Seok Hoon Jeong

Multidrug-Resistant Acinetobacter spp.: Increasingly Problematic Nosocomial Pathogens

Pathogenic bacteria have increasingly been resisting to antimicrobial therapy. Recently, resistance problem has been relatively much worsened in Gram-negative bacilli. Acinetobacter spp. are typical nosocomial pathogens causing infections and high mortality, almost exclusively in compromised hospital patients. Acinetobacter spp. are intrinsically less susceptible to antibiotics than Enterobacteriaceae, and have propensity to acquire resistance. A surveillance study in Korea in 2009 showed that resistance rates of Acinetobacter spp. were very high: to fluoroquinolone 67%, to amikacin 48%, to ceftazidime 66% and to imipenem 51%. Carbapenem resistance was mostly due to OXA type carbapenemase production in A. baumannii isolates, whereas it was due to metallo-β-lactamase production in non-baumannii Acinetobacter isolates. Colistin-resistant isolates were rare but started to be isolated in Korea. Currently, the infection caused by multidrug-resistant A. baumannii is among the most difficult ones to treat. Analysis at tertiary care hospital in 2010 showed that among the 1,085 isolates of Acinetobacter spp., 14.9% and 41.8% were resistant to seven, and to all eight antimicrobial agents tested, respectively. It is known to be difficult to prevent Acinetobacter spp. infection in hospitalized patients, because the organisms are ubiquitous in hospital environment. Efforts to control resistant bacteria in Korea by hospitals, relevant scientific societies and government agencies have only partially been successful. We need concerted multidisciplinary efforts to preserve the efficacy of currently available antimicrobial agents, by following the principles of antimicrobial stewardship.

Further Increases in Carbapenem-, Amikacin-, and Fluoroquinolone-Resistant Isolates of Acinetobacter spp. and P. aeruginosa in Korea: KONSAR Study 2009

Purpose The increasing prevalence of antimicrobial resistant bacteria has become a serious worldwide problem. The aim of this study was to analyze antimicrobial resistance data generated in 2009 by hospitals and commercial laboratories participating in the Korean Nationwide Surveillance of Antimicrobial Resistance program. Materials and Methods Susceptibility data were collected from 24 hospitals and two commercial laboratories. In the analysis, resistance did not include intermediate susceptibility. Duplicate isolates were excluded from the analysis of hospital isolates, but not from the commercial laboratory isolates. Results Among the hospital isolates, methicillin-resistant Staphylococcus aureus, penicillin G-non-susceptible Streptococcus pneumoniae based on meningitis breakpoint, and ampicillin-resistant Enterococcus faecium remained highly prevalent. The proportion of vancomycin-resistant E. faecium gradually increased to 29%. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae increased to 17% and 33%, respectively, and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp. and Pseudomonas aeruginosa increased to 33%, 67% and 39%, respectively. Amikacin-resistant Acinetobacter spp. increased to 48%. Imipenem-resistant Acinetobacter spp. and P. aeruginosa increased to 51% and 26%, respectively. Higher resistance rates were observed in intensive care unit (ICU) isolates than in non-ICU isolates among the isolates from hospitals. Resistance rates were higher in hospital isolates than in clinic isolates among the isolates from commercial laboratories. Conclusion Among the hospital isolates, ceftazidime-resistant K. pneumoniae and fluoroquinolone-resistant K. pneumoniae, Acinetobacter spp., and P. aeruginosa further increased. The increase in imipenem resistance was slight in P. aeruginosa, but drastic in Acinetobacter spp. The problematic antimicrobial-organism combinations were much more prevalent among ICU isolates.

Epidemiology and Characteristics of Metallo-β-Lactamase-Producing Pseudomonas aeruginosa

Metallo-β-lactamase-producing Pseudomonas aeruginosa (MPPA) is an important nosocomial pathogen that shows resistance to all β-lactam antibiotics except monobactams. There are various types of metallo-β-lactamases (MBLs) in carbapenem-resistant P. aeruginosa including Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany imipenemase (GIM), New Delhi metallo-β-lactamase (NDM), Florence imipenemase (FIM). Each MBL gene is located on specific genetic elements including integrons, transposons, plasmids, or on the chromosome, in which they carry genes encoding determinants of resistance to carbapenems and other antibiotics, conferring multidrug resistance to P. aeruginosa. In addition, these genetic elements are transferable to other Gram-negative species, increasing the antimicrobial resistance rate and complicating the treatment of infected patients. Therefore, it is essential to understand the epidemiology, resistance mechanism, and molecular characteristics of MPPA for infection control and prevention of a possible global health crisis. Here, we highlight the characteristics of MPPA.

Prevalence and diversity of carbapenemases among imipenem-nonsusceptible Acinetobacter isolates in Korea: emergence of a novel OXA-182

Increase in multidrug-resistant Acinetobacter poses a serious problem in Korea. In this study, 190 imipenem (IPM)-nonsusceptible (NS) Acinetobacter isolates from 12 Korean hospitals in 2007 were used to determine species, prevalence, and antimicrobial susceptibility of OXA carbapenemase- and metallo-β-lactamase (MBL)-producing isolates. bla(OXA)-₂₃-like and ISAba1-asssociated bla(OXA)-₅₁-like genes were detected in 80% and 12% of 178 IPM-NS Acinetobacter baumannii isolates, respectively. A novel bla(OXA)-₁₈₂ was detected in 12 IPM-NS A. baumannii isolates. Twelve out of 14 MBL-producing isolates were non-baumanniiAcinetobacter. A. baumannii isolates with OXA carbapenemase were more often resistant to aminoglycosides, ciprofloxacin, and tigecycline than non-baumannii Acinetobacter isolates with MBL. Identical pulsed- field gel electrophoresis patterns were observed in 89% of A. baumannii isolates with bla(OXA)-₂₃-like gene. In conclusion, extremely rapid increase of IPM-NS A. baumannii in previous Korean studies was mainly due to clonal spread of OXA-23-producing A. baumannii isolates. A novel OXA-182 emerged in Korea.

Changing epidemiology of nontuberculous mycobacterial lung disease in South Korea.

Abstract Objectives: Pulmonary nontuberculous mycobacteria (NTM) are increasing worldwide, but data from regions with an intermediate tuberculosis (TB) burden are insufficient, and the reason for the changing epidemiology of NTM lung disease is unclear. We investigated the trends of NTM lung disease at a tertiary hospital in Korea and evaluated the contribution of liquid culture systems. Methods: We conducted a retrospective observational study of mycobacterial cultures of respiratory specimens from 26,793 patients at Severance Hospital in South Korea from January 2006 to December 2010. Results: The recovery percent of Mycobacterium tuberculosis isolates was 5.9% in 2006 and 7.1% in 2010, and the recovery percent of NTM isolates was 2.0% in 2006 and 6.3% in 2010. The annual percent of NTM isolation has increased steadily every year (p for trend < 0.001), and the proportion of patients from whom NTM was isolated increased from 21.4% in 2006 to 55.0% in 2010 (p for trend < 0.001). The incidence (per 100,000 inpatients and outpatients) of patients with NTM lung disease was 1.82 in 2006 and increased to 4.38 in 2010 (p < 0.001). Although the proportion of positive cultures in liquid medium only was higher for NTM than for M. tuberculosis (p < 0.001), the NTM recovery rate has increased in solid medium culture systems. Conclusions: The incidence of patients with NTM isolated from respiratory specimens and NTM lung disease increased from 2006 to 2010 in South Korea, a region with an intermediate TB burden.

Extensively drug-resistant Acinetobacter baumannii: risk factors for acquisition and prevalent OXA-type carbapenemases—a multicentre study

In this study, we investigated the risk factors for and carbapenem resistance mechanisms of extensively drug-resistant Acinetobacter baumannii (XDR-AB). Isolates of XDR-AB were collected from seven tertiary care hospitals in South Korea. A case-control study for risk factor analysis was performed and the presence of the metallo-β-lactamase (MBL) and OXA genes was examined. The control group consisted of adult inpatients receiving care from the same hospital. XDR-AB were isolated from 26 patients who were studied for risk factor analysis. Third-generation cephalosporin use [odds ratio (OR)=9.6, 95% confidence interval (CI) 1.3-171.3; P=0.02] and Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR=1.2, 95% CI 1.1-1.5; P=0.004) were identified as risk factors for acquisition of XDR-AB. Pulsed-field gel electrophoresis (PFGE) showed clonal epidemic isolates in hospitals. MBLs were not detected, and all 30 XDR-AB isolates had upregulated OXA-type carbapenemase genes. These results suggest that third-generation cephalosporin use and disease severity are associated with XDR-AB acquisition amongst typical adult inpatients. This study also points to intrahospital spread of XDR-AB. Upregulated OXA-type carbapenemases are prevalent in XDR-AB founded in South Korean hospitals.

Boronic acid disk tests for identification of extended-spectrum β-lactamase production in clinical isolates of Enterobacteriaceae producing chromosomal AmpC β-lactamases

A study using boronic acid (BA) was designed to detect the extended-spectrum beta-lactamases (ESBLs) in Enterobacteriaceae producing chromosomal AmpC beta-lactamases. A total of 197 clinical isolates of Enterobacter spp. (n=100), Serratia marcescens (n=62) and Citrobacter freundii (n=35) were analysed. Genes encoding ESBLs were detected by polymerase chain reaction (PCR) amplification followed by direct sequencing of PCR products. The Clinical and Laboratory Standards Institute confirmatory test detected only 72.1% of the ESBL-producing isolates. When a > or =5mm increase in the zone diameter of either the cefotaxime/clavulanic acid and/or the ceftazidime/clavulanic acid disks tested in combination with BA versus cefotaxime and/or ceftazidime containing BA was considered to be a positive for ESBL, the method detected 60 (98.4%) of the 61 isolates that harboured ESBLs and showed no false-positive results for ESBL-non-producing isolates. In conclusion, the BA disk test is a highly sensitive and specific method for the detection of ESBLs in Enterobacteriaceae producing chromosomal AmpC beta-lactamases.

Further Increase of Vancomycin-Resistant Enterococcus faecium, Amikacin- and Fluoroquinolone-Resistant Klebsiella pneumoniae, and Imipenem-Resistant Acinetobacter spp. in Korea: 2003 KONSAR Surveillance

Monitoring temporal trends of antimicrobial resistance can provide useful information for the empirical selection of antimicrobial agents to treat infected patients and for the control of nosocomial infections. In this study, we analyzed antimicrobial resistance of clinically relevant bacteria in 2003 at Korean hospitals and at a commercial laboratory. The following organism-antimicrobial agent resistance combinations were very prevalent: oxacillin-resistant Staphylococcus aureus (68%), expanded-spectrum cephalosporin-resistant Klebsiella pneumoniae (25%), and fluoroquinolone-resistant Escherichia coli (33%), Acinetobacter spp. (58%), and Pseudomonas aeruginosa (40%). Moreover, gradual increases in vancomycin-resistant Enterococcus faecium (20%), cefoxitin-resistant E. coli (10%) and K. pneumoniae (23%), and imipenem-resistant P. aeruginosa (20%) and Acinetobacter spp. (13%) were also observed. The resistance rates of Acinetobacter spp. to most antimicrobial agents at hospitals and at the commercial laboratory were similar. Among the Acinetobacter spp. isolated at a tertiary-care hospital, 46.2% were multidrug-resistant to 9-12 of 13 antimicrobial agents, and 18.3% were panresistant. The exclusion of duplicate isolates at a tertiary-care hospital significantly lowered the proportion of oxacillin-resistant S. aureus, vancomycin-resistant E. faecium, and fluoroquinolone-resistant E. coli.

Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type I procollagen synthesis in human skin fibroblasts

UVB reduces type I procollagen levels and increases matrix metalloproteinases-1 (MMP-1) levels in human skin and plays a major role in the process of photoaging. We previously reported that fucoidan inhibits UVB-induced MMP-1 expression at the protein and mRNA levels in human skin fibroblasts (HS68). Yet, the effects of fucoidan on UVB-induced MMP-1 promoter activity and type I procollagen have not been investigated. In this study, we assessed the effects of fucoidan on the inhibition of MMP-1 promoter activity and on the increase of type I procollagen synthesis in human skin fibroblasts. Fucoidan treatment significantly inhibited MMP-1 promoter activity compared to UVB irradiation alone. Fucoidan treatment also increased type I procollagen mRNA and protein expression in a dose-dependent manner compared to the control. Our data indicate that fucoidan may prevent UVB-induced MMP-1 expression and inhibit down-regulation of type I procollagen synthesis. We suggest that fucoidan may be a potential therapeutic agent to prevent and treat skin photoaging.

In vivo emergence of colistin resistance in Acinetobacter baumannii clinical isolates of sequence type 357 during colistin treatment

This study was performed to investigate the mechanisms of in vivo acquisition of colistin resistance in A. baumannii during colistin treatment. Three colistin-susceptible/resistant pairs of A. baumannii were recovered from patients who underwent colistin treatment. All of the 6 isolates included in this study shared an identical sequence type (ST), ST375, and they showed identical SmaI-macrorestriction patterns by pulsed-field gel electrophoresis. The individual colistin-resistant isolates harbored distinct mutations in the pmrB gene. Mutations detected in the pmrB gene were Ala227Val, Pro233Ser, and frame shift from Phe26. In matrix-assisted laser desorption ionization-time of flight analysis, colistin-resistant isolates were different from their colistin-susceptible counterparts, and they showed additional distinct peaks at 1852 m/z, 1937 m/z, 1954 m/z, 1975 m/z, 2034 m/z, and 2157 m/z. In vivo selection of colistin-resistant A. baumannii occurred independently in strains of ST357 during colistin treatment, and the strains acquired colistin resistance via mutations in the pmrB gene resulting in modification of lipid A components.