Effectiveness and safety of polymyxin B for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria in Thailand

Thundon Ngamprasertchai,1 Adhiratha Boonyasiri,2 Lantharita Charoenpong,3 Sireethorn Nimitvilai,4 Narisorn Lorchirachoonkul,5 Luksame Wattanamongkonsil,2 Visanu Thamlikitkul6 1Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; 2Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Division of Medicine, Chaophraya Yommarat Hospital, Suphanburi, Thailand; 4Division of Medicine, Nakhornpathom Hospital, Nakhornpathom, Thailand; 5Division of Medicine, Ratchaburi Hospital, Ratchaburi, Thailand; 6Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand Background: Colistimethate sodium (colistin) has been used in the treatment of infections caused by extensively drug-resistant (XDR) Gram-negative bacteria in Thailand over the past decade, with a mortality rate of 50% and a nephrotoxicity rate of 40%. Polymyxin B has not been available in Thailand. We conducted a Phase II clinical study to determine the effectiveness and safety of polymyxin B, compared with colistin, for the treatment of XDR Gram-negative bacterial infections in Thai patients.Methods: A total of 73 adult patients hospitalized at four participating tertiary care hospitals from January 2015 to December 2015 who had infections caused by XDR Gram-negative bacteria and had to receive colistin were enrolled in the study. Polymyxin B (100 mg/day) was administered intravenously every 12 hours for 7–14 days.Results: Most of the patients were older males with comorbidities who had received antibiotics, particularly carbapenems, prior to receiving polymyxin B. More than half of the patients had pneumonia, and 51.5% of the infections were caused by XDR Acinetobacter baumannii, which was susceptible to colistin. Good clinical responses at the end of treatment were observed in 78.1% of cases, the overall 28-day mortality rate from all causes was 28.7%, the microbiological clearance of the targeted bacteria after therapy was 56.2% and nephrotoxicity occurred in 24.7% of cases. Neurotoxicity relating to reversible numbness was observed in two cases.Conclusion: Polymyxin B seems to be effective and safe for the treatment of XDR Gram-negative bacterial infections. Polymyxin B should be considered as an alternative to colistin for treatment of infections caused by XDR Gram-negative bacteria in Thai adult patients, especially those at risk of nephrotoxicity. Keywords: mortality, acute kidney injury, Acinetobacter baumanni