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Sixty-one extended-spectrum beta-lactamase (ESBL)-producing isolates were collected from Srinagarind Hospital, Thailand. These included 43 Enterobacteriaceae and 18 Pseudomonadaceae. The 43 Enterobacteriaceae were found to produce the following ESBLs: 26 (60.5%) SHV-12, 13 (30.2%) SHV-5, two (4.7%) SHV-2a, one (2.3%) VEB-1 and one (2.3%) unidentified. Twenty-four isolates (55.8%) also carried bla(TEM-1B), as well as bla(SHV) or bla(VEB-1). Plasmid DNA from transconjugants carrying the bla(SHV-12) gene showed various restriction patterns, indicating the distribution of the bla(SHV-12) gene among different antibiotic resistance plasmids. In contrast, bla(SHV-5) in 13 isolates was found on a single plasmid of c. 130 kb. Pulsed-field gel electrophoresis (PFGE) analysis of genomic DNA from these isolates revealed that nine of 11 Klebsiella pneumoniae gave the same pattern, indicating clonal spread of the strain within the hospital, together with the occasional spread of the plasmid to other strains. Among the pseudomonad isolates, 16 Pseudomonas aeruginosa and one Pseudomonas putida had bla(VEB-like) and one P. aeruginosa had bla(SHV-12). Nine of the 16 isolates carrying bla(VEB-like) (56.3%) had identical PFGE patterns, suggesting the dissemination of this gene, also by clonal spread. At least six different bla(VEB-like-)containing integrons were found among the 18 isolates. This is the first report of bacteria producing SHV-12 and SHV-2a in Thailand and the first report of SHV-12 in P. aeruginosa, of VEB-1 in Citrobacter freundii and a VEB-1-like beta-lactamase in P. putida. These findings indicate that ESBL genes in the Far East are part of a gene pool capable of broad horizontal gene transfer, in that these genes can transfer between different families of Gram-negative bacilli. [ABSTRACT FROM AUTHOR]

Background Ceftaroline (PPI-0903M, T-91825) is a novel cephalosporin, administered as an N-phosphono prodrug. We investigated its in vitro activity and resistance selection potential. Methods MICs were determined by CLSI agar dilution, but with varied inocula. Mutant selection was investigated in single- and multi-step procedures. Results MICs for methicillin-resistant Staphylococcus aureus (MRSA) were 0.5–2 mg/L, compared with 0.12–0.25 mg/L for methicillin-susceptible S. aureus; corresponding values for coagulase-negative staphylococci were 0.25–2 and 0.06–0.12 mg/L, respectively. Even with 2% NaCl added, all MRSA were susceptible at 2 mg/L. MICs for Enterococcus faecalis were from 0.25 to 8 mg/L; E. faecium was resistant. MICs for Escherichia coli, Klebsiella spp., Morganella morganii and Proteeae without acquired resistance were 0.06–0.5 mg/L versus 0.12–1 mg/L for Enterobacter, Serratia and Citrobacter spp. and 2–8 mg/L for Acinetobacter spp. MICs rose to 1–2 mg/L for many Enterobacteriaceae with classical TEM β-lactamases, and were much higher for those with extended-spectrum β-lactamases (ESBLs), hyperproduced AmpC or K1 enzymes. MICs for strains with classical TEM/SHV β-lactamases rose if the inoculum was increased to 106 cfu/spot; this effect was even more marked for those with ESBLs. Resistance due to Class A β-lactamases was reversed by clavulanate. Geometric mean MICs were 0.005, 0.05 and 0.09 mg/L for penicillin-susceptible, -intermediate and -resistant Streptococcus pneumoniae strains, respectively—lower than for any comparator β-lactam. Haemophilus influenzae and Moraxella catarrhalis were very susceptible, although with marginally raised MICs for β-lactamase-positive Moraxella strains and for haemophili with chromosomal ampicillin resistance. Ceftaroline selected AmpC-derepressed Enterobacter mutants similarly to cefotaxime in single-step experiments; in multi-step procedures it selected ESBL variants of blaTEM in E. coli. Resistance selection was not seen with S. aureus, H. influenzae or pneumococci. Conclusions Ceftaroline has impressive anti-MRSA and anti-pneumococcal activity. Slight lability to classical TEM and SHV β-lactamases is exceptional for an oxyimino-cephalosporin, but was reversible with clavulanate, as was the greater resistance mediated by ESBLs. Resistance selection occurred with Enterobacteriaceae, not MRSA. [ABSTRACT FROM AUTHOR]