Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Serious fungal infections in Korea.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

Empirical combination of a ß-lactam to vancomycin may not improve outcomes of methicillin-susceptible Staphylococcus aureus bacteremia, compared to vancomycin monotherapy.

To evaluate effect of empirical combination of a ß-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, ß-lactam; VAN group, vancomycin; BV group, combination of ß-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086-3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a ß-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.

Emergence of an extended-spectrum ß-lactamase-producing serotype K1 Klebsiella pneumoniae ST23 strain from Asian countries.

Extended-spectrum ß-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.

Sequence type 72 community-associated meticillin-resistant Staphylococcus aureus emerged as a predominant clone of nasal colonization in newly admitted patients.

Current knowledge of community-associated (CA) meticillin-resistant Staphylococcus aureus (MRSA) carriage in hospitalized patients is incomplete. Genotypic characteristics of 637 nasal MRSA isolates from newly admitted patients in South Korea were investigated. Sequence type (ST) 72 accounted for 52.1%, 46.3%, and 52.8% of the isolates during the periods of 2007-2008, 2009-2010, and 2013-2014, respectively. Instead of classic MRSA clones responsible for healthcare-associated infections, including ST5 and ST239, MRSA with community genotype ST72 was the predominant strain in newly admitted patients regardless of age and home province of the patients. Active strategies are needed to prevent healthcare-associated infection by CA-MRSA.

Generic piperacillin/tazobactam is not associated with galactomannan false-positivity in adult patients with cancer: a case-control study.

Recent products of piperacillin/tazobactam (PTZ) from the original manufacturer, previously considered a major cause of galactomannan (GM) false-positivity, are reported not to be related to it. However, data regarding generic PTZ are limited and controversial. To evaluate the effect of generic PTZ on GM false-positivity in Korea, we performed a case-control study in adult patients with cancer. A case-control study was designed. Electronic medical records of cancer patients who were admitted and tested for serum GM between March and June 2014 at a tertiary care university hospital were reviewed. During the study period, a single generic PTZ (C manufacturer, Korea) was used. Patients who received PTZ within 24 h prior to serum GM testing were enrolled. Age- and GM test date-matched non-PTZ patients were selected as controls. A total of 110 patients received PTZ within 24 h prior to serum GM testing during the study period. The GM optical density index (ODI) of the PTZ group did not vary significantly from that of the control group (p = 0.251). The percentage of false-positive patients in the PTZ group was also similar to that of the control group (p = 0.538). There was no statistical relationship between GM ODI titer and time interval from PTZ administration (p = 0.095) or cumulative PTZ dose (p = 0.416). In a case-control study that evaluated 220 patients, a generic PTZ in Korea was not related to GM false-positivity.

Fatal scedosporiosis in multiple solid organ allografts transmitted from a nearly-drowned donor.

Scedosporium spp. is the most common mold infection in pneumonia resulting from near-drowning. Three fatal scedosporiosis cases developed after solid organ transplantation, probably transmitted from the nearly-drowned donor. One heart transplant recipient and two kidney transplant recipients developed fatal scedosporiosis following deceased donor transplantation from the same donor, a nearly-drowned victim of a suicide attempt. Genotypically, indistinguishable strains of Scedosporium auratiacum were recovered from the three recipients. Two liver transplant recipients from the same donor received prophylactic voriconazole without any subsequent signs of infection. To determine the safety of donation from nearly-drowned donors, a national traceback investigation was also performed of the causes of deaths in all transplant recipients who received organs from drowned donors between 2001 and 2013. Over 13 years, 2600 deceased donor transplants were performed in Korea. Among these 2600 deceased donor transplants, 27 (1%) victims of drowning donated their organs. From these 27 donors, 84 patients received organ transplants and 18 died, including the above three. We found no microbiologic evidence of invasive mold transmission from the nearly-drowned donors to the other 15 recipients. Although disseminated infection in the donor could not be demonstrated by culture, undiagnosed disseminated donor infection and transmission of Scedosporium spp. should be considered in near-drowning events.

Risk factors for cytomegalovirus gastrointestinal diseases in adult patients with cancer.

Cytomegalovirus (CMV) gastrointestinal (GI) disease has been noticed frequently in cancer patients, causing abdominal pain, diarrhea, and GI bleeding. However, little is known about its actual incidence, clinical presentation, and the risk factors for its development among cancer patients. To answer these questions, we analyzed all cases that occurred during an 18-year period at our center. A case-control study was performed to identify risk factors for CMV GI disease. Electronic medical records were reviewed from individuals who were admitted and diagnosed with CMV GI disease during the period of January 1995 through March 2013 at a tertiary care center. Two CMV disease-free cancer patients were matched as controls. A total of 98 episodes of CMV GI disease were included in this study, and the overall incidence rate was 52.5 per 100,000 cancer patients, with an increasing trend throughout the study period. According to multivariate analysis, male sex, low body mass index, lymphopenia, hematological malignancy, and steroid use and red blood cell transfusion within 1 month prior to the CMV disease were identified to be independent risk factors. Among these factors, RBC transfusion showed the highest odds ratio (OR = 5.09). Male sex, low body mass index, lymphopenia, hematological malignancy, steroid use, and red blood cell transfusion within 1 month prior to the CMV disease diagnosis were independent risk factors for the development of CMV GI disease in adult patients with cancer.

Impact of acute kidney injury on mortality and medical costs in patients with meticillin-resistant Staphylococcus aureus bacteraemia: a retrospective, multicentre observational study.

BACKGROUND: Despite the frequent occurrence of acute kidney injury (AKI) associated with meticillin-resistant Staphylococcus aureus (MRSA) infection during treatment, the adverse impact of renal injury on clinical and economic outcomes has not been evaluated. AIM: To study the clinical and economic burdens of MRSA bacteraemia and the impact of AKI occurring during treatment on outcomes. METHODS: Medical records of patients hospitalized for MRSA bacteraemia between March 2010 and February 2011 in eight hospitals in Korea were reviewed retrospectively to evaluate the risk factors for AKI and mortality. Direct medical costs per patient of MRSA bacteraemia during treatment were estimated from the medical resources consumed. FINDINGS: In all, 335 patients were identified to have MRSA bacteraemia. AKI occurred in 135 patients (40.3%) during first-line antibiotic therapy. Independent risk factors for AKI were male sex, underlying renal disease, intra-abdominal and central venous catheter infection, and increase in Pitt bacteraemia score. Seventy-seven (23.0%) patients died during the study period. Underlying solid tumour, high Pitt bacteraemia score, and occurrence of AKI were independent risk factors for mortality. The mean total medical cost per MRSA patient was estimated as South Korean Won 5,435,361 (US$4,906), and occurrence of AKI and ICU admission were identified as independent predictors of increased direct medical costs. Compared with patients who retained their baseline renal function, patients with AKI had a 45% increase in medical costs. CONCLUSIONS: Patients who developed AKI showed significantly higher mortality rate and greater direct medical costs compared with patients who retained baseline renal function.

Impact of a computerized alert system for bacteremia notification on the appropriate antibiotic treatment of Staphylococcus aureus bloodstream infections.

A computerized alert system (CAS) has been introduced to notify bacteremia in real time. We evaluated the impact of the CAS on the administration of appropriate antibiotics in patients with Staphylococcus aureus bloodstream infections (BSIs). We retrospectively reviewed the medical records of patients with S. aureus BSI for each 1-year control and intervention periods, before and after the implementation of the CAS. The proportions of appropriate antibiotic treatment were compared between the control and intervention periods. The 30-day mortality of S. aureus bacteremia was also assessed in the study population. A total of 313 patients were included in the study. Appropriate antibiotics were initiated 7 h earlier in the intervention period (mean time, 13.5 h vs. 20.0 h; p = 0.136). The administration of appropriate antibiotics within the 24 h after blood acquisition was similar between the two periods, but this significantly increased from 3.3% in the control period to 10.6% in the intervention during the 24-36 h interval (p = 0.012). In the subgroup analysis, similar trends were observed in patients with methicillin-resistant isolates (6.7% vs. 18.2%; p = 0.032) and hospital-onset infection (3.5% vs. 17.1 %; p = 0.004). The independent risk factors for 30-day mortality of S. aureus bacteremia were age, a high Pitt bacteremia score, an increased Charlson's weighted index of comorbidity, and hospital-onset infection, although the appropriateness of antibiotic therapy within 36 h and the CAS were not identified as predictors. The CAS increased the proportion of appropriate antimicrobial therapy during the 24-36 h interval after bacteremia onset in patients with S. aureus BSIs.

Community-associated Panton-Valentine leukocidin-negative meticillin-resistant Staphylococcus aureus clone (ST72-MRSA-IV) causing healthcare-associated pneumonia and surgical site infection in Korea.

BACKGROUND: Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) has emerged as an important pathogen worldwide in a continent-specific manner. Clinical characteristics of infections caused by CA-MRSA other than USA300, especially in healthcare settings, have not been well established. AIM: To conduct a retrospective cohort study to determine the clinical characteristics of infections caused by Panton-Valentine leukocidin (PVL)-negative, multilocus sequence type (ST) 72 staphylococcal cassette chromosome mec (SCCmec) type IV, a major CA-MRSA clone in Korea. METHODS: ST72-IV isolates, which were susceptible to fluoroquinolones, gentamicin, rifampicin, and cotrimoxazole, were presumptively identified among 4667 MRSA isolates and then confirmed by SCCmec typing and multilocus sequence typing. A total of 124 cases of ST72-IV infections were analysed. FINDINGS: The annual incidence of infections by ST72-IV per 100,000 admissions increased from 45.5 to 66.3 cases during 2007-2009. The most frequently occurring type of infection was skin and soft tissue infection (SSTI) (46.0%), followed by pneumonia (27.4%) and bone and joint infection (9.7%). Surgical site infection accounted for 22.6% and 32.5% of community-onset (CO) healthcare-associated infection and hospital-onset (HO) infection, respectively. Pneumonia was most frequent (45.0%) among HO infection. Multivariate analysis showed that pneumonia increased the odds of all-cause mortality (odds ratio: 18.8; 95% confidence interval: 2.6-133.9) compared with other types of infection. CONCLUSIONS: Increasing trends were observed in annual incidence of CO and HO infections by ST72-IV in Korea. Pneumonia was the most frequent among HO infection and was associated with higher mortality. These findings pose important implications for successful antibiotic therapy and infection control in the era of CA-MRSA.

Tacrolimus as a risk factor for tuberculosis and outcome of treatment with rifampicin in solid organ transplant recipients.

BACKGROUND: The purpose of this study was to investigate the incidence, risk factors, and treatment outcome of tuberculosis (TB) in solid organ transplant (SOT) recipients treated with rifampicin. METHODS: The incidence density of TB was calculated by a retrospective cohort study. Risk factors for TB were analyzed by a nested case-control study. Treatment outcome and effects of anti-TB drugs on immunosuppressants and allograft were compared between patients whose initial 2-month intensive regimen included rifampicin and those whose intensive regimen did not. RESULTS: Among the 2144 SOT recipients over 16 years, 40 cases of TB were found (1.7%). The incidence density was 372 cases per 10(5) patient years (95% confidence interval [CI], 270-503), which was 4 times higher than for the general Korean population (90 cases per 10(5) person years). The median time to the development of TB was 234 days (range, 33-3940 days). The use of tacrolimus (odds ratio [OR] 4.90; 95% CI, 1.74-13.80; P = 0.003) and cytomegalovirus (CMV) infection within the prior 3 months (OR 4.62; 95% CI, 1.44-14.87; P = 0.01) were found to be risk factors for TB. Patients whose intensive regimen included rifampicin were more likely to have an increased dose of calcineurin inhibitors than patients whose intensive regimen did not include rifampicin (13/15 [86.7%] vs. 3/14 [21.4%], P = 0.001). Graft rejection and mortality did not differ between the 2 groups. CONCLUSIONS: Use of tacrolimus and CMV infection were major risk factors for TB in SOT recipients. The graft outcome and mortality did not differ whether rifampicin was used or not during the first 2-month intensive phase.

Impact of inappropriate empiric antimicrobial therapy on outcome in Pseudomonas aeruginosa bacteraemia: a stratified analysis according to sites of infection.

BACKGROUND: The purpose of this study was to evaluate the impact of inappropriate empiric antimicrobial therapy on the outcome of Pseudomonas aeruginosa bacteraemia according to the primary infection site. METHODS: A retrospective cohort study including 202 patients with P. aeruginosa bacteraemia was performed. High-risk sites of infection were defined as the lung, intra-abdominal non-hepatobiliary tract or unknown source. RESULTS: Of the 202 patients with P. aeruginosa bacteraemia, 80 (39.6%) had received inappropriate empiric antimicrobial therapy. No significant difference in the 30-day mortality rate was found between the inappropriate therapy group and the appropriate therapy group (19/80 [23.8%] vs. 32/122 [26.2%], P = 0.692). Patients with pneumonia or non-hepatobiliary tract intra-abdominal infection showed significant association with high mortality, while those with urinary tract or hepatobiliary tract infection showed negative associations with mortality. In the subgroup analysis including 98 patients with high-risk sites of infection, the mortality rate of the inappropriate therapy group was significantly higher than that of the appropriate therapy group (14/26 [53.8%] vs. 23/72 [31.9%], P = 0.035). Inappropriate empiric antimicrobial therapy was also found to be one of the independent risk factors for mortality in patients with high-risk sites of infection (odds ratio [OR] 8.69; 95% confidence interval [CI] 1.86-40.59), along with renal disease, corticosteroid use, polymicrobial infection and higher Pitt bacteraemia score. CONCLUSION: Inappropriate empiric antimicrobial therapy adversely affected the outcome of P. aeruginosa bacteraemia in patients with high-risk sites of infection. Our data suggest that the impact of inappropriate antimicrobial therapy on the outcome of P. aeruginosa bacteraemia may be dependent on the primary site of infection.