Leptospirosis is an important public health problem in the Republic of Korea (ROK), occurring sporadically or in outbreaks during the autumn season. Wild rodents, Apodemus agrarius, have been mainly involved in human leptospirosis. The majority of carrier animals are infected with Leptospira interrogans serovar lai. The characteristic pulmonary involvement or hemorrhage may increase the clinical severity or result in fatal outcomes, and these aspects continue to be a threat to people in endemic areas. While the disease incidence has been relatively low in recent years, there have been newer findings of livestock (zoo animals and racing horses) and rats (Rattus norvegicus) captured in urban environments as potential animal carriers. Many avenues of research are still open to define current changes in ecology, epidemiology, and the disease burden in both humans and animals in the ROK, together with global warming and climate change issues. In addition, national policy regarding the weighted wildlife monitoring system and the enhanced disease surveillance program is required to facilitate better monitoring and understanding of this disease.
Leptospira; Epidemiology; Reservoirs; Pulmonary hemorrhage
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
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
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
The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.
Pyelonephritis; Urinary Tract Infections; Ertapenem; Ceftriaxone
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.
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
To determine prevalence and genetic structures of new serotype 6D strains of pneumococci, we examined isolates from diverse clinical specimens in South Korea during 1991–2008. Fourteen serotype 6D strains accounted for 10.4% of serogroup 6 pneumococci from blood, sputum, nasopharynx, and throat samples. Serotype 6D strains consisted of 3 sequence types.
Streptococcus pneumoniae; serotype; epidemiology; bacteria; dispatch
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
Rhino-orbital-cerebral (ROC) mucormycosis is an uncommon, acute and aggressive fungal infection. It remains a challenging problem to clinicians despite aggressive debridement surgery and antifungal therapy. The authors describe a case of ROC mucormycosis with pericranial abscess occurring in a female patient with uncontrolled diabetes mellitus. The infection initially developed in the right-sided nasal sinus and later progressed through the paranasal sinuses with the invasion of the peri-orbital and frontotemporal region, due to the delayed diagnosis and treatment. Numerous non-septate hyphae of the zygomycetes were identified by a punch biopsy from the nasal cavity and by an open biopsy of the involved dura. The patient was treated successfully with extensive debridement of her necrotic skull and surrounding tissues, drainage of her pericranial abscess and antifungal therapy, including intravenous amphotericin B for 61 days and oral posaconazole for the following 26 days. She returned to a normal life and has had no recurrence since the end of her treatment 15 months ago.
Mucormycosis; Neurosurgery; Amphotericin B; Posaconazole
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 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
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.
Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic.
Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE).
Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical.
We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture.
We have previously identified the Legionella 19-kDa peptidoglycan-associated lipoprotein (PAL) as a species-common immunodominant antigen. We describe here for the first time the excretion and detection of the PAL antigen in infected urine specimens, which is useful for the diagnosis of Legionnaires' disease. Rabbit anti-PAL immunoglobulin G (IgG) antibody was produced by immunization with the purified, recombinant PAL of Legionella pneumophila serogroup 1 and used in the PAL antigen capture enzyme-linked immunosorbent assay (ELISA) to detect urinary PAL antigen. A soluble-antigen capture ELISA using rabbit IgG antibodies against Legionella soluble antigens was prepared independently and used as a broad-spectrum standard test to detect soluble antigens of several Legionella species. Urine samples were obtained from guinea pigs experimentally infected with each of L. pneumophila serogroups 1, 3, and 6, and other Legionella species. The absorbance values of the PAL antigen ELISA highly correlated with those of the soluble-antigen ELISA in infected urine samples, with a correlation coefficient of 0.84 (P < 0.01). When applied to 17 infected urine samples and 67 negative controls from guinea pigs, the sensitivity and specificity of the PAL antigen capture ELISA were 88.2 and 95.5%, respectively. Compared to the commercial Biotest enzyme immunoassay, the PAL antigen ELISA was more efficient for detecting pneumophila non-serogroup 1 and nonpneumophila species. None of the 161 control human urine specimens obtained from healthy adults and patients with either non-Legionella pneumonia or urinary tract infections tested positive in the PAL antigen ELISA. The present study shows that the Legionella PAL is a very useful broad-spectrum antigen for urinary diagnostic testing. Moreover, since recombinant PAL antigen can be produced more efficiently than the soluble antigens, the development of a broad-spectrum diagnostic immunoassay based on the detection of the PAL antigen appears to be warranted.
Leptospirosis is a spirochetal zoonosis that causes an acute febrile systemic illness in humans. Leptospira sp. hemolysins have been shown to be virulence factors for the pathogenesis of leptospirosis. Previously, we cloned a hemolysin SphH of Leptospira interrogans serovar lai, a homologue of L. borgpetersenii sphingomyelinase (SphA), from a genomic library (S. H. Lee, K. A. Kim, Y. K. Kim, I. W. Seong, M. J. Kim, and Y. J. Lee, Gene 254:19–28, 2000). Escherichia coli lysate harboring the sphH showed high hemolytic activities on sheep erythrocytes. However, it neither showed sphingomyelinase nor phospholipase activities, in contrast to SphA which was known to have sphingomyelinase activity. Interestingly, the SphH-mediated hemolysis on erythrocytes was osmotically protected by PEG 5000, suggesting that the SphH might have caused pore formation on the erythrocyte membrane. In the present study, we have prepared the Leptospira hemolysin SphH and investigated its hemolytic and cytotoxic activities on mammalian cells. SphH was shown to be a pore-forming protein on several mammalian cells: When treated with the SphH, the sheep erythrocyte membranes formed pores, which were morphologically confirmed by transmission electron microscopy. Furthermore, the SphH-mediated cytotoxicities on mammalian cells were demonstrated by the release of LDH and by inverted microscopic examinations. Finally, the immune serum against the full-length hemolysin could effectively neutralize the SphH-mediated hemolytic and cytotoxic activities. In conclusion, these results suggest that the virulence of Leptospira SphH was due to the pore formation on mammalian cell membranes.