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Gastrointestinal (GI) bleeding is a rare adverse event of dasatinib, which is known to be caused by dasatinib-induced colitis, severe thrombocytopenia, and platelet dysfunction.We present two cases of pediatric patients who developed hematochezia during treatment with dasatinib after hematopoietic stem cell transplantation (HSCT). A colonic tissue biopsy was performed to differentiate the cause of GI bleeding. Both patients were diagnosed with proven cytomegalovirus (CMV) colitis, but only one was treated with ganciclovir. The patient who did not receive antiviral therapy experienced recurrent GI bleeding during dasatinib administration, leading to multiple treatment interruptions. During dasatinib therapy after HSCT, patients with GI bleeding and confirmed CMV colitis may benefit from antiviral therapy to reduce interruptions in dasatinib therapy.
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Objective@#To report the clinical and radiological characteristics of patients with underlying B-cell lymphoma and coronavirus disease 2019 (COVID-19) showing migratory airspace opacities on serial chest computed tomography (CT) with persistent COVID-19 symptoms. @*Materials and Methods@#From January 2020 to June 2022, of the 56 patients with underlying hematologic malignancy who had undergone chest CT more than once at our hospital after acquiring COVID-19, seven adult patients (5 female; age range, 37–71 years; median age, 45 years) who showed migratory airspace opacities on chest CT were selected for the analysis of clinical and CT features. @*Results@#All patients had been diagnosed with B-cell lymphoma (three diffuse large B-cell lymphoma and four follicular lymphoma) and had received B-cell depleting chemotherapy, including rituximab, within three months prior to COVID-19 diagnosis. The patients underwent a median of 3 CT scans during the follow-up period (median 124 days). All patients showed multifocal patchy peripheral ground glass opacities (GGOs) with basal predominance in the baseline CTs. In all patients, followup CTs demonstrated clearing of previous airspace opacities with the development of new peripheral and peribronchial GGO and consolidation in different locations. Throughout the follow-up period, all patients demonstrated prolonged COVID-19 symptoms accompanied by positive polymerase chain reaction results from nasopharyngeal swabs, with cycle threshold values of less than 25. @*Conclusion@#COVID-19 patients with B-cell lymphoma who had received B-cell depleting therapy and are experiencing prolonged SARS-CoV-2 infection and persistent symptoms may demonstrate migratory airspace opacities on serial CT, which could be interpreted as ongoing COVID-19 pneumonia.
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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.
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Background@#Patients with hematologic diseases are at high risk of bloodstream infections (BSIs). This study aimed to analyze clinical features and distributions of microorganisms in patients with hematologic diseases presenting at a tertiary care university-affiliated hospital in Korea. @*Materials and Methods@#We retrospectively reviewed all BSI episodes recorded in patient medical records at two hematologic wards of the Catholic Hematology Hospital from January to December 2020. Our aim was to analyze demographic and clinical characteristics relevant to BSIs. We also described the antimicrobial resistance patterns of the major pathogens identified in this study, and evaluated risk factors for extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae isolates and for vancomycin resistance in enterococcal isolates. @*Results@#A total of 380 BSI episodes were identified in 334 patients over the course of 1 year (monomicrobial BSI episodes, 86.1%; polymicrobial BSI episodes, 13.9%). Gram-negative bacteria accounted for 242 isolates (54.8%). The most frequently isolated Gram-negative bacteria isolates were Escherichia coli (107 [24.2%]) followed by Klebsiella spp. (72 [16.3%]), Pseudomonas spp. (21 [4.8%]), and Enterobacter spp. (12 [2.7%]). The most commonly identified Gram-positive bacteria were Enterococcus spp. (72 [16.3%]) followed by viridans streptococci (54 [12.2%]), coagulase-negative staphylococci (CoNS) (24 [5.4%]), and Corynebacterium spp. (22 [5.0%]). ESBL-producing Enterobacteriaceae accounted for 25.1% of the total distribution. Among 54 Enterococcus faecium isolates, 100.0% were resistant to ampicillin and 55.6% showed resistance to vancomycin, while 100.0% (n = 12) of Enterococcus faecalis isolates were susceptible to ampicillin and vancomycin, respectively. Use of ciprofloxacin prophylaxis (odds ratio: 5.20; 95% confidence interval: 1.11 - 24.34; P = 0.04) was an independent risk factor for ESBL production in Enterobacteriaceae BSIs. @*Conclusion@#Compared with the results of a previous study conducted at the same institution, our findings demonstrated that Gram-negative bacteria remained dominant pathogens in BSIs occurring in patients with hematologic diseases. Our findings also demonstrated a comparatively decreased prevalence of ESBL-producing Enterobacteriaceae in the evaluated BSIs. However, the prevalence of enterococcal BSIs had not decreased, and the proportion of vfancomycin-resistant Enterococcus isolates from E. faecium BSIs had increased. In addition, we found that ciprofloxacin prophylaxis was statistically significantly associated with ESBL production in Enterobacteriaceae BSIs. We conclude that, in order to avoid critical complications and to reduce the burden of antimicrobial-resistant organisms in patients with hematologic diseases, it is necessary to conduct periodic examinations evaluating changes in BSI epidemiology within a single medical center.
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Reducing antibiotics overuse is essential to minimize antibiotics related side effects and to prevent the emergence of multidrug-resistant bacteria. Procalcitonin (PCT) guided antibiotics therapy has been reported to be safe in patients with acute respiratory infections and sepsis, improving clinical outcomes as well as reducing the duration of antibiotics use.However, there is still no universal agreement on clinical guidelines in Korea for optimal PCT applications. Through this expert consensus meeting, clinical research findings in the PCT-guided antibiotics treatment interventions and real-world clinical applications were discussed. From the perspective of antibiotic stewardship, PCT application target groups, cut-offs, and testing cycles were discussed to reach a consensus on the PCT-guided antibiotics treatment algorithm for application in Korea. Combining clinical assessment for patients with an appropriate PCT-guided antibiotics treatment algorithm could improve the diagnosis and treatment of acute respiratory infections and sepsis. In addition, continuous education and regular feedback would improve the effectiveness of antibiotic stewardship.
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Multidrug resistance in bacteria is an important issue and is increasing in frequency worldwide because of the limitations of therapeutic agents. From 2010 to 2019, 14 new systemic antibiotics received regulatory approval in the United States. However, few new antibiotics have been introduced in Republic of Korea to combat multidrug-resistant pathogens. Here, we introduce six novel antibiotics for Gram-positive bacteria and five for Gram-negative bacteria approved by the United States Food and Drug Administration and the European Medicines Agency from 2009 to October 2021, and recommend that they be approved for use in Republic of Korea at the earliest possible date.
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Schizophyllum commune is a mold in phylum Basidiomycota and is an uncommon human pathogen. Sinusitis and allergic bronchopulmonary mycosis are the two major diseases caused by S. commune. Although there have been several reports of invasive fungal diseases, most of them were invasive sinusitis. We present a case of invasive fungal pneumonia due to S. commune, developed in a patient with acute myeloid leukemia presenting neutropenic fever. The diagnosis was made by characteristic macroscopic and microscopic findings of fungal isolate and was confirmed via sequencing of internal transcribed spacer region. The patient was improved after 8 weeks of antifungal therapy based on the susceptibility result.We propose that S. commune should be considered as an emerging pathogen of invasive fungal pneumonia when a patient is under immunocompromised state. We also reviewed global literatures focused on the invasive fungal diseases caused by S. commune
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Invasive fungal infections (IFIs) are common causes of mortality and morbidity in patients with hematologic diseases. Delayed initiation of antifungal treatment is related to mortality. Aspergillus sp. is the leading cause of IFI followed by Candida sp. Diagnosis is often challenging owing to variable conditions related to underlying diseases. Clinical suspect and prompt management is important. Imaging, biopsy, and non-culture-based tests must be considered together. New diagnostic procedures have been improved, including antigen-based assays and molecular detection of fungal DNA. Among hematologic diseases, patients with acute myeloid leukemia, myelodysplastic syndrome, recipients of hematopoietic stem cell transplantation are at high risk for IFIs. Antifungal prophylaxis is recommended for these high-risk patients. There are continuous attempts to achieve ideal management of IFIs. Scoring system for quality control has been developed with important recommendations of current guidelines. Higher adherence to guidelines is related to decreased mortality in IFIs.
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Sepsis is one of the significant causes of morbidity and mortality. The burden caused by sepsis has continued to increase in recent years in the Korea, highlighting the urgent need for the implementation of strategies to improve sepsis treatment outcomes. We therefore designed a web-based sepsis registry system (“Korean Registry for Improving Sepsis Survival” [KISS]) protocol to be used in hospitals in the Korea for evaluation of the epidemiology and clinical characteristics of patients with sepsis, via an analysis of outcome predictors. The inclusion criteria of this registry are as follows: adult patients ≥18 years admitted to the participating hospitals who are diagnosed with sepsis or septic shock. Demographic and clinical information data of the patients will be collected from hospital medical records and will be recorded in a case report form, which will be entered into a web-based data management system. The analysis of the collected data will be performed as follows: (1) epidemiological and clinical characteristics of sepsis and septic shock, (2) application of sepsis bundles and antibiotic stewardship, and (3) audit and feedback. In conclusion, we aim to build the comprehensive web-based sepsis registry in the Korea through a nation-wide network of participating hospitals. Information collected and analyzed through the KISS can be used for further improvements in the clinical management of sepsis. Furthermore, the KISS will facilitate research leading to the formulation of public health policies regarding sepsis bundle and antibiotic stewardship strategies in the Korea.
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PURPOSE: Few studies have been investigated the in vivo efficacy of generic vancomycin products available outside of the United States. In this study, we aimed to compare the in vivo pharmacokinetics (PK) and pharmacodynamics (PD) of five generic vancomycin products available in Korea with those of the innovator.MATERIALS AND METHODS: The in vitro vancomycin purity of each product was examined using high-pressure liquid chromatography. Single-dose PK analyses were performed using neutropenic mice. The in vivo efficacy of vancomycin products was compared with that of the innovator in dose-effect experiments (25 to 400 mg/kg per day) using a thigh-infection model with neutropenic mice.RESULTS: Generic products had a lower proportion of vancomycin B (range: 90.3–93.8%) and a higher proportion of impurities (range: 6.2–9.7%) than the innovator (94.5% and 5.5%, respectively). In an in vivo single-dose PK study, the maximum concentration (C(max)) values of each generic were lower than that of the innovator, and the geographic mean area under the curve ratios of four generics were significantly lower than that of the innovator (all p<0.1). In the thigh-infection model, the maximum efficacies of generic products reflected in maximal effect (E(max)) values were not significantly different from the innovator. However, the PD profile curves of some generic products differed significantly from that of the innovator in mice injected with a high level of Mu3 (all p≤0.05).CONCLUSION: Some generic vancomycin products available in Korea showed inferior PK and PD profiles, especially in hetero-vancomycin-resistant mice infected with Staphylococcus aureus.
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The ichroma Chikungunya virus (CHIKV) IgG/IgM (Boditech Med Inc., Chuncheon, Korea) is a newly developed rapid lateral flow immunoassay for detection of anti- CHIKV-IgG/ IgM. This study conducted with thirty-six anti-CHIKV IgG positive sera, 57 anti-CHIKV IgM positive sera and 163 anti-CHIKV IgG/IgM negative sera which were confirmed by commercial enzyme-linked immunosorbent assays (ELISAs) (Inbios CHIKjj Detect™ IgM Capture ELISA, Inbios CHIKjj Detect™ IgG ELISA (InBios International Inc., Seattle, WA, USA), Anti-CHIKV ELISA (IgM), Anti- CHIKV ELISA (IgG) (Euroimmun, Lübeck, Germany)). The ichroma detected all 36 anti-CHIKV IgG and 57 anti-CHIKV IgM positivity (100% sensitivity). For 163 anti-CHIKV IgG/IgM negative sera, the ichroma showed one false positive for IgM (99.4% specificity). The ichroma showed no cross-reactivity and no interference. The ichroma demonstrated good diagnostic performance compared to the current ELISAs.
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The ichroma Chikungunya virus (CHIKV) IgG/IgM (Boditech Med Inc., Chuncheon, Korea) is a newly developed rapid lateral flow immunoassay for detection of anti- CHIKV-IgG/ IgM. This study conducted with thirty-six anti-CHIKV IgG positive sera, 57 anti-CHIKV IgM positive sera and 163 anti-CHIKV IgG/IgM negative sera which were confirmed by commercial enzyme-linked immunosorbent assays (ELISAs) (Inbios CHIKjj Detect™ IgM Capture ELISA, Inbios CHIKjj Detect™ IgG ELISA (InBios International Inc., Seattle, WA, USA), Anti-CHIKV ELISA (IgM), Anti- CHIKV ELISA (IgG) (Euroimmun, Lübeck, Germany)). The ichroma detected all 36 anti-CHIKV IgG and 57 anti-CHIKV IgM positivity (100% sensitivity). For 163 anti-CHIKV IgG/IgM negative sera, the ichroma showed one false positive for IgM (99.4% specificity). The ichroma showed no cross-reactivity and no interference. The ichroma demonstrated good diagnostic performance compared to the current ELISAs.
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The inappropriate use of antimicrobial agents results in collateral damages such as treatment failure, an increased frequency of adverse events related to antimicrobial agents, the emergence of resistant bacteria, and increased medical costs. The selection of appropriate antimicrobial agents begins with taking a detailed history and performing a thorough physical examination to determine whether the cause of the fever is infectious or non-infectious. Based on the patient's symptoms and signs, the site of infection (a system-oriented approach) and the causative organism with high possibility (a pathogenesis-oriented approach: intracellular vs. extracellular) can be estimated. In this process, host factors, microbial factors, and the characteristics of antimicrobial agents should be considered. Herein, we summarize the recently developed Korean guidelines for the use of antimicrobial agents for infectious diseases. We also introduce the antimicrobial website and application developed by Korean Society for Antimicrobial Therapy and the antimicrobial stewardship program.
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BACKGROUND@#Recently, Citrobacter freundii bacteremia outbreak in a neonatal intensive care unit has attracted public attention in Korea. However, Citrobacter bacteremia is uncommon and usually occurs in patients with underlying diseases such as malignancy and hepatobiliary diseases. Increase in resistance and emerging of multidrug resistance among Citrobacter species have gradually been reported. The aim of this study was to investigate the clinical characteristics and outcome of C. freundii and non-freundii bacteremia and antimicrobial susceptibility trends.@*MATERIALS AND METHODS@#We reviewed the medical records of patients with Citrobacter bacteremia at St. Mary's Hospital, from 2007 to 2017.@*RESULTS@#A total of 43 patients with a median age of 72 (24-93) years was identified and 90.7% of them had comorbidities. Twenty-nine (67.4%) patients had C. freundii bacteremia while 14 had non-freundii bacteremia (six of C. braakii, five of C. koseri, two of C. amalonaticus and one of C. youngae). A total of 26 (51.2%) patients had community-acquired infection and intra-abdominal infection including hepatobiliary tract was the most common portal of entry (24/43, 55.8%). Moreover, hepatobiliary tract was the leading primary site of nosocomial infection (9/17, 52.9%). Polymicrobial bacteremia was observed in 21 (48.8%) patients. The percentages of Citrobacter species susceptible to ampicillin, amikacin, aztreonam, cefazolin, cefoxitin, cefotaxime, cefepime, piperacillin-tazobactam, ciprofloxacin, and imipenem were 9.5%, 97.6%, 73.8%, 9.5%, 14.3%, 71.4%, 92.9%, 83.3%, 83.3% and 100%, respectively. The resistance rate did not increase during the study period. Of 39 patients treated with antibiotics, 36 (92.3%) received appropriate empirical antibiotics. Overall mortality was 18.6%. High Charlson comorbidity index and Pitt bacteremia score were significant risk factors for death in univariate analysis and showed trends in the multivariate analysis. No significant difference in clinical features and antimicrobial susceptibility rate was observed between C. freundii and non-freundii bacteremia.@*CONCLUSION@#Citrobacter bacteremia was predominant in the elderly with comorbidities, while no pediatric case was observed. Hepatobiliary tract is the leading primary focus of bacteremia both in community-acquired and nosocomial infection. The rate of susceptibility to antibiotics has not changed in the last 11 years.
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The authors found errors in their published article.
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The inappropriate use of antimicrobial agents results in collateral damages such as treatment failure, an increased frequency of adverse events related to antimicrobial agents, the emergence of resistant bacteria, and increased medical costs. The selection of appropriate antimicrobial agents begins with taking a detailed history and performing a thorough physical examination to determine whether the cause of the fever is infectious or non-infectious. Based on the patient's symptoms and signs, the site of infection (a system-oriented approach) and the causative organism with high possibility (a pathogenesis-oriented approach: intracellular vs. extracellular) can be estimated. In this process, host factors, microbial factors, and the characteristics of antimicrobial agents should be considered. Herein, we summarize the recently developed Korean guidelines for the use of antimicrobial agents for infectious diseases. We also introduce the antimicrobial website and application developed by Korean Society for Antimicrobial Therapy and the antimicrobial stewardship program.
Subject(s)
Anti-Infective Agents , Bacteria , Communicable Diseases , Fever , Physical Examination , Treatment FailureABSTRACT
PURPOSE: This study aimed to investigate the molecular epidemiology of a methicillin-resistant Staphylococcus aureus (MRSA) outbreak at a newborn nursery and neonatal intensive care unit (NICU).METHODS: During the outbreak, from August to September 2017, MRSA isolates collected from neonates and medical staff underwent genotyping and screened for virulence factors. Antibiotic susceptibilities were tested.RESULTS: During the study period, 41 neonates were admitted at the nursery (n=27) and NICU (n=14). Of these, 7 had MRSA infections (skin infection [n=6] and sepsis [n=1]) and 4 were colonized with MRSA. Associated medical staff (n=32) were screened; three were nasal MRSA carriers. Staphylococcal chromosomal cassette mec (SCCmec) type II, sequence type (ST) 89, spa type t375 was found to be the skin infection outbreak causing strain, with multi-drug resistance including low-level mupirocin resistance. SCCmec type IVa, ST 72, and a novel spa type designated t17879, was the cause of MRSA sepsis. Many different types of MRSA were colonized on the neonates; however, SCCmec type IVa, ST 72, spa type t664 was colonized in both neonates and a NICU nurse. All MRSA isolates from colonized infants were positive for the Panton-Valentine leukocidin (PVL) toxin gene.CONCLUSIONS: The strain causing an outbreak of skin infections had multi-drug resistance. Also, MRSA colonized in the neonates were found to carry the PVL toxin gene. Because different strains are present during an outbreak, molecular epidemiologic studies are important to identify the outbreak strain and colonized strains which aid in effective control and prevention of future MRSA outbreaks.
Subject(s)
Humans , Infant , Infant, Newborn , Colon , Disease Outbreaks , Drug Resistance, Multiple , Epidemiologic Studies , Intensive Care, Neonatal , Leukocidins , Medical Staff , Methicillin Resistance , Methicillin-Resistant Staphylococcus aureus , Molecular Epidemiology , Mupirocin , Nurseries, Infant , Sepsis , Skin , Virulence FactorsABSTRACT
ELISAs and rapid diagnostic tests (RDTs) are widely used for diagnosing dengue virus (DENV) infection. Using 138 single blood samples, we compared the ability to detect non-structural (NS)-1 antigen and anti-DENV IgM/IgG antibodies among (1) DENV Detect NS1 ELISA, DENV Detect IgM capture ELISA and DENV Detect IgG ELISA (InBios International, Inc.); (2) Anti-Dengue virus IgM Human ELISA and Anti-Dengue virus IgG Human ELISA (Abcam); (3) Dengue virus NS1 ELISA, Anti-Dengue virus ELISA (IgM) and Anti-Dengue virus ELISA (IgG) (Euroimmun); (4) Asan Easy Test Dengue NS1 Ag 100 and Asan Easy Test Dengue IgG/IgM (Asan Pharm); (5) SD BIOLINE Dengue Duo (Standard Diagnostics); and (6) Ichroma Dengue NS1 and Ichroma Dengue IgG/IgM (Boditech Med). For NS1 antigen detection, InBios and Euroimmun showed higher sensitivities (100%) than the RDTs (42.9–64.3%). All tests demonstrated variable sensitivities for IgM (38.1–90.5%) and IgG (65.7–100.0%). InBios and Boditech Med demonstrated higher sensitivity (95.6% and 88.2%, respectively) than the other tests for combined NS1 antigen and IgM antibody. Five NS1 antigen tests had good agreement (92.8–98.6%) without showing positivity for chikungunya. However, all IgG tests demonstrated potential false-positivity with variable ranges. Clinical laboratories should note performance variations across tests and potential cross-reactivity.
Subject(s)
Humans , Antibodies , Dengue Virus , Dengue , Diagnosis , Diagnostic Tests, Routine , Enzyme-Linked Immunosorbent Assay , Immunoglobulin G , Immunoglobulin MABSTRACT
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.
Subject(s)
Humans , Anti-Bacterial Agents , Antifungal Agents , Arm , Catheter-Related Infections , Ciprofloxacin , Fungemia , Immunocompromised Host , Incidence , Itraconazole , Leg , Mortality , Myelodysplastic Syndromes , Prognosis , Skin , Stem Cell Transplantation , Trichosporon , VoriconazoleABSTRACT
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.