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Antimicrobial stewardship programs (ASPs) can lower antibiotic use, decrease medical expenses, prevent the emergence of resistant bacteria, and enhance treatment for infectious diseases. This study summarizes the stepwise implementation and effects of ASPs in a single university-affiliated tertiary care hospital in Korea; it also presents future directions and challenges in resource-limited settings. At the study hospital, the core elements of the ASP such as leadership commitment, accountability, and operating system were established in 2000, then strengthened by the formation of the Antimicrobial Stewardship (AMS) Team in 2018. The actions of ASPs entail key components including a computerized restrictive antibiotic prescription system, prospective audit, post-prescription review through quantitative and qualitative intervention, and pharmacy-based interventions to optimize antibiotic usage. The AMS Team regularly tracked antibiotic use, the effects of interventions, and the resistance patterns of pathogens in the hospital. The reporting system was enhanced and standardized by participation in the Korea National Antimicrobial Use Analysis System, and educational efforts are ongoing. Stepwise implementation of the ASP and the efforts of the AMS Team have led to a substantial reduction in the overall consumption of antibiotics, particularly regarding injectables, and optimization of antibiotic use. Our experience highlights the importance of leadership, accountability, institution-specific interventions, and the AMS Team.

Background/Aims Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. Methods This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. Results The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). Conclusions The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.

Lateral flow assays are valuable rapid diagnostic tests, but low sensitivity can hinder their precision. Here, the authors report an enrichment method using nanoporous AAO and red blood cell membranes, which when applied to patient samples prior to analysis can improve sensitivity up to 20-fold.

The β-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA.

The prevention and management of cytomegalovirus (CMV) reactivation is important to improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data regarding the incidence and characteristics of CMV infections until 1 year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14 weeks, 24 weeks, and 1 year post-HCT, respectively. Through multivariate analysis, the risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036–6.510]; p < 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued receiving letermovir (p = 0.002). There were 18 (15.9%) refractory CMV infection cases in this study population. In summary, letermovir prophylaxis is effective at preventing CS-CMVi until day 100, which increased after the cessation of letermovir. GVHD is still a significant risk factor in the era of letermovir prophylaxis. Further research is needed to establish individualized management strategies, especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.

Cytomegalovirus (CMV) infection is a serious complication in hematopoietic cell transplantation (HCT) recipients. Drug-resistant strains make it more challenging to treat CMV infection. This study aimed to identify variants associated with CMV drug resistance in HCT recipients and assess their clinical significance. A total of 123 patients with refractory CMV DNAemia out of 2271 HCT patients at the Catholic Hematology Hospital between April 2016 and November 2021 were analyzed, which accounted for 8.6% of the 1428 patients who received pre-emptive therapy. Real-time PCR was used to monitor CMV infection. Direct sequencing was performed to identify drug-resistant variants in UL97 and UL54. Resistance variants were found in 10 (8.1%) patients, and variants of uncertain significance (VUS) were found in 48 (39.0%) patients. Patients with resistance variants had a significantly higher peak CMV viral load than those without (p = 0.015). Patients with any variants had a higher risk of severe graft-versus-host disease and lower one-year survival rates than those without (p = 0.003 and p = 0.044, respectively). Interestingly, the presence of variants reduced the rate of CMV clearance, particularly in patients who did not modify their initial antiviral regimen. However, it had no apparent impact on individuals whose antiviral regimens were changed due to refractoriness. This study highlights the importance of identifying genetic variants associated with CMV drug resistance in HCT recipients for providing appropriate antiviral treatment and predicting patient outcomes.

배경 Fusarium is a filamentous fungus, found in soil, water and plants. Fusarium is mostly harmless but some species cause opportunistic infection in the setting of immunosuppression. Disseminated Fusarium infection is fatal in neutropenic host, antifungal susceptibility is not well established, and some species are known to be resistant to all available antifungal agents. 방법 We retrospectively reviewed the electronical medical record of patients with culture-proven Fusarium infections at Seoul St Mary’s hospital from October 2012 through December 2021. Invasive fusariosis was defined according to the consensus of invasive fungal disease published in 2019 by the European Organization for Research and Treatment of Cancer and the Mycoses Study Group. 결과 We identified 19 cases of hematologic malignancy patients with invasive fusariosis. We found 12 cases of Fusarium fungemia. In the other 7 cases, Fusarium was isolated from specimen other than blood, such as anterior chamber aspiration, paranasal sinus, skin and sputum, and those cases were accom- panied with sign of infection attributable to Fusarium. The median age of patients was 57 years, 68.4% (13 cases) were male. The most common underlying hematologic disease was acute myeloid leukemia (63.2%, 12 cases). Among 19 cases, 57.9% (11 cases) were due to Fusarium solani, and 36.7 % (7 cases) were associated with non-solani Fusarium. Seven patients were coinfected with other fungi, mainly Aspergillus (31.6%, 6 cases). Overall mortality rate was 78.9% (15 cases), in which 26.3% (5 cases) were associated with fusariosis. We tested the minimum inhibitory concentrations (MIC) of antifungal agents in 8 available clinical isolates. For Fusarium solani species, MIC ranges were 4~16 ㎍/㎖ for voriconazole, 8~64 ㎍/㎖ for isavuconazium, and 1~32 ㎍/㎖ for amphotericin B. In non-solani Fusarium species, MIC ranges were 1~32 ㎍/㎖ for voriconazole, 2~64 ㎍/㎖ for isavuconazium and 2~4 ㎍/㎖ for amphotericin B. The activity of posaconazole was shown to be limited in both Fusarium solani and non-solani Fusarium species with an MIC50 of 64 ㎍/㎖. 결론 Invasive fusariosis is a life-threatening infection to immunocompromised host. Fusarium exhibits high MIC to antifungal agents. Further study with large number of patients and clinical isolates is necessary [ABSTRACT FROM AUTHOR]

배경: Letermovir is used for cytomegalovirus (CMV) prophylaxis in allogeneic hematopoietic stem cell transplantation (allo-HSCT). Letermovir should be initiated on D0~28 in CMV-seropositive recipient with undetectable plasma CMV DNA within 5 days, until D100 after HSCT. We evaluate the impact of early letermovir prophylaxis on the incidence of clinically significant CMV infection (CS-CMVi). 방법: Retrospective review was performed for allo-HSCT recipients from NOV 2020 to OCT 2021 at Seoul St. Mary’s Hospital. Blood CMV RQ-PCR was checked biweekly during hospitalization and at every visit after discharge. CS-CMVi, CMV end-organ disease, CMV blips were evaluated at week 24 after HSCT. We compared incidence of CS-CMVi in early prophylaxis group (D0~D3) with late prophylaxis group (D4~D28). 결과: A total of 358 patients underwent allo-HSCT, of which 306 received letermovir prophylaxis. Among 306 patients, 145 (47.4%) had high risk of CMV reactivation, and 206 patients (67.3%) started letermovir prophylaxis at D0~D3 after HSCT. The median day of letermovir initiation in our study was day 2 (range 0~27). At week 24, there were 96 patients (31.4%) with CS-CMVi, 20 (6.5%) had CMV end organ disease, and CMV blips were observed in 64 (20.9%) patients. In high risk group (n=145), CS-CMVi was developed in 30/96 (31.2%) and 20/49 (40.8%) of patients (p=0.289) in early and late prophylaxis group, respectively. CMV-related mortality was 1.0% at week 24. 결론: Letermovir prophylaxis is effective in preventing CMV infection in seropositive allo-HSCT recipients. Early initiation of letermovir did not have significant difference in incidence of CS-CMVi compared to late prophylaxis. However early prophylaxis showed lower incidence in high risk group. Further studies are needed for longer follow up duration, including timing of prophylaxis according to risk of CMV reactivation. [ABSTRACT FROM AUTHOR]

배경: Invasive mucormycosis (IM) are increasing worldwide according to the profound immune suppression and use of broad spectrum antifungal agents. The aim of this study was to determine the characteristics of IM, and also analyzed clinical courses and outcomes of patients with hematologic diseases. 방법: We retrospectively reviewed all consecutive proven or probable (PP-) IM cases between Jan. 2011 and Mar. 2022 in a cohort of invasive fungal diseases (IFDs) at Seoul St. Mary’s Hospital, Seoul, Korea. 결과: During the study period, a total of 44 cases of PP-IM were identified. Median age was 55 year-old and 59% were male. Most common underlying diseases were acute myelogenous leukemia (n=17), followed by acute lymphocytic leukemia (n=9). Primary infection site was lung (n=30), followed by paranasal sinus (n=8), intestines (n=4), and skin and soft tissue (n=2). Disseminated infection was found in 27% of patients. Anti-mold active antifungal agents were administered in 23% of patients with median duration of 32 (range 13–95) days prior to the diagnosis of IM. There were 16 isolates from 15 culture-positive PP-IM patients; Rhizopus sp. (n=4), Rhizomucor sp. (n=4), Cunninghamella sp. (n=3), Paecilomyces sp. (n=3), Lichthemia sp. (n=2). Coinfection with PP-invasive aspergillosis (IA) was found in 25% of patients. Surgery was performed concurrently in 75% of patients. Survival rate at 100-d was 66%. Surgery was performed in 42% and 86% in deceased and survivor group at 6-wks, respectively. Fifteen patients received subsequent chemotherapy (CTx) or hematopoietic cell transplantation (HCT) after the diagnosis of IM. Among them, 11 were survived, while four patients died from infectious complication other than IFD. Two patients started CTx within one month from the surgical resection of pulmonary IM, who recovered without any complications. 결론: IM shows high mortality rate. IM and IA coinfection is not rare. In cases with successful surgical resection of IM, subsequent CTx or HCT can be considered. [ABSTRACT FROM AUTHOR]

Nephrotoxicity limits the use of cisplatin, a widely used chemotherapeutic agent for treatment of various malignancies. Overall, CD4+ T cells mediate cisplatin-induced renal injury; however, the CD4+CD25+ regulatory T-cell subset (CD4+CD25+ Treg) has broad suppressive effects on many different cell types. In this study, we determined whether CD4+CD25+ Treg cells had protective effects against cisplatin-induced acute renal injury in nu/nu mice that lack mature T cells. In these mice, there was marked attenuation of the decreased survival, renal dysfunction and tubular injury, renal tumor necrosis factor-α, and interleukin-1β cytokine levels. Furthermore, renal macrophage accumulation was reduced in CD4+CD25+ Treg cell-adoptive transferred nu/nu mice compared with control mice. Infusion of CD4+CD25+Treg cells into wild-type Balb/c mice reduced serum blood urea nitrogen and creatinine levels equivalent to those in nu/nu mice and extended their survival time after cisplatin injection. In contrast, depletion of CD4+CD25+ Treg cells in wild-type mice exacerbated kidney injury after cisplatin administration. Transcription factor Foxp3-positive cells (Treg cells) were detected in the kidneys of nu/nu mice after cisplatin injection. Our results suggest that CD4+CD25+ Treg cells directly affect cisplatin nephrotoxicity and their modulation represents an additional treatment strategy. [ABSTRACT FROM AUTHOR]