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Sulbactam efficacy in experimental models caused by susceptible and intermediate Acinetobacter baumannii strains
M J Rodríguez-Hernández1, L Cuberos, C Pichardo
1Service of Infectious Diseases, University Hospital Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Sevilla, Spain. jpachon@hvr.sas.cica.es
Abstract:
Sulbactam and imipenem were compared in an experimental pneumonia model in immunocompetent mice, using a susceptible strain of Acinetobacter baumannii, and in an experimental endocarditis model in rabbits, using an intermediately susceptible strain. In the former, sulbactam was as efficacious as imipenem in terms of survival, sterility of lungs and in the bacterial clearance from lungs and blood, provided that the t > MIC for sulbactam (1.84 h) was similar to that for imipenem (2.01 h). In the endocarditis model, imipenem (t > MIC, 2.12 h) was more efficacious than sulbactam (t > MIC, 1.17 h) in bacterial clearance from vegetations. These results show the efficacy of sulbactam in infections caused by susceptible strains of A. baumannii, with an MIC up to 4 mg/L, provided that doses reach a t > MIC similar to that of imipenem. The activity of sulbactam was time dependent.
Insights
Sulbactam demonstrated efficacy comparable to imipenem in treating Acinetobacter baumannii pneumonia in mice. However, imipenem showed superior bacterial clearance in rabbit endocarditis models, highlighting sulbactam
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Acinetobacter baumannii is a significant opportunistic pathogen, frequently associated with hospital-acquired infections.
- Antibiotic resistance in A. baumannii necessitates the evaluation of alternative therapeutic strategies.
- Sulbactam, a beta-lactamase inhibitor, is often used in combination therapy, but its monotherapy efficacy requires further investigation.
Purpose of the Study:
- To compare the in vivo efficacy of sulbactam and imipenem against Acinetobacter baumannii.
- To evaluate the impact of time above minimum inhibitory concentration (t > MIC) on treatment outcomes.
- To determine the suitability of sulbactam as a therapeutic agent for specific A. baumannii infections.
Main Methods:
- Experimental pneumonia model in immunocompetent mice infected with a susceptible A. baumannii strain.
- Experimental endocarditis model in rabbits infected with an intermediately susceptible A. baumannii strain.
- Assessment of survival rates, lung and blood bacterial clearance, and vegetation bacterial clearance.
Main Results:
- In the pneumonia model, sulbactam showed efficacy similar to imipenem in survival and bacterial clearance when t > MIC was comparable (1.84 h vs 2.01 h).
- In the endocarditis model, imipenem (t > MIC, 2.12 h) was more effective than sulbactam (t > MIC, 1.17 h) in reducing bacterial load in vegetations.
- Sulbactam demonstrated efficacy against A. baumannii strains with minimum inhibitory concentrations (MIC) up to 4 mg/L, contingent on achieving a sufficient t > MIC.
Conclusions:
- Sulbactam is effective in treating experimental Acinetobacter baumannii infections, particularly when susceptible strains are involved and therapeutic targets for t > MIC are met.
- The time-dependent activity of sulbactam is crucial for its efficacy, requiring dosing strategies that maximize the time above the MIC.
- Imipenem remains a more potent agent for severe infections like endocarditis caused by intermediately susceptible A. baumannii strains.