viernes, 16 de agosto de 2019

Ahead of Print - Epidemiology of Carbapenemase-Producing Klebsiella pneumoniae in a Hospital, Portugal - Volume 25, Number 9—September 2019 - Emerging Infectious Diseases journal - CDC

Ahead of Print - Epidemiology of Carbapenemase-Producing Klebsiella pneumoniae in a Hospital, Portugal - Volume 25, Number 9—September 2019 - Emerging Infectious Diseases journal - CDC

CDC - Centers for Disease Control and Prevention - CDC 24/7: Saving Lives. Protecting People.â„¢

EMERGING INFECTIOUS DISEASES®

Volume 25, Number 9—September 2019
Synopsis

Epidemiology of Carbapenemase-Producing Klebsiella pneumoniae in a Hospital, Portugal

Marta Aires-de-Sousa, José Manuel Ortiz de la Rosa, Maria Luísa Gonçalves, Ana Luísa Pereira, Patrice Nordmann, and Laurent PoirelComments to Author 
Author affiliations: Escola Superior de Saúde da Cruz Vermelha Portuguesa, Lisbon, Portugal (M. Aires-de-Sousa)Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal (M. Aires-de-Sousa)Université de Fribourg, Fribourg, Switzerland (M. Aires-de-Sousa, J.M. Ortiz de la Rosa, P. Nordmann, L. Poirel); Hospital SAMS, Lisbon (M.L. Gonçalves, A.L. Pereira)Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg (P. Nordmann, L. Poirel)University of Lausanne, Lausanne, Switzerland (P. Nordmann)University Hospital Centre, Lausanne (P. Nordmann)

Abstract

We aimed to provide updated epidemiologic data on carbapenem-resistant Klebsiella pneumoniae in Portugal by characterizing all isolates (N = 46) recovered during 2013–2018 in a 123-bed hospital in Lisbon. We identified blaKPC-3 (n = 36), blaOXA-181 (n = 9), and blaGES-5 (n = 8) carbapenemase genes and observed co-occurrence of blaKPC-3 and blaGES-5 in 7 isolates. A single GES-5–producing isolate co-produced the extended-spectrum β-lactamase BEL-1; both corresponding genes were co-located on the same ColE1-like plasmid. The blaOXA-181 gene was always located on an IncX3 plasmid, whereas blaKPC-3was carried on IncN, IncFII, IncFIB, and IncFIIA plasmid types. The 46 isolates were distributed into 13 pulsotypes and 9 sequence types. All isolates remained susceptible to ceftazidime/avibactam, but some exhibited reduced antimicrobial susceptibility (MIC = 3 mg/L).
Klebsiella pneumoniae is a major cause of hospital-acquired infections, mainly responsible for urinary, respiratory, and bloodstream infections, as well as infections in intensive care unit (ICU) patients. The emergence of antimicrobial resistance, in particular the rise of carbapenem-resistant isolates, is a serious concern for the management of infections caused by K. pneumoniae because treatment alternatives are limited. Therefore, carbapenem-resistant K. pneumoniae are ranked among the recently published World Health Organization list of antibiotic-resistant “priority/critical” pathogens, for which research and development of new antibiotics is required (1).
Carbapenem resistance in K. pneumoniae arises from 2 main mechanisms: permeability defects combined with overexpression of a β-lactamase with weak carbapenemase activity (mostly CTX-M or AmpC cephalosporinases) and the acquisition of carbapenemases (2). Carbapenemase enzymes belong to 3 different Ambler classes (3). Class A includes the KPC-type enzyme, which has been extensively reported in K. pneumoniae; to date, although >20 different KPC variants have been described, KPC-2 and KPC-3 remain the most common types (4). In addition, a few studies reported the carbapenemase GES-5 (a point mutant derivative of the extended-spectrum β-lactamase [ESBL] GES-1) in K. pneumoniae (5). Class B includes the metallo-β-lactamases, which are mainly NDM-, VIM-, and IMP-type enzymes, and class D includes OXA-48–like β-lactamases.
The first clinical carbapenemase-producing K. pneumoniae in Portugal was isolated at a Lisbon hospital in 2009 (6). Since then, only sporadic infection isolates and single hospital cases have been reported (7,8), as well as a single outbreak of KPC-3–producing K. pneumoniae in 2013 (9). Surprisingly, no other carbapenemase type, such as OXA-48 and derivatives that are widespread in other countries in Europe (8), has been identified in K. pneumoniae in Portugal so far. A survey of Enterobacteriaceae collected in 13 hospitals in Portugal confirmed a low prevalence of carbapenemase producers in the country until 2013 (35/2105 [1.7%]) and a predominance of K. pneumoniae KPC-3 producers (10). However, in 2017, according to the annual report of the European Centre for Disease Prevention and Control on antimicrobial resistance in Europe, 8.6% of K. pneumoniae causing invasive infections in Portugal were resistant to carbapenems (11). That report also showed that Portugal faced an annual increasing trend of carbapenem resistance among K. pneumoniae since 2014 (1.8% in 2014, 3.4% in 2015, 5.2% in 2016, and 8.6% in 2017), exceeding the overall prevalence for Europe (7.2%). Nevertheless, data on the molecular epidemiology of nosocomial carbapenemase-producing K. pneumoniae in Portugal are still limited, and the existing studies include isolates recovered until 2014 only (10,12,13). Therefore, the aim of our study was to provide updated epidemiologic data on contemporary carbapenemase-producing K. pneumoniae in an acute-care facility hospital in Portugal by characterizing a collection of nonrepetitive isolates recovered during a 6-year period (2013–2018).

Materials and Methods

Bacterial Isolates
Carbapenemase-producing K. pneumoniae isolates (N = 46) recovered during 2013 (n = 1), 2014 (n = 1), 2016 (n = 9), 2017 (n = 12), and 2018 (n = 23) in a 123-bed hospital (SAMS Hospital) in Lisbon, Portugal, were used for our study. All isolates were from single patients and recovered from colonization and infection sites: rectal swabs (n = 20), urine (n = 15), sputum (n = 4), blood (n = 4), and other sites (n = 3). The isolates were obtained from 22 inpatients (ICU, n = 7; medicine ward, n = 11; surgery ward, n = 3; other, n = 1) and 24 outpatients (emergency department, n = 21; ambulatory consultation, n = 3).
Susceptibility Testing
We performed antimicrobial susceptibility testing by using the disk diffusion method on Mueller-Hinton agar plates (Bio-Rad, http://www.bio-rad.comExternal Link) for amoxicillin, amoxicillin/clavulanic acid, ticarcillin, ticarcillin/clavulanic acid, piperacillin, piperacillin/tazobactam, temocillin, ceftazidime, cefotaxime, cefoxitin, aztreonam, imipenem, ertapenem, meropenem, gentamicin, amikacin, ciprofloxacin, tigecycline, trimethoprim-sulfamethoxazole (SXT), and fosfomycin, following EUCAST recommendations (http://www.eucast.orgExternal Link). We determined MICs for imipenem, ertapenem, meropenem, and ceftazidime/avibactam by Etest (bioMérieux, http://www.biomerieux.comExternal Link). Interpretation of MICs and zone diameters followed EUCAST breakpoint tables (http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/Breakpoint_tables/v_9.0_Breakpoint_Tables.pdfExternal Link).
We assessed selection of carbapenemase producers by using the Rapidec Carba NP test (bioMérieux) (14). In addition, we evaluated colistin susceptibility by using the Rapid Polymyxin NP test (ELITechGroup Microbiology, http://www.elitechgroup.comExternal Link) (15).
Molecular Analysis
We identified carbapenemases (16) and ESBL genes (17) and detected the mcr-type colistin-resistance gene (18) by using PCR amplification, followed by sequencing of the amplicons. We used standard PCR conditions to amplify the β-lactamase gene blaCMY, encoding plasmid-mediated cephalosporinases (19), and the qnrS quinolone resistance gene (20). We detected the blaOXA-9 gene encoding a narrow-spectrum class D β-lactamase by using PCR amplification with primers OXA-9 FW 5′-ATGAAGGATACCTTGATGAAAAA-3′ and OXA-9 RW 5′-TCATTTGTTACCCATCAACACG-3′.
We evaluated the clonal relationship of the isolates by pulsed-field gel electrophoresis (PFGE), as described previously (21). We performed multilocus sequence typing (MLST) for a representative strain of each PFGE type and assigned sequence types (STs) by using the MLST database for K. pneumoniae (http://bigsdb.pasteur.fr/klebsiella/klebsiella.htmlExternal Link).
Conjugation Experiments and Plasmid Analysis
We performed mating-out assays by using the azide-resistant Escherichia coli J53 as the recipient. We separately inoculated donors carrying E. coli J53 and blaKPC-3 or blaOXA-181 overnight into LB broth (5 mL) and incubated, then subsequently mixed samples at a ratio of 10:1 (donor:recipient) for 5 h. We deposited 100 µL of this mix onto 22-µm filters and incubated overnight at 37°C on LB agar plates. After the incubation, we resuspended filters in 0.85% NaCl, then plated 100 µL of this mixture onto LB agar plates supplemented with ticarcillin (100 µg/mL) and azide (100 µg/mL). We performed susceptibility testing for all E. coli transconjugants and assessed positivity for blaKPC-3 or blaOXA-181 by using PCR.
We classified plasmids according to their incompatibility group by using the PCR-based replicon typing method as described previously (22). We characterized the plasmid carrying blaBEL-1 and blaGES-5 genes by using primers for ColE1-like plasmids, as previously described (23).

Results

Among the 46 carbapenemase-producing isolates, the most common carbapenemase identified was KPC-3 (n = 36 [78%]), followed by OXA-181 (n = 9 [20%]) and GES-5 (n = 8 [17%]) (Table). Seven isolates co-harbored >1 carbapenemase gene (blaKPC-3 and blaGES-5). The blaOXA-9 gene encoding a narrow-spectrum class D β-lactamase was identified in 31 isolates, all of which were KPC-3 producers. A single GES-5–producing isolate co-produced the ESBL BEL-1.
Mating-out assays followed by PCR-based replicon typing revealed that the blaOXA-181 gene was always located onto an IncX3 plasmid, whereas the blaKPC-3 gene was carried onto IncN, IncFII, IncFIB, and IncFIIA plasmid types. The genes blaGES-5 and blaBEL-1 were co-located on the same ColE1-like plasmid.
Antimicrobial susceptibility testing showed that 13 (28%) of the 46 carbapenemase producers were susceptible to imipenem (MIC <0.5 mg/L) and 10 (22%) isolates were susceptible to meropenem (MIC <1 mg/L). Eight (17%) isolates were susceptible to both carbapenems, and all except 1 were OXA-181 producers (p<0.001). The remaining isolate harbored blaGES-5 and blaBEL-1 and was also susceptible to ertapenem (MIC 0.25 mg/L). This isolate was the only isolate showing susceptibility to aztreonam. Despite the low MICs for carbapenems, all isolates grew on the chromID CARBA SMART agar (bioMérieux); the OXA-181 producers grew on the OXA side, whereas the GES-5/BEL-1 producer grew on the CARBA side, as did all KPC producers.
A substantial proportion of isolates showed reduced susceptibility to SXT (93%), ciprofloxacin (85%), gentamicin (76%), and amikacin (63%). In addition, nonsusceptibility to tigecycline was found in 28% of the isolates, resistance to fosfomycin in 3 isolates, and resistance to colistin in 1 isolate (i.e., negative for mcr-type genes). All isolates remained susceptible to ceftazidime/avibactam (MIC values ranging from 0.125 to 3 mg/L), although some exhibited reduced susceptibility (resistance breakpoint >8 mg/L). Isolates co-possessing blaKPC-3 and blaGES-5 genes showed higher MICs for ceftazidime/avibactam (>1.5 mg/L [p = 0.014]), whereas isolates producing carbapenemase OXA-181 had lower values (<0.25 mg/L [p<0.001]).
The plasmid-mediated quinolone resistance gene qnrS was present in all isolates. No isolates carried the β-lactamase gene blaCMY.
PFGE analysis distributed the 46 isolates into 13 pulsotypes (Table). PFGE type A included the 7 isolates co-producing KPC-3 and GES-5 carbapenemases. The 29 isolates producing KPC-3 alone belonged to 8 different PFGE types: B (n = 6), C (n = 3), D (n = 7), E (n = 3), F (n = 1), G (n = 7), H (n = 1), and I (n = 1). PFGE types J (n = 6), L (n = 1), and M (n = 2) included the 9 isolates that were positive for blaOXA-181, and the 1 isolate co-producing GES-5 and BEL-1 belonged to PFGE type N.
By using MLST, we found that the 13 PFGE types corresponded to 9 STs (Table). These STs were ST147 (n = 16 [35%]), ST13 (n = 7 [15%]), ST17 (n = 7 [15%]), ST348 (n = 7 [15%]), ST231 (n = 3 [7%]), ST35 (n = 3 [7%]), ST29 (n = 1), ST45 (n = 1), and ST960 (n = 1).
Thumbnail of Evolution of clonal types of carbapenem-producing Klebsiella pneumoniae in a hospital in Portugal, 2013–2018.
Figure. Evolution of clonal types of carbapenem-producing Klebsiella pneumoniae in a hospital in Portugal, 2013–2018.
Analyzing the different clonal types over time (Figure), we observed that clone F-ST960 (KPC-3), recovered in 2013 in a single isolate, was no longer detected in the following years. Clone A-ST147 (KPC-3/GES-5), which was 1 of the 2 major clones found in our study, was clearly predominant in 2016 (6/7 isolates) but became a sporadic clone in 2018 (1 isolate). Conversely, clone G-ST348 (KPC-3), which emerged as a single isolate in 2017, became the major clone in 2018; this clone and clone D-ST13 are currently the predominant KPC-3 clones in the hospital. The first OXA-181 isolate was detected in 2016 (clone J-ST17), and although the 9 isolates producing this enzyme were distributed into 3 clones, J-ST17 became the predominant OXA-181 clone in 2018. The diversity of clones among carbapenemase producers increased over time together with the increase of isolates, especially in 2017 (9 clones among 12 isolates) (Figure).

Discussion

Our epidemiologic study describes the evolution of carbapenem-resistant K. pneumoniae over time in a hospital in Portugal, including contemporary isolates recovered after 2014. We report an increasing rate of carbapenemase producers in this hospital since 2016, which is consistent with the rise of carbapenem-resistant isolates in the country as reported by the European Centre for Disease Prevention and Control (11).
We found a clear predominance (78%) of K. pneumoniae KPC-3 producers, as observed in previous studies describing isolates in Portugal until 2014 (10,24,25). The KPC-3 producers belonged to a high diversity of clones (n = 9), and the blaKPC-3 gene was carried onto 4 plasmid types (IncN, IncFII, IncFIB, and IncFIIA). Therefore, the increasing number of KPC-3–producing isolates in this hospital might result mainly from recurrent introductions of those strains rather than the dissemination of specific plasmids or particular clones. ST147 was the predominant background type identified, either producing KPC-3 or OXA-181, which correlates with previous findings showing that this ST (belonging to clonal complex 258, as commonly found with KPC-2 or KPC-3 producers worldwide) was mainly associated to the spread of KPC-3-producing K. pneumoniae in the community in North Portugal (25).
Furthermore, most KPC-3–producing isolates (n = 31 [86%]) also carried the narrow-spectrum class D β-lactamase blaOXA-9. This association has been previously described in an Enterobacter cloacae strain from a patient in France who was transferred from a hospital in the United States (26) and also among K. pneumoniae isolates from Italy (27). The co-production of OXA-9 contributes to the high-level resistance observed for amoxicillin/clavulanic acid because KPC-3 activity remains partially antagonized by clavulanate.
We have shown that OXA-181 producers have emerged among clinical isolates in Portugal and have been appearing at an increasing rate of over time in this hospital. This carbapenemase, which is emerging worldwide, was found in isolates recovered since 2016, and its prevalence among carbapenemases is on the rise, which is a worrying and unexplained phenomenon. We recently described the massive occurrence of K. pneumoniae isolates carrying the blaOXA-181 gene located onto an IncX3 plasmid in Angola (21,28) and also some isolates in São Tomé and Príncipe (29). The genetic backgrounds of those OXA-181–producing K. pneumoniae were different, with no ST17 detected, in contrast to our findings in this study; nevertheless, the identification of a very similar plasmid carrying blaOXA-181 likely suggests a wide plasmid dissemination as a source of carbapenemase gene acquisition. The frequent exchange of populations between these 2 countries, which are former colonies of Portugal, and Portugal itself could have driven the intercontinental spread of carbapenemase producers. Some recent studies have underscored the emergence of OXA-181 carbapenemase mediated by acquisition of similar IncX3-type plasmids, such as in China or South Africa (30,31), suggesting that spread of this carbapenem-resistance trait could be linked in large part to a wide plasmid diffusion.
Our data indicate the emergence and spread of K. pneumoniae isolates co-producing KPC-3 and GES-5. GES-5 has been found previously in Portugal in a K. pneumoniae environmental isolate (32) and in a single clinical strain (24) but never in combination with KPC. The fact that isolates co-possessing blaKPC-3 and blaGES-5 showed higher MICs to ceftazidime/avibactam is of concern.
β-lactamase GES-5 has been reported in K. pneumoniae, mainly among sporadic isolates with origins in Asia, namely from a patient from France that had been hospitalized in Bangkok, Thailand (33), in 1 isolate from China (34), and in 1 isolate from South Korea (35). A single study reported the spread of K. pneumoniae GES-5–producing isolates recovered during 2012–2013 in South Africa that carried blaGES-5 in an IncQ plasmid (36).
Our study identified 1 isolate coproducing GES-5 and the ESBL BEL-1. The 2 corresponding genes were embedded in the same class 1 integron structure, as first and second gene cassette positions, respectively (data not shown). The occurrence of the blaBEL-1 gene in an enterobacterial isolate is noteworthy because this gene has been identified mainly in Pseudomonas aeruginosa. Likewise, blaGES-5 is commonly identified in P. aeruginosa. Therefore, our finding suggests that this ColE1 plasmid bearing these 2 uncommon broad-spectrum β-lactamases might originate from P. aeruginosa. This isolate coproducing GES-5 and the ESBL BEL-1 showed only decreased susceptibility to imipenem, meropenem, and ertapenem. A similar isolate carrying both enzymes, also showing only decreased susceptibility to all carbapenems, was recovered in 2009 from an ICU patient in Portugal (23).
We detected several OXA-181 producers that remained susceptible to imipenem and meropenem. This phenomenon has been reported previously (37) and has contributed substantially to the misrecognition of such carbapenemase producers and therefore to their silent spread. Nevertheless, we must underscore that all isolates from our collection could be detected by using available commercial selective media, such as the chromID CARBA SMART agar (bioMérieux).
The high rate (n = 12 [26%]) of carbapenem producers in our study being pandrug-resistant (i.e., having resistance to fluoroquinolones, aminoglycosides, tigecycline, and SXT) is of concern. The high rate of fluoroquinolone resistance was partly related to the occurrence of the qnrS gene. We have highlighted its endemic spread because it was identified in all of the carbapenemase-producing isolates identified, regardless of their clonal background and type of carbapenemase produced. Moreover, some isolates exhibited a worrying decreased susceptibility to ceftazidime/avibactam (MIC 3 mg/L; resistance breakpoint >8 mg/L), likely suggesting that some isolates actually started developing reduced susceptibility to that drug combination and moving toward resistance. Selection of KPC-producing K. pneumoniaeexhibiting resistance to ceftazidime/avibactam has been observed recently in Italy, where KPC is endemic. This resistance occurred in particular through substitutions in the KPC enzyme, leading to increased hydrolysis of ceftazidime and decreased affinity to avibactam (38). In our study, we did not observe selection of KPC-3 variants; therefore, the reduced susceptibility probably is mainly related to the co-production of GES-5, permeability defects, or both. Nevertheless, all isolates remained susceptible to the combination ceftazidime/avibactam, independently of the clonal type and the carbapenemase produced (whether KPC-3, OXA-181, or GES-5). In addition, fosfomycin and polymyxins are still therapeutic alternatives because very few isolates exhibited resistance to these antimicrobial agents (3 to fosfomycin and 1 to polymyxins).
Our study has some limitations, given that we included isolates from a single hospital. However, this private hospital receives patients transferred from several public hospitals in Lisbon and its surroundings and therefore might reflect at least the global situation in this capital city of Portugal, which includes approximately one third of the national population. This phenomenon is evident in the diversity of enzymes, plasmids, and clonal backgrounds identified in our study.
In summary, KPC-3 was the most common carbapenemase identified in K. pneumoniae isolated at the SAMS Hospital in Lisbon, Portugal, followed by OXA-181, which emerged in 2016 and appears to be on the rise. In addition, a large proportion of isolates are pandrug-resistant, drastically diminishing the options for treatment. Finally, considering the increasing identification of carbapenemase-producing K. pneumoniae in this hospital, systematic carriage screening at hospital admission, additional surveillance studies, and early detection of such isolates are required to limit their further spread. These measures would help mitigate the spread of these isolates in Portugal and avert the endemic levels that have been observed in other countries in Europe.
Dr. Aires de Sousa is a professor at Escola Superior de Saúde da Cruz Vermelha Portuguesa, Lisbon, Portugal. Her research interests include the molecular epidemiology of antimicrobial-resistant bacteria.

Acknowledgments

We are grateful to Faustino Ferreira and Ana Bela Correia for providing us the local authorizations to perform this study.
This work was partly supported by the University of Fribourg; the Swiss National Science Foundation (project nos. FNS-31003A_163432 and FNS-407240_177381); INSERM (Paris, France); Fundação para a Ciência e a Tecnologia (project no. PTDC/DTP-EPI/0842/2014) (Portugal); and Programa Operacional Competitividade e Internacionalização (project no. LISBOA-01-0145-FEDER-007660 [Microbiologia Molecular, Estrutural e Celular] funded by FEDER funds through COMPETE2020).

References

  1. Tacconelli  AMagrini  N. Global priority list of antibiotic-resistant bacteria to guide research, discovery, and development of new antibiotics. Geneva: World Health Organization; 2017.
  2. Pitout  JDNordmann  PPoirel  LCarbapenemase-producing Klebsiella pneumoniae, a key pathogen set for global nosocomial dominance. Antimicrob Agents Chemother2015;59:587384DOIExternal LinkPubMedExternal Link
  3. Queenan  AMBush  KCarbapenemases: the versatile beta-lactamases. Clin Microbiol Rev2007;20:44058DOIExternal LinkPubMedExternal Link
  4. Munoz-Price  LSPoirel  LBonomo  RASchwaber  MJDaikos  GLCormican  Met al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. Lancet Infect Dis2013;13:78596DOIExternal LinkPubMedExternal Link
  5. Poirel  LCarrër  APitout  JDNordmann  PIntegron mobilization unit as a source of mobility of antibiotic resistance genes. Antimicrob Agents Chemother2009;53:24928DOIExternal LinkPubMedExternal Link
  6. Machado  PSilva  ALito  LMelo-Cristino  JDuarte  AEmergence of Klebsiella pneumoniae ST11-producing KPC-3 carbapenemase at a Lisbon hospital. Clin Microbiol Infect2010;16(Suppl 2):S28.
  7. Albiger  BGlasner  CStruelens  MJGrundmann  HMonnet  DLEuropean Survey of Carbapenemase-Producing Enterobacteriaceae. (EuSCAPE) Working Group. Carbapenemase-producing Enterobacteriaceae in Europe: assessment by national experts from 38 countries, May 2015. Euro Surveill2015;20:30062DOIExternal Link
  8. Grundmann  HGlasner  CAlbiger  BAanensen  DMTomlinson  CTAndrasević  ATet al.European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) Working GroupOccurrence of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli in the European survey of carbapenemase-producing Enterobacteriaceae (EuSCAPE): a prospective, multinational study. Lancet Infect Dis2017;17:15363DOIExternal LinkPubMedExternal Link
  9. Vubil  DFigueiredo  RReis  TCanha  CBoaventura  LDA Silva  GJOutbreak of KPC-3-producing ST15 and ST348 Klebsiella pneumoniae in a Portuguese hospital. Epidemiol Infect2017;145:5959DOIExternal LinkPubMedExternal Link
  10. Manageiro  VFerreira  EAlmeida  JBarbosa  SSimões  CBonomo  RAet al.Antibiotic Resistance Surveillance Program in Portugal (ARSIP)Predominance of KPC-3 in a survey for carbapenemase-producing Enterobacteriaceae in Portugal. Antimicrob Agents Chemother2015;59:358892DOIExternal LinkPubMedExternal Link
  11. European Center for Disease Prevention and Control. Surveillance of antimicrobial resistance in Europe—annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017 [cited 2019 Apr 10]. https://ecdc.europa.eu/sites/portal/files/documents/EARS-Net-report-2017-update-jan-2019.pdfExternal Link
  12. Pires  DZagalo  ASantos  CCota de Medeiros  FDuarte  ALito  Let al. Evolving epidemiology of carbapenemase-producing Enterobacteriaceae in Portugal: 2012 retrospective cohort at a tertiary hospital in Lisbon. J Hosp Infect2016;92:825DOIExternal LinkPubMedExternal Link
  13. Caneiras  CLito  LMayoralas-Alises  SDíaz-Lobato  SMelo-Cristino  JDuarte  AVirulence and resistance determinants of Klebsiella pneumoniae isolated from a Portuguese tertiary university hospital centre over a 31-year period. Enferm Infecc Microbiol Clin2019;37:38793DOIExternal LinkPubMedExternal Link
  14. Poirel  LNordmann  PRapidec Carba NP test for rapid detection of carbapenemase producers. J Clin Microbiol2015;53:30038DOIExternal LinkPubMedExternal Link
  15. Jayol  AKieffer  NPoirel  LGuérin  FGüneser  DCattoir  Vet al. Evaluation of the Rapid Polymyxin NP test and its industrial version for the detection of polymyxin-resistant Enterobacteriaceae. Diagn Microbiol Infect Dis2018;92:904DOIExternal LinkPubMedExternal Link
  16. Poirel  LWalsh  TRCuvillier  VNordmann  PMultiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis2011;70:11923DOIExternal LinkPubMedExternal Link
  17. Ortiz de la Rosa  JMNordmann  PPoirel  LESBLs and resistance to ceftazidime/avibactam and ceftolozane/tazobactam combinations in Escherichia coli and Pseudomonas aeruginosa. J Antimicrob Chemother2019;74:19349DOIExternal LinkPubMedExternal Link
  18. Lescat  MPoirel  LNordmann  PRapid multiplex polymerase chain reaction for detection of mcr-1 to mcr-5 genes. Diagn Microbiol Infect Dis2018;92:2679DOIExternal LinkPubMedExternal Link
  19. Philippon  AArlet  GJacoby  GAPlasmid-determined AmpC-type beta-lactamases. Antimicrob Agents Chemother2002;46:111DOIExternal LinkPubMedExternal Link
  20. Cattoir  VPoirel  LRotimi  VSoussy  CJNordmann  PMultiplex PCR for detection of plasmid-mediated quinolone resistance qnrgenes in ESBL-producing enterobacterial isolates. J Antimicrob Chemother2007;60:3947DOIExternal LinkPubMedExternal Link
  21. Kieffer  NNordmann  PAires-de-Sousa  MPoirel  LHigh prevalence of carbapenemase-producing Enterobacteriaceae among hospitalized children in Luanda, Angola. Antimicrob Agents Chemother2016;60:618992DOIExternal LinkPubMedExternal Link
  22. Carattoli  ABertini  AVilla  LFalbo  VHopkins  KLThrelfall  EJIdentification of plasmids by PCR-based replicon typing. J Microbiol Methods2005;63:21928DOIExternal LinkPubMedExternal Link
  23. Papagiannitsis  CCDolejska  MIzdebski  RDobiasova  HStudentova  VEsteves  FJet al. Characterization of pKP-M1144, a novel ColE1-like plasmid encoding IMP-8, GES-5, and BEL-1 beta-lactamases, from a Klebsiella pneumoniae sequence type 252 isolate.Antimicrob Agents Chemother2015;59:50658DOIExternal LinkPubMedExternal Link
  24. Manageiro  VRomão  RMoura  IBSampaio  DAVieira  LFerreira  Eet al.Network EuSCAPE-PortugalNetwork EuSCAPE-Portugal. Network EuSCAPE-Portugal. Molecular epidemiology and risk factors of carbapenemase-producing Enterobacteriaceae isolates in Portuguese hospitals: results from European survey on carbapenemase-producing Enterobacteriaceae (EuSCAPE). Front Microbiol2018;9:2834DOIExternal LinkPubMedExternal Link
  25. Rodrigues  CBavlovič  JMachado  EAmorim  JPeixe  LNovais  ÂKPC-3-producing Klebsiella pneumoniae in Portugal linked to previously circulating non-CG258 lineages and uncommon genetic platforms (Tn4401d-IncFIA and Tn4401d-IncN). Front Microbiol2016;7:1000DOIExternal LinkPubMedExternal Link
  26. Dortet  LRadu  IGautier  VBlot  FChachaty  EArlet  GIntercontinental travels of patients and dissemination of plasmid-mediated carbapenemase KPC-3 associated with OXA-9 and TEM-1. J Antimicrob Chemother2008;61:4557DOIExternal LinkPubMedExternal Link
  27. Kocsis  ELo Cascio  GPiccoli  MCornaglia  GMazzariol  AKPC-3 carbapenemase harbored in FIIk plasmid from Klebsiella pneumoniae ST512 and Escherichia coli ST43 in the same patient. Microb Drug Resist2014;20:37782DOIExternal LinkPubMedExternal Link
  28. Poirel  LGoutines  JAires-de-Sousa  MNordmann  PHigh rate of association of 16S rRNA methylases and carbapenemases in Enterobacteriaceae recovered from hospitalized children in Angola. Antimicrob Agents Chemother2018;62:e0002118DOIExternal LinkPubMedExternal Link
  29. Poirel  LAires-de-Sousa  MKudyba  PKieffer  NNordmann  PScreening and characterization of multidrug-resistant Gram-negative bacteria from a remote African area, São Tomé and Príncipe. Antimicrob Agents Chemother2018;62:e0102118DOIExternal LinkPubMedExternal Link
  30. Liu  YFeng  YWu  WXie  YWang  XZhang  Xet al. First report of OXA-181-producing Escherichia coli in China and characterization of the isolate using whole-genome sequencing. Antimicrob Agents Chemother2015;59:50225DOIExternal LinkPubMedExternal Link
  31. Lowe  MKock  MMCoetzee  JHoosien  EPeirano  GStrydom  KAet al. Klebsiella pneumoniae ST307 with blaOXA-181, South Africa, 2014-2016. Emerg Infect Dis2019;25:73947DOIExternal LinkPubMedExternal Link
  32. Manageiro  VFerreira  ECaniça  MManaia  CMGES-5 among the β-lactamases detected in ubiquitous bacteria isolated from aquatic environment samples. FEMS Microbiol Lett2014;351:649DOIExternal LinkPubMedExternal Link
  33. Bonnin  RAJousset  ABUrvoy  NGauthier  LTlili  LCreton  Eet al. Detection of GES-5 carbapenemase in Klebsiella pneumoniae, a newcomer in France. Antimicrob Agents Chemother2017;61:e0226316DOIExternal LinkPubMedExternal Link
  34. Chen  DQWu  AWYang  LSu  DHLin  YPHu  YWet al. Emergence and plasmid analysis of Klebsiella pneumoniae KP01 carrying blaGES-5 from Guangzhou, China. Antimicrob Agents Chemother2016;60:63624DOIExternal LinkPubMedExternal Link
  35. Yoon  EJYang  JWKim  JOLee  HLee  KJJeong  SHCarbapenemase-producing Enterobacteriaceae in South Korea: a report from the National Laboratory Surveillance System. Future Microbiol2018;13:77183DOIExternal LinkPubMedExternal Link
  36. Pedersen  TSekyere  JOGovinden  UMoodley  KSivertsen  ASamuelsen  Øet al. Spread of plasmid-encoded NDM-1 and GES-5 carbapenemases among extensively drug-resistant and pandrug-resistant clinical Enterobacteriaceae in Durban, South Africa.Antimicrob Agents Chemother2018;62:e0217817DOIExternal LinkPubMedExternal Link
  37. Potron  APoirel  LRondinaud  ENordmann  PIntercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. Euro Surveill2013;18:20549DOIExternal LinkPubMedExternal Link
  38. Gaibani  PCampoli  CLewis  REVolpe  SLScaltriti  EGiannella  Met al. In vivo evolution of resistant subpopulations of KPC-producing Klebsiella pneumoniae during ceftazidime/avibactam treatment. J Antimicrob Chemother2018;73:15259DOIExternal LinkPubMedExternal Link
Figure
Table
Suggested citation for this article: Aires-de-Sousa M, Ortiz de la Rosa JM, Gonçalves ML, Pereira AL, Nordmann P, Poirel L. Epidemiology of carbapenemase-producing Klebsiella pneumoniae in a hospital, Portugal. Emerg Infect Dis. 2019 Sep [date cited]. https://doi.org/10.3201/eid2509.190656
DOI: 10.3201/eid2509.190656


Original Publication Date: 8/2/2019

No hay comentarios:

Publicar un comentario