In vitro activity of temocillin (BRL 17421), a novel beta-lactam antibiotic

Abstract

The minimal inhibitory concentration of temocillin (BRL 17421) against 476 clinical isolates was determined by an agar dilution method. Temocillin was active against most of the Enterobacteriaceae, Haemophilus, and Neisseria strains tested. The compound showed low activity or was inactive against Bacteroides, Campylobacter, Acinetobacter, Pseudomonas, and Staphylococcus aureus strains. Within each species, individual strains showed a high degree of uniformity in their susceptibility to temocillin; the drug concentrations that inhibited the growth of 90% of organisms were the same or close to those which inhibited the growth of 50% of organisms. In contrast, the same strains showed a very wide range of susceptibility to the other antibiotics tested, including third-generation cephalosporins. Against strains of Enterobacteriaceae highly susceptible to thirdgeneration cephalosporins, temocillin was considerably less active than cefotaxime, ceftazidime, and moxalactam, although it was more active than cefazolin and piperacillin. Against certain strains of Enterobacter and Citrobacter resistant to third-generation cephalosporins, temocillin was more active than cefotaxime and ceftazidime. An increase in the inoculum size did not alter the activity of temocillin, indicating that the compound has high stability to ,-lactamases. The minimal lethal concentration was also very similar to the minimal inhibitory concentration when an inoculum of 105 colony-forming units was used.Temocillin (BRL 17421) is a new semisynthetic ,3-lactam antibiotic that is highly stable to the bacterial P-lactamases and is active against most Enterobacteriaceae, Haemophilus, and Neisseria strains (3, 4). We investigated the in vitro activity of temocillin and compared it with the activities of cephalothin, cefotaxime, ceftazidime, moxalactam, and piperacillin against a wide range of recent clinical isolates.

Temocillin susceptibility by BSAC methodology

“…Thirty-two urinary E. coli isolates previously shown to carry bla CTX-M-15 , 3 and 22 CTX-M-producing E. coli isolates from bronchoalveolar lavage and pus samples obtained during 2006, from Jawaharlal Nehru Medical College and Hospital, Aligarh Muslim University, Aligarh, India, were studied. The latter isolates were shown to carry bla CTX-M of genogroup-1 by PCR with primers 5 0 -AAA AAT CAC TGC GCC AGT-3 0 and 5 0 -AGC TTA TTC ATC GCC ACG TT-3 0 .…”

“…2,3 We have evaluated the in vitro efficacy of ceftriaxone/sulbactam, a combination recently launched in India, against Escherichia coli harbouring bla CTX-M-15 . Moreover, we describe the phenotypic detection of ESBL production by the synergy observed between cephalosporin and piperacillin/tazobactam discs and compare it with conventional disc synergy tests with co-amoxiclav.…”

“…Precise CTX-M types were not identified in these 22 isolates because of the lack of sequencing facilities, but CTX-M-15 is the only variant that has been described to date in India. 3,4 To ensure that multiple representatives of particular strains were eliminated, all isolates were …”

“…and Staphylococcus aureus. 1,3 In this study, temocillin MICs and zone diameters for a 30 mg temocillin disc (Oxoid, Basingstoke, UK) were obtained by BSAC methodology 4,5 …”

“…MICs of these antibiotics in the presence and absence of 10 mM of these antioxidants were determined by agar dilution method as outlined by the CLSI (formerly the NCCLS). 3 An inoculum of approximately 10 4 -10 5 cfu (simultaneously determined by plating) per spot (in a volume of 10 mL) was applied to the agar plates with increasing antibiotic concentration. MIC was the lowest concentration of antimicrobial agent that prevented visible growth after 20 h of incubation at 378C.…”