The purpose of this study was to compare the clinical efficacy and safety of vancomycin to those of teicoplanin for the treatment of adult patients with health care-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) bacteremia. A multicenter observational study was prospectively conducted in 15 teaching hospitals in Korea between February 2010 and July 2011. Adult patients (≥18 years old) with HA-MRSA bacteremia who were initially treated with vancomycin (VAN) (n = 134) or teicoplanin (TEC) (n = 56) were enrolled. Clinical and microbiological responses and drug-related adverse events were compared between the two treatment groups using univariate and multivariate logistic regression analyses. The vancomycin and teicoplanin MICs were determined by Etest. The MRSA-related mortality, duration of fever, and duration of MRSA bacteremia in the treatment groups were not significantly different. There was no significant difference in the occurrence of drug-related adverse events. Among the 190 MRSA isolates, the VAN MICs ranged from 0.5 to 2 μg/ml (MIC50 and MIC90, 1.5 μg/ml), and the TEC MIC ranged from 0.5 to 8 μg/ml (MIC50, 3 μg/ml; MIC90, 6 μg/ml). In multivariate analyses, the antibiotic type (vancomycin or teicoplanin) was not associated with treatment outcomes. This study indicates that teicoplanin is an effective and safe alternative to vancomycin for the treatment of HA-MRSA bacteremia.
A retrospective study was conducted to evaluate the efficacy of levofloxacin in the treatment of Stenotrophomonas maltophilia bacteremia. The 30-day mortality rates were similar between the trimerthoprim-sulfamethoxazole (TMP-SMX) and levofloxacin treatment groups. Adverse events related to antibiotics occurred more frequently in patients receiving TMP-SMX, and recurrent bacteremia due to levofloxacin-resistant S. maltophilia strains developed in patients treated with levofloxacin. Our data suggest that levofloxacin can be a useful alternative option for treating S. maltophilia infections.
To better understand extensively drug resistant Streptococcus pneumoniae, we assessed clinical and microbiological characteristics of 5 extensively drug-resistant pneumococcal isolates. We concluded that long-term care facility residents who had undergone tracheostomy might be reservoirs of these pneumococci; 13- and 23-valent pneumococcal vaccines should be considered for high-risk persons; and antimicrobial drugs should be used judiciously.
Streptococcus pneumoniae; extensively drug-resistant; bacteria; South Korea; antimicrobial drug resistance
Extended-spectrum beta-lactamase; Klebsiella pneumoniae; Endocarditis
Surgical site infection (SSI) is a potentially morbid and costly complication of surgery. While gastrointestinal surgery is relatively common in Korea, few studies have evaluated SSI in the context of gastric surgery. Thus, we performed a prospective cohort study to determine the incidence and risk factors of SSI in Korean patients undergoing gastric surgery.
Materials and Methods
A prospective cohort study of 2,091 patients who underwent gastric surgery was performed in 10 hospitals with more than 500 beds (nine tertiary hospitals and one secondary hospital). Patients were recruited from an SSI surveillance program between June 1, 2010, and August 31, 2011 and followed up for 1 month after the operation. The criteria used to define SSI and a patient's risk index category were established according to the Centers for Disease Control and Prevention and the National Nosocomial Infection Surveillance System. We collected demographic data and potential perioperative risk factors including type and duration of the operation and physical status score in patients who developed SSIs based on a previous study protocol.
A total of 71 SSIs (3.3%) were identified, with hospital rates varying from 0.0 - 15.7%. The results of multivariate analyses indicated that prolonged operation time (P = 0.002), use of a razor for preoperative hair removal (P = 0.010), and absence of laminar flow in the operating room (P = 0.024) were independent risk factors for SSI after gastric surgery.
Longer operation times, razor use, and absence of laminar flow in operating rooms were independently associated with significant increased SSI risk after gastric surgery.
Surgical site infection; Risk factors; Gastric surgery
The pneumonia severity index (PSI) and CURB-65 are widely used tools for the prediction of community-acquired pneumonia (CAP). This study was conducted to evaluate validation of severity scoring system including the PSI and CURB-65 scores of Korean CAP patients. In the prospective CAP cohort (participated in by 14 hospitals in Korea from January 2009 to September 2011), 883 patients aged over 18 yr were studied. The 30-day mortalities of all patients were calculated with their PSI index classes and CURB scores. The overall mortality rate was 4.5% (40/883). The mortality rates per CURB-65 score were as follows: score 0, 2.3% (6/260); score 1, 4.0% (12/300); score 2, 6.0% (13/216); score 3, 5.7% (5/88); score 4, 23.5% (4/17); and score 5, 0% (0/2). Mortality rate with PSI risk class were as follows: I, 2.3% (4/174); II, 2.7% (5/182); III, 2.3% (5/213); IV, 4.5% (11/245); and V, 21.7% (15/69). The subgroup mortality rate of Korean CAP patients varies based on the severity scores and CURB-65 is more valid for the lower scores, and PSI, for the higher scores. Thus, these variations must be considered when using PSI and CURB-65 for CAP in Korean patients.
Pneumonia; Prognosis; Severity Index
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.
Non-typhoidal Salmonella species are important foodborne pathogens that can cause gastroenteritis, bacteremia, and subsequent focal infections. Non-typhoidal salmonellosis is problematic, particularly in immunocompromised hosts. Any anatomical site can be affected by this pathogen via hematogenous seeding and may develop local infections. However, cervical lymphadenitis caused by non-typhoidal Salmonella species is rarely reported. Herein, we have reported a case of cervical lymphadenitis caused by group D non-typhoidal Salmonella associated with lymphoma.
Lymphadenitis; Salmonella; Lymphoma
Antimicrobial resistance has become one of the most serious public health concerns worldwide. Although circumstances may vary by region or country, it is clear that some Asian countries are epicenters of resistance, having seen rapid increases in the prevalence of antimicrobial resistance of major bacterial pathogens. In these locations, however, the public health infrastructure to combat this problem is very poor. The prevalence rates of methicillin-resistant Staphylococcus aureus (MRSA), macrolide-resistant Streptococcus pneumoniae, and multidrug-resistant enteric pathogens are very high due to the recent emergence of extremely drug-resistant gram-negative bacilli in Asia. Because antimicrobial options for these pathogens are extremely limited, infections caused by antimicrobial-resistant bacteria are often associated with inappropriate antimicrobial therapy and poor clinical outcomes. Physicians should be aware of the current epidemiological status of resistance and understand the appropriate use of antimicrobial agents in clinical practice. This review focuses on describing the epidemiology and clinical implications of antimicrobial-resistant bacterial infections in Asian countries.
Antimicrobial resistance; Epidemiology; Bacterial infections; Asia
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.
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.
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.
Fusobacterium species are uncommon causes of osteomyelitis. These organisms are normal flora of the oral cavity. Therefore, they mostly cause osteomyelitis of the head and neck. Hematogenous osteomyelitis at distant sites other than the head and neck has rarely been reported in pediatric or immunocompromised patients. Here, we report the first case of osteomyelitis of a long bone combined with a muscle abscess due to Fusobacterium nucleatum in an otherwise healthy adult.
A 59-year-old Korean man was admitted for pain and swelling of the right lower leg, which had been persistent for two weeks. Magnetic resonance imaging showed osteomyelitis of the right fibula with a surrounding muscle abscess of the right lower leg. Incision and drainage was performed, and repetitive tissue cultures grew F. nucleatum. In this patient, it was presumed that recurrent periodontitis caused hematogenous seeding of F. nucleatum to a distant site leading to osteomyelitis with a muscle abscess. The patient was successfully treated with intravenous ampicillin-sulbactam for three weeks and oral amoxicillin-clavulanate for eight weeks. He also underwent repeated surgical drainage. He has no evidence of recurrence after seven months of follow-up.
Clinicians should be aware that F. nucleatum could be the etiologic agent of hematogenous osteomyelitis of a long bone in an immunocompetent patient.
Fusobacterium nucleatum; Osteomyelitis; Periodontitis
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
The aim of this study is to investigate whether a combination of the Korean version of the mini-mental state examination (K-MMSE) and the Korean dementia screening questionnaire (KDSQ) is better than the use of test alone when differentiating patients with dementia from those without dementia in Korea.
The subjects (patients without dementia, 1120; patients with dementia, 908) were recruited from the Clinical Research Center for Dementia of South Korea. K-MMSE and KDSQ were used. Diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, fourth Edition. The weighted sum rule derived from logistic regression analysis was used for the combination of K-MMSE and KDSQ.
On comparing the Area Under the Curve for each test using the method of Hanley and McNeil, the weighted sum was significantly greater than KDSQ or K-MMSE, and K-MMSE was significantly greater than KDSQ.
This study shows that when differentiating patients with dementia from those without dementia in Korea, a combination of K-MMSE and KDSQ achieved using the weighted sum method is better than either test performed alone. Further epidemiological studies in community-based settings are required before our results can be generalized to nonclinical samples.
Dementia; screening; Korean version of the Mini-Mental State Examination; Korean Dementia Screening Questionnaire
Interleukin- (IL-) 17 is important in the development of asthma and host defense against pneumococci. We determined the role of IL-17 in the risk of pneumococcal pneumonia.
We challenged mice intranasally with a bioluminescent Streptococcus pneumoniae strain after sensitization and challenge with ovalbumin (OVA). We measured the levels of cytokines, including IL-17 (pg/mL), in the lung homogenate in experimental mice with and without OVA sensitization/challenge, as well as those with and without pneumococcal pneumonia. IL-17 levels were significantly lower in OVA-sensitized/challenged mice (9.69 ±
1.49), compared to the control mice (20.92 ±
1.82, P < 0.001). In our overall analysis, including IL-4 and IL-17 levels and OVA sensitization/challenge, IL-4 levels (OR: 81.9, 95%CI: 4.3–1523 per increment of 1.0 pg/mL, P = 0.003) were more significant than IL-17 levels (OR: 1.1, 95%CI: 1.03–1.17 per increment of 1.0 pg/mL, P = 0.003) in determining the risk of pneumococcal pneumonia. IL-17 levels result in a much smaller impact on the risk for pneumococcal pneumonia, compared to IL-4 levels.
Streptococcus suis infection is an emerging zoonosis in Asia. The most common disease manifestation is meningitis, which is often associated with hearing loss and cochleovestibular signs. S. suis infection in humans mainly occurs among risk groups that have frequent exposure to pigs or raw pork. Here, we report a case of S. suis meningitis in a 67-yr-old pig carcass handler, who presented with dizziness and sensorineural hearing loss followed by headaches. Gram-positive diplococci were isolated from cerebrospinal fluid (CSF) and blood cultures and showed gray-white colonies with α-hemolysis. S. suis was identified from CSF and blood cultures by using a Vitek 2 system (bioMérieux, France), API 20 STREP (bioMérieux), and performing 16S rRNA and tuf gene sequencing. Even after receiving antibiotic treatment, patients with S. suis infection frequently show complications such as hearing impairment and vestibular dysfunction. To the best of our knowledge, this is the first case of S. suis meningitis in Korea. Prevention through public health surveillance is recommended, especially for individuals who have occupational exposures to swine and raw pork.
Streptococcus suis; Meningitis; Hearing loss; Korea
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
Cisplatin causes auditory impairment due to the apoptosis of auditory hair cells. There is no strategy to regulate ototoxicity by cisplatin thus far. Dansam-Eum (DSE) has been used for treating the central nerve system injury including hearing loss in Korea. However, disease-related scientific investigation by DSE has not been elucidated. Here, we demonstrated that DSE and its component rosmarinic acid (RA) were shown to inhibit apoptosis of the primary organ of Corti explants as well as the auditory cells. Administration of DSE and RA reduced the thresholds of the auditory brainstem response in cisplatin-injected mice. A molecular docking simulation and a kinetic assay show that RA controls the activity of caspase-1 by interaction with the active site of caspase-1. Pretreatment of RA inhibited caspase-1 downstream signal pathway, such as the activation of caspase-3 and 9, release of cytochrome c, translocation of apoptosis-inducing factor, up-regulation of Bax, down-regulation of Bcl-2, generation of reactive oxygen species, and activation of nuclear factor-κB. Anticancer activity by cisplatin was not affected by treatment with RA in SNU668, A549, HCT116, and HeLa cells but not B16F10 cells. These findings show that blocking a critical step by RA in apoptosis may be useful strategy to prevent harmful side effects of ototoxicity in patients with having to undergo chemotherapy.