Frequency of Resistance to Aminog lycoside Antibiotics in Staphy lococcus aureus Isolated from Tertiary Hospitals / 감염

BACKGROUND: Staphylococcus aureus is one of the most important pathogens, causing severe morbidity and fatal infections. To date rapid evolution of antibiotic resistance in S. aureus, including recent emergence of vancomycin-resistant S. aureus (VRSA), has been a serious concern and an obstacle to the effective treatment. The purpose of this study is to update the resistance patterns against aminoglycoside antibiotics which play an important role in the therapy of serious staphylococcal infections. METHODS: Clinical isolates were collected from 8 university-affiliated hospitals during the period of June 1999 to January 2001. Susceptibility tests against 9 antibiotics were performed by disk diffusion method. Minimum inhibitory concentrations (MICs) of arbekacin against non-susceptible strains were determined by microbroth dilution method RESULTS: Among total 682 isolates exclusive of consecutive ones from the same patients, 199 (29%) were from pus, 152 (22%) from respiratory specimens, 137 (20%) from blood, 38 (6%) from urine. Of 682 isolates, 588 (87%) isolates were resistant to at least one of the aminoglycosides tested. Overall prevalence of MRSA was 64% (439/682), and resistance rates of MRSA were summarized as follows; kanamycin (KM) 98%, tobramycin (TOB) 98%, gentamicin (GM) 95%, amikacin (AMK) 90%, neomycin (NEO) 63%, streptomycin (SM) 31%, netilmicin (NET) 18%, arbekacin (ABK) 13%. MRSA isolates were resistant to multiple aminoglycosides, and 88% of them were resistant to all four aminoglycosides of KM, TOB, GM, and AMK. MICs of ABK against 58 non-susceptible strains ranged from 2 to 128 microgram/mL. CONCLUSION: More than 90% of MRSA isolates were resistant against kanamycin, tobramycin, gentamicin, and amikacin. Moreover, most of MRSA isolates were multi-drug resistant to all these four aminoglycosides. Resistance rates against arbekacin and netilmicin were less than 20%. Arbekacin was the most susceptible antibiotic of the aminoglycosides tested.

Identification of New Subtype of Human Immunodeficiency Virus Type 1 in a Korean Patient / 감염

BACKGROUD: In the previous study, we determined subtypes of Human Immunodeficiency Virus type 1 (HIV-1) in Korean patients by partial sequence analysis. We showed that eighteen of the nineteen sequences of HIV-1 from Korean fell into subtype B and one fell into subtype A. At that study, HIV-1 identified as subtype A showed 40% diversity from reference sequences and presumed to be a variant of subtype A. The aim of present study is to determine the molecuar biological characteristics of HIV-1 previously identified as subtype A. METHODS: Growth curve was determined. SI/NSI phenotype was determined using a cocultivation assay using MT-2 cells. A complete genome sequence was obtained by amplifying overlapping PCR fragments. Cowork was done to identify the subtype of HIV-1 previously identified as variant A from Korea (97KR004), Cyprus (94CY017), Democratic Republic of Congo (97CDKTB48, 97CDKFE4, 97CDKS10, 97CDKP58). Phylogenetic analysis, distance analysis, diversity plot analysis, bootstrap anlysis were done to identify the subtype of these newly characterized strains. RESULTS: We found that 97KR004 was SI phenotype. Complete sequence of 97KR004 was determined (AF286239). Phylogenetic analysis showed that the four newly characterized strains (94CY017, 97CDKTB48, 97CDKFE4, 97CDKS10) were closely related to subtype A. Subtype distance tool showed that these four strains fell to sub-subtype A2. Diversity plot analysis and bootstrap analysis were done to identify subtype of 97KR004. Nine subtype reference strains and 94CY017 strain were used as reference sequences. These analyses confirmed that 97KR004 represented sub-subtype A2/subtype D recombinant. CONCLUSOIN: We showed that 97KR004 fell into newly identified sub-subtype A2.

The Effect of Combination Therapy of Zidovudine, Lamivudine, and Indinavir in HIV Infected Patients / 감염

BACKGROUND: To evaluate the clinical efficacy, safety and tolerance of combination therapy of zidovudine, lamivudine and indinavir in HIV infected patients. METHODS: We reviewed medical records of HIV infected patients who had received combination therapy of zidovudine, lamivudine and indinavir at the Seoul National University Hospital between May 1998 and March 1999. The clinical end point was the time to the development of the opportunistic infection or death. Changes in plasma HIV-1 RNA levels and CD4 cell counts before and after combination treatments were also evaluated. RESULTS: Fifty-two patients were included in this study. Of these, 25 patients (48%) had continued the treatment more than 6 months, whereas 12 patients (23%) were lost to follow-up, and 15 patients (29%) had discontinued the treatment. The causes of discontinuation of the treatment were adverse drug effects in 67% (10/15), economic problem in 20% (3/15) and the development of drug resistance in 13% (2/15). Of the 25 patients who had been treated more than 6 months, 4 patients were excluded because they had not taken the necessary tests at the scheduled time points. Of the 21 evaluable patients, 3 patients (14%) developed opportunistic infections, but no patients died. In seventeen patients (81%), HIV RNA-1 titers decreased below the detectable level by 6 months of treatment. The mean decrease of HIV-1 RNA titer after 6 months of treatment was 2.65 log10 copies/mL. The mean increase of CD4 cell counts was 111 cells/mm3. CONCLUSION: Combination therapy of zidovudine, lamivudine and indinavir was effective in decrease of viral load and increase of CD4 cell counts. Half of the patients could not continue the combination therapy more than 6 months because of the adverse drug effects and/or economical problem.

Antibiotic Susceptibility of Enterococcal Isolates causing Bacteremia / 감염

BACKGROUND: Enterococci have emerged as an important nosocomial pathogen. Enterococcal infections are a therapeutic challange because of antibiotics resistance, especially high-level aminoglycoside resistance and vancomycin resistance. METHODS: We reviewed the medical records of enterococcal bacteremia patients admitted to Seoul National University Hospital between April 1996 and May 1998. The susceptibility of enterococci to ampicillin, vancomycin, teicoplanin, gentamicin, streptomycin, ciprofloxacin, imipenem, rifampin, and tetracyclin were determined by micro-dilution method. RESULTS: Forty-two episodes of enterococcal bacteremia were identified. Of the 42 bacteremia, 74% (31/42) were caused by E. faecalis, and 26% (11/42) by E. faecium. The most common underlying diseases were hepatobiliary diseases (24%) and cardiovascular diseases (24%). Cholangitis (21%), pneumonia (14%), catheter-related infection (10%), peritonitis (7%), urinary tract infection (7%) were the frequent primary infections for the enterococcal bacteremia. Of the 31 isolates of E. faecalis, 29 (94%) were susceptible to ampicillin, whereas only 36% (4/11) of E. faecium were susceptible to ampicillin. Of the isolates of E. faecalis, 61% (19/31) were highly resistant to gentamicin, 39% (12/31) highly resistant to streptomycin, and 32% (10/31) highly resistant to both gentamicin and streptomycin. Of the isolates of E. faecium, 45% (5/11), 55% (6/11), and 27% (3/11) were highly-resistant to gentamicin, streptomycin, and both gentamicin and streptomycin, respectively. Only one isolate of E. faecium showed resistance to vancomycin. CONCLUSION: Approximately one third of enterococcal blood isolates showed high-level resistance to gentamicin and streptomycin.

Prevalence of Staphylococcus aureus with Reduced Susceptibility to Vancomycin in a Tertiary Hospital / 감염

BACKGROUND: Recently isolates of S. aureus with intermediate (VISA) and heterogeneous resistance (hetero-VRSA) to vancomycin, which has been the only effective against MRSA infections, were identified. Several infections due to these isolates did not respond to adequate antibiotic treatments. In Japan, the prevalences of hetero-VRSA ranged from 0 to 48%. The aim of this study was to determine the prevalence of S. aureus heterogenously resistant to vancomycin and VISA. METHODS: The isolates were collected at Seoul National University Hospital from April 1998 to August 1999. To detect S. aureus with reduced susceptibility to vancomycin, brain heart infusion (BHI) agar with 4 mg/L of vancomycin and Mu-3 agar were used. Analysis of resistant subpopulations of bacteria (population analysis) was done. Minimum inhibitory concentration (MIC) for vancomycin was determined by microbroth and agar dilution methods, respectively according to NCCLS and Hiramatsu's recommendation. Coagulase type was determined with type I-VIII antisera. RESULTS: Total 235 MRSA, including 88 isolates from blood and 147 from other specimens, were collected. After 88 blood isolates were inoculated on BHI agar with 4 mg/L of vancomycin, 14 isolates (16 %) grew in variable colonies. But there were no subclones with vancomycin MIC > or =8 mg/L on population analysis and no isolates which grew confluently on Mu-3 agar with beta-lactam disks. In addition, 147 isolates from other specimens did not grow confluently on Mu-3 agar. Among 64 MRSA and 32 MSSA isolates, coagulase type II (49, 77%) and Vll(8, 25%) were respectively the most common types. CONCLUSION: In our tertiary-care hospital, there were no MRSA isolates with reduced susceptibilities to vancomycin.

Molecular Epidemiology and Surveillence of Vancomycin-resistant Enterococci at Seoul National University Hospital / 감염

BACKGROUND: The purpose of this study is to investigate the epidemiology and microbiological susceptibility patterns of vancomycin-resistant enterococci (VRE) in Seoul National University Hospital. METHODS: The VRE isolates between May 1998 and October 1999 were studied. We reviewed the medical records of VRE-isolated patients for clinical and epidemiologic data. The susceptibility of VRE to ampicillin, vancomycin, teicoplanin, gentamicin, streptomycin, ciprofloxacin, imipenem, rifampin, tetracyclin were determined by micro-dilution method. PCR for genotyping and PFGE for molecular epidemiology were performed. RESULTS: Twenty-nine VRE isolates were identified from 14 patients, 12 patients from clinical specimens and two from only rectal surveillence cultures. All strains were E. faecium and expressed vanA genotype. The vancomycin MIC and teicoplanin MIC were >128microgram/mL for all isolates. All isolates also resistant to most other antibiotics tested (ampicillin 84.2%, gentamicin 73.7%, streptomycin 73.7%, ciprofloxacin 84.2%, tetracycline 63.2%, rifampin 84.2%, imipenem 94.7%). PFGE analysis revealed 17 distinct PFGE strain types from 14 patients and there were no predominent types. Two patterns, each of them represented by two isolates, were identical. One of which was not associated epidemiologically but the other was associated with direct spread from colonized patient at the intensive care unit. CONCLUSION: The majority of VRE cases occurring at Seoul National University Hospital were not caused by epidemiologic strains but sporadic isolations although there was one case of patient to patient spread.