Cost-effectiveness analysis of adult pneumococcal conjugate vaccines for pneumococcal disease in Japan.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is used in the Japanese National Immunization Program for older adults and adults with increased risk for pneumococcal disease, however, disease incidence and associated burden remain high. We evaluated the cost-effectiveness of pneumococcal conjugate vaccines (PCVs) for adults aged 65 years and high-risk adults aged 60-64 years in Japan. RESEARCH DESIGN AND METHODS: Using a Markov model, we evaluated lifetime costs using societal and healthcare payer perspectives and estimated quality-adjusted life-years (QALYs), and number of prevented cases and deaths caused by invasive pneumococcal disease (IPD) and non-IPD. The base case analysis used a societal perspective. RESULTS: In comparison with PPSV23, the 20-valent PCV (PCV20) prevented 127 IPD cases 10,813 non-IPD cases (inpatients: 2,461, outpatients: 8,352) and 226 deaths, and gained more QALYs (+0.0015 per person) with less cost (-JPY22,513 per person). All sensitivity and scenario analyses including a payer perspective analysis indicated that the incremental cost-effectiveness ratios (ICERs) were below the cost-effectiveness threshold value in Japan (JPY5 million/QALY). CONCLUSIONS: PCV20 is both cost saving and more effective than PPSV23 for adults aged 65 years and high-risk adults aged 60-64 years in Japan.

Identification of Familial Infections Using Multilocus Microsatellite Typing in Tinea Corporis due to Microsporum canis.

Microsporum canis is a type of dermatophyte that causes zoonotic dermatophytosis in cats and dogs. We report three cases of tinea corporis due to M. canis from a single household with a domestic cat as a pet. The cases included a woman in her thirties (mother), a girl in her teens (older sister), and a girl in her teens (younger sister). Following sudden hair loss in the domestic cat, annular erythema with pruritus and scales appeared on the face, neck, and limbs of the older sister, younger sister, and mother, sequentially; they subsequently visited our hospital. Potassium hydroxide direct microscopy revealed filamentous fungi on all three women. In addition, short-haired colonies with a white to yellowish-white color and extending in a radial manner were found in cultures using a flat plate agar medium. A slide culture with the same medium indicated pointed spindle-shaped macroconidia with 7-8 septa. Therefore, the cases were diagnosed as tinea corporis due to M. canis. Genetic analysis of the cells of the cat and the mother, older sister, and younger sister using multilocus microsatellite typing (MLMT) indicated that all cases were classified into the same genotype, suggesting that the transmission route of these cases was familial. Here, we show that MLMT is useful in identifying the infection route in cases of tinea corporis due to M. canis.

Micafungin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia following cord blood transplant in a patient with acute myeloid leukemia successfully treated with voriconazole.

Phaeohyphomycosis is caused by dematiaceous (pigmented) fungi. Most phaeohyphomycosis is non-invasive infections, however, they can lead to invasive infections, including fungemia and disseminated disease, particularly in severely immunocompromised patients. Invasive phaeohyphomycosis has recently emerged, however, the treatment strategy was not determined because of the intrinsic resistance to antifungals and the lack of clinical experience. Here, we describe a novel case of echinocandin-breakthrough Coniochaeta hoffmannii (Lecythophora hoffmannii) fungemia after hematopoietic stem cell transplantation, which was identified using matrix-assisted laser desorption ionization time-of-flight mass spectrometry and ribosomal RNA sequencing. The patient was a female in her 40s who had acute myeloid leukemia refractory to chemotherapy before progressing to cord blood transplantation. Before developing fungemia, the patient was administered multiple broad-spectrum antibiotics and micafungin for recurrent infections and prophylaxis. Clinical and microbiological responses to liposomal amphotericin B were poor but improved after replacement to voriconazole and engraftment. A literature review of the previously reported cases with C. hoffmannii human infections imply that disruption of the cutaneous/mucosal barrier and the use of antimicrobial agents, both antibiotics and antifungals, could incite C. hoffmannii invasive infections.

Pulmonary Coccidioidomycosis Complicated by Nontuberculous Mycobacterial Pulmonary Diseases with a Literature Review.

Following an endobronchial examination, a young mine supervisor was treated with antibiotics for a pulmonary nontuberculous mycobacterial infection for approximately one year. However, a review of the radiological findings revealed a different possibility. Accordingly, pulmonary resection was performed, and histopathological analysis revealed numerous yeast-like fungi. Since the patient had stayed in the southwestern United States for two months in 2009, eight years previously, coccidioidomycosis was strongly suspected. The diagnosis of coccidioidomycosis was subsequently confirmed by serology and polymerase chain reaction testing of the excised specimen. Here, we report an educational case that emphasizes the importance of meticulous medical history-taking and awareness of endemic mycoses in other countries in the context of globalization.

In vitro and in vivo pharmacological profile of OPC-61815, a water-soluble phosphate ester pro-drug of tolvaptan.

Tolvaptan is an orally active vasopressin V2 receptor antagonist and used for the treatment of volume overload in some disease as an aquaretic. Tolvaptan sodium phosphate (OPC-61815) is a pro-drug of tolvaptan that was designed to improve water solubility and enable intravenous use. The conversion of OPC-61815 to tolvaptan was evaluated for in vitro and in vivo pharmacokinetic studies. The pharmacodynamics of OPC-61815 were evaluated for in vitro receptor binding affinity, in vivo aquaretic and anti-edematous action. The solubility of OPC-61815 in water at 25 °C was 72.4 mg/mL and more than 100,000 times the solubility of tolvaptan. OPC-61815 was hydrolyzed to tolvaptan by human tissue S9 fractions and main enzyme of hydrolysis was alkaline phosphatase. After intravenous administration of OPC-61815 to rats and dogs, tolvaptan was detected in plasma within 5 min and the bioavailability of tolvaptan was 57.7% and 50.9%, respectively. Binding affinity of OPC-61815 for the human V2 receptor was 1/14 weaker than that of tolvaptan. OPC-61815 exerted dose-dependent aquaretic action in rats and dogs and a corresponding anti-edematous action in rat edema models. These results suggest that OPC-61815, a water-soluble phosphate ester pro-drug of tolvaptan, is an effective aquaretic by converting to tolvaptan after intravenous administration.

Diversity of amino acid substitutions of penicillin-binding proteins in penicillin-non-susceptible and non-vaccine type Streptococcus pneumoniae.

PURPOSE: In Japan, the introduction of pneumococcal conjugate vaccine (PCV) in children has decreased vaccine-type (VT) pneumococcal infections caused by penicillin (PEN)-non-susceptible Streptococcus pneumoniae. PEN-non-susceptible strains have gradually emerged among non-vaccine types (NVT). In this study, we aim to investigate the pbp gene mutations and the characteristics of PEN-binding proteins (PBPs) that mediate PEN resistance in NVT strains. MATERIALS AND METHODS: Pneumococcal 41 strains of NVT isolated from patients with invasive pneumococcal infection were randomly selected. Nucleotide sequences for pbp genes encoding PBP1A, PBP2X, and PBP2B were analyzed, and amino acid (AA) substitutions that contribute to ß-lactam resistance were identified. In addition, the three-dimensional (3D) structure of abnormal PBPs in the resistant strain was compared with that of a reference R6 strain via homology modeling. RESULTS: In PEN-non-susceptible NVT strains, Thr to Ala or Ser substitutions in the conserved AA motif (STMK) were important in PBP1A and PBP2X. In PBP2B, substitutions from Thr to Ala, adjacent to the SSN motif, and from Glu to Gly were essential. The 3D structure modeling indicated that AA substitutions are characterized by accumulation around the enzymatic active pocket in PBPs. Many AA substitutions detected throughout the PBP domains were not associated with resistance, except for AA substitutions in or adjacent to AA motifs. Clonal complexes and sequence types showed that almost all NVT cases originated in other countries and spread to Japan via repeat mutations. CONCLUSIONS: NVT with diverse AA substitutions increased gradually with pressure from both antimicrobial agents and vaccines.

In Vitro Activity and Clinical Efficacy of Faropenem against Third-Generation Cephalosporin-Resistant Escherichia coli and Klebsiella pneumoniae.

Faropenem (FRPM) is active against extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales, but evidence for its efficacy is lacking. This study determined the correlation between the susceptibility by disk diffusion method and the MIC of FRPM for third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, and the effectiveness of FRPM for the treatment of urinary tract infection (UTI) caused by these two bacteria in a retrospective cohort analysis. Of the 48 third-generation cephalosporin-resistant clinical isolates tested, 44 isolates produced ESBL, and 8 isolates produced AmpC, including 4 isolates produced both ESBL and AmpC. Thirty-seven isolates had an FRPM MIC of ≤1 mg/L, and seven had an FRPM MIC of 2 mg/L. An FRPM MIC of >2 mg/L was observed with four isolates. In a retrospective cohort analysis, 63 patients with UTI treated with FRPM were identified. All isolates of ESBL-producing E. coli (n = 54) and K. pneumoniae (n = 9) treated with FRPM showed disk diffusion zone diameters larger than 16.0 mm (estimated MIC, 2.2 mg/L). All patients completed the scheduled treatment courses with FRPM, but 28- and 90-day relapses happened in 10 patients (16%) and 16 patients (25%), respectively. No significant risk factors for the 28- and 90-day relapses were found. FRPM can be used according to disk diffusion susceptibility testing in UTI. Further investigations are necessary to assess the clinical breakpoint of FRPM for ESBL-producing Enterobacterales and the candidates most likely to benefit from using FRPM.

Exhibition of antifungal resistance by sterol-auxotrophic strains of Candida glabrata with intact virulence.

Background: Candida glabrata is an emerging fungal pathogen in immune-compromised hosts. Previously undetected C. glabrata isolates were successfully recovered from clinical specimens by adding sterols to the growth medium. The clinical isolates are unable to synthesize ergosterol but can take up exogenous sterols under aerobic conditions. Objectives: This study characterizes the sterol-auxotrophic C. glabrata strains, examines the mutation(s) in sterol synthesis genes, characterizes the drug susceptibility and evaluates the virulence in a mouse infection model. Methods: Drug susceptibility of the C. glabrata strains was evaluated in a sterol-supplemented medium. The coding sequences of the sterol synthesis genes were analysed in six sterol-auxotrophic strains of C. glabrata. The fungal burden of mice infected with C. glabrata strain was determined. Results: The sterol-auxotrophic strains showed high-level resistance to both azoles and amphotericin B when sterols were supplied in the test medium. Additionally, the strains harbour missense mutations in either ERG1 or ERG7. Significant differences in fungal burden were not observed between the sterol-auxotrophic strain and the sterol-competent strain with the mice infection models. Conclusions: The sterol-auxotrophic C. glabrata strain investigated in this study seemed to maintain intact virulence, probably due to the supply of exogenous sterols from host organ(s). This suggests that exogenous sterol uptake develops antifungal resistance during infection.

Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report.

BACKGROUND: Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals. CASE PRESENTATION: We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period. CONCLUSIONS: Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus.

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.

Comparative characteristics of the background and blood test findings in adults with pneumococcal pneumonia and invasive pneumococcal disease: A retrospective study.

INTRODUCTION: Invasive pneumococcal disease (IPD) is often fatal, requiring prompt diagnosis and treatment. To evaluate the factors associated with IPD in adults, we retrospectively investigated its characteristics compared to pneumococcal pneumonia without confirmation of invasion (PP). METHODS: Patients >18 years with PP (n = 79) and IPD (n = 53) from whom Streptococcus pneumoniae was isolated were enrolled from two hospitals between 2011 and 2017. Clinical backgrounds, blood test results at admission, initial antimicrobials administered, isolate serotypes, and outcomes were compared between the PP and IPD groups. RESULTS: Patients with IPD exhibited higher mortality (28.3%) than those with PP (2.5%) (p<0.001), regardless of the type of antimicrobials first administered. The majority (80.0%) of fatal cases of IPD were due to vaccine serotypes. Almost all patients with PP (97.4%) and IPD (88.7%) had underlying disease. C-reactive protein (CRP) ≥17.0 mg/dL (odds ratio [OR], 7.1; 95% CI, 2.7-19.0; p<0.001), white blood cell counts <11.0 × 103/µL (OR, 3.2; 95% CI, 1.3-8.4; p = 0.016), and platelet (PLT) counts <16.2 × 104/µL (OR, 2.8; 95% CI, 1.1-7.4; p = 0.036) were significantly more common in IPD. Moreover, 89.5% of cases with both CRP ≥23.8 mg/dL and PLT <18.5 × 104/µL were diagnosed with IPD. CONCLUSION: Laboratory blood test findings at admission, particularly high CRP and low PLT values, are useful early indicators of IPD in adults. These results could be used to initiate rapid and intensive treatment and improve prognosis.

RSV infection-elicited high MMP-12-producing macrophages exacerbate allergic airway inflammation with neutrophil infiltration.

Respiratory syncytial virus (RSV) infection often exacerbates bronchial asthma, but there is no licensed RSV vaccine or specific treatments. Here we show that RSV-induced alveolar macrophages, which produce high levels of matrix metalloproteinase-12 (MMP-12), exacerbate allergic airway inflammation with increased neutrophil infiltration. When mice subjected to allergic airway inflammation via exposure to the house dust mite antigen (HDM) were infected with RSV (HDM/RSV), MMP-12 expression, viral load, neutrophil infiltration, and airway hyperresponsiveness (AHR) were increased compared to those in the HDM and RSV groups. These exacerbations in the HDM/RSV group were attenuated in MMP-12-deficient mice and mice treated with MMP408, a selective MMP-12 inhibitor, but not in mice treated with dexamethasone. Finally, M2-like macrophages produced MMP-12, and its production was promoted by increase of IFN-ß-induced IL-4 receptor expression with RSV infection. Thus, targeting MMP-12 represents a potentially novel therapeutic strategy for the exacerbation of asthma.

The Efficacy of Phage Therapy in a Murine Model of Pseudomonas aeruginosa Pneumonia and Sepsis.

The emergence of multi-drug resistant Pseudomonas aeruginosa necessitates the search for treatment options other than antibiotic use. The use of bacteriophages is currently being considered as an alternative to antibiotics for the treatment of bacterial infections. A number of bacteriophages were introduced to treat pneumonia in past reports. However, there are still lack of knowledge regarding the dosages, application time, mechanism and safety of phage therapy against P. aeruginosa pneumonia. We used the bacteriophage KPP10 against P. aeruginosa strain D4-induced pneumonia mouse models and observed their outcomes in comparison to control models. We found that the nasal inhalation of highly concentrated KPP10 (MOI = 80) significantly improved survival rate in pneumonia models (P < 0.01). The number of viable bacteria in both lungs and in serum were significantly decreased (P < 0.01) in phage-treated mice in comparison to the control mice. Pathological examination showed that phage-treated group had significantly reduced bleeding, inflammatory cell infiltration, and mucus secretion in lung interstitium. We also measured inflammatory cytokine levels in the serum and lung homogenates of mice. In phage-treated models, serum TNFα, IL-1ß, and IFN-γ levels were significantly lower (P < 0.05, P < 0.01, and P < 0.05, respectively) than those in the control models. In the lung homogenate, the mean IL-1ß level in phage-treated models was significantly lower (P < 0.05) than that of the control group. We confirmed the presence of phage in blood and lungs, and evaluated the safety of bacteriophage use in living models since bacteriophage mediated bacterial lysis arise concern of endotoxic shock. The study results suggest that phage therapy can potentially be used in treating lung infections caused by Pseudomonas aeruginosa.

Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants.

Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1-10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.

Elevation of HHV-6 viral load mimicking HHV-6 reactivation after second umbilical cord blood transplantation in chromosomally integrated human herpesvirus-6.

Human herpesvirus-6 (HHV-6) reactivation is an important complication in patients receiving umbilical cord blood transplantation (CBT). Chromosomally integrated human herpesvirus-6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germline genome and is transmitted in a Mendelian manner. The influence of ciHHV-6 in recipients or donors in cases of CBT is unknown. We report the first case with ciHHV-6 that received CBT twice for acute lymphoblastic T-cell leukemia. HHV-6 DNA in peripheral blood leukocytes (PBLs) was examined over time through two CBTs. After the first CBT, the HHV-6 viral load was significantly reduced by conversion to PBLs derived from the first donor. During the second CBT, an increase in HHV-6 DNA in PBLs and plasma were observed. However, HHV-6 mRNA was not detected in either the sample before 2nd CBT or at the time of HHV-6 DNA elevation. It is considered that the HHV-6 DNA detected in PBLs and plasma samples might be the HHV-6 genome released due to tissue damage. This case suggests that physicians should be aware of HHV-6 DNA variability during allogeneic hematopoietic stem cell transplantation in ciHHV-6 patients.

Morphological and genetic identification of fungal genus/species in formalin-fixed, paraffin-embedded specimens obtained from patients with histologically proven fungal infection.

BACKGROUND: Although fungi are found relatively easily by microscopic examination of pathological samples, identification of fungal genus and species in pathological samples is not easy because the morphological features of fungi are similar among genera and species. OBJECTIVES: A multiple real-time PCR was developed for identification of fungal genus/species, and morphological characterizations of fungi were analysed in pathological samples. PATIENTS/METHODS: Seventy-five formalin-fixed paraffin-embedded (FFPE) samples morphologically proven to contain any fungus were examined. A multiple real-time PCR system was developed to identify 25 fungal genus/species in pathological samples. Morphology of fungus in the specimens was re-reviewed retrospectively based on the results of real-time PCR. RESULTS: Real-time PCR identified fungal genus/species in 56 of 75 (74.6%) specimens with histologically proven fungal infection. In 53 specimens of filamentous fungi, Aspergillus spp. (22 specimens), Cladosporium (8), Scedosporium apiospermum (4), Malassezia sympodialis (1) and Candida albicans (1) were identified. Pseudohyphae of Candida were confused with filamentous fungus in a case. Morphological observation suggested differences in the presence of septated or non-septated hyphae, the filament size, and the branch angle among genus/species of filamentous fungi; however, genus/species was not able to be determined by their morphological features. In 22 specimens of yeasts, real-time PCR allowed for the identification of Candida albicans (12 specimens), Candida glabrata (2), Cladosporium (2), Scedosporium apiospermum (2), Pichia kudriavzevii (1) and Aspergillus sydowii (1). CONCLUSIONS: These data suggest that it is difficult to identify fungal genus/species by morphological features alone. Real-time PCR is useful to identify fungal genus/species in pathological samples.

[Disseminated aspergillosis due to Aspergillus udagawae during immunosuppressive treatment for myelodysplastic syndrome].

An 80 year old male who had received immunosuppressive therapy for myelodysplastic syndrome presented with fever, fatigue, and elevated serum Aspergillus antigen. Computed tomography revealed infiltrative shadows in the left lower lung and subcutaneous nodules. A polymerase chain reaction assay from lung and subcutaneous nodule samples identified the presence Aspergillus udagawae. A. udagawae is a cryptic species that shares similar morphological characteristics with A. fumigatus but genetically differs from the latter in its susceptibility to antifungal drugs. When immunosuppressed patients with hematological malignancies develop disseminated aspergillosis, biopsy and fungal tests are crucial to identify the causative fungus, including cryptic species, for deciding the appropriate therapeutic intervention.

Usefulness of a newly developed high-speed polymerase chain reaction analysis system for the diagnosis of Clostridioides difficile infection.

INTRODUCTION: The incidence of Clostridioides difficile infection (CDI) has been continuously increasing and thereby became an important issue worldwide. Appropriate diagnosis, management, and infection control are required for patients with CDI. Enzyme immunoassay (EIA) is a widely used standard diagnostic tool for C. difficile-specific glutamate dehydrogenase (GDH) and C. difficile toxins (toxins A and B). However, the sensitivity of EIA in detecting C. difficile toxins has been reported to be relatively low, resulting in CDI underdiagnosis. Therefore, nucleic acid amplification tests (NAAT) are recently developed for higher sensitivity/specificity test. METHODS: In this study, a total of 279 stool samples submitted for CDI diagnosis were examined using an independently developed new high-speed polymerase chain reaction (PCR) device (PathOC RightGene, Metaboscreen). In parallel, results were compared with those of definitive diagnosis and conventional diagnostic methods (EIA, real-time PCR) to assess the inspection accuracy. RESULTS: PathOC RightGene showed high sensitivity (96.7%) and specificity (96.7%). Regarding the measurement time, C. difficile-specific and C. difficile toxin genes were simultaneously detected in approximately 25 min for one sample (including the preprocessing and measurement time). CONCLUSION: PathOC RightGene has been found to show both excellent sensitivity and rapidity and thus can be used for the reliable and early diagnosis, which are needed for the appropriate management of CDI.

Hypertrophic pachymeningitis caused by Schizophyllum sp.: a novel case report.

BACKGROUND: The pathogenic fungus Schizophyllum sp. can cause allergic fungal rhinosinusitis and allergic bronchopulmonary mycosis in humans. Sinus and lung infections due to Schizophyllum sp. have been reported globally; however, no case of hypertrophic pachymeningitis due to this pathogen has been reported yet. Herein, we describe for the first time, a case of hypertrophic pachymeningitis due to Schizophyllum sp. CASE PRESENTATION: A 69-year-old woman visited the hospital with chief complaints of headache, right trigeminal neuralgia (third branch), ataxic gait, and deafness in the right ear. Magnetic resonance imaging revealed a tumor in the right sphenoidal sinus and thickening of the dura mater surrounding the right porus acusticus internus. Endoscopic sinus surgery and neuroendoscopic biopsy were performed to remove sinus lesions and intracranial lesions, respectively. Both pathological specimens showed findings indicative of filamentous fungi on Grocott's staining. DNA sequencing with the sinus specimen revealed Schizophyllum sp. as the causative pathogen, consistent with the diagnosis of fungal sinusitis and hypertrophic pachymeningitis. Intravenous liposomal amphotericin B was started, but owing to lack of improvement, the treatment was switched to intravenous voriconazole. We observed improvements in both radiological findings and symptoms. However, the symptoms exacerbated again when the trough level of voriconazole decreased. Upon increasing the voriconazole dose, a higher trough level was obtained and the symptoms improved. CONCLUSION: Our study suggests that when symptoms of central nervous system infection due to Schizophyllum sp. do not improve with liposomal amphotericin B, voriconazole can be administered at high trough levels to improve the symptoms.