Hui-Ying Wang

Emergence of extensively drug-resistant Acinetobacter baumannii complex over 10 years: Nationwide data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program

BackgroundAcinetobacter baumannii complex (ABC) has emerged as an important pathogen causing a variety of infections. Longitudinal multicenter surveillance data on ABC from different sources in Taiwan have not been published. Using data from the Taiwan Surveillance of Antimicrobial Resistance (TSAR) conducted biennially, we investigated the secular change in resistance of 1640 ABC from 2002 to 2010 (TSAR period III to VII) to different antimicrobial agents and identified factors associated with imipenem-resistant and extensively drug-resistant ABC (IRABC and XDRABC).MethodsIsolates were collected by TSAR from the same 26 hospitals located in all 4 regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined by reference broth microdilution method. Isolates nonsusceptible to all tested aminoglycosides, fluoroquinolones, β-lactam, β-lactam/β-lactam inhibitors, and carbapenems were defined as extensively drug-resistant (XDR). Multivariate logistic regression analysis was performed to assess the relationship between predictor variables among patients with resistant ABC and patients with non-resistant ABC.ResultsThe prevalence of IRABC increased from 3.4% in 2002 to 58.7% in 2010 (P < 0.001; odds ratio [OR], 2.138; 95% confidence interval [CI], 1.947 to 2.347) and that of XDRABC increased from 1.3% in 2002 to 41.0% in 2010 (P < 0.001; OR, 1.970; 95% CI, 1.773-2.189). The rates of non-susceptibility to other antimicrobial agents remained high (>55%) over the years with some fluctuations before and after TSAR V (2006) on some agents. Multivariate analysis revealed that recovery from elderly patients, origins other than blood, from ICU settings, or geographic regions are independent factors associated with IRABC and XDRABC. Although the prevalence of XDRABC increased in all four regions of Taiwan over the years, central Taiwan had higher prevalence of XDRABC starting in 2008. Susceptibility to polymyxin remained high (99.8%).ConclusionsThis longitudinal multicenter surveillance program revealed significant increase and nationwide emergence of IRABC and XDRABC in Taiwan over the years. This study also identified factors associated with IRABC and XDRABC to help guide empirical therapy and at-risk groups requiring more intense interventional infection control measures with focused surveillance efforts.

Epidemiology and Molecular Characterization of Macrolide-Resistant Streptococcus pyogenes in Taiwan

ABSTRACT Our multicenter nationwide surveillance data indicated that erythromycin (ERY) resistance among group A Streptococcus (GAS) isolates in Taiwan declined from 53.1% in 1998 and 2000 to 14.6% in 2002 and 2004 and 10.7% in 2006 to 2010 (P < 0.01). The present study aimed to assess the epidemiology of GAS in Taiwan and identify factors associated with ERY resistance. All 127 ERY-resistant (ERYr) isolates and 128 randomly selected ERY-susceptible (ERYs) isolates recovered from 1998 to 2010 were emm typed. ERYr isolates were also characterized by ERY resistance phenotype and mechanisms and pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing was performed on selected ERYr isolates. The predominant emm types in ERYr isolates were emm22 (n = 33, 26.0%), emm12 (n = 24, 18.9%), emm4 (n = 21, 16.5%), and emm106 (n = 15, 11.8%). In ERYs isolates, emm12 (n = 27, 21.9%), emm1 (n = 18, 14.1%), emm106 (n = 16, 12.5%), and emm11 (n = 9, 7.1%) predominated. The most common ERY resistance phenotype was the M phenotype (resistant to macrolides) (70.9%), with all but one isolate carrying mef(A), followed by the constitutive macrolide-lincosamide-streptogramin B resistance (cMLSB) phenotype (26.8%), with isolates carrying erm(B) or erm(TR). ERYr isolates of the emm12-sequence type 36 (ST36) lineage with the cMLSB phenotype were mostly present before 2004, while those of the emm22-ST46 lineage with the M phenotype predominated in later years. Recovery from respiratory (throat swab) specimens was an independent factor associated with ERY resistance. emm1 and emm11 GAS isolates were significantly associated with ERYs, while emm22 was detected only in ERYr GAS. In addition, emm106 isolates were prevalent among the abscess/pus isolates, whereas emm12 isolates were strongly associated with a respiratory (throat) origin. In addition to identifying factors associated with ERY resistance in GAS, our study provides helpful information on the changing GAS epidemiology in Taiwan.

Levofloxacin-Resistant Haemophilus influenzae, Taiwan, 2004–2010

Levofloxacin resistance in Haemophilus influenzae has increased significantly in Taiwan, from 2.0% in 2004 to 24.3% in 2010 (p<0.001). Clinical and molecular investigations of 182 levofloxacin-resistant isolates revealed that the increase was mainly the result of the spread of several clones in the elderly population in different regions.

Antimicrobial Non-Susceptibility of Escherichia coli from Outpatients and Patients Visiting Emergency Rooms in Taiwan.

Longitudinal nationwide surveillance data on antimicrobial non-susceptibility and prevalence of extended-spectrum β-lactamases (ESBLs) as well as AmpC β-lactamases producers among Escherichia coli from different sources in the community settings are limited. Such data may impact treatment practice. The present study investigated E. coli from outpatients and patients visiting emergency rooms collected by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program. A total of 3481 E. coli isolates were studied, including 2153 (61.9%) from urine and 1125 (32.3%) from blood samples. These isolates were collected biennially between 2002 and 2012 from a total of 28 hospitals located in different geographic regions of Taiwan. Minimum inhibitory concentrations (MIC) were determined using methods recommended by the Clinical Laboratory Standards Institute (CLSI). The prevalence and factors associated with the presence of ESBL and AmpC β-lactamase-producers were determined. Significant increases in non-susceptibility to most β-lactams and ciprofloxacin occurred during the study period. By 2012, non-susceptibility to cefotaxime and ciprofloxacin reached 21.1% and 26.9%, respectively. The prevalence of ESBL- and AmpC- producers also increased from 4.0% and 5.3%, respectively, in 2002–2004, to 10.7% for both in 2010–2012 (P < 0.001). The predominant ESBL and AmpC β-lactamase genes were CTX-M and CMY-types, respectively. Non-susceptibility of urine isolates to nitrofurantoin remained at around 8% and to fosfomycin was low (0.7%) but to cefazolin (based on the 2014 CLSI urine criteria) increased from 11.5% in 2002–2004 to 23.9% in 2010–2012 (P <0.001). Non-susceptibility of isolates from different specimen types was generally similar, but isolates from elderly patients were significantly more resistant to most antimicrobial agents and associated with the presence of ESBL- and AmpC- β-lactamases. An additional concern is that decreased ciprofloxacin susceptibility (MIC 0.12–1 mg/L) was as high as 25% in isolates from all age groups, including those from pediatric patients. Our data indicated that there is a need to re-evaluate appropriate treatment selection for community-acquired infections in Taiwan. Identification of community reservoirs of multidrug-resistant E. coli is also warranted.

The Antimicrobial Susceptibility of Klebsiella pneumoniae from Community Settings in Taiwan, a Trend Analysis

Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002–2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3rd generation cephalosporins and ciprofloxacin were found during the study period. By 2012, susceptibility to cefotaxime and ciprofloxacin was 83.6% and 81.6%, respectively. The prevalence of ESBL-producers increased from 4.8% in 2002 to 11.9% in 2012 (P = 0.012), while that of AmpC β-lactamase-producers increased from 0% to 9.5% in the same period (P < 0.001). Phylogenic analysis of the ESBL and AmpC-β-lactamase-producers by pulsed-field gel electrophoresis and multi-locus sequence typing revealed wide genetic diversity even among the most common sequence type 11 isolates (33.0%). By multivariate analysis, later study year, elderly, and urine isolates were associated with carriage of ESBL genes, while only urine isolates were associated with carriage of AmpC β-lactamase genes. Further studies are needed to determine which antibiotics are reasonable empirical therapy options for patients presenting with severe sepsis that might be caused by K. pneumoniae.

Prevalence and characteristics of pks genotoxin gene cluster-positive clinical Klebsiella pneumoniae isolates in Taiwan

The pks gene cluster encodes enzymes responsible for the synthesis of colibactin, a genotoxin that has been shown to induce DNA damage and contribute to increased virulence. The present study investigated the prevalence of pks in clinical K. pneumoniae isolates from a national surveillance program in Taiwan, and identified microbiological and molecular factors associated with pks-carriage. The pks gene cluster was detected in 67 (16.7%) of 400 isolates from various specimen types. Multivariate analysis revealed that isolates of K1, K2, K20, and K62 capsular types (p < 0.001), and those more susceptible to antimicrobial agents (p = 0.001) were independent factors strongly associated with pks-carriage. Phylogenetic studies on the sequence type (ST) and pulsed-field gel electrophoresis patterns indicated that the pks-positive isolates belong to a clonal group of ST23 in K1, a locally expanding ST65 clone in K2, a ST268-related K20 group, and a highly clonal ST36:K62 group. Carriage of rmpA, iutC, and ybtA, the genes associated with hypervirulence, was significantly higher in the pks-positive isolates than the pks-negative isolates (95.5% vs. 13.2%, p < 0.001). Further studies to determine the presence of hypervirulent pks-bearing bacterial populations in the flora of community residents and their association with different disease entities may be warranted.

Rapid Identification of Bacteria and Candida Pathogens in Peritoneal Dialysis Effluent from Patients with Peritoneal Dialysis-Related Peritonitis by Use of Multilocus PCR Coupled with Electrospray Ionization Mass Spectrometry

ABSTRACT PCR coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was compared with culture for pathogen detection in peritoneal dialysis (PD)-related peritonitis. Of 21 samples of PD effluent, PCR/ESI-MS identified microorganisms in 18 (86%) samples, including Mycobacterium tuberculosis in 1 culture-negative sample. Of 15 double-positive samples, PCR/ESI-MS and culture reached levels of agreement of 100% (15/15) and 87.5% (7/8) at the genus and species levels, respectively. PCR/ESI-MS can be used for rapid pathogen detection in PD-related peritonitis.

Prevalence of and risk factors for methicillin-resistant Staphylococcus aureus colonization among human immunodeficient virus–infected outpatients in Taiwan: oral Candida colonization as a comparator

ABSTRACT Human immuodeficency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) and community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have increased in recent years in Taiwan. This study was undertaken to determine the prevalence of and risk factors for nasal and oral S. aureus and MRSA colonization among contemporary HIV-infected populations. Clinical variables for S. aureus and MRSA colonization among HIV-infected outpatients from three hospitals were analyzed and compared with those for oral Candida colonization. Genetic characteristics of MRSA isolates were analyzed. A total of 714 patients were screened for nasal S. aureus colonization, and a subset of 457 patients were also screened for oral S. aureus colonization. Of all patients, 79.4% were receiving HAART, and their mean CD4 count was 472 cells/mm3. The colonization rates in the oral cavity, nasal cavity, and at either site were 18.8%, 31.7%, and 36.8%, respectively, for S. aureus, and 3.1%, 4.4%, and 5.5%, respectively, for MRSA. These rates were all much lower than the previously reported rate of oral Candida colonization (52.4%). By multivariate analysis, a suppressed viral load (<200 copies/mL) protected against oral S. aureus, MRSA, and Candida colonization, and recent use of antibacterial agents protected against oral and nasal S. aureus colonization. Recent incarceration increased the risk of nasal MRSA colonization, while recent hospitalization, tuberculosis, older age, and intravenous drug use increased the risk of oral Candida colonization. Candida spp. did not augment S. aureus or MRSA colonization in the oral cavity. Most of the 41 MRSA isolates recovered belonged to the SCCmec IV/pvl-negative (51.2%) and VT/pvl-positive (26.8%) ST59 local prevalent CA-MRSA clones. Distinct carriage rates demonstrated here suggested that mucosal immunity against colonization might differ in terms of microbes and sites. A decreased risk in oral carriage of MRSA and Candida might be a benefit of HAART.

Multiclonal emergence of levofloxacin-resistant group B Streptococcus, Taiwan

Objectives This study investigated the trend in antimicrobial resistance among group B Streptococcus (GBS) from a national surveillance programme in Taiwan and delineated characteristics of and factors associated with levofloxacin-resistant isolates. Methods Clinical isolates of all sample types and patient groups were collected from multiple hospitals biennially between 2002 and 2012. Susceptibilities to different antibiotics were determined by broth microdilution. Molecular studies of levofloxacin-resistant isolates included serotyping, PFGE, mutations in the QRDRs and MLST. Results A total of 1559 isolates were tested and all remained susceptible to penicillin, cephalosporins, meropenem and vancomycin. However, levofloxacin resistance increased from 2.2% (range 0%-3.3%) in 2002-06 to 6.2% (5.9%-7.5%) in 2008-12 (P = 0.016). Among the 88 levofloxacin-resistant isolates, the majority (79.5%) had the GyrA(S81L)+ParC(S79F/Y) double mutations and most (54.5%) were also resistant to clindamycin, erythromycin and tetracycline. The predominant genotype of the levofloxacin-resistant isolates was ST19/serotype III (43.2%). Four previously unreported genotypes, ST1 and its single-locus variants (ST920 and ST922)/serotype VI (28.4%) and ST1/serotype II (18.2%), were found to have circulated locally. Serotype III isolates were predominately from urine and female genital tract specimens and <65-year-old adult outpatients, while serotype II and VI isolates were mostly from respiratory and urine samples and >65-year-old inpatients. Multivariate analysis revealed that elderly age and respiratory samples were independent factors associated with levofloxacin resistance. Conclusions Multiclonal emergence and dissemination of levofloxacin-resistant GBS isolates occurred in healthcare and community settings in Taiwan. Continuous molecular-level surveillance is important to detect new epidemic trends.