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1.  Impact of preceding respiratory viral infections on the clinical severity of patients with pneumococcal pneumonia 
This study aimed to investigate the impact of preceding respiratory viral infections (RVI) on the clinical severity of pneumococcal pneumonia patients.
A retrospective observational study was conducted at a university hospital from January 2009 to March 2013. Study subjects included adults (aged ≥18 years) with pneumococcal pneumonia who had undergone laboratory tests for RVI. Multivariate logistic regression analysis was performed to identify risk factors associated with severe pneumococcal pneumonia, defined as severity with the Pneumonia Severity Index (PSI) score ≥91.
In total, 191 patients with pneumococcal pneumonia were included for analysis and stratified into 2 groups: the severe group with a PSI score ≥91 (n = 99) and the non-severe group with a PSI score <91 (n = 92). Preceding RVIs were detected in 48 patients, including influenza A virus (n = 20), influenza B virus (n = 4), parainfluenza viruses (n = 5), metapneumovirus (n = 4), rhinovirus (n = 4), respiratory syncytial viruses (n = 6), coronaviruses (n = 2), and mixed viral infections (n = 3). In the multivariate logistic regression analysis, preceding RVIs (odds ratio [OR], 2·49; 95% confidence interval [CI], 1·10–5·60), male sex (OR, 2·58; 95% CI, 1·24–5·38), old age (OR, 2·92; 95% CI, 1·37–6·24), hypoalbuminemia (OR, 3·26; 95% CI, 1·56–6·84)], and azotemia (OR, 2·24; 95% CI, 1·08–4·67) were significantly associated with severe pneumococcal pneumonia.
This study suggests that preceding RVIs might be one of the risk factors affecting the clinical severity of pneumococcal pneumonia.
PMCID: PMC4181819  PMID: 24962523
Clinical severity; pneumonia; respiratory viruses; Streptococcus pneumoniae
2.  Multicenter Prospective Observational Study of the Comparative Efficacy and Safety of Vancomycin versus Teicoplanin in Patients with Health Care-Associated Methicillin-Resistant Staphylococcus aureus Bacteremia 
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.
PMCID: PMC3910721  PMID: 24165181
3.  Leptospirosis in the Republic of Korea: Historical Perspectives, Current Status and Future Challenges 
Infection & Chemotherapy  2013;45(2):137-144.
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.
PMCID: PMC3780959  PMID: 24265962
Leptospira; Epidemiology; Reservoirs; Pulmonary hemorrhage
4.  Epidemiological and Clinical Characteristics of Community-Acquired Severe Sepsis and Septic Shock: A Prospective Observational Study in 12 University Hospitals in Korea 
Journal of Korean Medical Science  2012;27(11):1308-1314.
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.
PMCID: PMC3492663  PMID: 23166410
Epidemiology; Severe Sepsis; Septic Shock; Mortality; Risk Factor; Gender
5.  Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial 
Journal of Korean Medical Science  2012;27(5):476-483.
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.
PMCID: PMC3342536  PMID: 22563210
Pyelonephritis; Urinary Tract Infections; Ertapenem; Ceftriaxone
7.  Epidemiology and Control of an Outbreak of Vancomycin-Resistant Enterococci in the Intensive Care Units 
Yonsei Medical Journal  2009;50(5):637-643.
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.
PMCID: PMC2768237  PMID: 19881966
Vancomycin resistance; enterococcus; outbreak; epidemiology; infection control
8.  Epidemiological and Genetic Characterization of Methicillin-Resistant Staphylococcus aureus Isolates from the Ear Discharge of Outpatients with Chronic Otitis Media 
Journal of Korean Medical Science  2008;23(5):762-766.
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.
PMCID: PMC2579994  PMID: 18955778
Methicillin Resistance; Staphylococcus aureus; Otolaryngology; Epidemiology; Genotype
9.  Molecular Analysis of Isoleucyl-tRNA Synthetase Mutations in Clinical Isolates of Methicillin-Resistant Staphylococcus aureus with Low-Level Mupirocin Resistance 
Journal of Korean Medical Science  2006;21(5):827-832.
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.
PMCID: PMC2721991  PMID: 17043414
Staphylococcus aureus; Mupirocin; Drug Resistance; Isoleucine-tRNA Ligase; Mutation, Missense
10.  Epidemiology of Hemorrhagic Fever with Renal Syndrome in Endemic Area of the Republic of Korea, 1995-1998 
Journal of Korean Medical Science  2006;21(4):614-620.
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.
PMCID: PMC2729880  PMID: 16891802
Hemorrhagic Fever with Renal Syndrome; Hantaan virus; Epidemiology; Incidence; Prevalence; Korea
11.  Atypical Pathogens as Etiologic Agents in Hospitalized Patient with Community-Acquired Pneumonia in Korea: A Prospective Multi-Center Study 
Journal of Korean Medical Science  2006;21(4):602-607.
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.
PMCID: PMC2729878  PMID: 16891800
Chlamydophila pneumoniae; Mycoplasma pneumoniae; Legionella pneumophila; Community-Acquired Infections; Pneumonia
12.  An Imported Case of Severe Falciparum Malaria with Prolonged Hemolytic Anemia Clinically Mimicking a Coinfection with Babesiosis 
While imported falciparum malaria has been increasingly reported in recent years in Korea, clinicians have difficulties in making a clinical diagnosis as well as in having accessibility to effective anti-malarial agents. Here we describe an unusual case of imported falciparum malaria with severe hemolytic anemia lasting over 2 weeks, clinically mimicking a coinfection with babesiosis. A 48-year old Korean man was diagnosed with severe falciparum malaria in France after traveling to the Republic of Benin, West Africa. He received a 1-day course of intravenous artesunate and a 7-day course of Malarone (atovaquone/proguanil) with supportive hemodialysis. Coming back to Korea 5 days after discharge, he was readmitted due to recurrent fever, and further treated with Malarone for 3 days. Both the peripheral blood smears and PCR test were positive for Plasmodium falciparum. However, he had prolonged severe hemolytic anemia (Hb 5.6 g/dl). Therefore, 10 days after the hospitalization, Babesia was considered to be potentially coinfected. A 7-day course of Malarone and azithromycin was empirically started. He became afebrile within 3 days of this babesiosis treatment, and hemolytic anemia profiles began to improve at the completion of the treatment. He has remained stable since his discharge. Unexpectedly, the PCR assays failed to detect DNA of Babesia spp. from blood. In addition, during the retrospective review of the case, the artesunate-induced delayed hemolytic anemia was considered as an alternative cause of the unexplained hemolytic anemia.
PMCID: PMC4277030  PMID: 25548419
Plasmodium falciparum; imported malaria; falciparum malaria; babesiosis; hemolytic anemia; artesunate
13.  Effects of Group 1 versus Group 2 Carbapenems on the Susceptibility of Acinetobacter baumannii to Carbapenems: A Before and After Intervention Study of Carbapenem-Use Stewardship 
PLoS ONE  2014;9(6):e99101.
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.
PMCID: PMC4049602  PMID: 24911244
14.  Incidence and Risk Factors for Surgical Site Infection after Gastric Surgery: A Multicenter Prospective Cohort Study 
Infection & Chemotherapy  2013;45(4):422-430.
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.
PMCID: PMC3902821  PMID: 24475356
Surgical site infection; Risk factors; Gastric surgery
17.  Bromocriptine for Control of Hyperthermia in a Patient with Mixed Autonomic Hyperactivity after Neurosurgery: A Case Report 
Journal of Korean Medical Science  2012;27(8):965-968.
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.
PMCID: PMC3410249  PMID: 22876068
Central Fever; Bromocriptine; Suprasellar Tumor; Neurosurgery; Autonomic Dysfunction
18.  Necrotizing fasciitis involving the chest and abdominal wall caused by Raoultella planticola 
Raoultella planticola was originally considered to be a member of environmental Klebsiella. The clinical significance of R. planticola is still not well known.
Case presentation
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.
PMCID: PMC3362755  PMID: 22423899
19.  Prevalence and Genetic Structures of Streptococcus pneumoniae Serotype 6D, South Korea 
Emerging Infectious Diseases  2010;16(11):1751-1753.
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.
PMCID: PMC3294534  PMID: 21029535
Streptococcus pneumoniae; serotype; epidemiology; bacteria; dispatch
20.  Liver Abscess and Empyema due to Lactococcus lactis cremoris 
Journal of Korean Medical Science  2010;25(11):1669-1671.
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.
PMCID: PMC2967008  PMID: 21060760
Lactococcus lactis; Liver Abscess; Empyema
21.  Nosocomial Outbreak of Carbapenem-Resistant Acinetobacter baumannii in Intensive Care Units and Successful Outbreak Control Program 
Journal of Korean Medical Science  2010;25(7):999-1004.
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.
PMCID: PMC2890899  PMID: 20592889
Acinetobacter baumannii; Disease Outbreaks; Infection Control
22.  Successful Treatment of a Case with Rhino-Orbital-Cerebral Mucormycosis by the Combination of Neurosurgical Intervention and the Sequential Use of Amphotericin B and Posaconazole 
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.
PMCID: PMC2817523  PMID: 20157385
Mucormycosis; Neurosurgery; Amphotericin B; Posaconazole
23.  Legionella lipoprotein activates toll-like receptor 2 and induces cytokine production and expression of costimulatory molecules in peritoneal macrophages 
Experimental & Molecular Medicine  2009;41(10):687-694.
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.
PMCID: PMC2772971  PMID: 19561404
Legionella pneumophila; Legionnaires' disease; lipoproteins; macrophages, peritoneal; Toll-like receptors
24.  Paradoxical response during antituberculous therapy in a patient discontinuing infliximab: a case report 
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.
Case presentation
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.
PMCID: PMC2726479  PMID: 19830122

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