Introduction: Polymyxin B (PMB) is one of the remaining antibiotics that is effective against multidrug resistant (MDR) Gram-negative bacteria. However, PMB monotherapy is not able to achieve sustained killing hence, combination with other antibiotics are usually employed. Besides antibiotics, studies are now moving towards non-antibiotic alternatives such as metabolite feeding against MDR pathogens. This study aimed to investigate the susceptibility
and bacterial killing of PMB in combination with metabolite phenylpyruvate against Klebsiella pneumoniae isolates. Methods: Broth microdilution was used to determine PMB minimum inhibitory concentration (MIC) alone and with phenylpyruvate against two Klebsiella pneumoniae isolates. Time kill studies were performed over 24 h (initial inoculum: ~106 CFU/mL), using PMB 2 mg/L and phenylpyruvate 2 mmol/L, alone and in combination, against the
PMB-resistant isolate. Microbiological responses were examined using the log-change method. Results: The MIC of PMB was reduced by phenylpyruvate in both isolates. In the time kill studies, during the first hour, PMB monotherapy demonstrated the highest bacterial killing activity even compared to the combination. Phenylpyruvate monotherapy showed negligible activity against K. pneumoniae. A significant reduction in bacterial burden was seen at 1 h following PMB monotherapy and combination therapy but an equally rapid regrowth was seen at 4 h. Notably at 24 h, the regrowth following combination therapy was >1-log10 CFU/mL less than PMB monotherapy. Conclusion: Our results suggest that phenylpyruvate increased PMB susceptibility in K. pneumoniae and may minimise the emergence of resistance to PMB. Future studies investigating phenylpyruvate at higher concentrations against more isolates are
warranted.
Introduction: Polymyxins are used as the “last-line therapy” for multi drug resistant (MDR) Gram-negative bacterial infections. However, the development of nephrotoxicity is a major concern. The objectives of this study were to determine the incidence and severity of acute kidney injury (AKI) and to identify risk factors associated with AKI and mortality rate in Malaysian patients on polymyxin B (PMB) for MDR Gram-negative bacterial infections. Methods: A retrospective study was conducted in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). Medical and
medication charts were reviewed for all intensive care unit (ICU) patients who received intravenous (IV) PMB from 1st May 2008 to 1st May 2018. Simple and multiple logistic regression were performed to identify risk factors of PMB induced nephrotoxicity. Results: Among the total 572 patients identified, only 31 patients were eligible to be included. The incidence rate of AKI was 45.2% (14 of 31 patients). Univariate analysis showed that age was a significant risk factor of PMB associated nephrotoxicity [OR 1.074; 95% CI 1.002-1.151; P=0.045]. Other four variables (P