Between January 2021 and May 2023, we identified 164 patients admitted to our hospital with CRAB bacteraemia or VAP who received appropriate intravenous antibiotic therapy. Three patients who were discharged before 30 days could not be recontacted to assess primary outcome and hence were excluded from the analysis. Seventy per cent of included patients received monotherapy (112/161), and the rest received combination therapy. Among our patients, 46 (28.57%) had ventilator-associated pneumonia (VAP) and 55 (34.16%) had bacteraemia; 60 (37.27%) had both. Among the 112 patients who received monotherapy, 25 were treated with colistin and 73 received polymyxin B. Both polymyxins were given interchangeably for 14 patients.

Baseline characteristics were comparable across the two cohorts (Table 1). The mean age of the cohort was 46.14 (SD 16.24) years with male predominance (114/161, 71%). Neutropenia was present in 9% (14/161) of the study participants, and most received monotherapy (11 vs 3). The presence of existing malignancies was noted among 21 patients with no significant difference between the treatment groups. The median Charlson comorbidity index score observed in the study cohort was 2 (IQR 0–3) and was similar in the two treatment groups. The median duration of antibiotic therapy in our cohort was 6 (IQR 3–9) days with a significant difference between the monotherapy and combination therapy group (5 vs 6, p = 0.046). Previous serious bacterial infection was present in 84 (52.17%) patients. A significant proportion had previous carbapenem exposure (127, 81.41%). Ninety-one (56.52) patients had other concomitant bacterial infections. Septic shock was present in 129 (80.12%) patients and 26 (16.15%) required dialysis. There was a delay in initiating antibiotics (> 24 h from index culture) in 30.6% of combination therapy patients and 42.9% in the monotherapy group (p = 0.143).

Our cohort consisted of severely ill patients with 97% admitted to an ICU during their hospital stay. All patients (n = 49) in the combination therapy group required ICU stay compared to 95.5% (107/112) in the monotherapy group. PBS and ICS observed were higher with a median PBS of 6 (IQR 4–6) among bacteraemias, similar in the two treatment groups. The mean ICS among the bacteraemias was 11.53 (SD 3.94) and was significantly higher in the combination therapy group (12.77 vs 11.06, p = 0.039). Persistent bacteraemia was noted among 31% (15/49) receiving combination therapy and 12% (13/112) in the monotherapy group. Among the patients who received combination therapy, 38.8% received polymyxin with sulbactam, 26.5% received polymyxin with tigecycline, 22.4% received polymyxin with others, 6.1% received tigecycline with sulbactam, and 4.1% received polymyxin with minocycline. The primary outcome analysed for different combinations did not display any statistical difference between various drug combinations and against monotherapy.

The susceptibility for colistin, minocycline, tigecycline, and sulbactam was 156/157 (99.36%), 29/52 (55.76%), 61/94 (64.9%), and 3/50 (6%), respectively. Among patients who received monotherapy, the susceptibility for colistin was 100% while susceptibility for the other drugs using minocycline, tigecycline, and sulbactam was 14/31 (45%), 37/59 (62.7%), and 1/29 (3.4%), respectively. The predominant combination therapies used were polymyxin with sulbactam (19/49, 38.8%) and polymyxin with tigecycline (13/49, 26.5%). Among the patients receiving polymyxin and sulbactam combination, 11/19 had susceptibility reports available for both. Only one isolate was susceptible to both. Among patients who received polymyxin and tigecycline combination, 9/13 had susceptibility reports for both, of which 8/13 patients were susceptible to both.

Forty-three per cent of our patients (21/49) in the combination therapy group received a combination with both drugs susceptible. Among them, 71.4% (15/21) had primary outcome, and 12 succumbed to death within 14 days of the index date. Among people who received a therapy where the combination drug was resistant, 42.8% (6/14) had the primary outcome (p = 0.47). Notably, five patients received sulbactam along with polymyxin, where sulbactam was resistant (MIC > 8), and one patient received tigecycline with colistin, where tigecycline was resistant.

The overall 30-day mortality was 62% (99/161), where 63.27% (31/49) and 60.71% (68/112) were recorded in the combination therapy and monotherapy group, respectively. Unadjusted OR for primary outcome among people receiving combination therapy was 1.11 (0.55, 2.22), p = 0.760. The propensity score matching using IPTW did not show any statistical difference in 30-day mortality for receiving combination therapy with an adjusted OR of 1.29 (0.64, 2.58), p = 0.469.

Among the 99 deaths in our cohort, 87 (87.8%) happened by day 14. The receipt of combination therapy was not associated with improved adjusted 14-day mortality [OR 2.01 (0.67–5.99), p = 0.207].

The other secondary outcomes of interest were the duration of total hospital stay and hospital stay after infection onset. Duration of total hospital stay was significantly higher in the combination therapy group (29 vs 15), and the same was noticed with days of hospital stay after bacteraemia or pneumonia isolation (13 vs 7.5) (Table 2). Increasing age, patients having both bacteraemia and VAP, and septic shock were associated with poorer outcomes, while increased duration of antibiotic therapy was associated with better outcomes in univariate analysis. In multivariate analysis, patients having bacteraemia or both bacteraemia and VAP and septic shock were independent risk factors for mortality (See Table S6).