Activities of various β-lactams and β-lactam/β-lactamase inhibitor combinations against Acinetobacter baumannii and Acinetobacter DNA group 3 strains

Abstract

Acinetobacter baumannii and Acinetobacter DNA group 3 are members of the so-called A. calcoaceticus-A. baumannii complex and are important nosocomial pathogens. Multiresistance in these organisms is increasingly frequent, and alternative treatment options are needed. The beta-lactamase inhibitors clavulanate, sulbactam and tazobactam have intrinsic activity against Acinetobacter strains. In the present study, broth microdilution was used to assess the in-vitro activities of currently available beta-lactam/beta-lactamase inhibitor combinations and sulbactam alone against 469 Acinetobacter isolates (A. baumannii, n=395; Acinetobacter DNA group 3, n=74) collected from various laboratories in Germany. Fixed concentrations and fixed ratios of beta-lactamase inhibitors were used. Sulbactam-containing combinations (susceptibility rates of 90.4-92.7% for A. baumannii and 97.3-100% for Acinetobacter DNA group 3) and sulbactam alone were superior to clavulanate- and tazobactam-containing combinations. The activity of sulbactam-containing combinations against members of the A. calcoaceticus-A. baumannii complex was conferred exclusively by the intrinsic activity of the beta-lactamase inhibitor and did not result from enhanced beta-lactam activity. Testing with the inhibitor added at a fixed ratio of inhibitor to beta-lactam appeared to give more reliable results than testing at a fixed concentration of the inhibitor. Resistance to carbapenems (0.3%) remains low in Germany.

Acinetobacter Baumannii Nosocomial Infections

“…Although A. baumannii susceptibility at the level of 23% of in our study is not high, it could conceivably increase with other administration regimens. Studies confirm that the main effect on A. baumannii is achieved through sulbactam, however not due to β-lactamase inhibition but the compound's direct bactericidal properties (25).…”

Acinetobacter baumannii : Emergence of a Successful Pathogen

“…Sulbactam is commercially available in a combined formulation with either ampicillin or cefoperazone and also as a single agent in France, Germany, and Spain (55,326). Studies assessing the activity of sulbactam alone compared to its combination with a ␤-lactam clearly demonstrate the intrinsic activity of the agent rather than its ability to inhibit ␤-lactamase (55,102,235). In vitro susceptibilities of A. baumannii strains to sulbactam vary widely, depending on the geographic region (326).…”

“…Sulbactam is one of three commercially available ␤-lactamase inhibitors. Unlike clavulanic acid and tazobactam, it has clinically relevant intrinsic antimicrobial activity against certain organisms, specifically Acinetobacter (55,102,235,326,328,405,464) and Bacteroides spp. (596), mediated by its binding to penicillin-binding protein 2 (403).…”

Impact of appropriate antimicrobial therapy on survival in patients with Acinetobacter baumannii-associated infections

“…An infection was defined as nosocomial if the onset of signs and symptoms were on or after the third day of the admission, or were present at the admission or became apparent before the third day, but the patient had been discharged from a hospital less than thirty days before admission. When A. baumannii was consecutively isolated as a single pathogen from usually sterile sites or from non-sterile clinical material at concentration >10 5 CFU/ml, a case was considered to be etiologically confirmed.…”

“…[2][3][4] A. baumannii (genospecies 2) has proven to be the most clinically important species within the genus. 5,6 In the last 20 years A. baumannii has grown into a large clinical challenge, a fact primarily attributed to common presence of resistance to almost all antimicrobial agents, including carbapenems and occasionally polymyxins; and the worldwide expansion of hospital areas. 7,8 The ability of A. baumannii to survive for extended periods on dry and wet environmental surfaces is notorious and is likely important for circulation and transmission within the health care setting.…”