Clinical isolates of -related species with reduced carbapenem susceptibility, harboring amino acid substitutions in penicillin-binding proteins in Japan.

group isolates with reduced carbapenem susceptibility have been reported, but its isolation rate in Japan is unknown. We collected 356 clinical α-hemolytic streptococcal isolates and identified 142 of them as using partial sequencing. The rate of meropenem non-susceptibility was 17.

Hydroxyhexylitaconic acids as potent IMP-type metallo-β-lactamase inhibitors for controlling carbapenem resistance in .

Metallo-β-lactamases (MBLs) represent one of the main causes of carbapenem resistance in the order . To combat MBL-producing carbapenem-resistant , the development of MBL inhibitors can restore carbapenem efficacy for such resistant bacteria. Microbial natural products are a promising source of attractive seed compounds for the development of antimicrobial agents.

β-Lactam Susceptibility of Streptococcus dysgalactiae subsp. equisimilis.

All clinical isolates of Streptococcus dysgalactiae subsp. equisimilis (SDSE) are considered susceptible to β-lactams, the first-line drugs used to treat SDSE infections. However, given that penicillin-non-susceptible SDSE strains have been isolated in Denmark, in this study, we aimed to identify β-lactam-non-susceptible clinical isolates of SDSE in Japan.

Improved disk diffusion method for simple detection of group B streptococci with reduced penicillin susceptibility (PRGBS).

We used 73 group B Streptococcus with reduced penicillin susceptibility (PRGBS) isolates and determined more rational cutoff values of previously developed disk diffusion method for detecting PRGBS using oxacillin, ceftizoxime, and ceftibuten disks. Using the novel cutoff values, the three disks showed high sensitivity and specificity, which were above 90.0%.

Difference in the Inhibitory Effect of Thiol Compounds and Demetallation Rates from the Zn(II) Active Site of Metallo-β-lactamases (IMP-1 and IMP-6) Associated with a Single Amino Acid Substitution.

Gram-negative bacteria producing metallo-β-lactamases (MBLs) have become a considerable threat to public health. MBLs including the IMP, VIM, and NDM types are Zn(II) enzymes that hydrolyze the β-lactam ring present in a broad range of antibiotics, such as -benzylpenicillin, meropenem, and imipenem. Among IMPs, IMP-1 and IMP-6 differ in a single amino acid substitution at position 262, where serine in IMP-1 is replaced by glycine in IMP-6, conferring a change in substrate specificity.

Dissecting the clonality of I1 plasmids using ORF-based binarized structure network analysis of plasmids (OSNAp).

Objectives: We aimed to elucidate the relationship among bla-carrying plasmids and their transmission between humans and domestic animals.

Methods: Phylogenetic relationship of 90 I1 plasmids harboring bla genes encoding extended-spectrum β-lactamase (ESBL) was analyzed using the ORF-based binarized structure network analysis of plasmids (OSNAp).

Results: The majority of plasmids carrying bla or bla belonged to a single lineage, respectively, and were primarily associated with domestic animals especially chickens.

Isolation of Group A Streptococci with Reduced β-Lactam Susceptibility Harboring Amino Acid Substitutions in Penicillin-Binding Proteins in Japan.

Streptococcus pyogenes (group A Streptococcus [GAS]) has long been regarded as being susceptible to β-lactams. However, amino acid substitutions in penicillin-binding protein 2X (PBP2X) conferring reduced β-lactam susceptibility have been indicated since 2019 in the United States and Iceland. Here, we report the first isolation of Streptococcus pyogenes possessing the PBP2X substitution conferring reduced β-lactam susceptibility in Asia; however, the MICs were below the susceptible breakpoint of the CLSI.

Practical Agar-Based Disk Diffusion Tests Using Sulfamoyl Heteroarylcarboxylic Acids for Identification of Subclass B1 Metallo-β-Lactamase-Producing .

The worldwide distribution of carbapenemase-producing (CPE) is a serious public health concern as they exhibit carbapenem resistance, thus limiting the choice of antimicrobials for treating CPE infections. Combination treatment with a β-lactam and one of the newly approved β-lactamase inhibitors, such as avibactam, relebactam, or vaborbactam, provides a valuable tool to cope with CPE; however, these inhibitors are active only against serine-type carbapenemases and not against metallo-β-lactamases (MβLs). Therefore, it is important to readily differentiate carbapenemases produced by CPE by using simple and reliable methods in order to choose an appropriate treatment.

Crystal Structures of Metallo-β-Lactamase (IMP-1) and Its D120E Mutant in Complexes with Citrate and the Inhibitory Effect of the Benzyl Group in Citrate Monobenzyl Ester.

The emergence and rapid spread of carbapenem-resistant pathogens producing metallo-β-lactamases such as IMP-1 and NDM-1 have been of great concern in the global clinical setting. The X-ray crystal structures of IMP-1 from and its single mutant, D120E, in complexes with citrate were determined at resolutions of 2.00 and 1.

Molecular Epidemiology of Enterobacter cloacae Complex Isolates with Reduced Carbapenem Susceptibility Recovered by Blood Culture.

The Enterobacter cloacae complex (ECC) is one of the most common causes of bacteremia and leads to poor clinical outcomes. The aim of this study was to clarify the antimicrobial susceptibility profiles and genetic backgrounds of non-carbapenemase-producing reduced-carbapenem-susceptible (RCS) ECC blood isolates in Japan using agar dilution antimicrobial susceptibility testing, whole-genome sequencing, and quantitative polymerase chain reaction for ampC, ompC, and ompF transcripts. Forty-two ECC blood isolates were categorized into RCS and carbapenem-susceptible groups based on the minimum inhibitory concentration of imipenem.

Aminoglycoside Resistance: Updates with a Focus on Acquired 16S Ribosomal RNA Methyltransferases.

The clinical usefulness of aminoglycosides has been revisited as an effective choice against β-lactam-resistant and fluoroquinolone-resistant gram-negative bacterial infections. Plazomicin, a next-generation aminoglycoside, was introduced for the treatment of complicated urinary tract infections and acute pyelonephritis. In contrast, bacteria have resisted aminoglycosides, including plazomicin, by producing 16S ribosomal RNA (rRNA) methyltransferases (MTases) that confer high-level and broad-range aminoglycoside resistance.

Daptomycin Susceptibility of Group B Streptococcus.

We previously reported the emergence and high prevalence of group B streptococci (GBS) with reduced penicillin susceptibility (PRGBS) clinical isolates in Japan. PRGBS tend to be non-susceptible to macrolides and fluoroquinolones. In our previous study, we found that the minimum inhibitory concentration (MIC) of daptomycin for one clinical isolate of GBS was above the susceptible breakpoint settled by the Clinical and Laboratory Standards Institute (CLSI).

Sulfamoyl Heteroarylcarboxylic Acids as Promising Metallo-β-Lactamase Inhibitors for Controlling Bacterial Carbapenem Resistance.

Production of metallo-β-lactamases (MBLs), which hydrolyze carbapenems, is a cause of carbapenem resistance in Development of effective inhibitors for MBLs is one approach to restore carbapenem efficacy in carbapenem-resistant (CRE). We report here that sulfamoyl heteroarylcarboxylic acids (SHCs) can competitively inhibit the globally spreading and clinically relevant MBLs (i.e.

Characterization of /F1:A2:B20 Plasmids Harbored by Escherichia coli Sequence Type 131 Sublineage C1/30R Isolates Spreading among Elderly Japanese in Nonacute-Care Settings.

We characterized 29 -harboring plasmids of sequence type 131 (ST131) sublineage C1/30R isolates from healthy individuals and long-term-care facility (LTCF) residents. Most (27/29) plasmids were of the FIA, FIB, and FII multireplicon type with the same plasmid multilocus sequence typing (pMLST). Several plasmids (7/23) from LTCF residents harbored only as the resistance gene; however, their fundamental structures were very similar to those of previously isolated /F1:A2:B20 plasmids, suggesting their prevalence as a newly arising public health concern.

4-Amino-2-Sulfanylbenzoic Acid as a Potent Subclass B3 Metallo-β-Lactamase-Specific Inhibitor Applicable for Distinguishing Metallo-β-Lactamase Subclasses.

The number of cases of infection with carbapenem-resistant (CRE) has been increasing and has become a major clinical and public health concern. Production of metallo-β-lactamases (MBLs) is one of the principal carbapenem resistance mechanisms in CRE. Therefore, developing MBL inhibitors is a promising strategy to overcome the problems of carbapenem resistance conferred by MBLs.

Erythromycin-Susceptible but Clindamycin-Resistant Phenotype of Clinical ermB-PCR-Positive Group B Streptococci Isolates with IS1216E-Inserted ermB.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a pathogen which causes neo natal sepsis, meningitis, and invasive infections in the elderly and people with medical conditions. Macrolide and lincosamide resistance rates of GBS strains have been increasing worldwide. A macrolide resistance gene, erythromycin ribosomal methylase (erm), typically confers macrolides, lincosamides, streptogramin B resistance phenotype.

Intercellular Transfer of Chromosomal Antimicrobial Resistance Genes between Acinetobacter baumannii Strains Mediated by Prophages.

The spread of antimicrobial resistance genes (ARGs) among Gram-negative pathogens, including , is primarily mediated by transferable plasmids; however, ARGs are frequently integrated into its chromosome. How ARG gets horizontally incorporated into the chromosome of , and whether it functions as a cause for further spread of ARG, remains unknown. Here, we demonstrated intercellular prophage-mediated transfer of chromosomal ARGs without direct cell-cell interaction in We prepared ARG-harboring extracellular DNA (eDNA) components from the culture supernatant of a multidrug-resistant (MDR) NU-60 strain and exposed an antimicrobial-susceptible (AS) ATCC 17978 strain to the eDNA components.

Spread of -Positive Methicillin-Resistant SCC Type II-ST764 Among Elderly Japanese in Nonacute Care Settings.

We investigated the prevalence and molecular epidemiology of methicillin-resistant (MRSA) among 356 residents of nine long-term care facilities (LTCFs) in Japan during 2015 and 2017. In total, 800 specimens were tested and 39 MRSA isolates were recovered from 31 (8.71%) residents.

Isolation of group B Streptococcus with reduced β-lactam susceptibility from pregnant women.

β-Lactam antibiotics are first-line agents for the treatment and prevention of group B Streptococcus (GBS) infections. We previously reported clinical GBS isolates with reduced β-lactam susceptibility (GBS-RBS) and characterized them as harbouring amino acid substitutions in penicillin-binding proteins (PBPs). However, to our knowledge, GBS-RBS clinical isolates have never previously been isolated from pregnant women worldwide.

Relatively high rates of cefotaxime- and ceftriaxone-non-susceptible isolates among group B streptococci with reduced penicillin susceptibility (PRGBS) in Japan.

Objectives: We have previously identified group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) that were non-susceptible to cefotaxime; however, the rates of cefotaxime and ceftriaxone non-susceptibility among PRGBS isolates have never been reported. Therefore, we first determined the MICs of 22 antibacterial drugs/compounds for 74 PRGBS isolates and then determined the rates of cefotaxime and ceftriaxone non-susceptibility among these isolates.

Methods: We used 74 clinical PRGBS isolates, previously collected in Japan and confirmed to harbour relevant amino acid substitutions in PBP2X.

High prevalence of bla among genetically diverse Escherichia coli recovered from retail raw chicken meat portions in Japan.

Global widespread of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, especially Escherichia coli poses a greater threat in healthcare and community settings of humans. Raw meats from food animals colonized with ESBL producers may be one of important transmission routes for those bacteria in the community. This study investigated the presence of ESBL-producing E.

Prevalence of CTX-M-Type Extended-Spectrum β-Lactamase-Producing B2-O25-ST131 R Among Residents in Nonacute Care Facilities in Japan.

We investigated the prevalence and characteristics of extended-spectrum β-lactamase (ESBL)-producing among 258 residents of long-term care facilities (LTCFs) in Japan. Out of 258 fecal samples collected from nine LTCFs between November 2015 and March 2017, we recovered 59 ESBL-producing isolates. All isolates carried genes, mainly (42.

Carbapenem-Nonsusceptible Haemophilus influenzae with Penicillin-Binding Protein 3 Containing an Amino Acid Insertion.

The prevalence of β-lactamase-negative ampicillin-resistant (BLNAR) has become a clinical concern. In BLNAR isolates, amino acid substitutions in penicillin-binding protein 3 (PBP3) are relevant to the β-lactam resistance. Carbapenem-nonsusceptible isolates have been rarely reported.

High isolation rate and multidrug resistance tendency of penicillin-susceptible group B Streptococcus with reduced ceftibuten susceptibility in Japan.

Group B Streptococcus (GBS) clinical isolates with reduced penicillin susceptibility (PRGBS) have emerged through acquisition of amino acid substitutions in penicillin-binding protein 2X (PBP2X). Moreover, we also reported the emergence of penicillin-susceptible GBS clinical isolates with reduced ceftibuten susceptibility (CTB PSGBS) due to amino acid substitutions in PBPs. However, whether or not these amino acid substitutions are responsible for the reduced ceftibuten susceptibility (RCTBS) profile remains unclear.