High prevalence of colistin heteroresistance in Pseudomonas aeruginosa bloodstream isolates and associated clinical factors

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PURPOSE: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) has been classified by the World Health Organization as one of the most alarming antimicrobial-resistant microorganisms. Despite the availability of newer therapeutic options, polymyxins remain important last-resort agents for the treatment of CRPA infections in many settings. With the extended use of polymyxins in the treatment of extensively drug-resistant bacterial infections, both colistin resistance rates, colistin heteroresistance (CHR) rates and antibiotic treatment failures have risen. In this study, we aimed to: (i) determine the prevalence of CHR in P. aeruginosa bloodstream isolates, (ii) compare the accuracy of the antibiotic gradient test (GT) with the population analysis profiling (PAP) method, and (iii) identify clinical risk factors for CHR. METHODS: CHR was investigated among 70 colistin-susceptible P. aeruginosa strains isolated from blood cultures using PAP and GT methods. Clinical and demographical data were retrospectively reviewed, and risk factors for CHR were analyzed using logistic regression. RESULTS: We detected a remarkably high prevalence of CHR (61.4%) among colistin-susceptible P. aeruginosa bloodstream isolates. The gradient test failed to detect any of the heteroresistant strains. Our analysis revealed that age ≥ 60 years, lack of recent hospitalization, and a colistin MIC of 1 mg/L, compared with 2 mg/L, were independently associated with an increased risk of CHR. CHR was not significantly associated with 30-day or 90-day mortality. CONCLUSION: Despite the microbiological importance of heteroresistance, the clinical impacts and underlying mechanisms of this phenotype remain to be elucidated.

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