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

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

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage.Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzymelinked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

Intracerebral Hemorrhage due to Thrombosis with Thrombocytopenia Syndrome after Vaccination against COVID-19: the First Fatal Case in Korea

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4). This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein. Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis. A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination. He developed severe headache with vomiting 9 days after the vaccination. Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage.Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzymelinked immunosorbent assay antibody test was reported to be strongly positive. Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination. Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients. Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

History of Syphilis and Gonorrhea in Korea / 감염과화학요법

In Korea, systematic management of sexually transmitted infections (STIs), including syphilis and gonorrhea, began only after the end of the Korean War. Since the enactment of the Law on Prevention of Communicable Diseases of 1954, STI has been managed and regularly monitored in high risk group. However, the major turning point was the implementation of the Special Law on Prostitution, which was enacted in September 2004. The national policy on STI management had also changed from management of core groups by mandatory to voluntary examinations and treatment of patients by health examinations. The national surveillance system for STI was introduced in 2000 by the revision of the Prevention of Communicable Diseases Act of 1999. The incidence of STI had increased in the 1960s, but began to decline at the 1970s. In the 21st century, the incidence of STI has been increasing again. Currently, more thorough methods of STI management are needed in Korea.

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

The authors found errors in their published article.

Increasing Antimicrobial Resistance of Escherichia coli Makes Antimicrobial Stewardship More Important

No abstract available.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome / 감염과화학요법

Because primary antifungal prophylaxis is widely used for immunocompromised hosts, the incidences of unusual fungal infections have increased. Trichosporon asahii has emerged as an important life-threatening opportunistic systemic pathogen because of the increased use of cytotoxic or immunosuppressant agents, along with high mortality rates. Here, we describe a case of catheter-related T. asahii bloodstream infection with multiple septic skin nodules in both the arms and legs of the patient who was in the neutropenic period after allogeneic stem cell transplantation for myelodysplastic syndrome treated with prophylactic ciprofloxacin and itraconazole. We successfully treated her with intravenous voriconazole for more than a month without any complications. Clinicians should consider breakthrough Trichosporon infections when clinical progress in an immunocompromised patient with unexplained infection signs and symptoms does not improve despite proper treatment with antibiotics or various antifungal agents. In addition, voriconazole can be a good treatment choice for achieving better treatment results and prognosis.

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

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

A Case of Life-Threating Streptococcus suis Infection Presented as Septic Shock and Multiple Abscesses / 감염과화학요법

Streptococcus suis is a zoonotic pathogen that can cause severe systemic infections in humans as well as swine. In recent decades, the number of S. suis infections in humans has increased, particularly in Southeast Asia. Although most cases of S. suis human infections are reported as sporadic, a few outbreaks have been noted. Interestingly, these outbreaks have been proposed to be associated with concomitant outbreaks in swine. In Korea, four sporadic and non-fatal cases of S. suis infection have been reported. We herein report a case of life-threating S. suis infection with sepsis for the first time in Korea. The patient was a healthy pig farmer, and the gastrointestinal tract was considered the route of infection. This case emphasized the need for awareness and recognition of S. suis as a zoonotic pathogen.

Catheter-Related Trichosporon asahii Bloodstream Infection in a Neutropenic Patient with Myelodysplastic Syndrome / 감염과화학요법

Because primary antifungal prophylaxis is widely used for immunocompromised hosts, the incidences of unusual fungal infections have increased. Trichosporon asahii has emerged as an important life-threatening opportunistic systemic pathogen because of the increased use of cytotoxic or immunosuppressant agents, along with high mortality rates. Here, we describe a case of catheter-related T. asahii bloodstream infection with multiple septic skin nodules in both the arms and legs of the patient who was in the neutropenic period after allogeneic stem cell transplantation for myelodysplastic syndrome treated with prophylactic ciprofloxacin and itraconazole. We successfully treated her with intravenous voriconazole for more than a month without any complications. Clinicians should consider breakthrough Trichosporon infections when clinical progress in an immunocompromised patient with unexplained infection signs and symptoms does not improve despite proper treatment with antibiotics or various antifungal agents. In addition, voriconazole can be a good treatment choice for achieving better treatment results and prognosis.

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

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

A Case of Life-Threating Streptococcus suis Infection Presented as Septic Shock and Multiple Abscesses / 감염과화학요법

Streptococcus suis is a zoonotic pathogen that can cause severe systemic infections in humans as well as swine. In recent decades, the number of S. suis infections in humans has increased, particularly in Southeast Asia. Although most cases of S. suis human infections are reported as sporadic, a few outbreaks have been noted. Interestingly, these outbreaks have been proposed to be associated with concomitant outbreaks in swine. In Korea, four sporadic and non-fatal cases of S. suis infection have been reported. We herein report a case of life-threating S. suis infection with sepsis for the first time in Korea. The patient was a healthy pig farmer, and the gastrointestinal tract was considered the route of infection. This case emphasized the need for awareness and recognition of S. suis as a zoonotic pathogen.

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

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

Mycobacterium kansasii Pneumonia with Mediastinal Lymphadenitis in a Patient with Acute Myeloid Leukemia: Successful Treatment to Stem Cell Transplantation / 감염과화학요법

Non-tuberculous mycobacterial (NTM) disease is a relatively rare cause of neutropenic fever in patients with hematologic malignancies. During the neutropenic period, performing invasive procedures for microbiological or pathological confirmation is difficult. In addition, the optimal treatment duration for NTM disease in patients with leukemia, especially prior to stem cell transplantation (SCT), has not been documented. Therefore, we report a case of pneumonia with necrotizing lymphadenitis caused by Mycobacterium kansasii diagnosed during chemotherapy being performed for acute myeloid leukemia. The radiologic findings were similar to those of invasive fungal pneumonia; however, a bronchoalveolar washing fluid culture confirmed that the pathogen was M. kansasii. After 70 days from starting NTM treatment, allogeneic SCT was performed without any complications. The patient fully recovered after 12 months of NTM treatment, and neither reactivation of M. kansasii infection nor related complications were reported.

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

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

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

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

A Case of Alternaria Rhinosinusitis in a Patient with Myelodysplastic Syndrome during Neutropenic Period / 감염과화학요법

The genus Alternaria contains several species of melanized hypomycetes that cause opportunistic human infections. The most frequent clinical manifestations of alternariosis are cutaneous and subcutaneous infections, followed by oculomycosis, invasive and non-invasive rhinosinusitis, and onychomycosis. So far, only 17 cases of rhinosinusitis caused by Alternaria species have been reported since 1977. Although several domestic cases of cutaneous alternariosis have been reported, there is no report of Alternaria rhinosinusitis in Korea. The majority of Alternaria rhinosinusitis involves immunocompromised patients. We report the first case of alternariosis in a patient with neutropenia and myelodysplastic syndrome that was treated with endoscopic debridement and a conventional antifungal agent.

Central Nervous System Relapse in Patients with Acute Promyelocytic Leukemia Treated with All-trans Retinoic Acid / 대한내과학회지

Acute promyelocytic leukemia (APL) is distinguished from other subtypes of acute myeloid leukemia (AML) by its distinctive morphology, specific chromosomal abnormality, coagulopathy, and unique response to treatment with all-trans retinoic acid (ATRA). Central nervous system (CNS) involvement is rare in APL. Most CNS relapses occur in patients with hyperleukocytosis at initial presentation, and the optimal management of such patients is still controversial. We report five patients with APL who had CNS relapse with or without evidence of cytological and molecular disease of the bone marrow after ATRA treatment. Brain magnetic resonance imaging revealed leptomeningeal infiltration and cerebrospinal fluid examination showed the presence of promyelocytes. Patients were treated with a combination of systemic chemotherapy and radiotherapy with or without intrathecal chemotherapy, and most were subsequently treated with arsenic trioxide (ATO) as maintenance therapy. Among these patients, one received allogeneic stem cell transplantation in second complete remission.

Invasive Tracheobronchial Aspergillosis : Case Reports and a Literature Review / 감염과화학요법

Invasive tracheobronchial aspergillosis (iTBA) is an uncommon clinical manifestation of invasive aspergillosis and this is usually limited to the large airways. Its pathophysiology and clinical features are obscure, but some fatal cases of iTBA in immunocompetent patients have also been reported. We describe 4 cases of iTBA in the patients with hematologic malignancies, that was early diagnosed by bronchoscopy, a computed tomography and successfully treated by proper antifungal treatment. And we also review the cases of iTBA reported in Korea.

Efficacy and Safety Profile of Voriconazole as Salvage Therapy for Invasive Aspergillosis with Hematologic Diseases in Korea / 감염과화학요법

BACKGROUND: Invasive aspergillosis (IA) is associated with significant morbidity and mortality in patients with hematologic malignancies. We investigated the efficacy and safety of voriconazole (VCZ) when used as salvage therapy for IA in Korean adults with hematologic malignancies who had not responded to prior antifungal therapy. MATERIALS AND METHODS: We retrospectively reviewed data, collected from January 2007 to October 2008, from patients with proven or probable cases of IA. All were probable IA cases, except for one proven case. All cases were refractory or intolerant to antifungal therapy prior to administration of VCZ. Efficacy and safety were assessed in patients treated with VCZ for more than 3 days and for more than one dose, respectively. A favorable response [complete (CR) or partial (PR)] was defined by significant improvement of all clinical symptoms, signs, and radiologic abnormalities. RESULTS: Fifty patients who met the inclusion criteria were enrolled. There were 27 male and 23 female patients with mean age of 44.4 years (range, 15-65 years). Underlying diseases were acute leukemia (35 cases), chronic myelogenous leukemia (4 cases), myelodysplastic syndrome (3 cases), lymphoma (3 cases) and other hematologic diseases (5 cases). Twenty-two patients had received chemotherapy and 13 patients had undergone hematopoietic stem cell transplantation. The lung was the main infection site (94%) followed by the sinus (6%). Amphotericin B deoxycholate alone was the most frequent previous antifungal therapy. The mean duration of antifungal therapy prior to VCZ therapy was 13.9+/-8.8 days (2-44 days). The median duration of VCZ therapy was 19 days (interquartile range, 49 days). Sixteen patients (32.0%) showed favorable responses (CR:PR=8:8) at the end of VCZ therapy. The numbers of patients with stable disease, progression and death were, 6 (12%), 6 (12%) and 22 (44%) respectively. Most of those with unfavorable responses had relapsed underlying malignancies or refractory graft versus host diseases. Twelve patients developed drug-related adverse events but only one patient stopped VCZ treatment prematurely. CONCLUSIONS: VCZ demonstrated an acceptable level of toxicity in patients with hematologic malignancies but further studies are required to prove its efficacy as salvage therapy.