Open Access

Acinetobacter baumannii producing OXA-23 detected in the Czech Republic

  • Marketa Senkyrikova1Email author,
  • Vendula Husickova1,
  • Magdalena Chroma2,
  • Pavel Sauer1,
  • Jan Bardon3 and
  • Milan Kolar1
SpringerPlus20132:296

https://doi.org/10.1186/2193-1801-2-296

Received: 12 April 2013

Accepted: 28 June 2013

Published: 2 July 2013

Abstract

Background

Acinetobacter baumannii is an opportunistic pathogen posing an increased risk to hospitalized persons, causing nosocomial pneumonias, urinary tract infections and postoperative infections.

Methods

Between 1 December 2011 and 30 September 2012, strains of Acinetobacter spp. were isolated from clinical samples obtained from hospitalized patients. Susceptibility to antibiotics was determined by the standard microdilution method and phenotypic testing was used to detect the presence of serine carbapenemases and metallo-beta-lactamases. The polymerase chain reaction was used to detect the genes encoding carbapenemases. Pulsed field gel electrophoresis was used to investigate the genetic relationship among the carbapenem resistant isolates of Acinetobacter baumannii.

Results

In three strains of Acinetobacter baumannii enzyme OXA-23 was detected. This positive result was confirmed by restriction analysis and sequencing. The study reported an OXA-23-producing strains of Acinetobacter baumannii in the Czech Republic. All three strains isolated from Military Hospital patients had a completely identical restriction profile, indicating clonal spread of a strain carrying serine carbapenemase OXA-23 in this health care facility. Moreover this was the first time the strain was detected in the country in patients who had not stayed abroad.

Background

At present, one of the most serious issues in medicine is increasing resistance of bacterial pathogens to antimicrobial agents. This fact is associated with higher mortality and morbidity rates, prolonged hospital stays and increased treatment-related costs (Rello et al., 1994; Scaife et al., 1995; Luna et al., 1997; Micek et al., 2005; Uvizl et al., 2011; Trecarichi et al. 2011). Such negative trends have also been observed in Acinetobacter spp. strains. Together with isolates of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Burkholderia cepacia complex, these belong to the clinically most important aerobic non-fermenting Gram-negative rods. The species Acinetobacter baumannii is an opportunistic pathogen with increasing clinical significance, particularly in immunocompromised patients, causing nosocomial infections of the lungs, urinary tract and surgical wounds (Lee et al., 2009).

Moreover, the role of Acinetobacter baumannii is strengthened by relatively high resistance to numerous antibiotics which is determined by both natural and acquired mechanisms (Jeon et al., 2005). In multiresistant strains of Acinetobacter baumannii, the drugs of choice are carbapenems. Unfortunately, the development of resistance did not spare even this group of antimicrobial drugs, with the main mechanism being production of carbapenemases, enzymes belonging to Ambler classes B, A and D (Ambler, 1980; Bush et al., 2010). From class B carbapenemases known as metallo-beta-lactamases (MBLs), were in Acinetobacter spp. strains detected type of IMP, VIM and SIM enzymes (Zarrilli et al., 2009). However, resistance of Acinetobacter baumannii to carbapenems is more frequently caused by production of class D serine carbapenemases. These enzymes are called carbapenem-hydrolyzing class D beta-lactamases (CHDLs) (Higgins et al., 2010). The first reported acquired class D beta-lactamases with carbapenemase in Acinetobacter baumannii originated from Scotland and is known as OXA-23 (initially refered as ARI-1) (Scaife et al., 1995; Mugnier et al., 2010). The most common CHDL subgroups in Acinetobacter baumannii are OXA-23, OXA-24/40 OXA-58, OXA-143 and OXA-51 (Dijkshorn et al., 2007; Higgins et al., 2009). The gene for OXA-51 is located on a chromosome and, unlike the other OXA types able to hydrolyze carbapenems, it has a very low level of expression and does not cause resistance (Dijkshorn et al., 2007).

Nowadays CHDLs are spread worldwide and they are often involved in nosocominal infection (Peleg et al., 2008). Isolates carrying CHDLs were detected in North and South America (Peleg et al., 2008; Villegas et al.,2007; Merkier et al., 2008; Dalla-Costa et al., 2003; Lolans et al., 2006), Africa (Marais et al., 2004), Australia (Peleg et al., 2006), Asian area like China (Zong et al., 2008; Hsueh et al., 2002) Korea (Kim et al., 2008), Thailand (Mendes et al., 2009), Indonesia (Mendes et al., 2009) and also in European countries like the United Kigdom (Coelho et al.; 2006), the Netherlands (van den Broek et al., 2006), France (Corvec et al., 2007), Belgium (Wybo et al., 2007), Burglaria (Stoeva et al., 2008), Belgium (Bogaerts et al., 2006), Greece (Tsakris et al., 2008) or Spain (Acosta et al., 2011).

It must be stressed that resistance of Acinetobacter spp. to carbapenems may be caused by other mechanisms such as changes in porin expression, modification of PBPs or efflux of an antibiotic from a cell (Poirel et al., 2010).

Carbapenem resistance in Acinetobacter baumannii associated with OXA-type enzymes was first occurred in 2008 in the Czech republic. There were detected OXA-58-like and OXA-24-like enzymes from patients hospitalized at intensive care units (Nemec et al., 2008). Then a few years later in 2011 was in the Czech republic detected a multiresistant strain of Acinetobacter baumannii carrying the genes for NDM-1 and OXA-23 was detected in 2011 (Křížová et al., 2012). However, this strain was isolated in a patient who had returned from a stay in Egypt and belonged to the European (EU) clone I (Křížová et al., 2012).

This is the first report in the Czech Republic of Acinetobacter baumannii strains producing OXA-23 isolated from a patient who did not stay abroad.

Material and methods

Strain selection

Between 1 December 2011 and 30 September 2012, Acinetobacter spp. strains were isolated from clinical samples (endotracheal secretion, bronchoalveolar lavage, sputum, blood, urine, pus, aspirate, wound secretion, blood culture). These strains were obtained from patients hospitalized at intensive care units in the University Hospital Olomouc and Military Hospital Olomouc. The identification was performed by standard microbiology procedures including the use of the Phoenix automated system (Becton, Dickinson and Company) and MALDI-TOF Biotyper (Bruker Daltonics).

Determining resistance to antimicrobial agents

In all Acinetobacter spp. isolates, susceptibility to antibiotics was determined by a standard microdilution method according to the EUCAST (European Committee on Antimicrobial Susceptibility Testing) criteria (European Committee on Antimicrobial Susceptibility Testing, 2012). The reference strains for quality controls were Escherichia coli ATCC 25922, Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 27853. Resistance to meropenem determined by the microdilution method was confirmed by the E-test (bioMérieux, France). In case of imipenem and ertapenem, the E-test was also used to determine the minimum inhibitory concentrations (MIC).

Phenotypic determination of carbapenemase production

Carbapenemase production in Acinetobacter spp. isolates with a MIC for meropenem of >2 mg/L was phenotypically determined by the CD test (Figure 1) for detection of carbapenemases class A, combined disc (Figure 2) and modified Hodge test for serine carbapenemases and MBL detection (Lee et al., 2009; Pasteran et al., 2009; Pournaras et al., 2010).
Figure 1

CD test for class A carabapenemase detection. Legend: 3-APB - 3-aminophenylboronic acid.

Figure 2

Combined test for serine carbapenemases and metallo-beta-lactamase detection. Legend: EDTA – ethylenediaminetetraacetic acid.

Genotypic determination of carbapenemase production

In Acinetobacter baumannii strains with a MIC for meropenem of >2 mg/L, positively phenotypically tested for carbapenemase, the relevant genes were determined. This was carried out by PCR using specific oligonucleotide primers encoding serine carbapenemases of class A (NMC, SME, IMI, KPC and GES types) and two selected class D types (OXA-23 and OXA-48). Sequences of primers for amplification are shown in Table 1. The positive control was a strain with a known content of carbapenemases (producing KPC-2 enzyme) provided by Ing. J. Hrabák, Ph.D. from the Department of Microbiology, Faculty of Medicine in Pilsen, Charles University in Prague.
Table 1

Primers for detecting carbapenemases of class A and two selected class D subgroups

Primer

Sequence

Product size (bp)

Ta

Reference

(5′→3′)

SME-F

AGATAGTAAATTTTATAG

1138

50°C

Radice et al.; 2004

SME-R

CTCTAACGCTAATAG

IMI-F

ATAGCCATCCTTGTTTAGCTC

818

50°C

Queenan et al.; 2000

IMI-R

TCTGCGATTACTTTATCCTC

NMC1

GCATTGATATACCTTTAGCAGAGA

2158

50°C

Aubron et al.; 2005

NMC4

CGGTGATAAAATCACACTGAGCATA

KPC-F

ATGTCACTGTATCGCCGTCT

893

60°C

Bradford et al.; 2004

KPC-R

TTTTCAGAGCCTTACTGCCC

GES-F

GTTTTGCAATGTGCTCAACG

371

50°C

Weldhagen et al.; 2004

GES-R

TGCCATAGCAATAGGCGTAG

OXA-23 F

AAGCATGATGAGCGCAAAG

1066

50°C

Donald et al.; 2000

OXA-23R

AAAAGGCCCATTTATCTCAAA

OXA-48 F

TTGGTGGCATCGATTATCGG

744

50°C

Poirel et al., 2004

OXA-48R

GAGCACTTCTTTTGTGATGGC

Legend: Ta – annealing temperature.

Strains selected for gene detection were inoculated onto Mueller Hinton agar (Trios, Czech Republic) and aerobically cultured at 37°C for 18 hours. 1–2 colonies from this fresh culture were resuspended in 100 μL of sterile water and heated at 95°C for 10 minutes. This was followed by centrifugation at 13,000×g for 2 minutes. The obtained supernatant served as a template for subsequent PCR using the Robocycler Gradient 96 Temperature Cycler with specific primers shown in Table 1.

The obtained amplicons were subsequently separated on 1.5% agarose gel and compared with a DNA molecular weight marker (Top-Bio, Czech Republic). Then, OXA-23-positive PCR products were cleaved with the Hph I restriction endonuclease (New England Biolabs, Great Britain) and separated on 1.5% agarose gel, with cleaved fragment sizes being compared with the molecular weight marker. The amplified gene sequence was confirmed by direct sequencing of a PCR amplicon provided by Elisabeth Pharmacon (Czech Republic) and by comparing the obtained DNA sequence in BLAST (Basic Local Alignment Searching Tool, National Center for Biotechnology Information, http://www.ncbi.nlm.nih.gov).

Determination of epidemiological relationship

To determine epidemiological relationship of strains with positive genotypic assay results, macrorestriction profiles of genome DNA were compared by pulsed-field gel electrophoresis (PFGE).

The PFGE analysis was carried out with bacterial DNA isolated from culture freshly grown on Mueller Hinton broth as described previously (Husičková et al., 2012). Bacterial DNA was then cleaved with the Sma I restriction endonuclease (Takara, Japan). The restriction fragments were separated in 1.2% agarose gel using the CHEF-DRII (Bio-Rad, USA) under the following conditions: 5 V/cm, switch interval 2–20 seconds, for 20 hours at 14°C in 0.5 × TBE buffer. The gel was stained with ethidium bromide at 0.75 μg/ml for 1 h and visualized by UV transllumination. A 50–1,000 kb Pulse marker (Sigma, USA) was used to determine the size of DNA fragments. The PFGE results were analysed with GelCompar II (Applied Maths) software.

Results

Over the study period, a total of 166 Acinetobacter spp. strains were isolated in the two participating hospitals. Figure 3 shows the resistance to antimicrobial agents in a group of 140 isolates assumed to play a role in the etiology of the particular infection. The results revealed a prevalence of meropenem-resistant strains of 10.7%.
Figure 3

Resistance of Acinetobacter spp. to selected antimicrobial agents (percentages).

From the group of 140 strains, a total of 15 strains were found to be resistant to meropenem using the standard microdilution method. The phenotypic assay demonstrating production of carbapenemases (modified Hodge test) was positive in 3 strains. In these 3 strains, MICs to selected antimicrobial agents (ertapenem, imipenem and meropenem) were determined by the E-test, as shown in Table 2.
Table 2

MICs (in mg/L) of the tested carbapenems

Strain no.

MIC(mg/L)

Meropenem

Imipenem

Ertapenem

21678/C

12

16

>32

12257/C

>32

16

>32

15848/C

>32

>32

>32

E-test MICs testing.

All the three Acinetobacter baumannii strains originated from the Military Hospital. Strain no. 21678/C was isolated from blood culture of a patient with bloodstream infection staying at a department of anesthesiology and intensive care medicine. Samples nos. 12257/C and 15848/C were isolated from endotracheal secretions collected from two patients with late-onset ventilator-associated pneumonia hospitalized at a department of chronic intensive care.

Genetic determination of the presence of resistance genes confirmed the presence of a gene encoding class D carbapenemase, namely OXA-23 enzyme in all three strains. Restriction fragment length polymorphism analysis in positive PCR amplicons and final confirmation by direct sequencing showed the presence of OXA-23 enzyme in all three Acinetobacter baumannii strains. Comparison of macrorestriction profiles of genomic DNA using PFGE revealed that the strains had an identical restriction profile. This suggested clonal spread of a genetically identical strain.

Discussion

Class D serine carbapenemase in an Acinetobacter baumannii strain was first reported in Scotland in 1985, that is, before imipenem started to be widely used in clinical practice (Paton et al., 1993;Carvalho et al., 2011). This enzyme, originally called ARI-I, was sequenced and subsequently labeled as OXA-23 (Scaife et al., 1995;Mugnier et al., 2010).

Until now, this enzyme has been reported in Acinetobacter baumannii strains throughout the world (Mugnier et al., 2010).

In the Czech republic a multiresistant strain of Acinetobacter baumannii carrying the genes for NDM-1 and OXA-23 was detected in 2011. However, this strain was isolated in a patient who had returned from a stay in Egypt and belonged to the European (EU) clone I (Křížová et al., 2012). Thus, the above description of Acinetobacter baumannii strains producing OXA-23 is their first report in the Czech Republic in patients who did not stay abroad, suggesting their domestic origin. All three strains isolated from Military Hospital patients had a completely identical restriction profile, indicating clonal spread of a strain carrying serine carbapenemase OXA-23 in this health care facility.

Increasing resistance of bacterial pathogens to antimicrobial agents poses a severe threat to management of many infections. Of particular risk is the rise in the use of carbapenems resulting from a high prevalence of ESBL- and AmpC-positive Enterobacteriaceae which may determine the development of resistance to this group of still effective drugs (Coelho et al., 2004). Our data suggest that in the case of Acinetobacter spp. strains, the prevalence of carbapenem-resistant isolates is low. However, this situation needs to be carefully monitored and if this type of resistance spreads it must be adequately analyzed using modern molecular biology methods.

Consent

Written informed consent was obtained from the patient for the publication of this report and any accompanying images.

Declarations

Acknowledgments

Supported by the grant project LF_2012_006.

Infrastructural part of this project (Institute of Molecular and Translational Medicine) was supported from the Operational Programme Research and Development for Innovations (project CZ.1.05/2.1.00/01.0030).

Many thanks to Ing. Jaroslav Hrabák, Ph.D. for providing bacterial strains with positive carbapenemase production.

Authors’ Affiliations

(1)
Department of Microbiology, Faculty of Medicine and Dentistry, Palacky University Olomouc
(2)
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc
(3)
State Veterinary Institute in Olomouc

References

  1. Acosta J, Merino M, Viedma E, et al.: Multidrug-resistant Acinetobacter baumannii harboring OXA-24 carbapenemase, Spain. Emerg Infect Dis 2011, 17: 1064-1067. 10.3201/eid1706.091866View ArticleGoogle Scholar
  2. Ambler RP: The structure of β-lactamases. Philo Tran R Soc Lon B Biol Sci 1980, 289: 321-331. 10.1098/rstb.1980.0049View ArticleGoogle Scholar
  3. Aubron C, Poirel L, Ash RJ, et al.: Carbapenemase-producing Enterobacteriaceae , U.S. rivers. Emerg Infect Dis 2005, 11: 260-264. 10.3201/eid1102.030684View ArticleGoogle Scholar
  4. Bogaerts P, Naas T, Wybo I, et al.: Outbreak of infection by carbapenem-resistant Acinetobacter baumannii producing the carbapenemase OXA-58 in Belgium. J Clin Microbiol 2006, 44: 4189-4192. 10.1128/JCM.00796-06View ArticleGoogle Scholar
  5. Bradford PA, Bratu S, Urban C, et al.: Emergence of carbapenem-resistant Klebsiella species possessing the class A carbapenemhydrolyzing KPC-2 and inhibitor-resistant TEM-30 beta-lactamases in New York City. Clin Infect Dis 2004, 39: 55-60. 10.1086/421495View ArticleGoogle Scholar
  6. Bush K, Jacoby GA: Updated functional classification of β-lactamases. Antimicrob Agent Chemother 2010, 54: 969-976. 10.1128/AAC.01009-09View ArticleGoogle Scholar
  7. Carvalho KR, D’Alincourt Carvalho-Assef AP, Galvão dos Santos L, et al.: Occurrence of blaOXA-23 gene in imipenem-susceptible Acinetobacter baumannii . Mem Inst Oswaldo Cruz 2011, 106: 505-506. 10.1590/S0074-02762011000400020View ArticleGoogle Scholar
  8. Coelho J, Woodford N, Livermore DM: Multiresistant acinetobacter in the UK: how big a threat? J Hosp Infect 2004, 58: 167-169. 10.1016/j.jhin.2003.12.019View ArticleGoogle Scholar
  9. Coelho JM, Turton JF, Kaufmann ME, et al.: Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J Clin Microbiol 2006, 44: 3623-3627. 10.1128/JCM.00699-06View ArticleGoogle Scholar
  10. Corvec S, Poirel L, Naas T, et al.: Genetics and expression of the carbapenem-hydrolyzing oxacillinase gene bla OXA-23 in Acinetobacter baumannii . Antimicrob Agents Chemother 2007, 51: 1530-1533. 10.1128/AAC.01132-06View ArticleGoogle Scholar
  11. Dalla-Costa LM, Coelho JM, Souza HAPHM, et al.: Outbreak of carbapenem-resistant Acinetobacter baumannii producing the OXA-23 enzyme in Curitiba, Brazil. J Clin Microbiol 2003, 41: 3403-3406. 10.1128/JCM.41.7.3403-3406.2003View ArticleGoogle Scholar
  12. Dijkshoorn L, Nemec A, Seifert H: An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii . Natur Rev Microbiol 2007, 5: 939-951. 10.1038/nrmicro1789View ArticleGoogle Scholar
  13. Donald HM, Scaife W, Amyes SG, et al.: Sequence analysis of ARI-1, a novel OXA beta-lactamase, responsible for imipenem resistance in Acinetobacter baumannii 6B92. Antimicrob Agents Chemother 2000, 44: 196-199. 10.1128/AAC.44.1.196-199.2000View ArticleGoogle Scholar
  14. European Committee on Antimicrobial Susceptibility Testing: Växjö. Sweden: Breakpoint tables for interpretation of MICs and zone diameters; 2012. Available from: http://www.eucast.org/clinical_breakpoints Google Scholar
  15. Higgins PG, Poirel L, Lehmann M, et al.: OXA-143, a novel carbapenem-hydrolyzing class D β-lactamase in Acinetobacter baumannii . Antimicrob Agents Chemother 2009, 53: 5035-5038. 10.1128/AAC.00856-09View ArticleGoogle Scholar
  16. Higgins PG, Dammhayn C, Hackel M, et al.: Global spread of carbapenem-resistant Acinetobacter baumannii . J Antimicrob Chemother 2010, 65: 233-238. 10.1093/jac/dkp428View ArticleGoogle Scholar
  17. Hsueh P-R, Teng L-J, Chen C-Y, et al.: Pandrug-resistant Acinetobacter baumannii causing nosocomial infections in a university hospital, Taiwan. Emerg Infect Dis 2002, 8: 827-832. 10.3201/eid0808.020014View ArticleGoogle Scholar
  18. Husičková V, Čekanová L, Chromá M, et al.: Carriage of ESBL- and AmpC-positive Enterobacteriaceae in the gastrointestinal tract of community subjects and hospitalized patients in the Czech Republic. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2012, 156: 348-353.Google Scholar
  19. Jeon BC, Jeong SH, Bae IK, et al.: Investigation of a nosocomial outbreak of imipenem-resistant Acinetobacter baumannii producing the OXA-23 beta-lactamase in Korea. J Clin Microbiol 2005, 43: 2241-2245. 10.1128/JCM.43.5.2241-2245.2005View ArticleGoogle Scholar
  20. Kim JW, Heo ST, Jin JS, et al.: Characterization of Acinetobacter baumannii carrying bla OXA-23, bla PER-1 and armA in a Korean hospital. Clin Microbiol Infect 2008, 14: 716-718. 10.1111/j.1469-0691.2008.02022.xView ArticleGoogle Scholar
  21. Křížová L, Bonnin RA, Nordmann P, et al.: Characterization of a multidrug-resistant Acinetobacter baumannii strain carrying the blaNDM-1 and blaOXA-23 from the Czech republic. J Antimicrob Chemother 2012, 67: 1550-1552. 10.1093/jac/dks064View ArticleGoogle Scholar
  22. Lee K, Chong Y, Shin HB, et al.: Modified Hodge and EDTA-disk synergy tests to screen metallo-β-lactamase-producing strains of Pseudomonas and Acinetobacter species. J Clin Microbiol 2009, 47: 1631-1639. 10.1128/JCM.00130-09View ArticleGoogle Scholar
  23. Lolans K, Rice TW, Munoz-Price LS, Quinn JP: Multicity outbreak of carbapenem-resistant Acinetobacter baumannii isolates producing the carbapenemase OXA-40. Antimicrob Agents Chemother 2006, 50: 2941-2945. 10.1128/AAC.00116-06View ArticleGoogle Scholar
  24. Luna CM, Vujacich P, Niederman MS, et al.: Impact of BAL data on the therapy and outcome of ventilator-associated pneumonia. Chest 1997, 111: 676-685. 10.1378/chest.111.3.676View ArticleGoogle Scholar
  25. Marais E, de Jong G, Ferraz V, et al.: Interhospital transfer of pan-resistant Acinetobacter strains in Johannesburg, South Africa. Am J Infect Control 2004, 32: 278-281. 10.1016/j.ajic.2003.11.004View ArticleGoogle Scholar
  26. Mendes RE, Bell JM, Turnidge JD, et al.: Emergence and widespread dissemination of OXA-23, -24/40 and −58 carbapenemases among Acinetobacter spp. in Asia-Pacific nations: report from the SENTRY surveillance program. J Antimicrob Chemother 2009, 63: 55-59.View ArticleGoogle Scholar
  27. Merkier AK, Catalano M, Ramirez MS, et al.: Polyclonal spread of bla OXA-23 and bla OXA-58 in Acinetobacter baumannii isolates from Argentina. J Infect Dev Countr 2008, 2: 235-240.Google Scholar
  28. Micek ST, Lloyd AE, Ritchie DJ, et al.: Pseudomonas aeruginosa bloodstream infection: importance of appropriate initial antimicrobial treatment. Antimicrob Agents Chemother 2005, 49: 1306-1311. 10.1128/AAC.49.4.1306-1311.2005View ArticleGoogle Scholar
  29. Mugnier PD, Poirel L, Naas T, et al.: Worldwide Dissemination of the bla OXA-23 Carbapenemase Gene of Acinetobacter baumannii . Emerg Infect Dis 2010, 16: 35-40.View ArticleGoogle Scholar
  30. Nemec A, Křížová L, Maixnerová M, et al.: Emergence of carbapenem resistance in Acinetobacter baumannii in the Czech republic is associated with the spread of multidrug-resistant strains of European clone II. J Antimicrob Chemother 2008, 62: 484-489. 10.1093/jac/dkn205View ArticleGoogle Scholar
  31. Pasteran F, Mendez T, Guerriero L, et al.: Sensitive screening tests for suspected class A carbapenemase production in species of Enterobacteriaceae. J Clin Microbiol 2009, 47: 1631-1639. 10.1128/JCM.00130-09View ArticleGoogle Scholar
  32. Paton R, Miles RS, Hood J, et al.: ARI-1: beta-lactamase-mediated imipenem resistance in Acinetobacter baumannii . Int J Antimicrob Agents 1993, 2: 81-88. 10.1016/0924-8579(93)90045-7View ArticleGoogle Scholar
  33. Peleg AY, Bell JM, Hofmeyr A, et al.: Inter-country transfer of Gram-negative organisms carrying the VIM-4 and OXA-58 carbapenem-hydrolysing enzymes. J Antimicrob Chemother 2006, 57: 794-795. 10.1093/jac/dkl036View ArticleGoogle Scholar
  34. Peleg AY, Seifert H, Paterson DL: Acinetobacter baumannii : emergence of a successful pathogen. Clin Microbiol 2008, 21: 538-582. 10.1128/CMR.00058-07View ArticleGoogle Scholar
  35. Poirel L, Heritier C, Toluen V, et al.: Emergence of oxacillinase-mediated resistance to imipenem in Klebsiella pneumoniae . Antimicrob Agents Chemother 2004, 48: 15-22. 10.1128/AAC.48.1.15-22.2004View ArticleGoogle Scholar
  36. Poirel L, Naas T, Nordmann P: Diversity, epidemiology, and genetics of class D beta-lactamases. Antimicrob Agents Chemother 2010, 54: 24-38. 10.1128/AAC.01512-08View ArticleGoogle Scholar
  37. Pournaras S, Poulou A, Tsakris A: Inhibitor-based methods for the detection of KPC carbapenemase-producing Enterobacteriaceae in clinical practice by using boronic acid compounds. J Antimicrob Chemother 2010, 65: 1319-1321. 10.1093/jac/dkq124View ArticleGoogle Scholar
  38. Queenan AM, Torres-Viera C, Gold HS, et al.: SME-type carbapenem-hydrolyzing class A β-lactamases from geographically diverse Serratia marcescens strains. Antimicrob Agents Chemother 2000, 44: 3035-3039. 10.1128/AAC.44.11.3035-3039.2000View ArticleGoogle Scholar
  39. Radice M, Power P, Gutkind G, et al.: First class A carbapenemase isolated from Enterobacteriaceae in Argentina. Antimicrob Agents Chemother 2004, 48: 1068-1069. 10.1128/AAC.48.3.1068-1069.2004View ArticleGoogle Scholar
  40. Rello J, Torres A, Ricart M, et al.: Ventilator-associated pneumonia by Staphylococcus aureus. Comparison of methicillin-resistant and methicillin-sensitive episodes. Am J Respir Crit Care Med 1994, 150: 1545-1549. 10.1164/ajrccm.150.6.7952612View ArticleGoogle Scholar
  41. Scaife W, Young HK, Paton RH, et al.: Transferable imipenem-resistance in Acinetobacter species from a clinical source. J Antimicrob Chemother 1995, 36: 585-586. 10.1093/jac/36.3.585View ArticleGoogle Scholar
  42. Stoeva T, Higgins PG, Bojkova K, et al.: Clonal spread of carbapenem-resistant OXA-23-positive Acinetobacter baumannii in a Bulgarian university hospital. Clin Microbiol Infect 2008, 14: 723-727. 10.1111/j.1469-0691.2008.02018.xView ArticleGoogle Scholar
  43. Trecarichi EM, Tubarello M, Caira M, et al.: Multidrug resistant Pseudomonas aeruginosa bloodstream infection in adult patients with hematologic malignancies. Haematologica 2011, 96: e1-e3. 10.3324/haematol.2010.036640View ArticleGoogle Scholar
  44. Tsakris A, Ikonomidis A, Poulou A: Clusters of imipenem-resistant Acinetobacter baumannii clones producing different carbapenemases in an intensive care unit. Clin Microbiol Infect 2008, 14: 588-594. 10.1111/j.1469-0691.2008.01996.xView ArticleGoogle Scholar
  45. Uvizl R, Hanulik V, Husickova V, et al.: Hospital-acquired pneumonia in ICU patients. Pap Med Fac Univ Palacky Olomouc Czech Repub 2011, 155: 373-378. 10.5507/bp.2011.067View ArticleGoogle Scholar
  46. Van Den Broek PJ, Arends J, Bernards AT, et al.: Epidemiology of multiple Acinetobacter outbreaks in The Netherlands during the period 1999–2001. Clin Microbiol Infect 2006, 12: 837-843. 10.1111/j.1469-0691.2006.01510.xView ArticleGoogle Scholar
  47. Villegas MV, Kattan JN, Correa A, et al.: Dissemination of Acinetobacter baumannii clones with OXA-23 carbapenemase in Colombian hospitals. Antimicrob Agents Chemother 2007, 51: 2001-2004. 10.1128/AAC.00226-07View ArticleGoogle Scholar
  48. Weldhagen GF, Prinsloo A: Molecular detection of GES-2 extended spectrum beta-lactamase producing Pseudomonas aeruginosa in Pretoria, South Africa. Int J Antimicrob Agents 2004, 24: 35-38.View ArticleGoogle Scholar
  49. Wybo I, Blommaert L, De Beer T, et al.: Outbreak of multidrug-resistant Acinetobacter baumannii in a Belgian university hospital after transfer of patients from Greece. J Hosp Infect 2007, 67: 374-380. 10.1016/j.jhin.2007.09.012View ArticleGoogle Scholar
  50. Zarrilli M, Giannouli M, Tomasone F, et al.: Carbapenem resistance in Acinetobacter baumannii: the molecular epidemic features of an emerging problem in health care facilities. J Infect Dev Ctries 2009, 3: 335-340.View ArticleGoogle Scholar
  51. Zong Z, Lü X, Valenzuela JK, et al.: An outbreak of carbapenem-resistant Acinetobacter baumannii producing OXA-23 carbapenemase in western China. Int J Antimicrob Agents 2008, 31: 50-54. 10.1016/j.ijantimicag.2007.08.019View ArticleGoogle Scholar

Copyright

© Senkyrikova et al.; licensee Springer. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.