Twelve clarithromycin-resistant Helicobacter pylori isolates (100% of resistant isolates examined) from seven different patients each contained an A-->G transition mutation within a conserved loop of 23S rRNA. A-->G transition mutations at positions cognate with Escherichia coli 23S rRNA positions 2058 and 2059 were identified. Clarithromycin-susceptible H. pylori isolates from 14 different patients displayed no polymorphisms in a conserved loop within domain V of 23S rRNA. The study is the first to report mutations in H. pylori associated with resistance to an antimicrobial agent used in established peptic ulcer treatment regimens.
Fifty-four of 59 (91.5%) clarithromycin-resistant isolates of Helicobacter pylori from different patients possessed either the A2143G (formerly A2058G) or the A2144G (formerly A2059G) mutation in the gene encoding 23S rRNA. The A2143G mutation was significantly more likely to occur in isolates with MICs exceeding 64 mg/L (65% versus 30% with the A2144G mutation; P = 0.01). The majority (26 of 31; 83.9%) of isolates with the A2143G mutation had MICs exceeding 64 mg/L. Peptic ulcer disease recurred in a substantial proportion of patients infected with H. pylori strains containing either the A2143G or the A2144G mutation.
We evaluated the activity of meropenem-vaborbactam against contemporary nonfastidious Gram-negative clinical isolates, including Enterobacteriaceae isolates with resistance phenotypes and carbapenemase genotypes. Meropenemvaborbactam (inhibitor at 8 g/ml) and comparators were susceptibility tested by reference broth microdilution methods against 14,304 Gram-negative clinical isolates collected worldwide during 2014. Carbapenemase-encoding genes were screened by PCR and sequencing. , Յ0.015/0.06 g/ml) inhibited 99.1 and 99.3% of the 10,426 Enterobacteriaceae isolates tested at Յ1 and Յ2 g/ml, respectively. Meropenem inhibited 97.3 and 97.7% of these isolates at the same concentrations. Against Enterobacteriaceae isolates displaying carbapenemresistant Enterobacteriaceae (CRE) (n ϭ 265), multidrug-resistant (MDR) (n ϭ 1,210), and extensively drug-resistant (XDR) (n ϭ 161) phenotypes, meropenem-vaborbactam displayed MIC 50/90 values of 0.5/32, 0.03/1, and 0.5/32 g/ml, respectively, whereas meropenem activities were 16/Ͼ32, 0.06/32, and 0.5/32 g/ml, respectively. Among all geographic regions, the highest meropenem-vaborbactam activities were observed for CRE and MDR isolates from the United States (MIC 50/90 , 0.03/1 and 0.03/ 0.12 g/ml, respectively). Meropenem-vaborbactam was very active against 135 KPC producers, and all isolates were inhibited by concentrations of Յ8 g/ml (133 isolates by concentrations of Յ2 g/ml). This combination had limited activity against isolates producing metallo--lactamases (including 25 NDM-1 and 16 VIM producers) and/or oxacillinases (27 OXA-48/OXA-163 producers) that were detected mainly in Asia-Pacific and some European countries. The activity of meropenem-vaborbactam was similar to that of meropenem alone against Pseudomonas aeruginosa, Acinetobacter spp., and Stenotrophomonas maltophilia. Meropenem-vaborbactam was active against contemporary Enterobacteriaceae isolates collected worldwide, and this combination demonstrated enhanced activity compared to those of meropenem and most comparator agents against CRE isolates and KPC producers, the latter of which are often MDR.
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