Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis.

Unique alterations in penicillin-binding protein 2B of multidrug-resistant Streptococcus pneumoniae from Korea / 감염

BACKGROUND: Pneumococcal resistance became a global issue during the past decades. Korea is reported to be the hottest spot in the world with regard to the prevalence of penicillin and multidrug resistance. Previous molecular epidemiologic studies strongly suggested that antibiotic-resistant pneumococci from Korea are genetically related. To investigate the molecular characteristics of multidrug-resistant (MDR) pneumococcal isolates in Korea, we performed the DNA sequencing of the gene encoding penicillin-binding protein (PBP) 2B. METHODS: A total of 9 invasive MDR strains which were collected from 1990 to 1995 in various parts of Korea and one internationally epidemic Spanish 23F clone were analyzed. The 1.5 kb transpeptidase-encoding region (TER) of PBP 2B gene was amplified and directly sequenced using ABI PRISM Big Dye Terminator cycle sequencing kit (Perkin Elmer). Sequence data were compared with that of a penicillin-susceptible R6 strain. RESULTS: Alterations in nucleotide sequence (5.4-7.8%) and amino acids (3.0-4.3%) of the PBP 2B gene were relatively uniform among 9 Korean MDR strains. Most alterations in nucleotides (86-94%) and amino acids (86-100%) were noted in the hypervariable region between 408 and 993 bp. All 9 strains possessed 14 common alterations in amino acids, among which Asn-276-->Lys, Arg-285-->Cys and Ser-305-->Phe substitutions were unique to Korean MDR strains. CONCLUSION: Sequence analysis of invasive MDR strains showed that a limited number of amino acid substitutions were noted in the wild-type Korean MDR strains in the transpeptidase domain of the PBP 2B gene. Data strongly suggest the possibility of the spread of a few epidemic clones of resistant pneumococci within Korea, which could partly explain the rapid increase of pneumococcal resistance.

A Study on Modes of Transmission and Role of Nasal Carriage to Subsequent Infection with Methicillin-Resistant Staphylococcus aureus in Medical ICU Using PFGE / 병원감염관리

BACKGROUND: In Korea, methicillin-resistant Staphylococcus aureus (MRSA) is the most common nosocomial pathogen, which is particularly prevalent in ICU. We performed this study to investigate the modes of transmission of MRSA and the role of nasal carriage of11RSA to subsequent MRSA infections in medical ICU. METHODS: All patients admitted to the medical lCU during 10 months were studied prospectively. Nasal swabs were done in all patients within 24 hours of admission and weekly thereafter. For patients who developed MRSA infections, additional cultures were done before start of antibiotics. Surveillance cultures of nostril, hands of health care workers and environment were done once at the end of the study. Bacterial typing was performed with pulsed-field gel electrophoresis (PFGE) using Smal. RESULTS: Among 138 patients enrolled, 24 patients (17.4 %) were nasal colonizers, and 9 patients (6.5%) were already infected with MRSA prior to admission. New nasal colonization among patients, in whom follow up nasal cultures were done at the interval of 3 days or more, developed at 36.2 % (21/58 patients). New infections of MRSA in patients who were admitted for more than 3 days, developed at 11.7 % (13/111 patients). Patients in isolation room were infected with MRSA less frequently (P <0.05). No other risk factors for nasal colonization of MRSA or MRSA infections were found. There were no significant differences between nasal colonizers and non-colonizers in the incidence of MRSA infections. PFGE analysis of MRSA isolates from patients showed several major patterns, which were similar in both MRSA isolates obtained prior to admission and those acquired after admission. PFGE patterns of MRSA isolates from health care workers and environment were different from those of patients. CONCLUSION: Patients who were infected or colonized with MRSA seemed to be a major source for transmission of MRSA in medical ICU. In medical lCU, where MRSA were prevalent, nasal colonization was not related to the increased incidence of MRSA infections.

PCR Fingerprinting Analysis of Genes Encoding Penicillin-binding Proteins of Multidrug-resistant Streptococcus pneumoniae Isolated from Korea / 감염

BACKGROUND: The rate of pneumococcal resistance in Korea has surged up to the world's highest level in a short period. To investigate the genetic relatedness and the spread of resistant pneumococci within Korea, and to obtain the basic data about structural changes of penicillin-binding proteins(PBPs), we performed a fingerprinting analysis of PBP 1A, 2X, and 2B genes of multidrug-resistant pneumococci isolated in Korea. METHODS: A total of 22 pneumococcal strains isolated from clinical specimens in 2 university-affiliated hospitals during the period from 1989 to 1996 were tested. PBP 1A, 2X, and 2B genes were amplified from chromosomal DNA by the polymerase chain reaction with specific primers. Amplified products were digested with HinfI or MseI and DdeI and were followed by end-labeling with [alpha-32P] dCTP. Direct comparison of fingerprinting patterns between resistant strains and dendrogram analysis which was based on the UPGMA method were carried out. RESULTS: Fingerprinting analysis of PBP 1A, 2X, and 2B genes digested with HinfI showed that 17 out of 22 strains had almost identical patterns. Dendrogram showed that clusters with greater than 90% similarities existed in 77%, 77%, and 82% of strains with PBP 1A, PBP 2X, PBP 2B, respectively. Fingerprinting patterns with MseI and DdeI were the same as those with HinfI. CONCLUSION: Data from PCR fingerprinting analysis of PBP 1A, 2X, 2B genes of multidrug- resistant pneumococci in this study indicate the genetic relatedness between the resistant strains and suggest the possible spread of pneumococcal resistance within Korea.

Ribotyping of Multidrug-resistant Streptococcus pneumoniae from Korea and Other Countries / 감염

BACKGROUND: Recent data from Korea showed that penicillin-resistance in pneumococci was more than 70% with 35% of multidrug-resistance (MDR) among invasive isolates. One of the most important reasons for the rapid increase of pneumococcal resistance in Korea would be the spread of resistance. Previous data of pulsed-field gel electrophoresis (PFGE) and penicillin-binding protein profile suggested the spread of pneumococcal resistance. To investigate the genetic relatedness of multidrug-resistant strains, we performed the ribotyping with resistant strains isolated from different countries. METHODS: A total of 42 pneumococcal isolates from Korea(33), Spain(5), and the United States(4), which were resistant to more than 3 classes of antimicrobial agents on agar dilution methods, and a R6 penicillin-susceptible strain were used for ribotyping. Ribotyping was performed with the restriction enzyme Pvu II by using a [alpha- 32P]dCTP-labeled gene probe from Escherichia coil 16S+23S RNA. RESULTS: Ribotype of a R6 strain was quite different form those of resistant strains. A total of 12 different ribotypes were noted in multidrug-resistant strains. Nineteen of 33 Korean strain (57.6%), 3 strains from the United States (75%), and 4 strains form Spain (80%) belonged to ribotype A or A subtypes. Discriminatory index of the ribotyping was 0.83. Ribotyping produced more patterns which could denote more discriminatory power than PFGE. CONCLUSION: The data strongly suggest the genetic relatedness of resistant strains from different countries. It might suggest the spread of pneumococcal resistance within Korea, which could partly explain the rapid increase of resistance in a short period.