Study design, sites, and participants
This prospective cohort study included consecutive patients with XDRAB pneumonia in Phramongkutklao Hospital, a 1200-bed tertiary care military hospital in Thailand, from 1 July 2016 to 30 September 2017. After the approval of the protocol by the Institutional Review Board, Royal Thai Army Medical Department (www.irbrta.pmk.ac.th reference number R061h/59), patients aged ≥18 years with XDRAB pneumonia, who received definite treatment with colistin, combined with sulbactam or carbapenems (imipenem or meropenem) were enrolled in the study. XDRAB pneumonia was diagnosed when patients with clinical diagnosis of pneumonia had a single pathogen of XDRAB isolated from their sputum culture, which was collected from tracheal suction or mouth on the date of diagnosis. The sputum collected from mouth must have >25 neutrophils and <10 squamous epithelial cells per low power field to be determined as significant. The exclusion criteria included patients who developed a new infection during the treatment, had concurrent diagnosis of another site of infection, had organisms other than XDRAB obtained from blood or sputum culture or received switch regimens between sulbactam and carbapenems.
Eligible patients were categorized in 2 groups as followed; those who received colistin with sulbactam (CL+SB) and those who received colistin with carbapenems (CL+CB). The maximum dosage of 6 g/day of sulbactam was derived from ampicillin/sulbactam and cefoperazone/sulbactam. The maximum dosage of imipenem and meropenem were 2g and 3g/day, respectively. Colistin was used at the maximum dosage of 300 mg/day. These antibiotics were intravenously administered with dosage adjustment according to renal function.
Variables and definitions
The primary outcome was 28-day mortality rate after initiation of antibiotic. The secondary outcomes were 7-day and 14-day mortality rates, length of hospital stay, length of ICU stay and ventilator days. The baseline demographics data included: sex, age, underlying condition, hospital service, ventilator status, antimicrobial treatment (empirical and definite), intubation and susceptibility data of sputum. Additionally, blood culture samples were collected. The clinical outcomes included: duration of admission, duration of ventilator use, length of hospital stay, length of ICU stay, vital signs, APACHEII severity score (14), kidney functions and complete blood counts.
XDRAB was defined as A. baumannii with at least 1 drug resistance in 3 or more drug groups including antipseudomonal carbapenems, antipseudomonal fluoroquinolones, and antipseudomonal cephalosporins by using automate broth microdilution test. CLSI recommendations were used for susceptibility interpretation.(15) Pneumonia and definition of HAP and VAP were defined according to CDC definition.(16)
Mortality rates were measured regarding the day when sputum culture was collected (considered as day 1). Ventilator day was defined as duration between the day of intubation (in HAP patients with respiratory failure) or the day when sputum culture was collected (in VAP patients) and the day of extubation or death. Acute kidney injury was defined according to KDIGO 2012 guidelines,(17) and disseminated intravascular coagulation (DIC) was defined if ISTH score ≥5,(18) septic shock was defined when patients received vasopressor.
Comparisons between the groups were performed using Pearson’s chi-square test, or Fisher’s exact test, as appropriate for proportions and with Student’s T-test or Mann-Whitney U test, as appropriate for continuous outcomes. Variables with a p-value <0.2 in univariate analysis were introduced into multivariate analyses, which were performed using Cox regression analyses. All p-values were two-tailed with those less than 0.05 considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows v.22.0 (IBM Corp., Armonk, NY, USA).