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      Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in Japan, 2012–2014

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          Abstract

          After the introduction of pneumococcal conjugate vaccines, the incidence of pneumococcal infections due to meropenem-resistant serotype 15A-ST63 strains increased in Japan. By using whole-genome sequencing and comparing sequences with those of clones from the United Kingdom, the United States, and Canada, we clarified the traits of the serotype 15A-ST63 clone. Our analysis revealed that the meropenem-resistant serotype 15A-ST63 strains from Japan originated from meropenem-susceptible strains from Japan. Recombination site prediction analysis showed that the meropenem-resistant strain-specific recombination regions included the pbp1a and pbp2b regions. A detailed analysis of the composition of these genes indicated that resistance seems to be caused by pbp1a recombination. The pbp1a gene in meropenem-resistant isolates was identical to that in multidrug (including meropenem)–resistant serotype 19A-ST320 pneumococci, which have spread in the United States. The global spread of pneumococci of this lineage is noteworthy because serotype 15A is not included in the currently used 13-valent pneumococcal conjugate vaccine.

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          Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions.

          L Tzouvelekis, A Markogiannakis, M Psichogiou … (2012)
          The spread of Enterobacteriaceae, primarily Klebsiella pneumoniae, producing KPC, VIM, IMP, and NDM carbapenemases, is causing an unprecedented public health crisis. Carbapenemase-producing enterobacteria (CPE) infect mainly hospitalized patients but also have been spreading in long-term care facilities. Given their multidrug resistance, therapeutic options are limited and, as discussed here, should be reevaluated and optimized. Based on susceptibility data, colistin and tigecycline are commonly used to treat CPE infections. Nevertheless, a review of the literature revealed high failure rates in cases of monotherapy with these drugs, whilst monotherapy with either a carbapenem or an aminoglycoside appeared to be more effective. Combination therapies not including carbapenems were comparable to aminoglycoside and carbapenem monotherapies. Higher success rates have been achieved with carbapenem-containing combinations. Pharmacodynamic simulations and experimental infections indicate that modification of the current patterns of carbapenem use against CPE warrants further attention. Epidemiological data, though fragmentary in many countries, indicate CPE foci and transmission routes, to some extent, whilst also underlining the lack of international collaborative systems that could react promptly and effectively. Fortunately, there are sound studies showing successful containment of CPE by bundles of measures, among which the most important are active surveillance cultures, separation of carriers, and assignment of dedicated nursing staff.
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            Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study.

            Pauline Waight, Nicholas Andrews, Shamez Ladhani … (2015)
            The 13-valent pneumococcal conjugate vaccine (PCV13) protects against key serotypes that increased after routine immunisation with the seven-valent vaccine (PCV7), but its potential for herd protection and serotype replacement is uncertain. The aim of this study was to analyse the effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction.
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              Penicillin-Binding Protein Transpeptidase Signatures for Tracking and Predicting β-Lactam Resistance Levels in Streptococcus pneumoniae

              Yuan-Yuan Li, Benjamin J. Metcalf, Sopio Chochua … (2016)
              ABSTRACT β-Lactam antibiotics are the drugs of choice to treat pneumococcal infections. The spread of β-lactam-resistant pneumococci is a major concern in choosing an effective therapy for patients. Systematically tracking β-lactam resistance could benefit disease surveillance. Here we developed a classification system in which a pneumococcal isolate is assigned to a “PBP type” based on sequence signatures in the transpeptidase domains (TPDs) of the three critical penicillin-binding proteins (PBPs), PBP1a, PBP2b, and PBP2x. We identified 307 unique PBP types from 2,528 invasive pneumococcal isolates, which had known MICs to six β-lactams based on broth microdilution. We found that increased β-lactam MICs strongly correlated with PBP types containing divergent TPD sequences. The PBP type explained 94 to 99% of variation in MICs both before and after accounting for genomic backgrounds defined by multilocus sequence typing, indicating that genomic backgrounds made little independent contribution to β-lactam MICs at the population level. We further developed and evaluated predictive models of MICs based on PBP type. Compared to microdilution MICs, MICs predicted by PBP type showed essential agreement (MICs agree within 1 dilution) of >98%, category agreement (interpretive results agree) of >94%, a major discrepancy (sensitive isolate predicted as resistant) rate of <3%, and a very major discrepancy (resistant isolate predicted as sensitive) rate of <2% for all six β-lactams. Thus, the PBP transpeptidase signatures are robust indicators of MICs to different β-lactam antibiotics in clinical pneumococcal isolates and serve as an accurate alternative to phenotypic susceptibility testing.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (iso-abbrev): Emerging Infect. Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): February 2018
                Volume: 24
                Issue: 2
                Pages: 275-283
                Affiliations
                [1]Kyoto University Graduate School of Medicine, Kyoto, Japan (S. Nakano, Y. Matsumura, M. Yamamoto, M. Nagao, S. Ichiyama);
                [2]National Hospital Organization Mie National Hospital, Tsu, Japan (T. Fujisawa, S. Suga);
                [3]Nagoya City University Graduate School of Medical Science, Nagoya, Japan (Y. Ito);
                [4]National Institute of Infectious Diseases, Tokyo, Japan (B. Chang, M. Ohnishi)
                Author notes
                Address for correspondence: Satoshi Nakano, Kyoto Daigaku Igakubu Fuzoku Byoin, 54 Kawahara-cho, Syogoin, Sakyo-ku, Kyoto, Kyoto 606-8507, Japan; email: snakano@ 123456kuhp.kyoto-u.ac.jp
                Article
                Publisher ID: 17-1268
                DOI: 10.3201/eid2402.171268
                PMC ID: 5782878
                PubMed ID: 29350141
                SO-VID: 37dde932-d891-4eef-87d6-be591c7ed2e1
                History
                Categories
                Subject: Research
                Subject: Research
                Subject: Spread of Meropenem-Resistant Streptococcus pneumoniae Serotype 15A-ST63 Clone in Japan, 2012–2014

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: streptococcus pneumoniae,meropenem resistance,antimicrobial resistance,serotype 15a,st63,pcv7,pcv13,bacteria,japan,vaccines,vaccination,pneumococcal conjugate vaccine
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: streptococcus pneumoniae, meropenem resistance, antimicrobial resistance, serotype 15a, st63, pcv7, pcv13, bacteria, japan, vaccines, vaccination, pneumococcal conjugate vaccine

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