Nosocomial infection caused by Acinetobacter baumannii is common among immunocompromised patients. Treatment strategy is limited due to rapid resistance development and lack of novel antibiotic. Colistin has been the last line therapy with good in vitro activity against infections caused by multi-drug resistance A. baumannii. However, pharmacological updates are required to support dosing optimisation. This study aimed to determine the time-kill kinetic and resistance development after antibiotic exposure as well as post-antibiotic effect of colistin at different static concentrations in in vitro A. baumannii system. The static in vitro time-kill and post-antibiotic effect experiments were conducted against two clinical isolates as well as one reference isolate ATCC 19606. Time-kill and postantibiotic effect were studied at colistin concentrations ranging from 0.25MIC to 16.0MIC and 0.5MIC to 4.0MIC, respectively. Post-exposure resistance development was examined in time-kill study. Killing activity and post-antibiotic effect were in a concentration-dependent manner. However, delayed killing activity indicates colistin tolerance. Development of resistance after exposure was not detected except for the ATCC 19606 strain. Dosing suggestion based on the observations include administration of supplemental dose 3 MIU at 12 hours after loading dose, administration of maintenance dose 9 MIU in two divided doses and application of extended interval in renal adjustment dose. However, the information is applicable for non-colistin-heteroresistance A. baumannii with colistin MIC < 1.0 mg/L. As for heteroresistance and strain with colistin MIC > 1.0 mg/L, combination therapy would be the more appropriate treatment strategy.

Background:Patients after head and neck cancer reconstructive surgical procedures are predisposed to have post-operative surgical site infections (SSI) develop. They are very often caused by multi-drug resistant strains, includingAcinetobacter baumanniias the most common one. Methods:The aim of the study was to determine important risk factors contributing to SSI ofA. baumanniiorigin. The analysis included 134 head and neck cancer patients after salvage operations with microvascular free flap reconstruction. TheA. baumanniiwas cultured in 27 of all 48 infected patients. Results:The following risk factors were significantly associated withA. baumanniiinfection: re-hospitalization before reconstructive operation (p = 0.00011), massive blood loss (p = 0.00277), and need of revision surgical procedure (p = 0.00419). Of patients withA. baumanniiinfection, 48% were hospitalized in a general intensive care unit (ICU) after operation that, together with prolonged intubation, constituted a strong risk factor of that infection (p = 0.01077). Mean time of hospital stay was significantly longer in theA. baumanniigroup (58 days vs. 35 days; p = 0.02697). Conclusions:Our analysis identified a subset of head and neck cancer patients after salvage operation with microvascular free flap reconstruction who are at high risk ofA. baumanniiinfection developing. Previously hospitalized patients with extensive blood loss and need of surgical revision necessitate increased monitoring for the development of this complication. Mechanical ventilation and hospital stay in an ICU should be shortened maximally or avoided in that challenging group of patients. Early recognition of patients at high risk remains a key point to prevent or limit the spread ofA. baumanniiinfections.