Se Yoon Park

Risk Factors for Mortality in Patients with Acinetobacter baumannii Bacteremia.

Background Acinetobacter baumannii, an opportunistic nosocomial pathogen that can cause significant morbidity and mortality, has emerged as a worldwide problem. The aim of this study was to evaluate the risk factors for mortality in patients with A. baumannii bacteremia. Materials and Methods We retrospectively evaluated 118 patients who had A. baumannii bacteremia between July 2003 and December 2011. The aim of this study was to identify the 30-day mortality in patients with A. baumannii bacteremia and relevant risk factors. Results The bacteremia-related 30-day mortality rate was 34.1%. Univariate analysis revealed that the risk factors for mortality included malignancy, longer hospital stay before bacteremia, intensive care unit (ICU) stay at the time of bacteremia, mechanical ventilation, use of a central venous catheter, unknown origin of bacteremia, bacteremia due to pneumonia, antimicrobial resistance to carbapenems, and elevated Acute Physiology and Chronic Health Evaluation II and Pitt bacteremia scores. Multivariate logistic regression analysis revealed that resistance to carbapenems (odds ratio [OR]: 4.01, 95% confidence interval [CI]: 1.51 to 0.68, P = 0.005), need for mechanical ventilation (OR: 3.97, 95% CI: 1.41 to 11.13, P = 0.005), and presence of malignancy (OR: 4.40, 95% CI: 1.60 to 12.08, P = 0.004) were significantly related to mortality risk. Conclusions Risk factors such as resistance to carbapenems, mechanical ventilation, and presence of malignancy were found to be associated with high mortality rates in the patients with A. baumannii bacteremia.

Use of Plasma Therapy for Severe Fever with Thrombocytopenia Syndrome Encephalopathy.

To the Editor: The central nervous system (CNS) manifestations of severe fever with thrombocytopenia syndrome (SFTS) include apathy, seizure, muscular tremor, and coma (1,2); however, the mechanism underlying CNS manifestations in SFTS is not clear. Deng et al. reported that illness of 15 (13%) of 115 patients with SFTS met the case definition for suspected encephalitis (1). However, they did not present any straightforward evidence of CNS invasion by STFS virus (SFTSV). Cui et al. similarly reported that encephalitis developed in one fifth of 538 patients with SFTS (2). They found evidence of SFTSV by isolating the virus from the cerebrospinal fluid (CSF) in 1 of 2 patients with SFTS whose CSF was obtained, but they did not mention CSF pleocytosis (2). We report a case of SFTS-associated encephalopathy, without pleocytosis and with normal CSF protein and glucose levels, that was confirmed by real-time reverse transcription PCR of the CSF. The patient was treated with experimental plasma exchange followed by convalescent plasma therapy. During 2015, a 62-year-old woman who had a history of treated tuberculous meningitis 10 years earlier was admitted to a tertiary hospital in Seoul, South Korea (Republic of Korea), with a 5-day fever, myalgia, and headache. On hospital day (HD) 2, CSF examination revealed 1 leukocyte/mm3, protein 35 mg/dL (reference 9–58 mg/dL), glucose 74 mg/dL (reference 45–80 mg/dL), and CSF/blood glucose ratio 0.66 (reference 0.50–0.80). No bacteria or fungi were isolated from CSF. On HD 4, her headache worsened, and she displayed confused verbal responses and lacked orientation of time and place. No focal neurologic signs were observed. On HD 5, magnetic resonance imaging of the brain indicated no additional abnormalities of the parenchyma and extra-axial structures except for a focal parenchymal defect in the right midbrain that had been discovered as a sequelae of tuberculous meningitis 10 years earlier. On HD 7, follow-up CSF examination revealed no leukocytes, protein 57 mg/dL, glucose 209 mg/dL, and CSF/blood glucose ratio 0.62. SFTSV was detected by real-time reverse transcription PCR (Technical Appendix) in plasma and CSF (Figure). On HD 8, the patient became comatose and had no eye, verbal, and motor responses to noxious stimuli (Glasgow coma scale 3). Bilateral exotropia was noted with spared light and corneal reflexes and oculocephalic responses. Experimental plasma exchange was performed, and her viral load declined slightly; however, consciousness and platelet count did not change. An ABO-identical nurse who had recovered from SFTS in September 2014 agreed to donate plasma; her indirect immunofluorescence antibody assay (IFA) for SFTSV IgG had been 1:1,024 in October 2014. On HD 17, the patient’s titer of SFTSV IgG was 1:64 before the plasma therapy. We obtained ≈400 mL of convalescent plasma (IFA assay for SFTSV IgG 1:256 at the time of donation) from the donor and transfused it into the patient on HD 17. The viral load in the blood decreased steeply by a factor of 10 (6 × 102 to 6 × 101 copies/mL) during the first 7 hours (4–11 pm on HD 17); it then gradually decreased from 3 × 101 at 7 am on HD 18 to 6 × 100 copies/mL on HD 20, by which time the patient’s mental status had fully recovered (Figure). Figure Changes in viral RNA load and immunofluorescence antibody titer and timing of therapies for a 62-year-old woman with SFTSV-associated encephalopathy in response to plasma exchange followed by convalescent plasma therapy, South Korea, 2015. CSF, cerebrospinal ... This case is unique in that SFTS was detected in CSF in the absence of pleocytosis and with normal CSF protein and glucose levels, as in previous reports on influenza-associated acute encephalopathy (3). Although headache and encephalitis can occur in patients with SFTS (1,2), the pathophysiology of CNS manifestations in SFTS is unknown. As with influenza-associated acute encephalopathy, a possible hypothesis is direct invasion of SFTSV into the CNS; another hypothesis is that elevated cytokine levels or renal and hepatic dysfunction are associated with SFTS encephalopathy. We are aware of 1 report of a favorable outcome of plasma exchange and ribavirin in 2 patients with SFTS and multiorgan failure in South Korea (4). However, the patients’ clinical condition did not substantially improve despite the 5-day plasma exchange therapy and viral load only slightly decreased. Use of convalescent plasma therapy in severe acute respiratory syndrome, influenza A(H1N1) and A(H5N1), and Ebola virus disease has been reported (5–7), but little evidence exists to support its use. However, given the lack of conclusive data, these potential experimental treatments for emerging infectious diseases warrant further study in a clinical trial. Response was favorable in a mouse model of SFTS treated postexposure with antiserum from a patient who had recovered from SFTS (8). We do not know whether the convalescent plasma therapy given to the patient described here actually had a positive effect because her IFA titer was already increasing around the time she received the plasma therapy. At the time of this writing, 2 patients with SFTS who were treated with intravenous immunoglobulin and corticosteroid had been reported (9). Cautious interpretation of these experimental therapies is necessary because these therapies may not have had anything to do with the patients’ recovery. Technical Appendix: Performance of real-time reverse transcription PCR to detect severe fever with thrombocytopenia syndrome virus RNA. Click here to view.(82K, pdf)

An isothermal, label-free, and rapid one-step RNA amplification/detection assay for diagnosis of respiratory viral infections.

Abstract Recently, RNA viral infections caused by respiratory viruses, such as influenza, parainfluenza, respiratory syncytial virus, coronavirus, and Middle East respiratory syndrome-coronavirus (MERS-CoV), and Zika virus, are a major public health threats in the world. Although myriads of diagnostic methods based on RNA amplification have been developed in the last decades, they continue to lack speed, sensitivity, and specificity for clinical use. A rapid and accurate diagnostic method is needed for appropriate control, including isolation and treatment of the patients. Here, we report an isothermal, label-free, one-step RNA amplification and detection system, termed as iROAD, for the diagnosis of respiratory diseases. It couples a one-step isothermal RNA amplification method and a bio-optical sensor for simultaneous viral RNA amplification/detection in a label-free and real-time manner. The iROAD assay offers a one-step viral RNA amplification/detection example to rapid analysis (<20min). The detection limit of iROAD assay was found to be 10-times more sensitive than that of real-time reverse transcription-PCR method. We confirmed the clinical utility of the iROAD assay by detecting viral RNAs obtained from 63 human respiratory samples. We envision that the iROAD assay will be useful and potentially adaptable for better diagnosis of emerging infectious diseases including respiratory diseases.

Factors predicting life-threatening infections with respiratory syncytial virus in adult patients.

Abstract Background: Respiratory syncytial virus (RSV) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. However, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with RSV. Methods: We conducted a retrospective cohort study from October 2013 to September 2015. Adult patients with RSV who visited the emergency department were enrolled. Primary outcome was life-threatening infection (admission to intensive care unit, need for ventilator care or in-hospital death). Results: A total of 227 patients were analysed. Thirty-four (15%) were classified as having life-threatening infections. By logistic regression, lower respiratory infection, chronic lung disease and bacterial co-infection were independent predictors of life-threatening infections. We developed a simple clinical scoring system using these variables (lower respiratory tract infection = score 4, chronic respiratory disease = score 3, bacterial co-infection = score 3 and fever ≥38 °C = score 2) to predict life-threatening infection. A score of >5 differentiated life-threatening RSV from non-life-threatening RSV with 82% sensitivity (95% CI, 66–93) and 72% specificity (95% CI, 65–78). Conclusions: The use of a clinical scoring system based on lower respiratory infection, chronic respiratory disease, bacterial co-infection and fever appears to be useful for outcome prediction and risk stratification in order to select patients who may need early antiviral therapy.

Use of Dimethyl Pimelimidate with Microfluidic System for Nucleic Acids Extraction without Electricity

The isolation of nucleic acids in the lab on a chip is crucial to achieve the maximal effectiveness of point-of-care testing for detection in clinical applications. Here, we report on the use of a simple and versatile single-channel microfluidic platform that combines dimethyl pimelimidate (DMP) for nucleic acids (both RNA and DNA) extraction without electricity using a thin-film system. The system is based on the adaption of DMP into nonchaotropic-based nucleic acids and the capture of reagents into a low-cost thin-film platform for use as a microfluidic total analysis system, which can be utilized for sample processing in clinical diagnostics. Moreover, we assessed the use of the DMP system for the extraction of nucleic acids from various samples, including mammalian cells, bacterial cells, and viruses from human disease, and we also confirmed that the quality and quantity of the nucleic acids extracted were sufficient to allow for the robust detection of biomarkers and/or pathogens in downstream analysis. Furthermore, this DMP system does not require any instruments and electricity, and has improved time efficiency, portability, and affordability. Thus, we believe that the DMP system may change the paradigm of sample processing in clinical diagnostics.

Diagnostic performance of the (1–3)-β-D-glucan assay in patients with Pneumocystis jirovecii compared with those with candidiasis, aspergillosis, mucormycosis, and tuberculosis, and healthy volunteers

Background Diagnosis of pneumocystis pneumonia (PCP) relies on microscopic visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory specimens, which involves invasive procedures such as bronchoalveolar lavage. The (1–3)-β-D-glucan (BG) assay has been proposed as a less invasive and less expensive diagnostic test to rule out PCP. We therefore compared blood levels of BG in patients with PCP with those of patients with candidemia, chronic disseminated candidiasis (CDC), invasive aspergillosis, mucormycosis, and tuberculosis and those of healthy volunteers. Methods Adult patients who were diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and tuberculosis whose blood samples were available, and healthy volunteers were enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period. The blood samples were assayed with the Goldstream Fungus (1–3)-β-D-glucan test (Gold Mountain River Tech Development, Beijing, China). Results A total of 136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15 invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy volunteers) were included. The mean±SD of the concentration of 1–3-β-D-glucan in the patients with PCP (290.08 pg/mL±199.98) were similar to those of patients with candidemia (314.14 pg/mL±205.60, p = 0.90 at an α = 0.005) and CDC (129.74 pg/mL±182.79, p = 0.03 at an α = 0.005), but higher than those of patients with invasive aspergillosis (131.62 pg/mL±161.67, p = 0.002 at an α = 0.005), mucormycosis (95.08 pg/mL±146.80, p<0.001 at an α = 0.005), and tuberculosis (103.31 pg/mL±140.81, p<0.001 at an α = 0.005) as well as healthy volunteers (101.18 pg/mL±197.52, p<0.001 at an α = 0.005). At a cut-off value > 31.25 pg/mL, which is highly sensitive for PCP versus tuberculosis plus healthy volunteers at the expense of specificity, the BG assay had a sensitivity of 92% (95% CI 81%-98%) and a specificity of 55% (95% CI 39%-71%). Conclusions The BG assay appears to be a useful adjunct test for PCP.

Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Streptococcus pneumoniae: A Matched Case-Control Study.

AbstractStreptococcus pneumoniae is a well-known cause of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. However, little information is available regarding clinical characteristics and outcomes of SBP caused by S. pneumoniae. It has been suggested that spontaneous pneumococcal peritonitis (SPP) often spreads hematogenously from concomitant pneumococcal pneumonia, and is associated with a higher rate of mortality.During the period between January 1997 and December 2013, 50 SPP cases were identified. These cases were then age/sex-matched with 100 patients with SBP due to causes other than S. pneumoniae (controls).SPP accounted for 4.3% (50/1172) of all culture-proven SBPs. The baseline Child-Pugh class, etiology of cirrhosis, and model for end-stage liver disease scores were comparable for the 2 groups. SPP patients were more likely than control patients to have a community-acquired infection (90.0% vs. 76.0%; P = 0.04), concurrent bacteremia (84.0% vs. 59.0%; P = 0.002), and to present with variceal bleeding (10.0% vs. 1.0%; P = 0.02). None of the study patients had pneumococcal pneumonia. The most common initial empirical therapy for both groups was third-generation cephalosporins (96.0% vs. 91.0%; P = 0.34) which was active against a significantly higher proportion of the cases than of the controls (97.8% vs. 78.7%; P = 0.003). Thirty-day mortality was significantly lower in the case group than in the control group (10.0% vs. 24.0%; P = 0.04).SPP was not associated with pneumococcal pneumonia and showed lower mortality than SBP caused by other organisms. However, the present study was constrained by the natural limitations characteristic of a small, retrospective study. Therefore, large-scale, well-controlled studies are required to demonstrate the influence of SPP on mortality, which was marginal in the present study.

Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis

Background Cytomegalovirus (CMV) retinitis is one of the most important tissue-invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive diagnostic methods, notably the CMV antigenemia assay, have been widely used as adjunct tests to diagnose tissue-invasive CMV diseases. However, there are limited data on the diagnostic value of the CMV antigenemia assay for diagnosing CMV retinitis. Materials and Methods We performed a retrospective review of all cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year period. The diagnosis of CMV retinitis was made by experienced ophthalmologists according to medical history and an ophthalmoscopic appearance of typical retinopathy, together with absence of an alternative diagnosis. Results We analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia assay was 66% (95% confidence interval [CI] 50–80%). The test’s sensitivity showed a non-significant trend towards being higher in HIV-infected patients than in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40–74%). Conclusions The CMV antigenemia assay has limited value as a non-invasive diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay need to be interpreted in the context of underlying disease, clinical presentation, and ophthalmoscopic findings.

Needle-Stick Injury Caused by a Patient With Severe Fever With Thrombocytopenia Syndrome in Korea

To the Editor—Several studies have identified clusters of severe fever with thrombocytopenic syndrome (SFTS) infections among family members and that appear to have been transmitted by human contact. In addition, possible transmission from the index patient with SFTS to healthcare workers (HCWs) has been reported. Blood and body fluids were suggested as the possible transmission route. Therefore, strict adherence to routine blood and body fluid precautions is required when HCWs come into contact with any patient, especially anyone with suspected viral hemorrhagic fever or a tick-borne rickettsial disease. Herein we report the result of needle-stick injury to an HCW caused by a patient with a high viral load of SFTS. A 62-year-old woman was admitted to Asan Medical Center with a 5-day fever, myalgia, and a headache (July 1, 2015). On her hospital day (HD) 6, her blood pressure decreased to 80/45 mm Hg and her condition rapidly declined, causing a need for mechanical ventilation. The patient was admitted to the intensive care unit. On HD 7, SFTS-associated encephalopathy was diagnosed from detection of SFTS virus (SFTSV) by real-time polymerase chain reaction assay (RT-PCR) from plasma and cerebrospinal fluid. On HD 12, a nurse who took care of the patient experienced needle-stick injury on her finger during blood sampling. The needle was filled with the patient’s blood. The needle penetrated her left third finger skin with a notable amount of bleeding. The viral load of the patient was 1 × 10 on HD 13. Four days later (July 16, 2015), we checked her blood for SFTSV by RT-PCR and immunofluorescence assay titer for evaluation of possible SFTSV transmission, despite no development of symptoms, because there was a previous report of subclinical infection in 1 HCW who had contacted an index patient. SFTSV was not found by RT-PCR and the total immunoglobulin G level for SFTSV immunofluorescence assay was less than 1:32. The HCW had not developed any symptoms 6 weeks after the needle-stick injury. Her convalescent serum drawn 1 month after the injury recheck (August 13, 2015) revealed SFTSV was not detected by RT-PCR and the total immunoglobulin G level for SFTSV immunofluorescence assay was less than 1:32. Recently, viral hemorrhagic fevers, such as Ebola virus disease, have attracted renewed attention owing to the large Ebola virus disease outbreak in West Africa. Therefore, nosocomial transmission to HCWs from patients with suspected viral hemorrhagic fever is of paramount importance. SFTSV is a third group within the genus phlebovirus, family Bunyaviridae, one of the 5 families causing viral hemorrhagic fever. Interestingly, the overall transmission rate of SFTS in a previous study by our group was 15%, which is comparable to the household transmission rate (16%) of Ebola virus disease in the absence of personal protective devices. Therefore, it is theoretically possible that direct inoculation of blood that contains sufficient volumes of infectious SFTS can cause infection via needle-stick injury. Fortunately, SFTSV was not transmitted in our case despite the high viral load in the index patient’s blood. However, the possible effects of needle-stick injury, such as Ebola virus disease transmission, deserve further scrutiny.

A rapid bio-optical sensor for diagnosing Q fever in clinical specimens

Recent zoonotic outbreaks, such as Zika, Middle East respiratory syndrome and Ebola, have highlighted the need for rapid and accurate diagnostic assays that can be used to aid pathogen control. Q fever is a zoonotic disease caused by the transmission of Coxiella burnetii that can cause serious illness in humans through aerosols and is considered a potential bioterrorism agent. However, the existing assays are not suitable for the detection of this pathogen due to its low levels in real samples. We here describe a rapid bio-optical sensor for the accurate detection of Q fever and validate its clinical utility. By combining a bio-optical sensor, that transduces the presence of the target DNA based on binding-induced changes in the refractive index on the waveguide surface in a label-free and real-time manner, with isothermal DNA amplification, this new diagnostic tool offers a rapid (<20 min), 1-step DNA amplification/detection method. We confirmed the clinical sensitivity (>90%) of the bio-optical sensor by detecting C. burnetii in 11 formalin-fixed, paraffin-embedded liver biopsy samples from acute Q fever hepatitis patients and in 16 blood plasma samples from patients in which Q fever is the cause of fever of unknown origin.