Emerg Infect DisEmerging Infect. DisEIDEmerging Infectious Diseases1080-60401080-6059Centers for Disease Control and Prevention24963645407385613-163810.3201/eid2007.131638Letters to the EditorLetterCarbapenemase-producing Bacteria in Patients Hospitalized Abroad, FranceCarbapenemase-Producing Bacteria, FranceCompainFabriceDecréDominiqueFrazierIsabelleRamahefasoloAstridLavollayMarieCarbonnelleEtienneRostaneHidayethTackinArzuBerger-CarbonneAnnePodglajenIsabelleHôpital Européen Georges Pompidou, AP-HP, Paris, France (F. Compain, I. Frazier, A. Ramahefasolo, M. Lavollay, E. Carbonnelle, H. Rostane, A. Tackin, A. Berger-Carbonne, I. Podglajen); Université Pierre et Marie Curie, Paris (D. Decré); Université Paris Descartes, Paris (M. Lavollay, E. Carbonnelle, I. Podglajen); Collège de France, Centre de Recherche Interdisciplinaire en Biologie, Paris (I. Podglajen); Institut National de la Santé et de la Recherche Médicale, Paris (M. Lavollay, E. Carbonnelle, I. Podglajen)Address for correspondence: Isabelle Podglajen, Service de Microbiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015, Paris, France; email: isabelle.podglajen@egp.aphp.fr7201420712461248Keywords: carbapenemasecolonizationglycopeptide resistancehospitalization historyrepatriated patientsFrancebacteriaantimicrobial resistance
To the Editor: The emergence and rapid worldwide dissemination of carbapenemase-producing bacteria (CPB), especially carbapenemase-producing Enterobacteriaceae (CPE), have prompted public health authorities to reconsider prevention strategies to control the spread of these organisms (1–5). In France, national guidelines recommend systematic screening for commensal CPE and glycopeptide-resistant enterococci (GRE) in all patients admitted to hospitals who have been hospitalized in other countries during the preceding 12 months (6,7) (repatriated patients), independently of whether transfer was direct from hospital to hospital (DT) or not (NDT). These guidelines also recommend implementation of presumptive patient isolation and contact precautions on admission (6,7). We conducted a 33-month survey at Hôpital Européen Georges Pompidou (HEGP), a university teaching hospital in Paris, of CPE and GRE in repatriated patients; we also investigated incidence of extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae and carbapenemase-producing Acinetobacter baumannii and Pseudomonas spp. in the same patient group.
During November 2010–July 2013, a total of 541 patients who had previously been hospitalized in a total of 71 other countries were admitted to HEGP. Rectal swab specimens were taken from 510 patients; 82 (16.1%) were DT, 415 (81.4%) were NDT, and 13 (2.5%) had an unclear history of transfer. Median patient age was 61 (range 12–98) years; 70% of patients were male. Results of screening by using antibiotic-containing Luria Bertani broths for enrichment and plating on selective media were negative for 354 (69.4%) of the 510 patients surveyed; 33 (6.5%; 16 DT, 17 NDT) patients were colonized with >1 CPB and/or GRE and 123 (24.1%; 22 DT, 99 NDT, 2 unclear) with ESBL producers only. More specifically, 19.5% (16/82) of DT patients and 4.1% (17/415) of NDT patients were colonized with CPB and/or GRE (p<10−5 by χ2 test); 26.8% (22/82) of DT patients and 23.9% (99/415) of NDT patients were colonized with ESBL producers only (p = 0.67). Characteristics of the 33 patients carrying CPB and/or GRE are shown in the Table. Of all isolates, 191 produced ESBLs only.
Clinical and laboratory data on 33 patients hospitalized in France who were previously hospitalized in other countries and were carrying carbapenemase-producing bacteria, glycopeptide-resistant enterococci, or both*
Patient no.
Year of initial hospital admission
Patient transfer status
Country of hospitalization
Species of infection
β-lactamase content
Glycopeptide resistance gene
ESBL
Carbapenemase
1†
2010
DT
Egypt
E. coli
Pos
OXA-48
2†
2010
DT
Thailand
A. baumannii
Pos
OXA-23
3†
2010
DT
Iraq
A. baumannii
Neg
OXA-23
E. faecium
vanA‡
4
2010
NDT
USA
E. faecium
vanA
5
2011
NDT
Morocco
K. pneumoniae
Neg
OXA-48
K. pneumoniae
Neg
OXA-48
6†
2011
DT
Senegal
K. pneumoniae
Pos
OXA-48
7
2011
DT
Congo
E. faecium
vanA‡
8†
2011
NDT
Benin
A. baumannii
Neg
OXA-23‡
9
2011
NDT
Kuwait
P. aeruginosa
Neg
VIM-2
10†
2011
NDT
Kuwait
K. pneumoniae
Neg
OXA-48
11†
2011
NDT
Kuwait
P. aeruginosa
Neg
VIM-2
12†
2011
NDT
Kuwait
E. faecium
vanA
13†
2011
DT
Libya
K. pneumoniae
Pos
OXA-48
14†
2011
DT
Libya
E. coli
Pos
OXA-48
K. pneumoniae
Pos
OXA-48
A. baumannii
Neg
OXA-23
E. faecium
vanA
15
2011
NDT
Saudi Arabia
E. faecium
vanA
16†
2011
NDT
Pakistan
E. faecium
vanA
17
2011
NDT
Italy
A. baumannii
Neg
OXA-23
K. pneumoniae
Neg
KPC-3
18†
2011
DT
Spain
K. pneumoniae
Neg
OXA-48
19
2011
NDT
Israel
K. pneumoniae
Neg
KPC-3
20†
2012
DT
Egypt
A. baumannii
Neg
NDM-1
A. baumannii
Neg
NDM-1
P. putida
Neg
VIM-2
21†
2012
DT
Tunisia
E. coli
Pos
OXA-48
K. pneumoniae
Pos
OXA-48
K. pneumoniae
Neg
OXA-48
22†
2012
NDT
Tunisia
A. baumannii
Neg
OXA-23
23†
2012
DT
India
E. coli
Neg
NDM-1
M. morgannii
Pos
NDM-1
P. aeruginosa
Neg
VIM-2
24†
2012
NDT
Cambodia
E. coli
Neg
NDM-4‡
E. coli
Pos
OXA-48‡
25†
2012
DT
Sri Lanka
E. coli
Pos
OXA-48‡
K. pneumoniae
Pos
OXA-181‡
26
2013
NDT
Algeria
E. coli
Neg
OXA-48
27†
2013
NDT
Algeria
E. coli
Neg
OXA-48
28
2013
DT
Tunisia
A. baumannii
Neg
NDM-1
29†
2013
DT
Libya
K. pneumoniae
Pos
OXA-48
30
2013
DT
Libya
K. pneumoniae
Pos
OXA-48
K. pneumoniae
Pos
OXA-48
31
2013
NDT
India
E. coli
Pos
OXA-181
E. coli
Neg
NDM-7‡
K. pneumoniae
Neg
NDM-7‡
32
2013
NDT
Georgia
P. aeruginosa
Pos
VIM-2‡
33†
2013
DT
Montenegro
E. faecium
vanA‡
*ESBL, extended-spectrum β-lactamase; DT, direct transfer from hospital abroad to HEGP; E. coli, Echerichia coli; Pos, positive; A. baumannii, Acinetobacter baumannii; Neg, negative; E. faecium, Enterococcus faecium; NDT, nondirect transfer (hospitalized abroad within 12 mo before transfer to HEGP); K. pneumoniae, Klebsiella pneumoniae; P. aeruginosa; Pseudomonas aeruginosa; P. putida, Pseudomonas putida; M. morganii, Morganella morganii. †Patient carrying an ESBL producer in addition to the carbapenemase-producing bacteria and/or glycopeptide-resistant enterococci. ‡Resistance gene not reported previously in the country of initial hospitalization.
Rates of resistance for ESBL-producing Enterobacteriaceae and CPE were, respectively, 53.1% and 57.1% to gentamicin, 16.7% and 32.1% to amikacin, 77.1% and 82.1% to nalidixic acid, 63% and 75% to levofloxacin, and 70.3% and 75% to ciprofloxacin. The Pseudomonas spp. and A. baumannii isolates were also multidrug resistant; all isolates were colistin susceptible.
Among the 33 colonized patients, 13 (39.4%) were not infected; 1 of the uninfected patients died. Seven patients were infected with >1 CPB (health care–related in 2 patients, 1 of whom died), 4 patients with ESBL-producing Enterobacteriaceae (health care–related in 1 patient, who died), and 9 patients with other bacteria (health care–related in 4 patients, 1 of whom died). No patients were infected with GRE. Overall, 60.6% of colonized patients were infected and 12.1% died; 35% (7/20) of the infections were health care–related (3 urinary tract device–related infections, 2 cases of ventilator-associated pneumonia, 1 infection at the site of a portacath, and 1 case of cellulitis).
Almost 25% of the repatriated patients carried ESBL-producing Enterobacteriaceae (mostly CTX-M-15 producers; Technical Appendix); 6.7% carried CPB and/or GRE. By comparison, during the study period, only 10.8% of 2,314 systematically screened patients in the medical and general surgery intensive care units at HEGP (repatriated patients excluded) carried ESBL-producing Enterobacteriaceae; 1 carried vanAEnterococcus faecium (data not shown). For patients with no record of hospitalization abroad, no CPE isolates were found; other bacterial isolates included 1 vanAE. faecalis, 13 vanA E. faecium (all known from previous outbreaks), 4 OXA-23–producing A. baumannii, and 4 VIM- and 1 IMP-producing P. aeruginosa.
Of the repatriated patients, 19.5% of DT patients (vs. 4.1% of NDT) and 23.9% (7 DT, 4 NDT) of those who were transferred to medical and general surgery intensive care units (ICUs) were CPB and/or GRE carriers. This finding highlights the role of severe underlying disease or injury and recent antimicrobial drug treatment. Among ICU patients, 3 died, most likely from underlying conditions, findings in line with the observation that carriage of or infection with multidrug-resistant bacteria is not the only predictor of death (8). Most of the 28 CPE isolates were resistant to fluoroquinolones and aminoglycosides except amikacin; 21 carried OXA-48–type genes, 7 of which were non-ESBL producers and were detected only around an ertapenem disk on Drigalski agar (Bio-Rad, Marnes-la-Coquette, France). All CPB, irrespective of species, showed imipenem hydrolysis in a recently described test (9) that was shortened and simplified by incubating colonies directly in antibiotic solution.
Although time-consuming and certainly perfectible, implementation of strict control measures to limit CPB and GRE spread (6,7) seems justified, a conclusion supported by the occurrence, since November 2010, of just 1 cross-transmission–linked CPB outbreak in an ICU at HEGP (after urgent intervention for cardiac arrest). Of particular concern is the high proportion of OXA-48–producing isolates in persons with no documented link to repatriation in France (10). This finding could be explained in part by the historical and demographic relationships between France and North Africa, where prevalence of OXA-48 is high, reflected in results from patients repatriated from that part of the continent.
Technical Appendix
β-lactamase profiles of multidrug-resistant Gram-negative bacilli isolated in 2010 and 2011, France.
Suggested citation for this article: Compain F, Decré D, Frazier I, Ramahefasolo A, Lavollay M, Carbonnelle E, et al. Carbapenemase-producing bacteria in patients hospitalized abroad, France [letter]. Emerg Infect Dis [Internet]. 2014 Jul [date cited]. http://dx.doi.org/10.3201/eid2007.131638
Acknowledgments
We thank Patrick Grohs and Solen Kerneis for data retrieval and Patrice Nordmann, Laurent Poirel, and Gaelle Cuzon for initial carbapenemase typing.
ReferencesSavardP, PerlTM. A call for action: managing the emergence of multidrug-resistant Enterobacteriaceae in the acute care settings.Curr Opin Infect Dis. 2012;25:371–7 . 10.1097/QCO.0b013e3283558c1722766646GlasnerC, AlbigerB, BuistG, Tambić AndrasevićA, CantonR, CarmeliY, European Survey on Carbapenemase-Producing Enterobacteriaceae Working Group. Carbapenemase-producing Enterobacteriaceae in Europe: a survey among national experts from 39 countries, February 2013.Euro Surveill. 2013;18:20525 .23870096Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases. Guidance for control of infections with carbapenem-resistant or carbapenemase-producing Enterobacteriaceae in acute care facilities [cited 2013 Mar 5]. http://www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdfVauxS, CarbonneA, ThioletJM, JarlierV, CoignardB; RAISIN and Expert Laboratories Groups. Emergence of carbapenemase-producing Enterobacteriaceae in France, 2004 to 2011.Euro Surveill. 2011;16:19880 .21663708CantónR, AkóvaM, CarmeliY, GiskeCG, GlupczynskiY, GniadkowskiM, ; European Network on Carbapenemases. Rapid evolution and spread of carbapenemases among Enterobacteriaceae in Europe.Clin Microbiol Infect. 2012;18:413–3110.1111/j.1469-0691.2012.03821.x22507109LepelletierD, AndremontA, GrandbastienB; National Working Group. Risk of highly resistant bacteria importation from repatriates and travelers hospitalized in foreign countries: about the French recommendations to limit their spread.J Travel Med. 2011;18:344–5110.1111/j.1708-8305.2011.00547.x21896099Haut Conseil de la Santé Publique. Prévention de la transmission croisée des Bactéries Hautement Résistantes aux antibiotiques émergentes (BHRe) [cited 2013 Jul 10]. http://www.hcsp.fr/Explore.cgi/Telecharger?NomFichier=hcspr20130710_recoprevtransxbhre.pdf.VardakasKZ, RafailidisPI, KonstanteliasAA, FalagasME. Predictors of mortality in patients with infections due to multi-drug resistant Gram negative bacteria: the study, the patient, the bug or the drug?J Infect. 2013;66:401–1410.1016/j.jinf.2012.10.02823142195DortetL, PoirelL, NordmannP. Rapid identification of carbapenemase types in Enterobacteriaceae and Pseudomonas spp. by using a biochemical test.Antimicrob Agents Chemother. 2012;56:6437–4010.1128/AAC.01395-1223070158DortetL, CuzonG, NordmannP. Dissemination of carbapenemase-producing Enterobacteriaceae in France.J Antimicrob Chemother. 2014;69:623–710.1093/jac/dkt43324275115