There have been conflicting data about the interactions between vancomycin and beta-lactam agents against Staphylococcus aureus strains with heterogeneous resistance to vancomycin. We evaluated the efficacy of these combinations against Mu 3 and heterogeneously vancomycin-resistant S. aureus (hetero-VRSA) strains which were isolated from Korean patients using a population analysis method. Antagonistic effects were observed when less than 1 g/mL of beta-lactam antibiotics was combined with vancomycin, whereas synergistic effects were noticed with more than 4 microgram/mL of beta-lactam antibiotics. The antagonistic effects at low concentrations of beta-lactams were most prominent at 2 microgram/mL of vancomycin, which were the vancomycin MICs of tested hetero-VRSA strains. This study showed the variable effects of vancomycin- beta-lactam combinations depending on the concentrations of beta-lactam antibiotics and this property could be used to develop screening methods for hetero-VRSA strains.
Anti-Bacterial Agents/*pharmacology ; Cefotaxime/pharmacology ; Drug Synergism ; Human ; In Vitro ; Microbial Sensitivity Tests ; Oxacillin/*pharmacology ; Staphylococcus aureus/*drug effects ; Vancomycin/*pharmacology ; Vancomycin Resistance ; beta-Lactam Resistance

Antimicrobial resistance surveillance is necessary to determine the size of the problem and to guide empirical selection of antimicrobial agents for treating infected patients. The aim of this study was to analyze the results of susceptibility tests performed by hospitals participating in the Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) program. The rates of oxacillin-resistant staphylococci, penicillin-nonsusceptible pneumococci, and ampicillin-resistant E. faecium were over 70%. Ampicillin-resistant H. influenzae increased to 68%. Expanded-spectrum cephalosporin-resistant K. pneumoniae, fluoroquinolone-resistant E. coli, and imipenem-resistant P. aeruginosa remained at 16% through 27%, depending on the species. The proportions of vancomycin-resistant E. faecium and imipenem-resistant P. aeruginosa were 18 - 24% and 19-21%, respectively, indicating the seriousness of antimicrobial resistance. In conclusion, the increasing prevalence of resistant bacteria indicates that more concerted effort is required to conserve the usefulness of precious new antimicrobial agents.
Anti-Bacterial Agents/*pharmacology ; Cephalosporins/*pharmacology ; *Drug Resistance, Microbial ; Enterococcus/*drug effects ; Gram-Negative Bacteria/*drug effects ; Human ; Imipenem/*pharmacology ; Korea ; *Vancomycin Resistance

The trend of antimicrobial resistance of bacteria isolated from patients in 30 Korean hospitals in 1999 was analyzed with a particular attention to cefotaxime- or fluoroquinolone-resistant gram-negative bacilli, imipenem-resistant Pseudomonas aeruginosa, and vancomycin-resistant enterococci. Adequacy of susceptibility testing, and any change in the frequencies of isolated species were also analyzed. The results showed that only 20% and 30% of hospitals tested the piperacillin-tazobactam and cefoxitin susceptibility of Enterobacteriaceae, respectively, only 24% of hospitals the piperacillin-tazobactam susceptibility of P. aeruginosa, and 17% of hospitals the fusidic acid susceptibility of staphylococci. Among the isolates 26.3% were glucose-nonfermenting gram-negative bacilli, and 34.7% of Enterococcus were Enterococcus faecium. Slight decline of cefotaxime-resistance rate to 20% was noted in Klebsiella pneumoniae, while fluoroquinolone-resistantce rate was 68% in Acinetobacter baumannii. The ceftazidime- and imipenem-resistance rates were 17% and 18%, respectively in P. aeruginosa. The vancomycin-resistance rate of E. faecium rose significantly to 15.1%, but the rates varied significantly depending on hospitals suggesting presence of different degree of selective pressure or nosocomial spread. In conclusion, the prevalence of imipenem-resistant P. aeruginosa and the increase of vancomycin-resistant E. faecium were the particularly worrisome phenomena observed in this study.
Anti-Infective Agents, Fluoroquinolone/*pharmacology ; Antibiotics/*pharmacology ; Cephalosporins/*pharmacology ; Drug Resistance, Microbial ; Enterobacteriaceae/drug effects ; Enterococcus/*drug effects ; Gram-Negative Bacteria/*drug effects ; Human ; Imipenem/*pharmacology ; Korea ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa/drug effects ; *Vancomycin Resistance

OBJECTIVETo investigate the homology and resistant mechanism of vancomycin-resistant Enterococci (VRE) isolates.

METHODSA total of 9 VRE isolates were collected from 2006 to 2007 at PUMC hospital. The susceptibility of these isolates to 10 different antibiotics including vancomycin was tested by E-test. These strains were processed by brain heart infusion agar screening in the presence of vancomycin (6 microg/ml), and were analyzed for genotypic characteristics using the multiplex PCR. The homology of the isolates was determined by pulsed-field gel electrophoresis (PFGE).

RESULTSAll the 9 VRE isolates were identified as Enterococci faecium. The visual analysis of PFGE patterns revealed 6 different PFGE types. The vanA gene was confirmed by PCR and sequencing in 9 VRE isolates, which were consistent between phenotype and genotype for glycopeptides resistance.

CONCLUSIONSOnly vanA genotype was detected in PUMC hospital. Clonal dissemination, horizontal gene transfer, and the selective pressure of antimicrobial agents may contribute to the increase of VRE.

Bacterial Proteins ; genetics ; Bacterial Typing Techniques ; Drug Resistance, Multiple, Bacterial ; Enterococcus faecium ; classification ; drug effects ; genetics ; isolation & purification ; Gram-Positive Bacterial Infections ; microbiology ; Humans ; Vancomycin Resistance

OBJECTIVETo analyze the infection status and the drug resistance of enterococci in patients with severe hepatitis to guide future treatment.

METHODSAll bacteria from infected patients with severe hepatitis were cultured with BacT/Alert120 automation instrument (Aksu) and identified with Vitek-AMS60 (Biomerieux). Drug sensitivities of the isolated enterococci were tested with 11 antibacterial agents.

RESULTSAmong the 112 isolated enterococci, Enterococcus faecalis was the most preponderant bacterium, and the second was E. faecium. Their isolation rates were 79.5% and 14.3%, respectively. 57.1% of all the enterococci were found in the ascetic fluid of patients with severe hepatitis. Fifty-eight (51.8%) isolated enterococci were found to be high level aminoglycoside resistant (HLAR), 19 (17.0%) enterococci were ampicillin-resistant enterococcus (ARE) and 7 (6.3%) were both HLAR and ARE. The susceptive rates of the enterococci to vancomycin and teicoplanin were very high, namely 96.4% and 100%, respectively. No vancomycin or teicoplanin resistant enterococci were found, but 4 enterococci were mildly sensitive to vancomycin.

CONCLUSIONEnterococcus faecalis is the most prevalent species isolated in severe hepatitis patients infected with enterococcal infection. From our study, vancomycin and teicoplanin are the drugs of first choice to treat those infections.

Aminoglycosides ; pharmacology ; Ampicillin Resistance ; Drug Resistance, Bacterial ; Enterococcus faecalis ; drug effects ; Gram-Positive Bacterial Infections ; complications ; microbiology ; Hepatitis ; microbiology ; Humans ; Microbial Sensitivity Tests ; Teicoplanin ; pharmacology ; Vancomycin ; pharmacology

INTRODUCTIONVancomycin-resistant enterococci (VRE) have emerged as one of the major nosocomial antimicrobial-resistant pathogens globally. In this article, we describe the epidemiology of VRE in Singaporean public hospitals in the 5 years following the major local VRE outbreak in 2005.

MATERIALS AND METHODSA passive laboratory surveillance programme identified non-duplicate VRE isolates from 7 hospitals from 2006 to 2010. Descriptive statistics and time-series analysis was performed on all clinical VRE isolates for each individual hospital as well as for the combined dataset.

RESULTSThere were a total of 418 VRE isolates over 5 years, of which 102 isolates (24.4%) were from clinical cultures. Between 0.4% and 0.7% of all clinical enterococcal isolates were resistant to vancomycin. The overall incidence-density of VRE did not change over time in Singapore despite 2 separate outbreaks in tertiary hospitals in 2009 and 2010. Incidence-density of clinical VRE cases fell in 2 secondary hospitals, while another 2 hospitals experienced no significant VRE infections after 2008.

CONCLUSIONThe prevalence of VRE clinical isolates remains low in Singaporean public sector hospitals. However, the presence of at least 2 outbreaks in separate hospitals over the past 5 years indicates the need for continued vigilance in order to prevent any further increase in VRE prevalence locally.

Anti-Bacterial Agents ; pharmacology ; Cross Infection ; epidemiology ; Enterococcus ; drug effects ; isolation & purification ; Gram-Positive Bacterial Infections ; drug therapy ; Hospitals, Public ; Humans ; Population Surveillance ; Singapore ; epidemiology ; Vancomycin ; therapeutic use ; Vancomycin Resistance ; drug effects

Enterococci recently became the second-to-third most commonly isolated organism from nosocomial infections. Enterococci are intrinsically more resistant to many antimicrobial agents and often show acquired resistance to many antimicrobial agents including high-level aminoglycosides. With the increased use of vancomycin, vancomycin-resistant enterococci (VRE) has become an important nosocomial pathogen. In Korea, the proportion of VRE among all enterococcal of VRE is no longer low in some settings and recent observations of a sudden increase of VRE isolation in several hospitals in Korea suggests that VRE infection may become a serious problem in the near future. The most important considerations are that vancomycin-resistant genes may spread to other highly virulent genera, such as MRSA, and that there are no approved and convincingly effective antibiotics for the treatment of VRE. Therefore, current efforts have concentrated on limiting the spread of these organisms within the hospital environment. Prudent use of antimicrobial agents and strict adherence to preventive measures such as aggressive communication, education, and infection control practices are essential to control the spread of this organism. However, hospital infection control protocols and the laboratory support they require are costly in terms of space and supplies, as well as in personnel resources. These factors add further pressure to already stretched hospital budgets. Nevertheless, policies or programs defining and managing VRE infection or colonization should be established and now is the time to enforce an overall management strategy against VRE.
Antibiotics, Glycopeptide/therapeutic use* ; Bacterial Infections/prevention & control ; Bacterial Infections/drug therapy* ; Drug Resistance, Microbial* ; Enterococcus/drug effects* ; Human ; Korea ; Microbial Sensitivity Tests ; Prevalence ; Vancomycin/therapeutic use*

An increase in vancomycin-resistant enterococcal (VRE) bacteremia in hemato-oncological patients (n=19) in our institution from 2000 through 2001 led us to analyze the molecular epidemiologic patterns and clinical features unique to our cases. The pulsed field gel electrophoresis of the isolates revealed that the bacteremia was not originated from a single clone but rather showed endemic pattern of diverse clones with small clusters. A different DNA pattern of blood and stool isolates from one patient suggested exogenous rather than endogenous route of infection. Enterococcus faecium carrying vanA gene was the causative pathogen in all cases. Patients with VRE bacteremia showed similar clinical courses compared with those with vancomycin-susceptible enterococcal (VSE) bacteremia. Vancomycin resistance did not seem to be a poor prognostic factor because of similar mortality (5/8, 62.5%) noted in VSE bacteremia. Initial disease severity and neutropenic status may be major determinants of prognosis in patients with VRE bacteraemia.
Adolescent ; Adult ; Bacteremia/*drug therapy/microbiology ; Bacterial Proteins/genetics ; Carbon-Oxygen Ligases/genetics ; Electrophoresis, Gel, Pulsed-Field ; Enterococcus/*drug effects/genetics ; Female ; Humans ; Male ; Middle Aged ; *Vancomycin Resistance

BACKGROUNDVancomycin-resistant Enterococci (VRE) cause serious infections that are difficult to treat. We carried out this study to determine the mutant prevention concentration (MPC) of linezolid when combined with minocycline against VRE strains, to determine the mechanism of drug resistance in vitro, and to provide a theoretical basis for the rational use of drugs against VRE.

METHODSThe minimum inhibitory concentrations (MICs) of linezolid and minocycline against 30 Enterococci (E.) isolates (including 20 VRE strains) were determined by the broth microdilution method. Drug interactions were assessed by the checkerboard microdilution tests and confirmed by time-kill studies. Two vancomycin-susceptible strains N27 and N40 (linezolid MIC, 2 g/ml; minocycline MIC, 4 µg/ml) and control strains E. faecalis ATCC 29212 and ATCC 51299 were also tested. The MPCs of linezolid and minocycline (alone and combined) were determined using the agar dilution method. Strains showing stable resistance were analyzed by polymerase chain reaction (PCR) amplification of domain V of the 23S rRNA gene.

RESULTSCheckerboard titration studies revealed synergistic effects of combination therapy in 26.7% of 30 E. isolates. Antagonism was not observed. The G2576U mutation was detected in stable linezolid-resistant strains of ATCC 29212, N40, and N27 before and after resistance screening, and MIC values increased with the number of G2576U mutations. The MPC of linezolid against E. decreased dramatically when combined with minocycline, and vice versa.

CONCLUSIONLinezolid or minocycline alone produce resistant strains; however, their joint use may reduce the MPC of each agent against VRE, thereby decreasing resistant mutants and bacterial infections.

Acetamides ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Anti-Infective Agents ; pharmacology ; Drug Therapy, Combination ; Enterococcus ; drug effects ; genetics ; Linezolid ; Microbial Sensitivity Tests ; Minocycline ; pharmacology ; Mutation ; Oxazolidinones ; pharmacology ; Vancomycin Resistance

Continued antimicrobial resistance surveillance can provide valuable information for the empirical selection of antimicrobial agents for patient treatment, and for resistance control. In this 6th annual study for 2002, the susceptibility data at 39 Korean Nationwide Surveillance of Antimicrobial Resistance (KONSAR) hospitals were analyzed. Resistance rates of S. aureus were 67% to oxacillin, and 58% to clindamycin. The ampicillin and vancomycin resistance rates of E. faecium were 89% and 16%, respectively. To penicillin, 71% of S. pneumoniae were nonsusceptible. Resistance rates of E. coli were 11% to cefotaxime, 8% to cefoxitin, and 34% to fluoroquinolone, and those of K. pneumoniae were 22% to ceftazidime, and 16% to cefoxitin. Lowest resistance rates to cephalosporins shown by E. cloacae and S. marcescens were to cefepime, 7% and 17%, respectively. This is the first KONSAR surveillance, which detected imipenem-resistant E. coli and K. pneumoniae. To imipenem, 22% of P. aeruginosa and 9% of Acinetobacter spp. were resistant. Trends of resistances showed a slight reduction in MRSA and in penicillin- nonsusceptible S. pneumoniae, but an increase in ampicillin-resistant E. faecium. Ampicillin-resistant E. coli and H. influenzae remained prevalent. Compared to the previous study, amikacin- and fluoroquinolone- resistant Acinetobacter spp. increased to 60% and 62%, respectively. Ceftazidime- resistant K. pneumoniae decreased slightly, and imipenem- resistant P. aeruginosa and Acinetobacter spp., and vancomycin-resistant E. faecium increased. In conclusion, vancomycin-resistant E. faecium, cefoxitin-resistant E. coli and K. pneumoniae, and imipenem-resistant P. aeruginosa and Acinetobacter spp. increased gradually, and imipenem- resistant E. coli and K. pneumoniae appeared for the first time. Continued surveillance is required to prevent further spread of these serious resistances.
Anti-Bacterial Agents/*therapeutic use ; Cefoxitin/*therapeutic use ; Drug Resistance, Bacterial ; Enterococcus/*drug effects ; Fluoroquinolones/therapeutic use ; Gram-Negative Bacterial Infections/*drug therapy/*epidemiology ; Gram-Positive Bacterial Infections/drug therapy/epidemiology ; Humans ; Imipenem/therapeutic use ; Korea/epidemiology ; Prevalence ; *Vancomycin Resistance