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. 2026 Feb 20:19:584186.
doi: 10.2147/IDR.S584186. eCollection 2026.

Comparison of Two Different Doses of Ampicillin-Sulbactam as Part of Combination Therapy in the Treatment of Multidrug Resistant Acinetobacter baumannii Ventilator Associated Pneumonia: A Randomized Clinical Trial

Elmira Niknami  1 , Ilad Alavi Darazam  2   3 , Arash Mahboubi  4 , Minoosh Shabani  2   3 , Jamshid Salamzadeh  1 , Zahra Sahraei  1
Affiliations

Comparison of Two Different Doses of Ampicillin-Sulbactam as Part of Combination Therapy in the Treatment of Multidrug Resistant Acinetobacter baumannii Ventilator Associated Pneumonia: A Randomized Clinical Trial

Elmira Niknami et al. Infect Drug Resist. .

Abstract

Purpose: Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) Acinetobacter baumannii is associated with high morbidity and mortality, and optimal antimicrobial dosing strategies remain uncertain. Although ampicillin-sulbactam is increasingly used for MDR Acinetobacter baumannii infections, limited clinical data exist regarding the efficacy and safety of different dosing regimens when used as part of combination therapy. This study aimed to compare the clinical outcomes of low- versus high-dose ampicillin-sulbactam in combination of meropenem and colistin in patients with MDR Acinetobacter baumannii associated VAP.

Patients and methods: In this randomized clinical trial, patients with MDR Acinetobacter baumannii associated VAP admitted to the intensive care unit were allocated to receive either low-dose ampicillin-sulbactam (6 g IV every 6 h; total 24 g/day) or high-dose ampicillin-sulbactam (9 g IV every 6 h; total 36 g/day). Meropenem and colistin were administered concomitantly in both groups, as they remain commonly used standard therapies for severe MDR infections despite increasing resistance and toxicity concerns. Clinical outcomes, including fever duration, pulmonary secretions, Clinical Pulmonary Infection Score (CPIS), duration of mechanical ventilation, length of ICU and hospital stay, mortality, and adverse drug reactions, were assessed over a 10-day follow-up period.

Results: A total of 77 patients were enrolled (39 in the low-dose group and 38 in the high-dose group). The high-dose group demonstrated significantly shorter hospital stay (15.34 ± 4.99 vs 19.46 ± 6.91 days; P = 0.007), ICU length of stay (11.66 ± 6.11 vs 17.08 ± 7.40 days; P < 0.001), and duration of mechanical ventilation (6.39 ± 2.14 vs 7.74 ± 2.60 days; P = 0.003).

Conclusion: Among patients receiving combination therapy for MDR Acinetobacter baumannii associated VAP, higher-dose ampicillin-sulbactam was associated with improved clinical outcomes without increased toxicity. However, the small sample size, short follow-up period, and use of concomitant antibiotics limit attribution of outcomes solely to ampicillin-sulbactam dosing. Larger, well-controlled studies are needed to define the optimal dosing strategy.

Keywords: Acinetobacter baumannii; ampicillin; pneumonia; sulbactam; ventilator-associated.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Figure 1
Figure 1
The Consolidated Standards of Reporting Trails (CONSORT) flowchart of study.
See this image and copyright information in PMC

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