of the Study:
- To compare the safety and efficacy of cefepime versus ceftazidime in pediatric oncology patients.
- To investigate the association between cefepime use and all-cause mortality in this vulnerable population.
Main Methods:
- Retrospective study of 532 pediatric oncology patients.
- Comparison of outcomes between patients treated with cefepime and those treated with ceftazidime for suspected serious bacterial infections.
- Primary outcomes assessed were 30- and 90-day all-cause mortality.
Main Results:
- Demographics and clinical characteristics were similar between the cefepime (n=195) and ceftazidime (n=337) groups.
- No significant difference in 30-day (OR 3.48, P=0.3) or 90-day (OR 0.99, P=1.0) all-cause mortality rates between cefepime and ceftazidime.
- No differences observed in infection-related mortality, secondary infections, or adverse drug events. Secondary infection was a significant predictor of mortality.
Conclusions:
- Cefepime use in pediatric oncology patients is not associated with increased mortality compared to ceftazidime.
- The small number of deaths limits the definitive strength of this conclusion.
- All-cause mortality may be an insensitive outcome for evaluating antibiotic efficacy and safety in this context, with secondary infections being a key factor.
Background:
Concern has been raised about possible increased mortality associated with the use of cefepime. There are limited data available on the pragmatic use of beta-lactam antibiotics, especially in children.
Procedure:
This retrospective study included 532 pediatric oncology patients. The outcomes of patients treated with cefepime for suspected serious bacterial infections were compared to those of patients treated with ceftazidime. Primary outcomes included 30- and 90-day all-cause mortality.
Results:
The demographic and clinical characteristics of 337 patients treated with ceftazidime were similar to those of 195 patients receiving cefepime. Thirty-day and 90-day all cause mortality rates were comparable (30-day OR for cefepime: 3.48, 95% CI 0.31-38.84, P = 0.3; 90-day OR: 0.99, 95% CI 0.29-3.42, P = 1.0). There were also no differences in infection-related mortality rates, secondary infections, or adverse drug events. Deaths occurring within 30 days of hospitalization were judged to be attributable to infection, but not the result of treatment failure or adverse drug events. Deaths occurring between 30 and 90 days were associated with progressive or new malignancy. Secondary infection was significantly associated with mortality.
Conclusions:
The use of cefepime in pediatric oncology patients is not associated with increased mortality when compared to ceftazidime, however the small number of deaths in this study limits the strength of this conclusion. Previous associations between antimicrobial therapy and increased all-cause mortality may have been confounded by patients' demographic characteristics and co-morbid conditions. All-cause mortality may be an insensitive outcome for studies examining the efficacy and safety of these agents.
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