Diabetic Foot Osteomyelitis Undergoing Amputation: Epidemiology and Prognostic Factors for Treatment Failure.

Background: When treating diabetic foot osteomyelitis (DFO), it remains difficult to determine the presence of residual infection and the optimal treatment after bone resection. In this study, we aimed to investigate the clinical characteristics of and prognostic factors in patients with DFO undergoing amputation. Methods: This retrospective study involved 101 patients with DFO who underwent amputation. Data on their demographics, clinical characteristics, tissue culture, and surgery type were collected. Patients were grouped according to primary closure status and clinical outcome postamputation. A good outcome was defined as a successful complete remission, characterized by the maintenance of complete wound healing with no sign of infection at 6 months postamputation. Multivariate logistic regression analysis was performed. Outcomes according to surgery type were also analyzed. Results: Staphylococcus aureus (17%) and Pseudomonas species (14%) were the most prevalent pathogens. Gram-negative bacteria were isolated from 62% of patients. In patients with primary closure, hemodialysis and ankle brachial index (ABI) <0.6 were associated with poor outcomes. In patients with DFO, ABI <0.6 was the only prognostic factor associated with treatment failure. Antimicrobial stewardship allows patients who underwent major amputation to reduce the duration of antibiotic therapy compared to those after minor amputation, although it did not contribute to reducing mortality. Conclusions: Peripheral artery disease and hemodialysis were associated with poor outcomes despite radical resection of the infected bone. Vigilant monitoring after amputation and antimicrobial stewardship implemented based on microbiological epidemiology, prognostic factors, and the type of surgery are important. A multidisciplinary team could assist in these activities to ensure treatment success.

Cytokine and Chemokine Profiles in Acute Severe Fever with Thrombocytopenia Syndrome and Scrub Typhus in South Korea.

In East Asia, severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus, which are common endemic tick- and mite-mediated diseases sharing common clinical manifestations, are becoming public health concerns. However, there are limited data on the comparative immunopathogenesis between the two diseases. We compared the cytokine profiles of SFTS and scrub typhus to further elucidate immune responses that occur during the disease courses. We prospectively enrolled 44 patients with confirmed SFTS and 49 patients with scrub typhus from July 2015 to December 2020. In addition, 10 healthy volunteers were enrolled as healthy controls. A cytometric bead array was used to analyze plasma samples for 16 cytokines. A total of 68 plasma samples, including 31 (45.6%) from patients with SFTS and 37 (54.4%) from patients with scrub typhus, were available for cytokine measurement. There were three cytokine expression patterns: increased levels in both SFTS and scrub typhus (interleukin 6 [IL-6], IL-10, interferon gamma induced protein 10 [IP-10], and granulocyte-macrophage colony-stimulating factor [GM-CSF]), highest levels in SFTS (interferon alpha [IFN-α], IFN-γ, granulocyte-CSF [G-CSF], monocyte chemotactic protein 1 [MCP-1], macrophage inflammatory protein 1α [MIP-1α], and IL-8), and distinct levels in scrub typhus (IL-12p40, tumor necrosis factor alpha [TNFα], IL-1ß, regulated on activation and normally T-cell expressed and secreted [RANTES], IL-17A, and vascular endothelial growth factor [VEGF]). Although patients with acute SFTS and scrub typhus exhibited partly shared expression patterns of cytokines related to disease severity, the different profiles of cytokines and chemokines might contribute to higher mortality in SFTS than in scrub typhus. Discrete patterns of helper T cell-related cytokines and VEGF might reflect differences in CD4 T-cell responses and vascular damage between these diseases.

Correlates of burnout among healthcare workers during the COVID-19 pandemic in South Korea.

Burnout is a form of negative emotional and physical response to job stress. This study aimed to investigate the prevalence of burnout among healthcare workers responding to the coronavirus disease 2019 (COVID-19) outbreak in Korea and to explore correlates of burnout among healthcare workers. A nationwide questionnaire-based survey was conducted from December 1, 2020, to January 29, 2021 on 1425 healthcare workers who worked in one of the 16 healthcare facilities designated for COVID-19 care, in public health centers, or as paramedics in Korea. Burnout was assessed using 16 Korean-adapted items based on the Oldenburg Burnout Inventory (OLBI). Data were collected using a structured questionnaire and analyzed using the R version 4.1.1 software program. OLBI results indicate clinically exhaustion in 84.5% (1204/1425) and clinically disengagement in 91.1% (1298/1425), and 77.3% (1102/1425) met the score criteria for both the exhaustion and disengagement subscales for burnout. Burnout rate was significantly increased in the group with chronic fatigue symptoms (Fatigue Severity Scale ≥ 3.22) after the outbreak of COVID-19 (OR, 3.94; 95% CI 2.80-5.56), in the female group (OR, 2.05; 95% CI 1.46-2.86), in the group with physical symptoms (Patient Health Questionnaire-15 ≥ 10) after the outbreak of COVID-19 (OR, 2.03; 95% CI 1.14-3.60), in the group with a higher Global Assessment of Recent Stress scale (OR, 1.71; 95% CI 1.46-2.01), in the group with post-traumatic stress symptoms (Primary Care Post-Traumatic Stress Disorder-5 ≥ 2) (OR, 1.47; 95% CI 1.08-2.01), and in the younger age group(OR, 1.45; 95% CI 1.22-1.72). The chronic fatigue symptoms were correlated with cumulative days of care (OR, 1.18; 95% CI 1.02-1.37). The physical symptoms were correlated with average contact hours with COVID-19 patients per day (OR, 1.34; 95% CI 1.17-1.54), and cumulative days of care (OR, 1.21; 95% CI 1.06-1.38). Most Korean healthcare workers suffered from burnout related to excessive workload during the COVID-19 pandemic. During a widespread health crisis like COVID-19, it is necessary to regularly check the burnout status in healthcare workers and reduce their excessive workload by supplementing the workforce and providing appropriate working hours sufficient rest hours.

Actinomycosis presenting as an isolated pleural effusion in a patient with an HIV infection: a case report and literature review.

BACKGROUND: Thoracic actinomycosis is an uncommon, chronic, and progressive infection, especially in patients with HIV. We report a case of thoracic actinomycosis presenting as an isolated pleural effusion in a patient with an HIV infection. CASE PRESENTATION: A 68-year-old patient with progressive dyspnea and fever was admitted. On the right side, an ipsilateral massive pleural effusion was confirmed on the chest radiograph, and an HIV infection was newly diagnosed. A pleural biopsy was performed for the further differential diagnosis of potential opportunistic infections and malignancies. The pathology findings were consistent with actinomycosis. CONCLUSIONS: Active diagnostic approaches such as a pleural biopsy should be considered for indeterminate pleural effusions in immunocompromised patients.

Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM. MATERIAL AND METHODS: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machine-learning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information. RESULTS: The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machine-learning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03). CONCLUSION: The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.

Factors of Severity in Patients with COVID-19: Cytokine/Chemokine Concentrations, Viral Load, and Antibody Responses.

The severity of COVID-19 ranges from mild to critical diseases. However, limited data have been published on the detailed kinetics of viral load and host immune response throughout the disease course depending on disease severity. In this study, we comprehensively analyzed viral load, antibody responses to SARS-CoV-2, and cytokines/chemokines during the disease course, and identified the factors related to severity. Nasopharyngeal (NP) and plasma specimens were obtained from 31 patients with COVID-19 during hospitalization. Viral RNA in NP specimens was quantified by reverse transcription-PCR. Anti-SARS-CoV-2 antibodies and cytokines/chemokines in plasma specimens were analyzed by ELISA and cytometric bead array. The viral load in patients with COVID-19 peaked at the early stage of the disease and continuously decreased. Severe and critical cases showed higher viral load and prolonged viral shedding than asymptomatic and mild cases. Whereas plasma IgG was gradually increased and maintained during hospitalization, plasma IgM peaked at 3 weeks after symptom onset and dissipated. The antibody response in severe and critical cases was slightly delayed but stronger than those in others. High levels of interferon (IFN)-α, IFN-γ-induced protein-10, monokine induced by IFN-γ, and interleukin-6 at 5-10 days from symptom onset were associated with the severity of COVID-19. Our data indicate that high viral load in the respiratory tract and excessive production of cytokines and chemokines between 1 and 2 weeks from the symptom onset were significantly associated with the severity of COVID-19.

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

IMPORTANCE: There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). OBJECTIVE: To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea. MAIN OUTCOMES AND MEASURES: Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients' symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription-polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients. RESULTS: Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (ß = -0.065 [SE, 0.023]; P = .005). CONCLUSIONS AND RELEVANCE: In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.

Persistent severe acute respiratory syndrome coronavirus 2 detection after resolution of coronavirus disease 2019-associated symptoms/signs.

There are limited data on the duration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory specimens after resolution of coronavirus disease 2019 (COVID-19)-associated symptoms/signs. We determined duration of SARS-CoV-2 virus shedding in symptomatic patients after remission of symptoms. We investigated the duration of SARS-CoV-2 RNA detection using real-time reverse transcriptase polymerase chain reaction for SARS-CoV-2 in nasopharyngeal/oropharyngeal swabs or sputum or saliva. Six patients were included in the final analysis. The median (range) duration of SARS-CoV-2 viral detection after hospitalization was 34 days (22 to 67). After resolution of symptoms/signs, SARS-CoV-2 RNA was detected for median (range) of 26 days (9 to 48). Among the six patients, one had persistent detection of SARS-CoV-2 RNA until day 67 of hospitalization, which was 30 days after symptom resolution. This case represents the longest duration of SARS-CoV-2 detection, and highlights the need for long-term follow up of COVID-19 patients despite resolution of symptoms to confirm SARS-CoV-2 clearance.

Etiology, characteristics, and outcomes of community-onset necrotizing fasciitis in Korea: A multicenter study.

BACKGROUND: Necrotizing fasciitis (NF) is a serious skin and soft tissue infection causing high mortality. Investigating region specific epidemiologic factors associated with NF is important for establishing appropriate treatment strategies. This multicenter study was done to provide an update of the microbial etiology, clinical characteristics, and outcomes of NF in Korea. MATERIALS AND METHODS: A retrospective cohort of adult patients with NF was established using patient data from 13 general hospitals between January 2012 and December 2015 in Korea. We evaluated microbial etiology and clinical characteristics to identify risk factors associated with in-hospital mortality; analyses were performed using binary logistic regression models. RESULTS: A total of 161 patients with NF were included. The most common underlying disease was diabetes mellitus (66 cases, 41.0%). A total of 148 organisms were isolated from 119 (73.9%) patients. Enteric Gram-negative organisms (36 patients) were the most common pathogen, followed by Staphylococcus aureus (30 patients) and streptococci (28 patients). Methicillin-resistant Staphylococcus aureus (MRSA) was identified in 6.2% (10/161) of patients. Of 37 enteric Gram-negative isolates tested, 26 (70.3%) isolates were susceptible to ceftriaxone. The in-hospital mortality rate was 22.4%. Intensive care unit admission, septic shock, and Gram-negative organism infections were significantly associated with in-hospital mortality, and surgery was not a favorable prognostic factor. CONCLUSIONS: As initial empirical antibiotics, glycopeptides against MRSA and broad-spectrum antibiotics against third-generation cephalosporin-resistant organisms should be considered for patients with community-onset NF in Korea.

Prevalence and Risk Factors for Positive Nasal Methicillin-Resistant Staphylococcus aureus Carriage Among Orthopedic Patients in Korea.

Methicillin-resistant Staphylococcus aureus (MRSA) causes purulent skin and soft tissue infections as well as other life-threatening diseases. Recent guidelines recommend screening for MRSA at the time of admission. However, few studies have been conducted to determine the prevalence and risk factors for MRSA colonization. A prospective data collection and retrospective analysis was performed. MRSA screening tests were performed using nasal swabs in patients enrolled between January 2017 and July 2018. Demographic data, socio-economic data, medical comorbidities, and other risk factors for MRSA carriage were evaluated among 1577 patients enrolled in the study. The prevalence of MRSA nasal carriage was 7.2%. Univariate regression analysis showed that colonization with MRSA at the time of hospital admission was significantly related to patient age, body mass index, smoking, alcohol, trauma, recent antibiotic use, and route of hospital admission. Multiple logistic regression analysis for the risk factors for positive MRSA nasal carriage showed that being under- or overweight, trauma diagnosis, antibiotic use one month prior to admission, and admission through an emergency department were related to MRSA colonization. This study highlights the importance of a preoperative screening test for patients scheduled to undergo surgery involving implant insertion, particularly those at risk for MRSA.

Risk Factors for Delayed Isolation of Patients with Active Pulmonary Tuberculosis in an Acute-care Hospital.

The objective of the current study was to determine the factors associated with delayed isolation of pulmonary tuberculosis (TB). In this retrospective study, data of patients newly diagnosed with pulmonary TB from January 2015 through December 2017 at a referral hospital were reviewed. Delayed recognition of pulmonary TB was defined as failure to initiate airborne isolation within the first 3 days of admission. We analyzed the clinical, microbiological, and radiological factors associated with delayed isolation of pulmonary TB. A total of 134 patients with positive sputum acid-fast bacilli (AFB) cultures were analyzed, of which 44 (33%) were isolated within 3 days after admission. In multivariate logistic regression analysis, older age (p = 0.01), admission to departments other than Infectious Disease or Pulmonology (p = 0.005), and presence of malignancy (p = 0.02) were associated with delayed isolation. Patients with a radiologic diagnosis of active pulmonary TB were likely to be isolated early (p = 0.01). Better awareness of pulmonary TB among attending practitioners in hospital settings is required. Delay in isolation is associated with older age, malignancy, hospitalization to departments other than Infectious Disease or Pulmonology, and non-confident radiologic diagnosis of active pulmonary TB.

Monomicrobial gram-negative necrotizing fasciitis: An uncommon but fatal syndrome.

This study aimed to characterize patients with monomicrobial gram-negative necrotizing fasciitis in three university hospitals in Korea. In this study, of the 115 patients with community-acquired necrotizing fasciitis, 67 (58%) had monomicrobial infections: 31 (27%) in the gram-negative group and 36 (31%) in the gram-positive group. The majority of patients in the gram-negative group were infected with Escherichia coli followed by Klebsiella pneumoniae and Vibrio vulnificus. More patients in the gram-negative group showed liver cirrhosis than those in the gram-positive group (39% vs. 14%, P = 0.02). In a multivariable logistic regression analysis, liver cirrhosis (adjusted odds ratio [aOR], 13.7; 95% confidence interval [CI], 2.9-67.0), treatment with antibiotics without surgery (aOR, 10.2; 95% CI, 2.1-48.3), and lower level of albumin (aOR 4.9; 95% CI, 1.6-14.9) were associated with 30-day mortality. Our findings suggest that gram-negative necrotizing fasciitis is more often associated with liver cirrhosis and has poorer outcomes than gram-positive necrotizing fasciitis.

Molecular detection of Coxiella burnetii in heart valve tissue from patients with culture-negative infective endocarditis.

Coxiella burnetii is a common cause of blood culture-negative infective endocarditis (IE). Molecular detection of C burnetii DNA in clinical specimens is a promising method of diagnosing Q fever endocarditis. Here, we examined the diagnostic utility of Q fever polymerase chain reaction (PCR) of formalin-fixed heart valve tissue from patients with blood culture-negative IE who underwent heart valve surgery. Clinical and laboratory data of patients with blood culture-negative IE who underwent heart valve surgery during a 6-year period and for whom biopsy tissues were available were reviewed retrospectively. Blood culture-positive IE patients who underwent heart valve surgery within the last 3 years were used as controls. Heart valve samples were cultured and also subjected to histological examination and PCR for Q fever, brucellosis, and bartonellosis. Data from 20 patients with blood culture-negative IE and 20 with blood culture-positive IE were analyzed. Eight cases of blood culture-negative IE were PCR-positive for C burnetii (40%; 95% confidence interval, 19-64). No specimen was PCR-positive for brucellosis or bartonellosis. Histologically, 4 of 8 specimens with a positive Q fever PCR result were characterized by clusters of multinucleated giant cells without a fibrin ring. None of 20 patients with blood culture-negative IE received anti-Coxiella antibiotic therapy due to lack of clinical suspicion. Six-month mortality was higher in the Q fever PCR-positive group than in the Q fever PCR-negative group [38% (3/8) vs 0% (0/12), P = .049). Of the 20 patients with blood culture-positive IE, none yielded a positive Q fever PCR result for valve tissue. Approximately 40% of patients with culture-negative IE who received heart valve surgery were PCR-positive for Q fever; patients without clinical suspicion suffered high mortality. These data suggest that Q fever IE in patients with culture-negative IE is often missed in routine clinical practice.

Retrospective analysis of culture-negative versus culture-positive postoperative spinal infections.

Retrospective analysis.This study aimed to investigate the characteristics, clinical features, and outcomes of culture-negative (CN) and culture-positive (CP) postoperative spinal infections (PSIs).Causative organism cultures and the use of adequate antibiotics are essential for treating postoperative spinal wound infections. However, managing infected surgical sites with negative wound culture results is a common clinical problem. Although the outcomes of microbiologically confirmed PSIs have been well studied, the outcomes and clinical characteristics of CN PSIs have not been previously published.Between January 1995 and December 2014, 69 patients diagnosed with PSIs were enrolled. Enrolled patients were classified into 2 groups: CN (28 patients) and CP (41 patients). Baseline data, clinical manifestations, specific treatments, and treatment outcomes were compared with the groups.The overall rate of CN PSI was 40.6% (28/69). Baseline data and clinical manifestations were similar between the 2 groups. There were no significant differences in the duration of parenteral antibiotic use between the CN and CP groups. Revision surgery was required less often for the CN group (64.3%) than for the CP group (87.8%) (P = .020). Revision surgeries were repeated 0.82 times/case in the CN group and 1.34 times/case in the CP group (P = .014). Treatment outcomes, such as poor radiologic findings, need for additional anterior surgery, extension of fusion to adjacent segment surgery, and total length of hospital stay, were not different between groups.Revision surgery was performed less often for the CN group than for the CP group. From the perspective of revision surgery, CN PSIs have better prognosis than CP PSIs. However, clinical presentations and radiologic prognoses were not different between the two groups. We suggest that CN PSIs may be treated in the same way as CP PSIs.

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.

Clinical Isolation of Anaplasma phagocytophilum in South Korea.

We report the first isolation of Anaplasma phagocytophilum in South Korea. A 61-year-old woman presented with a 6-day history of fever, headache, and myalgia. Initial investigation showed neutropenia and thrombocytopenia. We diagnosed human granulocytic anaplasmosis by microscopic examination and serologic testing. The patient recovered fully without antibiotic therapy. The isolate was obtained from the patient's blood by cell culture and mouse inoculation. Its identity was confirmed by an immunofluorescence assay, sequencing of the 16S rRNA gene, msp2 (p44), and ankA genes, and staining and electron microscopy of morulae of A. phagocytophilum in cultured human promyelocytic leukemia HL-60 cells.

Voriconazole-refractory invasive aspergillosis.

Invasive aspergillosis (IA) is one of the most common life-threatening complications in immunocompromised patients. Voriconazole is currently the drug of choice for IA treatment. However, some patients with IA suffer clinical deterioration despite voriconazole therapy. Management of voriconazole-refractory IA remains challenging; no useful recommendations have yet been made. Voriconazole-refractory IA can be further categorized as disease attributable to misdiagnosis or co-infection with another mold; inadequate blood voriconazole blood; inadequate tissue drug concentrations attributable to angioinvasion; immune reconstitution inflammatory syndrome; or infection with voriconazole-resistant Aspergillus. Hence, when encountering a case of voriconazole-refractory IA, it is necessary to schedule sequential tests to decide whether medical treatment or surgical intervention is appropriate; to adjust the voriconazole dose via drug monitoring; to seek CYP2C19 polymorphisms; to monitor serum galactomannan levels; and to examine the drug susceptibility of the causative Aspergillus species.

Molecular detection of Coxiella burnetii from the formalin-fixed tissues of Q fever patients with acute hepatitis.

BACKGROUND: Serologic diagnosis is one of the most widely used diagnostic methods for Q fever, but the window period in antibody response of 2 to 3 weeks after symptom onset results in significant diagnostic delay. We investigated the diagnostic utility of Q fever PCR from formalin-fixed liver tissues in Q fever patients with acute hepatitis. METHODS: We reviewed the clinical and laboratory data in patients with Q fever hepatitis who underwent liver biopsy during a 17-year period, and whose biopsied tissues were available. We also selected patients who revealed granuloma in liver biopsy and with no Q fever diagnosis within the last 3 years as control. Acute Q fever hepatitis was diagnosed if two or more of the following clinical, serologic, or histopathologic criteria were met: (1) an infectious hepatitis-like clinical feature such as fever (≥ 38°C) with elevated hepatic transaminase levels; (2) exhibition of a phase II immunoglobulin G (IgG) antibodies titer by IFA of ≥ 1:128 in single determination, or a four-fold or greater rise between two separate samples obtained two or more weeks apart; (3) histologic finding of biopsy tissue showing characteristic fibrin ring granuloma. RESULTS: A total of 11 patients with acute Q fever hepatitis were selected and analyzed. Of the 11 patients, 3 (27%) had exposure to zoonotic risk factors and 7 (63%) met the serologic criteria. Granulomas with either circumferential or radiating fibrin deposition were observed in 10 cases on liver biopsy and in 1 case on bone marrow biopsy. 8 (73%) revealed positive Coxiella burnetii PCR from their formalin-fixed liver tissues. In contrast, none of 10 patients with alternative diagnosis who had hepatic granuloma revealed positive C. burnetii PCR from their formalin-fixed liver tissues. CONCLUSIONS: Q fever PCR from formalin-fixed liver tissues appears to be a useful adjunct for diagnosing Q fever hepatitis.

Tuberculous Meningitis-Mimicking Varicella-Zoster Meningitis.

BACKGROUND: Varicella-zoster virus (VZV) is one of the most common etiologies of aseptic meningitis. The severest manifestation of VZV meningitis is occasionally confused with tuberculous meningitis (TBM). Thus, we investigated the clinical manifestations of VZV meningitis as compared with those of TBM. MATERIALS AND METHODS: All adult patients who were diagnosed with VZV meningitis or TBM were enrolled at a tertiary hospital in Seoul, South Korea, during an 8-year period. The clinical characteristics and cerebrospinal fluid (CSF) profile of patients were analyzed. RESULTS: Seventy-nine patients with VZV meningitis and 24 patients with TBM were enrolled in this study. Of the 79 patients with VZV meningitis, 63 (80%) did not received empirical anti-tuberculous therapy (Group 1) and the remaining 16 (20%) received empirical anti-tuberculous therapy (Group 2), compared with 24 patients with TBM (Group 3). Altered mental status, intensive care unit (ICU) admission, neurologic sequelae, CSF protein levels, and CSF adenosine deaminase levels revealed a trend of being higher in Group 3 than Group 2, which was higher than Group 1. However, the CSF/serum glucose ratio was significantly lower in Group 3 than in Group 1 or Group 2. CONCLUSION: About one fifth of VZV meningitis cases presented as severe manifestations, mimicking TBM. The CSF/serum glucose ratio might be useful to differentiate VZV meningitis from TBM until definite diagnostic tests are available. Physicians should keep in mind that a differential diagnosis between severe VZV meningitis and TBM is needed.

Pneumocystis pneumonia versus rituximab-induced interstitial lung disease in lymphoma patients receiving rituximab-containing chemotherapy.

It is difficult to differentiate Pneumocystis pneumonia (PCP) from rituximab-induced interstitial lung disease (RILD) in lymphoma patients with diffuse pulmonary infiltrates who are receiving rituximab-containing chemotherapy. Using a clinical scoring system, we aim to differentiate PCP from RILD who are receiving rituximab-containing chemotherapy. We reviewed the medical records of lymphoma patients who had received rituximab-containing chemotherapy between 2012 and 2015 in a tertiary hospital. Among 613 lymphoma patients receiving rituximab-containing chemotherapy, 97 (16%) had diffuse pulmonary infiltrates. Of these, 16 (16%) with an alternative diagnosis and 22 (23%) with an indeterminate diagnosis were excluded. Finally, 21 (22%) patients were classified as having PCP and the remaining 38 (39%) as having RILD. Fever, short duration of symptoms (≤5 days), systemic inflammatory response syndrome (SIRS), and severe extent of disease on CT scan (>75%) were more common in patients with PCP than in those with RILD. Clinical scores were determined using the following system: SIRS = score 1, symptom duration ≤5 days = score 1, extent of disease on CT >75% = score 4. A score of ≥2 differentiated PCP from RILD with 91% sensitivity (95% CI, 70-99) and 71% specificity (95% CI, 54-84). A clinical scoring system based on presence of SIRS, short duration of symptoms, and severe extent of disease on CT scan appears to be useful in differentiation of PCP from RILD.