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.
Antimicrobial stewardship programs have been proposed for reducing bacterial resistance in the hospital environment. The purpose of this study was to investigate the impact of a carbapenem-use stewardship program on the susceptibility of Acinetobacter baumannii to Group 2 carbapenems.
A before and after intervention study was conducted at a university hospital from September 2008 to February 2013. Three study periods were defined: Phase I, pre-intervention (months 1–18); Phase II, a postintervention period during which ertapenem use was mandated but carbapenem use was not restricted (months 19–36); and Phase III, a postintervention period during which Group 2 carbapenem use was restricted (months 37–54).
During the study period, intervention resulted in diminished consumption of Group 2 carbapenems (antimicrobial use density (AUD): 21.3±6.0 in Phase I, 18.8±6.0 in Phase II, 16.1±4.4 in Phase III; P = 0.028) and increased consumption of ertapenem (AUD: 2.7±1.7 in Phase I, 7.2±4.5 in Phase II, 9.1±5.3 in Phase III; P<0.001). The use of autoregressive-error models showed that in contrast with ertapenem use, the use of Group 2 carbapenem during the previous one month was positively and significantly associated with a subsequent increase in the proportion of carbapenem-resistant A. baumannii (CRAB) (P = 0.031).
Implementing a carbapenem-use stewardship program featuring the preferential use of ertapenem for treating appropriate indications of infection resulted in reduced use of Group 2 carbapenems and had a positive impact on the susceptibility of A. baumannii to carbapenems. This approach could be integrated into CRAB-control strategies in hospitals.
The number of cases of pertussis reported has increased gradually in the last decade. Pertussis vaccination is the most effective strategy for the prevention of infection. Despite the fact that young infants are at the highest risk for pertussis, the rate of tetanus-diphtheria-acellular pertussis (Tdap) vaccination is presumed to be very low among women of childbearing age in Korea. The purpose of this study was to investigate the perceptions of women of childbearing age regarding Tdap vaccination in Korea.
Materials and Methods
Women of childbearing age, who visited the Department of Obstetrics and Gynecology at 3 University hospitals in the Seoul and Gyeonggi-do provinces of Korea, were surveyed. Individual questionnaires were administered from April to May 2012. Demographic data, Tdap vaccination history, general knowledge about pertussis, and information on factors associated with decision on vaccination were collected.
Of the 500 reproductive-age women enrolled, only 4 (0.8%) had received the Tdap. The most common reason for non-vaccination was the lack of awareness of pertussis and information about the Tdap. Totally, 171 (34.2%) responded that they would receive a Tdap vaccination in the future. By multivariate analysis, general confidence in the effectiveness of the vaccine (odds ratio [OR] = 1.88, 95% confidence interval [CI] 1.17 to 3.01) was indicated as an important factor for deciding whether to receive the Tdap vaccine (P < 0.01).
The coverage of Tdap vaccination of women of childbearing age, including pregnant women, is very low because of the lack of awareness of pertussis and the Tdap. Education of women of childbearing age about pertussis is very important to increase Tdap vaccination rates among these women, particularly during the perinatal period.
Pertussis; Vaccination; Tdap; Childbearing age; Perception
Streptococcus pneumoniae causes a broad spectrum of illnesses ranging from mild upper respiratory tract infections to invasive pneumococcal disease (IPD). Quantitative data on the burden of pneumococcal disease, important for the establishment of appropriate vaccination strategies, is currently lacking in adults.
This multicenter, retrospective cohort study was designed to estimate the clinical and economic burden of IPD in adults over the last decade. Data were collected from patients with IPD at 10 university hospitals in South Korea. We estimated the proportion of IPD among all hospitalized patients, the case fatality rate, and the direct medical costs of IPD. Data were further analyzed according to age and risk groups.
During the study period, 970 patients with IPD were identified. The mean age for all patients was 60.9 years; patients aged 50–64 years (33.0%) were most numerous, followed by those aged 65–74 years (27.4%). Overall, the proportion of IPD was 0.36 cases/1000 hospitalized patients and the case fatality rate was 30.9%, which increased significantly with age (p < 0.01). The mean direct medical costs were estimated to be US $7,452 without a difference between age and risk groups. On multivariate analysis, old age, advanced ECOG performance status, bacteremic pneumonia, and nosocomial infection were independent risk factors of 30-day case fatality.
The clinical disease burden of IPD increased significantly with age and direct medical costs from IPD were substantial, regardless of age and co-morbid conditions. The current age-based vaccination strategy appears to be appropriate.
Cost of illness; Pneumococcal infection; Pneumococcal vaccines; Streptococcus pneumoniae
A prospective multicenter observational study was performed to investigate the epidemiology and outcomes of community-acquired severe sepsis and septic shock. Subjects included 1,192 adult patients admitted to the 22 participating intensive care units (ICUs) of 12 university hospitals in the Korean Sepsis Registry System from April, 2005 through February, 2009. Male accounted for 656 (55%) patients. Mean age was 65.0 ± 14.2 yr. Septic shock developed in 740 (62.1%) patients. Bacteremia was present in 422 (35.4%) patients. The 28-day and in-hospital mortality rates were 23.0% and 28.0%, respectively. Men were more likely to have comorbid illnesses and acute organ dysfunctions, and had higher mortality and clinical severity compared to women. While respiratory sources of sepsis were common in men, urinary sources were predominant in women. In the multivariate logistic regression analysis, cancer (odds ratio 1.89; 95% confidence interval 1.13-3.17), urinary tract infection (0.25; 0.13-0.46), APACHE II score (1.05; 1.02-1.09), SOFA score on day 1 (1.13; 1.06-1.21) and metabolic dysfunction (2.24, 1.45-3.45) were independent clinical factors for gender-related in-hospital mortality. This study provided epidemiological and clinical characteristics of community-acquired severe sepsis and septic shock in ICUs in Korea, and demonstrated the impact of clinical factors on gender difference in mortality.
Epidemiology; Severe Sepsis; Septic Shock; Mortality; Risk Factor; Gender
Mixed autonomic hyperactivity disorder (MAHD) among patients with acquired brain injury can be rare. A delayed diagnosis of MAHD might exacerbate the clinical outcome and increase healthcare expenses with unnecessary testing. However, MAHD is still an underrecognized and evolving disease entity. A 25-yr-old woman was admitted the clinic due to craniopharyngioma. After an extensive tumor resection, she complained of sustained fever, papillary contraction, hiccup, lacrimation, and sighing. An extensive evaluation of the sustained fever was conducted. Finally, the cause for MAHD was suspected, and the patient was successfully treated with bromocriptine for a month.
Central Fever; Bromocriptine; Suprasellar Tumor; Neurosurgery; Autonomic Dysfunction
Women who are pregnant, planning to become pregnant in the influenza season or caring for infant 6-59 months of age are identified as priority groups for influenza vaccination. Vaccination rate is presumed to be low in those women. The purpose of this study was to investigate perceptions of childbearing age women about influenza vaccination.
Materials and Methods
Childbearing age women visiting the department of Obstetrics and Gynecology in 3 University hospitals in Seoul and Gyeonggi-do province were surveyed. Individual interviews were performed to them with questionnaire for 2 months from April to May 2012. Demographic data, Immunization history, general understanding and factors associated with vaccination were asked.
Three hundred fifty-five (71.0%) of total 500 reproductive age women had the experience of influenza vaccination. Among 343 women who has been pregnant at least once, 48 women (16.4%) had vaccination during pregnancy, and 46 of them got vaccination since 2009. One hundred ninety women of total 500 women responded that they would get vaccination if pregnant in the next influenza season (38.0%). In multivariate analysis, statistically significant factors associated with plans of influenza vaccination in pregnancy were as follows: experience of childbirth (odds ratio [OR], 1.97; 95% CI, 1.32 to 2.93), high level of education (OR, 1.96; 95% CI, 1.22 to 3.15), previous influenza vaccination (OR, 1.88; 95% CI, 1.17 to 3.01).
Influenza vaccine coverage on childbearing age women including pregnant women is low because of misperception of vaccination during pregnancy. It is necessary for healthcare provider to correct misunderstanding and to recommend vaccination actively.
Influenza; Vaccination; Pregnancy; Childbearing age; Perception
Raoultella planticola was originally considered to be a member of environmental Klebsiella. The clinical significance of R. planticola is still not well known.
We describe the first case of necrotizing fasciitis involving the chest and abdominal wall caused by R. planticola. The identity of the organism was confirmed using 16S rRNA sequencing. The patient was successfully treated with the appropriate antibiotics combined with operative drainage and debridement.
R. planticola had been described as environmental species, but should be suspected in extensive necrotizing fasciitis after minor trauma in mild to moderate immunocompromised patients.
Carbapenem-resistant Klebsiella pneumoniae isolates producing K. pneumoniae carbapenemases (KPC) were first reported in the USA in 2001, and since then, this infection has been reported in Europe, Israel, South America, and China. In Korea, the first KPC-2-producing K. pneumoniae sequence type (ST) 11 strain was detected in 2010. We report the case of a patient with a urinary tract infection caused by KPC-2-producing K. pneumoniae. This is the second report of a KPC-2-producing K. pneumoniae infection in Korea, but the multilocus sequence type was ST258. The KPC-2-producing isolate was resistant to all tested β-lactams (including imipenem and meropenem), amikacin, tobramycin, ciprofloxacin, levofloxacin, and trimethoprim-sulfamethoxazole, but was susceptible to gentamicin, colistin, polymyxin B, and tigecycline. The KPC-2-producing isolate was negative to phenotypic extended-spectrum β-lactamase (ESBL) and AmpC detection tests and positive to modified Hodge test and carbapenemase inhibition test with aminophenylboronic acid.
KPC-2; Klebsiella pneumoniae; ST258
Lactococcus lactis cremoris infections are very rare in humans. We experienced liver abscess and empyema due to L. lactis cremoris in an immunocompetent adult. A 42-yr-old man was admitted with fever and abdominal pain. Abdominal computed tomography (CT) revealed a liver abscess and chest CT showed loculated pleural effusion consistent with empyema. L. lactis cremoris was isolated from culture of the abscess material and blood. The patient was treated with pus drainage from liver abscess, video-assisted thoracoscopic decortications for empyema, and antibiotics including cefotaxime and levofloxacin. The patient was completely recovered with the treatment. To our knowledge, this is the first report of a L. lactis cremoris infection in Korea.
Lactococcus lactis; Liver Abscess; Empyema
Acinetobacter baumannii has been increasingly reported as a significant causative organism of various nosocomial infections. Here we describe an outbreak of carbapenem-resistant A. baumannii (CRAB) in the ICUs of a Korean university hospital, along with a successful outbreak control program. From October 2007 through July 2008, CRAB was isolated from 57 ICU patients. Nineteen patients were diagnosed as being truly infected with CRAB, four of whom were presumed to have died due to CRAB infection, producing a case-fatality rate of 21.1%. In surveillance of the environment and the healthcare workers (HCWs), CRAB was isolated from 24 (17.9%) of 135 environmental samples and seven (10.9%) of 65 HCWs. The pulsed field gel electrophoresis patterns showed that the isolates from patients, HCWs, and the environment were genetically related. Control of the outbreak was achieved by enforcing contact precautions, reducing environmental contamination through massive cleaning, and use of a closed-suctioning system. By August 2008 there were no new cases of CRAB in the ICUs. This study shows that the extensive spread of CRAB can happen through HCWs and the environmental contamination, and that proper strategies including strict contact precautions, massive environmental decontamination, and a closed-suctioning system can be effective for controlling CRAB outbreaks.
Acinetobacter baumannii; Disease Outbreaks; Infection Control
This study was aimed to describe a vancomycin-resistant enterococci (VRE) outbreak across three intensive care units (ICUs) of a Korean hospital from September 2006 to January 2007 and the subsequent control strategies.
Materials and Methods
We simultaneously implemented multifaceted interventions to control the outbreak, including establishing a VRE cohort ward, active rectal surveillance cultures, daily extensive cleaning of environmental surfaces and environmental cultures, antibiotic restriction, and education of hospital staff. We measured weekly VRE prevalence and rectal acquisition rates and characterized the VRE isolates by polymerase chain reaction (PCR) of the vanA gene and Sma1-pulsed-field gel electrophoresis (PFGE).
During the outbreak, a total of 50 patients infected with VRE were identified by clinical and surveillance cultures, and 46 had vancomycin-resistant Enterococcus faecium (VREF). PFGE analysis of VREF isolates from initial two months disclosed 6 types and clusters of two major types. The outbreak was terminated 5 months after implementation of the interventions: The weekly prevalence rate decreased from 9.1/100 patients-day in September 2006 to 0.6/100 by the end of January 2007, and the rectal acquisition rates also dropped from 6.9/100 to 0/100 patients-day.
Our study suggests that an aggressive multifaceted control strategy is a rapid, effective approach for controlling a VRE outbreak.
Vancomycin resistance; enterococcus; outbreak; epidemiology; infection control
Legionella bacterium, an intracellular pathogen of mononuclear phagocytes, causes acute fatal pneumonia, especially in patients with impaired cellular immune responses. Until recently, however, the toll-like receptor (TLR) engagement of bacterial proteins derived from Legionella is uncertain. We previously showed that a 19-kDa highly conserved peptidoglycan-associated lipoprotein (PAL) of Legionella pneumophila induced the PAL-specific B cell and T cell responses in mice. In this study, we observed that the rPAL antigen of L. pneumophila, as an effector molecule, activated murine macrophages via TLR2 and produced proinflammatory cytokines such as IL-6 and TNF-α. In both BALB/c and TLR4-deficient C3H/HeJ mice, pretreatment of macrophages with anti-TLR2 mAb showed severely impaired cytokine production in response to the rPAL. In addition, in vitro the rPAL treatment increased the cell surface expression of CD40, CD80, CD86 and MHC I/II molecules. We further showed that the synthetic CpG-oligodeoxynucleotides (CpG ODN) coadministered with the rPAL enhanced IL-12 and IL-6 production and expression of CD40, CD80 and MHC II compared to the rPAL treatment alone. In conclusions, these results indicate that Legionella PAL might activate macrophages via a TLR2-dependent mechanism which thus induce cytokine production and expression of costimulatory and MHC molecules.
Legionella pneumophila; Legionnaires' disease; lipoproteins; macrophages, peritoneal; Toll-like receptors
The use of the drug infliximab for the treatment of patients with Crohn's disease can be complicated by tuberculosis. A paradoxical reaction during antituberculosis chemotherapy and immunologic reconstitution after discontinuation of infliximab can result in severe disseminated tuberculosis.
A 38-year-old Korean man with severe Crohn's disease presented with fever and diffuse abdominal pain. Infliximab had been started 2 months before admission. A chest X-ray and abdominal computed tomography scan revealed numerous miliary nodules in both lung fields and microabscesses in the spleen. Given the diagnosis of disseminated tuberculosis, the infliximab therapy was discontinued and antituberculosis therapy was promptly started. Over the next 3 months, the patient was diagnosed with tuberculosis lymphadenitis on a right supraclavicular lymph node and surgical excision of the lesion was performed. With the diagnosis of a paradoxical response, anti-tuberculous therapy was continued for 12 months.
Our case suggests that patients who develop tuberculosis after infliximab exposure are at an increased risk of developing a paradoxical reaction. The current recommendation of discontinuing infliximab during tuberculosis treatment should be re-evaluated.
The origin of methicillin-resistant Staphylococcus aureus (MRSA) strains from otolaryngology outpatients has not been evaluated yet in Korea. We analyzed epidemiologic and genetic characteristics of MRSA isolates from the ear discharge of 64 outpatients with chronic otitis media in a Korean University Hospital during 2004. MRSA strains were grouped as either from the initial visit (n=33) or the follow-up visit (n=31) based on the timing of isolation. Healthcare-associated risk factors were frequently present among patients of the initial visit group, especially prior visit to primary clinic (79%) and antibiotic use (73%). SCCmec typing and multilocus sequence typing results showed that two genotypes, ST5-MRSA-II and ST239-MRSA-III, were prevalent in both the initial visit (73% vs. 24%) and the follow-up visit (55% vs. 42%). Pulsed-field gel electrophoresis identified eight types, including two major types shared by both groups. We conclude that majority of MRSA strains from ear discharge of chronic otitis media belonged to nosocomial clones that might be circulating in the community. This is the first report of the genetic analysis of MRSA strains from otolaryngology practices in Korea.
Methicillin Resistance; Staphylococcus aureus; Otolaryngology; Epidemiology; Genotype
The performance of the SD Bioline rapid antigen test kit for influenza virus detection was evaluated with 295 respiratory specimens during the influenza season. The overall sensitivity and specificity of the SD Bioline test were 61.9% and 96.8% for the influenza A virus antigen and 54.5% and 100% for the influenza B virus antigen, respectively. The results were consistent with peak influenza activities.
Histoplasmosis is a very rare disease in Korea. Clinical manifestations are very similar to those of tuberculosis. This is the first case report of combined disseminated histoplasmosis and tuberculosis in a patient with HIV infection in Korea. A 42-year-old Korean with Acquired Immunodeficiency Syndrome (AIDS) was diagnosed with tuberculosis. He had lived in Guatemala for the past five years. Upon diagnosis of disseminated tuberculosis with HIV infection, he was treated with anti-tuberculosis medications and anti-retroviral agents. Fever, weakness, hepatosplenomegaly and pancytopenia were persistent despite treatment. The patient's history of living in Guatemala caused us to seek opportunistic infectious organisms other than tuberculosis. Bone marrow aspiration and biopsy were performed and the result revealed numerous intracellular organisms consistent with Histoplasma capsulatum; therefore, the diagnosis of disseminated histoplasmosis was made.
Histoplasmosis; HIV infections; AIDS; tuberculosis
Disseminated mycobacterium avium complex (MAC) occurs mainly in immunocompromised hosts, which is associated with abnormal cellular immunity.
A 26-year-old pregnant woman presented with fever and general weakness. Miliary lung nodules were noted on chest X-ray. Under the impression of miliary tuberculosis, anti-tuberculosis medication was administered. However, the patient was not improved. Further work-up demonstrated MAC in the sputum and placenta. The patient was treated successfully with clarithromycin-based combination regimen.
This appears to be the first case of disseminated MAC in an otherwise healthy pregnant woman. Clinicians should be alert for the diagnosis of MAC infection in diverse clinical conditions.
Emergence and spread of low-level mupirocin resistance in staphylococci have been increasingly reported in recent years. The aim of this study was to characterize missense mutations within the chromosomal isoleucyl-tRNA synthetase gene (ileS) among clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) with low-level mupirocin resistance. A total of 20 isolates of MRSA with low-level mupirocin resistance (minimal inhibitory concentration, 16-64 µg/mL) were collected from 79 patients in intensive care units for six months. The isolates were analyzed for isoleucyl-tRNA synthetase (IleS) mutations that might affect the binding of mupirocin to the three-dimensional structure of the S. aureus IleS enzyme. All isolates with low-level mupirocin resistance contained the known V588F mutation affecting the Rossman fold, and some of them additionally had previously unidentified mutations such as P187F, K226T, F227L, Q612H, or V767D. Interestingly, Q612H was a novel mutation that was involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif. In conclusion, this study confirms that molecular heterogeneity in ileS gene is common among clinical MRSA isolates with low-level mupirocin resistance, and further study on clinical mutants is needed to understand the structural basis of low-level mupirocin resistance.
Staphylococcus aureus; Mupirocin; Drug Resistance; Isoleucine-tRNA Ligase; Mutation, Missense
Spontaneous bacterial peritonitis (SBP) is an ascitic fluid infection as a complication of end stage liver disease. The outcome is related to the severity of hepatorenal function, gastrointestinal bleeding, and many others; however it is not well known whether the infection acquisition sites have an effect on the prognosis of SBP. In order to identify the prognostic significance of the acquisition sites, we studied 106 patients who were diagnosed as culture positive SBP between October 1998 and August 2003. Thirty-two episodes were nosocomial and 74 were community acquired. Gram-negative bacilli such as Escherichia coli were dominant in both of the nosocomial and community-acquired SBPs. Despite significantly higher resistance to cefotaxime in nosocomial isolates compared to community-acquired isolates (77.8% vs. 13.6%, p=0.001), no difference was found regarding short or long term prognosis. Infection acquisition sites were not related to short or long term prognosis either. Shock, gastrointestinal bleeding and renal dysfunction were related to short term prognosis. Only Child-Pugh class C was identified as an independent prognostic factor of long-term survival.
Liver Cirrhosis; Peritonitis; Cross Infection; Community-Acquired Infections
We conducted an epidemiologic study to understand temporal and spatial patterns of hemorrhagic fever with renal syndrome (HFRS) in the Republic of Korea (ROK). We estimated the incidence among civilians in endemic areas through the active surveillance system during the major epidemic periods, from September to December, between 1996 and 1998. We also estimated the prevalence among Korean military personnel from 1995 to 1998. In addition, we assessed seroprevalence, subclinical infection rate, and vaccination rates in both civilians and military personnel. The incidence in civilians ranged from 2.1 to 6.6 per 100,000 person-months. The annual prevalence in the military personnel was 40-64 per 100,000 military populations, and remained generally constant throughout the study period with seasonal variation. This is the prospective epidemiologic data set on HFRS in the ROK since the inactivated Hantaan virus vaccine was licensed for use in the late 1990s. These results will be invaluable in establishing a national immunization program against HFRS.
Hemorrhagic Fever with Renal Syndrome; Hantaan virus; Epidemiology; Incidence; Prevalence; Korea
Local epidemiologic data on the etiologies of patients hospitalized with community-acquired pneumonia (CAP) is needed to develop guidelines for clinical practice. This study was conducted prospectively to determine the proportion of atypical bacterial pathogens in adults patients hospitalized with CAP in Korea between October 2001 and December 2002. Microbiological diagnosis was determined by serology for antibodies to Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. Nucleic acid of M. pneumoniae and C. pneumoniae in respiratory samples and Legionella antigen in urine samples were detected. The study population consisted of 126 patients (71 males, 55 females), averaging 54.6 yr (SD±17.8), whose paired sera were available. An etiologic diagnosis for atypical pathogens was made in 18 patients (14.3%): C. pneumoniae 9 (7.1%), M. pneumoniae 8 (6.3%), and L. pneumophila 3 patients (2.4%). Streptococcus preumoniae and other typical pathogens were isolated from 36 patients (28.6%). Of 126 patients, 16 (12.7%) were admitted to intensive care unit and atypical pathogens were identified in 5 patients (31.3%). Initial clinical features of patients with pneumonia due to atypical, typical or undetermined pathogens were indistinguishable. We conclude that atypical pathogens should be seriously considered in hospitalized patients with CAP, when initiating empiric treatment in Korea.
Chlamydophila pneumoniae; Mycoplasma pneumoniae; Legionella pneumophila; Community-Acquired Infections; Pneumonia
We developed a novel PCR-restriction fragment length polymorphism test for the ccrB gene by using HinfI and BsmI for rapid typing of staphylococcal cassette chromosome mec (SCCmec). When tested with reference strains and methicillin-resistant Staphylococcus aureus isolates, the method proved to be valid and useful for rapid identification of four SCCmec types, especially type IV.