Mi-Ran Seo

Association of QnrB Determinants and Production of Extended-Spectrum β-Lactamases or Plasmid-Mediated AmpC β-Lactamases in Clinical Isolates of Klebsiella pneumoniae

ABSTRACT Clinical isolates of Escherichia coli and Klebsiella pneumoniae producing extended-spectrum β-lactamases or plasmid-mediated AmpC β-lactamases were screened for qnrA and qnrB genes. QnrB was present in 54 of 54 DHA-1-producing K. pneumoniae isolates and 10 of 45 SHV-12-producing ones, suggesting that the distribution of plasmids conferring resistance to extended-spectrum cephalosporins and quinolones in clinical isolates of K. pneumoniae is widespread.

Epidemiology of Clostridium difficile infections in a tertiary-care hospital in Korea.

To survey healthcare-associated Clostridium difficile infection (HA-CDI) in a 900-bed tertiary-care hospital, we prospectively investigated the epidemiology of CDI and distribution of PCR-ribotypes. From February 2009 through January 2010, all patients with HA-CDI were enrolled. Epidemiological information and prescription records for antibiotics were collected. The C. difficile isolates were characterized using reference strains and were tested for antibiotic susceptibility. During the survey, incidence of HA-CDI was 71.6 per 100 000 patient-days. In total, 140 C. difficile isolates were obtained from 166 patients with HA-CDI. The PCR-ribotyping yielded 38 distinct ribotypes. The three most frequently found ribotypes made up 56.4% of all isolates; they comprised 37 isolates (26.4%) of PCR-ribotype 018, 22 (15.7%) of toxin A-negative PCR-ribotype 017, and 20 (14.3%) of PCR-ribotype 001. Clostridium difficile PCR-ribotype 018 was present in all departments throughout the hospital during the 11 months, whereas ribotype 017 and ribotype 001 appeared mostly in the pulmonary department. Hypervirulent C. difficile PCR-ribotype 027 was detected in 1 month on two wards. The incidence of CDI in each department showed a seven-fold difference, which correlated significantly with the amount of prescribed clindamycin (R = 0.783, p 0.013) or moxifloxacin (R = 0.733, p 0.025) in the departments. The rates of resistance of the three commonest ribotypes to clindamycin and moxifloxacin were significantly higher than those of other strains (92.1% versus 38.2% and 89.5% versus 27.3%, respectively). CDI is an important nosocomially acquired infection and this study emphasizes the importance of implementing country-wide surveillance to detect and control CDI in Korea.

Risk factors and clinical features of infections caused by plasmid-mediated AmpC β-lactamase-producing Enterobacteriaceae

A case-control study was performed with the objective of analysing risk factors and clinical features of infections caused by plasmid-mediated AmpC beta-lactamase (plasmid AmpC)-producing Enterobacteriaceae. All patients infected with plasmid AmpC-producing Enterobacteriaceae in two tertiary care hospitals from December 2006 to August 2007 were included. Plasmid AmpC enzymes were characterised by isoelectric focusing, enzyme inhibition assay and enzyme-specific polymerase chain reaction. A total of 30 patients (20 with Klebsiella pneumoniae and 10 with Escherichia coli) were recruited prospectively. CMY-2 and DHA-1 were the most common plasmid AmpC in E. coli and K. pneumoniae, respectively. An independent risk factor for infection with plasmid AmpC-producing Enterobacteriaceae was the use of an oxyimino-cephalosporin within 1 month of plasmid AmpC infection [adjusted odds ratio (aOR), 10.8, 95% confidence interval (CI), 1.6-75.4; P=0.016], with the use of a urinary catheter showing borderline significance (aOR, 6, 95% CI 0.93-38.4; P=0.06). An independent risk factor for treatment failure at 72 h was infection due to plasmid AmpC-producing Enterobacteriaceae (aOR, 9.78, 95% CI 1.34-71.17; P=0.02). These results suggest that infections caused by plasmid AmpC-producing isolates significantly increase treatment failure at 72 h and that prior use of an oxyimino-cephalosporin is a risk factor for infections caused by plasmid AmpC-producing Enterobacteriaceae.

Epidemiology and clinical characteristics of Clostridium difficile infection in a Korean tertiary hospital.

In order to investigate the incidence, clinical and microbiologic characteristics of Clostridium difficile infection (CDI) in Korea, a prospective observational study was performed. From September 2008 through January 2010, all patients whose stool was tested for toxin assay A&B and/or C. difficile culture were studied for clinical characteristics. Toxin types of the isolates from stool were tested. The mean incidence of CDI per 100,000 patient-days was 71.6 by month (range, 52.5-114.0), and the ratio of CDI to antibiotic-associated diarrhea was 0.23. Among 200 CDI patients, 37.5% (75/200) was severe CDI based on severity score. Clinical outcome of 189 CDI was as followed; 25.9% (49/189) improved without treatment, 84.3% (118/140) achieved clinical cure and attributed mortality was 0.7% (1/140) with the treatment. Recurrence rate was 21.4% (30/140) and cure without recurrence was 66.4% (93/140). The most common type of toxin was toxin A-positive/toxin B-positive strain (77.5%), toxin A-negative/toxin B-positive strains or binary toxin-producing strains comprised 15.4% or 7.1%, respectively. In conclusion, the incidence of CDI in Korea is a little higher than other reports during the non-epidemic setting. We expect that the change of epidemiology and clinical severity in CDI can be evaluated based on these results.

Clinical and microbiologic characteristics of tcdA-negative variant Clostridium difficile infections.

BackgroundThe tcdA-negative variant (A-B+) of Clostridium difficile is prevalent in East Asian countries. However, the risk factors and clinical characteristics of A-B+C. difficile infections (CDI) are not clearly documented. The objective of this study was to investigate these characteristics.MethodsFrom September 2008 through January 2010, the clinical characteristics, medication history and treatment outcomes of CDI patients were recorded prospectively. Toxin characterization and antibiotic susceptibility tests were performed on stool isolates of C. difficile.ResultsDuring the study period, we identified 22 cases of CDI caused by tcdA-negative tcdB-positive (A-B+) strains and 105 cases caused by tcdA-positive tcdB-positive (A+B+) strains. There was no significant difference in disease severity or clinical characteristics between the two groups. Previous use of clindamycin and young age were identified as significant risk factors for the acquisition of A-B+ CDI (OR = 4.738, 95% CI 1.48–15.157, p = 0.009 and OR = 0.966, 95% CI 0.935–0.998, p = 0.038, respectively) in logistic regression.Rates of resistance to clindamycin were 100% and 69.6% in the A-B+ and A+B+ isolates, respectively (p = 0.006), and the ermB gene was identified in 17 of 21 A-B+ isolates (81%). Resistance to moxifloxacin was also more frequent in the A-B+ than in the A+B+ isolates (95.2% vs. 63.7%, p = 0.004).ConclusionsThe clinical course of A-B+ CDI is not different from that of A+B+ CDI. Clindamycin use is a significant risk factor for the acquisition of tcdA-negative variant strains.

Characteristics of Plasmid-Mediated Quinolone Resistance Genes in Extended-Spectrum Cephalosporin-Resistant Isolates of Klebsiella pneumoniae and Escherichia coli in Korea

Background: Quinolone resistance is frequently associated with extended-spectrum cephalosporin resistance in Enterobacteriaceae. Methods: The characteristics of plasmid-mediated quinolone resistance (PMQR) genes [qnr genes, aac(6′)-Ib-cr and qepA] in clinical isolates of Klebsiella pneumoniae and Escherichia coli resistant to extended-spectrum cephalosporin were studied. Results: 5 and 4 of 95 E. coli isolates but 46 (86/187) and 6% (12/187) of K. pneumoniae had qnr and aac(6′)-Ib-cr, respectively, and 8 K. pneumoniae contained both genes.qepA was not identified. qnrB, especially qnrB4, was the predominant qnr subtype in K. pneumoniae [94 (88 qnrB of 94 qnr) and 88% (77 qnrB4 of 88 qnrB), respectively], and presence of qnrB4 was closely related with DHA-1 β-lactamase (99%). However, K. pneumoniae isolates with qnrB4 and blaDHA-1 were clonally diverse. β-Lactamases produced by PMQR-containing isolates were variable: CMY-1, CTX-M-14, CTX-M-15, DHA-1, OXA type, SHV-2a, and SHV-12. Conclusion: PMQR genes are widely distributed among clinical isolates of K. pneumoniae, and qnrB4 associated with blaDHA-1 was the most common PMQR gene in Korea.

Clinical characteristics of relapses and re-infections in Clostridium difficile infection.

The purpose of this study was to identify factors associated with relapses or re-infections in patients with recurring Clostridium difficile infections (CDIs). From September 2008 to January 2012, cases with two or more isolates from consecutive CDI episodes were included. PCR-ribotyping and multilocus variable-number tandem-repeat analysis were performed using paired isolates. Among 473 patients, 68 (14.4%) experienced one to five recurrences. Fifty-one of these with two or more isolates from consecutive CDI episodes were included in the study; 25 (49%) were classified as relapses and 26 (51%) as re-infections. Recurrence interval was shorter in the relapse group (26.0 versus 67.5 p 0.001), but more patients in the re-infection group were hospitalized during recurrence interval (53.8% versus 8.0%, p<0.001). Relapse rates in infections by ribotype 017, ribotype 018 and other ribotypes were 63.6%, 63.6% and 22.2%, respectively (p 0.274, p 0.069, and p 0.005). In multivariate logistic regression, infections by ribotypes 017 and 018 were associated with CDI relapse (OR 4.77, 95% CI 1.02-22.31, p 0.047; OR 11.49, 95% CI 2.07-63.72, p 0.005). Conversely, admission during recurrence interval lowered the risk of relapse (OR 0.044, 95% CI 0.006-0.344, p 0.003). In conclusion, relapse was more likely when infection was caused by PCR ribotypes 017 and 018.

Prevalence, genetic relatedness and antibiotic resistance of hospital-acquired clostridium difficile PCR ribotype 018 strains

Clostridium difficile infection (CDI) is a major healthcare-associated infection. The aim of this study was to investigate the genetic relatedness of the endemic C. difficile PCR ribotype 018 strains in an institution and changes to their characteristics during a five-year period. A total of 207 isolates from inpatients at Hanyang University Hospital from 2009 to 2013 were analysed using multilocus variable-number tandem-repeat analysis (MLVA). Minimum inhibitory concentrations (MICs) of several antibiotics were determined. In total, 204 (98.6%) were genetically related, with a summed tandem-repeat distance (STRD) ≤ 10. Minimum-spanning-tree analysis identified 78 MLVA types, categorized into six clonal complexes (CCs). The largest cluster, CC-I, included 51 MLVA types from 148 isolates (71.5%) and the second largest cluster, CC-II, included 10 MLVA types from 36 isolates (17.4%). Resistance rates for antibiotics were: clindamycin (CLI), 97.6%; moxifloxacin (MXF), 98.6%; vancomycin (VAN), 1.4%; and rifaximin (RFX), 8.2%. All isolates were susceptible to piperacillin/tazobactam (TZP) and metronidazole (MTZ). Comparing the MICs of antibiotics for the isolates each year from 2009 to 2013, MICs of antibiotics that promote CDI, such as CLI, MXF, TZP and RFX, increased over the five-year period (P-value by Kruskal-Wallis test: < 0.0001, <0.0001, <0.0001, and <0.0001 respectively); however, MICs of VAN or MTZ, antibiotics for treatment of CDI, did not increase or decreased over the same time period (P-value by Kruskal-Wallis test: 0.166, <0.0001). C. difficile RT018 isolates in a tertiary hospital over a five-year period presented a close clonal relationship. MICs of antibiotics promoting CDI increased with this clonal expansion.