Skip to main content
Download PDF

High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital: a cross sectional study

BMC Infectious Diseases volume 18, Article number: 491 (2018) Cite this article

Abstract

Background

Carbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital.

Methods

A total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression.

Results

Of the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex.

Conclusions

This study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium.

Peer Review reports

Background

Acinetobacter is a gram-negative coccobacillus that has rapidly emerged as one of the most common nosocomial pathogens worldwide [1]. There are currently at least 31 described Acinetobacter genomic species [2], of which A. calcoaceticus, A. baumannii, A. pittii, and A. nosocomialis are very closely related, and difficult to distinguish from each other by phenotypic properties [3]. A. calcoaceticus-A. baumannii (Acb) complex has therefore been proposed to refer to these species [2]. Nevertheless, A. baumannii is the most clinically relevant and is notorious for its ability to accumulate diverse mechanisms of resistance [4, 5].

The carbapenem class of antibiotics is considered as the last-resort choice when treating Acinetobacter infections. However, an increasing prevalence of carbapenem resistance has been observed in clinical A. baumannii isolates from many parts of the world. Carbapenem-associated multiclass resistance among 55,330 U.S. A. baumannii isolates from The Surveillance Network database has increased from 20.6% in 2002 to 49.2% in 2008 [6]. In China, the resistance rate of clinical A. baumannii to carbapenem gradually increased from < 10% in 2000 to > 60% at present [7, 8]. The major mechanism of carbapenem resistance is production of OXA β-lactamases, which are clustered in three major groups, OXA-23-like, OXA-24/40-like, and OXA-58-like [9,10,11].

OXA-24/40 β-lactamase was first identified in A. baumannii from Spain in 1997 [12]. After that, A further 6 enzyme variants have since been discovered, including OXA-72 [11]. Unlike OXA-23-like, OXA-24/40 β-lactamases were less commonly identified in carbapenem resistant Acinetobacter spp. isolates [13]. A large surveillance of OXA-type β-lactamase gene clusters for a total of 2880 Acinetobacter spp. isolates collected from 23 Chinese provinces found that blaOXA-23-like and blaOXA-24/40-like genes were identified in 1316 isolates (45.7%) and 11 isolates (0.4%), respectively [14]. Therefore, OXA-24/40-like β-lactamases were only responsible for a small number of carbapenem-resistance isolates in China, their dissemination and epidemiology in healthcare settings deserves further surveillance and investigation.

This study aimed to demonstrate the occurrence, clinical manifestation and genotypic characterizations of OXA-72-producing A. baumannii in a Chinese hospital.

Methods

Study settings and isolates information

A total of 107 clinical Acb complex isolates from 107 patients were collected at a tertiary-care comprehensive hospital in northeastern China with 1800 beds, from Oct 2014 to Oct 2016. These isolates were recovered from various specimens including sputum, blood, urine, pleural fluid, secretions and throat swab sample. For each patient, only a single colony of the first isolate was selected for subsequent analysis. All the clinical isolates were stored at − 80 °C until use. Data for each isolate and each patient were obtained through review of microbiology lab results and medical records. Risk factor data, including ICU stay, presence of invasive procedures and antibiotic treatment, referred to those which were present before the isolation of the index Acinetobacter strains. All data were anonymously collected and interpreted.

Strain identification and in vitro antibiotic susceptibility testing

Identification of Acb complex isolates was initially performed using automated identification systems the VITEK 2 compact system (BioMérieux, Craponne, France). Further identification of the Acb complex to the species level was performed by gyrB multiplex PCR [15, 16].

In vitro susceptibilities to ampicillin-sulbactam, piperacillin-tazobactam, ceftazidime, cefepime, meropenem, imipenem, gentamicin, amikacin, ciprofloxacin, levofloxacin, colistin, minocyline were determined by the VITEK 2 compact system (BioMérieux, Craponne, France). Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) were used as quality control strains. Results were interpreted according to the Clinical and Laboratory Standards Institute (CLSI, 2016) guidelines.

Detection of carbapenemases genes

One white loop (1 μl) of 24 h plate culture of Acinetobacter bacteria was resuspended in 200 μl of sterilized and DNA free water. The bacterial suspensions were then heated for 10 min at 96 °C and centrifuged 5 min at 13000 rpm. The supernatant was used as the genomic DNA for the following molecular experiments.

Genes encoding for major classes of A, B, and D carbapenemases for all the Acb isolates were investigated by PCR. The presence of blaOXA-23-like, blaOXA-24-like, blaOXA-51-like, and blaOXA-58-like genes were detected through multiplex PCR assay [17]. Metallo-β-lactamase encoding genes, blaNDM-like, blaIMP-like and blaVIP-like, were detected with PCR conditions and primers as previously described [18]. The blaOXA-24-like variant was further identified through PCR and DNA sequencing as described [19].

Molecular typing

Rep-PCR was used for genotyping of all the A. baumannii isolates, using the primer pair REP 1(5’-IIIGCGCCGICAGGC-3′) and REP 2(5’-ACGTCTTATCAGGCCTAC-3′) [20]. The conditions for PCR and the gel electrophoresis were the same as previously described [21]. Rep-PCR results of each isolate was compared to all of the other isolates in a pairwise manner, isolates with identical band patterns were considered to be of identical Rep-PCR types. A minimum spanning tree was created to show the differences between patterns through BioNumerics 6.6 software (Applied Maths, Kortrijk, Belgium). The spanning tree was limited to those patterns that differ by a single band, two Rep-PCR types that differ by two or more bands were connected. Nine blaOXA-24-like gene positive representative isolates from each different Rep-PCR type were randomly chosen for multilocus sequence typing (MLST) analysis according to ‘Pasteur’ scheme [22].

A review of literature

Currently, there were two MLST schemes available for Acinetobacter. In order to differentiate between the two schemes, STs and CCs were designated as STB/CCB for the Bartual scheme and STP/CCP for the Pasteur scheme. A search of previous published papers giving the MLST results of OXA-24/40-like producing Acinetobacter spp. was conducted to illustrate the population structure of OXA-24/40 strains from different countries. The MLST data from ‘Pasteur’ scheme and ‘Bartual’ scheme were separately analyzed by Bionumerics 6.6 and presented as a minimum spanning tree for categorical data with default settings.

Statistical analysis

Statistical analyses were performed using SPSS 19.0 (IBM, Armonk, NY, USA). The comparisons of patients’ characterics were conducted by chi-square test or Mann-Whitney U test. The risk factors for carriage of blaOXA-72-positive or blaOXA-23-like-positive A. baumannii were analyzed through univariate and multivariate logistic regression. In multivariate logistic regression, ICU stay and length of ICU stay were not included as they were highly associated with many other predisposing factors, including invasive procedures and antibiotic use. The index of diversity and the 95% confidence intervals (CIs) were calculated as described previously [23]. P values < 0.05 are considered statistically significant.

Results

Of the 107 Acinetobacter isolates, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. Five A. pittii isolates were susceptible to all the antibiotics tested and one isolate exhibited an intermediate resistance phenotype to minocycline. Among the 101 A. baumannii isolates, 78 isolates (77.2%) were resistant to carbapenems (meropenem or imipenem). The rates of resistance to piperacilin/tazobactam, ampicillin/sulbactam, amikacin, gentamicin, ceftazidime, ciprofloxacin and levofloxacin in A. baumannii were all above 60%, as most of the carbapenem-resistance isolates exhibited a multidrug resistance phenotype. Four A. baumannii isolates were resistant to polymyxin.

The 107 Acinetobacter isolates were cultured from 71 male and 46 female patients. Fifty-one isolates were cultured from patients in ICU and all these isolates were carbapenem-resistant. The detection of carbapenemase genes showed that 33 (42.3%) of the 78 carbapenem-resistant A. baumannii (CRAB) were positive for the blaOXA-23-like gene, while the other 45 isolates (57.7%) were positive for the blaOXA-24/40-like gene. All these isolates harboured blaOXA-51-like gene. DNA sequencing showed that all the blaOXA-24/40-like amplicons belonged to blaOXA-72 (GenBank accession number MF781069). The blaOXA-58-like gene was detected in one carbapenem-susceptible A. baumannii (CSAB) isolate, the MICs for imipenem and meropenem were 0.5 μg/ml and 0.25 μg/ml, respectively. None of these Acinetobacter isolates were positive for blaIMP-like, blaVIM-like or blaNDM-like genes.

Eighty-four (83.2%) of 101 A. baumannii isolates were associated with an infection (primarily low respiratory tract infection) and antibiotic treatment, while the other 27 isolates were just colonized. The characterics of 101 patients colonized or infected with A. baumannii were shown in Table 1. There were no significant differences over age and gender distribution among patients colonized or infected with CRAB and CSAB strains. More than 60% of the CRAB patients stayed at ICU at the time of bacteria isolation, while only one CSAB patient stayed at ICU.

Table 1 Characteristics of 101 patients colonized or infected with Acinetobacter baumannii in a Chinese hospital
Full size table

The results of univariate logistic analysis showed that there were many common risk factors for carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii, such as ICU stay, mechanical ventilation, nasogastric intubation and carbapenem treatment (Table 2). In multivarite analysis, prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. An additional risk factor, urinary catheter, was also significantly associated with carriage of blaOXA-23-like-positive A. baumannii (Table 3).

Table 2 Univariate logistic analysis of risk factors for carriage of OXA-72-producing Acinetobacter baumannii or OXA-23-producing A. baumannii
Full size table
Table 3 Multivariate logistic analysis of risk factors for carriage of OXA-72-producing Acinetobacter baumannii or OXA-23-producing A. baumannii
Full size table

The results of Rep-PCR patterns and corresponding strain information for the 101 A. baumannii were shown in Table 4. In total, 9 Rep-PCR types were assigned to 78 CRAB isolates, while 22 Rep-PCR types were assigned to 23 CSAB isolates. The index of diversity (DI) for CRAB was 0.750 (95% CI: 0.671–0.829), which was significantly lower than for CSAB (DI = 0.996, 95% CI: 0.986–1.006). Twenty-six and 7 OXA-23-producing A. baumannii isolates were identified as Rep-PCR type 1 and 2, respectively, while 45 OXA-72-producing A. baumannii isolates were distributed in the 9 Rep-PCR types. Minimum spanning tree analysis of Rep-PCR patterns showed that all the 78 CRAB isolates were clustered into one clone complex, while most of the CSAB isolates were not connected to each other (Fig. 1). MLST analysis showed that all the 9 representative OXA-72 isolates in this study belong to ST2 (Table 4).

Table 4 The Rep-PCR type, MLST type, presence of carbapenemase genes and antimicrobial resistance profile of 101 Acinetobacter baumannii isolates
Full size table
Fig. 1
figure1

Minimum spanning tree of 101 Acinetobacter baumannii isolates based on Rep-PCR patterns. Each circle represents one unique genotype. OXA-72-producing carbapenem-resistant A. baumannii (CRAB), OXA-23-producing CRAB and carbapenem-susceptible A. baumannii (CSAB) isolates are indicated with red, green, and blue colors, respectively. The size of each circle corresponds to the number of isolates. The lines connecting the circles indicate those patterns that differ by a single band. R: carbapenem-resistant strains. S: carbapenem-susceptible strains

Full size image

A literature review of previous published MLST data showed that there were at least 19 ST types (Bartual scheme) for 29 OXA-24/40-like producing Acinetobacter spp. isolates from 11 countries and 21 ST types (Pasteur scheme) for 52 OXA-24/40-like producing Acinetobacter spp. isolates from 15 countries. Minimum spanning tree analysis of these isolates based on two different MLST schemes was shown in Fig. 2, which suggested that CC92B/CC2P represented the predominant clone for the OXA-24/40-like producing Acinetobacter spp. isolates from around the world.

Fig. 2
figure2

Minimum spanning tree analysis of blaOXA-72-positive Acinetobacter baumannii isolates based on multilocus sequence typing (MLST) data from published literatures. The left panel (a) showed the results from ‘Bartual’ scheme, the right panel (b) showed the results from ‘Pasteur’ scheme. Each circle represents an independent sequence type (ST). The size of each circle corresponds to the number of isolates. The lines connecting the circles indicate the relationship between different STs. Black arrows are used to indicate the strains originated from China

Full size image

Discussions

Carbapenem-resistant Acinetobacter spp. (mainly CRAB) are increasingly recognized as major nosocomial pathogens and considered to be serious threat for human health by US Centers for Disease Control and Prevention and World Health Organization [24, 25]. OXA-23-like carbapenemases were the main reason for the high prevalence and wide dissemination of CRAB from many parts of the world, including China [14, 26, 27]. OXA-24/40-like carbapenemases, which have been reported to be associated with outbreak of nosocomial infection in United States, Spain, Turkey and Ecuador [28,29,30,31], accounted for only a small part of CRAB in China [14, 32]. OXA-72, which was first identified in 2004 in an A. baumannii isolate from Thailand, belonged to one of the most important variant of OXA-24/40-like carbapenemases [29]. This study reported firstly a high prevalence and clonal dissemination of OXA-72-producing A. baumannii in a hospital from northeastern China.

Carbapenem resistance in A. baumannii was not significantly associated with 14-day mortality in this study (Table 1), which is in accordance with previous studies [33, 34]. However, carbapenem resistance limits the available therapeutic agents, makes the infection difficult to treat, and might be associated with an additional cost of hospitalization [34]. In this study, there was no significant difference over length of hospital stay for carbapenem resistance and susceptible A. baumannii, which might be related with the limited sample size.

In vitro antimicrobial susceptibility testing showed that OXA-72-producing A. baumannii and OXA-23-producing A. baumannii exhibited similar multidrug resistance profile, suggesting that they could not be differentiated through detection of antimicrobial phenotype. The risk factor analyses implicated that admitted into ICU and length of ICU stay were the most important risk factors for carriage of OXA-72-producing A. baumannii and OXA-23-producing A. baumannii, as ICU patients are always critical ill and subjected to a lot of risk factors for the acquisition of multidrug resistance organisms (MDROs) [35]. When ICU stay was removed for multivariable analyses, nasogastric intubation and carbapenem use were significantly associated with acquisition of both classes of CRAB, which is in accordance with previous studies [36,37,38]. The reason for why urinary catheter was significantly associated with carriage of OXA-23-producing A. baumannii, but not OXA-72-producing A. baumannii deserves further investigation. One possible explanation was that the complex conditions and combined therapy of ICU patients compromised the accuracy of multiple logistics analysis, urinary catheter might be just an indicator for critical ill patients who have a high probability of acquiring certain MDROs through contaminated environment or nursing behavior.

CC92B/CC2P was by far the largest and most widely distributed A. baumannii clone in the world, especially among OXA-23-producing A. baumannii [27, 39, 40]. Although not so widely disseminated, CC92B/CC2P was still the most important clone in OXA-24/40-producing A. baumannii (Fig. 2). The Rep-PCR and MLST analysis of A. baumannii in this study suggested that OXA-72-producing and OXA-23-producing A. baumannii isolates were genetically related and belonged to the same clone, CC92B/CC2P. It seems that OXA-72-producing A. baumannii has already become endemic in the ICU since 2014, as most of these isolates were continuously cultured without obvious clustering of isolation time. Enhanced infection control measures, such as hand hygiene education programs, environmental cleaning, antimicrobial stewardship, contact precautions [41], have to be implemented in ICU of this hospital in order to reduce the wide spread of high risk clone, CC92B/CC2P, which represents the most prevalent clone of CRAB in Chinese hospitals.

There are some limitations for this study. The first is the inclusion criteria of Acb complex strains, it has been demonstrated that a single patient may have more than one genetic type of Acinetobacter [42, 43]. To avoid the problem of duplicate data, this study adopted a simple inclusion method of allowing only a single isolate per patient. it might limit the ability to monitor the dynamic changes and complex conditions in patients who may be at particular risk of acquiring antibiotic resistant strains through cross-infection or the development of resistance during antibiotic treatment [44]. Another limitation comes from the design of this study, as this is just an one-center study, the epidemiological characterizations of OXA-72 strains in this study might not be generalized to other healthcare settings in China.

Conclusions

This study described firstly a high prevalence of OXA-72-producing A. baumannii in ICU of a Chinese hospital, which have circulated in this ICU through clonal dissemination for at least two years. Strict infection control measures must be implemented to contain the ongoing dissemination of OXA carbapenemases-producing A. baumannii in Chinese ICUs.

Abbreviations

Acb:

Acinetobacter calcoaceticus-A. baumannii

CC:

Clone complex

CRAB:

Carbapenem-resistant A. baumannii

CSAB:

Carbapenem-susceptible A. baumannii

DI:

Index of diversity

ICU:

Intensive care unit

MDROs:

Multidrug resistance organisms

MLST:

Multilocus sequence typing

ST:

Sequence type

References

  1. 1.

    Lima AL, Oliveira PR, Paula AP. Acinetobacter infection. N Engl J Med. 2008;358(12):1271–81.

    Article  Google Scholar 

  2. 2.

    Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: emergence of a successful pathogen. Clin Microbiol Rev. 2008;21(3):538–82.

    CAS  Article  Google Scholar 

  3. 3.

    Nemec A, Krizova L, Maixnerova M, van der Reijden TJ, Deschaght P, Passet V, et al. Genotypic and phenotypic characterization of the Acinetobacter calcoaceticus-Acinetobacter baumannii complex with the proposal of Acinetobacter pittii sp. nov. (formerly Acinetobacter genomic species 3) and Acinetobacter nosocomialis sp. nov. (formerly Acinetobacter genomic species 13TU). Res Microbiol. 2011;162(4):393–404.

    CAS  Article  Google Scholar 

  4. 4.

    Antunes LC, Visca P, Towner KJ. Acinetobacter baumannii: evolution of a global pathogen. Pathog and Dis. 2014;71(3):292–301.

    CAS  Article  Google Scholar 

  5. 5.

    Doi Y, Murray GL, Peleg AY. Acinetobacter baumannii: evolution of antimicrobial resistance-treatment options. Semin Respir Rrit Care Med. 2015;36(1):85–98.

    Article  Google Scholar 

  6. 6.

    Mera RM, Miller LA, Amrine-Madsen H, Sahm DF. Acinetobacter baumannii 2002-2008: increase of carbapenem-associated multiclass resistance in the United States. Microb Drug Resist. 2010;16(3):209–15.

    Article  Google Scholar 

  7. 7.

    Xiao YH, Giske CG, Wei ZQ, Shen P, Heddini A, Li LJ. Epidemiology and characteristics of antimicrobial resistance in China. Drug Resist Updat. 2011;14(4–5):236–50.

    Article  Google Scholar 

  8. 8.

    Hu FP, Guo Y, Zhu DM, Wang F, Jiang XF, Xu YC, et al. Resistance trends among clinical isolates in China reported from CHINET surveillance of bacterial resistance, 2005-2014. Clin Microbiol Infect. 2016;22(Suppl 1):S9–14.

    CAS  Article  Google Scholar 

  9. 9.

    Docquier JD, Mangani S. Structure-function relationships of class D Carbapenemases. Curr Drug Targets. 2016;17(9):1061–71.

    CAS  Article  Google Scholar 

  10. 10.

    Antunes NT, Lamoureaux TL, Toth M, Stewart NK, Frase H, Vakulenko SB. Class D -lactamases: are they all Carbapenemases? Antimicrob Agents Chemother. 2014;58(4):2119–25.

    Article  Google Scholar 

  11. 11.

    Evans BA, Amyes SG. OXA beta-lactamases. Clin Microbiol Rev. 2014;27(2):241–63.

    Article  Google Scholar 

  12. 12.

    Bou G, Oliver A, Martinez-Beltran J. OXA-24, a novel class D beta-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother. 2000;44(6):1556–61.

    CAS  Article  Google Scholar 

  13. 13.

    Mendes RE, Bell JM, Turnidge JD, Castanheira M, Jones RN. 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 Agents Chemother. 2009;63(1):55–9.

    CAS  Article  Google Scholar 

  14. 14.

    Ji S, Chen Y, Ruan Z, Fu Y, Ji J, Fu Y, et al. Prevalence of carbapenem-hydrolyzing class D beta-lactamase genes in Acinetobacter spp. isolates in China. Eur J Clin Microbiol Infect Dis. 2014;33(6):989–97.

    CAS  Article  Google Scholar 

  15. 15.

    Higgins PG, Lehmann M, Wisplinghoff H, Seifert H. gyrB multiplex PCR to differentiate between Acinetobacter calcoaceticus and Acinetobacter genomic species 3. J Clin Microbiol. 2010;48(12):4592–4.

    CAS  Article  Google Scholar 

  16. 16.

    Higgins PG, Wisplinghoff H, Krut O, Seifert H. A PCR-based method to differentiate between Acinetobacter baumannii and Acinetobacter genomic species 13TU. Clin Microbiol Infect. 2007;13(12):1199–201.

    CAS  Article  Google Scholar 

  17. 17.

    Woodford N, Ellington MJ, Coelho JM, Turton JF, Ward ME, Brown S, et al. Multiplex PCR for genes encoding prevalent OXA carbapenemases in Acinetobacter spp. Int J Antimicrob Agents. 2006;27(4):351–3.

    CAS  Article  Google Scholar 

  18. 18.

    Poirel L, Walsh TR, Cuvillier V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis. 2011;70(1):119–23.

    CAS  Article  Google Scholar 

  19. 19.

    Afzal-Shah M, Woodford N, Livermore DM. Characterization of OXA-25, OXA-26, and OXA-27, molecular class D beta-lactamases associated with carbapenem resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother. 2001;45(2):583–8.

    CAS  Article  Google Scholar 

  20. 20.

    Vila J, Marcos MA, Jimenez de Anta MT. A comparative study of different PCR-based DNA fingerprinting techniques for typing of the Acinetobacter calcoaceticus-A. baumannii complex. J Med Microbiol. 1996;44(6):482–9.

    CAS  Article  Google Scholar 

  21. 21.

    Bou G, Cervero G, Dominguez MA, Quereda C, Martinez-Beltran J. PCR-based DNA fingerprinting (rep-PCR, AP-PCR) and pulsed-field gel electrophoresis characterization of a nosocomial outbreak caused by imipenem- and meropenem-resistant Acinetobacter baumannii. Clin Microbiol Infect. 2000;6(12):635–43.

    CAS  Article  Google Scholar 

  22. 22.

    Diancourt L, Passet V, Nemec A, Dijkshoorn L, Brisse S. The population structure of Acinetobacter baumannii: expanding multiresistant clones from an ancestral susceptible genetic pool. PLoS One. 2010;5(4):e10034.

    Article  Google Scholar 

  23. 23.

    Grundmann H, Hori S, Tanner G. Determining confidence intervals when measuring genetic diversity and the discriminatory abilities of typing methods for microorganisms. J Clin Microbiol. 2001;39(11):4190–2.

    CAS  Article  Google Scholar 

  24. 24.

    Kim UJ, Kim HK, An JH, Cho SK, Park KH, Jang HC. Update on the epidemiology, treatment, and outcomes of Carbapenem-resistant Acinetobacter infections. Chonnam Med J. 2014;50(2):37–44.

    CAS  Article  Google Scholar 

  25. 25.

    Wernli D, Jorgensen PS, Harbarth S, Carroll SP, Laxminarayan R, Levrat N, et al. Antimicrobial resistance: the complex challenge of measurement to inform policy and the public. PLoS Med. 2017;14(8):e1002378.

    Article  Google Scholar 

  26. 26.

    Mugnier PD, Poirel L, Naas T, Nordmann P. Worldwide dissemination of the bla OXA-23 carbapenemase gene of Acinetobacter baumannii. Emerg Infect Dis. 2010;16(1):35–40.

    CAS  Article  Google Scholar 

  27. 27.

    Wu W, He Y, Lu J, Lu Y, Wu J, Liu Y. Transition of bla OXA-58-like to bla OXA-23-like in Acinetobacter baumannii clinical isolates in southern China: an 8-year study. PLoS One. 2015;10(9):e0137174.

    Article  Google Scholar 

  28. 28.

    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(9):2941–5.

    CAS  Article  Google Scholar 

  29. 29.

    Nunez Quezada T, Rodriguez CH, Castro Canarte G, Nastro M, Balderrama Yarhui N, et al. Outbreak of bla OXA-72-producing Acinetobacter baumannii in South America. J Chemother. 2017;29(5):321–4.

    Article  Google Scholar 

  30. 30.

    Sari AN, Bicmen M, Gulay Z. The first report on the outbreak of OXA-24/40-like Carbapenemase-producing Acinetobacter baumannii in Turkey. Jpn J Infect Dis. 2013;66(5):439–42.

    Article  Google Scholar 

  31. 31.

    Merino M, Acosta J, Poza M, Sanz F, Beceiro A, Chaves F, et al. OXA-24 carbapenemase gene flanked by XerC/XerD-like recombination sites in different plasmids from different Acinetobacter species isolated during a nosocomial outbreak. Antimicrob Agents Chemother. 2010;54(6):2724–7.

    CAS  Article  Google Scholar 

  32. 32.

    Wang H, Guo P, Sun H, Wang H, Yang Q, Chen M, et al. Molecular epidemiology of clinical isolates of carbapenem-resistant Acinetobacter spp. from Chinese hospitals. Antimicrob Agents Chemother. 2007;51(11):4022–8.

    CAS  Article  Google Scholar 

  33. 33.

    Lemos EV, de la Hoz FP, Alvis N, Einarson TR, Quevedo E, Castaneda C, et al. Impact of carbapenem resistance on clinical and economic outcomes among patients with Acinetobacter baumannii infection in Colombia. Clin Microbiol Infect. 2014;20(2):174–80.

    CAS  Article  Google Scholar 

  34. 34.

    Huang ST, Chiang MC, Kuo SC, Lee YT, Chiang TH, Yang SP, et al. Risk factors and clinical outcomes of patients with carbapenem-resistant Acinetobacter baumannii bacteremia. J Microbiol Immunol Infect. 2012;45(5):356–62.

    Article  Google Scholar 

  35. 35.

    Carlet J, Ben Ali A, Chalfine A. Epidemiology and control of antibiotic resistance in the intensive care unit. Curr Opin Infect Dis. 2004;17(4):309–16.

    Article  Google Scholar 

  36. 36.

    Chusri S, Silpapojakul K, McNeil E, Singkhamanan K, Chongsuvivatwong V. Impact of antibiotic exposure on occurrence of nosocomial carbapenem-resistant Acinetobacter baumannii infection: a case control study. J Infect Chemother. 2015;21(2):90–5.

    CAS  Article  Google Scholar 

  37. 37.

    Surasarang K, Narksawat K, Danchaivijitr S, Siripanichgon K, Sujirarat D, Rongrungrueng Y, et al. Risk factors for multi-drug resistant Acinetobacter baumannii nosocomial infection. J Med Assoc Thail. 2007;90(8):1633–9.

    Google Scholar 

  38. 38.

    Kim T, Chong YP, Park SY, Jeon MH, Choo EJ, Chung JW, et al. Risk factors for hospital-acquired pneumonia caused by carbapenem-resistant gram-negative bacteria in critically ill patients: a multicenter study in Korea. Diagn Microbiol Infect Dis. 2014;78(4):457–61.

    Article  Google Scholar 

  39. 39.

    Karah N, Sundsfjord A, Towner K, Samuelsen O. Insights into the global molecular epidemiology of carbapenem non-susceptible clones of Acinetobacter baumannii. Drug Resist Updat. 2012;15(4):237–47.

    CAS  Article  Google Scholar 

  40. 40.

    Ruan Z, Chen Y, Jiang Y, Zhou H, Zhou ZH, Fu Y, et al. Wide distribution of CC92 carbapenem-resistant and OXA-23-producing Acinetobacter baumannii in multiple provinces of China. Int J Antimicrob Agents. 2013;42(4):322–8.

    CAS  Article  Google Scholar 

  41. 41.

    Tacconelli E, Cataldo MA, Dancer SJ, De Angelis G, Falcone M, Frank U, et al. ESCMID guidelines for the management of the infection control measures to reduce transmission of multidrug-resistant gram-negative bacteria in hospitalized patients. Clin Microbiol Infect. 2014;20(Suppl 1):1–55.

    Article  Google Scholar 

  42. 42.

    Johnson JK, Robinson GL, Zhao L, Harris AD, Stine OC, Thom KA. Comparison of molecular typing methods for the analyses of Acinetobacter baumannii from ICU patients. Diagn Microbiol Infect Dis. 2016;86(4):345–50.

    CAS  Article  Google Scholar 

  43. 43.

    Thom KA, Hsiao WW, Harris AD, Stine OC, Rasko DA, Johnson JK. Patients with Acinetobacter baumannii bloodstream infections are colonized in the gastrointestinal tract with identical strains. Am J Infect Control. 2010;38(9):751–3.

    Article  Google Scholar 

  44. 44.

    Morris AK, Masterton RG. Antibiotic resistance surveillance: action for international studies. J Antimicrob Chemother. 2002;49(1):7–10.

    CAS  Article  Google Scholar 

Download references

Funding

The study was supported by a grant from the National Key Program for Infectious Diseases of China (2018ZX10733402), Beijing Natural Science Foundation (7172157) and the Beijing Nova Program (Z181100006218107).

Availability of data and materials

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Author information

Author notes

  1. Yong Chen, Yuying Yang and Lin Liu contributed equally to this work.

Affiliations

  1. Department of Hospital Infection Control, Chinese PLA Institute for Disease Control and Prevention, 20# Dongda Str, Beijing, 100071, China

    Yong Chen, Lin Liu, Xuelin Han, Shuguang Tian, Jingya Zhao, Fangyan Chen & Li Han

  2. School of Public Health, Shenyang Medical College, Shenyang, China

    Yuying Yang & Jinke Sun

  3. The 202nd Hospital of PLA, Shenyang, 110003, China

    Yuying Yang & Jinke Sun

  4. Laboratory of Tropical Biomedicine Technology, School of Tropical Medicine and Laboratory Medicine, Hainan Medical University, Haikou, China

    Lin Liu

  5. Department of Clinical Microbiology, The 202nd Hospital of PLA, Shenyang, China

    Guangbin Qiu

  6. Department of Infection Prevention and Hospital Hygiene, Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Hajo Grundmann

  7. Department of Medical Microbiology, University Medical Center Groningen, Rijksuniversteit Groningen, Groningen, The Netherlands

    Hajo Grundmann

  8. Department of Hospital Infection Control, The 202nd Hospital of PLA, Shenyang, 110003, China

    Haifeng Li

  9. Chinese PLA 202 Hospital, Shenyang, 110003, China

    Jinke Sun

Authors
  1. Yong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuying Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guangbin Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuelin Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuguang Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jingya Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fangyan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hajo Grundmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Haifeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jinke Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Li Han
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LH, HL, JS and HG conceptualized and designed the study. YY, LL, GQ, XH, ST, JZ, FC were involved in the data collection, generation, and performed laboratory analysis. YC, YY and LL analyzed and interpreted the data, drafted the manuscript. LH and HG revised the manuscript critically for important intellectual content. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Haifeng Li or Jinke Sun or Li Han.

Ethics declarations

Ethics approval and consent to participate

The study was approved by the institutional ethics committees of the Academy of Military Medical Sciences of the Chinese People’s Liberation Army, Beijing, China. Because the study was epidemiological without any interventions and all the data were collected and analyzed anonymously, the requirement for informed consent was waived.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

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.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Chen, Y., Yang, Y., Liu, L. et al. High prevalence and clonal dissemination of OXA-72-producing Acinetobacter baumannii in a Chinese hospital: a cross sectional study. BMC Infect Dis 18, 491 (2018). https://doi.org/10.1186/s12879-018-3359-3

Download citation

Keywords

  • Acinetobacter baumannii
  • OXA carbapenemases
  • Risk factor
  • Molecular typing
  • Clone dissemination

BMC Infectious Diseases

ISSN: 1471-2334

Contact us

\