Scholarly article on topic 'Emergence of OXA-48 carbapenemase-producing Enterobacter cloacae ST89 infection in Poland'

Emergence of OXA-48 carbapenemase-producing Enterobacter cloacae ST89 infection in Poland Academic research paper on "Clinical medicine"

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{"Infection control" / "Antimicrobial drug resistance" / OXA-48 / Carbapenemase / " Enterobacter cloacae "}

Abstract of research paper on Clinical medicine, author of scientific article — Piotr Majewski, Piotr Wieczorek, Paweł Tomasz Sacha, Marek Frank, Grzegorz Juszczyk, et al.

Summary Background The utility of carbapenems, which are considered ‘last-line’ agents, is being diminished by the growing incidence of various resistance mechanisms in bacteria. We aimed to investigate the molecular mechanism of carbapenem resistance in Enterobacter cloacae recovered from a 76-year-old patient who had undergone coronary artery bypass grafting and repair of the mitral and tricuspid valves. Interestingly, the patient had no prior history of hospital admission abroad. Methods The Carba-NP test II and synergy testing were performed to confirm carbapenemase activity. PCR was used to detect carbapenemase-encoding genes. Nucleotide and amino acid sequence analysis was performed to identify OXA-48 variants. Moreover, we performed multilocus sequence typing (MLST) of multidrug-resistant (MDR) E. cloacae. Results We detected no significant increase in zone diameter around disks with inhibitors. However, the Carba-NP test II revealed carbapenemase activity in all isolates. All isolates showed the presence of the exact OXA-48 carbapenemase variant. Furthermore, MLST analysis revealed that the MDR E. cloacae isolates belonged to ST89. Conclusions We report a case of infection caused by a unique carbapenem-resistant E. cloacae ST89 producing OXA-48 carbapenemase. Interestingly, these pathogens developed resistance to other ‘last-resort’ agents, namely colistin and tigecycline. There is a crucial need for surveillance programs aimed at screening for carbapenemase-producing Gram-negative bacteria, especially in patients transferred from high-incidence areas.

Academic research paper on topic "Emergence of OXA-48 carbapenemase-producing Enterobacter cloacae ST89 infection in Poland"

ARTICLE IN PRESS

International Journal of Infectious Diseases xxx (2014) e1-e3

ELSEVIER

Contents lists available at ScienceDirect

International Journal of Infectious Diseases

journal homepage www.elsevier.com/locate/ijid

Short Communication

Emergence of OXA-48 carbapenemase-producing Enterobacter cloacae ST89 infection in Poland

qi Piotr Majewski3'*, Piotr Wieczoreka, Pawel Tomasz Sacha a, Marek Frank b, Grzegorz Juszczykc, Dominika Ojdanaa, Wioletta Klosowskaa, Anna Wieczoreka, Anna SieM<o a, Anna Diana Michalska a, Tomasz Hirnle b, Elzbieta Anna Tryniszewska a

a Department of Microbiological Diagnostics and Infectious Immunology, Medical University of Bialystok, ul. Waszyngtona 15A, 15-629 Bialystok, Poland b Department of Cardiac Surgery, Medical University of Bialystok, Bialystok, Poland c Department of Anaesthesiology and Intensive Care, Medical University of Bialystok, Bialystok, Poland

ARTICLE INFO

SUMMARY

Article history:

Received 25 January 2014

Received in revised form 26 February 2014

Accepted 27 February 2014

Corresponding Editor: Eskild Petersen,

Aarhus, Denmark

Keywords: Infection control Antimicrobial drug resistance OXA-48

Carbapenemase Enterobacter cloacae

Background: The utility of carbapenems, which are considered 'last-line' agents, is being diminished by the growing incidence of various resistance mechanisms in bacteria. We aimed to investigate the molecular mechanism of carbapenem resistance in Enterobacter cloacae recovered from a 76-year-old patient who had undergone coronary artery bypass grafting and repair of the mitral and tricuspid valves. Interestingly, the patient had no prior history of hospital admission abroad.

Methods: The Carba-NP test II and synergy testing were performed to confirm carbapenemase activity. PCR was used to detect carbapenemase-encoding genes. Nucleotide and amino acid sequence analysis was performed to identify OXA-48 variants. Moreover, we performed multilocus sequence typing (MLST) of multidrug-resistant (MDR) E. cloacae.

Results: We detected no significant increase in zone diameter around disks with inhibitors. However, the Carba-NP test II revealed carbapenemase activity in all isolates. All isolates showed the presence of the exact OXA-48 carbapenemase variant. Furthermore, MLST analysis revealed that the MDR E. cloacae isolates belonged to ST89.

Conclusions: We report a case of infection caused by a unique carbapenem-resistant E. cloacae ST89 producing OXA-48 carbapenemase. Interestingly, these pathogens developed resistance to other 'lastresort' agents, namely colistin and tigecycline. There is a crucial need for surveillance programs aimed at screening for carbapenemase-producing Gram-negative bacteria, especially in patients transferred from high-incidence areas.

© 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-

nc-sa/3.0/).

1. Introduction

Nowadays, the utility of carbapenems is being diminished by the growing worldwide incidence of various resistance mechanisms in Gram-negative bacteria. The occurrence of microorganisms resistant to 'last-line' agents represents a particularly high risk in the healthcare setting. To date, novel carbapenemases of the OXA-48 family have been distributed mainly in Klebsiella pneumoniae, but they have begun to emerge in another pathogen prone to exhibiting multiple drug resistance mechanisms,

* Corresponding author. Tel.: +48 85 746 8571; fax: +48 85 746 8571. E-mail addresses: piotr.majewski@umb.edu.pl, piotr.majewski@onet.pl (P. Majewski).

Enterobacter cloacae.1-7 In the present study we performed clinical 21

and retrospective molecular investigations of an infection due to 22

OXA-48 carbapenemase-producing E. cloacae. 23

2. Case report 24

A 76-year-old male with coexisting significant mitral and 25

tricuspid valve regurgitation was admitted to the Department of 26

Cardiac Surgery. The patient had developed coronary artery 27

disease, hypertension and bradycardia-tachycardia syndrome, 28

and was in the third stage of chronic kidney disease. Furthermore, 29

the patient had no history of travel or admission to a hospital 30

abroad. 31

In August 2012 a combined cardiac operation was performed: 32

coronary artery bypass grafting and repair of the mitral and 33

http://dx.doi.org/10.1016/j.ijid.2014.02.024

1201-9712/© 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

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P. Majewski et al. / International Journal of Infectious Diseases xxx (2014) el-e3

Figure 1. Scheme presenting the administration of antimicrobial agents during the patient's hospitalization compared to the microbiological diagnostics and susceptibility testing. Colistin: 2 x 2 MIU administered intravenously (IV) between day 14 and day 27; 3 x 2 MIUIV administered from day 28. Imipenem: 4 x 0.5 g administered IV every 6 h from day 27. Tigecycline: initial dose of 100 mg administered IV on day 28, followed by 2 x 50 mg administered IV. *See Table 1 for resistance patterns of Enterobacter cloacae 6185 and 6186.

tricuspid valves. The procedure was performed in cardiopulmonary bypass (CPB). The left internal thoracic artery (LIMA) was anastomosed to the left anterior descending coronary artery (LAD). Mitral and tricuspid valve plasties were performed with the implantation of prosthetic rings. During the first hour after the procedure the patient developed heart failure despite pharmacological support. The patient underwent an urgent second procedure with the use of CPB. Two saphenous grafts were implanted into the LAD and right coronary artery (RCA). Intra-aortic balloon counterpulsation (IABP) was introduced through a right femoral artery access as mechanical circulatory support. After the operation, the patient was transferred to the intensive care unit.

After gradual improvement in his general condition and stabilization of the circulatory system, the patient subsequently developed a water-electrolyte imbalance with decreased diuresis and a high creatinine level. Continuous renal replacement therapy was started 11 days after surgery. His further postoperative course included physical rehabilitation, enteral and parenteral nutrition, and intensive drug treatment with respect to antimicrobial therapy, which is presented in Figure 1.

On postoperative day 38, after another cardiac decompensation, coagulation disorders, acute renal failure, and multiple organ dysfunction syndrome, the patient developed cardiac arrest. Attempts at resuscitation were unsuccessful and the patient died. Bronchial secretions recovered on days 37 and 38 after surgery revealed the failure of antimicrobial treatment to eradicate carbapenem-resistant E. cloacae.

3. Materials and methods

The first isolates of carbapenem non-susceptible E. cloacae were obtained from blood and bronchial secretions on day 24 after surgery. Further isolates were recovered from urine and subsequent samples of blood and bronchial secretions.

Antimicrobial susceptibility testing of all isolates was performed using the V1TEK2 system, following the manufacturer's guidelines. Resistance patterns of the selected isolates, interpreted in accordance with the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria, are presented in Table 1.

Moreover, we conducted detailed phenotypic and molecular analysis of the first isolates obtained from bronchial aspirate and blood and the last isolate obtained from bronchial secretions 1 day before the patient's death.

Synergy testing of carbapenems (meropenem and imipenem) with beta-lactamase inhibitors and a biochemical carbapenemase assay (Carba NP test 11) were performed, as described previously.8 We performed PCR with the use of primers allowing the amplification of all currently identified blaOXA-48-like and subsequent amino acid sequence analysis.

Multilocus sequence typing (MLST) was used to classify E. cloacae isolates. The procedure was performed according to the scheme evaluated by Miyoshi-Akiyama et al.9, and results were interpreted according to the protocols on the MLST website (http:// pubmlst.org/ecloacae/) developed by Keith and Jolley10 and sited q2 at the University of Oxford.

Table 1

Resistance profile of selected OXA-48 carbapenemase-producing Enterobacter cloacae

Date of specimen collection

Amikacin Gentamicin Tobramycin Piperacillin

Piperacillin-tazobactam

Aztreonam

Cefepime

Ceftazidime

Imipenem

Meropenem

Trimethoprim-sulfamethoxazole

Ciprofloxacin

Colistin

Tigecycline3

6185 6186 7029

24/09/2012 24/09/2012 7/10/2012

Blood Bronchial Bronchial

aspirate secretion

R >64 R >64 R >64

R >16 R >16 R >16

R >16 R >16 R >16

R >128 R >128 R >128

R >128 R >128 R >128

R > 64 R >64 R >64

R > 64 R >64 R >64

R 16 R 16 R 16

S 2 I 8 I 8

I 4 R >16 R >16

R >320 R >320 R >320

R >4 R >4 R >4

S <0.5 R 12 R >16

R 8a R4 R4

80 81 82

R, resistant; 1, intermediate; S, susceptible.

a Tigecycline susceptibility testing was performed retrospectively using the Etest (bioMerieux, Marcy l'Etoile, France).

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4. Results

Phenotypic analysis revealed no significant increase in zone diameter around disks with inhibitors, indicating the absence of metallo-beta-lactamases and K. pneumoniae carbapenemase (KPC). However, the Carba NP test 11 confirmed the production of enzyme with carbapenemase activity.

PCR experiments showed the presence of a resistance gene belonging to the OXA-48 family. Nucleotide sequencing and analysis of the amino acid sequence confirmed the exact OXA-48 carbapenemase variant. Moreover, MLST analysis allowed us to classify all isolates as sequence type 89 (ST89).

5. Discussion

We report the first case of infection caused by a unique carbapenem-resistant E. cloacae ST89 producing OXA-48 carba-penemase in Central Europe (Poland). To date, the appearance of E. cloacae producing carbapenemase from the OXA-48 family has been reported in Turkey,1 Senegal,2 Morocco,3 France,4 Belgium,5 the UK,6 and Germany.7 The patient, who had no prior history of hospital admission abroad, did not develop the infection caused by the carbapenem-resistant E. cloacae until day 24 after surgery, hence the primary source of the pathogens appears to be nosocomial.

Furthermore, the microorganisms studied in our research developed resistance to other 'last-resort' agents, namely colistin and tigecycline. 1nterestingly, cases of tigecycline resistance have been reported previously,4-6 while OXA-48-producing E. cloacae resistant to colistin has not been described before. Pathogens originating from bronchial secretions exhibited resistance to both tigecycline and colistin.

Since the occurrence of bacteria resistant to virtually all available antimicrobial agents is increasing constantly, it appears that in the future we will have to manage untreatable infections, similar to those occurring before the introduction of the first antimicrobial compound to therapy. Constant monitoring of the local epidemiology could prevent potential outbreaks of infections caused by multidrug-resistant bacteria. There is a crucial need for

surveillance programs aimed at screening for carbapenemase-producing Gram-negative bacteria, especially in patients transferred from high-incidence areas.

Acknowledgements

We thank Steven J. Snodgrass for editorial assistance and Malgorzata Dzieduszow for technical assistance. The paper submitted was supported in part by departmental sources and The Leading National Research Centre (52-KNÜW-2013).

Conflict of interest: The authors have no conflicts of interest to declare.

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