Characteristics and biomarkers associated with mortality in COVID-19 patients presenting to the emergency department.

This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n = 41; 8.6%) and cardiac manifestations (n = 31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796-0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.

Clinical outcomes and treatment necessity in patients with toxin-negative Clostridioides difficile stool samples.

PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.

Clinical characteristics and risk factors for septic shock in patients with pyometra: A retrospective multicenter cohort study.

BACKGROUND: Pyometra is a disease characterized by the collection of pus in the uterus. The clinical characteristics and etiology of pyometra have not been sufficiently described. In this study, we investigated the clinical characteristics, epidemiology, outcomes, and risk factors of septic shock in patients with pyometra. METHODS: Patients with pyometra admitted to one of four university-affiliated hospitals between January 2010 to August 2022 were enrolled. Pyometra cases associated with peripartum infection and surgical site infection were excluded. Clinical characteristics and outcomes of pyometra were described, and pyometra patients with or without septic shock were compared. RESULTS: A total of 192 patients was included. Twenty-eight-day all-cause mortality was 5.0%, and the 1-year recurrence rate was 6.3%. Median patient age was 77.5 years. The two most common symptoms were abdominal pain (49.0%) and vaginal discharge (47.9%). Escherichia coli (40.1%), Klebsiella pneumoniae (16.7%), and Streptococcus spp.(16.0%) were the pathogens most frequently isolated by conventional culture; those isolated from polymerase chain reaction were Mycoplasma hominis (48.0%), and Ureaplasma spp. (32.0%). In multivariable analysis, fever, uterine perforation, and dementia were associated with increased incidence of septic shock, while vaginal discharge was associated with a lower incidence of septic shock. CONCLUSIONS: Our findings suggest that pyometra is a unique gynecological infectious syndrome in post-menopausal individuals. The most common associated pathogens are similar to those involved in urinary tract infections rather than those of sexually transmitted diseases. Decreased cognitive function could delay early diagnosis of pyometra and lead to septic shock and higher mortality.

Ineffectiveness of colistin monotherapy in treating carbapenem-resistant Acinetobacter baumannii Pneumonia: A retrospective single-center cohort study.

BACKGROUND: Acinetobacter baumannii, a common carbapenem-resistant gram-negative bacillus, usually causes nosocomial infections. Colistin has been used for carbapenem-resistant A. baumannii (CRAB) infections; however, only a few studies have evaluated colistin as a treatment option compared to appropriate controls. We investigated the effectiveness of colistin monotherapy in treating CRAB pneumonia compared to those treated without an active drug. METHODS: Adult patients (≥ 18 years) with CRAB isolated from respiratory specimens were screened from September 2017 to August 2022. Only patients with pneumonia treated with colistin monotherapy (colistin group) were included and compared to those without any active antibiotics (no active antibiotics [NAA] group). The primary and secondary outcomes were 30-day all-cause mortality and acute kidney injury within 30 days. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare mortality between groups. RESULTS: Among the 826 adult patients with CRAB in their respiratory specimens, 45 and 123 patients were included in the colistin and NAA groups, respectively. Most of the CRAB pneumonia (91.1%) cases were hospital-acquired pneumonia. The 30-day all-cause mortality rates in the colistin and NAA groups were 58.3% and 56.1%, respectively, and no difference was observed after adjustments (adjusted hazard ratio, 0.74; 95% CI, 0.47-1.17). The incidence of acute kidney injury was higher in the colistin group (65.3%) compared to the NAA group (39.0%) (P = 0.143). CONCLUSIONS: Colistin monotherapy did not significantly improve treatment outcomes for CRAB pneumonia. The development and evaluation of new antimicrobials for CRAB pneumonia should be advocated in clinical practice.

Prevention of Cytomegalovirus Infection in Solid Organ Transplant Recipients: Guidelines by the Korean Society of Infectious Diseases and the Korean Society for Transplantation.

Cytomegalovirus (CMV) is the most important opportunistic viral pathogen in solid organ transplant (SOT) recipients. The Korean guideline for the prevention of CMV infection in SOT recipients was developed jointly by the Korean Society for Infectious Diseases and the Korean Society of Transplantation. CMV serostatus of both donors and recipients should be screened before transplantation to best assess the risk of CMV infection after SOT. Seronegative recipients receiving organs from seropositive donors face the highest risk, followed by seropositive recipients. Either antiviral prophylaxis or preemptive therapy can be used to prevent CMV infection. While both strategies have been demonstrated to prevent CMV infection post-transplant, each has its own advantages and disadvantages. CMV serostatus, transplant organ, other risk factors, and practical issues should be considered for the selection of preventive measures. There is no universal viral load threshold to guide treatment in preemptive therapy. Each institution should define and validate its own threshold. Valganciclovir is the favored agent for both prophylaxis and preemptive therapy. The evaluation of CMV-specific cell-mediated immunity and the monitoring of viral load kinetics are gaining interest, but there was insufficient evidence to issue recommendations. Specific considerations on pediatric transplant recipients are included.

Conversion to colistin susceptibility by tigecycline exposure in colistin-resistant Klebsiella pneumoniae and its implications to combination therapy.

OBJECTIVES: This study investigated the effect of tigecycline exposure on susceptibility of colistin-resistant Klebsiella pneumoniae isolates to colistin and explored the possibility of antibiotic combination at low concentrations to treat colistin-resistant K. pneumoniae isolates. METHODS: Twelve tigecycline-resistant (TIR) mutants were induced in vitro from wild-type, colistin-resistant, and tigecycline-susceptible K. pneumoniae isolates. Antibiotic susceptibility was determined using the broth microdilution method. The deduced amino acid alterations were identified for genes associated with colistin resistance, lipid A biosynthesis, and tigecycline resistance. Expression levels of genes were compared between wild-type stains and TIR mutants using quantitative real-time polymerase chain reaction (PCR). Lipid A modification was explored using MALDI-TOF mass spectrometry. Time-killing assay was performed to assess the efficiency of combination therapy using low concentrations of colistin and tigecycline. RESULTS: All TIR mutants except one were converted to be susceptible to colistin. These TIR mutants had mutations in the ramR gene and increased expression levels of ramA. Three genes associated with lipid A biosynthesis, lpxC, lpxL, and lpxO, were also overexpressed in TIR mutants, although no mutation was observed. Additional polysaccharides found in colistin-resistant, wild-type strains were modified in TIR mutants. Colistin-resistant K. pneumoniae strains were eliminated in vitro by combining tigecycline and colistin at 2 mg/L. In this study, we found that tigecycline exposure resulted in reduced resistance of colistin-resistant K. pneumoniae to colistin. Such an effect was mediated by regulation of lipid A modification involving ramA and lpx genes. CONCLUSION: Because of such reduced resistance, a combination of colistin and tigecycline in low concentrations could effectively eradicate colistin-resistant K. pneumoniae strains.

Prevalence of Non-Toxigenic Clostridioides difficile in Diarrhoea Patients and Their Clinical Characteristics.

Non-toxigenic Clostridioides difficile (NTCD) has been shown to decrease the risk of recurrent C. difficile infection (CDI) in patients following metronidazole or vancomycin treatment for CDI. Limited data on the prevalence of NTCD strains in symptomatic patients and their clinical characteristics are available. We conducted this study to investigate the prevalence of NTCD in diarrhoea patients and their clinical characteristics. Between July 2017 and June 2018, unduplicated stool specimens were collected from patients with diarrhoea. The characteristics and episodes of C. difficile infection in patients with NTCD and toxigenic strains were compared. Among the 1182 stool specimens collected, 236 (18.5%) were identified as growing C. difficile, and 19.5% of the identified isolates were found to be NTCD. Multivariate analysis showed that community-onset diarrhoea (OR = 4.13, 95% CI 1.07-15.97; p = 0.040), underlying diabetes (OR = 3.64, 95% CI 1.46-9.25; p = 0.006), previous use of glycopeptides (OR = 4.75, 95% CI 1.37-16.42; p = 0.014), and the lack of use of proton pump inhibitors (PPIs) (OR = 3.57, 95% CI 1.39-9.09; p = 0.009) were independently associated with the NTCD group. Although there was no statistical significance, the number of CDI episodes occurring after 90 days tended to be lower in the NTCD group (2.2%) than in the toxigenic group (11.2%). A considerable portion of the C. difficile strains isolated from patients with diarrhoea showed NTCD. Further, more extensive studies are needed to clearly define the protective effects of NTCD strains in patients with diarrhoea.

Recommendations for SARS-CoV-2 testing and organ procurement from deceased donors in the Republic of Korea.

We present a summary of the evidence on testing for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and organ procurement from deceased donors and provide recommendations based on current clinical data and the guidelines from major transplant organizations. Because of the limited historical experience with coronavirus disease 2019 (COVID-19), certain recommendations in this document are based on theoretical rationales rather than clinical data. The recommendations in this manuscript may be subject to revision as subsequent clinical studies provide definitive evidence regarding COVID-19 in organ procurement.

Factors for mortality in patients with persistent Staphylococcus aureus bacteremia: The importance of treatment response rather than bacteremia duration.

BACKGROUND: The criteria for antibiotic failure in persistent Staphylococcus aureus bacteremia (SAB) are unclear, but treatment response and bacteremia duration are commonly used indicators of antibiotic failure. We evaluated the effects of treatment response and bacteremia duration on mortality in persistent SAB. METHODS: We retrospectively identified patients with persistent SAB in four university-affiliated hospitals between 2017 and 2021. Bacteremia duration was calculated from the first day of active antibiotic therapy, and persistent SAB was defined as bacteremia lasting for 2 or more days. Defervescence and Pitt bacteremia score (PBS) were used to evaluate treatment response at treatment day 4. The primary outcome was 30-day in-hospital mortality. Time-dependent multivariable Cox regression analysis and subgroup analysis according to methicillin resistance were performed. RESULTS: A total of 221 patients was included in the study, and the 30-day in-hospital mortality was 28.5%. There was no significant difference in bacteremia duration between survived and deceased patients. Independent factors for mortality included age, Charlson comorbidity index, initial PBS, pneumonia, and removal of the eradicable focus. PBS at treatment day 4 ≥ 3 was the strongest risk factor (adjusted hazard ratio [HR] = 4.260), but defervescence was not. Bacteremia duration was not an independent factor except for 13 days or more of methicillin-resistant SAB (adjusted HR = 1.064). CONCLUSIONS: In patients with persistent SAB, PBS at treatment day 4 was associated with 30-day in-hospital mortality rather than defervescence and bacteremia duration. The results of this study could help determine early intensified treatment strategies in persistent SAB patients.

Clinical Effectiveness of Tetracycline-Class Agents Based Regimens in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Single-Center Retrospective Cohort Study.

This study evaluated the clinical outcome of carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia and the clinical effectiveness of tetracyclines-based therapy. In a retrospective cohort study over 5 years period, 108 patients were included in the study. The overall 30-day mortality rate was 71.4%. Pitt's bacteremia score (PBS) (adjusted hazard ratio [aHR], 1.32; 95% confidence interval [CI], 1.22-1.42 per 1-point), colistin-single regimens (aHR, 0.34; 95% CI, 0.17-0.69), and tetracyclines single/tetracyclines-colistin combination regimens (aHR, 0.18; 95% CI, 0.07-0.48) were independently associated with 30-day mortality. Among patients with a PBS < 6, only tetracycline-containing regimens were associated with decreased mortality. Among patients receiving appropriate definite antimicrobials, the tetracyclines-colistin combination (7 of 7, 100%) tended to a higher 30-day survival rate compared to a tetracycline (7 of 12, 57.1%) or colistin single regimen (10 of 22, 41.6%, P = 0.073). Our findings suggest tetracyclines might be effective for treating CRAB infections when combined with colistin.

Carbapenem Use in the Last Days of Life: A Nationwide Korean Study.

The appropriate use of carbapenem is a critical concern for patient safety and public health, and is a national priority. We investigated the nationwide status of carbapenem prescription in patients within their last 14 days of life to guide judicious-use protocols from the previous study comprised of 1350 decedents. Carbapenem use was universally controlled through computerised authorisation system at all centres during the study period. Carbapenem prescribing patterns and their optimality were evaluated. A total of 1201 patients received antimicrobial agents within the last two weeks of their lives, of whom 533 (44.4%) received at least one carbapenem. The median carbapenem treatment duration was seven days. Of the 533 patients receiving carbapenems, 510 (95.7%) patients had microbiological samples drawn and 196 (36.8%) yielded carbapenem-resistant pathogens. A total of 200 (37.5%) patients were referred to infectious disease (ID) specialists. Of the 333 patients (62.5%) who did not have ID consultations, 194 (58.2%) were assessed as "not optimal", 79 (23.7%) required escalation, 100 (30.0%) required de-escalation, and 15 (4.5%) were discontinued. Notwithstanding the existing antibiotic restriction program system, carbapenems are commonly prescribed to patients in their last days of life.

Clinical effectiveness of zoster vaccine live in kidney transplant recipients immunized prior to transplantation: a retrospective single-centre cohort study.

OBJECTIVES: Kidney transplant (KT) recipients have an increased risk of herpes zoster (HZ) and its complications. Although recombinant zoster vaccine is favoured over zoster vaccine live (ZVL), ZVL is also recommended to prevent HZ for KT candidates. We aimed to evaluate the clinical effectiveness of ZVL in KT recipients immunized before transplantation. METHODS: Adult patients who received kidney transplantation from January 2014 to December 2018 were enrolled. Patients were observed until HZ occurrence, death, loss of allograft, loss to follow-up, or 5 years after transplantation. The inverse probability of the treatment-weighted Cox proportional hazard model was used to compare the incidence of HZ after transplantation between vaccinated and unvaccinated patients. RESULTS: A total of 84 vaccinated and 340 unvaccinated patients were included. The median age was higher in the vaccinated group (57 vs. 54 years, p 0.003). Grafts from deceased donors were more frequently transplanted in the unvaccinated group (16.7% vs. 51.8%, p < 0.001). Five-year cumulative HZ incidence was 11.9%, which translated to 26.27 (95% CI, 19.33-34.95) per 1000 person-years. The incidence in the vaccinated and unvaccinated groups was 3.9% and 13.7%, respectively. After adjustment, vaccination showed significant protective effectiveness against HZ (adjusted hazard ratio, 0.18, 95% CI, 0.05-0.60). In addition, all four cases of disseminated zoster occurred in the unvaccinated group. DISCUSSION: Our study, the first on the clinical effectiveness of zoster vaccines for KT recipients, suggests that ZVL before transplantation effectively prevents HZ.

Multifaceted Evaluation of Antibiotic Therapy as a Factor Associated with Candidemia in Non-Neutropenic Patients.

We aimed to evaluate various aspects of antibiotic therapy as factors associated with candidemia in non-neutropenic patients. A retrospective, matched, case-control study was conducted in two teaching hospitals. Patients with candidemia (cases) were compared to patients without candidemia (controls), matched by age, intensive care unit admission, duration of hospitalization, and type of surgery. Logistic regression analyses were performed to identify factors associated with candidemia. A total of 246 patients were included in the study. Of 123 candidemia patients, 36% had catheter-related bloodstream infections (CRBSIs). Independent factors in the whole population included immunosuppression (adjusted odds ratio [aOR] = 2.195; p = 0.036), total parenteral nutrition (aOR = 3.642; p < 0.001), and anti-methicillin-resistant S. aureus (MRSA) therapy for ≥11 days (aOR = 5.151; p = 0.004). The antibiotic factor in the non-CRBSI population was anti-pseudomonal beta-lactam treatment duration of ≥3 days (aOR = 5.260; p = 0.008). The antibiotic factors in the CRBSI population included anti-MRSA therapy for ≥11 days (aOR = 10.031; p = 0.019). Antimicrobial stewardship that reduces exposure to these antibacterial spectra could help prevent the development of candidemia.

Current and Emerging Knowledge in COVID-19.

COVID-19 has emerged as a pandemic leading to a global public health crisis of unprecedented morbidity. A comprehensive insight into the imaging of COVID-19 has enabled early diagnosis, stratification of disease severity, and identification of potential sequelae. The evolution of COVID-19 can be divided into early infectious, pulmonary, and hyperinflammatory phases. Clinical features, imaging features, and management are different among the three phases. In the early stage, peripheral ground-glass opacities are predominant CT findings, and therapy directly targeting SARS-CoV-2 is effective. In the later stage, organizing pneumonia or diffuse alveolar damage pattern are predominant CT findings and anti-inflammatory therapies are more beneficial. The risk of severe disease or hospitalization is lower in breakthrough or Omicron variant infection compared with nonimmunized or Delta variant infections. The protection rates of the fourth dose of mRNA vaccination were 34% and 67% against overall infection and hospitalizations for severe illness, respectively. After acute COVID-19 pneumonia, most residual CT abnormalities gradually decreased in extent, but they may remain as linear or multifocal reticular or cystic lesions. Advanced insights into the pathophysiologic and imaging features of COVID-19 along with vaccine benefits have improved patient care, but emerging knowledge of post-COVID-19 condition, or long COVID, also presents radiology with new challenges.

Clinical characteristics and manifestations in patients with hypermucoviscous Klebsiella pneumoniae bacteremia from extra-hepatobiliary tract infection.

PURPOSE: Hypermucoviscous strains of Klebsiella pneumoniae (KP) are associated with invasive liver abscess syndrome. However, little is known about the characteristics of this phenotype in non-hepatobiliary infections. In this study, we investigated the clinical characteristics of patients with hypermucoviscous Kp (hmvKp) bacteremia from non-hepatobiliary tract infection. METHODS: This retrospective cohort study was implemented at Samsung Changwon Hospital. From March 2018 to December 2019, adult patients (≥ 18 years) with KP bacteremia of the extra-hepatobiliary system were enrolled. Hypermucoviscosity was defined by the string test. Clinical characteristics and 30-day all-cause mortality between patients with hmvKp and non-hmvKp bacteremia were compared. RESULTS: Among 179 cases of non-hepatobiliary KP bacteremia, 67 (37.4%) and 112 (62.6%) isolates were classified as hmvKp and non-hmvKp, respectively. In the hmvKp group, metastatic infection (9.0 vs. 1.8%, P = 0.054) and purulent or necrotizing infection (31.3 vs. 9.8%, P < 0.001) were more frequently observed. Additionally, non-hmvKp had more frequent resistance to cefotaxime (11.9 vs. 38.4%, P < 0.001). Thirty-day all-cause mortality was similar in the hmvKp (41.8%) and non-hmvKp (39.3%) groups (P = 0.643). In multivariable analysis, septic shock (adjusted hazard ratio [aHR] = 3.05, 95% confidence interval [CI]: 1.22-7.63) and Pitt bacteremia score (aHR = 1.23 per 1 point, 95% CI 1.14-1.33) were associated with increased mortality in patients with Kp bacteremia, while urinary-tract infection (aHR = 0.38, 95% CI 0.18-0.76) was associated with decreased mortality. CONCLUSION: hmvKp was associated with less frequent drug resistance and metastatic-purulent presentation in non-hepatobiliary infection like in hepatobiliary infection. However, hmvKp was not associated with clinical outcomes.

Pneumocystis jirovecii Pneumonia in Patients with Solid Malignancies: A Retrospective Study in Two Hospitals.

Pneumocystis jirovecii pneumonia (PJP) is a rare opportunistic infection in patients with solid malignancies. This study aimed to examine the characteristics of patients with solid cancers and PJP. We retrospectively reviewed the medical records of patients with solid tumors and PJP over an 11-year period, enrolling a total of 47 patients (30-day survival group: n = 20, 30-day mortality group: n = 27). Only 34% of patients received ≥20 mg of prednisolone for ≥2 weeks, and the 30-day mortality rate was 57.4%. The 30-day survival group included more women and patients with colon cancer than the mortality group. Furthermore, absolute lymphocyte counts (ALCs) were decreased at PJP symptom onset, as compared with the values observed 1-3 months earlier. Increased oxygen demand and low ALCs after 5-7 days of PJP treatment were also related to poor prognosis. Due to the limitations of this retrospective study, further studies that adhere to the PJP criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium will be needed to evaluate PJP in solid malignancies more clearly.

Impact of vancomycin use trend change due to the availability of alternative antibiotics on the prevalence of Staphylococcus aureus with reduced vancomycin susceptibility: a 14-year retrospective study.

BACKGROUND: We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available. METHODS: Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005-2018 was analyzed. RESULTS: Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531-0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981-1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend. CONCLUSIONS: During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems.

10-Year Retrospective Review of the Etiologies for Meningitis With Elevated Adenosine Deaminase in Cerebrospinal Fluid: Etiologies Other Than TB.

Purpose: An elevated adenosine deaminase (ADA) level in the cerebrospinal fluid (CSF) is considered a reliable marker of tuberculous meningitis (TBM). However, CSF-ADA levels can also be elevated in other diseases. We aimed to find the most common diagnosis of patients with elevated CSF-ADA levels for the last 10 years. Methods: We retrospectively investigated the diagnoses of all patients with elevated CSF-ADA (ADA ≥ 10 IU/L) levels between 2010 and 2019 at the Samsung Medical Center. Definite TBM was defined based on microbiological evidence. Clinical TBM was defined based on the brain imaging and response to the standard TB treatment. We compared the laboratory characteristics of the three most common diagnoses. Results: CSF-ADA levels were elevated in 137 (5.6%) of 2,600 patients. The most common diagnoses included hematologic malignancy (HM; n = 36, 26.2%), TBM (n = 26, 19.0%), and viral meningitis (VM; n = 25, 18.2%). CSF-ADA levels did not differ significantly between TBM [median (interquartile range (IQR)), 20.2 IU/L (13.8-29.3)] and HM [16.5 (12.8-24.0)]. However, CSF-ADA levels were lower in VM [14.0 (11.0-16.1)] than in TBM (p = 0.027). Lymphocyte-dominant pleocytosis was more common in VM [77.0% (70.8-81.5)] than in TBM [16.0 (3.0-51.0), p = 0.015] or HM [36.0 (10.0-72.0); p = 0.032]. Interestingly, the CSF characteristics of clinical TBM were similar to those of VM but not definite TBM. Conclusion: The most common diagnoses with elevated CSF-ADA levels were HM, followed by TBM and VM. Clinicians should carefully consider the differential diagnoses in patients with elevated CSF-ADA levels, especially those in the early stage of meningitis without microbiological evidence for TBM.

Risk Factors for Coronavirus Disease 2019 (COVID-19)-Associated Pulmonary Aspergillosis in Critically Ill Patients: A Nationwide, Multicenter, Retrospective Cohort Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. METHODS: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. RESULTS: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). CONCLUSION: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.