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Clin Microbiol Infect

Abstract

Acinetobacter baumannii has emerged as an important cause of community-acquired infection. To characterize the microbiological and genotypic features of community-associated Acinetobacter baumannii, 32 isolates associated with community-acquired pneumonia were collected. These isolates were diverse in resistance patterns and had multiple clonal origins. blaOXA-23 was the main acquired oxacillinases-encoding gene detected.

Acinetobacter baumannii is responsible for a variety of nosocomial infections [1] and has also been found to be an important cause of community-acquired infection [2]. Community-acquired pneumonia due to A. baumannii (CAP-AB) is characterized by a fulminate course with high mortality rates, which was significantly different from hospital-acquired pneumonia due to A. baumannii (HAP-AB) [2–4]. Recent studies found that HAP-AB and CAP-AB isolates were significantly different in antimicrobial susceptibility profiles [2,4,5]. The aim of the study was to characterize the microbiological and genotypic features of A. baumannii isolates associated with CAP.

Thirty-two adult patients with CAP were studied. Pneumonia was defined according to the Infectious Diseases Society of America (IDSA) guidelines [6]. CAP was considered if pneumonia was acquired outside a hospital and the interval between symptom onset and previous discharge was >30 days. Community-associated A. baumannii was defined as isolates grown from sputum and/or blood from CAP patients and collected within 48 h after admission. All sputum specimens were in good quality for culture as checked by microscopy. Species identifications were initially performed using the MicroScan Walkaway 96 SI automated system (Siemens Healthcare Diagnostic, Deerfield, IL, USA). The identification of A. baumannii was confirmed partially by sequencing the recA gene as described previously [7,8]. Susceptibilities of the isolates to antimicrobial agents including piperacillin-tazobactam, ceftazidime, cefepime, aztreonam, amikacin, imipenem, meropenem, ciprofloxacin, sulbactam, polymyxin and minocycline, were tested using the agar dilution method and were interpreted following the recommendations of the Clinical and Laboratory Standards Institute (CLSI) [9]. Multiplex PCR was used to detect the presence of carbapenemase-encoding genes, including the oxacillinase genes(blaOXA-23, blaOXA-24, blaOXA-58 and blaOXA-51) and the metallo-β-lactamases (MBL) genes (blaGIM-1, blaSIM-1, blaSPM-1, blaIMP and blaVIM) as described previously [10,11]. In addition, PCR was also used to detect blaOXA-143, blaNDM-1 [12] and whether ISAba1 was located upstream of blaOXA-51-like or blaOXA-23 genes. All clinical isolates were typed using pulsed-field gel electrophoresis (PFGE) analysis. PFGE was performed on a CHEF-DRII system (Bio-Rad, Hercules, California, USA) for 20 h at 14°C, using a linear ramped pulse time of 5–20 s at 200 V. DNA fingerprints were interpreted as recommended by Tenover et al. [13]. Univariate analysis was conducted using Pearson’s chi-square test for categorical variables and the Mann–Whitney U-test for continuous variables. A p value of <0.05 was considered significant.

Of the CAPs associated with A. baumannii, 27 (84.4%) were patients with underlying chronic obstructive pulmonary disease. Susceptibility testing showed that 15 isolates were multidrug-resistant A. baumannii (MDR-AB) [14] and 17 isolates were non-MDR-AB (Table 1). A. baumannii was considered as MDR if it was resistant to three or more classes of antimicrobial agents. The clinical characteristics and predisposing factors of patients from whom MDR-AB and non-MDR-AB were isolated are shown in Table 2. The mortality of MDR-AB was significantly higher than that of non-MDR-AB. Histories of mechanical ventilation and previous antibiotic use were significantly more frequent in patients with MDR-AB than in those with non-MDR-AB. The isolates all contained a blaOXA-51-like gene but no ISAbal was detected upstream; blaOXA-23 with ISAba1 detected upstream was only found in MDR isolates. MBL and other blaOXA genes were not detected in any isolates (the results of PCR are shown in Table 3). PFGE showed that these isolates could be grouped into 11 clonal patterns, distinct from the mainly clonal dissemination hospital isolates [15,16]. Isolates with the clonal pattern were diverse in resistance profiles including MDR and non-MDR and those from patients with a hospitalization history, third-generation cephalosporin use and mechanical ventilation were more frequently MDR-AB isolates.

Table 1.  In vitro susceptibility of the 32 isolates to 11 antimicrobial agents tested.
Antimicrobial agentMIC (mg/L)Susceptible rate (%)
Range50%90%
  1. *The breakpoints were not defined by the Clinical and Laboratory Standards Institute.

Sulbactam0.03–160.2516−*
Meropenem0.03–320.03887.5
Imipenem0.03–160.06251665.625
Cefepime0.03–12811659.375
Ceftazidime0.03–12826450
Aztreonam0.03–51286421.875
Piperacillin-tazobactam0.03–1288850
Minocycline0.03–10.030.25100
Polymyxins0.03–0.030.030.03100
Ofloxacin0.03–1280.036446.875
Amikacin0.03–5120.062551253.125
Table 2.   Clinical characteristics and predisposing factors of patients from whom Acinetobacter baumannii were isolated
VariableMDR (= 15)non-MDR (= 17)
  1. *p <0.05.

Male gender11 (73.3%)12 (70.6%)
Age (years), mean ± SD68.2 ± 13.159 ± 13.5
Hospitalization history, no. (%)13 (86.7%)7 (41.2%)*
Co-morbid disease, no. (%)
 Chronic obstructive pulmonary disease15 (100%)12 (70.6%)
 Other pulmonary disease5 (38.5%)7 (41.2%)
 Malignancy3 (20.0%)3 (17.6%)
Medication, no. (%)
 Immunosuppressive therapy8 (53.3%) 
 Mechanical ventilation10 (66.7%)2 (11.8%)*
 Previous use of antibiotics within 2 months12 (80.0%)7 (41.2%)*
 Cephalosporins
  First-generation01 (5.9%)
  Second-generation3 (33.3%)1 (5.9%)
  Third-generation8 (53.3%)4 (23.5%)*
 Fluoroquinolones7 (46.7%)3 (17.6%)*
 Aminoglycosides4 (26.7%)5 (29.4%)
 Carbapenems3 (20.0%)0
Mortality7 (46.7%)2 (11.8%)*
Table 3.   PCR results of 15 MDR isolates
IsolatePCR
MBLgene blaNDM-1 blaOXA-51 blaOXA-23 blaOXA51+ISAba1 blaOXA23+ISAba1
1+++
2+++
3++
4++
5+++
6++
7+
8++
9+
10+
11+++
12++
13+++
14++
15+++

According to studies published previously [2,4,5], resistance rates of A. baumannii in the community and their MIC to most antimicrobial agents were lower than those in hospital. However, in this study over 30% of A. baumannii isolates were resistant to most commonly-used antimicrobial agents and the resistant rates of imipenem and meropenem were 18.75% and 9.375%, respectively. Of note, the resistance phenotypes of the isolates with the same PFGE pattern were different, which appear to be related to predisposing factors of host patients. Mechanical ventilation, hospitalization history and third-generation cephalosporin or fluoroquinolone use appeared to be associated with resistance level and resistance genes detected in isolates with the same PFGE pattern. We hypothesize that chronic obstructive pulmonary disease may result in repeated hospitalizations during which patients are more likely to become colonized with A. baumannii and probably develop invasive diseases sometime after discharge, even after 30 days post-discharge. The different resistance profiles of isolates with the same clonal origin but different hospitalization history seemed to suggest that the resistant strains in the community may come from the hospital environment and the selective pressure of third-generation cephalosporins affected the antimicrobial resistance of A. baumannii. Nonetheless, further studies are warranted as only a small number of isolates was included here.

Several previous studies have demonstrated that acquired resistance to carbapenems in A. baumannii is mainly mediated by class D β-lactamases and MBLs [1]. blaOXA-23 and blaOXA-51-like genes were detected in this study while other OXA-type carbapenemase and MBLs were not detected. blaOXA-51-like genes are widely distributed in A. baumannii, including carbapenem-susceptible isolates [17]. blaOXA-23 contributes to carbapenem resistance in A. baumannii globally [1] and was recently detected in environmental A. baumannii resistant to carbapenem [18]. In these isolates from the community, the data also indicated that the blaOXA-23 gene was consistently associated with isolates resistant to, or at least with reduced susceptibility to, carbapenems (MIC2-32 mg/L compared with MIC0-8 mg/L). However, blaOXA-23 was not only found in carbapenem-resistant isolates but was also present in imipenem-intermediate or meropenem-susceptible isolates, as exemplified by Wang et al. [19]. The genetic backgrounds in the process of acquiring blaOXA-23 are diverse [20] and another non-enzymic mechanism could also mediate carbapenem resistance [1].

In conclusion, our results suggest that the epidemiology of A. baumannii from the community is of multiclonal origins, different from those in hospital settings. The resistant phenotypes of isolates from the community are diverse. Mechanical ventilation and third-generation cephalosporin use seem to be the risk factors for acquiring MDR-AB. blaOXA-23 is the main oxacillinases enzyme detected.

Transparency Declaration

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Reference

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  2. Abstract
  3. Transparency Declaration
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