Antibiotic over-use has led to an increase in the prevalence of drug-resistant strains of
Acinetobacter. In the United States, South America, India, and China, more than 50% of
Acinetobacter species are resistant to carbapenems [
4]. At the same time, carbapenem-resistant
A. baumannii has become the most common genospecies of the CRACB complex. Our study showed that different hospitals had different CRAB/CRACB complex ratios, but a common feature was that CRAB accounted for most of our CRACB complex blood isolates. Researchers previously reported similar results for three other hospitals in Taiwan and in the US, but different results for Hong Kong, Denmark, and Norway [
16‐
20].
In our study, all CRAB isolates had the
blaOXA-51-like gene. The
blaOXA-23–like gene was the second commonest carbapenemase gene (88.10%), and its prevalence among CRAB isolates was higher than in previous reports in Taiwan. For example, Kuo et al. reported that the prevalence of the
blaOXA-23-like gene was 58% in a hospital in northern Taiwan [
21], while Lin et al. reported a 4.2% prevalence in a hospital in northern Taiwan [
22]. Chuang et al. reported a prevalence of 7.7% in Taiwan [
23]. Our data thus indicate that the prevalence of the
blaOXA-23like gene among CRAB isolates is increasing in Taiwan. In agreement with our findings, a report from Italy showed that the
blaOXA-23-like enzyme was the most common carbapenemase (81.7%) [
24]. Chusri et al. also reported that the prevalence of the
blaOXA-23-like gene was 95% in their hospital in Thailand [
25]. We think that carbapenem and/or cephalosporin antibiotics overuse could be responsible for the increased prevalence of the
blaOXA-23like gene among CRAB isolates. Lack of strict infection control strategy is another cause. We also found that only 4.09% of CRAB isolates had the
blaOXA-24–like gene, similar to two other studies in Taiwan (3% and 7.7%) [
21,
23]. The findings of Hu et al. report are similar to our study [
26]. They found that the prevalence of the
blaOXA-23-like gene was 93.5% and the
blaOXA-24-like gene was 4.6% in MacKay Memorial Hospital in Taiwan. Our study differed from Hu et al. in that firstly, we investigated the prevalence of different carbapenemase genes among CRAB in multiple tertiary centres (all > 1500 beds) in northern and central Taiwan. Secondly, we compared the MICs to imipenem and meropenem between the
blaOXA-23-like gene and the
blaOXA-24-like gene. Lastly, we compared the MICs of the bla
OXA-24-like highly resistant gene to ceftazidime, cefepime, amikacin, ampicillin/sulbactam, colistin and piperacillin/tazobactam. Although the
blaOXA-24-like gene accounts for only a small percentage of carbapenemase genes, it confers high resistance to carbapenems (Figs.
1 and
2). Since the occurrence of the
blaOXA-24–like gene was so rare, we performed PFGE analysis and antimicrobial susceptibility tests for this group. We found that the
blaOXA-24–like gene was almost totally resistant to amikacin, cefepime, ceftazidime, piperacillin/tazobactam and ampicillin/sulbactam. In our study, the isolates with
blaOXA-24–like gene were 100% sensitive to colistin. The second recommended antibiotic is tigecycline despite the absence of Clinical and Laboratory Standards Institute (CLSI) MICs breakpoints for tigecycline.
Our study showed that the MICs to imipenem and meropenem among CRAB isolates with the
blaOXA-23-like gene were much lower than that for those with the
blaOXA-24-like gene. Thus, the
blaOXA-24-like gene appears to confer greater resistance to carbapenem than the
blaOXA-23-like gene. We also identified 3 major PFGE types of
blaOXA-24-like genes in Taiwan based on ApaI digestion. Six
blaOXA-24-like genes of same cluster came from 3 different hospitals (Fig.
3). This suggested that inter-hospital transmission of this resistant gene could occur in Taiwan, and may help to explain the increasing prevalence of more drug-resistant strains of CRAB in Taiwan. There are two reasons that could lead to the facilitated transmission of CRAB strains among hospitals. Firstly, in Taiwan, a patient can gain admission to any tertiary teaching hospital freely, without a doctor’s referral. Usually, the same patient had also visited several different tertiary teaching hospitals for different diseases. Secondly, after discharge, many patients carry resistant pathogens from different hospitals in which they were cared for back to the private nursing home or private respiratory care unit where they reside. The resistant strains are easily transmitted in these sites there if no strict infection control strategy. Therefore, we recommend additional infection control interventions for these patients to reduce the spread of resistant strains of CRAB.
What is the prevalence in other countries of the carbapenemase genes found in our study and do they have similar or differing antibiotic susceptibilities? What are the MICs of the blaOXA-23-like gene and the blaOXA-24-like gene to ceftazidime-avibactam, meropenem-vaborbactam or fosfomycin? Future multicenter, multi-country investigations could provide more data on the worldwide prevalence of carbapenemase genes in CRAB isolates and help the treatment of CRAB.
There were some limitations in our study. Firstly, the analysis of antibiotics consumption is not listed in our study. We could not analyse the relationship between the prevalence of the OXA genes and antibiotic drug consumption data in these 4 tertiary teaching hospitals. We were also unable to compare the relationship between the prevalence of the OXA genes and infection control strategy between these 4 tertiary teaching hospitals. Secondly, we did not perform PFGE and antimicrobial susceptibility tests on all CRAB blood isolates. Thirdly, under or over estimation of imipenem and meropenem non-sensitivity for the blaOXA-24-like gene is possible due to the small number of blaOXA-24-like genes (only 11 isolates). Large-scale studies throughout Taiwan are needed to address this limitation.