The population structure of vancomycin-resistant and -susceptible Enterococcus faecium in a low-prevalence antimicrobial resistance setting is highly influenced by circulating global hospital-associated clones.

Between 2010 and 2015 the incidence of vancomycin-resistant Enterococcus faecium (VREfm) in Norway increased dramatically. Hence, we selected (1) a random subset of vancomycin-resistant enterococci (VRE) from the Norwegian Surveillance System for Communicable Diseases (2010-15; n=239) and (2) Norwegian vancomycin-susceptible E. faecium (VSEfm) bacteraemia isolates from the national surveillance system for antimicrobial resistance in microbes (2008 and 2014; n=261) for further analysis. Whole-genome sequences were collected for population structure, van gene cluster, mobile genetic element and virulome analysis, as well as antimicrobial susceptibility testing. Comparative genomic and phylogeographical analyses were performed with complete genomes of global E. faecium strains from the National Center for Biotechnology Information (NCBI) (1946-2022; n=272). All Norwegian VREfm and most of the VSEfm clustered with global hospital-associated sequence types (STs) in the phylogenetic subclade A1. The vanB2 subtype carried by chromosomal Tn1549 integrative conjugative elements was the dominant van type. The major Norwegian VREfm cluster types (CTs) were in accordance with concurrent European CTs. The dominant vanB-type VREfm CTs, ST192-CT3/26 and ST117-CT24, were mostly linked to a single hospital in Norway where the clones spread after independent chromosomal acquisition of Tn1549. The less prevalent vanA VRE were associated with more diverse CTs and vanA carrying Inc18 or RepA_N plasmids with toxin-antitoxin systems. Only 5 % of the Norwegian VRE were Enterococcus faecalis, all of which contained vanB. The Norwegian VREfm and VSEfm isolates harboured CT-specific virulence factor (VF) profiles supporting biofilm formation and colonization. The dominant VREfm CTs in general hosted more virulence determinants than VSEfm. The phylogenetic clade B VSEfm isolates (n=21), recently classified as Enterococcus lactis, harboured fewer VFs than E. faecium in general, and particularly subclade A1 isolates. In conclusion, the population structure of Norwegian E. faecium isolates mirrors the globally prevalent clones and particularly concurrent European VREfm/VSEfm CTs. Novel chromosomal acquisition of vanB2 on Tn1549 from the gut microbiota, however, formed a single major hospital VREfm outbreak. Dominant VREfm CTs contained more VFs than VSEfm.

Nationwide, population-based observational study of the molecular epidemiology and temporal trend of carbapenemase-producing Enterobacterales in Norway, 2015 to 2021.

IntroductionNational and regional carbapenemase-producing Enterobacterales (CPE) surveillance is essential to understand the burden of antimicrobial resistance, elucidate outbreaks, and develop infection-control or antimicrobial-treatment recommendations.AimThis study aimed to describe CPE and their epidemiology in Norway from 2015 to 2021.MethodsA nationwide, population-based observational study of all verified clinical and carriage CPE isolates submitted to the national reference laboratory was conducted. Isolates were characterised by antimicrobial susceptibility testing, whole genome sequencing (WGS) and basic metadata. Annual CPE incidences were also estimated.ResultsA total of 389 CPE isolates were identified from 332 patients of 63 years median age (range: 0-98). These corresponded to 341 cases, 184 (54%) being male. Between 2015 and 2021, the annual incidence of CPE cases increased from 0.6 to 1.1 per 100,000 person-years. For CPE-isolates with available data on colonisation/infection, 58% (226/389) were associated with colonisation and 38% (149/389) with clinical infections. WGS revealed a predominance of OXA-48-like (51%; 198/389) and NDM (34%; 134/389) carbapenemases in a diversified population of Escherichia coli and Klebsiella pneumoniae, including high-risk clones also detected globally. Most CPE isolates were travel-related (63%; 245/389). Although local outbreaks and healthcare-associated transmission occurred, no interregional spread was detected. Nevertheless, 18% (70/389) of isolates not directly related to import points towards potentially unidentified transmission routes. A decline in travel-associated cases was observed during the COVID-19 pandemic.ConclusionsThe close-to-doubling of CPE case incidence between 2015 and 2021 was associated with foreign travel and genomic diversity. To limit further transmission and outbreaks, continued screening and monitoring is essential.

Molecular Epidemiological Characterisation of ESBL- and Plasmid-Mediated AmpC-Producing Escherichia coli and Klebsiella pneumoniae at Kamuzu Central Hospital, Lilongwe, Malawi.

The global rise in infections caused by multidrug resistant (MDR) Enterobacterales poses a public health problem. We have performed a molecular epidemiological characterisation of representative plasmid-mediated AmpC (pAmpC) and ESBL-positive clinical isolates of Escherichia coli (n = 38) and Klebsiella pneumoniae (n = 17) from a tertiary hospital in Malawi collected in 2017. BlaCTX-M-15 was the most prevalent ESBL-determinant in E. coli (n = 30/38) and K. pneumoniae (n = 17/17), whereas blaCMY-2 was detected in nearly all AmpC-phenotype E. coli (n = 15/17). Whole genome sequencing revealed dominant globally disseminated E. coli sequence types (STs); ST410 (n = 16), ST131 (n = 7), and ST617 (n = 6). The ST distribution in K. pneumoniae was more diverse but included ST101 (n = 2), ST14 (n = 2), and ST340 (n = 2), all considered high-risk MDR clones. The isolates expressed an MDR profile, including resistance against commonly used antibiotics, such as fluoroquinolones, aminoglycosides, and/or trimethoprim-sulfamethoxazole, and harboured corresponding resistance determinants. Clonal analyses of the major STs of E. coli revealed closely related genetic clusters within ST410, ST131, and ST617 supporting within-hospital transmission between patients and/or via a common reservoir. The overall findings add to the limited knowledge on the molecular epidemiology of MDR E. coli and K. pneumoniae in Malawi and may help health policy makers to identify areas to target when addressing this major threat of antibiotic resistance.

Antimicrobial susceptibility profiles of clinically important bacterial pathogens at the Kamuzu Central Hospital in Lilongwe, Malawi.

Background: The aim of this prospective study was to ascertain antimicrobial resistance (AMR) in clinical bacterial pathogens from in-hospital adult patients at a tertiary hospital in Lilongwe, Malawi. Methods: Clinical specimens (blood culture, pus, urine and cerebrospinal fluid) collected during June to December 2017 were examined for bacterial growth in standard aerobic conditions. One specimen per patient was included. Antimicrobial susceptibility testing (AST) was performed using the disk diffusion method and interpreted according to EUCAST guidelines. Results: A total of 694 specimens were collected during the study period, of which 336 (48%) specimen yielded visible bacterial growth. Of the 336 specimens, a total of 411 phenotypically different isolates were recovered. Of the 411 isolates, 84 isolates (20%) were excluded and the remaining 327 (80%) were further characterised. The characterised isolates were identified as ESKAPE pathogens (n=195/327; 60%), Escherichia coli (n=92/327; 28%), Proteus mirabilis (n=33/327; 10) or Salmonella spp. (n=7/327; 2%) and were included for further analysis. The excluded isolates (n=84) comprised of coagulase-negative staphylococci (n=25), streptococci (n=33), and low-prevalence Gram-negative bacilli (n=26). E. coli (n=92; 28%) and S. aureus (n=86; 26%) were the most dominant species. A multidrug resistant (MDR) extended spectrum ß- lactamase (ESBL)-positive phenotype was detected in Klebsiella pneumoniae (n=20/29; 69%) and E. coli (n=49/92; 53%). One third of the Pseudomonas aeruginosa isolates were resistant to meropenem (MEM), but did not appear to be carbapenemase-producers. Methicillin resistant Staphylococcus aureus (MRSA) was molecularly confirmed in 10.5% of S. aureus (n=9/86). Conclusion: The high proportion of the MDR ESBL-phenotype in clinical isolates of Enterobacterales, strongly limits antimicrobial treatment options and has consequences for empirical and targeted antimicrobial treatment as well as clinical microbiology services and hospital infection control. There is need for a continuous surveillance and an antimicrobial stewardship (AMS) program to contain and prevent the spread of AMR.

High prevalence of multidrug resistant ESBL- and plasmid mediated AmpC-producing clinical isolates of Escherichia coli at Maputo Central Hospital, Mozambique.

BACKGROUND: Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum ß-lactamase (ESBL) - and plasmid-mediated AmpC (pAmpC)-producing clinical strains of Escherichia coli at Maputo Central Hospital (MCH), a 1000-bed reference hospital in Maputo, Mozambique. METHODS: A total of 230 clinical isolates of E. coli from urine (n = 199) and blood cultures (n = 31) were collected at MCH during August-November 2015. Antimicrobial susceptibility testing was performed by the disc diffusion method and interpreted according to EUCAST guidelines. Isolates with reduced susceptibility to 3rd generation cephalosporins were examined further; phenotypically for an ESBL-/AmpC-phenotype by combined disc methods and genetically for ESBL- and pAmpC-encoding genes by PCR and partial amplicon sequencing as well as genetic relatedness by ERIC-PCR. RESULTS: A total of 75 isolates with reduced susceptibility to cefotaxime and/or ceftazidime (n = 75) from urine (n = 58/199; 29%) and blood (n = 17/31; 55%) were detected. All 75 isolates were phenotypically ESBL-positive and 25/75 (33%) of those also expressed an AmpC-phenotype. ESBL-PCR and amplicon sequencing revealed a majority of blaCTX-M (n = 58/75; 77%) dominated by blaCTX-M-15. All AmpC-phenotype positive isolates (n = 25/75; 33%) scored positive for one or more pAmpC-genes dominated by blaMOX/FOX. Multidrug resistance (resistance ≥ three antibiotic classes) was observed in all the 75 ESBL-positive isolates dominated by resistance to trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin. ERIC-PCR revealed genetic diversity among strains with minor clusters indicating intra-hospital spread. CONCLUSION: We have observed a high prevalence of MDR pAmpC- and/or ESBL-producing clinical E. coli isolates with FOX/MOX and CTX-Ms as the major ß-lactamase types, respectively. ERIC-PCR analyses revealed genetic diversity and some clusters indicating within-hospital spread. The overall findings strongly support the urgent need for accurate and rapid diagnostic services to guide antibiotic treatment and improved infection control measures.

Emergence and dissemination of antimicrobial resistance in Escherichia coli causing bloodstream infections in Norway in 2002-17: a nationwide, longitudinal, microbial population genomic study.

BACKGROUND: The clonal diversity underpinning trends in multidrug resistant Escherichia coli causing bloodstream infections remains uncertain. We aimed to determine the contribution of individual clones to resistance over time, using large-scale genomics-based molecular epidemiology. METHODS: This was a longitudinal, E coli population, genomic, cohort study that sampled isolates from 22 512 E coli bloodstream infections included in the Norwegian surveillance programme on resistant microbes (NORM) from 2002 to 2017. 15 of 22 laboratories were able to share their isolates, and the first 22·5% of isolates from each year were requested. We used whole genome sequencing to infer the population structure (PopPUNK), and we investigated the clade composition of the dominant multidrug resistant clonal complex (CC)131 using genetic markers previously reported for sequence type (ST)131, effective population size (BEAST), and presence of determinants of antimicrobial resistance (ARIBA, PointFinder, and ResFinder databases) over time. We compared these features between the 2002-10 and 2011-17 time periods. We also compared our results with those of a longitudinal study from the UK done between 2001 and 2011. FINDINGS: Of the 3500 isolates requested from the participating laboratories, 3397 (97·1%) were received, of which 3254 (95·8%) were successfully sequenced and included in the analysis. A significant increase in the number of multidrug resistant CC131 isolates from 71 (5·6%) of 1277 in 2002-10 to 207 (10·5%) of 1977 in 2011-17 (p<0·0001), was the largest clonal expansion. CC131 was the most common clone in extended-spectrum ß-lactamase (ESBL)-positive isolates (75 [58·6%] of 128) and fluoroquinolone non-susceptible isolates (148 [39·2%] of 378). Within CC131, clade A increased in prevalence from 2002, whereas the global multidrug resistant clade C2 was not observed until 2007. Multiple de-novo acquisitions of both blaCTX-M ESBL-encoding genes in clades A and C1 and gain of phenotypic fluoroquinolone non-susceptibility across the clade A phylogeny were observed. We estimated that exponential increases in the effective population sizes of clades A, C1, and C2 occurred in the mid-2000s, and in clade B a decade earlier. The rate of increase in the estimated effective population size of clade A (Ne=3147) was nearly ten-times that of C2 (Ne=345), with clade A over-represented in Norwegian CC131 isolates (75 [27·0%] of 278) compared with the UK study (8 [5·4%] of 147 isolates). INTERPRETATION: The early and sustained establishment of predominantly antimicrobial susceptible CC131 clade A isolates, relative to multidrug resistant clade C2 isolates, suggests that resistance is not necessary for clonal success. However, even in the low antibiotic use setting of Norway, resistance to important antimicrobial classes has rapidly been selected for in CC131 clade A isolates. This study shows the importance of genomic surveillance in uncovering the complex ecology underlying multidrug resistance dissemination and competition, which have implications for the design of strategies and interventions to control the spread of high-risk multidrug resistant clones. FUNDING: Trond Mohn Foundation, European Research Council, Marie Sklodowska-Curie Actions, and the Wellcome Trust.

Performance of the EUCAST disc diffusion method and two MIC methods in detection of Enterobacteriaceae with reduced susceptibility to meropenem: the NordicAST CPE study.

Objectives: To examine performance of EUCAST disc diffusion and supplementary MIC methods for detection of Enterobacteriaceae with reduced susceptibility to meropenem using EUCAST screening recommendations. Methods: Sixty-one Nordic laboratories delivered data on EUCAST disc diffusion (n = 61), semi-automated meropenem MIC (n = 23; VITEK2, n = 20 and Phoenix, n = 3) and gradient meropenem MIC (n = 58) methods. The strains (n = 27) included the major carbapenemase classes (A, n = 4; B, n = 9; D, n = 6) involved in the global spread of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE strains (n = 8) covering a range of broth microdilution (BMD) meropenem MICs. Results: A triplicate Klebsiella variicola (meropenem MIC 0.5 mg/L) harbouring OXA-48 and Escherichia coli ATCC 25922 showed an overall good precision. Meropenem zone diameters below the EUCAST screening cut-off (<27 mm) were reported for strains with MIC ≥1 mg/L (n = 21), irrespective of resistance mechanism. For three strains (MIC = 0.5 mg/L) with OXA-48/-181, eight laboratories provided meropenem zone diameters above the screening cut-off. Very major errors (VMEs) were not observed. The overall distributions of major errors (MEs) and minor errors (mEs) were 9% and 36% (disc diffusion), 26% and 18% (VITEK2) and 7% and 20% (gradient MIC), respectively. Differences in ME and mE distributions between disc diffusion and MIC gradient tests compared with semi-automated methods were significant (P < 0.0001), using BMD MICs as a reference for categorization. Conclusions: The EUCAST disc diffusion method is a robust method to screen for CPE but isolates with meropenem MICs <1 mg/L pose challenges. The high ME rate in semi-automated methods might deter appropriate use of carbapenems in CPE infections with limited therapeutic options.

Molecular and epidemiological characterization of carbapenemase-producing Enterobacteriaceae in Norway, 2007 to 2014.

The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. Here we present associated patient data and molecular, epidemiological and phenotypic characteristics of all CPE isolates in Norway from 2007 to 2014 confirmed at the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance. All confirmed CPE isolates were characterized pheno- and genotypically, including by whole genome sequencing (WGS). Patient data were reviewed retrospectively. In total 59 CPE isolates were identified from 53 patients. Urine was the dominant clinical sample source (37%) and only 15% of the isolates were obtained from faecal screening. The majority of cases (62%) were directly associated with travel or hospitalization abroad, but both intra-hospital transmission and one inter-hospital outbreak were observed. The number of CPE cases/year was low (2-14 cases/year), but an increasing trend was observed. Klebsiella spp. (n = 38) and E. coli (n = 14) were the dominant species and blaKPC (n = 20), blaNDM (n = 19), blaOXA-48-like (n = 12) and blaVIM (n = 7) were the dominant carbapenemase gene families. The CPE isolates were genetically diverse except for K. pneumoniae where clonal group 258 associated with blaKPC dominated. All isolates were multidrug-resistant and a significant proportion (21%) were resistant to colistin. Interestingly, all blaOXA-48-like, and a large proportion of blaNDM-positive Klebsiella spp. (89%) and E. coli (83%) isolates were susceptible in vitro to mecillinam. Thus, mecillinam could have a role in the treatment of uncomplicated urinary tract infections caused by OXA-48- or NDM-producing E. coli or K. pneumoniae. In conclusion, the impact of CPE in Norway is still limited and mainly associated with travel abroad, reflected in the diversity of clones and carbapenemase genes.

Identification of VIM-2-producing Pseudomonas aeruginosa from Tanzania is associated with sequence types 244 and 640 and the location of blaVIM-2 in a TniC integron.

Epidemiological data on carbapenemase-producing Gram-negative bacteria on the African continent are limited. Here, we report the identification of VIM-2-producing Pseudomonas aeruginosa isolates in Tanzania. Eight out of 90 clinical isolates of P. aeruginosa from a tertiary care hospital in Dar es Salaam were shown to harbor bla(VIM-2). The bla(VIM-2)-positive isolates belonged to two different sequence types (ST), ST244 and ST640, with bla(VIM-2) located in an unusual integron structure lacking the 3' conserved region of qacΔE1-sul1.

Evaluation of the total MBL confirm kit (ROSCO) for detection of metallo-ß-lactamases in Pseudomonas aeruginosa and Acinetobacter baumannii.

Phenotypic tests for carbapenemase production in Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with unspecific metallo-ß-lactamase (MBL) inhibitor activity in synergy tests and low positive predictive value. In this study, a collection of well-characterized P. aeruginosa and A. baumannii isolates was used to evaluate the inhibitor-based Total MBL Confirm Kit and the MBL Etest.

Performance of the EUCAST disk diffusion method, the CLSI agar screen method, and the Vitek 2 automated antimicrobial susceptibility testing system for detection of clinical isolates of Enterococci with low- and medium-level VanB-type vancomycin resistance: a multicenter study.

Different antimicrobial susceptibility testing methods to detect low-level vancomycin resistance in enterococci were evaluated in a Scandinavian multicenter study (n=28). A phenotypically and genotypically well-characterized diverse collection of Enterococcus faecalis (n=12) and Enterococcus faecium (n=18) strains with and without nonsusceptibility to vancomycin was examined blindly in Danish (n=5), Norwegian (n=13), and Swedish (n=10) laboratories using the EUCAST disk diffusion method (n=28) and the CLSI agar screen (n=18) or the Vitek 2 system (bioMérieux) (n=5). The EUCAST disk diffusion method (very major error [VME] rate, 7.0%; sensitivity, 0.93; major error [ME] rate, 2.4%; specificity, 0.98) and CLSI agar screen (VME rate, 6.6%; sensitivity, 0.93; ME rate, 5.6%; specificity, 0.94) performed significantly better (P=0.02) than the Vitek 2 system (VME rate, 13%; sensitivity, 0.87; ME rate, 0%; specificity, 1). The performance of the EUCAST disk diffusion method was challenged by differences in vancomycin inhibition zone sizes as well as the experience of the personnel in interpreting fuzzy zone edges as an indication of vancomycin resistance. Laboratories using Oxoid agar (P<0.0001) or Merck Mueller-Hinton (MH) agar (P=0.027) for the disk diffusion assay performed significantly better than did laboratories using BBL MH II medium. Laboratories using Difco brain heart infusion (BHI) agar for the CLSI agar screen performed significantly better (P=0.017) than did those using Oxoid BHI agar. In conclusion, both the EUCAST disk diffusion and CLSI agar screening methods performed acceptably (sensitivity, 0.93; specificity, 0.94 to 0.98) in the detection of VanB-type vancomycin-resistant enterococci with low-level resistance. Importantly, use of the CLSI agar screen requires careful monitoring of the vancomycin concentration in the plates. Moreover, disk diffusion methodology requires that personnel be trained in interpreting zone edges.

Increased prevalence of aminoglycoside resistance in clinical isolates of Escherichia coli and Klebsiella spp. in Norway is associated with the acquisition of AAC(3)-II and AAC(6')-Ib.

In this study, we show that the increasing prevalence of aminoglycoside resistance observed in Norway among clinical Escherichia coli and Klebsiella spp. isolates is mainly due to the presence of the aminoglycoside-modifying enzymes AAC(3)-II and AAC(6')-Ib. A frequent co-association of aminoglycoside resistance with Cefotaximase-München group 1 extended-spectrum ß-lactamases was also observed.

Species identification and molecular characterization of Acinetobacter spp. blood culture isolates from Norway.

OBJECTIVES: The study investigated the species distribution, antibiotic susceptibility patterns and genotypic resistance characteristics of 113 consecutive blood culture isolates of Acinetobacter species collected between 2005 and 2007 throughout Norway. METHODS: Species identification was performed by partial rpoB sequence analysis, and verified by 16S rDNA and recA sequence analyses. Susceptibility testing was performed by agar disc diffusion and Etest. Distribution of OXA carbapenemase genes and epidemic clonality of Acinetobacter baumannii isolates were detected by PCR assays. Analyses of blaOXA-51-like variants and quinolone resistance-determining regions (QRDRs) were done by sequencing. RESULTS: The most prevalent species in the collection were Acinetobacter genomic species (gen. sp.) 13TU (46.9%) and Acinetobacter gen. sp. 3 (19.5%), followed by A. baumannii (8.8%) and Acinetobacter lwoffii/Acinetobacter gen. sp. 9 (7.1%). Carbapenem resistance was observed in one blaOXA-23-like-positive A. baumannii isolate. Quinolone resistance was detected in five isolates from the Acinetobacter calcoaceticus-A. baumannii complex, of which two had point mutations in the QRDRs, including one novel ParC mutation. None of the A. baumannii isolates belonged to European/international clones I, II or III. Six blaOXA-51-like variants, including two novel variants, were identified. CONCLUSIONS: Acinetobacter gen. sp. 13TU and Acinetobacter gen. sp. 3 were predominant in Norwegian blood cultures, in contrast to in other countries where A. baumannii has dominated. The study demonstrated the importance of genotypic identification to determine the exact epidemiology of non-baumannii Acinetobacter species.

Emergence of OXA-carbapenemase- and 16S rRNA methylase-producing international clones of Acinetobacter baumannii in Norway.

This study was designed to investigate the molecular epidemiology and antibiotic-resistance characteristics of 11 carbapenem-resistant clinical isolates of Acinetobacter baumannii obtained in Norway between 2004 and 2009. Interestingly, all the isolates were linked with recent hospitalization outside Norway. The epidemiological status was investigated by multilocus sequence typing (MLST), multiplex PCR assays for major international clones, typing of blaOXA-51-like variants and PFGE. The genotypic-resistance characteristics, including the occurrence of OXA-carbapenemase-encoding and 16S rRNA methylase-encoding genes and class 1 integrons, were investigated by PCR assays and sequencing. Seven isolates were found to harbour blaOXA-66 and belong to MLST clonal complexes (CCs) CC2P (Pasteur Institute scheme) and CC92B (Bartual scheme), and international clone II. One isolate harboured blaOXA-69, and belonged to CC1P, CC109B and international clone I. Two isolates belonged to sequence group 9, probably a subgroup of international clone I, and one isolate belonged to sequence group 4, a proposed novel international clone. All isolates contained an acquired OXA-carbapenemase-encoding gene: blaOXA-23-like (n=9), blaOXA-24-like (n=1) and blaOXA-58-like (n=1). Four isolates with high-level aminoglycoside-resistance contained the 16S rRNA methylase-encoding armA gene. Class 1 integrons with six different variable regions were detected. Sequence analysis of gene cassettes identified four aminoglycoside (aacA4, aac(6')-Im, aadA1 and aacC1), two chloramphenicol (catB8 and cm1A5), one ß-lactamase (blaOXA-20) and one rifampicin (arr-2) resistance gene in various combinations. In conclusion, the occurrence of A. baumannii isolates producing OXA carbapenemase and 16S rRNA methylase in Norway was related to the worldwide distribution of international clones I and II, and the emergence of novel international clones.

Molecular characterization of CTX-M-15-producing clinical isolates of Escherichia coli reveals the spread of multidrug-resistant ST131 (O25:H4) and ST964 (O102:H6) strains in Norway.

Nationwide, CTX-M-producing clinical Escherichia coli isolates from the Norwegian ESBL study in 2003 (n=45) were characterized on strain and plasmid levels. Bla(CTX-M) allele typing, characterization of the genetic environment, phylogenetic groups, pulsed field gel electrophoresis (PFGE), serotyping and multilocus sequence typing were performed. Plasmid analysis included S1-nuclease-PFGE, polymerase chain reaction-based replicon typing, plasmid transfer and multidrug resistance profiling. Bla(CTX-M-15) (n=23; 51%) and bla(CTX-M-14) (n=11; 24%) were the major alleles of which 18 (78%) and 6 (55%), respectively, were linked to ISEcp1. Thirty-two isolates were of phylogenetic groups B2 and D. Isolates were of 29 different XbaI-PFGE-types including six regional clusters. Twenty-three different O:H serotypes were found, dominated by O25:H4 (n=9, 20%) and O102:H6 (n=9, 20%). Nineteen different STs were identified, where ST131 (n=9, 20%) and ST964 (n=7, 16%) were dominant. Bla(CTX-M) was found on > or =100 kb plasmids (39/45) of 10 different replicons dominated by IncFII (n=39, 87%), FIB (n=20, 44%) and FIA (n=19, 42%). Thirty-nine isolates (87%) displayed co-resistance to other classes of antibiotics. A transferable CTX-M phenotype was observed in 9/14 isolates. This study reveals that the majority of CTX-M-15-expressing strains in Norway are part of the global spread of multidrug-resistant ST131 and ST-complex 405, associated with ISEcp1 on transferrable IncFII plasmids.

[Broad-spectrum beta-lactamases in Gram-negative bacteria]. / Bredspektrede betalaktamaser hos gramnegative stavbakterier.

BACKGROUND: beta-lactams are our most valuable and frequently used antibiotics. Resistance towards them, in both Gram-positive and Gram-negative bacteria, challenges their antimicrobial effect. beta-lactamases are the most important resistance mechanism against beta-lactams in Gram-negative bacteria. MATERIAL AND METHODS: This review is based on literature retrieved through a non-systematic search of Pubmed (with the terms "ESBL", "AmpC", and "carbapenemases"), as well as the authors' own research experience. RESULTS AND INTERPRETATION: We now observe a global dissemination of particularly broad spectrum beta-lactamases; extended-spectrum beta-lactamases (ESBLs), plasmid-mediated AmpC, and carbapenemases. These beta-lactamases are hosted by multidrug-resistant clones of Enterobacteriaceae, Pseudomonas aeruginosa with few, if any, therapeutic alternatives. We have observed that this pandemic has reached Norway with an increase in ESBL-producing Escherichia coli in particular, but also pan-resistant carbapenemase-producing K. pneumoniae, P. aeruginosa OG A. baumannii during the last years. The latter ones have been associated with import after hospitalization abroad, but this situation may change due to the epidemic potential of these resistant clones. Rapid diagnostic service and targeted infection control measures are important to prevent them from spreading.