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Background: Azithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory properties. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently administered before specific treatments were developed. However, the efficacy of this treatment has not been verified. We retrospectively investigated the effects of its intravenous (IV) administration in patients with severe/critical COVID-19 using the National Administrative Database of Japan during the first wave (February-April 2020)., Methods: Patients were categorized based on whether they received IV azithromycin within three days of hospitalization. An overlap weighting method with estimated propensity scores was used to reduce bias., Results: Among the 830 patients with severe/critical COVID-19, 148 (17.8 %) received azithromycin, and 682 (82.2 %) did not. After adjustment, the use of azithromycin was associated with a shorter duration of intensive care unit (ICU) management (-3.48 days, 95 % confidence interval [CI]: 4.59 to -2.38). However, other endpoints, including mortality rate, duration of mechanical ventilation, and duration of hospital stay, did not suggest any associations. Furthermore, of the 115 ICU patients, 27 (23.5 %) were treated with IV azithromycin and 88 (76.5 %) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95 % CI: 0.22 to 0.92), 30-day mortality (OR, 0.46, 95 % CI: 0.22 to 0.94), and a shorter duration of ICU management (-2.94 days, 95 % CI: 5.15 to -0.73)., Conclusion: We verified that IV azithromycin was associated with favorable impact in patients with COVID-19 requiring ICU management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hiroshi Mukae reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. Koichi Izumikawa reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. Takahiro Takazono reports a relationship with Pfizer Japan Inc that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: The diagnostic tools of nucleic acid amplification tests and antigen tests have been extensively employed for the detection of Coronavirus disease 2019 (COVID-19). Although the reverse-transcriptase polymerase chain reaction (RT)-PCR test has high sensitivity and specificity, it is a time-consuming and labor-intensive process. On the other hand, antigen tests are simple and prompt, however, their low sensitivity and potential for false positives have been identified as limitations. In light of these factors, the development of novel tests that combine speed and clinical dependability is a promising prospect., Methods: Surface plasmon field-enhanced fluorescence spectroscopy (SPFS) excites chromophores by means of an enhanced electromagnetic field induced on a gold film surface. It enables the highly sensitive measurement of biomarkers in a short and simple 20-min window. In this study, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) SPFS-based antigen test targeting the SARS-CoV-2 nucleocapsid protein was performed and evaluated in 25 patients with COVID-19 and 10 non-infected controls., Results: A positive correlation was observed between antigen levels determined by SPFS and RNA levels determined via RT-PCR. The sensitivity values were 100 %, 92 %, and 62.5 %; and the specificity values were 100 %, 90 %, and 100 %; for nasopharyngeal swabs, nasal swabs, and saliva specimens when the cutoff values were set to 65.1, 0.2, and 1.5 pg/mL, respectively. No clinically problematic cross-reactivity with analogous coronaviruses was observed., Conclusions: The SARS-CoV-2 SPFS antigen test showed excellent clinical diagnostic accuracy for nasopharyngeal and nasal swabs, with a rapid turnaround., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP., Methods: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis., Result: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed., Conclusion: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications., Competing Interests: Declaration of competing interest Hiroshi Mukae received lecture honoraria and research grants from KYORIN Pharmaceutical Co., Ltd. Outside of the submitted work., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Cryobiopsy use is anticipated to become more common in diagnosing lung diseases. In Japan, inserting a Fogarty catheter through a suction channel above the endotracheal tube's cuff for hemostasis is common practice. However, the rigid nature of the endotracheal tube poses challenges to tracheal intubation using a bronchoscope. The endotracheal tube cuff must be removed to prevent interference during Fogarty catheter insertion. To simplify the procedure and enhance safety, we devised and implemented a method of inserting a hemostatic Fogarty catheter with a suction tube externally attached to a softer endotracheal tube. This study aimed to evaluate the sustainability of this Fogarty catheter insertion method using suction tubes., Methods: The hemostatic Fogarty catheter insertion method was retrospectively validated. We compared outcomes between 60 patients who underwent the conventional method with a suction channel above the cuff and 50 patients who underwent the novel approach with an externally attached suction tube., Results: The physicians performing bronchoscopy and inserting the Fogarty catheter in the group in which the suction tube was externally attached for Fogarty catheter insertion had little experience. However, the overall bronchoscopy time was shorter; the two groups showed no significant differences in complications., Conclusion: Regarding cryobiopsy procedures, using an externally attached suction tube for Fogarty catheter insertion was practical and comparable to the conventional method of using a suction channel above the cuff. This method made the procedure more simple and safe., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Author. Published by Elsevier B.V. All rights reserved.)

Background: No comprehensive analysis of the pulmonary sequelae of coronavirus disease 2019 (COVID-19) in Japan based on respiratory function tests and chest computed tomography (CT) has been reported. We evaluated post-COVID-19 conditions, especially focusing on pulmonary sequelae assessed by pulmonary function tests and chest CT., Methods: For this prospective cohort study, we enrolled 1069 patients who presented pneumonia at the time of admission in 55 hospitals from February 2020 to September 2021. Disease severity was classified as moderateⅠ, moderate II, and severe, defined primarily according to the degree of respiratory failure. The data on post-COVID-19 conditions over 12 months, pulmonary function, and chest CT findings at 3 months were evaluated in this study. Additionally, the impact of COVID-19 severity on pulmonary sequelae, such as impaired diffusion capacity, restrictive pattern, and CT abnormalities, was also evaluated., Results: The most frequently reported post-COVID-19 conditions at 3 months after COVID-19 were muscle weakness, dyspnea, and fatigue (48.4%, 29.0%, and 24.7%, respectively). The frequency of symptoms gradually decreased over subsequent months. In pulmonary function tests at 3 months, the incidence of impaired diffusion capacity and restrictive pattern increased depending on disease severity. There also were differences in the presence of chest CT abnormalities at the 3 months, which was markedly correlated with the severity., Conclusion: We reported a comprehensive analysis of post-COVID-19 condition, pulmonary function, and chest CT abnormalities in Japanese patients with COVID-19. The findings of this study will serve as valuable reference data for future post-COVID-19 condition research in Japan., Competing Interests: Declaration of Competing interest The authors have no conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Evidence regarding the association of the usage of biologic agents (Etanercept, Tocilizumab, adalimumab and so on), such as anti-tumor necrosis factor α, with the incidence and risk factors of non-tuberculous Mycobacteria (NTM) infection is limited. Therefore, this study aimed to investigate the incidence and risk factors of NTM and their associations with biologic agents' usage, and also investigated the potential of Mycobacterium avium complex (MAC) antibodies as a predictor of NTM infection development., Methods: This retrospective study included 672 patients with autoimmune diseases from four hospitals in Nagasaki, Japan, from January 1, 2011, to June 30, 2019, who fulfilled the inclusion criteria., Results: Of the 672 patients, 9 (1.3%) developed complicated NTM infection, including two with disseminated infection, after the introduction of biologic agents. Of the nine patients, two died due to NTM infection but none tested positive for MAC antibodies prior to initiation of biologic agents. The mortality rate was higher in patients complicated with NTM than without NTM (22.2% vs 2.6%, P = 0.024). The corticosteroids dosage at the time of initiating the biologic agents was significantly higher in the NTM group than in the non-NTM group (median, 17 mg vs 3 mg, P = 0.0038)., Conclusion: In the patients undergoing therapy with biologic agents, although NTM complication was rare, it could be fatal. In particular, for patients on a relatively high dose corticosteroids, careful observation is essential for identifying NTM complication, even if the MAC antibody test is negative., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Introduction: Sequential vaccination with the 13-valent pneumococcal protein conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for patients undergoing hemodialysis; however, evidence for the efficacy of these pneumococcal vaccines for patients undergoing hemodialysis is limited to a single dose. We aimed to evaluate the prognosis of patients undergoing hemodialysis who received vaccination with PPSV23 alone versus sequential vaccination with PCV13 and PPSV23., Methods: Patients undergoing hemodialysis who were vaccinated with PPSV23 alone (PPSV23 group) or PCV13 followed by PPSV23 (PCV13+PPSV23 group) between 2014 and 2016 were included; the observation period was three years from the first injection. Patients who underwent hemodialysis between 2011 and 2012 were included as controls. After propensity score matching using age, sex, dialysis vintage, diabetes history, pneumonia history, and serum albumin and creatinine levels, survival analysis was performed., Results: The study included 89, 71, and 319 patients in the PPSV23, PCV13+PPSV23, and control groups, respectively. After propensity score matching, the PPSV23 and control group 1 (79 patients each) and the PCV13+PPSV23 and control group 2 (61 patients each) were compared. Significant differences were observed in the survival rate between the PPSV23 group and control group 1 (p = 0.005) but not between the PCV13+PPSV23 group and control group 2. Pneumonia-related mortality in the two vaccinated groups did not differ significantly during the observation period., Conclusions: Patients who received PPSV23 had a favorable prognosis; however, no positive effect was demonstrated in the PCV13+PPSV23 group., Competing Interests: Declaration of interest The authors declare no competing interests., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: Isavuconazole is a convenient triazole antifungal agent with a broad antifungal spectrum. A randomized, open-label study (ClinicalTrials.gov, NCT03471988) was conducted to evaluate the efficacy and safety of isavuconazole in Japanese patients with deep-seated mycoses., Patients and Methods: In Cohort A, patients with aspergillosis (chronic pulmonary aspergillosis and invasive aspergillosis) were randomized in a 2:1 ratio to isavuconazole or voriconazole, and in Cohort B, patients with cryptococcosis and mucormycosis were assigned to isavuconazole for up to 84 days of treatment. The overall outcome was evaluated according to the clinical, radiological, and mycological responses at Days 42 and 84 and at the end of treatment (EOT)., Results: A total of 103 participants were enrolled and received the study drug. The overall response rate of patients with chronic pulmonary aspergillosis in the isavuconazole (52 patients) and voriconazole (27 patients) groups was 82.7% and 77.8% at EOT, respectively. The response rate in patients with cryptococcosis (10 patients, isavuconazole group only) was 90.0%. One of three participants with invasive aspergillosis and one of three participants with mucormycosis responded in the isavuconazole group. In the safety evaluation, the incidence of adverse events in participants with chronic pulmonary aspergillosis was similar in both groups. Adverse drug reactions were reported in 32 (61.5%) patients receiving isavuconazole and 23 (85.2%) patients receiving voriconazole., Conclusions: Isavuconazole showed efficacy and safety in Japanese patients with chronic pulmonary aspergillosis and cryptococcosis, for which the drug is not currently indicated., Competing Interests: Declaration of competing interest K.I. has received financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants, consulting fees, and honoraria from Asahi Kasei Pharma Corporation, and honoraria from Pfizer, outside the submitted work. T.T. has received non-financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants from MSD, Sumitomo Dainippon Pharma, Takeda Pharmaceutical, and Shionogi Pharma; honoraria from Sumitomo Dainippon Pharma, Pfizer, Kyorin Pharmaceutical, Fisher & Paykel Healthcare, and MSD; and participated on the advisory boards of GlaxoSmithKline, Roche Diagnostics, and Pfizer, outside the submitted work. T.M. has received non-financial support for the present manuscript from Asahi Kasei Pharma Corporation; grants from Asahi Kasei Pharma Corporation, Pfizer, MSD, Astellas Pharma, Otsuka Pharmaceutical, Taisho Pharmaceutical, Daiichi Sankyo, Teijin Pharma, Mitsubishi Tanabe Pharma, Shionogi Pharma, Kyowa Kirin, Chugai Pharmaceutical, and AbbVie; consulting fees from Asahi Kasei Pharma Corporation, Pfizer, and Kyorin Pharmaceutical; honoraria and support for attending meetings from Asahi Kasei Pharma Corporation, Pfizer, MSD, Astellas Pharma, Sumitomo Dainippon Pharma, Janssen Pharmaceutical, AstraZeneca, GlaxoSmithKline, Taisho Pharmaceutical, Daiichi Sankyo, Meiji Seika Pharma, Eli Lilly, Novartis Pharma, Boehringer Ingelheim, Shionogi Pharma, Takeda Pharmaceutical, Gilead Sciences, Insmed, and Sanofi; and drugs and medical writing services from Pfizer and MSD, outside the submitted work. K.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; K.K. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and MSD, outside the submitted work. K.A. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and Takeda Pharmaceutical, and honoraria from Pfizer and Janssen Pharmaceutical, outside the submitted work. H.M. has received consulting fees and honoraria from Asahi Kasei Pharma Corporation, outside the submitted work. F.O. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; F.O. has received consulting fees from Asahi Kasei Pharma Corporation, outside the submitted work. Y.K. has received grants from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, and Pfizer, and honoraria from Asahi Kasei Pharma Corporation, Sumitomo Dainippon Pharma, Pfizer, MSD, Astellas Pharma, and Janssen Pharmaceutical, outside the submitted work. H.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; H.K. has received honoraria from MSD, Sumitomo Dainippon Pharma, Astellas Pharma, Pfizer, and Shionogi Pharma, outside the submitted work. S.K. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; S.K. has received consulting fees from Asahi Kasei Pharma Corporation, and honoraria from MSD, Sumitomo Dainippon Pharma, Pfizer, Bristol-Myers Squibb, Eisai, Takeda Pharmaceutical, Janssen Pharmaceutical, Meiji Seika Pharma, Astellas Pharma, Kyowa Kirin, Chugai Pharmaceutical, Ono Pharmaceutical, Nippon Kayaku, SymBio Pharmaceuticals, and Nippon Shinyaku, outside the submitted work. M.K. is an employee and stockholder of Asahi Kasei Pharma Corporation; M.K. also has patent 2021-157676 pending with Asahi Kasei Pharma Corporation. M.M. is an employee of Asahi Kasei Pharma Corporation; M.M. also has patent 2021-157676 pending with Asahi Kasei Pharma Corporation. Y.N. was a member of the Data Review Committee for Asahi Kasei Pharma Corporation during the conduct of the study; Y.N. has received consulting fees from Asahi Kasei Pharma Corporation, outside the submitted work. All other authors: none to declare., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza., Methods: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted., Results: Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors., Conclusions: Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989)., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Lemierre's syndrome is a serious disease that typically causes oropharyngeal infection with internal jugular vein thrombosis, followed by distant infection focus, such as septic pulmonary embolism. The main causative organisms are anaerobic bacteria in the oral cavity, namely Fusobacterium necrophorum. We encountered an extremely rare case of Lemierre's syndrome, where double vision was found to be the first symptom. The patient's blood culture results showed the presence of F. nucleatum, which spread from the sphenoid sinus to the skull base because of chronic sinusitis; the patient presented with longus colli abscess, clivus osteomyelitis, venous thrombosis, and hematogenous infection. Antibiotic treatment with sulbactam/ampicillin was continued for 14 weeks, and no recurrence has been observed so far. Lemierre's syndrome can be complicated with atypical symptoms such as double vision if the cranial nerves are involved. It might be important to consider this disease in the differential diagnosis in the presence of cranial nerve symptoms of unknown origin with fever or inflammatory findings., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This study aimed to clarify the involvement of anaerobes in aspiration pneumonia by measuring volatile sulfur compounds (VSCs), which are metabolites of anaerobic bacteria in the mouth., Methods: This study included 84 older adult patients (mean age, 82.5 ± 7.34 years) who had dementia and were hospitalized for more than 6 months. We measured the VSCs in the patient's mouth with Oral Chroma and obtained the data of pneumonia development in the past 6 months. We also evaluated the association or correlation of VSCs and some factors which might be the risk factors of aspiration pneumonia., Results: The development of pneumonia had no significant association with the VSCs in the patient's mouth., Conclusion: The present pilot study suggests that anaerobes might not be the main causative pathogens of aspiration pneumonia in older adult patients., Competing Interests: Conflict of Interest The authors declare no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

An internet questionnaire survey for investigating empirical antibiotic usage and bacterial superinfections in patients with coronavirus disease-2019 (COVID-19) in Japan was conducted among the chief physicians of respiratory disease departments of 715 Japanese Respiratory Society-certified hospitals using Google Forms between January 28, 2021 and February 28, 2021. Responses to the questionnaire survey were obtained from 198 of 715 hospitals (27.6%). The survey revealed that the complication incidences of community-acquired pneumonia; hospital-acquired pneumonia, including ventilator-associated pneumonia; and sepsis were 2.86, 5.59, and 0.99%, respectively, among patients with moderate/severe and critical COVID-19. Bacterial co-infection and secondary infection rarely affected patients with COVID-19 in Japan, and the isolated pathogens were not specific to these patients. Moreover, the anti-inflammatory effects of macrolides for COVID-19 were not observed in several studies. These results might be useful in clinical practice for COVID-19., Competing Interests: Conflict of Interest H·K received honoraria from MSD Co., Ltd., Astellas Pharma Inc., Pfizer Inc., Asahi Kasei Pharma Corporation, Shionogi Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd. The other authors have no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly., Methods: Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured., Results: A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p < 0.00001). All three IGRAs exhibited the same specificity (100%), as assessed using blood samples from healthy, low TB-risk individuals (n = 118; median age: 39, IQR; 32-47 years). Positivity in 43 active TB patients with CD4 T-cell counts <200/μL, 39 of whom were ≥80 years of age, was as follows: QFT-Plus, 83.7%; QFT-GIT, 74.4%; and T-SPOT, 58.1%. The difference between TB2-TB1 of the QFT-Plus assay was statistically correlated with CD8 but not CD4 T-cell counts in blood (r = 0.193, p = 0.0298)., Conclusions: QFT-Plus showed high performance in the detection of TB infection in patients irrespective of their advanced age (≥80 years) or lower CD4 counts. QFT-Plus can be useful for the diagnosis of TB infection in all patients, including those who are elderly and/or immunocompromised., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD., Methods: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients., Results: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis., Conclusion: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Polymerase chain reaction (PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is necessary for confirming a diagnosis of Coronavirus disease 2019 (COVID-19). Here we present a COVID-19 case of an elderly woman whose SARS-CoV-2 PCR tests showed false negative repeatedly by evaluating with different sampling sites and procedures. Nasopharyngeal swabs, suctioned sputum, and tongue swabs were collected for SARS-CoV-2-PCR. As for tongue swabs, we compared between two different sample conditions; one obtained with dry condition and the other obtained with moistened condition inside the oral cavity. SARS-CoV-2-PCR showed positive for an extended period with suctioned sputum samples compared with nasopharyngeal swabs and tongue swabs. No SARS-CoV-2 from a nasopharyngeal swab sample obtained on day 46 after symptoms onset was isolated despite high viral load (183740.5 copies/5μL). An adequate production of neutralizing antibody in a serum sample on day 46 was also confirmed. The number of RNA copies of the tongue swab samples was higher with moistened condition than with dry condition. The present case suggests that the difference of sampling site or sample condition can affect PCR results. High loads viral RNA detection does not always correlate with infectivity., (Copyright © 2021. Published by Elsevier Ltd.)

Introduction: Liposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown., Methods: Patients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period., Results: We identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001)., Conclusion: Early L-AMB administration at septic shock onset may be associated with early shock cessation., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests exists commercially; however, their performance using clinical samples is limited. Although insufficient to detect SARS-CoV-2 in the early phase of infection, antibody assays can be of great use for surveillance studies or for some coronavirus disease 2019 (COVID-19) patients presenting late to the hospital., Methods: This study evaluated the sensitivity and specificity of four commercial SARS-CoV-2 lateral flow antibody tests using 213 serum specimens from 90 PCR-positive confirmed COVID-19 patients. Of 59 negative control sera, 50 were obtained from patients with other respiratory infectious diseases before COVID-19 pandemic began while nine were from patients infected with other respiratory viruses, including two seasonal coronaviruses., Results: The varied sensitivities for the four commercial kits were 70.9%, 65.3%, 45.1%, and 65.7% for BioMedomics, Autobio Diagnostics, Genbody, and KURABO, respectively, between sick days 1 and 155 in COVID-19 patients. The sensitivities of the four tests gradually increased over time after infection before sick day 5 (15.0%, 12.5%, 15.0%, and 20.0%); from sick day 11-15 (95.7%, 87.2%, 53.2%, and 89.4%); and after sick day 20 (100%, 100%, 68.6%, and 96.1%), respectively. For severe illness, the sensitivities were quite high in the late phase after sick day 15. The specificities were over 96% for all four tests. No cross-reaction due to other pathogens, including seasonal coronaviruses, was observed., Conclusions: Our results demonstrated the large differences in the antibody test performances. This ought to be considered when performing surveillance analysis., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the annual variation in the frequency of patient-acquired azole-resistant Aspergillus fumigatus (ARAf), and correlate it to the amount of oral triazole prescribed, in Nagasaki, Japan., Methods: A. fumigatus isolates from respiratory specimens collected in the Nagasaki University Hospital (NUH) between 1996 and 2017 were included in the study. The amount of oral triazole prescribed in NUH since 2001 was obtained from the medical ordering system. Mutations in cyp51A, hmg1, and erg6 genes of ARAf were also analysed., Results: From a total of 240 ARAf strains, 12 (5%), 6 (2.5%), 15 (6.25%), and 3 (1.25%) strains were resistant to itraconazole (ITC), voriconazole (VRC), to either ITC or VRC, and both triazoles, respectively. The amount of prescribed VRC increased annually, and was three times as large as that of ITC in 2017. All eleven patients harbouring ITC-resistant strains had a history of prior ITC treatment, while only one of six patients harbouring VRC-resistant strains had a history of prior VRC treatment. cyp51A mutations were recorded in 10 strains; however, tandem repeat mutations of the promoter region of cyp51A were not observed. Several azole-resistant strains had non-cyp51A mutations., Conclusions: The frequency of patient-acquired ARAf is not increasing in Nagasaki, Japan. Furthermore, the prevalence of VRC-induced ARAf was rare despite the remarkable increase in the amount of prescribed VRC. Mutations in genes other than cyp51A should also be considered when ARAf strains are obtained from patients treated with azole antifungals., Competing Interests: Declaration of competing interest All authors meet the ICMJE authorship criteria. All authors have no conflicts of interest to be declared., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza., Methods: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system., Results: A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67-84), and the patients in the 2015-2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality., Conclusions: Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989)., Competing Interests: Declaration of competing interest Seki M received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Fujita J received honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Kadota J received scholarship from Daiichi Sankyo Co., Ltd. Izumikawa K received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Kakeya H received scholarship and honorarium from Shionogi Pharmaceutical Co., Ltd. and Daiichi Sankyo Co., Ltd. Watanabe A received honorarium from Shionogi Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Taisyo Phar, Co., Ltd., Tanabe Mitsubishi Pharmaceutical Co., Ltd., MSD Co., Ltd., FUJIFILM Toyama Chemical Co., Ltd., and Pfizer Co., Ltd. He received scholarship from Astellas Pharmaceutical Co., Ltd. and Daiicgi Sankyo Co., Ltd. Ishida T, Oishi K, Tateda K, Kawana A, Kikuchi T, Ohmagari N, Yamada M, Maruyama T, Takazono T, Miki M, Miyazaki Y, Yamazaki Y, Ogawa K, Nagai H have no conflict of interest., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Before advance care planning, it is essential to understand the differences in preferences for medical care of terminal-phase pneumonia in elderly patients among the patients, their families, and their doctors. This study aimed to clarify these differences and investigate the actual care provided to elderly patients with pneumonia in nursing hospitals., Methods: Multicenter questionnaire surveys of 179 patients admitted to nursing homes and long-term care beds in hospitals of three healthcare corporations, their families, and their physicians were conducted between January and August 2018. The questionnaires mainly assessed preferences for life-prolonging medical care procedures, including antibiotic treatments, in terminal-phase pneumonia. A follow-up survey regarding the prognosis and the actual care provided by the physicians was conducted 1 year after the first survey., Results: Only 16.2% of the patients had sufficient prior discussions with their families about their care. More families preferred cardiac massage, intubation, and tracheostomy, while fewer families preferred peripheral intravenous fluids or antibiotics than physicians. A total of 30 patients' families (16.7%) answered to withhold antibiotic treatment, while all physicians supported antibiotic administration. The only significant factor related to withholding antibiotics was high age (P = 0.0057). The follow-up survey administered to the doctors revealed that 49 patients (35.7%) had died within one year. Of the 137 patients, 54 patients (39.4%) had developed pneumonia during this observation period and all were treated with antibiotics., Conclusions: This study revealed large discrepancies between patients/families and physicians regarding preferences for care. Medical staff should make efforts to fill the gap by ensuring advance care planning., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Due to the increase in the number of azole-resistant Aspergillus fumigatus, there is an urgent need of data to predict future trends and prevent further spreading. The intercountry transfer of resistant A. fumigatus on plant bulbs have been reported. We investigated existence and characteristics of resistant isolates attached to agricultural products imported to Japan. We purchased 292 samples in Japan. All samples were screened for the existence of azole-resistant A. fumigatus. For positive isolates, minimum inhibitory concentrations of the drugs were determined. We also analyzed Cyp51A, Hmg1, and Erg6 mutations of these isolates and conducted microsatellite genotyping. Fourteen azole-resistant isolates were detected, of which 13 were cultured from flower bulbs imported from the Netherlands. Among them 5 were from 11 bulbs of Hippeastrum (45.5%), 5 were from 24 bulbs of Gladiolus (20.8%), 2 were from 4 bulbs of Ixia (50.0%), and 1 was from 22 bulbs of Tulipa (4.5%). Only 1 resistant isolate was cultured from the 10 bulbs of Narcissus (10.0%) originating in Japan. Various novel mutations including Y121F/T289A in Cyp51A with no tandem repeat in promoter region were discovered from imported strains. Our study provides important data showing that agricultural imports provide a possible route for their intercontinental spread and raises the concern that strains harboring highly diverse Cyp51A mutations might increase in clinical settings in the future., (Copyright © 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Endobronchial volatile sulfur compounds in patients with lung abscess or lung cancer were measured using the Oral Chroma™ gas chromatograph. High levels of hydrogen sulfide and methyl mercaptan were observed in some patients with lung abscess but not in patients with lung cancer. Measuring endobronchial volatile sulfur compounds could be useful for the rapid diagnosis of lung abscess caused by obligate anaerobes., Competing Interests: Declarations of interest None., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Oral antibiotic therapy for patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves an aminopenicillin with clavulanic acid, a macrolide, or a quinolone. To date, however, the clinical efficacy and safety of the oral cephalosporin cefditoren pivoxil has not been evaluated in Japanese patients with acute exacerbations of COPD. We conducted a prospective, multicenter, single arm, interventional study from January 2013 to March 2017 to determine the efficacy and safety of oral administration of 200 mg cefditoren pivoxil three times daily for 7 days in a cohort of 29 eligible patients from 15 hospitals. The mean age (SD) of participants was 73.1 (8.1) years and 28 had a smoking history (the mean [SD] of smoking index, 1426.7 [931.7]). The primary efficacy endpoint was clinical response (cure rate) at test of cure, which was set at 5-10 days after treatment ceased. Of the 23 patients finally analyzed, cure was achieved in 15 (65.2%), while 8 (34.8%) remained uncured. Previous experience of acute exacerbations significantly affected the cure rate: none of the three patients who had at least two prior exacerbations were cured, while 15 of the 20 patients with one or fewer prior exacerbations were cured (p = 0.032). The microbiological eradication rate was 88.9% at test of cure. During treatment, mild pneumonia was reported as an adverse event in one patient (3.4%) but resolved within 10 days of onset. We conclude that cefditoren pivoxil represents a viable alternative for antibiotic therapy in patients with few prior exacerbations., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Emphysematous pyelonephritis (EPN) is a life-threatening renal infection characterized by the formation of gas within the renal parenchyma and collecting duct system, as well as perinephric tissues. We herein report a case of bilateral EPN accompanied by the urinary tract infection caused by spherical growth of Candida albicans in a patient with underlying diabetes mellitus and prostate cancer. The diagnosis was assisted by computed tomography, urography, and gram staining. Despite immediate percutaneous catheter drainage and a 4-week course of antifungal treatment, the C. albicans infection was refractory, as indicated by continuous isolation from the urine, and the patient eventually died. A local autopsy of urinary organs revealed C. albicans in the renal tissue. EPN caused by Candida species frequently occurs in men, and almost all cases have underlying poorly controlled diabetes. This condition is subject to delayed diagnosis, which may lead to extended disease and high mortality. Candida species should be considered as causative microorganism for refractory EPN in patients with poorly controlled diabetes who are receiving antibiotic treatment. Gram staining may contribute to an early diagnosis of EPN caused by Candida species, which may require long-term antifungal therapy., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Histoplasmosis is a common endemic mycosis that is usually asymptomatic but occasionally results in severe illness. Histoplasmosis and its causative agent, Histoplasma capsulatum, are found worldwide but rarely in Japan. In recent years, however, the number of histoplasmosis patients in Japan has increased. In addition, to our knowledge, there are no previous reports of increased serum soluble interleukin-2 receptor (sIL-2R) levels in patients with histoplasmosis. We report a case series of histoplasmosis in three Japanese temporary workers in Manzanillo, Mexico. All three patients developed a persistent high fever and general fatigue. Laboratory tests showed increased C-reactive protein levels and mild liver dysfunction. All patients also showed increased soluble interleukin-2 receptor (sIL-2R) levels. Chest computed tomography revealed multiple nodules in both lung fields. All patients were positive for serum anti-Histoplasma antibodies, and two patients were positive for Histoplasma on polymerase chain reaction tests. After treatment that included antifungals, their conditions gradually improved and laboratory data normalized. Although one patient developed respiratory failure, this patient recovered with antifungal therapy in combination with methylprednisolone. Serum sIL-2R levels in all patients gradually declined to normal levels, indicating their recovery from Histoplasma infection. From our experience with these patients, sIL-2R levels may be a useful biomarker for patients with histoplasmosis., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV), a novel phlebovirus belonging to the family Bunyaviridae, was reported in China for the first time in 2009. We observed two cases where the SFTSV was isolated for the first time in Nagasaki, Japan, in 2005. Two males in their 60s, a farmer and a hunter, respectively, living in Nagasaki developed SFTS during the same period. The patients developed similar clinical symptoms and signs, such as fever, loss of consciousness, and multiple organ dysfunction. The farmer died and the hunter survived. A retrospective diagnosis of SFTS was made in 2013, and genetic analysis revealed that the patients were infected with different SFTSV strains. Retrospective analysis of cytokine production in non-fatal case revealed interleukin (IL)-6, IL-8 and interferon-γ level of acute phase was low and could be potential prognostic factors. As there are no epidemiological studies of positive rate of SFTSV antibody in people living in endemic areas in Japan, a field study was performed. Volunteers at high risk for tick bites, such as hunters, farmers, and soldiers, were recruited in 6 regions, including the areas where the SFTS cases occurred. Three hundred and twenty six volunteers in Nagasaki prefecture were examined and none of these tested positive for the SFTSV antibody. Our data indicates that the risk for SFTSV infection is not high in Nagasaki prefecture. Further collection of blood samples from endemic areas is warranted for the prevention of SFTSV infection., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The novel biological agent recombinant human thrombomodulin (rhTM) has been used clinically in Japan to treat disseminated intravascular coagulation (DIC) since 2008. Previous studies have shown the efficacy of rhTM versus heparin therapy or non-rhTM therapy. We retrospectively evaluated and compared the efficacies of rhTM and gabexate mesilate (GM) in patients diagnosed with sepsis-induced DIC. From September 2010 to October 2012, patients with sepsis-induced DIC who were treated with rhTM (n = 13) or GM (n = 10) at Nagasaki Municipal Hospital were extracted. Patients receiving other anticoagulants in combination were excluded. Clinical information, laboratory data, Sequential Organ Failure Assessment (SOFA) scores, and DIC scores were obtained from the medical records. Mortality at days 7 and 30 after DIC diagnosis and changes in laboratory data and SOFA scores from days 1-7 were evaluated. The groups' clinical characteristics did not differ, except for the relatively higher C-reactive protein (CRP) levels in the rhTM group (P = 0.0508). The survival rates of the rhTM and GM groups on days 7 and 30 were 92.3%, 69.2% and 80%, 70%, respectively, both group indicated similar mortality. However, on day 7, the platelet counts, SOFA scores, and CRP levels significantly improved in the rhTM group; the platelet counts and SOFA scores did not improve significantly in the GM group. The platelet counts of the rhTM group significantly improved compared to the GM group (P = 0.004). Recombinant human thrombomodulin might be more effective for sepsis-induced DIC than GM., (Copyright © 2014 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: The pathogenesis of chronic pulmonary aspergillosis (CPA) including chronic necrotizing pulmonary aspergillosis (CNPA), chronic cavitary pulmonary aspergillosis (CCPA), and simple aspergilloma (SA) has been poorly investigated. We examined all types of CPA cases with histopathological evidence to clarify the differences in pathogenesis and clinical features., Method: We searched for cases diagnosed as pulmonary aspergillosis by histopathological examination in Nagasaki University Hospital between 1964 and September 2010. All available clinical information including radiological findings were collected and analyzed., Result: We found 7, 5, 8, and 7 cases of proven CNPA, probable CNPA, CCPA, and SA, respectively. The radiograph of proven and probable CNPA was initially infiltrates or nodules that progress to form cavities with or without aspergilloma, whereas the radiograph of CCPA showed pre-existed cavities and peri-cavitary infiltrates with or without aspergilloma. The patients with proven and probable CNPA exhibited not only respiratory symptoms but also systemic symptoms and malnutrition. Aspergillus fumigatus was the most frequently isolated Aspergillus species (n = 14), however, Aspergillus niger was the predominant isolated species in proven CNPA cases (n = 4)., Conclusion: Our data indicate that the cases with chronic infiltration, progressive cavitation, and subsequent aspergilloma formation should be diagnosed as CNPA, and the cases with pre-existed cavities showing peri-cavitary infiltrates with or without aspergilloma would mean CCPA. However, it may be difficult to distinguish the two subtypes if a series of adequate radiography films are not available. We propose the term "chronic progressive pulmonary aspergillosis (CPPA)" for the clinical syndrome including both CNPA and CCPA., (Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Mycoplasma pneumoniae (MP) is one of the most common causes of community-acquired pneumonia in children and young adults. Although MP sometimes causes self-limiting pneumonia, severe and fulminant cases with hypoxia occur, but their clinical features have rarely been reported. This study aimed to reveal the clinical manifestations, risk factors, and treatment of fulminant MP pneumonia (MPP). Using PubMed and abstracts from the proceedings of several domestic Japanese academic societies, we reviewed the Japanese and English literature for cases of fulminant or severe MPP reported in Japan. All clinical information such as sex, age, underlying diseases, clinical symptoms, clinical course, laboratory and radiological findings, and treatment was collected and analyzed. In total, 52 fulminant MPP cases were reported between September, 1979 and February, 2010. The dominant population of fulminant MPP was young adults without severe underlying diseases. Cough (97.3%), fever (100.0%), and dyspnea (83.3%) with diffuse abnormal findings in radiological examinations were noted. Antibiotics without anti-mycoplasmal activity were used in 32 cases (61.5%) as initial treatment prior to the onset of hypoxia. Anti-mycoplasmal drugs were appropriately used in 41 cases (78.8%) after onset of respiratory failure with steroids (23 cases, 45.1%) and effective. The majority of patients improved within 3-5 days after steroid administration. There were only 2 fatal cases. Although this small retrospective study did not reveal the apparent risk factors of fulminant MPP, initial inappropriate use of antibiotics may be a risk factor, and early administration of appropriate anti-mycoplasmal drugs with steroids as a cellular immune suppressor is required., (Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Invasive pulmonary mucormycosis is a life-threatening fungal infection encountered in immunocompromised patients. An intravenous high-dose lipid formulation of amphotericin B, such as liposomal amphotericin B (L-AMB), is the recommended treatment. The efficacy of inhaled L-AMB against mucormycosis has not been evaluated. We evaluated the efficacy of inhaled aerosolized L-AMB in murine invasive pulmonary mucormycosis. ICR female mice were immunosuppressed with cortisone acetate and cyclophosphamide and challenged on day 0 with 1 × 10⁶ conidia of Rhizopus oryzae (TIMM 1327) intratracheally. Infected mice were assigned to one of the following 3 treatment groups: (i) control, (ii) treatment only (aerosolized L-AMB from day 1-5 after challenge), and (iii) prophylaxis followed by treatment (aerosolized L-AMB from day -2 to 5 before and after challenge). Survival was monitored until 12 days after challenge. For fungal-burden and histopathological examination, mice were sacrificed 4 h after treatment on day 3. Numbers of colony-forming units per lung were calculated. To study the distribution of AMB after inhalation of L-AMB, immunohistochemical studies using AMB antibody were performed. Aerosolized L-AMB significantly improved survival rate and decreased fungal burden compared with control group, and histopathology findings were superior to those of control group. However, no significant differences were detected between the treatment-only and prophylaxis followed by treatment groups. Immunohistochemical analysis showed that L-AMB was promptly distributed in lung tissue after inhalation therapy. Aerosolized L-AMB showed modest efficacy against R. oryzae infection in mice treated after fungal challenge. Prophylaxis with aerosolized L-AMB was not effective in this animal model., (Copyright © 2013 Japanese Society of Chemotherapy and The Japanese Association for Infectious Disease. Published by Elsevier Ltd. All rights reserved.)