Among 39 carbapenem-resistant Enterobacteriaceae (2.7% overall; Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae strains) isolated in 2006 and 2007 in India, 15 strains carried bla NDM-1 and 10 harbored a gene encoding a variant of the carbapenemase OXA-48, named bla OXA-181 . One E. cloacae strain harbored bla VIM-6 , and one K. pneumoniae strain carrying bla OXA-181 also possessed bla VIM-5 . Multiple pulsed-field gel electrophoresis patterns and clonal dissemination within and among sites were observed. Isolates producing NDM-1 were disseminated in Indian health care facilities as early as 2006.

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Linezolid resistance has dominantly been mediated by mutations in 23S rRNA or ribosomal protein L4 genes. Recently, cfr has demonstrated the ability to produce a phenotype of resistance to not only oxazolidinones, but also other antimicrobial classes (phenicols, lincosamides, pleuromutilins, and streptogramin A). We describe the first detection of cfr-mediated linezolid resistance in Staphylococcus aureus and Staphylococcus epidermidis recovered from human infection cases monitored during the 2007 LEADER Program.

Community-acquired and nosocomial infections caused by multidrug-resistant Gram-positive pathogens continue to increase in prevalence and have become a serious problem in many parts of the world. BAL9141 is a member of the class of parenteral pyrrolidinone-3-ylidenemethyl cephalosporins, and has a broad spectrum of activity. In the current study, BAL9141 was tested against a large number (n = 2263) of recent isolates from various international surveillance programmes including 1097 Gram-positive strains. Susceptibility to (S) and activity of (mg/L) to BAL9141, based on proposed breakpoints (MIC50/MIC90/% S) were as follows: methicillin-susceptible Staphylococcus aureus (0.5/0.5/100%), methicillin-resistant S. aureus (MRSA) (1/2/100%), methicillin-susceptible coagulase-negative staphylococci (CoNS) (0.12/0.25/100%), methicillin-resistant CoNS (MR-CoNS) (1/2/100%), Streptococcus pneumoniae (< or = 0.015/0.25/100%), viridans group streptococci (0.03/0.5/99%), beta-haemolytic streptococci (< or = 0.015/< or = 0.015/100%), Enterococcus faecalis (0.5/16/90%), Enterococcus faecium (>32/>32/22%), Haemophilus influenzae (0.06/0.06/100%), Moraxella catarrhalis (0.06/0.5/100%), Neisseria gonorrhoeae (0.03/0.06/100%) and Neisseria meningitidis (< or = 0.002/0.004/100%). BAL9141 susceptibility at < pr = 4 mg/L (100% S) surpassed that of ceftriaxone (CRO; 1% S) and quinupristin/dalfopristin (Q-D; 92% S) against MRSA and MR-CoNS (CRO 0.9% S; Q-D 94% S). All S. pneumoniae were inhibited by BAL9141 at < or = 1 mg/L compared with CRO (90% S) and levofloxacin (LVX; 98% S). Susceptibility rates for viridans group streptococci to BAL9141 (>98%) were also higher than to CRO (86%) and LVX (96%). BAL9141 demonstrated excellent activity against most species of wild-type enteric bacilli, with > or = 95% of isolates being susceptible; however, only modest activity was observed for BAL9141 against non-fermentative Gram-negative species and ESBL-producing Escherichia coli or Klebsiella pneumoniae. BAL9141 demonstrated excellent activity against many tested pathogens displaying various resistance phenotypes, and should be particularly valuable in the treatment of MRSA as well as for drug-resistant streptococci, while maintaining a spectrum resembling a 'third-generation' cephalosporin against other clinically important species.

Increasing MβL prevalence is worrisome in various European countries; however, intrinsic resistance mechanisms in a highly genetically diverse population of carbapenem-non-susceptible P. aeruginosa are probably a matter for greater concern in these countries.

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Background A total of 178 825 Enterobacteriaceae isolates collected in 199 hospitals from 42 countries worldwide over 20 years (1997 to 2016) of the SENTRY Program were susceptibility tested by reference broth microdilution methods. Methods Trends in percentages over time were analyzed by the χ2 test. Results were reported as the percentage difference between the first (1997–2000) and the last (2013–2016) time period. Results Enterobacteriaceae exhibiting resistance to cephalosporins (extended-spectrum β-lactamase [ESBL] phenotype) and carbapenem resistance (CRE) significantly increased (P &lt; 0.05; χ2 test) from 10.3% to 24.0% and 0.6% to 2.9%, respectively. Similar trends were noted for all regions and infection sources. Klebsiella pneumoniae mainly drove the CRE increase. Multidrug-resistance (MDR) rates significantly increased from 7.3% to 15.3% overall, with important trends in all regions and infection sources. Significant increases were noted for MDR K. pneumoniae and Escherichia coli, polymyxin-resistant K. pneumoniae (2.0% to 5.5% overall), and aminoglycoside-resistant E. coli (7.0% to 18.0%) and K. pneumoniae (18.1% to 26.9%) over time in North America and Latin America. Carbapenemase-encoding genes were screened after 2007, and the occurrence of these genes was compared for 2007–2009 and 2014–2016. Among 1298 CRE isolates from the 2 study periods, blaKPC was detected among 186 (49.7%) and 501 (54.2%) isolates in 2007–2009 and 2014–2016, respectively. Metallo-β-lactamase genes were detected among 4.3% of the isolates from 2007 to 2009 and 12.7% of the isolates from 2014 to 2016, mainly due to the dissemination of isolates carrying blaNDM. Genes encoding IMP and VIM enzymes were observed in 1.9% and 2.4% (7 and 9 isolates) of the isolates from 2007 to 2009 and 0.4% and 1.9% of the isolates from 2014 to 2016. OXA-48 and variants increased from 4.3% in 2007–2009 to 12.6% in 2014–2016 (mainly in Europe). Conclusions A change in the epidemiology of carbapenemases and important increases in ESBL, CRE, MDR, and other resistant phenotypes among virtually all geographic regions and infection sources were noted in the 20 years of surveillance, highlighting the impact of antimicrobial resistance and the importance of its continuous monitoring.

A total of 104 carbapenemase (serine-and metallo-␤-lactamase [M␤L])-producing strains of theEnterobacteriaceae family collected from 2000 to 2005 in medical centers distributed worldwide were tested against tigecycline and 25 comparators by reference broth microdilution methods. The most frequent carbapenemase was KPC-2 or -3 (73 strains), followed by VIM-1 (14), IMP-1 (11), SME-2 (5), and NMC-A (1). All serine carbapenemases were detected in the United States, while M␤L-producing strains were isolated in Europe. Carbapenemase-producing Enterobacteriaceae showed high rates of resistance to most antimicrobial agents tested. The rank order of in vitro activity against these strains was as follows: tigecycline (100.0% susceptible) > polymyxin B (88.1%) > amikacin (73.0%) > imipenem (37.5%). Tigecycline was very active (MIC 90 , 1 g/ml) against this significant, contemporary collection of wellcharacterized strains and appears to be an excellent option compared to the polymyxins for treatment of infections caused by these multidrug-resistant Enterobacteriaceae.