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
Although pandemic community-associated (CA-) methicillin-resistant Staphylococcus aureus (MRSA) ST30 clone has successfully spread into many Asian countries, there has been no case in Korea. We report the first imported case of infection caused by this clone in a Korean traveler returning from the Philippines. A previously healthy 30-yr-old Korean woman developed a buttock carbuncle while traveling in the Philippines. After coming back to Korea, oral cephalosporin was given by a primary physician without any improvement. Abscess was drained and MRSA strain isolated from her carbuncle was molecularly characterized and it was confirmed as ST30-MRSA-IV. She was successfully treated with vancomycin and surgery. Frequent international travel and migration have increased the risk of international spread of CA-MRSA clones. The efforts to understand the changing epidemiology of CA-MRSA should be continued, and we should raise suspicion of CA-MRSA infection in travelers with skin infections returning from CA-MRSA-endemic countries.
Staphylococcus aureus; Methicillin Resistance; Community-Acquired Infections; Carbuncle; Travel
Although extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has emerged as a significant community-acquired pathogen, there is little epidemiological information regarding community-onset bacteremia due to ESBL-EC. A retrospective observational study from 2006 through 2011 was performed to evaluate the epidemiology of community-onset bacteremia caused by ESBL-EC. In a six-year period, the proportion of ESBL-EC responsible for causing community-onset bacteremia had increased significantly, from 3.6% in 2006 to 14.3%, in 2011. Of the 97 clinically evaluable cases with ESBL-EC bacteremia, 32 (33.0%) were further classified as healthcare-associated infections. The most common site of infection was urinary tract infection (n=35, 36.1%), followed by biliary tract infections (n=29, 29.9%). Of the 103 ESBL-EC isolates, 43 (41.7%) produced CTX-M-14 and 36 (35.0%) produced CTX-M-15. In the multilocus sequence typing (MLST) analysis of 76 isolates with CTX-M-14 or -15 type ESBLs, the most prevalent sequence type (ST) was ST131 (n=15, 19.7%), followed by ST405 (n=12, 15.8%) and ST648 (n=8, 10.5%). No significant differences in clinical features were found in the ST131 group versus the other group. These findings suggest that epidemic ESBL-EC clones such as CTX-M-14 or -15 type ESBLs and ST131 have disseminated in community-onset infections, even in bloodstream infections, which are the most serious type of infection.
Escherichia coli; Community-Acquired Infections; Cephalosporin Resistance; Bacteremia; Epidemiology
The emergence of antimicrobial resistance threatens the successful treatment of pneumococcal infections. Here we report a case of bacteremic pneumonia caused by an extremely drug-resistant strain of Streptococcus pneumoniae, nonsusceptible to at least one agent in all classes but vancomycin and linezolid, posing an important new public health threat in our region.
Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain23F-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. Over 700 recombinations were detected, with genes encoding major antigens frequently affected. Among these were ten capsule switching events, one of which accompanied a population shift as vaccine-escape serotype 19A isolates emerged in the USA following the introduction of the conjugate polysaccharide vaccine. The evolution of resistance to fluoroquinolones, rifampicin and macrolides was observed to occur on multiple occasions. This study details how genomic plasticity within lineages of recombinogenic bacteria can permit adaptation to clinical interventions over remarkably short timescales.
Staphylococcus aureus; Methicillin resistance; Community-acquired infections; Genotype
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