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Masafumi Seki,1,* Haruka Karaushi,1,* Noriko Arai,2 Takeshi Hayashi,2 Kotaro Mitsutake1 1Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Hidaka City, Saitama, Japan; 2Division of Neurology, Saitama Medical University International Medical Center, Hidaka City, Saitama, Japan*These authors contributed equally to this workCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, Saitama Medical University International Medical Center, Yamane 1397-1, Hidaka City, Saitama, 350-1298, Japan, Tel +81-42-984-4392, Fax +81-42-984-0280, Email sekimm@saitama-med.ac.jpBackground: Secondary bacterial infection was initially rare in SARS-CoV-2 infectious disease (COVID-19) patients, but COVID-19-associated bacterial infectious diseases have recently been increasing. Furthermore, it might be difficult to distinguish COVID-19 from bacterial meningitis by the symptoms, and one might be uncertain about antibiotic therapy for Listeria meningitis infection—typically caused by eating contaminated food—in elderly persons and pregnant women.Case Report: A 96-year-old woman who had been living alone was found to have SARS-CoV-2 infection in February 2023. She was admitted to our hospital with high fever and disturbance of consciousness and was started on treatment with remdesivir. Two days later, her consciousness was still disturbed, and she was found to have a stiff neck. In addition, increased white blood cell counts and C-reactive protein suggested bacterial infection. Therefore, a lumbar puncture was done, and Listeria monocytogenes was ultimately isolated from blood cultures and its genetic material was detected in cerebrospinal fluid. She had previously eaten refrigerated food and cheese products. Intravenous ampicillin 1.0 g 6×/day was started, but one week later, loss of consciousness continued, and the cerebrospinal findings were not improved, although nasal swab became negative for SARS-CoV-2. Intravenous sulfamethoxazole/trimethoprim (ST) 80/400 mg 3×/day was added, and her consciousness and fever improved by one week later. A drug rash appeared after ST was started, and she was switched to meropenem. Her condition finally improved.Conclusion: COVID-19-associated secondary listeria infection was found in an elderly woman. She was treated with not only ampicillin, but also ST and meropenem. Meningitis caused by Listeria monocytogenes should be considered as a secondary complication and carefully treated with antibiotics during the period of the COVID-19 pandemic.Keywords: penicillin, carbapenem, antibiotics, drug rash, SARS-CoV-2

Masafumi Seki,1,2 Kosuke Hashimoto,2 Nami Kondo,2 Yoshitaka Ohya,2 Futoshi Kotajima,2 Kotaro Mitsutake1,2 1Division of Infectious Diseases and Infection Control, International Medical Center, Saitama Medical University, Hidaka City, Saitama, Japan; 2COVID-19 Management Team, International Medical Center, Saitama Medical University, Hidaka City, Saitama, JapanCorrespondence: Masafumi Seki, Division of Infectious Diseases and Infection Control, International Medical Center, Saitama Medical University, Yamane 1397-1, Hidaka City, Saitama, 350-1298, Japan, Tel +81-42-984-4392, Fax +81-42-984-0280, Email sekimm@saitama-med.ac.jpBackground: The detailed treatment regimen of COVID-19 patients with hematological malignancies has been unclear, and some fatalities have occurred, although combination therapy with antiviral agents and corticosteroids has been established for moderate to severe COVID-19 patients.Case Series: Case 1 was a 57-year-old woman who had malignant lymphoma and received CHOP therapy with obinutuzumab, and case 2 was a 70-year-old-man who had myeloma and received molecular targeted therapy with weekly corticosteroid. In both cases, SARS-CoV-2 genes and antigens were detected from their nasal swabs, and treatment was started for moderate to severe COVID-19. Case 1 received antiviral agents with high doses of corticosteroids for a long term simultaneously, but the high titer of viral antigens in her nasal swabs persisted. Ground-glass opacities and interstitial shadows also worsened in both lungs, and she finally died on day 60. In contrast, in case 2, antiviral agents were started first, and restarted the immunosuppressive agents, such as gamma globulin and corticosteroids after no titer of SARS-CoV-2 antigens was confirmed. The patient survived, and his abnormal chest shadows showed gradual improvement. Both of the patients received two vaccinations, but showed the low antibody titers for SARS-CoV-2.Conclusion: Administration of both antiviral agents and corticosteroids has been recommended for moderate to severe COVID-19 patients, but in patients with hematological malignancies, it might be better to use antiviral agents first to reduce the viral titers, and then add steroid and related immunosuppressive agents later appropriately to inhibit the excessive inflammatory state. The dose, timing, and order of the antivirals and immunosuppressive agents for COVID-19 should be considered carefully in the patients with hematological malignancies who showed low vaccine effectiveness.Keywords: SARS-CoV-2, B cell depleting agents, corticosteroid, obinutuzumab, rituximab

The in-vitro and in-vivo activities of SCH56592, a triazole antifungal agent, against Cryptococcus neoformans were studied. MIC90s for 16 strains of C. neoformans measured by microdilution method (NCCLS M27-A) were 1 mg/L of SCH56592, 16 mg/L of fluconazole, 32 mg/L of flucytosine, and 0.5 mg/L of amphotericin B. In a murine model of pulmonary cryptococcosis, 10 mg/kg of SCH56592 was more effective than fluconazole. The fungal burden of the lung of animals treated with SCH56592 was significantly reduced (7.40 ± 0.21 log10 cfu/g), as compared with fluconazole (7.77 ± 0.07 log10 cfu/g) and control (7.79 ± 0.1 log10 cfu/g) (P < 0.01). For C. neoformans-infected mice following 7 days treatment with 10 mg/kg of SCH56592 there was a higher concentration in lung (3.36 ± 0.62 ng/ml) than in plasma (2.16 ± 0.86 ng/mL), and this was maintained for 12 h after administration. [ABSTRACT FROM PUBLISHER]

Background: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis., Methods: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019., Results: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis., Conclusion: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents., Competing Interests: Declaration of Competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co. Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals, Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Ltd. Japan, Kowa Co. Ltd., Gilead Sciences K.K., GSK Group of Companies, Saraya Co. Ltd., Tsumura & Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., grant supports from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (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: Infective endocarditis (IE) caused by MRSA (methicillin-resistant Staphylococcus aureus) is associated with a high mortality rate. This study aimed to elucidate the characteristics of patients with MRSA-IE in Japan and identify the factors associated with prognosis., Methods: This retrospective study included patients with a confirmed diagnosis of IE caused by MRSA, between January 2015 and April 2019., Results: A total of 65 patients from 19 centers were included, with a mean age of 67 years and 26 % were female. Fifty percent of the patients with IE were had nosocomial infections and 25 % had prosthetic valve involvement. The most common comorbidities were hemodialysis (20 %) and diabetes (20 %). Congestive heart failure was present in 86 % of patients (NYHA class I, II: 48 %; III, IV: 38 %). The 30-day and in-hospital mortality rates were 29 % and 46 %, respectively. Multi-organ failure was the primary cause of death, accounting for 43 % of all causes of death. Prognostic factors for in-hospital mortality were age, disseminated intravascular coagulation, daptomycin and/or linezolid as initial antibiotic therapy, and surgery. Surgical treatment was associated with a lower mortality rate (odds ratio [OR], 0.026; 95 % confidence interval [CI], 0.002-0.382; p = 0.008 for 30-day mortality and OR, 0.130; 95 % CI; 0.029-0.584; p = 0.008 for in-hospital mortality)., Conclusion: Mortality due to MRSA-IE remains high. Surgical treatment is a significant prognostic predictor of MRSA-IE., Competing Interests: Declaration of competing interest Tokimatsu I. received scholarship donations from Shionogi Pharmaceuticals, Inc. and Daiichi Sankyo Co., Ltd. Ukimura A. received scholarship donations from Shionogi Pharmaceuticals Inc. Hiroshige Mikamo received speaker honoraria from MSD K.K., FUJIFILM Toyama Chemical Co., Ltd., Miyarisan Pharmaceutical Co., Daiichi Sankyo Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd., Shionogi & Co., Japan. Ltd., Kowa Co. Ltd., Gilead Sciences K.K., the GSK Group of Companies, Saraya Co. Ltd., and Tsumura and Co. Japan, Nippon Becton Dickinson Company, Ltd., and FUKOKU Co., Ltd., and grant support from Asai Kasei Pharma Co., Shionogi & Co., Ltd., Sumitomo Pharma Co., Ltd., and FUKOKU Co., Ltd. Mitsutake K, Shinya N, Seki M, Ohara T, Uemura K, Fukunaga M, Sakai J, Nagao M, Sata M, Hamada Y, Kawasuji H, Yamamoto Y, Nakamatsu M, Koizumi Y, Aoyagi T, Sawai T, Tanaka T, Izumikawa K, Takayama Y, Nakamura K, Kanemitsu K, Nakajima K, and Akine D have no conflict of interest., (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 In patients with hematologic malignancies, faster species identification is particularly important in the management of bloodstream infection because of their immunocompromised and neutropenic status. In the present study, we analyzed direct species identification in patients with hematologic malignancies, and the factors that might influence the results of species identification. Methods We performed direct species identification using a Sepsityper ® kit (Bruker Corporation, Billerica, Massachusetts, United States) and compared the results with a conventional method in patients with hematologic malignancies. Forty-five positive blood culture bottles containing single microorganisms from 37 patients were analyzed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). And patients' clinical data were compared between the groups with spectral scores at acceptable and unacceptable levels. Results Direct species identification correctly identified 42 of 45 isolates and three were misidentified. While 35 of 45 isolates showed a spectral score ≥1.7 (acceptable identification), 10 isolates had a spectral score <1.7 (unacceptable identification) including three misidentified isolates. The group with a spectral score ≥1.7 had significantly lower white blood cell (p<0.01), neutrophil (p<0.01), and platelet (p<0.01) counts in addition to more frequent central venous (CV) line insertion (p=0.01). Multivariate analysis revealed that pathogen type (gram-positive or negative) and CV line insertion were associated with spectral scores. Conclusion Direct species identification using the Sepsityper kit is an upcoming approach for blood culture bottles, which were flagged as positive even in patients with hematologic malignancies when the spectral score was ≥ 1.7. Our study also indicates that direct identification is more accurate in patients with CV lines, and may be less accurate when gram-positive bacteria are detected., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Watanabe et al.)

Candidemia, linked to high mortality rates, requires prompt antifungal therapy for better outcomes. Treatment is structured as an action bundle, which is beneficial when followed closely. However, the Japanese action bundle lacks detailed guidance on severe complications like endocarditis or ocular issues. To address this, we adjusted the action bundle and assessed outcomes with and without AFT intervention. We strengthened protocols for blood cultures and organ assessments, and the AFT contacted the primary physician when yeast-like fungi were detected in the patient's blood culture bottles. Analyzing 204 candidemia cases from 2008-2021, we observed increased adherence and reduced mortality post-AFT intervention. Ophthalmology consultations rose significantly, but many patients had only one visit, suggesting inadequate follow-up. If endophthalmitis is diagnosed, a change in the treatment approach may be necessary. There is a possibility that abnormal ocular findings will be detected during subsequent visits, which highlights the need for improvement in ophthalmology follow-up rates as a future challenge for our AFT activities.

It is unclear whether anti-methicillin-resistant Staphylococcus aureus (MRSA) drugs should be uniformly administered to patients with pneumonia when MRSA is isolated from respiratory specimens. A systematic review was conducted to evaluate the efficacy of the uniform administration of anti-MRSA drugs. Two researchers independently searched the literature as of December 2022, extracted relevant papers, and performed a meta-analysis. The outcomes were mortality and adverse events. No applicable randomized controlled trials were found during the study period, but four observational studies were extracted. The relative risk of mortality in the anti-MRSA group was 1.67 [95% confidence interval 0.65-4.30], which did not differ significantly from the non-administered group. Further investigation into the background of patients demonstrated that anti-MRSA drugs were administered to groups in which only MRSA was cultured. However, the pneumonia severity index did not differ from that in the non-treated group. No studies of adverse events were found. Our review did not find a beneficial contribution to mortality from uniform anti-MRSA medication to patients with pneumonia when MRSA was isolated from respiratory specimens. Factors determining risk-based individualized treatment should be validated as the future question., Competing Interests: Declaration of competing interest There are no COIs related to the present study, but Masafumi Seki declares the following COIs related to MRSA pneumonia: payment or honoraria for lectures from Pfizer Inc., Kyorin Pharmaceutical Co., Ltd., Shionogi Co., Ltd., MSD Co., Ltd, Daiichi Sankyo Co., Ltd., Meiji Seika Pharma Co., Ltd., Sumitomo Pharma Co., Ltd., (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.)

Neuromodulation through magnetic fields irradiation with ait® (AT-04), a device that irradiates a mixed alternating magnetic fields (2 kHz and 83.3 MHz), has been shown to have high efficacy for fibromyalgia and low back pain in our previous clinical trials. The aim of this study was to elucidate the underlying analgesic mechanism of the AT-04 using the partial sciatic nerve ligation (PSL) model as an animal model of neuropathic pain. AT-04 was applied to PSL model rats with hyperalgesia and its pain-improving effect was verified by examining mechanical allodynia using the von Frey method. The results demonstrated a significant improvement in hyperalgesia in PSL model rats. We also examined the involvement of descending pain modulatory systems in the analgesic effects of AT-04 using antagonism by serotonin and noradrenergic receptor antagonists. These antagonists significantly reduced the analgesic effect of AT-04 on pain in PSL model rats by approximately 50%. We also measured the amount of serotonin and noradrenaline in the spinal fluid of PSL model rats using microdialysis during AT-04 treatment. Both monoamines were significantly increased by magnetic fields irradiation with AT-04. Furthermore, we evaluated the involvement of opioid analgesia in the analgesic effects of AT-04 using naloxone, the main antagonist of the opioid receptor, and found that it significantly antagonized the effects by approximately 60%. Therefore, the analgesic effects of AT-04 in PSL model rats involve both the endogenous pain modulation systems, including the descending pain modulatory system and the opioid analgesic system., (© 2023. The Author(s).)

Vancomycin (VCM) and daptomycin (DAP) are standard therapies for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia, despite concerns regarding clinical utility and growing resistance. Linezolid (LZD) affords superior tissue penetration to VCM or DAP and has been successfully used as salvage therapy for persistent MRSA bacteremia, indicating its utility as a first-choice drug against MRSA bacteremia. In a systematic review and meta-analysis, we compared the effectiveness and safety of LZD with VCM, teicoplanin (TEIC), or DAP in patients with MRSA bacteremia. We evaluated all-cause mortality as the primary effectiveness outcome, clinical and microbiological cure, hospital length of stay, recurrence, and 90-day readmission rates as secondary effectiveness outcomes, and drug-related adverse effects as primary safety outcomes. We identified 5328 patients across 2 randomized controlled trials (RCTs), 1 pooled analysis of 5 RCTs, 1 subgroup analysis (1 RCT), and 5 case-control and cohort studies (CSs). Primary and secondary effectiveness outcomes were comparable between patients treated with LZD versus VCM, TEIC, or DAP in RCT-based studies and CSs. There was no difference in adverse event incidence between LZD and comparators. These findings suggest that LZD could be a potential first-line drug against MRSA bacteremia as well as VCM or DAP.

Aims: Standard doses of daptomycin at 4 and 6 mg/kg were used for the treatment of skin and soft tissue for infections and bacteraemia, respectively. However, increased doses of daptomycin are recommended for complicated infections by Gram-positive organisms., Methods: A systematic review was conducted using 4 databases. We compared treatment success between standard-dose (SD, 4-6 mg/kg) and high-dose (HD, >6 mg/kg) daptomycin in patients with all-cause bacteraemia, complicated bacteraemia, infective endocarditis, osteomyelitis and foreign body/prosthetic infection as the primary outcome. We also compared the success between SD and HD2 (≥8 mg/kg) daptomycin treatments in patients with these diseases as the secondary outcome. The incidence of creatine phosphokinase (CPK) elevation was evaluated as safety., Results: In patients with complicated bacteraemia and infective endocarditis, the treatment success was significantly lower in the SD group than in the HD group (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76 and OR 0.50, 95% CI 0.30-0.82) and HD2 group (OR 0.38, 95% CI 0.21-0.69 and OR 0.30, 95% CI 0.15-0.60), respectively. A significant difference was demonstrated only in the HD2 group in patients with bacteraemia, including simple infection. SD did not decrease the success rate for the treatment of osteomyelitis and foreign body/prosthetic infection. The incidence of elevated CPK was significantly lower in SD group than in HD group., Conclusion: SD daptomycin was associated with significantly lower treatment success than HD in patients with complicated bacteraemia/infective endocarditis. The CPK elevation should be considered in patients treated with high daptomycin doses., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

BACKGROUND Mycobacterium tuberculosis (M. tuberculosis) is usually treated by oral antimycobacterial agents, including rifampicin, ethambutol, and pyrazinamide, but the treatment regimen with intravenous and/or intramuscular antimycobacterial agents for patients who cannot take medications orally remains unclear. CASE REPORT A 77-year-old man with chronic renal failure had an esophageal-skin fistula after he had surgeries for removal of esophageal and gastric cancers and reconstruction using jejunum, and he showed a cavity, tree-in-bud formation, and pleural effusions in his left upper lung fields on his chest X-ray after treatment of cellulitis and bacteremia/candidemia by meropenem, teicoplanin, and micafungin. M. tuberculosis was isolated from his sputum and exudate fluid from the reconstructed esophageal-skin fistula. Although he could not take antimycobacterial agents orally, treatment was started with intravenous agents combining levofloxacin (LVFX) every other day, isoniazid (INH), and linezolid (LZD). However, his platelets were decreased 21 days after treatment started, and it was thought to be an adverse effect of LZD and/or INH. After changing LZD to tedizolid (TZD), in addition to changing from INH to intramuscular streptomycin twice per week, his platelet counts increased. Intravenous TZD could be continued, and it maintained his condition without exacerbations of thrombocytopenia and renal failure. The M. tuberculosis disappeared, and the abnormal chest X-ray shadows were improved 2 months after the start of treatment. CONCLUSIONS Administration of intravenous TZD, in addition to intravenous LVFX and intramuscular SM in combination, might be a candidate regimen for M. tuberculosis patients who cannot take oral medications.

Introduction: We evaluated the performance of Rapid Sepsityper Kit in species identification (ID) and antimicrobial susceptibility testing (AST)., Methods: Positive blood culture bottles (n = 227) containing single microorganisms were enrolled. We compared the direct method using Rapid Sepsityper Kit for ID and AST with the conventional method. The analyses of ID and AST were performed using MALDI Biotyper and BD Phoenix platform, respectively., Results: The direct ID method correctly identified 89.4% (203/227) of samples, and Gram-negative bacilli (95.2%) had a higher ID rate than Gram-positive cocci (84.4%). Five cases were misidentified, and non-acceptable identification was high among Streptococcus species. Direct AST results were obtained from 168 isolates. Non-acceptable ID occurred among 24 isolates; 4 Streptococcus species, and 31 isolates, which did not grow in the direct AST method, were excluded. A total of 1714 antibiotic susceptibility tests (625 from 69 Gram-positive cocci and 1089 from 99 Gram-negative bacilli) were performed. The direct AST methods showed 98.3% (1685/1714) of categorical agreement (CA), 0.7% (12/1714) of very major errors, 0.2% (4/1714) of major errors, and 0.8% (13/1714) of minor errors. Complete CA was obtained for methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase-producing Escherichia coli., Conclusions: The direct ID method using Rapid Sepsityper Kit and the direct AST method in combination with the BD Phoenix platform, which was associated with a reduction of turnaround time, may be a reliable approach for blood culture bottles. However, additional validation and further improvements, especially for Gram-positive cocci, would have an impact on microbiological diagnoses., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The in vitro susceptibilities of Bacteroides fragilis to antimicrobial agents, especially to carbapenem, are a major concern in the treatment of patients with bloodstream infections. In this study, 50 isolates of B. fragilis were obtained from positive blood bottles from 2014 to 2019 in Saitama, Japan. Their susceptibility to ampicillin/sulbactam was reduced to 70.0% compared with a previous report, whereas they were still sufficiently susceptible to piperacillin/tazobactam (94.0%). Five cfiA-positive isolates (5/50, 10.0%) were identified that were resistant to doripenem and meropenem, and two of them carried an insertion sequence located upstream of the cfiA-coding region. In particular, imipenem should be considered as a first-line carbapenem for the empirical treatment of B. fragilis infection because only insertion sequence and cfiA double-positive strains showed resistance to imipenem. Thirty-six percent of the isolates had a reduced minimum inhibitory concentration for moxifloxacin. In addition, metronidazole should still be considered as an active agent for B. fragilis because all isolates were susceptible to this antibiotic and the prevalence of the nim gene was low in Japan., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)