Evaluation of the efficacy of sulbactam combination therapy for monomicrobial and polymicrobial pulmonary infections caused by multidrug-resistant Acinetobacter baumannii

Abstract

The efficacy in treatment of monomicrobial versus polymicrobial Acinetobacter baumannii (mono-AB vs poly-AB) pulmonary infections remains unclear. This study mainly investigated the efficacy of sulbactam combination regimens against mono-AB and poly-AB pulmonary infections. A multicenter retrospective study of adult patients who received sulbactam or cefoperazone/sulbactam for multidrug-resistant A. baumannii (MDRAB) between August 2021 and July 2023 was conducted. The outcomes of 7-day microbiological efficacy and 14-day clinical efficacy were measured. A total of 366 patients were enrolled, including 75 mono-AB patients. Among the 291 poly-AB cases, 82 patients were co-infected with Pseudomonas aeruginosa and 76 patients with Klebsiella pneumoniae. All A. baumannii isolates exhibited multidrug resistance. The antibiotics demonstrating the highest sensitivity against these isolates were polymyxins and tigecycline, with sensitivity rates of 91.25% and 71.63%, respectively. In the multivariable analysis, patients receiving sulbactam-based treatment for poly-AB pulmonary infections exhibited significantly higher microbial clearance of A. baumannii compared with those with mono-AB infections. Microbial efficacy analysis of A. baumannii co-infection with K. pneumoniae or P. aeruginosa showed similar results to overall poly-AB infections. Sulbactam doses ≥ 8 g/day showed the best microbiological and clinical efficacy. Sulbactam combined with tigecycline and/or polymyxins demonstrated significantly better microbiological efficacy compared with sulbactam alone. Sulbactam combined with polymyxins resulted in better microbiological and clinical efficacy than when combined with tigecycline. In conclusion, patients with poly-AB lung infections exhibit a higher microbial clearance rate of A. baumannii following treatment compared with those with mono-AB infections. A daily dose ≥8 g sulbactam may be optimal for treating MDRAB pneumonia. The combination of sulbactam and polymyxins demonstrates significant advantages over other sulbactam-containing regimens in terms of microbiological and clinical efficacy.IMPORTANCEThis is the first multicenter retrospective study to investigate the efficacy of sulbactam combination regimens in the treatment of monomicrobial and polymicrobial AB-related pulmonary infections. Our study found that patients receiving sulbactam-based treatment for poly-AB pulmonary infections exhibited significantly higher microbial clearance of A. baumannii compared with those with mono-AB infections. Microbial efficacy analysis of A. baumannii co-infection with K. pneumoniae or P. aeruginosa showed similar results to overall poly-AB infections. These findings are significantly important for further analyzing the potential mechanisms underlying the differences in efficacy between antimicrobial treatments for monomicrobial and polymicrobial infections, as well as for optimizing clinical antimicrobial combination strategies.

Keywords: Acinetobacter baumannii; combination therapy; efficacy; multidrug-resistant; polymicrobial pulmonary infection; sulbactam.

Fig 1

Flowchart of patient enrollment. MDRAB, multidrug-resistant A. baumannii; Mono-AB, monomicrobial A. baumannii; Poly-AB, polymicrobial A. baumannii; AB, A. baumannii; KP, K. pneumoniae; PA, P. aeruginosa. * Indicates the number of cases analyzed for clinical efficacy.

Fig 2

Distribution of bacterial species in patients with poly-AB.

Fig 3

Antimicrobial sensitivity patterns of A. baumannii clinical isolates against 19 antibiotics. The abbreviations, as they appear in the figure, are as follows: SAM, ampicillin/sulbactam (2/1); CSL, cefoperazone/sulbactam (2/1); TZP, piperacillin/tazobactam; TCC, ticarcillin/clavulanic acid; CAZ, ceftazidime; CRO, ceftriaxone; FEP, cefepime; IPM, imipenem; MEM, meropenem; AN, amikacin; GM, gentamicin; TM, tobramycin; CIP, ciprofloxacin; LEV, levofloxacin; SXT, trimethoprim/sulfamethoxazole; DO, doxycycline; MNO, minocycline; TGC, tigecycline; CS, colistin. * The sensitivity results for colistin and polymyxin B are equivalent.