Risk factors and clinical impact of COVID-19-associated pulmonary aspergillosis: Multicenter retrospective cohort study

Background/Aims@#The risk factors and clinical impacts of coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) remain controversial, and no data have been reported in Korea. This study aimed to investigate the epidemiology and importance of CAPA diagnostic efforts and to identify the predictors of CAPA and the impacts on clinical outcomes. @*Methods@#Between January 2020 and May 2021, data of severely to critically ill COVID-19 patients were extracted from seven hospitals of the Catholic Medical Center through a clinical data warehouse. Corticosteroid use was subcategorized into total cumulative dose, early 7-day dose, mean daily dose, and duration of use. @*Results@#A total of 2,427 patients were screened, and 218 patients were included. CAPA was diagnosed in 4.6% (10/218) of all hospitalized and 11.2% (10/89) of intensive care unit patients. Total cumulative dose (over 1,000 mg as methylprednisolone) and daily high-dose corticosteroid use (over 60 mg/day) were independent predictors but not early 7-day high-dose corticosteroid use (over 420 mg/week) (odds ratio [OR], 1.731; 95% confidence interval [CI], 0.350 to 8.571) nor prolonged use (OR, 2.794; 95% CI, 0.635 to 13.928). In-hospital overall mortality was 11.9% (26 of 218). CAPA itself did not affect the outcome; rather, daily high-dose steroid use significantly increased the 30-day mortality (hazard ratio, 5.645; 95% CI, 1.225 to 26.091). @*Conclusions@#CAPA was not uncommon, especially in critically ill patients. Daily high-dose corticosteroid use was the predictor of CAPA and associated with high mortality rates. High-dose corticosteroids use after early inflammatory phase should be avoided, and active surveillance methods for CAPA are essential for those high-risk patients.

Comparison of In Vivo Pharmacokinetics and Pharmacodynamics of Vancomycin Products Available in Korea

PURPOSE: Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator.MATERIALS AND METHODS: The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice.RESULTS: Generic products had a lower proportion of vancomycin B (range: 90.3–93.8%) and a higher proportion of impurities (range: 6.2–9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (C(max)) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all p<0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (E(max)) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all p≤0.05).CONCLUSION: Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in hetero-vancomycin-resistant mice infected with Staphylococcus aureus.

A Phase III Study to Evaluate the Immunogenicity and Safety of GC1107 (Adult Tetanus Diphtheria Vaccine) in Healthy Adults

BACKGROUND: This study was conducted to assess the immunogenicity and safety of GC1107 (adult tetanus diphtheria [Td] vaccine). The primary goal was to evaluate the non-inferiority of the immunogenicity of GC1107 compared to the control vaccine. Additionally, the safety profiles of GC1107 and the control vaccine were compared. METHODS: The subjects were adults ≥ 18 years old who were not injected with Td or adult tetanus-diphtheria-pertussis (TdaP) vaccine within the recent 5 years. A total of 253 subjects were enrolled and randomized to either the GC1107 group or the control group. For immunogenicity assessment, blood samples were collected at baseline and 28 days after vaccination and antibody titer of diphtheria and tetanus were assessed. RESULTS: The seroprotection rates of diphtheria and tetanus were 89.76% and 91.34%, respectively, in the GC1107 group, and 87.80% and 86.99% in the control group. The geometric mean titer (GMT) of the anti-diphtheria antibody increased after vaccination in both groups, showing no significant difference between the groups (P = 0.139). The anti-tetanus GMTs after vaccination also showed comparable increases in both groups, and showed no significant difference (P = 0.860). In the safety evaluation, solicited local adverse reactions occurred in 81.2% of the subjects in the GC1107 group and in 86.4% of the subjects in the control group. Solicited systemic adverse events occurred in 33.2% of the subjects in the GC1107 group and in 47.2% of the subjects in the control group, which did not reach statistical significance. CONCLUSION: This phase III study demonstrated non-inferiority in immunogenicity and comparable safety of GC1107 compared with the control Td vaccine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02361866

Principles of selecting appropriate antimicrobial agents

The inappropriate use of antimicrobial agents results in collateral damages such as treatment failure, an increased frequency of adverse events related to antimicrobial agents, the emergence of resistant bacteria, and increased medical costs. The selection of appropriate antimicrobial agents begins with taking a detailed history and performing a thorough physical examination to determine whether the cause of the fever is infectious or non-infectious. Based on the patient's symptoms and signs, the site of infection (a system-oriented approach) and the causative organism with high possibility (a pathogenesis-oriented approach: intracellular vs. extracellular) can be estimated. In this process, host factors, microbial factors, and the characteristics of antimicrobial agents should be considered. Herein, we summarize the recently developed Korean guidelines for the use of antimicrobial agents for infectious diseases. We also introduce the antimicrobial website and application developed by Korean Society for Antimicrobial Therapy and the antimicrobial stewardship program.

Clinical Characteristics and Antimicrobial Susceptibility Trends in Citrobacter Bacteremia: An 11-Year Single-Center Experience

BACKGROUND@#Recently, Citrobacter freundii bacteremia outbreak in a neonatal intensive care unit has attracted public attention in Korea. However, Citrobacter bacteremia is uncommon and usually occurs in patients with underlying diseases such as malignancy and hepatobiliary diseases. Increase in resistance and emerging of multidrug resistance among Citrobacter species have gradually been reported. The aim of this study was to investigate the clinical characteristics and outcome of C. freundii and non-freundii bacteremia and antimicrobial susceptibility trends.@*MATERIALS AND METHODS@#We reviewed the medical records of patients with Citrobacter bacteremia at St. Mary's Hospital, from 2007 to 2017.@*RESULTS@#A total of 43 patients with a median age of 72 (24-93) years was identified and 90.7% of them had comorbidities. Twenty-nine (67.4%) patients had C. freundii bacteremia while 14 had non-freundii bacteremia (six of C. braakii, five of C. koseri, two of C. amalonaticus and one of C. youngae). A total of 26 (51.2%) patients had community-acquired infection and intra-abdominal infection including hepatobiliary tract was the most common portal of entry (24/43, 55.8%). Moreover, hepatobiliary tract was the leading primary site of nosocomial infection (9/17, 52.9%). Polymicrobial bacteremia was observed in 21 (48.8%) patients. The percentages of Citrobacter species susceptible to ampicillin, amikacin, aztreonam, cefazolin, cefoxitin, cefotaxime, cefepime, piperacillin-tazobactam, ciprofloxacin, and imipenem were 9.5%, 97.6%, 73.8%, 9.5%, 14.3%, 71.4%, 92.9%, 83.3%, 83.3% and 100%, respectively. The resistance rate did not increase during the study period. Of 39 patients treated with antibiotics, 36 (92.3%) received appropriate empirical antibiotics. Overall mortality was 18.6%. High Charlson comorbidity index and Pitt bacteremia score were significant risk factors for death in univariate analysis and showed trends in the multivariate analysis. No significant difference in clinical features and antimicrobial susceptibility rate was observed between C. freundii and non-freundii bacteremia.@*CONCLUSION@#Citrobacter bacteremia was predominant in the elderly with comorbidities, while no pediatric case was observed. Hepatobiliary tract is the leading primary focus of bacteremia both in community-acquired and nosocomial infection. The rate of susceptibility to antibiotics has not changed in the last 11 years.

Erratum: Carbapenem-Resistant Enterobacteriaceae: Prevalence and Risk Factors in a Single Community-Based Hospital in Korea

The authors found errors in their published article.

Principles of selecting appropriate antimicrobial agents

The inappropriate use of antimicrobial agents results in collateral damages such as treatment failure, an increased frequency of adverse events related to antimicrobial agents, the emergence of resistant bacteria, and increased medical costs. The selection of appropriate antimicrobial agents begins with taking a detailed history and performing a thorough physical examination to determine whether the cause of the fever is infectious or non-infectious. Based on the patient's symptoms and signs, the site of infection (a system-oriented approach) and the causative organism with high possibility (a pathogenesis-oriented approach: intracellular vs. extracellular) can be estimated. In this process, host factors, microbial factors, and the characteristics of antimicrobial agents should be considered. Herein, we summarize the recently developed Korean guidelines for the use of antimicrobial agents for infectious diseases. We also introduce the antimicrobial website and application developed by Korean Society for Antimicrobial Therapy and the antimicrobial stewardship program.

Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review

Dasatinib, a tyrosine kinase inhibitor, is widely used for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Although the drug has a potent immunosuppressive effect, infectious complications during dasatinib treatment have been reported rarely. We describe five patients who developed cytomegalovirus (CMV) colitis during dasatinib treatment, in whom the colitis was initially confused with other causes. The patients, three with chronic myeloid leukemia, and two with acute lymphoblastic leukemia, were diagnosed with CMV colitis based on endoscopic and histologic findings. The patients who examined blood CMV polymerase chain reaction were all positive. The patients received antiviral therapy in the form of either ganciclovir or valganciclovir, and the overall treatment outcome was fair. These cases suggest that physicians should consider the possibility of CMV reactivation when treating diarrhea and/or hematochezia in patients on dasatinib.

Cytomegalovirus Colitis during Dasatinib Treatment for Patients with Hematologic Malignancy: Case Series and Literature Review

Dasatinib, a tyrosine kinase inhibitor, is widely used for patients with chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. Although the drug has a potent immunosuppressive effect, infectious complications during dasatinib treatment have been reported rarely. We describe five patients who developed cytomegalovirus (CMV) colitis during dasatinib treatment, in whom the colitis was initially confused with other causes. The patients, three with chronic myeloid leukemia, and two with acute lymphoblastic leukemia, were diagnosed with CMV colitis based on endoscopic and histologic findings. The patients who examined blood CMV polymerase chain reaction were all positive. The patients received antiviral therapy in the form of either ganciclovir or valganciclovir, and the overall treatment outcome was fair. These cases suggest that physicians should consider the possibility of CMV reactivation when treating diarrhea and/or hematochezia in patients on dasatinib.

Implementation of Hospital Policy for Healthcare Workers and Patients Exposed to Varicella-Zoster Virus

Varicella-zoster virus (VZV) causes a highly contagious and generally benign, self-limited disease. However, in high-risk populations including immunocompromised patients, pregnant women, and neonates, VZV infection can be associated with significant morbidity and mortality. Healthcare-associated transmission of VZV occurs among healthcare workers (HCWs) and patients by airborne transmission or by direct contact with the index case. To minimize the risk of transmission in healthcare settings, all VZV-susceptible HCWs should be encouraged strongly to be immunized with the varicella vaccine. For post-exposure management, active immunization (varicella vaccine), passive immunization (varicella-zoster immune globulin) and/or antiviral agents, and isolation could be used in specific situations. To prevent the transmission of VZV infection in the hospital settings, the development and implementation of hospital policies for appropriate infection control is also warranted. This article reviews the general information and healthcare-associated transmission of VZV and summarizes the recommendations for the pre- and post-exposure management of HCWs and patients, in hospital settings.

Primary Sternal Osteomyelitis caused by Staphylococcus aureus in an Immunocompetent Adult

Primary sternal osteomyelitis (PSO) is a rare condition that may develop without any contiguous focus of infection. Due to the rarity of the disease, early diagnosis and appropriate treatment are often delayed. Herein, we describe a patient with PSO caused by Staphylococcus aureus that presented with chest pain and fever. The patient had no predisposing factors for sternal osteomyelitis. The chest pain was thought to be non-cardiogenic, as electrocardiography and cardiac enzyme did not reveal ischemic changes when he visited the emergency room. After blood culture revealed the presence of S. aureus, every effort was made to identify the primary focus of infection. Bone scan and magnetic resonance imaging revealed osteomyelitis with soft tissue inflammation around the sternum. After 8 weeks of antibiotics treatment, the patient recovered without any complications.

Lower Respiratory Tract Diseases Caused by Common Respiratory Viruses among Stem Cell Transplantation Recipients: A Single Center Experience in Korea

PURPOSE: To describe the incidence, clinical courses, and risk factors for mortality of lower respiratory tract diseases (LRDs) caused by common respiratory viruses (CRVs) in stem cell transplantation (SCT) recipients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 1038 patients who received SCT between January 2007 and August 2011 at a single center in Korea. RESULTS: Seventy-one CRV-LRDs were identified in 67 (6.5%) patients. The human parainfluenza virus (HPIV) was the most common causative pathogen of CRV-LRDs at 100 days [cumulative incidence estimate, 23.5%; 95% confidence interval (CI), 3.3–43.7] and 1 year (cumulative incidence estimate, 69.2%; 95% CI, 45.9–92.5) following SCT. The 30-day overall mortality rates due to influenza-LRDs, respiratory syncytial virus-LRDs, HPIV-LRDs, and human rhinovirus-LRDs were 35.7, 25.8, 31.6, and 42.8%, respectively. Co-pathogens in respiratory specimens were detected in 23 (33.8%) patients. The overall mortality at day 30 after CRV-LRD diagnosis was 32.8% (22/67). High-dose steroid usage (p=0.025), a severe state of immunodeficiency (p=0.033), and lymphopenia (p=0.006) were significantly associated with death within 30 days following CRV-LRD diagnosis in a univariate analysis. Multivariate logistic regression analysis revealed that high-dose steroid usage [odds ratio (OR), 4.05; 95% CI, 1.12–14.61; p=0.033] and lymphopenia (OR, 6.57; 95% CI, 1.80–24.03; p=0.004) were independent risk factors for mortality within 30 days of CRV-LRDs. CONCLUSION: CRV-LRDs among SCT recipients showed substantially high morbidity and mortality rates. Therefore, the implement of an active diagnostic approaches for CRV infections is required for SCT recipients with respiratory symptoms, especially those receiving high-dose steroids or with lymphopenia.

Late Onset Candida albicans Spondylodiscitis Following Candidemia: A Case Report / 대한의진균학회지

Candida albicans infections of the spine are relatively uncommon in spite of the increasing frequency of predisposing factors. Moreover, late onset spondylodiscitis after bloodstream candidiasis is extremely rare. A 66-year-old woman to have been underwent chemotherapy was diagnosed with candidemia. Antifungal agent was administrated until two weeks after no detection of fungus in the blood culture. The chemotherapy was continued. But, she was hospitalized due to abdominal pain and diarrhea. Pseudomembranous colitis was diagnosed. After metronidazole administration, she was improved and discharged. However, she revisited because of back pain and fever. Spondylitis and discitis on the 10th~11th thoracic spine was shown in magnetic resonance images. Open curettage and spinal stabilization was performed. C. albicans was identified. Antifungal agent was administrated and the patient improved well postoperatively. We present a rare case of late onset Candida spondylodiscitis after candidemia with review of the literatures.

Amikacin therapy for urinary tract infections caused by extended-spectrum beta-lactamase-producing Escherichia coli

BACKGROUND/AIMS: The number of urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) is increasing. In an outpatient setting, there are limited therapeutic options to treat ESBL-producing pathogens. We evaluated the outcomes of amikacin outpatient parenteral antibiotic therapy (OPAT) for UTIs caused by ESBL-EC in patients not pre-treated with carbapenem. METHODS: We retrospectively evaluated the outcomes of amikacin OPAT for UTIs caused by ESBL-EC. RESULTS: From November 2011 to October 2012, eight females, who could not be hospitalized for carbapenem treatment, were treated with amikacin OPAT for nine episodes of non-bacteremic ESBL-EC UTIs. Seven of the eight patients had one or more comorbidities. Of the nine UTI cases, three had symptomatic lower UTIs and six had non-bacteremic upper UTIs. In all of the cases, symptomatic and laboratory improvements were observed following amikacin OPAT. One patient showed a delayed relapse with bilateral microabscesses 3 weeks after treatment cessation; however, a clinical and microbiological cure was eventually reached. All of the patients were able to tolerate amikacin OPAT without any significant nephrotoxicity or ototoxicity. CONCLUSIONS: Amikacin OPAT represents a feasible therapeutic option for non-bacteremic UTIs caused by ESBL-EC in settings with limited resources.

Carbapenem-resistant Enterobacteriaceae: Prevalence and Risk Factors in a Single Community-Based Hospital in Korea

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) are Gram-negative bacteria with increasing prevalence of infection worldwide. In Korea, 25 cases of CPE isolates were reported by the Korea Centers for Disease Control and Prevention in 2011. Most CPE cases were detected mainly at tertiary referral hospitals. We analyzed the prevalence and risk factors for carbapenem-resistant Enterobacteriaceae (CRE) in a mid-sized community-based hospital in Korea. MATERIALS AND METHODS: We retrospectively analyzed all consecutive episodes of Enterobacteriaceae in a mid-sized community-based hospital from January 2013 to February 2014. CRE was defined as organisms of Enterobacteriaceae showing decreased susceptibility to carbapenems. Risk factors for CRE were evaluated by a case–double control design. Carbapenemase was confirmed for CRE using a combined disc test. RESULTS: During 229,710 patient-days, 2,510 Enterobacteriaceae isolates were obtained. A total of 41 (1.6%) CRE isolates were enrolled in the study period. Thirteen species (31.7%) were Enterobacter aerogenes, 8 (19.5%) Klebsiella pneumoniae, 5 (12.2%) Enterobacter cloacae, and 15 other species of Enterobacteriaceae, respectively. Among the 41 isolates, only one (2.4%) E. aerogenes isolate belonged to CPE. For evaluation of risk factors, a total of 111 patients were enrolled and this included 37 patients in the CRE group, 37 in control group I (identical species), and 37 in control group II (different species). Based on multivariate analysis, regularly visiting the outpatient clinic was a risk factor for CRE acquisition in the control group I (P = 0.003), while vascular catheter and Charlson comorbidity index score ≥ 3 were risk factors in control group II (P = 0.010 and 0.011, each). Patients with CRE were more likely to experience a reduced level of consciousness, use a vasopressor, be under intensive care, and suffer from acute kidney injury. However, CRE was not an independent predictor of mortality compared with both control groups. CONCLUSION: In conclusion, the prevalence of CRE was higher than expected in a mid-sized community-based hospital in Korea. CRE should be considered when patients have a vascular catheter, high comorbidity score, and regular visits to the outpatient clinic. This study suggests the need for appropriate prevention efforts and constant attention to CRE infection control in a mid-sized community-based hospital.

A Case of Spontaneous Bacterial Peritonitis with Bacteremia Caused by Shewanella algae

Human infection caused by Shewanella algae is rare, which usually occurred after direct contact with seawater or ingestion of raw seafood in the immunocompromised host. There have been anecdotal reports about Shewanella infections in human, but their pathogenic role and microbiologic data are limited. Here, we report a fatal case of spontaneous bacterial peritonitis with bacteremia due to S. algae in a 57-year-old male with liver cirrhosis who had no history of exposure to seawater or raw seafood. Polymicrobial infection with Streptococcus mitis and Escherichia coli was combined and the patient died in spite of early appropriate antimicrobial therapy and early goal-directed therapy for sepsis.

Clinical characteristics and the usefulness of the QuantiFERON-TB Gold In-Tube test in hematologic patients with hepatic or splenic lesions

BACKGROUND/AIMS: Hepatic or splenic lesions in hematologic patients are not defined well because they are not easy to evaluate due to limitations of invasive procedures. Management typically depends on the clinical diagnosis with few microbiological data. METHODS: We reviewed the medical records of consecutive hematologic patients with hepatic or splenic lesions in the infectious diseases unit from April 2009 to December 2010 at the Catholic Hematopoietic Stem Cell Transplantation Center in Korea. RESULTS: Twenty-six patients were identified. Their mean age was 46.0 +/- 14.7 years, and 16 (61.5%) were male. Underlying diseases were acute myelogenous leukemia (n = 15, 57.7%) and myelodysplastic syndrome (n = 6, 23.1%). Among the nine nontuberculous infectious lesions, two bacterial, six fungal, and one combined infection were identified. The numbers of confirmed, probable, and possible tuberculosis (TB) cases were one, three, and four, respectively. Two patients had concurrent pulmonary TB. QuantiFERON-TB Gold In-Tube (QFT-GIT, Cellestis Ltd.) was positive in seven cases, among which six were diagnosed with TB. The sensitivity and specificity of QFT-GIT were 75% and 81.3%. Nine (34.6%) were defined as noninfectious causes. CONCLUSIONS: Causes of hepatic or splenic lesion in hematologic patients were diverse including TB, non-TB organisms, and noninfectious origins. TB should be considered for patients not responding to antibacterial or antifungal drugs, even in the absence of direct microbiological evidence. QFT-GIT may be useful for a differential diagnosis of hepatosplenic lesions in hematologic patients.

Posaconazole Treatment in Korea: Single-Center Experience Over 5 Years

PURPOSE: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. MATERIALS AND METHODS: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. RESULTS: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. CONCLUSION: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.

Epidemiology and Clinical Features of Bloodstream Infections in Hematology Wards: One Year Experience at the Catholic Blood and Marrow Transplantation Center

BACKGROUND: The aim of this study was to investigate the clinical features and epidemiology of bloodstream infections (BSIs) in 2 distinctive hematological wards of the Catholic Blood and Marrow Transplantation (BMT) center. MATERIALS AND METHODS: We retrospectively reviewed the medical data of patients who developed BSIs from June 2009 to May 2010 in 2 hematologic wards at the Catholic BMT center. Ward A is a 44-bed unit mainly conducting conventional high dose chemotherapy and ward B is a 23-bed unit exclusively conducting BMT. RESULTS: Overall, 222 BSI episodes were developed from 159 patients. Acute myeloid leukemia in ward A and multiple myeloma in ward B were more frequent than in ward B and A, respectively. Sex, age, presence of neutropenia, shock, Pitt bacteremia score, type of central catheter, level of C-reactive protein, duration of admission days, type of BSI, overall mortality and distribution of organisms were not different between the 2 wards. There were 202 monomicrobial and 20 polymicrobial BSI episodes, including 2 fungemia episodes. The incidence rate of overall BSIs per 1,000 patient-days was higher in ward A than in ward B (incidence rate ratio 2.88, 95% confidence interval 1.97-4.22, P<0.001). Among 243 organisms isolated, the number of gram positives, gram negatives and fungi were 122, 119 and 2, respectively. Escherichia coli was the most common organism in both ward A and B (27.6% and 42.4%), followed by viridians streptococci (18.6% and 15.2%) and Klebsiella pneumoniae (13.3% and 9.0%). Extended spectrum beta-lactamase (ESBL) producers accounted for 31.9% (23/72) of E. coli and 71.0% (22/31) of K. pneumoniae. Out of 19 Enterococcus faecium, 7 isolates (36.8%) were resistant to vancomycin. The crude mortality rates at 7 and 30 days after each BSI episode were 4.5% (10/222) and 13.1% (29/222), and were significantly higher in the patients with shock compared with those without shock (20.5% vs. 1.1%, P<0.001 and 38.5% vs. 7.7%, P<0.001, respectively). CONCLUSIONS: The incidence rate of BSIs was higher in patients receiving chemotherapy than those receiving BMT, but the distribution of organisms was not different between the 2 wards. E. coli was the most common causative BSI organism in hematologic wards followed by viridians streptococci and K. pneumoniae.

Inappropriateness of Quinolone in Scrub Typhus Treatment Due to gyrA Mutation in Orientia tsutsugamushi Boryong Strain

The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.