This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillin-sulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.
Arbekacin; habekacin; Rifampin; Sultamicillin; Teicoplanin quinipristin-dalfopristin; Vancomycin Resistance; Staphylococcus aureus; hetero-VISA; Time-kill assay
We describe the first reported case of endocarditis due to Neisseria skkuensis. The organism from the blood cultures taken on admission day was identified initially as unidentified Gram-negative cocci by Vitek2. Finally, it was identified as Neisseria skkuensis by 16 rRNA gene sequence analysis.
This study reports for the first time the AbaR4-type resistance island with the blaOXA-23 gene in two carbapenem-resistant A. nosocomialis isolates from South Korea and Thailand.
Vancomycin-intermediate resistance has not been previously reported among sequence type 72 (ST72) methicillin-resistant Staphylococcus aureus (MRSA) isolates of SCCmec type IV (ST72-MRSA-IV), which are distinctive community genotype strains in Korea. We report the first case of vancomycin treatment failure due to development of vancomycin-intermediate resistance in infection caused by an ST72-MRSA-IV isolate.
We compared the 16S rRNA gene sequencing results analyzed with the GenBank, EzTaxon, and BIBI databases for blood culture specimens for which identifications were incomplete, conflicting, or unidentifiable using conventional methods. Analyses performed using GenBank combined with EzTaxon (kappa = 0.79) were more discriminative than those using other databases alone or in combination with a second database.
Antimicrobial resistance in Streptococcus pneumoniae remains a serious concern worldwide, particularly in Asian countries, despite the introduction of heptavalent pneumococcal conjugate vaccine (PCV7). The Asian Network for Surveillance of Resistant Pathogens (ANSORP) performed a prospective surveillance study of 2,184 S. pneumoniae isolates collected from patients with pneumococcal infections from 60 hospitals in 11 Asian countries from 2008 to 2009. Among nonmeningeal isolates, the prevalence rate of penicillin-nonsusceptible pneumococci (MIC, ≥4 μg/ml) was 4.6% and penicillin resistance (MIC, ≥8 μg/ml) was extremely rare (0.7%). Resistance to erythromycin was very prevalent in the region (72.7%); the highest rates were in China (96.4%), Taiwan (84.9%), and Vietnam (80.7%). Multidrug resistance (MDR) was observed in 59.3% of isolates from Asian countries. Major serotypes were 19F (23.5%), 23F (10.0%), 19A (8.2%), 14 (7.3%), and 6B (7.3%). Overall, 52.5% of isolates showed PCV7 serotypes, ranging from 16.1% in Philippines to 75.1% in Vietnam. Serotypes 19A (8.2%), 3 (6.2%), and 6A (4.2%) were the most prominent non-PCV7 serotypes in the Asian region. Among isolates with serotype 19A, 86.0% and 79.8% showed erythromycin resistance and MDR, respectively. The most remarkable findings about the epidemiology of S. pneumoniae in Asian countries after the introduction of PCV7 were the high prevalence of macrolide resistance and MDR and distinctive increases in serotype 19A.
To investigate the characteristics of main Streptococcus pneumoniae clones of serotype 6D (ST282 and ST3171) in South Korea, antimicrobial susceptibility testing was performed, and 11 genes around the cps locus were sequenced on ST2826D, ST31716D, and ST816A isolates. The antimicrobial susceptibility patterns were very similar between clones belonging to the same clonal complex, ST816A and ST2826D; nonsusceptibilities to penicillin and cefuroxime, high MICs of ceftriaxone, and high resistance rates to trimethoprim-sulfamethoxazole. However, ST31716D isolates showed resistance to only macrolides and clindamycin. The sequences of 11 genes around the cps locus indicated the same genetic backgrounds between the ST816A and ST2826D isolates. On the other hand, ST31716D isolates showed nucleotide and amino acid differences from ST816A and ST2826D isolates in most genes, indicating a different genetic background. The mosaic structure of dexB gene in ST2826D isolates indicated that recombination might occur in the dexB gene. Our results suggest that the multidrug-resistant ST2826D pneumococcal clone has emerged by serial genetic recombination, including capsular switch.
Limited clinical information is available regarding community onset infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli. A case-control study was performed to evaluate the epidemiology and risk factors of these types of infections. A case patient was defined as a person whose clinical sample yielded ESBL-producing E. coli. For each case patient, one control was randomly chosen from a group of outpatients from whom non-ESBL-producing E. coli had been isolated and for whom a clinical sample had been sent to the same laboratory for culturing during the following week. Of 108 cases of ESBL-producing E. coli, 56 (51.9%) were classified as health care associated (HCA). Univariate analysis showed male gender, HCA infection, severe underlying illness, and a prior receipt of antibiotics to be associated with ESBL-producing E. coli. In the multivariate analysis, HCA infection (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.67 to 6.06; P < 0.001) and previous use of antibiotics (OR, 4.88; 95% CI, 2.08 to 11.48; P < 0.001) were found to be significantly associated with the ESBL group. In a multivariate analysis that included each antibiotic, previous use of fluoroquinolone (OR, 7.32; 95% CI, 1.58 to 34.01; P = 0.011) was significantly associated with ESBL-producing E. coli. Of 101 isolates in which ESBLs and their molecular relationships were studied, all isolates produced ESBLs from the CTX-M family (CTX-M-14, 40 isolates; CTX-M-15, 39 isolates; and other members of the CTX-M family, 22 isolates). In conclusion, this study confirms that ESBL-producing E. coli strains are a notable cause of community onset infections in predisposed patients. HCA infection and previous use of fluoroquinolone were significant factors associated with ESBL-producing E. coli in community onset infections.
Panton-Valentine leukocidin (PVL)-positive USA300 clone has been the most successful community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) clone spreading in North America. In contrast, PVL-negative ST72-CA-MRSA has been predominant in Korea, and there has been no report of infections by the USA300 strain except only one case report of perianal infection. Here, we describe the first case of pneumonia caused by the USA300 strain following pandemic influenza A (H1N1) in Korea. A 50-year-old man was admitted with fever and cough and chest radiograph showed pneumonic consolidation at the right lower lung zone. He received a ventilator support because of respiratory failure. PCR for pandemic influenza A (H1N1) in nasopharyngeal swab was positive, and culture of sputum and endotracheal aspirate grew MRSA. Typing of the isolate revealed that it was PVL-positive, ST 8-MRSA-SCCmec type IV. The analysis of the PFGE patterns showed that this isolate was the same pulsotype as the USA300 strain.
Influenza, Human; Methicillin-Resistant Staphylococcus aureus; Pneumonia
Chronic active Epstein-Barr virus (CAEBV) infection is characterized by persistent infectious mononucleosis-like symptoms, an unusual pattern of Epstein-Barr virus (EBV) antibodies, detection of the EBV genome in affected tissues or peripheral blood, and chronic illness that cannot be attributed to any other known disease. This is the first reported Korean case of an immunocompetent adult with CAEBV-associated interstitial pneumonitis. A 28-year-old female was admitted with a fever that persisted for 3 weeks. She had multiple lymphadenopathy, hepatosplenomegaly, pancytopenia, and elevated serum aminotransferase levels. Serology for antibodies was positive and chest computed tomography showed diffuse ground glass opacities in both lungs. Histopathology of the lung tissue showed lymphocyte infiltration, and EBV DNA was detected in those lymphocytes using in situ hybridization with an EBV-encoded RNA probe. After 1 month of hospitalization, she improved without specific treatment.
Epstein-Barr virus infection; Immunocompetence; Lung diseases; Interstitial pneumonitis
Recently, Streptococcus pneumoniae serotypes 6C and 6D have been identified. It is thought that they emerged by the replacement of wciNβ in the capsular loci of serotypes 6A and 6B, respectively. However, their evolution has not been unveiled yet. To investigate the evolution of four serotypes of S. pneumoniae serogroup 6, four genes of the capsular polysaccharide synthesis (cps) locus, wchA, wciN, wciO, and wciP, of isolates of S. pneumoniae serotypes 6A, 6B, 6C, and 6D were sequenced. Multilocus sequence typing (MLST) was performed to investigate their genetic backgrounds. The wchA gene of serotype 6C and 6D isolates was distinct from that of serotype 6A and 6B isolates, which may suggest cotransfer of wchA with wciNβ. Otherwise, serotypes 6C and 6D displayed different genetic backgrounds from serotypes 6A and 6B, which was suggested by MLST analysis. In addition, serotype 6C isolates showed distinct wciP polymorphisms from other serotypes, which also indicated that serotype 6C had not recently originated from serotype 6A. Although serotype 6D shared the same amino acid polymorphisms of wciO with serotype 6B, wciP of serotype 6D differed from that of serotype 6B. The data indicate the implausibility of the scenario of a recent emergence of the cps locus of serotype 6D by genetic recombination between serotypes 6B and 6C. In addition, five serotype 6A and 6B isolates (6X group) displayed cps loci distinct from those of other isolates. The cps locus homogeneity and similar sequence types in MLST analysis suggest that most of the 6X group of isolates originated from the same ancestor and that the entire cps locus might have recently been transferred from an unknown origin. Serotype 6B isolates showed two or more cps locus subtypes, indicating a recombination-mediated mosaic structure of the cps locus of serotype 6B. The collective data favor the emergence of cps loci of serotypes 6A, 6B, 6C, and 6D by complicated recombination.
The purpose of this study was to evaluate the value of initial C-reactive protein (CRP) as a predictor of clinical outcome and to investigate whether follow-up CRP measurement is useful for the prediction of the clinical outcome of bloodstream infections in patients with liver cirrhosis (LC), whose CRP production in response to infection may be attenuated.
A retrospective, observational study including 202 LC patients with Escherichia coli or Klebsiella pneumoniae bacteremia was conducted to assess the usefulness of serial CRP measurements in predicting clinical outcome in LC patients. The CRP ratio was defined as the ratio of the follow-up CRP level to the initial CRP level.
The overall 30-day mortality rate of the study population was 23.8% (48/202). In the multivariate analysis, advanced age (≥ 70 years), healthcare-associated or nosocomial infections, model for end-stage liver disease (MELD) score of ≥ 30, and initial body temperature of < 37℃ were significant factors associated with mortality (all p < 0.05). No association between initial CRP level and mortality was found. In a further analysis including 87 evaluable cases who had repeated CRP measurements at day 4 and/or 5, a CRP ratio of ≥ 0.7 was found to be a significant factor associated with mortality (odds ratio, 19.12; 95% confidence interval, 1.32 to 276.86; p = 0.043) after adjusting for other confounding variables.
Initial CRP level did not predict mortality of sepsis in LC patients. However, serial CRP measurements during the first week of antimicrobial therapy may be useful as a prognostic factor for mortality in LC patients.
C-reactive protein; Bacteremia; Liver cirrhosis; Treatment outcome
Laribacter hongkongensis is an emerging pathogen in patients with community-acquired gastroenteritis and traveler's diarrhea. We herein report a case of L. hongkongensis infection in a 24-yr-old male with liver cirrhosis complicated by Wilson's disease. He was admitted to a hospital with only abdominal distension. On day 6 following admission, he complained of abdominal pain and his body temperature reached 38.6℃. The results of peritoneal fluid evaluation revealed a leukocyte count of 1,180/µL (polymorphonuclear leukocyte 74%). Growth on blood culture was identified as a gram-negative bacillus. The isolate was initially identified as Acinetobacter lwoffii by conventional identification methods in the clinical microbiology laboratory, but was later identified as L. hongkongensis on the basis of molecular identification. The patient was successfully treated with cefotaxime. To the best of our knowledge, this case is the first report of hospital-acquired L. hongkongensis bacteremia with neutrophilic ascites.
Laribacter hongkongensis; Neutrophilic Ascites; Bacteremia
We describe here the first case of a concurrent brain abscess caused by Norcardia spp. and semi-invasive pulmonary aspergillosis in an immunocompetent patient. After one year of appropriate antimicrobial therapy and surgical drainage of the brain abscess, the nocardia brain abscess and pulmonary aspergillosis have resolved.
Brain nocardiosis; Semi-invasive pulmonary aspergillosis; Immunocompetent
We evaluated the clinical features of ciprofloxacin-resistant Proteus mirabilis bacteremia and risk factors for ciprofloxacin resistance.
From October 2000 to July 2009, 37 patients with clinically significant P. mirabilis bacteremia were identified and data from patients with ciprofloxacin-resistant and ciprofloxacin-susceptible P. mirabilis bacteremia were compared.
The most common underlying diseases were neurologic disease (37.8%) and solid tumors (29.7%). The most common site of infection was the urinary tract (35.1%). Ten of the 37 patients (27.0%) were infected with ciprofloxacin-resistant isolates, and univariate analysis revealed a significant relationship between ciprofloxacin-resistant P. mirabilis bacteremia and neurologic disease, recent operation, L-tube insertion, percutaneous tube use, and extended-spectrum β-lactamase (ESBL) production (all p < 0.05). ESBL was detected in six of 10 (60%) ciprofloxacin-resistant isolates, while only three of 27 (11%) ciprofloxacin-susceptible isolates produced ESBL (p = 0.005). In a logistic regression analysis, ESBL production remained a significant factor associated with ciprofloxacin resistance, after adjusting for other variables.
These data indicate a close association between ciprofloxacin resistance and ESBL-production in P. mirabilis bacteremia. This association is particularly troublesome because the therapeutic options for serious infections caused by ESBL-producing P. mirabilis are severely restricted.
Proteus mirabilis; Ciprofloxacin; Drug resistance; Bacterial; Risk factors; Cephalosporin resistance
Candidaemia associated with intravascular catheter-associated infections is of great concern due to the resulting high morbidity and mortality. The antibiotic lock technique (ALT) was previously introduced to treat catheter-associated bacterial infections without removal of catheter. So far, the efficacy of ALT against Candida infections has not been rigorously evaluated. We investigated in vitro activity of ALT against Candida biofilms formed by C. albicans, C. glabrata, and C. tropicalis using five antifungal agents (caspofungin, amphotericin B, itraconazole, fluconazole, and voriconazole). The effectiveness of antifungal treatment was assayed by monitoring viable cell counts after exposure to 1 mg/mL solutions of each antibiotic. Fluconazole, itraconazole, and voriconazole eliminated detectable viability in the biofilms of all Candida species within 7, 10, and 14 days, respectively, while caspofungin and amphotericin B did not completely kill fungi in C. albicans and C. glabrata biofilms within 14 days. For C. tropicalis biofilm, caspofungin lock achieved eradication more rapidly than amphotericin B and three azoles. Our study suggests that azoles may be useful ALT agents in the treatment of catheter-related candidemia.
Candida; Biofilms; Antibiotic Lock Technique
Nocardia farcinica is an emerging pathogen in immunocompromised hosts. Even though several species of Nocardia have been reported as causative pathogens of catheter-related blood stream infections (CRBSI), CRBSI caused by N. farcinica has not been reported. A 70-yr-old man with a tunneled central venous catheter (CVC) for home parenteral nutrition was admitted with fever for two days. Norcardia species was isolated from the blood through CVC and peripheral bloods and identified to N. farcinica by 16S rRNA and rpoB gene sequence analyses. This report emphasizes the rapid and correct identification of causative agents in infectious diseases in the selection of antimicrobial agents and the consideration of catheter removal.
Nocardia farcinica; Catheter-related Blood Stream Infection (CRBSI); rpoB
In vitro activities of colistin and other drugs were tested against 221 Klebsiella pneumoniae isolates that were collected between 2006 and 2007 in nine tertiary care South Korean hospitals from patients with bacteremia. The clonality of colistin-resistant K. pneumoniae (CRKP) isolates was assessed by multilocus sequence typing (MLST). We found that 15 isolates (6.8%) were resistant to colistin. MLST showed that CRKP isolates were nonclonal, with colistin resistance in K. pneumoniae occurring independently and not by clonal spreading.
Recent changes in healthcare systems have changed the epidemiologic paradigms in many infectious fields including bloodstream infection (BSI). We compared clinical characteristics of community-acquired (CA), hospital-acquired (HA), and healthcare-associated (HCA) BSI. We performed a prospective nationwide multicenter surveillance study from 9 university hospitals in Korea. Total 1,605 blood isolates were collected from 2006 to 2007, and 1,144 isolates were considered true pathogens. HA-BSI accounted for 48.8%, CA-BSI for 33.2%, and HCA-BSI for 18.0%. HA-BSI and HCA-BSI were more likely to have severe comorbidities. Escherichia coli was the most common isolate in CA-BSI (47.1%) and HCA-BSI (27.2%). In contrast, Staphylococcus aureus (15.2%), coagulase-negative Staphylococcus (15.1%) were the common isolates in HA-BSI. The rate of appropriate empiric antimicrobial therapy was the highest in CA-BSI (89.0%) followed by HCA-BSI (76.4%), and HA-BSI (75.0%). The 30-day mortality rate was the highest in HA-BSI (23.0%) followed by HCA-BSI (18.4%), and CA-BSI (10.2%). High Pitt score and inappropriate empirical antibiotic therapy were the independent risk factors for mortality by multivariate analysis. In conclusion, the present data suggest that clinical features, outcome, and microbiologic features of causative pathogens vary by origin of BSI. Especially, HCA-BSI shows unique clinical characteristics, which should be considered a distinct category for more appropriate antibiotic treatment.
Bloodstream infection; Bacteremia; Community-acquired; Hospital-acquired; Healthcare-associated
The methicillin-resistant Staphylococcus aureus (MRSA) clonal group known as ST239-MRSA-III is notable for its hybrid origin and for causing sustained hospital epidemics worldwide since the late 1970s. We studied the population structure of this MRSA clonal group using a sample of 111 isolates that were collected over 34 years from 29 countries. Genetic variation was assessed using typing methods and novel ascertainment methods, resulting in approximately 15 kb of sequence from 32 loci for all isolates. A single most parsimonious tree, free of homoplasy, partitioned 28 haplotypes into geographically-associated clades, including prominent European, Asian, and South American clades. The rate of evolution was estimated to be approximately 100× faster than standard estimates for bacteria, and dated the most recent common ancestor of these isolates to the mid-20th century. Associations were discovered between the ST239 phylogeny and the ccrB and dru loci of the methicillin resistance genetic element, SCCmec type III, but not with the accessory components of the element that are targeted by multiplex PCR subtyping tools. In summary, the evolutionary history of ST239 can be characterized by rapid clonal diversification that has left strong evidence of geographic and temporal population structure. SCCmec type III has remained linked to the ST239 chromosome during clonal diversification, but it has undergone homoplasious losses of accessory components. These results provide a population genetics framework for the precise identification of emerging ST239 variants, and invite a re-evaluation of the markers used for subtyping SCCmec.
As bacterial resistance to antimicrobial agents has grown due to the increasing use of antimicrobial agents, we sought to evaluate the suitability of ceftriaxone usage (representative of third generation cephalosporins) at 10 university hospitals in Korea.
We prospectively evaluated the appropriateness of antibiotic usage in 400 adult patients who received ceftriaxone between February 1, 2006 and June 30, 2006. Drug utilization evaluation (DUE) methods were based on standards set forth by the American Society of Hospital Pharmacists. The DUE criteria used in this study were modified to be more suitable in our hospital setting: justification of drug use, critical and process indications, complications, and outcome measures.
The average patient age was 64.4 years. The utilization of ceftriaxone was appropriate in 262 cases (65.5%) for the justification of use, while inappropriate use was observed in 138 cases (34.5%). Common reasons for inappropriate use of ceftriaxone included continued empiric use for presumed infections, prophylactic perioperative injection, and empiric therapy for fever. Most of the critical indications showed a high rate of suitability (66.5-98.5%). Complications occurred in 37 cases (9.3%). With respect to outcome measures, clinical responses were observed in 60.7% of cases, while only 15.7% of cases showed evidence of infection eradication via negative cultures.
Appropriate use (65.5%) of ceftriaxone was higher than inappropriate use (34.5%) at university hospitals in Korea. Inappropriate utilization, however, including continued empiric use for presumed infections and prophylactic perioperative injection remained high. Intensification of educational programs and antibiotic control systems for ceftriaxone is needed to improve the suitability of antimicrobial use.
Drug utilization review; Ceftriaxone
This multinational study from Asia revealed that reduced susceptibility to ciprofloxacin (MIC, 0.125 to 1 μg/ml) in nontyphoid Salmonella isolates was common in Taiwan (48.1%) and Thailand (46.2%) and in S. enterica serotype Choleraesuis (68.8%) and S. Virchow (75.0%) from all countries. Reduced susceptibility to ceftriaxone (MIC, 2 to 8 μg/ml) remained uncommon in Asia, except in Taiwan (38.0%) or in S. Typhimurium (25.0%) from all countries.