Abstract
The aim of this study was to assess the clinical and microbiological efficacy and toxicity of different high-dose regimens of colistin in the ICU patients with colistin-sensitive MDR Gram-negative infections. In this prospective, open label, randomized clinical trial, patients with clinical features of infection and positive culture for MDR colistin-sensitive Gram-negative bacteria were randomly allocated to receive colistin, 3 or 9 million units every 8 and 24 hours, (groups A and B), respectively. For each dose regimen, clinical and microbiological response, the rates of nephrotoxicity, and its risk factors were analyzed. Forty-three patients were enrolled, and 35 completed the study protocol, of whom 30 (88.2%) had ventilator-associated pneumonia (VAP) and 5 (14%) had bacteremia. Although there were no statistically significant differences in the clinical or microbiological response between the study groups, the microbiological response favored the divided dose group numerically ( p = 0.40 ). Clinical response was achieved in 27 of 35 (77.1%) patients ( p = 0.999 ). Twelve (34.28%) patients developed AKI during colistin treatment, 4 and 8 in groups A and B, respectively ( p value =0.193). Significant risk factors for nephrotoxicity related to colistin were age, hyperbilirubinemia, and coadministration of other nephrotoxic agents. In multivariate regression analysis, the only independent risk factor for CMS-associated AKI was hyperbilirubinemia ( p value =0.008). Although the clinical and microbiological responses to colistin administration were not statistically different in two groups, the microbiological response favored the divided dose regimen group numerically. We did not observe any significant safety concerns with high-dose colistin administration in this population.
Highlights
Multidrug-resistant (MDR) infections, defined as infections caused by the microbial pathogens resistant to two or more classes of antibiotics, has significant adverse effects on morbidity, mortality, and health economy which extend into all aspects of medicine [1]. e emergence of carbapenem-resistant Gram-negative bacteria is of particular concern, as there are limited therapeutic options available for effective treatment of these microorganisms in critically ill patients
In group A, 4 bacterial isolates were sensitive to gentamicin, 4 were intermediately susceptible to levofloxacin and ciprofloxacin, and 1 was intermediately susceptible to gentamicin. e remaining 7 isolates were only sensitive to colistin
In group B, 4 bacterial isolates were sensitive to gentamicin or amikacin and 1 was intermediately susceptible to ciprofloxacin. e remaining isolates were sensitive only to colistin. e median duration of CMS treatment was days (IQR, 4) for group A and 14 days (IQR, 10) for group B
Summary
CMS was administered to 43 critically ill patients with colistin-sensitive Gram-negative MDR infections. irty-five patients (66% male), completed the study protocol (Figure 1). e baseline characteristics of the patients were not statistically different between study groups (Table 1). E baseline characteristics of the patients were not statistically different between study groups (Table 1). Twenty-one (60%) bacterial isolates were sensitive to colistin only, and the remaining 14 (40%) showed either full or intermediate susceptibility to gentamicin, amikacin, or levofloxacin. In group A, 4 bacterial isolates were sensitive to gentamicin, 4 were intermediately susceptible to levofloxacin and ciprofloxacin, and 1 was intermediately susceptible to gentamicin. In group B, 4 bacterial isolates were sensitive to gentamicin or amikacin and 1 was intermediately susceptible to ciprofloxacin. Superinfection by an inherently colistin-resistant organism (Proteus mirabilis) was detected in 2 patients on days 5 and 10 of CMS treatment, one in each study group. E serum creatinine levels before the initiation and at the end of CMS treatment, clinical and microbiological responses, and CMS toxicity were compared between the two study groups (Table 2). We did not observe any hypersensitivity reaction during the CMS treatment in our study patients
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