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. 2022 Aug 17;11(8):1112.
doi: 10.3390/antibiotics11081112.

A Randomized Controlled Trial of Colistin Combined with Sulbactam: 9 g per Day versus 12 g per Day in the Treatment of Extensively Drug-Resistant Acinetobacter baumannii Pneumonia: An Interim Analysis

Chutchawan Ungthammakhun  1 , Vasin Vasikasin  1 , Dhitiwat Changpradub  1
Affiliations

A Randomized Controlled Trial of Colistin Combined with Sulbactam: 9 g per Day versus 12 g per Day in the Treatment of Extensively Drug-Resistant Acinetobacter baumannii Pneumonia: An Interim Analysis

Chutchawan Ungthammakhun et al. Antibiotics (Basel). .

Abstract

Extensively drug-resistant A. baumannii (XDRAB) pneumonia has a high mortality rate in hospitalized patients. One of the recommended treatments is colistin combined with sulbactam; however, the optimal dosage of sulbactam is unclear. In an open-label, superiority, randomized controlled trial, patients diagnosed with XDRAB pneumonia were randomly assigned (1:1) to receive colistin in combination with sulbactam at either 9 g/day or 12 g/day. The primary outcome was the 28-day mortality rate in the intention-to-treat population. A total of 88 patients received colistin in combination with sulbactam at a dosage of either 12 g/day (n = 45) or 9 g/day (n = 43). Trends toward a lower mortality rate were observed in the 12 g/day group at 7 days (11.1% vs. 23.3%), 14 days (33.3% vs. 41.9%), and 28 days (46.7% vs. 58.1%). The microbiological cure rate at day 7 was significantly higher in the 12 g/day group (90.5% vs. 58.1%; p = 0.02). Factors associated with mortality at 28 days were asthma, cirrhosis, APACHEII score ≥ 28, and a dosage of sulbactam of 9 g/day for mortality at any timepoint. Treatment with colistin combined with sulbactam at 12 g/day was not superior to the combination treatment with sulbactam at 9 g/day. However, due to being an interim analysis, this trial was underpowered to detect mortality differences.

Keywords: A. baumannii XDR pneumonia; colistin; mortality rate; sulbactam.

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Conflict of interest statement

The authors received the research drug, sulbactam, from Siam pharmaceutical. CO., LTD. The funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript.

Figures

Figure 1
Figure 1
Enrollment and follow-up of the participants.
Figure 2
Figure 2
Distribution of sulbactam MIC for XDRAB. The value labels indicate the number of isolates. Error bars indicate the 95% confidence interval.
Figure 3
Figure 3
Kaplan–Meier survival curves for 28-day mortality of XDRAB pneumonia patients in relation to the administered dose of sulbactam.
Figure 4
Figure 4
Risk difference for mortality at day 7, 14, 28 in patients treated with 12 g/day vs. 9 g/day of sulbactam. Abbreviation: CI, confidence interval.
Figure 5
Figure 5
Kaplan–Meier survival curves for 28-day mortality of XDRAB pneumonia patients in relation to dose with subgroup analysis of MIC of sulbactam. (A) MIC of sulbactam ≤ 48 mcg/mL, (B) MIC of sulbactam > 48 mcg/mL (C) MIC of sulbactam ≤ 96 mcg/mL, (D) MIC of sulbactam > 96 mcg/mL.
Figure 6
Figure 6
Kaplan-Meier survival curves for 28-day mortality in XDRAB pneumonia patients in relation to sulbactam dose, with subgroup analysis of complications from pneumonia. (A) Pneumonia with septic shock, (B) pneumonia without septic shock, (C) pneumonia with bacteremia, (D) pneumonia without bacteremia, (E) pneumonia with DIC, (F) pneumonia without DIC.
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