Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Extended spectrum beta-lactamase producing Enterobacterales faecal carriage in a medical intensive care unit: low rates of cross-transmission and infection

Extended spectrum beta-lactamase producing Enterobacterales faecal carriage in a medical... Background: Extended-spectrum beta-lactamases-producing Enterobacterales (ESBL-E) are disseminating worldwide especially in Intensive Care Units (ICUs) and are responsible for increased health costs and mortality. The aims of this work were to study ESBL-E dissemination in ICU and to assess the impact of ESBL-E fecal carriage on subsequent infections during a non-outbreak situation. Methods: We therefore screened every patient at admission then once a week in a medical ICU between January and June 2015. Each ESBL-E isolate was characterized by ESBL genes PCR amplification and the clonal dissemination was assessed by Pulsed-Field Gel Electrophoresis (PFGE). Results: Among the 608 screened patients, 55 (9%) were colonized by ESBL-E. Forty-four isolates were available for further analysis. Most of them (43/44, 98%) contained a ESBL gene from the CTX-M group. Only one case of ESBL-E cross-transmission occurred, even for acquired ESBL-E colonization. Subsequent infection by ESBL-E occurred in 6/55 (11%) patients and infecting ESBL-E strains were the colonizing ones. ESBL-E faecal carriage had a negative predictive value of 100% and a positive predictive value of 40% to predict ESBL-E ventilator associated-pneumonia (VAP). Alternatives to carbapenems consisting in piperacillin-tazobactam, ceftolozane-tazobactam and ceftazidime-avibactam were all active on this panel of ESBL-E. Conclusions: ESBL-E expansion and acquisition in ICU in a non-outbreak situation are not any more fully explained by cross-transmission. Mechanisms underlying ESBL-E dissemination in ICU are still to investigate. Interestingly, as far as we know, our study demonstrates for the first time by PFGE that the colonizing strain is indeed the infecting one in case of subsequent ESBL-E infection. Nevertheless, subsequent ESBL-E infection remains a rare event conferring poor positive predictive value for ESBL-E colonization to predict ESBL-E VAP. Relevance of systematic ESBL-E faecal screening at ICU admission and during ICU stay needs further investigation. Keywords: Extended-spectrum beta-lactamase, Carriage, Cross-transmission, Infection, Ventilator-associated pneumonia, Intensive care * Correspondence: renaud.prevel@hotmail.fr Medical Intensive Care Unit, CHU Bordeaux, Pellegrin universitary hospital, Place Amélie Raba-Léon, F-33000 Bordeaux, France UMR 5234 CNRS, Bordeaux University, F-33000 Bordeaux, France Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 2 of 7 Background year with a mean length of stay of 5 days. All patients The increase in antimicrobial resistance remains a major were hospitalized in single rooms. Standard isolation threat [1]. Among resistant bacteria, extended-spectrum procedures for all patients and contact isolation proce- β-lactamase-producing Enterobacterales (ESBL-E) are of dures for ESBL-E faecal carriers were applied according special concern. In fact, ESBL-E faecal carriage is increas- to the French Society of Hygiene guidelines [17] includ- ing worldwide [2, 3] , especially in long term care facilities ing hand hygiene procedures, dedicated medical supplies and ICUs, but even among healthy people with up to ten- and single room. fold increase in a 5 years French Survey [4, 5]. ESBL-E fae- For each ESBL-E carriers, demographic information, cal carriage rates vary between western and non-western medical history, exposure to antibiotics for the past 12 countries probably because of discrepancies in water sani- months, prior ESBL-E fecal carriage for the past 12 tation procedures (from 1 to 6% in Europe and North months, hospitalization or health-care facility contact for America but up to 60% in India) [3] . Known risk factors the past 12 months and mortality at day 28 and year 1 are previous antibiotic exposure, previous admission to a were retrospectively collected through medical records. healthcare facility, previous hospitalization and previous The patients were characterized as imported carriers if ESBL-E carriage [6–8]. Cross-transmission in ICU has they were colonized at admission (from the community been mainly described during outbreaks leading to en- or from a non-ICU medical unit) and acquired carriers if forcement of hygiene isolation procedures [9]. However, the first screening was negative but any of the weekly hygiene procedures were not able to fully prevent ESBL-E screening was subsequently positive. Recording of pa- increase in ICU despite increased standard precautions tients suffering from VAP or pneumonia without intub- and an efficient prevention from nosocomial cross- ation was made retrospectively through our prospective transmission [10, 11]. The environment of healthcare fa- patient database. Patient status was assessed by two cilities (such as floors and walls contamination) was also independent clinicians for all data including the con- suspected to play a role in ESBL-E cross-transmission but firmation of VAP diagnosis according to French current its role does not seem to be that important [12]. Finally, guidelines [18]. Bloodstream infection was defined by little is known about the mechanisms of ESBL-E faecal any positive blood culture except for coagulase-negative carriage dissemination during ICU stay in a non-outbreak Staphylococcus. situation when cross-transmission by healthcare workers is controlled by thorough hygiene procedures. Samples processing Moreover, to date, the link between ESBL-E faecal car- Each rectal swab was inoculated on the chromID ESBL® riage and the risk of subsequent ESBL-E infection is not plate for 16-24hours at 37°C. Confirmation of the pres- fully understood even if colonization by ESBL Klebsiella ence of ESBL was assessed by MAST AMPC&ESBL de- pneumoniae seems to be at higher risk than colonization tection discs D68C® (Mast Group). Identification of each by Escherichia coli [13]. A better understanding of this selected colony was assessed by mass spectrometry link between colonization and infection is of paramount (Maldi Biotyper Microflex®, Brucker). If 2 different importance since ESBL-E ICU infections lead to in- ESBL-E isolates were identified on a screening test, each creased healthcare costs, length of stay and mortality isolate was characterized individually. In case of positive [14]. In a non-ICU low-endemy environment, ESBL-E in- screening at admission, the isolates collected during fections among ESBL-E faecal carriers were shown to be a weekly screenings were considered as duplicate if being rare event but this remains an issue regarding ICU pa- the same species and carrying the same resistance genes tients, especially those developing ventilator-associated and not investigated. Susceptibilities to ceftolozane- pneumonia (VAP) [15, 16]. The aim of this work was to tazobactam and ceftazidime-avibactam were assessed by assess the ESBL-E dissemination (acquisition and clonal E-test® (BioMérieux). ESBL-E isolates were then stored transmission) and subsequent infection among ESBL-E at -20°C. faecal carriers in ICU during a non-outbreak situation. ESBL type determination Methods Detection and characterization of bla genes were Design of the study performed by multiplex PCRs for bla , bla , CTX − M SHV st th From January 1 to June 30 2015, all patients of the bla , and bla and then confirmed by simplex TEM OXA-1 medical ICU at Pellegrin Hospital, a 1300-bed tertiary PCRs [19]. center, were screened by rectal swab at admission and then weekly until they were discharged and isolates were Clonality assessment by pulsed-field gel electrophoresis collected. Our ICU is divided into 2 ICU wards of re- The clonality of ESBL-E dissemination in the ICU was spectively 13 and 14 beds and one 12 beds ward dedi- determined by pulsed-field gel electrophoresis (PFGE) of cated to post-intensive care, admitting 1200 patients per XbaI-digested genomic DNA of all collected ESBL-E Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 3 of 7 isolates available as previously described [20]. Patterns were not available for analysis (loss of ESBL after freezing were visually compared and analyzed according to previ- n = 8, the isolate did not grow after – 20°C freezing n =83, ously reported criteria [21]. Plasmids were not analyzed by and the wrong isolate was frozen at -20°C n = 82)). Among PFGE as concerns exist about its discriminative power. these 13 isolates, 10 were imported and 3 acquired in ICU. One of the missing acquired ESBL-E isolate was a Statistics analysis Citrobacter freundii with no other patient carrying that Quantitative variables were summarized as mean ± standard bacteria during his/her stay in ICU. Forty-four isolates deviation or median (interquartile range). Categorical data from faecal carriage were available for PFGE and 2 isolates were summarized as count (%). from weekly samplings of imported ESBL-E faecal carriage were considered as duplicate and used as positive control Results (8C and 18C, Fig. 2). ESBL prevalence in ICU patients No case of cross transmission regarding E. coli and Among 613 patients admitted to ICU during the 6 only one case of K. pneumoniae cross transmission months study-period, 608 were screened (371 (61%) only (39CT, Fig. 3) was identified. ESBL gene PCR identified at admission and 237 (39%) at admission and weekly 103 different ESBL-E genes mostly from bla CTX-M during their ICU stay). Fifty-five (9%) were positive for (43, 42%), bla (27, 26%), bla (18, 17%) and TEM OXA-1 ESBL-E faecal carriage. No ESBL-E outbreak was de- bla (14, 15%) groups. SHV tected during the study. Only 6 (1%) patients acquired ESBL-E faecal carriage during their ICU stay (Figure 1): ESBL-E infections among carriers during ICU stay 2 came from the community and 4 were already hospi- Among the 55 ESBL-E faecal carriers, 38 were infected talized at our universitary hospital before the transfer in and 16 of them received carbapenems as part of ICU. Mean time to acquisition was 31 (±17) days, me- empirical antimicrobial therapy during their ICU stay. dian time 30 (4-53) days. Each patient who acquired Infection sites were distributed as follow: pulmonary in- ESBL-E during ICU stay received several courses of fections 23/38, bloodstream infection 9/38 (5 patients broad-spectrum antimicrobial therapy between time of having both pulmonary and bloodstream infections), admission in ICU and ESBL-E acquisition. skin infection 5/38, urinary tract infection 4/38, abdom- inal infection 2/38. Among the 38 infected ESBL-E ESBL-E faecal carriers’ characteristics and risk factors faecal carriers, a non ESBL-E isolate was identified for ESBL-E faecal carriers are described in Table 1. ESBL-E 22 patients and 10 patients had no documentation be- faecal carriers were mainly colonised with Escherichia cause cultures remain sterile. Thus, only 6/38 patients coli (37/55, 67%), 37/47 (79%) patients had at least 1 risk were subsequently infected by an ESBL-E. None of these factor of EBL-E faecal carriage with 32/47 (68%) having 6 ESBL-E infected patients had acquired the ESBL-E fae- several risk factors (Table 2) including previous anti- cal carriage during their ICU stay. Respectively for E. coli microbial therapy Table 2. and K. pneumonia carriers, 2/37 (6%) and 4/16 (25%) were subsequently infected with ESBL-E. ESBL-E clonality assessment by pulsed-field gel The 6 ESBL-E infections were as follow: 2 ventilator- electrophoresis (Figs. 2 and 3) associated pneumonias (VAP), 2 pneumonias in non- Fifty-seven ESBL-E isolates from faecal carriage were intubated patients (2 E. coli and 2 K. pneumoniae), 1 collected from the 55 patients. Unfortunately, 13 isolates bloodstream infection (K. pneumoniae) and 1 urinary Fig. 1 Flow-chart Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 4 of 7 Table 1 ESBL-E faecal carriers’ characteristics at admission VAP among the ESBL-E faecal carriers (n = 55), 2 ESBL-E VAP among the ESBL-E faecal carriers and 0 ESBL-E VAP ESBL-E faecal carriers’ characteristics at admission Patients (%age) among the non ESBL-E faecal carriers. ESBL-E faecal car- Age (years, mean ± SD) 61 ± 22 riage had thus a positive predictive value (PPV) of 40%, a Sex ratio (women/men) 0,49 18/37 negative predictive value (NPV) of 100%, a sensitivity of Simplified Acute Physiology Score 2 (mean ± SD) 50 ± 32 100% and a specificity of 10% for ESBL-E causing the VAP. Admission from community 24/55 44% Admission from another hospitalization unit 31/55 56% Alternatives to carbapenems D28 mortality 19/54 35% In vitro, all the available isolates (n = 44) were suscep- tible to imipenem, ertapenem, ceftolozane-tazobactam 1-year mortality 20/45 44% and ceftazidime-avibactam, 43/44 to temocillin and to Escherichia coli carriage 37/55 67% piperacillin-tazobactam (according to the EUCAST 2016 Klebsiella pneumoniae carriage 16/55 29% Version 6.0 breakpoint recommandations). Citrobacter koseri carriage 2/55 3% Citrobacter freundii carriage 1/55 3% Discussion Serratia fonticola carriage 1/55 1% ESBL-E fecal carriage rate was 9% with only one case of ESBL-E cross-transmission whereas 6 cases of ESBL-E tract infection (K. pneumoniae). Three isolates involved in acquisition were observed. In case of subsequent ESBL-E pneumonia episodes (1 K. pneumoniae: 37I and 2 E. coli: infection, our data demonstrate that the colonizing 2I and 15I) were also available for PFGE analysis. The ESBL-E strain is indeed involved but it remains a rare PFGE analysis, according to Tenover’s criteria, classified event conferring poor predictive value to ESBL-E the strains 15I and 37I as indistinguishable from strains 15 colonization status for subsequent ESBL-E infection. and 37 respectively and closely related which means prob- A prevalence of ESBL-E faecal carriage of 9% is con- ably the same strain for 2I when compared to strain 2 sistent with a previous rate of 13,2% found in another which confirmed that the same clone was involved in col- study [22]. Most of the ESBL genes were of CTX-M onisation and infection (Figs. 2 and 3). Both VAP occurred group as previously described [2, 3]. Only 6 patients early in the ICU course (2 and 3 days after intubation). (1%) acquired ESBL-E fecal carriage during their stay in ICU and this can be over-estimated. In fact, the rate of ESBLE-E VAP prediction among ESBL-E faecal carriers false negatives is a major concern regarding ESBL-E During the study, 433 patients received mechanical ventila- screening by rectal swab and 2 patients acquired the tion among whom 39 VAP were observed: 34 non-ESBL-E ESBL-E in only 4 days, suggesting a possible false nega- VAP among the non ESBL-E faecal carriers, 3 non-ESBL-E tive screening at admission [23]. However, the low rate of ESBL faecal carriage cross Table 2 ESBL-E faecal carriage risk factors transmission (1%), even among patients acquiring faecal ESBL-E faecal carriage risk factors Patients (%age) carriage in the ICU, underlines the respect of isolation pro- cedures by ICU healthcare givers but also the limitation of ESBL-E previous colonization within 12 months 16/55 29% these measures as suggested by Tschudin-Sutter et al. [10]. Travel in a ESBL-E endemic area within 12 months 2/55 3,6% These results are consistent with those of three recent Previous hospitalization within 12 months 37/55 67% studies but our study is the first assessing ESBL-E clonal Health-care associated 26/55 47% dissemination in ICU by PFGE. One shows no case of Previous antimicrobial therapy within 12 months 35/47 74% cross transmission with the respect of the sole standard Penicillin 26/41 63% hygiene precautions in 3 Dutch hospitals but the study did not focus on ICU [11]. The second found only two 3rd generation cephalosporins 17/41 41% cases of cross transmission in a ICU with no single room Fluroquinolones 9/41 22% but the major limitation of this work is that no clonal Trimethoprim/sulfamethoxazole 7/41 17% analysis (by PFGE or whole genome sequencing) was Aminoglycosids 9/41 22% performed [22]. The third one found only one case of 0 risk factor 10/47 21% cross transmission in a medical ICU by repetitive 1 risk factor 5/47 11% element sequence-based PCR (repPCR) [24]. RepPCRis another tool to assess clonality based on the amplifica- 2 risk factors 9/47 19% tion of repetitive and non-coding parts of the genome 3 risk factors 12/47 26% but PFGE has a better ability to discriminate between 4 risk factors 11/47 23% E. coli isolates belonging to different subtypes [25]. 5 risk factors 0/47 0% New techniques such as whole genome sequencing or Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 5 of 7 Fig. 2 PFGE analysis for Escherichia.coliPFGE migration for Escherichia coli colonizing isolates. 8C and 18C: duplicate colonizing isolates used as positive control. 2I and 15I: infecting isolates. L: ladder Maldi-Tof clonality determination will provide an easier Another mechanism could correspond to the expansion of and faster assessment of cross-transmission avoiding time- a previously present but not detectable ESBL-E clone. This and staff-consuming techniques as PFGE [26, 27]. non detectable clone could be acquired in the community These data suggest that other mechanisms than cross or during a previous hospitalization. Antimicrobial therapy transmission occur in ICU and should be investigated to before admission or at the early phase of the ICU stay is better fight ESBL-E faecal carriage acquisition. In fact, be- thought to favor such ESBL-E expansion [29]. sides clonal dissemination, ESBL plasmid-mediated dis- The fact that only 6/38 ESBL-E faecal carriers with in- semination can occur with horizontal transfer of genetic fection had a proven subsequent ESBL-E infection ques- determinants for antimicrobial resistance which is en- tions the systematic use of carbapenems in that case, hanced during the exposure to antibiotics [28]. Neverthe- currently a hot topic [30–32]. Piperacillin-tazobactam, less, ESBL gene and plasmid incompatibility groups ceftazidime-avibactam and ceftolozane-tazobactam could determinations (data not shown for incompatibility groups) represent safe alternatives to spare carbapenems [33–36]. do not suggest horizontal transfer to be involved even if Regarding piperacillin-tazobactam, the only randomized definitive conclusions cannot be drawn for 8 of the strains. controlled trial available did not manage to prove the Fig. 3 PFGE analysis for Klebsiella pneumoniaPFGE migration for Klebsiella pneumoniae colonizing isolates. Patient 3 was colonized with both E. coli and K. pneumonia. 37I: infecting strain. 39CT: isolate involved in cross-transmission. L: ladder Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 6 of 7 non-inferiority of piperacillin-tazobactam compared with Abbreviations ESBL-E: Extended-spectrum beta-lactamase producing Enterobacterales; meropenem for the documented treatment of BSI due to ICU: Intensive care unit; NPV: Negative predictive value; PCR: Polymerase-chain 3CG-resistant E.coli or K. pneumoniae but some limita- reaction; PFGE: Pulsed-field gel electrophoresis; PPV: Positive predictive value; tions apply and so the results should be interpreted cau- repPCR: Repetitive element sequence-based PCR; VAP: Ventilator-associated pneumonia tiously [37, 38]. Nevertheless, in case of high-inoculum or in case of septic shock, carbapenems use remains a gold Acknowledgements standard according to the current guidelines [16, 23]. We thank Mrs Catherine Andre for technical assistance and the medical ICU team. This study confirms that ESBL-E VAP is a rare event even among ESBL-E carriers and that ESBL-E faecal car- Authors’ contributions riage has a very good NPV for ESBL-E VAP but a poor TC collected the strains, RP performed the collection of patients’ data, the PPV [39] but it demonstrates for the first time that the PCR and the PFGE and wrote the manuscript, AL participate to the collection of patients’ data, DG and VD designed the study, FMZ, AB, DG, AL and VD infecting strain corresponds to the colonizing one in substantially revised the manuscript. All authors read and approved the case of subsequent ESBL-E infection. The low rate of final manuscript. VAP (39/433, 9%) in this cohort can decrease the PPV of ESBL-E fecal carriage for subsequent infection. Funding This work was supported by “Centre National de la Recherche Scientifique” Besides, infection by ESBL-E seems to be more UMR 5234, Microbiologie Fondamentale et PAthogénicité and Pellegrin frequent in the case of Klebsiella pneumoniae than universitary hospital (Bordeaux, France) subventions. Escherichia coli as previously suggested [13, 40]. Unfor- Availability of data and materials tunately, in front of the small number of events we can- The datasets generated during the current study are not publicly available not definitely conclude here. due to the recommendations of French law regarding patients’ data but are Our study has some limitations. First some isolates were available from the corresponding author on reasonable request. missing (3 regarding acquired ESBL-E faecal carriage) and Ethics approval and consent to participate we cannot exclude other cases of cross-transmission. According to the French legislation, all patients or family were informed and Nevertheless, one of the 3 missing isolates was a Citrobac- non-opponent to the collect and analysis of the bacterial strains and the use ter freundii with no other patient carrying a ESBL Citro- of their data. bacter freundii at that time excluding a cross-transmission Consent for publication in that case. Not applicable Systematic ESBL-E faecal carriage screening has long been a standard of care for ICU-hospitalized patients but Competing interests RP, FMZ, TC, AL, VD and DG have not conflict of interest to declare. AB those results question the relevance of screening proce- reports congress fees from Pfizer and Gilead and a symposium moderation dures. In other terms, the paradigm of ESBL-E faecal car- for Basilea. riage in ICU patients is changing with a low rate of cross Author details transmission and a majority of imported ESBL-E. Medical Intensive Care Unit, CHU Bordeaux, Pellegrin universitary hospital, Investigation of the mechanisms leading to plasmid- Place Amélie Raba-Léon, F-33000 Bordeaux, France. UMR 5234 CNRS, mediated dissemination or to the expansion of ESBL Bordeaux University, F-33000 Bordeaux, France. Bacteriology laboratory, CHU Bordeaux, F-33000 Bordeaux, France. Hygiene unit, CHU Bordeaux, F-33000 clones up to detectable ESBL faecal carriage is also Bordeaux, France. needed to resolve ESBL-E colonization issue. Received: 22 March 2019 Accepted: 4 July 2019 Conclusions In this single-centre ICU study, a 9% rate of ESBL-E faecal References carriers was observed. Only 1% of patients acquired the 1. Carlet J. The World Alliance Against Antibiotic Resistance: Consensus for a ESBL-E faecal carriage during their ICU stay with only one Declaration. Clin Infect Dis. 2015;60:1837–41. 2. Woerther P-L, Burdet C, Chachaty E, Andremont A. Trends in Human Fecal case of cross-transmission. Interestingly, as far as we know, Carriage of Extended-Spectrum -Lactamases in the Community: Toward the our study demonstrates for the first time by PFGE that the Globalization of CTX-M. Clin Microbiol Rev. 2013;26:744–58. colonizing strain is indeed the infecting one in case of sub- 3. Karanika S, Karantanos T, Arvanitis M, Grigoras C, Mylonakis E. Fecal Colonization With Extended-spectrum Beta-lactamase–Producing sequent ESBL-E infection. Nevertheless, only 6/55 ESBL-E Enterobacteriaceae and Risk Factors Among Healthy Individuals: A faecal carriers were subsequently infected by a proven Systematic Review and Metaanalysis. Clin Infect Dis. 2016;63:310–8. ESBL-E strain. A negative ESBL-E faecal carriage ruled out 4. Flokas ME, Alevizakos M, Shehadeh F, Andreatos N, Mylonakis E. ESBL- producing Enterobacteriaceae Colonization in Long-Term Care Facilities its participation in VAP but positive predictive value was (LTCFs): A Systematic Review and Meta–analysis. Int J Antimicrob Agents. poor. The paradigm of ICU transmitted ESBL-E faecal car- 2017 [cited 2017 Oct 6]; Available from: http://linkinghub.elsevier.com/ riage may be changing with a majority of imported ESBL-E retrieve/pii/S0924857917302959. 5. Nicolas-Chanoine M-H, Gruson C, Bialek-Davenet S, Bertrand X, Thomas-Jean F, and a low rate of cross transmission. Relevance of system- Bert F, et al. 10-Fold increase (2006-11) in the rate of healthy subjects with atic ESBL-E faecal screening at ICU admission and during extended-spectrum -lactamase-producing Escherichia coli faecal carriage in a ICU stay needs further investigation. Parisian check-up centre. J Antimicrob Chemother. 2013;68:562–8. Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 7 of 7 6. Boyer A, Couallier V, Clouzeau B, Lasheras A, M’zali F, Kann M, et al. Control 24. Alves M, Lemire A, Decré D, Margetis D, Bigé N, Pichereau C, et al. of extended-spectrum β-lactamase–producing Enterobacteriaceae Extended-spectrum beta-lactamase − producing enterobacteriaceae in the nosocomial acquisition in an intensive care unit: A time series regression intensive care unit: acquisition does not mean cross-transmission. BMC analysis. Am J Infect Control. 2015;43:1296–301. Infect Dis. 2016;16. [cited 2017 Oct 6] Available from: http://bmcinfectdis. 7. Zahar J-R, Lesprit P, Ruckly S, Eden A, Hikombo H, Bernard L, et al. biomedcentral.com/articles/10.1186/s12879-016-1489-z. Predominance of healthcare-associated cases among episodes of community- 25. Bae IK, Kim J, Sun JYH, Jeong SH, Kim Y-R, Wang K-K, et al. Comparison of onset bacteraemia due to extended-spectrum β-lactamase-producing pulsed-field gel electrophoresis & repetitive sequence-based PCR methods Enterobacteriaceae. Int J Antimicrob Agents. 2017;49:67–73. for molecular epidemiological studies of Escherichia coli clinical isolates. Indian J Med Res. 2014;140:679–85. 8. Arnan M, Gudiol C, Calatayud L, Liñares J, Dominguez MÁ, Batlle M, et al. 26. Clark CG, Kruczkiewicz P, Guan C, McCorrister SJ, Chong P, Wylie J, et al. Risk factors for, and clinical relevance of, faecal extended-spectrum Evaluation of MALDI-TOF mass spectroscopy methods for determination of β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic Escherichia coli pathotypes. J Microbiol Methods. 2013;94:180–91. patients with haematological malignancies. Eur J Clin Microbiol Infect Dis. 27. Ruppé E, Ghozlane A, Tap J, Pons N, Alvarez A-S, Maziers N, et al. Prediction 2011;30:355–60. of the intestinal resistome by a three-dimensional structure-based method. 9. Asakura T, Ikeda M, Nakamura A, Kodera S. Efficacy of empirical therapy with Nat Microbiol. 2018 [cited 2018 Dec 7]; Available from: http://www.nature. non-carbapenems for urinary tract infections with extended-spectrum com/articles/s41564-018-0292-6. beta-lactamase-producing Enterobacteriaceae. Int J Infect Dis. 2014;29:91–5. 28. Woerther P-L, Angebault C, Jacquier H, Hugede H-C, Janssens A-C, Sayadi S, 10. Tschudin-Sutter S, Frei R, Dangel M, Stranden A, Widmer AF. Rate of et al. Massive increase, spread, and exchange of extended spectrum transmission of extended-spectrum beta-lactamase–producing β-lactamase-encoding genes among intestinal Enterobacteriaceae in Enterobacteriaceae without contact isolation. Clin Infect Dis. 2012;55:1505–11. hospitalized children with severe acute malnutrition in Niger. Clin Infect Dis 11. Souverein D, Euser SM, Herpers BL, Hattink C, Houtman P, Popma A, et al. Off Publ Infect Dis Soc Am. 2011;53:677–85. No nosocomial transmission under standard hygiene precautions in short 29. Kim S, Covington A, Pamer EG. The intestinal microbiota: Antibiotics, term contact patients in case of an unexpected ESBL or Q&A E. coli positive colonization resistance, and enteric pathogens. Immunol Rev. 2017;279:90–105. patient: a one-year prospective cohort study within three regional hospitals. 30. Stupica D, Lusa L, Klevišar MN, Terzić S, Pirš M, Premru MM, et al. Should we Antimicrob Resist Infect Control. 2017;6. [cited 2017 Oct 6] Available from: consider faecal colonisation with extended-spectrum β-lactamase-producing http://aricjournal.biomedcentral.com/articles/10.1186/s13756-017-0228-6. Enterobacteriaceae in empirical therapy of community-onset sepsis? Int J 12. Dziri R, Klibi N, Alonso CA, Said LB, Bellaaj R, Slama KB, et al. Characterization Antimicrob Agents. 2017;50:564–71. of extended-spectrum β-lactamase (ESBL)-producing Klebsiella, 31. Carbonne H, Le Dorze M, Bourrel A-S, Poupet H, Poyart C, Cambau E, et al. Enterobacter, and Citrobacter obtained in environmental samples of a Relation between presence of extended-spectrum β-lactamase-producing Tunisian hospital. Diagn Microbiol Infect Dis. 2016;86:190–3. Enterobacteriaceae in systematic rectal swabs and respiratory tract 13. Gorrie CL, Mirčeta M, Wick RR, Edwards DJ, Thomson NR, Strugnell RA, et al. specimens in ICU patients. Ann Intensive Care. 2017;7. [cited 2017 Oct 6] Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Available from: http://annalsofintensivecare.springeropen.com/articles/10.11 Infection in Intensive Care Patients. Clin Infect Dis. 2017;65:208–15. 86/s13613-017-0237-x. 14. Tansarli GS, Karageorgopoulos DE, Kapaskelis A, Falagas ME. Impact of 32. Jalalzaï W, Boutrot M, Guinard J, Guigon A, Bret L, Poisson D-M, et al. antimicrobial multidrug resistance on inpatient care cost: an evaluation of Cessation of screening for intestinal carriage of extended-spectrum the evidence. Expert Rev Anti-Infect Ther. 2013;11:321–31. β-lactamase-producing Enterobacteriaceae in a low-endemicity intensive 15. Lindblom A, Karami N, Magnusson T, Åhrén C. Subsequent infection with care unit with universal contact precautions. Clin Microbiol Infect. 2017 extended-spectrum β-lactamase-producing Enterobacteriaceae in patients [cited 2017 Dec 4]; Available from: http://linkinghub.elsevier.com/retrieve/ with prior infection or fecal colonization. Eur J Clin Microbiol Infect Dis Off pii/S1198743X17304329. Publ Eur Soc Clin Microbiol. 2018;37:1491–7. 33. Boucher A, Meybeck A, Patoz P, Valette M, Thellier D, Delannoy PY, et al. 16. Bruyère R, Vigneron C, Bador J, Aho S, Toitot A, Quenot J-P, et al. Alternatives to carbapenems in ventilator-associated pneumonia due to Significance of Prior Digestive Colonization With Extended-Spectrum ESBL-producing Enterobacteriaceae. J Inf Secur. 2016;73:293–6. β-Lactamase–Producing Enterobacteriaceae in Patients With Ventilator-Associated 34. Torres A, Zhong N, Pachl J, Timsit J-F, Kollef M, Chen Z, et al. Ceftazidime- Pneumonia. Crit Care Med. 2015;1. avibactam versus meropenem in nosocomial pneumonia, including 17. Société française d’hygiène hospitalière (SF2H). Prévention de la ventilator-associated pneumonia (REPROVE): a randomised, double-blind, transmission croisée: précations complémentaires contact. 2009;XII:81. phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–95. 18. ADARPEF, GFRUP, Leone M, Bouadma L, Bouhemad B, Brissaud O, et al. Brief 35. Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. summary of French guidelines for the prevention, diagnosis and treatment Ceftolozane-tazobactam compared with levofloxacin in the treatment of of hospital-acquired pneumonia in ICU. Ann Intensive Care. 2018;8. [cited complicated urinary-tract infections, including pyelonephritis: a randomised, 2018 Dec 7] Available from: https://annalsofintensivecare.springeropen.com/ double-blind, phase 3 trial (ASPECT-cUTI). Lancet Lond Engl. 2015;385:1949–56. articles/10.1186/s13613-018-0444-0. 36. Timsit J-F, Pilmis B, Zahar J-R. How Should We Treat Hospital-Acquired and 19. Saladin M, Cao VTB, Lambert T, Donay J-L, Herrmann J-L, Ould-Hocine Z, et Ventilator-Associated Pneumonia Caused by Extended-Spectrum β-Lactamase– al. Diversity of CTX-M beta-lactamases and their promoter regions from Producing Enterobacteriaceae? Semin Respir Crit Care Med. 2017;38:287–300. Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol Lett. 37. Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, et al. Effect of 2002;209:161–8. Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients 20. Saenz Y, Brinas L, Dominguez E, Ruiz J, Zarazaga M, Vila J, et al. Mechanisms With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone of Resistance in Multiple-Antibiotic-Resistant Escherichia coli Strains of Resistance: A Randomized Clinical Trial. JAMA. 2018;320:984–94. Human, Animal, and Food Origins. Antimicrob Agents Chemother. 38. Prevel R, Berdaï D, Boyer A. Antibiotics for Ceftriaxone-Resistant Gram- 2004;48:3996–4001. Negative Bacterial Bloodstream Infections. JAMA. 2019;321:613. 21. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et 39. Razazi K, Mekontso Dessap A, Carteaux G, Jansen C, Decousser J-W, de Prost N, al. Interpreting chromosomal DNA restriction patterns produced by pulsed- et al. Frequency, associated factors and outcome of multi-drug-resistant field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. intensive care unit-acquired pneumonia among patients colonized with 1995;33:2233. extended-spectrum β-lactamase-producing Enterobacteriaceae. Ann Intensive 22. Repessé X, Artiguenave M, Paktoris-Papine S, Espinasse F, Dinh A, Charron C, Care. 2017;7:61. et al. Epidemiology of extended-spectrum beta-lactamase-producing 40. Gurieva T, Dautzenberg MJD, Gniadkowski M, Derde LPG, Bonten MJM, Enterobacteriaceae in an intensive care unit with no single rooms. Ann Intensive Bootsma MCJ. The Transmissibility of Antibiotic-Resistant Enterobacteriaceae Care. 2017;7. [cited 2017 Oct 6] Available from: http://annalsofintensivecare. in Intensive Care Units. Clin Infect Dis. 2018;66:489–93. springeropen.com/articles/10.1186/s13613-017-0295-0 23. Dyakova E, Bisnauthsing KN, Querol-Rubiera A, Patel A, Ahanonu C, Tosas Auguet O, et al. Efficacy and acceptability of rectal and perineal sampling Publisher’sNote for identifying gastrointestinal colonization with extended spectrum Springer Nature remains neutral with regard to jurisdictional claims in β-lactamase Enterobacteriaceae. Clin Microbiol Infect. 2017;23:577.e1–3. published maps and institutional affiliations. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Antimicrobial Resistance & Infection Control Springer Journals

Extended spectrum beta-lactamase producing Enterobacterales faecal carriage in a medical intensive care unit: low rates of cross-transmission and infection

Download PDF
7 pages

Loading next page...
 
/lp/springer-journals/extended-spectrum-beta-lactamase-producing-enterobacterales-faecal-kaP7MHD1Tl

References (30)

Publisher
Springer Journals
Copyright
Copyright © 2019 by The Author(s).
Subject
Biomedicine; Medical Microbiology; Drug Resistance; Infectious Diseases
eISSN
2047-2994
DOI
10.1186/s13756-019-0572-9
Publisher site
See Article on Publisher Site

Abstract

Background: Extended-spectrum beta-lactamases-producing Enterobacterales (ESBL-E) are disseminating worldwide especially in Intensive Care Units (ICUs) and are responsible for increased health costs and mortality. The aims of this work were to study ESBL-E dissemination in ICU and to assess the impact of ESBL-E fecal carriage on subsequent infections during a non-outbreak situation. Methods: We therefore screened every patient at admission then once a week in a medical ICU between January and June 2015. Each ESBL-E isolate was characterized by ESBL genes PCR amplification and the clonal dissemination was assessed by Pulsed-Field Gel Electrophoresis (PFGE). Results: Among the 608 screened patients, 55 (9%) were colonized by ESBL-E. Forty-four isolates were available for further analysis. Most of them (43/44, 98%) contained a ESBL gene from the CTX-M group. Only one case of ESBL-E cross-transmission occurred, even for acquired ESBL-E colonization. Subsequent infection by ESBL-E occurred in 6/55 (11%) patients and infecting ESBL-E strains were the colonizing ones. ESBL-E faecal carriage had a negative predictive value of 100% and a positive predictive value of 40% to predict ESBL-E ventilator associated-pneumonia (VAP). Alternatives to carbapenems consisting in piperacillin-tazobactam, ceftolozane-tazobactam and ceftazidime-avibactam were all active on this panel of ESBL-E. Conclusions: ESBL-E expansion and acquisition in ICU in a non-outbreak situation are not any more fully explained by cross-transmission. Mechanisms underlying ESBL-E dissemination in ICU are still to investigate. Interestingly, as far as we know, our study demonstrates for the first time by PFGE that the colonizing strain is indeed the infecting one in case of subsequent ESBL-E infection. Nevertheless, subsequent ESBL-E infection remains a rare event conferring poor positive predictive value for ESBL-E colonization to predict ESBL-E VAP. Relevance of systematic ESBL-E faecal screening at ICU admission and during ICU stay needs further investigation. Keywords: Extended-spectrum beta-lactamase, Carriage, Cross-transmission, Infection, Ventilator-associated pneumonia, Intensive care * Correspondence: renaud.prevel@hotmail.fr Medical Intensive Care Unit, CHU Bordeaux, Pellegrin universitary hospital, Place Amélie Raba-Léon, F-33000 Bordeaux, France UMR 5234 CNRS, Bordeaux University, F-33000 Bordeaux, France Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 2 of 7 Background year with a mean length of stay of 5 days. All patients The increase in antimicrobial resistance remains a major were hospitalized in single rooms. Standard isolation threat [1]. Among resistant bacteria, extended-spectrum procedures for all patients and contact isolation proce- β-lactamase-producing Enterobacterales (ESBL-E) are of dures for ESBL-E faecal carriers were applied according special concern. In fact, ESBL-E faecal carriage is increas- to the French Society of Hygiene guidelines [17] includ- ing worldwide [2, 3] , especially in long term care facilities ing hand hygiene procedures, dedicated medical supplies and ICUs, but even among healthy people with up to ten- and single room. fold increase in a 5 years French Survey [4, 5]. ESBL-E fae- For each ESBL-E carriers, demographic information, cal carriage rates vary between western and non-western medical history, exposure to antibiotics for the past 12 countries probably because of discrepancies in water sani- months, prior ESBL-E fecal carriage for the past 12 tation procedures (from 1 to 6% in Europe and North months, hospitalization or health-care facility contact for America but up to 60% in India) [3] . Known risk factors the past 12 months and mortality at day 28 and year 1 are previous antibiotic exposure, previous admission to a were retrospectively collected through medical records. healthcare facility, previous hospitalization and previous The patients were characterized as imported carriers if ESBL-E carriage [6–8]. Cross-transmission in ICU has they were colonized at admission (from the community been mainly described during outbreaks leading to en- or from a non-ICU medical unit) and acquired carriers if forcement of hygiene isolation procedures [9]. However, the first screening was negative but any of the weekly hygiene procedures were not able to fully prevent ESBL-E screening was subsequently positive. Recording of pa- increase in ICU despite increased standard precautions tients suffering from VAP or pneumonia without intub- and an efficient prevention from nosocomial cross- ation was made retrospectively through our prospective transmission [10, 11]. The environment of healthcare fa- patient database. Patient status was assessed by two cilities (such as floors and walls contamination) was also independent clinicians for all data including the con- suspected to play a role in ESBL-E cross-transmission but firmation of VAP diagnosis according to French current its role does not seem to be that important [12]. Finally, guidelines [18]. Bloodstream infection was defined by little is known about the mechanisms of ESBL-E faecal any positive blood culture except for coagulase-negative carriage dissemination during ICU stay in a non-outbreak Staphylococcus. situation when cross-transmission by healthcare workers is controlled by thorough hygiene procedures. Samples processing Moreover, to date, the link between ESBL-E faecal car- Each rectal swab was inoculated on the chromID ESBL® riage and the risk of subsequent ESBL-E infection is not plate for 16-24hours at 37°C. Confirmation of the pres- fully understood even if colonization by ESBL Klebsiella ence of ESBL was assessed by MAST AMPC&ESBL de- pneumoniae seems to be at higher risk than colonization tection discs D68C® (Mast Group). Identification of each by Escherichia coli [13]. A better understanding of this selected colony was assessed by mass spectrometry link between colonization and infection is of paramount (Maldi Biotyper Microflex®, Brucker). If 2 different importance since ESBL-E ICU infections lead to in- ESBL-E isolates were identified on a screening test, each creased healthcare costs, length of stay and mortality isolate was characterized individually. In case of positive [14]. In a non-ICU low-endemy environment, ESBL-E in- screening at admission, the isolates collected during fections among ESBL-E faecal carriers were shown to be a weekly screenings were considered as duplicate if being rare event but this remains an issue regarding ICU pa- the same species and carrying the same resistance genes tients, especially those developing ventilator-associated and not investigated. Susceptibilities to ceftolozane- pneumonia (VAP) [15, 16]. The aim of this work was to tazobactam and ceftazidime-avibactam were assessed by assess the ESBL-E dissemination (acquisition and clonal E-test® (BioMérieux). ESBL-E isolates were then stored transmission) and subsequent infection among ESBL-E at -20°C. faecal carriers in ICU during a non-outbreak situation. ESBL type determination Methods Detection and characterization of bla genes were Design of the study performed by multiplex PCRs for bla , bla , CTX − M SHV st th From January 1 to June 30 2015, all patients of the bla , and bla and then confirmed by simplex TEM OXA-1 medical ICU at Pellegrin Hospital, a 1300-bed tertiary PCRs [19]. center, were screened by rectal swab at admission and then weekly until they were discharged and isolates were Clonality assessment by pulsed-field gel electrophoresis collected. Our ICU is divided into 2 ICU wards of re- The clonality of ESBL-E dissemination in the ICU was spectively 13 and 14 beds and one 12 beds ward dedi- determined by pulsed-field gel electrophoresis (PFGE) of cated to post-intensive care, admitting 1200 patients per XbaI-digested genomic DNA of all collected ESBL-E Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 3 of 7 isolates available as previously described [20]. Patterns were not available for analysis (loss of ESBL after freezing were visually compared and analyzed according to previ- n = 8, the isolate did not grow after – 20°C freezing n =83, ously reported criteria [21]. Plasmids were not analyzed by and the wrong isolate was frozen at -20°C n = 82)). Among PFGE as concerns exist about its discriminative power. these 13 isolates, 10 were imported and 3 acquired in ICU. One of the missing acquired ESBL-E isolate was a Statistics analysis Citrobacter freundii with no other patient carrying that Quantitative variables were summarized as mean ± standard bacteria during his/her stay in ICU. Forty-four isolates deviation or median (interquartile range). Categorical data from faecal carriage were available for PFGE and 2 isolates were summarized as count (%). from weekly samplings of imported ESBL-E faecal carriage were considered as duplicate and used as positive control Results (8C and 18C, Fig. 2). ESBL prevalence in ICU patients No case of cross transmission regarding E. coli and Among 613 patients admitted to ICU during the 6 only one case of K. pneumoniae cross transmission months study-period, 608 were screened (371 (61%) only (39CT, Fig. 3) was identified. ESBL gene PCR identified at admission and 237 (39%) at admission and weekly 103 different ESBL-E genes mostly from bla CTX-M during their ICU stay). Fifty-five (9%) were positive for (43, 42%), bla (27, 26%), bla (18, 17%) and TEM OXA-1 ESBL-E faecal carriage. No ESBL-E outbreak was de- bla (14, 15%) groups. SHV tected during the study. Only 6 (1%) patients acquired ESBL-E faecal carriage during their ICU stay (Figure 1): ESBL-E infections among carriers during ICU stay 2 came from the community and 4 were already hospi- Among the 55 ESBL-E faecal carriers, 38 were infected talized at our universitary hospital before the transfer in and 16 of them received carbapenems as part of ICU. Mean time to acquisition was 31 (±17) days, me- empirical antimicrobial therapy during their ICU stay. dian time 30 (4-53) days. Each patient who acquired Infection sites were distributed as follow: pulmonary in- ESBL-E during ICU stay received several courses of fections 23/38, bloodstream infection 9/38 (5 patients broad-spectrum antimicrobial therapy between time of having both pulmonary and bloodstream infections), admission in ICU and ESBL-E acquisition. skin infection 5/38, urinary tract infection 4/38, abdom- inal infection 2/38. Among the 38 infected ESBL-E ESBL-E faecal carriers’ characteristics and risk factors faecal carriers, a non ESBL-E isolate was identified for ESBL-E faecal carriers are described in Table 1. ESBL-E 22 patients and 10 patients had no documentation be- faecal carriers were mainly colonised with Escherichia cause cultures remain sterile. Thus, only 6/38 patients coli (37/55, 67%), 37/47 (79%) patients had at least 1 risk were subsequently infected by an ESBL-E. None of these factor of EBL-E faecal carriage with 32/47 (68%) having 6 ESBL-E infected patients had acquired the ESBL-E fae- several risk factors (Table 2) including previous anti- cal carriage during their ICU stay. Respectively for E. coli microbial therapy Table 2. and K. pneumonia carriers, 2/37 (6%) and 4/16 (25%) were subsequently infected with ESBL-E. ESBL-E clonality assessment by pulsed-field gel The 6 ESBL-E infections were as follow: 2 ventilator- electrophoresis (Figs. 2 and 3) associated pneumonias (VAP), 2 pneumonias in non- Fifty-seven ESBL-E isolates from faecal carriage were intubated patients (2 E. coli and 2 K. pneumoniae), 1 collected from the 55 patients. Unfortunately, 13 isolates bloodstream infection (K. pneumoniae) and 1 urinary Fig. 1 Flow-chart Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 4 of 7 Table 1 ESBL-E faecal carriers’ characteristics at admission VAP among the ESBL-E faecal carriers (n = 55), 2 ESBL-E VAP among the ESBL-E faecal carriers and 0 ESBL-E VAP ESBL-E faecal carriers’ characteristics at admission Patients (%age) among the non ESBL-E faecal carriers. ESBL-E faecal car- Age (years, mean ± SD) 61 ± 22 riage had thus a positive predictive value (PPV) of 40%, a Sex ratio (women/men) 0,49 18/37 negative predictive value (NPV) of 100%, a sensitivity of Simplified Acute Physiology Score 2 (mean ± SD) 50 ± 32 100% and a specificity of 10% for ESBL-E causing the VAP. Admission from community 24/55 44% Admission from another hospitalization unit 31/55 56% Alternatives to carbapenems D28 mortality 19/54 35% In vitro, all the available isolates (n = 44) were suscep- tible to imipenem, ertapenem, ceftolozane-tazobactam 1-year mortality 20/45 44% and ceftazidime-avibactam, 43/44 to temocillin and to Escherichia coli carriage 37/55 67% piperacillin-tazobactam (according to the EUCAST 2016 Klebsiella pneumoniae carriage 16/55 29% Version 6.0 breakpoint recommandations). Citrobacter koseri carriage 2/55 3% Citrobacter freundii carriage 1/55 3% Discussion Serratia fonticola carriage 1/55 1% ESBL-E fecal carriage rate was 9% with only one case of ESBL-E cross-transmission whereas 6 cases of ESBL-E tract infection (K. pneumoniae). Three isolates involved in acquisition were observed. In case of subsequent ESBL-E pneumonia episodes (1 K. pneumoniae: 37I and 2 E. coli: infection, our data demonstrate that the colonizing 2I and 15I) were also available for PFGE analysis. The ESBL-E strain is indeed involved but it remains a rare PFGE analysis, according to Tenover’s criteria, classified event conferring poor predictive value to ESBL-E the strains 15I and 37I as indistinguishable from strains 15 colonization status for subsequent ESBL-E infection. and 37 respectively and closely related which means prob- A prevalence of ESBL-E faecal carriage of 9% is con- ably the same strain for 2I when compared to strain 2 sistent with a previous rate of 13,2% found in another which confirmed that the same clone was involved in col- study [22]. Most of the ESBL genes were of CTX-M onisation and infection (Figs. 2 and 3). Both VAP occurred group as previously described [2, 3]. Only 6 patients early in the ICU course (2 and 3 days after intubation). (1%) acquired ESBL-E fecal carriage during their stay in ICU and this can be over-estimated. In fact, the rate of ESBLE-E VAP prediction among ESBL-E faecal carriers false negatives is a major concern regarding ESBL-E During the study, 433 patients received mechanical ventila- screening by rectal swab and 2 patients acquired the tion among whom 39 VAP were observed: 34 non-ESBL-E ESBL-E in only 4 days, suggesting a possible false nega- VAP among the non ESBL-E faecal carriers, 3 non-ESBL-E tive screening at admission [23]. However, the low rate of ESBL faecal carriage cross Table 2 ESBL-E faecal carriage risk factors transmission (1%), even among patients acquiring faecal ESBL-E faecal carriage risk factors Patients (%age) carriage in the ICU, underlines the respect of isolation pro- cedures by ICU healthcare givers but also the limitation of ESBL-E previous colonization within 12 months 16/55 29% these measures as suggested by Tschudin-Sutter et al. [10]. Travel in a ESBL-E endemic area within 12 months 2/55 3,6% These results are consistent with those of three recent Previous hospitalization within 12 months 37/55 67% studies but our study is the first assessing ESBL-E clonal Health-care associated 26/55 47% dissemination in ICU by PFGE. One shows no case of Previous antimicrobial therapy within 12 months 35/47 74% cross transmission with the respect of the sole standard Penicillin 26/41 63% hygiene precautions in 3 Dutch hospitals but the study did not focus on ICU [11]. The second found only two 3rd generation cephalosporins 17/41 41% cases of cross transmission in a ICU with no single room Fluroquinolones 9/41 22% but the major limitation of this work is that no clonal Trimethoprim/sulfamethoxazole 7/41 17% analysis (by PFGE or whole genome sequencing) was Aminoglycosids 9/41 22% performed [22]. The third one found only one case of 0 risk factor 10/47 21% cross transmission in a medical ICU by repetitive 1 risk factor 5/47 11% element sequence-based PCR (repPCR) [24]. RepPCRis another tool to assess clonality based on the amplifica- 2 risk factors 9/47 19% tion of repetitive and non-coding parts of the genome 3 risk factors 12/47 26% but PFGE has a better ability to discriminate between 4 risk factors 11/47 23% E. coli isolates belonging to different subtypes [25]. 5 risk factors 0/47 0% New techniques such as whole genome sequencing or Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 5 of 7 Fig. 2 PFGE analysis for Escherichia.coliPFGE migration for Escherichia coli colonizing isolates. 8C and 18C: duplicate colonizing isolates used as positive control. 2I and 15I: infecting isolates. L: ladder Maldi-Tof clonality determination will provide an easier Another mechanism could correspond to the expansion of and faster assessment of cross-transmission avoiding time- a previously present but not detectable ESBL-E clone. This and staff-consuming techniques as PFGE [26, 27]. non detectable clone could be acquired in the community These data suggest that other mechanisms than cross or during a previous hospitalization. Antimicrobial therapy transmission occur in ICU and should be investigated to before admission or at the early phase of the ICU stay is better fight ESBL-E faecal carriage acquisition. In fact, be- thought to favor such ESBL-E expansion [29]. sides clonal dissemination, ESBL plasmid-mediated dis- The fact that only 6/38 ESBL-E faecal carriers with in- semination can occur with horizontal transfer of genetic fection had a proven subsequent ESBL-E infection ques- determinants for antimicrobial resistance which is en- tions the systematic use of carbapenems in that case, hanced during the exposure to antibiotics [28]. Neverthe- currently a hot topic [30–32]. Piperacillin-tazobactam, less, ESBL gene and plasmid incompatibility groups ceftazidime-avibactam and ceftolozane-tazobactam could determinations (data not shown for incompatibility groups) represent safe alternatives to spare carbapenems [33–36]. do not suggest horizontal transfer to be involved even if Regarding piperacillin-tazobactam, the only randomized definitive conclusions cannot be drawn for 8 of the strains. controlled trial available did not manage to prove the Fig. 3 PFGE analysis for Klebsiella pneumoniaPFGE migration for Klebsiella pneumoniae colonizing isolates. Patient 3 was colonized with both E. coli and K. pneumonia. 37I: infecting strain. 39CT: isolate involved in cross-transmission. L: ladder Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 6 of 7 non-inferiority of piperacillin-tazobactam compared with Abbreviations ESBL-E: Extended-spectrum beta-lactamase producing Enterobacterales; meropenem for the documented treatment of BSI due to ICU: Intensive care unit; NPV: Negative predictive value; PCR: Polymerase-chain 3CG-resistant E.coli or K. pneumoniae but some limita- reaction; PFGE: Pulsed-field gel electrophoresis; PPV: Positive predictive value; tions apply and so the results should be interpreted cau- repPCR: Repetitive element sequence-based PCR; VAP: Ventilator-associated pneumonia tiously [37, 38]. Nevertheless, in case of high-inoculum or in case of septic shock, carbapenems use remains a gold Acknowledgements standard according to the current guidelines [16, 23]. We thank Mrs Catherine Andre for technical assistance and the medical ICU team. This study confirms that ESBL-E VAP is a rare event even among ESBL-E carriers and that ESBL-E faecal car- Authors’ contributions riage has a very good NPV for ESBL-E VAP but a poor TC collected the strains, RP performed the collection of patients’ data, the PPV [39] but it demonstrates for the first time that the PCR and the PFGE and wrote the manuscript, AL participate to the collection of patients’ data, DG and VD designed the study, FMZ, AB, DG, AL and VD infecting strain corresponds to the colonizing one in substantially revised the manuscript. All authors read and approved the case of subsequent ESBL-E infection. The low rate of final manuscript. VAP (39/433, 9%) in this cohort can decrease the PPV of ESBL-E fecal carriage for subsequent infection. Funding This work was supported by “Centre National de la Recherche Scientifique” Besides, infection by ESBL-E seems to be more UMR 5234, Microbiologie Fondamentale et PAthogénicité and Pellegrin frequent in the case of Klebsiella pneumoniae than universitary hospital (Bordeaux, France) subventions. Escherichia coli as previously suggested [13, 40]. Unfor- Availability of data and materials tunately, in front of the small number of events we can- The datasets generated during the current study are not publicly available not definitely conclude here. due to the recommendations of French law regarding patients’ data but are Our study has some limitations. First some isolates were available from the corresponding author on reasonable request. missing (3 regarding acquired ESBL-E faecal carriage) and Ethics approval and consent to participate we cannot exclude other cases of cross-transmission. According to the French legislation, all patients or family were informed and Nevertheless, one of the 3 missing isolates was a Citrobac- non-opponent to the collect and analysis of the bacterial strains and the use ter freundii with no other patient carrying a ESBL Citro- of their data. bacter freundii at that time excluding a cross-transmission Consent for publication in that case. Not applicable Systematic ESBL-E faecal carriage screening has long been a standard of care for ICU-hospitalized patients but Competing interests RP, FMZ, TC, AL, VD and DG have not conflict of interest to declare. AB those results question the relevance of screening proce- reports congress fees from Pfizer and Gilead and a symposium moderation dures. In other terms, the paradigm of ESBL-E faecal car- for Basilea. riage in ICU patients is changing with a low rate of cross Author details transmission and a majority of imported ESBL-E. Medical Intensive Care Unit, CHU Bordeaux, Pellegrin universitary hospital, Investigation of the mechanisms leading to plasmid- Place Amélie Raba-Léon, F-33000 Bordeaux, France. UMR 5234 CNRS, mediated dissemination or to the expansion of ESBL Bordeaux University, F-33000 Bordeaux, France. Bacteriology laboratory, CHU Bordeaux, F-33000 Bordeaux, France. Hygiene unit, CHU Bordeaux, F-33000 clones up to detectable ESBL faecal carriage is also Bordeaux, France. needed to resolve ESBL-E colonization issue. Received: 22 March 2019 Accepted: 4 July 2019 Conclusions In this single-centre ICU study, a 9% rate of ESBL-E faecal References carriers was observed. Only 1% of patients acquired the 1. Carlet J. The World Alliance Against Antibiotic Resistance: Consensus for a ESBL-E faecal carriage during their ICU stay with only one Declaration. Clin Infect Dis. 2015;60:1837–41. 2. Woerther P-L, Burdet C, Chachaty E, Andremont A. Trends in Human Fecal case of cross-transmission. Interestingly, as far as we know, Carriage of Extended-Spectrum -Lactamases in the Community: Toward the our study demonstrates for the first time by PFGE that the Globalization of CTX-M. Clin Microbiol Rev. 2013;26:744–58. colonizing strain is indeed the infecting one in case of sub- 3. Karanika S, Karantanos T, Arvanitis M, Grigoras C, Mylonakis E. Fecal Colonization With Extended-spectrum Beta-lactamase–Producing sequent ESBL-E infection. Nevertheless, only 6/55 ESBL-E Enterobacteriaceae and Risk Factors Among Healthy Individuals: A faecal carriers were subsequently infected by a proven Systematic Review and Metaanalysis. Clin Infect Dis. 2016;63:310–8. ESBL-E strain. A negative ESBL-E faecal carriage ruled out 4. Flokas ME, Alevizakos M, Shehadeh F, Andreatos N, Mylonakis E. ESBL- producing Enterobacteriaceae Colonization in Long-Term Care Facilities its participation in VAP but positive predictive value was (LTCFs): A Systematic Review and Meta–analysis. Int J Antimicrob Agents. poor. The paradigm of ICU transmitted ESBL-E faecal car- 2017 [cited 2017 Oct 6]; Available from: http://linkinghub.elsevier.com/ riage may be changing with a majority of imported ESBL-E retrieve/pii/S0924857917302959. 5. Nicolas-Chanoine M-H, Gruson C, Bialek-Davenet S, Bertrand X, Thomas-Jean F, and a low rate of cross transmission. Relevance of system- Bert F, et al. 10-Fold increase (2006-11) in the rate of healthy subjects with atic ESBL-E faecal screening at ICU admission and during extended-spectrum -lactamase-producing Escherichia coli faecal carriage in a ICU stay needs further investigation. Parisian check-up centre. J Antimicrob Chemother. 2013;68:562–8. Prevel et al. Antimicrobial Resistance and Infection Control (2019) 8:112 Page 7 of 7 6. Boyer A, Couallier V, Clouzeau B, Lasheras A, M’zali F, Kann M, et al. Control 24. Alves M, Lemire A, Decré D, Margetis D, Bigé N, Pichereau C, et al. of extended-spectrum β-lactamase–producing Enterobacteriaceae Extended-spectrum beta-lactamase − producing enterobacteriaceae in the nosocomial acquisition in an intensive care unit: A time series regression intensive care unit: acquisition does not mean cross-transmission. BMC analysis. Am J Infect Control. 2015;43:1296–301. Infect Dis. 2016;16. [cited 2017 Oct 6] Available from: http://bmcinfectdis. 7. Zahar J-R, Lesprit P, Ruckly S, Eden A, Hikombo H, Bernard L, et al. biomedcentral.com/articles/10.1186/s12879-016-1489-z. Predominance of healthcare-associated cases among episodes of community- 25. Bae IK, Kim J, Sun JYH, Jeong SH, Kim Y-R, Wang K-K, et al. Comparison of onset bacteraemia due to extended-spectrum β-lactamase-producing pulsed-field gel electrophoresis & repetitive sequence-based PCR methods Enterobacteriaceae. Int J Antimicrob Agents. 2017;49:67–73. for molecular epidemiological studies of Escherichia coli clinical isolates. Indian J Med Res. 2014;140:679–85. 8. Arnan M, Gudiol C, Calatayud L, Liñares J, Dominguez MÁ, Batlle M, et al. 26. Clark CG, Kruczkiewicz P, Guan C, McCorrister SJ, Chong P, Wylie J, et al. Risk factors for, and clinical relevance of, faecal extended-spectrum Evaluation of MALDI-TOF mass spectroscopy methods for determination of β-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic Escherichia coli pathotypes. J Microbiol Methods. 2013;94:180–91. patients with haematological malignancies. Eur J Clin Microbiol Infect Dis. 27. Ruppé E, Ghozlane A, Tap J, Pons N, Alvarez A-S, Maziers N, et al. Prediction 2011;30:355–60. of the intestinal resistome by a three-dimensional structure-based method. 9. Asakura T, Ikeda M, Nakamura A, Kodera S. Efficacy of empirical therapy with Nat Microbiol. 2018 [cited 2018 Dec 7]; Available from: http://www.nature. non-carbapenems for urinary tract infections with extended-spectrum com/articles/s41564-018-0292-6. beta-lactamase-producing Enterobacteriaceae. Int J Infect Dis. 2014;29:91–5. 28. Woerther P-L, Angebault C, Jacquier H, Hugede H-C, Janssens A-C, Sayadi S, 10. Tschudin-Sutter S, Frei R, Dangel M, Stranden A, Widmer AF. Rate of et al. Massive increase, spread, and exchange of extended spectrum transmission of extended-spectrum beta-lactamase–producing β-lactamase-encoding genes among intestinal Enterobacteriaceae in Enterobacteriaceae without contact isolation. Clin Infect Dis. 2012;55:1505–11. hospitalized children with severe acute malnutrition in Niger. Clin Infect Dis 11. Souverein D, Euser SM, Herpers BL, Hattink C, Houtman P, Popma A, et al. Off Publ Infect Dis Soc Am. 2011;53:677–85. No nosocomial transmission under standard hygiene precautions in short 29. Kim S, Covington A, Pamer EG. The intestinal microbiota: Antibiotics, term contact patients in case of an unexpected ESBL or Q&A E. coli positive colonization resistance, and enteric pathogens. Immunol Rev. 2017;279:90–105. patient: a one-year prospective cohort study within three regional hospitals. 30. Stupica D, Lusa L, Klevišar MN, Terzić S, Pirš M, Premru MM, et al. Should we Antimicrob Resist Infect Control. 2017;6. [cited 2017 Oct 6] Available from: consider faecal colonisation with extended-spectrum β-lactamase-producing http://aricjournal.biomedcentral.com/articles/10.1186/s13756-017-0228-6. Enterobacteriaceae in empirical therapy of community-onset sepsis? Int J 12. Dziri R, Klibi N, Alonso CA, Said LB, Bellaaj R, Slama KB, et al. Characterization Antimicrob Agents. 2017;50:564–71. of extended-spectrum β-lactamase (ESBL)-producing Klebsiella, 31. Carbonne H, Le Dorze M, Bourrel A-S, Poupet H, Poyart C, Cambau E, et al. Enterobacter, and Citrobacter obtained in environmental samples of a Relation between presence of extended-spectrum β-lactamase-producing Tunisian hospital. Diagn Microbiol Infect Dis. 2016;86:190–3. Enterobacteriaceae in systematic rectal swabs and respiratory tract 13. Gorrie CL, Mirčeta M, Wick RR, Edwards DJ, Thomson NR, Strugnell RA, et al. specimens in ICU patients. Ann Intensive Care. 2017;7. [cited 2017 Oct 6] Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Available from: http://annalsofintensivecare.springeropen.com/articles/10.11 Infection in Intensive Care Patients. Clin Infect Dis. 2017;65:208–15. 86/s13613-017-0237-x. 14. Tansarli GS, Karageorgopoulos DE, Kapaskelis A, Falagas ME. Impact of 32. Jalalzaï W, Boutrot M, Guinard J, Guigon A, Bret L, Poisson D-M, et al. antimicrobial multidrug resistance on inpatient care cost: an evaluation of Cessation of screening for intestinal carriage of extended-spectrum the evidence. Expert Rev Anti-Infect Ther. 2013;11:321–31. β-lactamase-producing Enterobacteriaceae in a low-endemicity intensive 15. Lindblom A, Karami N, Magnusson T, Åhrén C. Subsequent infection with care unit with universal contact precautions. Clin Microbiol Infect. 2017 extended-spectrum β-lactamase-producing Enterobacteriaceae in patients [cited 2017 Dec 4]; Available from: http://linkinghub.elsevier.com/retrieve/ with prior infection or fecal colonization. Eur J Clin Microbiol Infect Dis Off pii/S1198743X17304329. Publ Eur Soc Clin Microbiol. 2018;37:1491–7. 33. Boucher A, Meybeck A, Patoz P, Valette M, Thellier D, Delannoy PY, et al. 16. Bruyère R, Vigneron C, Bador J, Aho S, Toitot A, Quenot J-P, et al. Alternatives to carbapenems in ventilator-associated pneumonia due to Significance of Prior Digestive Colonization With Extended-Spectrum ESBL-producing Enterobacteriaceae. J Inf Secur. 2016;73:293–6. β-Lactamase–Producing Enterobacteriaceae in Patients With Ventilator-Associated 34. Torres A, Zhong N, Pachl J, Timsit J-F, Kollef M, Chen Z, et al. Ceftazidime- Pneumonia. Crit Care Med. 2015;1. avibactam versus meropenem in nosocomial pneumonia, including 17. Société française d’hygiène hospitalière (SF2H). Prévention de la ventilator-associated pneumonia (REPROVE): a randomised, double-blind, transmission croisée: précations complémentaires contact. 2009;XII:81. phase 3 non-inferiority trial. Lancet Infect Dis. 2018;18:285–95. 18. ADARPEF, GFRUP, Leone M, Bouadma L, Bouhemad B, Brissaud O, et al. Brief 35. Wagenlehner FM, Umeh O, Steenbergen J, Yuan G, Darouiche RO. summary of French guidelines for the prevention, diagnosis and treatment Ceftolozane-tazobactam compared with levofloxacin in the treatment of of hospital-acquired pneumonia in ICU. Ann Intensive Care. 2018;8. [cited complicated urinary-tract infections, including pyelonephritis: a randomised, 2018 Dec 7] Available from: https://annalsofintensivecare.springeropen.com/ double-blind, phase 3 trial (ASPECT-cUTI). Lancet Lond Engl. 2015;385:1949–56. articles/10.1186/s13613-018-0444-0. 36. Timsit J-F, Pilmis B, Zahar J-R. How Should We Treat Hospital-Acquired and 19. Saladin M, Cao VTB, Lambert T, Donay J-L, Herrmann J-L, Ould-Hocine Z, et Ventilator-Associated Pneumonia Caused by Extended-Spectrum β-Lactamase– al. Diversity of CTX-M beta-lactamases and their promoter regions from Producing Enterobacteriaceae? Semin Respir Crit Care Med. 2017;38:287–300. Enterobacteriaceae isolated in three Parisian hospitals. FEMS Microbiol Lett. 37. Harris PNA, Tambyah PA, Lye DC, Mo Y, Lee TH, Yilmaz M, et al. Effect of 2002;209:161–8. Piperacillin-Tazobactam vs Meropenem on 30-Day Mortality for Patients 20. Saenz Y, Brinas L, Dominguez E, Ruiz J, Zarazaga M, Vila J, et al. Mechanisms With E coli or Klebsiella pneumoniae Bloodstream Infection and Ceftriaxone of Resistance in Multiple-Antibiotic-Resistant Escherichia coli Strains of Resistance: A Randomized Clinical Trial. JAMA. 2018;320:984–94. Human, Animal, and Food Origins. Antimicrob Agents Chemother. 38. Prevel R, Berdaï D, Boyer A. Antibiotics for Ceftriaxone-Resistant Gram- 2004;48:3996–4001. Negative Bacterial Bloodstream Infections. JAMA. 2019;321:613. 21. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH, et 39. Razazi K, Mekontso Dessap A, Carteaux G, Jansen C, Decousser J-W, de Prost N, al. Interpreting chromosomal DNA restriction patterns produced by pulsed- et al. Frequency, associated factors and outcome of multi-drug-resistant field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol. intensive care unit-acquired pneumonia among patients colonized with 1995;33:2233. extended-spectrum β-lactamase-producing Enterobacteriaceae. Ann Intensive 22. Repessé X, Artiguenave M, Paktoris-Papine S, Espinasse F, Dinh A, Charron C, Care. 2017;7:61. et al. Epidemiology of extended-spectrum beta-lactamase-producing 40. Gurieva T, Dautzenberg MJD, Gniadkowski M, Derde LPG, Bonten MJM, Enterobacteriaceae in an intensive care unit with no single rooms. Ann Intensive Bootsma MCJ. The Transmissibility of Antibiotic-Resistant Enterobacteriaceae Care. 2017;7. [cited 2017 Oct 6] Available from: http://annalsofintensivecare. in Intensive Care Units. Clin Infect Dis. 2018;66:489–93. springeropen.com/articles/10.1186/s13613-017-0295-0 23. Dyakova E, Bisnauthsing KN, Querol-Rubiera A, Patel A, Ahanonu C, Tosas Auguet O, et al. Efficacy and acceptability of rectal and perineal sampling Publisher’sNote for identifying gastrointestinal colonization with extended spectrum Springer Nature remains neutral with regard to jurisdictional claims in β-lactamase Enterobacteriaceae. Clin Microbiol Infect. 2017;23:577.e1–3. published maps and institutional affiliations.

Journal

Antimicrobial Resistance & Infection Control – Springer Journals

Published: Jul 10, 2019

There are no references for this article.