Comparison of colistin–carbapenem, colistin–sulbactam, and colistin plus other antibacterial agents for the treatment of extremely drug-resistant Acinetobacter baumannii bloodstream infections

Abstract

The purpose of this investigation was to compare the efficacy of colistin-based therapies in extremely drug-resistant Acinetobacter spp. bloodstream infections (XDR-ABSI). A retrospective study was conducted in 27 tertiary-care centers from January 2009 to August 2012. The primary end-point was 14-day survival, and the secondary end-points were clinical and microbiological outcomes. Thirty-six and 214 patients [102 (47.7%): colistin-carbapenem (CC), 69 (32.2%): colistin-sulbactam (CS), and 43 (20.1%: tigecycline): colistin with other agent (CO)] received colistin monotherapy and colistin-based combinations, respectively. Rates of complete response/cure and 14-day survival were relatively higher, and microbiological eradication was significantly higher in the combination group. Also, the in-hospital mortality rate was significantly lower in the combination group. No significant difference was found in the clinical (p = 0.97) and microbiological (p = 0.92) outcomes and 14-day survival rates (p = 0.79) between the three combination groups. Neither the timing of initial effective treatment nor the presence of any concomitant infection was significant between the three groups (p> 0.05) and also for 14-day survival (p > 0.05). Higher Pitt bacteremia score (PBS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, Charlson comorbidity index (CCI), and prolonged hospital and intensive care unit (ICU) stay before XDR-ABSI were significant risk factors for 14-day mortality (p = 0.02, p = 0.0001, p = 0.0001, p = 0.02, and p = 0.01, respectively). In the multivariable analysis, PBS, age, and duration of ICU stay were independent risk factors for 14-day mortality (p < 0.0001, p < 0.0001, and p = 0.001, respectively). Colistin-based combination therapy resulted in significantly higher microbiological eradication rates, relatively higher cure and 14-day survival rates, and lower in-hospital mortality compared to colistin monotherapy. CC, CS, and CO combinations for XDR-ABSI did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (PSM). PBS, age, and length of ICU stay were independent risk factors for 14-day mortality.

Combination of polymyxin B and meropenem eradicates persister cells from Acinetobacter baumannii strains in exponential growth

“…Although the standard antimicrobial scheme against A. baumannii infections has not been fully established, evidence supports the fact that combination therapies including polymyxin B are more effective than polymyxin B monotherapies. Moreover, polymyxin B combined with a second antimicrobial agent was able to reduce hospital mortality rates, and has been widely recommended due to resistance emerging in some A. baumannii strains during treatments [2][3][4]. Nevertheless, antimicrobial therapy failure has been reported, especially in recalcitrance of chronic infections, which may be due to the tolerance mediated by persister cells [5,6] -a microbial subpopulation able to survive to normally lethal concentrations of bactericidal antimicrobials [7], as has been previously described in Acinetobacter spp.…”

Intravenous polymyxins: Revival with puzzle

“…A case series reported (55) 80% (4/5) of the transplant recipients with XDR A. baumannii infections were treated successfully with colistin-carbapenem combination therapy based on positive interactions in vitro tests, while 91% (10/11) patients died in the combination treatment of colisitn and other antibiotics. Batirel A et al found that, for BSI patients due to XDR A. baumannii, colistin-carbapenem, colistin-sulbactam, and colistin with other agent combinations did not reveal significant differences with respect to 14-day survival and clinical or microbiological outcome before and after propensity score matching (47). A similar conclusion was draw in XDR A. baumannii pneumonia (VAP and hospital-acquired pneumonia) by Khawcharoenporn T et al (56).…”

“…Several studies indicated that no neurological side effects were noted (52,54,71,99) with intravenous or inhaled colistin. While two studies noted very low incidence of neurotoxicity, 3 (0.14%) patients (47), and 1 (0.99%) patient (53), respectively. Neurotoxicity was observed in 2 (6%) patients who received intravenous polymyxin B (43).…”

“…This maybe because these data are generated from a number of small, non-comparative studies or case series, with heterogeneous patient populations, and varying dosing schemes. It's also because different definitions of nephrotoxicity, such as AKIN (Acute Kidney Injury Network) criteria (51,93), RIFLE (33,34,47,53,54), KIDIGO (56), and other criteria (19,36,42). So it's difficult to compare nephrotoxicity between trials.…”

“…No difference was found between IV colistin monotherapy or combination therapy with rifampicin (53), glycopeptides (28), fosfomycin (54), carbapenem or sulbactam (31,47). But the combination of intravenous colistin plus intravenous vancomycin is associated with an increased risk of renal failure (51).…”