The Role of Cefoperazone-Sulbactam for Treatment of Severe Melioidosis

SIR—We read with interest the recent article by Chetchotisakd et al. [1], which reported the results of a clinical trial comparing 2 regimens for treatment of severe melioidosis. The authors concluded that cefoperazone-sulbactam plus cotrimoxazole might be used as an alternative to treatment with ceftazidime plus cotrimoxazole.

Since the late 1980s, several trials [2–5] have evaluated new medications for the treatment of severe melioidosis. However, with regard to reducing the mortality rate, none of these medications have been shown to be superior to ceftazidime with or without cotrimoxazole. Chetchotisakd and colleagues found equivalent mortality rates among patients treated with the 2 studied regimens. However, they failed to point out that the mortality rates observed in their study (18% and 14%) were much lower than the rates of 30%–40% observed in previous studies of ceftazidime (with or without cotrimoxazole) for treatment of patients with severe melioidosis [2–5].

The study by Chetchotisakd et al. [1] did not have sufficient power to detect significant differences in the efficacy of the 2 regimens studied. For example, the sample size for this trial would have had to have been 146 subjects per group to have 80% power to detect a 2-fold reduction in mortality rates between the 2 patient groups, as determined by use of Epi Info 2000 (Centers for Disease Control and Prevention). Similarly, the study is severely underpowered to provide statistical evidence of equivalent efficacy. Therefore, it is risky to recommend cefoperazone-sulbactam as an alternative to ceftazidime on the basis of the results of this underpowered study.

Melioidosis affects mainly poor rural persons who live in tropical regions, and cost is a big issue when considering new treatments. We believe that Chetchotisakd and colleagues should have provided information regarding the cost of the 2 treatment regimens (including vitamin K injections) used in this study in order to give readers information on the financial implications of their recommendation.

Along with gram-negative enteric bacilli, oxacillin-susceptible Staphylococcus aureus and Burkholderia pseudomallei were regarded as the most common causes of community-acquired septicemia in northeastern Thailand [6]. If this is the case, a fourth-generation cephalosporin, such as cefepime, might be a useful alternative to ceftazidime as empiric treatment for sepsis in that region. However, before recommending use of any fourth-generation cephalosporins, in vitro testing of their activity against B. pseudomallei and clinical trials involving patients with melioidosis would need to be performed. Therefore, we believe that ceftazidime (with or without cotrimoxazole) should still be regarded as first-line therapy for patients with suspected or proven severe melioidosis.

Acknowledgments

We thank Dr. Gary J. Weil for his comments on this letter.