Invasive Aspergillosis in Liver Transplant Recipients in The Current Era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

MicroRNAs in infectious diseases: potential diagnostic biomarkers and therapeutic targets.

MicroRNAs (miRNAs) are conserved, short, non-coding RNAs that play a crucial role in the post-transcriptional regulation of gene expression. They have been implicated in the pathogenesis of cancer and neurological, cardiovascular, and autoimmune diseases. Several recent studies have suggested that miRNAs are key players in regulating the differentiation, maturation, and activation of immune cells, thereby influencing the host immune response to infection. The resultant upregulation or downregulation of miRNAs from infection influences the protein expression of genes responsible for the immune response and can determine the risk of disease progression. Recently, miRNAs have been explored as diagnostic biomarkers and therapeutic targets in various infectious diseases. This review summarizes our current understanding of the role of miRNAs during viral, fungal, bacterial, and parasitic infections from a clinical perspective, including critical functional mechanisms and implications for their potential use as biomarkers and therapeutic targets.

Immunogenicity and Safety of Booster SARS-CoV-2 mRNA Vaccine Dose in Allogeneic Hematopoietic Stem Cell Transplantation Recipients.

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are susceptible to severe outcomes of Coronavirus disease 2019 (COVID-19). Most guidelines recommend a fourth dose (ie, booster) of COVID-19 vaccine to reduce the infection risk, and observational studies are needed to determine the immunogenicity and safety of the booster dose in this population. The primary outcome was to determine the quantitative anti-receptor-binding domain (RBD) antibody titers after the fourth dose of the COVID-19 vaccine. The secondary outcomes included adverse effects and all-cause mortality. This single-group prospective cohort included allogeneic HSCT recipients age ≥18 years who received their fourth dose of COVID-19 mRNA vaccine between December 15, 2021, and August 2, 2022. We excluded patients with a history of COVID-19 diagnosis and those who received i.v. Ig within 21 days of antibody testing or rituximab within 6 months before study entry. We used regression models to determine the contributing factors significantly associated with post-fourth dose anti-RBD titer. Sixty-seven patients (median age, 59.5 years; IQR, 53.5 to 65.5 years; 33 males [61%]) received the fourth dose of vaccine, and 54 were included in the anti-RBD titer analysis. The median anti-RBD titers at 4 to 6 weeks after the third and fourth doses differed significantly (13,350 U/mL [IQR, 2618 to 34,740 U/mL] and 44,500 U/mL [IQR, 11,163 to 84,330 U/mL], respectively; P < .0001). In univariate analysis, the post-third dose anti-RBD titer (ß = .70; 95% CI, .54 to .87; P < .001) and treatment with mycophenolate compounds (ß = -1.05; 95% CI, -1.97 to -1.12; P = .03) significantly predicted the antibody response to the fourth dose. In multivariate analysis, the inverse association between treatment with mycophenolate compounds and the post-fourth dose anti-RBD antibody titer was not significant (ß = -.57; 95% CI, -1.32 to .19; P = .14), whereas the significant association between the anti-RBD titers following the third and fourth doses did not change considerably (ß = .66; 95% CI, .47 to .86; P < .001). The most frequent adverse event was vaccination site soreness (44%), followed by fatigue (16%), myalgia (4%), and headache (2%). No recipient experienced new or worsened preexisting graft-versus-host disease within 40 days of vaccination, and no patient died. Six patients (11%) developed breakthrough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection not associated with hospitalization or severe outcomes. The fourth dose of the COVID-19 vaccine appears to be highly immunogenic and safe in allogeneic HSCT recipients. Further studies are needed to determine the neutralizing antibody titers against SARS-CoV-2 subvariants and the effectiveness and immunogenicity of bivalent vaccines in allogeneic HSCT recipients.

Predictive scoring system for distinguishing Stenotrophomonas maltophilia bacteremia from Pseudomonas aeruginosa bacteremia in patients with hematological malignancies.

Difficulties in immediately distinguishing Stenotrophomonas maltophilia (SM) bacteremia from Pseudomonas aeruginosa (PA) bacteremia in the clinical setting can lead to treatment delay. We aimed to develop a scoring system to immediately distinguish SM bacteremia from PA bacteremia using clinical indicators. We enrolled cases of SM and PA bacteremia in adult patients with hematological malignancies between January 2011 and June 2018. The patients were randomized into derivation and validation cohorts (2:1), and a clinical prediction tool for SM bacteremia was developed and verified. In total, 88 SM and 85 PA bacteremia cases were identified. In the derivation cohort, the following independent predictors of SM bacteremia were identified: no evidence of PA colonization, antipseudomonal ß-lactam breakthrough bacteremia, and central venous catheter insertion. We scored each of the three predictors according to their regression coefficient (2, 2, and 1, respectively). Receiver operating characteristic curve analysis confirmed the score's predictive performance, with an area under the curve of 0.805. The combined sensitivity and specificity (0.655 and 0.821) was highest with a cut-off value of 4 points. Positive and negative predictive values were 79.2% (19/24) and 69.7% (23/33), respectively. This novel predictive scoring system is potentially useful for distinguishing SM bacteremia from PA bacteremia, which would facilitate immediate administration of appropriate antimicrobial therapy.

Universal admission screening for COVID-19 using quantitative antigen testing and questionnaire screening to prevent nosocomial spread.

BACKGROUND: In this study, we investigated diagnostic accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing and whether universal screening was effective to prevent a nosocomial outbreak of coronavirus disease 2019 (COVID-19). METHODS: All adult patients admitted to an acute-care hospital in Tokyo, Japan, after receiving LUMIPULSE SARS-CoV-2 Ag using a nasopharyngeal swab and a brief questionnaire to evaluate symptoms and exposures from December 3, 2020 to March 20, 2021 were included. RESULTS: Of the 5191 patients, 53 were antigen-positive, 19 were inconclusive and 5119 were negative. The sensitivity and specificity (positive or inconclusive results) of the quantitative antigen test for COVID-19 diagnosis at admission was 0.957 (95% confidence interval [CI]: 0.855-0.995) and 0.995 (95% CI: 0.992-0.997), respectively. Six asymptomatic patients were identified on admission. Two patients were antigen-negative and diagnosed with COVID-19 later; however, they had been isolated prior to diagnosis because both had symptoms of COVID-19 and exposure. No nosocomial infections occurred during the period. CONCLUSION: Quantitative SARS-CoV-2 antigen testing was found to be valid for the early detection of asymptomatic COVID-19 patients as a universal screening test on admission.

Safety and Immunogenicity After a Three-Dose SARS-CoV-2 Vaccine Schedule in Allogeneic Stem Cell Transplant Recipients.

In allogeneic stem cell transplant (Allo-SCT) recipients, the cell-mediated and humoral immunogenicity of the 3-dose SARS-CoV-2 vaccination schedule has not been investigated in prospective studies. In a prospective cohort, we recruited 122 Allo-SCT recipients since August 2021, when Ontario began offering a 3-dose vaccine schedule for Allo-SCT recipients. We determined humoral and cell-mediated immunity and adverse effects of the 3-dose SARS-COV-2 vaccination schedule in Allo-SCT recipients. In immunogenicity analysis (n = 95), the median (interquartile range [IQR]) antibody titer against the receptor-binding domain (RBD) of the spike (S) protein after the third dose (10,358.0 U/mL [IQR = 673.9-31,753.0]) was significantly higher than that after the first (10.2 U/mL [IQR = 0.6-37.0]) and the second doses (125.6 U/mL [IQR = 2.8-1251.0]) (P < .0001). The haploidentical donor status was an independent risk factor (adjusted odds ratio = 7.67, 95% confidence interval [CI], 1.86-31.60) for suboptimal antibody response (anti-RBD < 100 U/mL). S-specific CD4+ and CD8+ T-cell responses were measured in a subset of Allo-SCT recipients (n = 20) by flow cytometry. Most developed antigen-specific CD4+ (55%-80%) and CD8+ T-cells (80%) after 2 doses of vaccine. Frequencies of CD4+ polyfunctional (P = .020) and IL-2 monofunctional (P = .013) T-cells significantly increased after the third dose. Twenty-three episodes (23/301 doses [7.6%]) of new-onset or worsening pre-existing graft-versus-host disease (GVHD) occurred, including 4 episodes after the third dose. We observed 4 relapses (3.27%). Seven patients developed SARS-CoV-2 infection despite vaccination, although none required hospitalization. In conclusion, the 3-dose SARS-CoV-2 vaccine schedule provided immunity associated with a low risk of GVHD and other adverse effects. This prospective cohort showed that the third dose of SARS-CoV-2 vaccine in allogeneic stem cell transplant recipients promoted better humoral and cellar immune responses than after the initial series without increasing the risk of GVHD or severe adverse effects.

Factors Associated with Breakthrough Fungemia Caused by Candida, Trichosporon, or Fusarium Species in Patients with Hematological Disorders.

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan. A total of 121 cases of breakthrough fungemia were identified. Of the 121 involved patients, 83, 11, 5, and 22 were receiving micafungin, voriconazole, itraconazole, and liposomal amphotericin B, respectively, when the breakthrough occurred. Of the 121 causative breakthrough fungal strains, 96 were Candida species, and the rest were 13 cases of Trichosporon species, 7 of Fusarium species, 2 of Rhodotorula mucilaginosa, and 1 each of Cryptococcus neoformans, Exophiala dermatitidis, and Magnusiomyces capitatus. The crude 14-day mortality rate of breakthrough fungemia was 36%. Significant independent factors associated with the crude 14-day mortality rate were age of ≥60 years (P = 0.011), chronic renal failure (P = 0.0087), septic shock (P < 0.0001), steroid administration (P = 0.0085), and liposomal amphotericin B breakthrough fungemia (P = 0.0011). An absolute neutrophil count of >500/µL was significantly more common in candidemia in the multivariate analysis (P = 0.0065), neutropenia and nonallogeneic hematopoietic stem cell transplants were significantly more common in Trichosporon fungemia (P = 0.036 and P = 0.033, respectively), and voriconazole breakthrough fungemia and neutropenia were significantly more common in Fusarium fungemia (P = 0.016 and P = 0.016, respectively). The epidemiological and clinical characteristics of breakthrough fungemia of patients with hematological disorders were demonstrated. Some useful factors to predict candidemia, Trichosporon fungemia, and Fusarium fungemia were identified.

Clinical and Microbiological Characteristics of Proven Invasive Aspergillosis Due to Rare/Cryptic Species in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

There are few reports on the clinical course of proven invasive aspergillosis (IA) due to rare/cryptic species in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. We retrospectively reviewed the electronic medical records of patients who underwent allo-HSCT between January 2012 and December 2018. Of 934 allo-HSCT recipients, 10 were diagnosed with proven IA and 61 were diagnosed with probable IA. DNA sequencing was performed in cases of proven IA, and Aspergillus could be identified to the species level in 8 of the 10 cases. Three were due to A. fumigatus, and 5 were due to rare/cryptic Aspergillus species, namely, A. turcosus, A. felis, A. viridinutans, A. nidulans, and A. calidoustus. In these 8 patients, no patients with IA due to A. fumigatus died, whereas 3 of the 5 with IA due to rare/cryptic species died within 12 weeks. The 2 surviving cases of IA due to rare/cryptic species were treated with surgical resection and antifungal treatment. Susceptibility testing for cryptic species in 4 cases showed an amphotericin B MIC > 1 mg/L in 3 cases, itraconazole MIC > 1 mg/L in 2 cases, and voriconazole MIC > 1 mg/L in 2 cases. In conclusion, more than half of the causative pathogens of proven IA were rare/cryptic species, so it is important to accurately identify the Aspergillus species. In addition, surgical treatment might be an important option in cases of proven IA, given the possibility that the causative organisms are azole-resistant A. fumigatus or rare/cryptic species.

Clinical characteristics and drug susceptibility patterns of Corynebacterium species in bacteremic patients with hematological disorders.

The aim of this study was to clarify the clinical and microbiological characteristics of Corynebacterium bacteremia in hematological patients. We retrospectively reviewed the medical records of patients with Corynebacterium bacteremia from April 2013 to June 2018. The causative Corynebacterium species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Drug susceptibility tests were performed using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. In total, 147 cases of Corynebacterium bacteremia were identified during the study period. Corynebacterium striatum was the most frequent pathogen. Catheter-related bloodstream infection was diagnosed in 19.7% of all patients, and moderate/severe oral or severe gastrointestinal mucosal impairment was detected in 19.7%. Polymicrobial infection was found in about 20% of cases, with Enterococcus faecium being the most frequent isolate. The overall 30-day mortality was 34.7% (51/147). Multivariate analysis showed that E. faecium co-infection (odds ratio (OR) 9.3; 95% confidence interval (CI) 2.1-40), systemic corticosteroids (OR 3.6; 95% CI 1.4-8.9), other immunosuppressive drugs (OR 0.32; 95% CI 0.13-0.76), and a Pitt bacteremia score ≥4 (OR 12; 95% CI 3.9-40) were significant risk factors for overall 30-day mortality. The drug susceptibility rates for beta-lactam antimicrobial agents were quite low. All isolates were susceptible to glycopeptides and linezolid. However, some C. striatum isolates were resistant to daptomycin. Corynebacterium bacteremia can occur in the presence of several types of mucosal impairment. Our drug susceptibility data indicate that Corynebacterium bacteremia in hematological patients could be treated by glycopeptides or linezolid.

Stenotrophomonas maltophilia bloodstream infections in adult recipients of umbilical cord blood transplantation.

Limited data are available on Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) and the therapeutic efficacy of trimethoprim-sulfamethoxazole (SXT) against SM-BSI in umbilical cord blood transplant (uCBT) recipients. Medical and microbiological records of adult patients who received uCBTs between December 2008 and December 2015 at Toranomon Hospital (Tokyo, Japan) were reviewed. The efficacy and safety of SXT were evaluated only for recipients who were treated with ≥7 days of intravenous SXT for SM-BSI (evaluation cohort). Of 561 uCBT recipients, 34 developed SM-BSI. Diabetes mellitus (P = .005) and age ≥ 60 years (P = .013) were significant independent risk factors for SM-BSI. Moreover, SM-BSI was identified as an independent risk factor for all-cause mortality up to 100 days following uCBT (P = .025). Of the 34 recipients with SM-BSI, 24 were treated with an intravenous SXT-containing regimen (iSXT-CR). Septic shock (P = .0021), pneumonia (P = .011), neutropenia (P = .0015), and systemic steroid administration (P = .018) were identified as significant independent risk factors for 7-day crude mortality. The evaluation cohort included nine recipients. Doses of SXT were 2.4 to 6.9 mg/kg/day of the trimethoprim component. Of the nine recipients, five developed SM-BSI during the pre-engraftment phase. The 30-day crude-mortality rate and clinical cure rate of the cohort were 22% and 67%, respectively. Only one of the nine recipients experienced significant neutrophil toxicity. In this study, the epidemiology of SM-BSI in uCBT recipients was determined and its negative impact on survival was demonstrated. A low- to moderate-dose iSXT-CR appeared to be a tolerable and important therapeutic option for SM-BSI in the uCBT setting, including during the pre-engraftment phase.

The impact of graft cell source on bloodstream infection in the first 100 days after allogeneic hematopoietic cell transplantation.

Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0-46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40-2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14-2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.

Reverse Transcription Loop-Mediated Isothermal Amplification Assay-Based Infection Control Strategies for COVID-19 in a Hospital Under the State of Emergency in Tokyo, Japan in Spring 2020.

Studies describing reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay-based infection control strategies (LAMP-based ICSs) for coronavirus disease 2019 (COVID-19) are limited. We reviewed the medical records of cases in which RT-LAMP was performed. Standard ICSs and LAMP-based ICSs were implemented during the study period. The strategies were intended to impose longer periods of infection control precautions (ICPs) for specific patients, such as those with a history of exposure to COVID-19 patients and/or bilateral ground glass opacities (bGGO) on chest computed tomography (CT). Of 212 patients, which included 13 confirmed COVID-19 patients in the diagnostic cohort, exposure to COVID-19 patients (P <0.0001) and chest CT bGGO (P = 0.0022) were identified as significant predictors of COVID-19. In the 173 hospitalized patients in which the results of the first RT-LAMP were negative, the duration of ICPs was significantly longer in patients with exposure to COVID-19 and/or a high clinical index of suspicion and patients with bGGO than in the remaining patients (P = 0.00046 and P = 0.0067, respectively). Additionally, no confirmed COVID-19 cases indicating nosocomial spread occurred during the study period. Establishing a comprehensive system that combines rational LAMP-based ICSs with standard ICSs might be useful for preventing nosocomial spread.

Characteristics of gram-negative bacteremia during febrile neutropenia among allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis.

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum ß-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

Safety of bronchoscopy in patients with malignant hematologic disorders.

BACKGROUND: Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. METHODS: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. RESULTS: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09-0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18-25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14-0.73, p = 0.01). CONCLUSIONS: Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient's procedural tolerance and lower complications.

Matrix-assisted laser desorption ionization-time of flight mass spectrometry can be used to identify Helicobacter cinaedi.

We examined the applicability of Matrix-assisted laser desorption ionization-time of flight mass spectrometry using 54 Helicobacter cinaedi isolates from humans. In all 54 isolates, MALDI-TOF MS detected H. cinaedi as the best match organism. Our findings suggest that MALDI TOF-MS can be used effectively to identify H. cinaedi.

Cryptococcal meningitis following umbilical cord blood transplantation, association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients.

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.

Differences in Ocular Complications Between Candida albicans and Non-albicans Candida Infection Analyzed by Epidemiology and a Mouse Ocular Candidiasis Model.

Objectives: Candida species are a major cause of hospital infections, including ocular candidiasis, but few studies have examined the propensities of specific species to invade the eye or the unique immunological responses induced. This study examined the frequency and characteristics of species-specific Candida eye infections by epidemiology and experiments using a mouse ocular candidiasis model. Methods: We reviewed medical records of candidemia patients from January 2012 to March 2017. We also evaluated ocular fungal burden, inflammatory cytokine and chemokine profiles, and inflammatory cell profiles in mice infected with Candida albicans, Candida glabrata, or Candida parapsilosis. Results: During the study period, 20 ocular candidiasis cases were diagnosed among 99 candidemia patients examined by ophthalmologists. Although C. parapsilosis was the most frequent candidemia pathogen, only C. albicans infection was significantly associated with ocular candidiasis by multivariate analysis. In mice, ocular fungal burden and inflammatory mediators were significantly higher during C. albicans infection, and histopathological analysis revealed invading C. albicans surrounded by inflammatory cells. Ocular neutrophil and inflammatory monocyte numbers were significantly greater during C. albicans infection. Conclusion: Candida albicans is strongly associated with ocular candidiasis due to greater capacity for invasion, induction of inflammatory mediators, and recruitment of neutrophils and inflammatory monocytes.

First case of sexually transmitted asymptomatic female genital tuberculosis from spousal epididymal tuberculosis diagnosed by active screening.

Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. This appears to be the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman, detected by active screening for genital tuberculosis and molecular analysis, including whole genome sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis, even when the female partner is asymptomatic.

Clinical and Microbiological Characteristics of Candida guilliermondii and Candida fermentati.

A total of 46 clinical isolates of Candida guilliermondii and Candida famata were reidentified genetically, resulting in 27 C. guilliermondii and 12 Candida fermentati strains. The majority of C. guilliermondii strains, but not C. fermentati strains, were isolated from blood cultures. C. fermentati was more sensitive to antifungals, hydrogen peroxide, and killing by murine macrophages than was C. guilliermondii The C. guilliermondii isolates were echinocandin susceptible in vitro but resistant to micafungin in a murine model of invasive candidiasis.

Micafungin Breakthrough Fungemia in Patients with Hematological Disorders.

Limited data are available on micafungin breakthrough fungemia (MBF), fungemia that develops on administration of micafungin, in patients with hematological disorders. We reviewed medical and microbiological records of patients with hematological disorders who developed MBF between January 2008 and June 2015. A total of 39 patients with MBF were identified, and Candida (30 strains) and non-Candida (9 strains) fungal species were recognized as causative strains. Among 35 stored strains, Candida parapsilosis (14 strains), Trichosporon asahii (7 strains), Candida glabrata (5 strains), and other fungal species (9 strains) were identified by sequencing. Neutropenia was identified as an independent predictor of non-Candida fungemia (P = 0.023). T. asahii was the most common causative strain (7/19) during neutropenia. The 14-day crude mortality rate of patients treated with early micafungin change (EMC) to other antifungal agents was lower than that of the patients not treated with EMC (14% versus 43%, P = 0.044). Most of the stored causative Candida strains were susceptible (80%) or showed wild-type susceptibility (72%) to micafungin. The MICs of voriconazole for T. asahii were low (range, 0.015 to 0.12 µg/ml), whereas the MICs of amphotericin B for T. asahii were high (range, 2 to 4 µg/ml). MBF caused by non-Candida fungus should be considered, especially in patients with neutropenia. EMC could improve early mortality. Based on epidemiology and drug susceptibility profiling, empirical voriconazole-containing therapy might be suitable for treating MBF during neutropenia to cover for T. asahii.