Background: The genera Abiotrophia and Granulicatella, previously known as nutritionally variant streptococci (NVS), are fastidious bacteria requiring vitamin B₆ analogs for growth. They are members of human normal oral microbiota, and are supposed to be one of the important pathogens for so-called "culture-negative" endocarditis. Methods: The type strains and oral isolates identified, by using both phenotypic profiles and the DNA⁻DNA hybridization method, were examined for susceptibilities to 15 antimicrobial agents including penicillin (benzylpenicillin, ampicillin, amoxicillin, and piperacillin), cephem (cefazolin, ceftazidime, ceftriaxone, and cefaclor), carbapenem (imipenem), aminoglycoside (gentamicin), macrolide (erythromycin), quinolone (ciprofloxacin), tetracycline (minocycline), glycopeptide (vancomycin), and trimethoprim-sulfamethoxazole complex. The minimum inhibitory concentration and susceptibility criterion were determined, according to the consensus guideline from the Clinical and Laboratory Standards Institute. Results: Isolates of Abiotrophia defectiva were susceptible to ampicillin, amoxicillin ceftriaxone, cefaclor, imipenem, ciprofloxacin, and vancomycin. Isolates of Granulicatella adiacens were mostly susceptible to benzylpenicillin, ampicillin, amoxicillin, cefazolin, ceftriaxone, imipenem, minocycline, and vancomycin. The susceptibility profile of Granulicatella elegans was similar to that of G. adiacens, and the susceptibility rate was higher than that of G. adiacens. Conclusions: Although Abiotrophia and Granulicatella strains are hardly distinguishable by their phenotypic characteristics, their susceptibility profiles to the antimicrobial agents were different among the species. Species-related differences in susceptibility of antibiotics should be considered in the clinical treatment for NVS related infections.

The superbug infection caused by New Delhi metallo-β-lactamase (NDM-1) has grown into an emerging threat, labelling and inhibition of NDM-1 has proven challenging due to its shuttling between pathogenic bacteria. Here, we report a potent covalent scaffold, ebsulfur, for targeting the protein in vitro and in vivo. Enzymatic kinetic study indicated that eighteen ebsulfurs gained except 1a-b and 1f inhibited NDM-1, exhibiting an IC50 value ranging of 0.16-9 μM, and 1g was found to be the best, dose- and time-dependent inhibitor with an IC50 of 0.16 μM. Also, these ebsulfurs effectively restored the antibacterial activity of cefazolin against E. coli expressing NDM-1, and the best effect was observed to be from 1g, 1i and 1n, resulting in an 256-fold reduction in MIC of the antibiotic at a dose of 16 μg/mL. The equilibrium dialysis study implied that the ebsulfur disrupted the coordination of one Zn(II) ion at active site of NDM-1. Labelling of NDM-1 using a constructed fluorescent ebsulfur Ebs-R suggested that the inhibitor covalently bound to the target through SDS-PAGE analysis in vitro. Also, labelling NDM-1 in living E. coli cells with Ebs-R by confocal microscopic imaging showed the real-time distribution change process of intracellular recombinant protein NDM-1. Moreover, the cytotoxicity of these ebsulfurs against L929 mouse fibroblastic cells was tested, and their capability to restore antibacterial activity of antibiotic against clinical strains E. coli EC08 producing NDM-1 was determined. The ebsulfur scaffold proposed here is valuable for development of the covalent irreversible inhibitors of NDM-1, and also for labelling the target in vitro and in vivo.

A systematic literature review and meta-analysis was conducted to evaluate the comparative efficacy and tolerability of cefazolin versus anti-staphylococcal penicillins (ASPs) for methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSI). Utilizing published regression models, included studies were stratified into high and low pre-probability of mortality subgroups. Cefazolin was associated with significantly lower rates of treatment failure (OR: 0.70; 95% CI: 0.61-0.82; P<0.001; I2=14%) and crude, all-cause mortality (OR: 0.69; 95% CI: 0.59-0.81; P<0.001; I2=18%) when compared to ASP therapy. The overall risk of treatment-related adverse drug reactions was numerically lower with cefazolin (OR: 0.39; 95% CI: 0.15-1.00; P=0.05). Subgroup sensitivity analyses of studies conducted in less severely ill patients were similar to the combined analysis. The role of cefazolin in the most severely ill patients with MSSA BSI should be prospectively evaluated.

Suspected urinary tract infection is a common indication for antimicrobial therapy in long-term care residents. We sought to characterize antimicrobial susceptibilities among urine isolates collected from women long-term care residents enrolled in a clinical trial across 21 long-term care facilities in Connecticut, United States of America between August 2012 and October 2015. Among 967 urine cultures collected from 175 women long-term care residents with and without suspected urinary tract infection, we identified 456 bacterial isolates. Escherichia coli (55.3%), Klebsiella (13.8%) and Enterococcus (8.3%) species were the predominant organisms identified. Among all 456 urine isolates, 68.1% were ciprofloxacin-susceptible, 77.2% were trimethoprim/sulfamethoxazole-susceptible, 86.3% were cefazolin-susceptible, and 72.6% were nitrofurantoin-susceptible. Among 252 Escherichia coli urine isolates, 60.2% were ciprofloxacin-susceptible, 73.7% were trimethoprim/ sulfamethoxazole-susceptible, 84.5% were cefazolin-susceptible, and 86.5% were nitrofurantoin-susceptible. These findings suggest that trimethoprim/sulfamethoxazole may be favorable empiric therapy while the urinary isolate is unknown, and nitrofurantoin may be optimal therapy for uncomplicated urinary tract infection due to Escherichia coli in women long-term care residents.