Colistin versus Colistin Combined with Ampicillin. Sulbactam for Multiresistant Acinetobacter baumannii Ventilator. Associated Pneumonia Treatment: An Open. Label Prospective Study

Abstract

Background:Retrospective studies have reported good clinical success rates using colistin as monotherapy to treat Acinetobacter baumannii ventilator-associated pneumonia (VAP), comparable to that obtained with colistin combined with other antibiotics. However, inadequate penetration into the pulmonary parenchyma for colistin has been shown in animal models.Aim:The aim of the study was to study prospectively the outcome, measured as clinical response and survival, of intravenously administered colistin versus colistin combined with high-dose ampicillin-sulbactam in Intensive Care Unit (ICU) patients with multiresistant A. baumannii VAP.Methods and Subjects:This prospective, open-label, randomized study included consecutive patients who developed microbiologically documented VAP due to A. baumannii with carbapenem-resistant strains but susceptible to colistin and ampicillin-sulbactam. Seventy-four patients were screened, but finally, 39 participants were enrolled and finished the study Patients received colistin (Group A – 19 patients) or colistin and ampicillin/sulbactam (Group B – 20 patients). The clinical response of VAP was assessed on day 4th to 5th of treatment (early response). If therapy was considered unsuccessful after this period, ampicillin/sulbactam was added in Group A or changed therapy in B.Results:Early cure rates in Group A and B were 15.8% and 70%, respectively (P = 0.001). Multiple regression analysis revealed that combination treatment (odds ratio [OR]: 43.6, 95% confidence interval [CI]: 3.594–530.9) and Sequential Organ Failure Assessment score <8 (OR: 0.022, 95% CI: 0.001–0.43) were independently associated with favorable clinical response. APACHE II score ≤15 (OR: 0.049, 95% CI: 0.003–0.0942) and an early favorable response to treatment (OR: 244.4, 95% CI: 2.151–27850.9) were associated with survival and discharge from ICU.Conclusion:Combination therapy with colistin and a high dose of ampicillin/sulbactam was associated with a more favorable clinical response to VAP due to carbapenem-resistant A. baumannii than colistin monotherapy.

Intravenous colistin combination is superior to monotherapy against carbapenem-resistant gram-negative bacterial infections: evidence from seven randomized controlled trials

“…Pneumonia, including ventilator-associated pneumonia and hospital-acquired pneumonia, was primary Infection type, and bloodstream infection was the next (Table 1). Carbapenem-resistant A. baumannii presented in the studies by Aydemir et al [22], Makirs et al [25], and Sirijatuphat et al [24], extensive-drug including carbapenem resistant A. baumannii in the study by Durante-Mangoni et al [23],Colistin-resistant A. baumannii in the study by Park et al [28], carbapenem-resistant K. pneumoniae in the study by Abdelsalam et al [27], and carbapenem-resistant gram-negative bacteria, including A. baumannii, Enterobacteriaceae, Pseudomonas, and others, in the study by Paul et al [26]. There are 25.0% patients who complicated chronic kidney diseases.…”

“…All included studies designed intravenous colistin monotherapy and colistin-based combination regimens, the latter of which included colistin plus rifampicin [22,23,28], fosfomycin [24], meropenem [26,27], or ampicillin-sulbactam [25]. Five studies [22,[24][25][26][27] adopted a high dose of colistin, among which two studies [26,27] used a loading dose of colistin, one study [23] used a low dose of colistin, and another study [28] did not report the dose of colistin.…”

“…Six studies [22][23][24][25][26][27] reported the outcome of microbial response, seven [22][23][24][25][26][27][28] reported the outcome of crude mortality, four [22][23][24][25] reported the outcome of infection-related mortality, and four [23,24,26,28] reported the outcome of nephrotoxicity (Table 2).…”

“…Four studies [22][23][24][25] (Table 2) reported the results of infection-related mortality, and intravenous colistin-based combination therapy showed a trend towards lower infection-related mortality (RR, 0.75; P = 0.09; 95% CI, 0.53-1.05; I 2 = 0%; Figure 6).…”

“…To resolve these inconsistent findings, four meta-analyses were performed by Zusman et al in 2017 [18], Vardakaset et alin 2018 [19], Wang et al in 2018 [20] and Cheng et al in 2018 [21], respectively. But only the meta-analysis conducted by Cheng et al [21] provided higher quality evidence based on five prospective randomized controlled trials (RCTs [22][23][24][25][26]) to find that intravenous colistin-based combination therapy was not superior to monotherapy. Recently, two additional RCTs [27,28] compared the effects of intravenous colistin combination therapy and monotherapy on carbapenem-and colistin-resistant gram-negative bacteria infections.…”