Molecular and epidemiological investigation of a colistin-resistant OXA-23-/NDM-1-producing Acinetobacter baumannii outbreak in the Southwest Indian Ocean Area.

Dual resistance to colistin and carbapenems is a milestone reached by certain extensively-drug resistant (XDR) Gram-negative bacteria. This study describes the first outbreak of XDR colistin- and carbapenem-resistant OXA-23-/NDM-1-producing Acinetobacter baumannii (CCRAB) in the European overseas territory of Reunion Island (France, Indian Ocean). Between April 2019 and June 2020, 13 patients admitted to the University Hospital of Reunion Island were involved in the outbreak, of whom eight were infected and six died. The first case was traced to a medical evacuation from Mayotte Island (Comoros archipelago). An epidemiological link could be established for 11 patients. All of the collected CCRAB isolates showed the same resistance profile and co-produced intrinsic ß-lactamases OXA-69 and ADC-191, together with acquired carbapenem-hydrolysing ß-lactamases OXA-23 and NDM-1. A mutation likely involved in colistin resistance was detected in the two-component system PmrAB (D82N in PmrA). All of the isolates were found to belong to STPas1/STOx231 clonal complex and were phylogenetically indistinguishable. Their further characterization by whole-genome sequence analyses (whole-genome multi-locus sequence typing, single nucleotide polymorphisms) provided hints about the transmission pathways. This study pleads for strict application of control and prevention measures in institutions where the risk of imported XDR bacteria is high.

Assessment of the National French recommendations regarding the dosing regimen of 8mg/kg of gentamicin in patients hospitalised in intensive care units.

INTRODUCTION: To assess the French National Agency for Medicines and Health Products Safety (ANSM) guidelines concerning the peak plasma concentration (Cmax) of gentamicin when using a loading dose of 8mg/kg administered in patients hospitalised in the intensive care unit (ICU). PATIENTS AND METHODS: A prospective observational cohort study conducted in one ICU. RESULTS: During the study period, 34 patients with a median simplified acute physiology score 2 of 54 [44-70] received a median dose of 8 [7.9-8.1] mg/kg of gentamicin. The median Cmax was 17.5 [15.4-20.7] mg/L and no patient had a Cmax>30mg/L. Twenty-four of 34 patients (71%) had a Cmax>16mg/L. Following multivariate analysis, the only factor associated with Cmax<16mg/L was a positive fluid balance 24hours before gentamicin administration (per 1000mL increment) (OR: 0.37, 95% CI: 0.18-0.77, P=0.008). CONCLUSIONS: These results suggest that a Cmax>30mg/L [which corresponds to approximately 8 times the minimal inhibiting concentrations (MIC) breakpoints for Pseudomonas aeruginosa and Enterobacteriaceae with intermediate sensitivity] of gentamicin as recommended by ANSM guidelines seems impossible to obtain with a loading dose of 8mg/kg in the ICU. A loading dose of 8mg/kg should probably not be used in the empiric antibiotic treatment of infection due to non-fermenting Gram-negative bacilli and Enterobacteriaceae with intermediate sensitivity whose MIC breakpoint is 4mg/L. A Cmax>16mg/L was not reached in almost 30% of patients, particularly in the group with a positive fluid balance who require higher doses than currently recommended.