Primary syphilis of the oropharynx mimicking a neoplasm.

Syphilis is surging in Japan and worldwide among both homosexual and heterosexual individuals. Diagnosis can be challenging because syphilis is "the great imitator" and clinical manifestations are highly variable. Oral manifestations of syphilis are usually seen in the second stage and the primary syphilis in the oral cavity is rare. We describe a heterosexual man with isolated tonsillar lesions initially misdiagnosed as pharyngeal lymphoma and subsequently diagnosed as primary syphilis. Clinicians should be aware that isolated oropharyngeal involvement can occur in the primary syphilis and can mimic a neoplasm.

Clinical characteristics of patients with coronavirus disease 2019-associated pulmonary aspergillosis on mechanical ventilation: A single-center retrospective study in Japan.

BACKGROUND: Aspergillus is one of the important pathogens that contribute to high mortality in patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). Although incidence rates of Aspergillus coinfection are high globally, a Japanese national survey reported a low incidence. This study aimed to describe the clinical characteristics of patients with COVID-19-associated pulmonary aspergillosis at our institute. METHODS: We identified patients with microbiologically confirmed COVID-19 on mechanical ventilation in the ICU. Of these patients, we identified patients in whom Aspergillus was cultured from the respiratory specimen. RESULTS: Of a total of 169 patients, seven had aspergillosis (4.1%), which included three patients, three patients, and one patient with possible, probable, and proven aspergillosis, respectively, according to the criteria of the European Confederation of Medical Mycology International Society. All patients received systemic steroid therapy. Two patients (one each with proven and probable aspergillosis) had tracheobronchitis diagnosed by bronchoscopy. All patients in whom Aspergillus was repeatedly isolated from samples died. The mortality rates for all cases and probable and proven cases were 57% (4/7) and 75% (3/4), respectively. CONCLUSIONS: The incidence rate of aspergillosis in patients with COVID-19 in the ICU was higher in our institute than that reported by a Japanese national survey (4.1% vs. 0.5%). Repeated detection of Aspergillus might suggest a true Aspergillus infection, such as chronic aspergillosis, rather than colonization. In patients with severe COVID-19 patients, it is important to always keep CAPA in mind.

Characteristics and prognosis of patients with Edwardsiella tarda bacteremia at a single institution, Japan, 2005-2022.

BACKGROUND: Edwardsiella tarda is a member of Enterobacteriaceae isolated from freshwater and sea. E. tarda infection in humans commonly causes gastroenteritis, but rarely causes bacteremia. However, few studies have described the clinical features of E. tarda bacteremia (ETB); therefore, we conducted a case review in our hospital. METHODS: We conducted a single-center, retrospective descriptive study using electronic medical records. Patient and microbial features were extracted and evaluated for 30- and 90-day mortality rates. RESULTS: From April 2005 to April 2022, the total set of blood cultures positive for any microorganisms was 9368, 38 of which were positive for E. tarda. Underlying cancer was observed in 65.8% of patients. The most common source of bacteremia was cholangitis, followed by cholecystitis, and endoscopic or surgical drainage was performed in almost all cases. Diarrhea was observed in only one patient, and there were no cases in which gastroenteritis was the source of bacteremia. All cases, except for one, were susceptible to all ß-lactams, such as ampicillin. The 30- and 90-day overall mortality rates were 8.6% (3/35) and 25.8% (8/31). Of these, 75% patients died because of cancer progression after successful ETB treatment. CONCLUSION: ETB may occur in patients with malignant underlying conditions. Biliary tract infections are common in ETB cases, whereas gastroenteritis may be an atypical cause of bacteremia. This study suggests that although the mortality rate for ETB at 30 day was low, it increased at 90 day as a result of the development of unfavorable underlying conditions.

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12-20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.

Disseminated Verruconis gallopava infection in a patient with systemic lupus erythematosus in Japan: A case report, literature review, and autopsy case.

Disseminated Verruconis gallopava infection is often reported in patients with severe immunodeficiency, such as those who have received an organ transplant or have hematological malignancies. The present report describes the first case of disseminated V. gallopava in a patient with systemic lupus erythematosus who used FK506 (Tacrolimus). In this case, ß-D glucan was useful for diagnosis.

Corynebacterium pseudodiphtheriticum as a Pathogen in Bacterial Co-Infection in COVID-19 Patients on Mechanical Ventilation.

Many studies have been conducted on ventilator-associated complications (VACs) in patients with coronavirus 2019 (COVID-19). However, in these studies, the causative organisms were similar, and there were no reports on VAC corresponding with Corynebacteria. Coryneforms are frequently cultured in cases of polymicrobial infections and are usually considered contaminants in respiratory specimens. However, Corynebacterium pseudodiphtheriticum or C. striatum is known to be a pathogen in lower respiratory tract infections. We report three cases of VAC, probably due to C. pseudodiphtheriticum, in patients with COVID-19. If purulent lower respiratory tract specimens showed coryneform predominantly upon Gram staining, empirical therapy should be started. Furthermore, species identification and drug susceptibility testing should be performed.

Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), is an enveloped, single-stranded RNA virus. Favipiravir is an orally administrable antiviral drug whose mechanism of action is to selectively inhibit RNA-dependent RNA polymerase. A preliminary trial in COVID-19 patients reported significant improvements across a multitude of clinical parameters, but these findings have not been confirmed in an adequate well-controlled trial. We conducted a randomized, single-blind, placebo-controlled Phase III trial assessing the efficacy and safety of favipiravir in patients with moderate pneumonia not requiring oxygen therapy. METHODS: COVID-19 patients with moderate pneumonia (SpO2 ≥ 94%) within 10 days of onset of fever (temperature ≥ 37.5 °C) were assigned to receive either placebo or favipiravir (1800 mg twice a day on Day 1, followed by 800 mg twice a day for up to 13 days) in a ratio of 1:2. An adaptive design was used to re-estimate the sample size. The primary endpoint was a composite outcome defined as the time to improvement in temperature, oxygen saturation levels (SpO2), and findings on chest imaging, and recovery to SARS-CoV-2-negative. This endpoint was re-examined by the Central Committee under blinded conditions. RESULTS: A total of 156 patients were randomized. The median time of the primary endpoint was 11.9 days in the favipiravir group and 14.7 days in the placebo group, with a significant difference (p = 0.0136). Favipiravir-treated patients with known risk factors such as obesity or coexisting conditions provided better effects. Furthermore, patients with early-onset in the favipiravir group showed higher odds ratio. No deaths were documented. Although adverse events in the favipiravir group were predominantly transient, the incidence was significantly higher. CONCLUSIONS: The results suggested favipiravir may be one of options for moderate COVID-19 pneumonia treatment. However, the risk of adverse events, including hyperuricemia, should be carefully considered. TRIAL REGISTRATION: Clinicaltrials.jp number: JapicCTI-205238.

Assessing the effects of exposure to a SARS-CoV-2 re-positive patient in healthcare personnel.

OBJECTIVE: To evaluate whether patients with COVID-19 who have tested re-positive with the PCR test for the SARS-CoV-2 virus are infectious is a challenge in the current circumstances. A follow-up survey was conducted with healthcare personnel (HCP) who were exposed to a patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative PCR results. RESULTS: We studied a total of 15 HCP who had contact exposures (15/15) and aerosol exposures (7/15). None of them tested positive for IgG against SARS-CoV-2 on blood examination. None of them had any symptoms during 10 days of active isolation. All PCR tests conducted using the nasopharyngeal swabs collected from the HCP on day 10 were negative. No apparent infection was found in any of the HCP who had contact exposure with and/or aerosol exposure to the patient whose PCR test results for SARS-CoV-2 were re-positive 18 days after the initial confirmation of negative results of PCR tests for SARS-CoV-2. CLINICAL TRIAL: Trial Registration: No. 170, approved June 10th, 2020 by the ethics committee of Sakai City Medical Center.

Clinical characteristics and molecular epidemiology of invasive Streptococcus agalactiae infections between 2007 and 2016 in Nara, Japan.

Invasive Streptococcus agalactiae (GBS) infections are increasingly common among neonates and the elderly. Therefore, GBS surveillance for better antibiotic treatment and prophylaxis strategies are needed. We retrospectively evaluated the clinical aspects of invasive infections and the phenotypic and genetic diversity of infectious isolates from Nara, Japan, collected between 2007 and 2016, by using information from hospital records. GBS strains collected from the blood and cerebrospinal fluid cultures were evaluated for capsular types, multi-locus sequence typing (MLST), antibiotic susceptibility, antibiotics resistance gene, and pulsed-field gel electrophoresis. Forty GBS isolates (10 from children and 30 from adults) were analyzed, and the distribution of molecular serotype and allelic profiles varied between children and adults. We found the rates of early-onset disease in neonates with birth complications to be higher than that of previous reports, indicating that there could be relevance between complications at birth and early-onset disease. Standard antibiotic prophylaxis strategies may need to be reconsidered in patients with birth complications. In adults, the mean age of the patients was 68 years (male: 63%). Primary bacteremia was the most common source of infection. In the neonates, six had early-onset diseases and four had late-onset diseases. The most frequently identified strains were molecular serotype Ia ST23 (40%) and molecular serotype Ib ST10 (20%) in children and molecular serotype Ib ST10 (17%), molecular serotype VI ST1 (13%), and molecular serotype V ST1 (13%) in adults. Levofloxacin-resistant molecular serotype Ib strains and molecular serotypes V and VI ST1 were common causes of GBS infection in adults but were rarely found in children. Furthermore, pulsed-field gel electrophoresis in our study showed that specific clone isolates, that tend to have antibiotics resistance were widespread horizontally for a decade. Continuous surveillance and molecular investigation are warranted to identify the transmission route and improve antibiotic treatment strategies.

Analysis of the predictive factors for a critical illness of COVID-19 during treatment － relationship between serum zinc level and critical illness of COVID-19.

OBJECTIVES: Because most severely ill patients with COVID-19 in our hospital showed zinc deficiency, we aimed to examine the relationship between the patient's serum zinc level and severe cases of COVID-19. METHODS: Serum zinc <70 µg/dL was defined as the criterion for hypozincemia, and patients continuously with serum zinc <70 µg/dL were classified in the hypozincemia cohort. To evaluate whether hypozincemia could be a predictive factor for a critical illness of COVID-19, we performed a multivariate analysis by employing logistic regression analysis. RESULTS: Prolonged hypozincemia was found to be a risk factor for a severe case of COVID-19. In evaluating the relationship between the serum zinc level and severity of patients with COVID-19 by multivariate logistic regression analysis, critical illness can be predicted through the sensitivity and false specificity of a ROC curve with an error rate of 10.3% and AUC of 94.2% by only two factors: serum zinc value (P = 0.020) and LDH value (P = 0.026). CONCLUSIONS: Proper management of the prediction results in this study can contribute to establishing and maintaining a safe medical system, taking the arrival of the second wave, and the spread of COVID-19 in the future into consideration.

Necessity to screen and treat latent tuberculosis before ruxolitinib treatment-Ruxolitinib-associated disseminated tuberculosis: A case report and literature review.

Ruxolitinib, a Janus kinase inhibitor, considerably improves symptoms of patients with polycythemia vera and primary or secondary myelofibrosis. However, its association with the development of infectious complications is a concern. Herein, we report the case of an 80-year-old man with primary myelofibrosis who developed disseminated tuberculosis during treatment with ruxolitinib at 15 mg twice daily and prednisone at 5 mg. We also reviewed the literature on patients who developed tuberculosis during treatment with ruxolitinib. There are 13 case reports of patients who developed tuberculosis during treatment with ruxolitinib, including our case. Disseminated tuberculosis manifestations were observed in 84.6 % of the patients and 50 % of them died. Although the interferon-gamma release assay was performed for seven of the patients with six positive results at the time of tuberculosis diagnosis, none were tested before the commencement of ruxolitinib. We suggest taking a history of tuberculosis and screening for and treating latent tuberculosis before administering ruxolitinib, especially in areas where the risk of tuberculosis is high.

Spinal epidural abscess caused by non-typhoidal Salmonella: A case report and literature review.

Non-typhoidal Salmonellae are Gram negative bacilli commonly causing self-limiting gastroenteritis, representing a public health issue particularly in tropical countries. Further, the epidemiology of invasive infection by non-typhoidal Salmonella species is poorly understood. Herein, we presented a case of an unusual Salmonella enterica subsp. enterica serovar Altona epidural abscess that cause osteomyelitis and psoas abscess in a 52-year-old Japanese man. To ensure adequate antibiotics penetration into the epidural space, the patient was treated with antibiotics in doses similar to those administered for meningitis. We also reviewed the literature on patients who developed non-typhoidal Salmonella epidural abscesses, and we found 10 other previously reported cases. Salmonella Enteritidis was the pathogen most commonly identified, similar to gastroenteritis. More surveillance of non-typhoidal Salmonella serovars, especially in cases of severe infection, and investigation of antibiotic penetration rate into the epidural space are warranted to decide the best treatment course.

A prolonged multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales due to horizontal transmission of the IncN plasmid.

A multispecies outbreak of IMP-6 carbapenemase-producing Enterobacterales (IMP-6-CPE) occurred at an acute care hospital in Japan. This study was conducted to understand the mechanisms of IMP-6-CPE transmission by pulsed-field gel electrophoresis (PFGE), multilocus sequence typing and whole-genome sequencing (WGS), and identify risk factors for IMP-6-CPE acquisition in patients who underwent abdominal surgery. Between July 2013 and March 2014, 22 hospitalized patients infected or colonized with IMP-6-CPE (Escherichia coli [n = 8], Klebsiella oxytoca [n = 5], Enterobacter cloacae [n = 5], Klebsiella pneumoniae [n = 3] and Klebsiella aerogenes [n = 1]) were identified. There were diverse PFGE profiles and sequence types (STs) in most of the species except for K. oxytoca. All isolates of K. oxytoca belonged to ST29 with similar PFGE profiles, suggesting their clonal transmission. Plasmid analysis by WGS revealed that all 22 isolates but one shared a ca. 50-kb IncN plasmid backbone with blaIMP-6 suggesting interspecies gene transmission, and typing of plasmids explained epidemiological links among cases. A case-control study showed pancreatoduodenectomy, changing drains in fluoroscopy room, continuous peritoneal lavage and enteric fistula were associated with IMP-6-CPE acquisition among the patients. Plasmid analysis of isolates in an outbreak of IMP-6-CPE suggested interspecies gene transmission and helped to clarify hidden epidemiological links between cases.

Comparison of the inoculum size effects of antibiotics on IMP-6 ß-lactamase-producing Enterobacteriaceae co-harboring plasmid-mediated quinolone resistance genes.

Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened ß-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum ß-lactamases. All isolates carried one or more PMQRs; aac(6')-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-ß-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.

Peritonitis due to Moraxella osloensis: A case report and literature review.

A-26-year-old man was admitted to our hospital with diffuse abdominal pain, nausea, and vomiting. He had a history of malignant nephrosclerosis, for which he had been receiving peritoneal dialysis (PD) for the past 14 months. His PD effluent was cloudy and turbid (white blood cell count, 10,528/µL; neutrophils 95.2%). A Gram-negative coccobacillus was isolated from peritoneal fluid culture. However, the organism could not be identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) (Vitek MS, bioMérieux), but was identified as Moraxella osloensis by the 16S rRNA gene sequencing. He was successfully treated with intraperitoneal cefazolin therapy for 3 weeks without removing the intra-abdominal catheter. A literature review revealed three previous case reports all of which were diagnosed by MALDI Biotyper (Bruker Daltonics), suggesting that the identification of M. osloensis may vary depending on the type of MALDI-TOF MS system. In conclusion, we experienced a case of M. osloensis infection in a PD patient, which was successfully treated by antibiotic treatment, without removing the PD catheter.