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.

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.

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.

Rat-Bite Fever in Human with Streptobacillus notomytis Infection, Japan.

We report a case of rat-bite fever in a 94-year-old woman with Streptobacillus notomytis infection. We established an epidemiologic link between exposure to rats and human infection by performing nested PCRs that detected S. notomytis in the intraoral swab specimens obtained from rats captured in the patient's house.

Molecular diagnosis and characterization of a culture-negative mycotic aneurysm due to ST54 Haemophilus influenzae type b with PBP 3 alterations.

Mycotic aneurysm is a rare but life-threatening disease that warrants an integrated therapeutic approach involving surgical intervention and prolonged antibiotic use. However, the causative organisms are often unidentified because antibiotics started empirically render blood and tissue cultures negative. Molecular diagnosis has been reported to be useful in such culture-negative cases. We report a case of a culture-negative mycotic aortic aneurysm due to Haemophilus influenzae, diagnosed by direct 16S rRNA polymerase chain reaction (PCR) and sequencing of the resected aneurysm tissue. PCR for serotype revealed type b, and PCR and sequencing of the ftsI gene revealed alterations in penicillin-binding protein 3, suggesting resistance to ampicillin. Multilocus sequence typing demonstrated that the isolate belonged to sequence type 54.

Characteristics of health problems in returned overseas travelers at a tertiary teaching hospital in a suburban area in Japan.

Few studies have analyzed the characteristics of patients who develop physical disorders after overseas travel. We retrospectively reviewed the medical records of 183 patients who visited Nara Medical University Hospital from 2008 to 2016 because of physical problems after traveling abroad. The main travel destinations were Southeast Asia (n = 100), Africa (n = 27), and South Asia (n = 23). The main reasons for the travel were leisure (n = 96), business (n = 51), and volunteer work (n = 19). The most common final diagnosis was gastrointestinal disease (n = 72), followed by febrile disease (n = 59) and respiratory disease (n = 19). There were eight malaria cases, including one patient who was infected after <14 days of overseas travel. Additionally, 61 of 71 cases of travelers' diarrhea and 15 of 21 cases of dengue fever occurred after <14 days travel. 26 cases of vaccine preventable diseases, such as hepatitis A, typhoid fever, and influenza, were observed. Consequently, healthcare providers should notify Japanese overseas travelers that there is a non-negligible health risk inherent to short-term travel, while stressing on the importance of pre-travel medical consultation.

Bacteremia secondary to Alloscardovia omnicolens urinary tract infection.

A 70-year-old woman was admitted to our hospital with malaise, bilateral leg edema, and oliguria. She had a history of advanced uterine cancer. Bilateral double-J catheters were inserted because growth of intra-abdominal metastases led to bilateral ureteral stricture and hydronephrosis. Two days later, she suddenly developed high fever. Thin gram-positive bacilli of moderate length were detected in the anaerobic blood culture bottles. We performed 16S ribosomal RNA analysis of the isolate and it showed 100% match with Alloscardovia omnicolens DSM 21503(T). She was successfully treated with cefmetazole in addition to percutaneous nephrostomy.

A first case of isolation of Kerstersia gyiorum from urinary tract.

An 82-year-old man with percutaneous nephrostomy presented to our Hospital with dysuria for one day. The patient's percutaneous nephrostomy tube was exchanged, with about 20 mL of creamy purulent urine being collected. Direct smear of the urine specimen showed polymorphonuclear leukocytes and small Gram-negative bacilli, some of which had undergone phagocytosis. This organism was identified as Kerstersia gyiorum using 16S ribosomal RNA gene analysis. He was successfully recovered with exchange of his percutaneous nephrostomy tube and fluoroquinolone internal use treatment. This is the first case report of urinary tract infection due to K. gyiorum.

Disease progression of HIV-1 infection in symptomatic and asymptomatic seroconverters in Osaka, Japan: a retrospective observational study.

BACKGROUND: Estimates of the interval from HIV-1 infection to disease progression may be affected by selection bias, and data concerning asymptomatic early seroconverters are limited. We examined the interval until disease progression in HIV-1 seroconverters in whom the timing of infection could be estimated within 1 year before diagnosis. METHODS: Subjects included newly diagnosed patients at Osaka National Hospital between 2003 and 2010 who had either (1) symptomatic acute HIV-1 infection with a negative or intermediate reaction on Western blotting and a positive reaction on an HIV RNA test (symptomatic acute group) or (2) a positive reaction on Western blotting at diagnosis and a <1-year interval from the last negative HIV test until the first positive test. The latter was divided into symptomatic recent or asymptomatic recent groups based on the presence or absence, respectively, of any transient fever between the last negative and first positive tests. Disease progression was defined as a fall in the CD4 count to <350 cells/microL on 2 consecutive tests, the start of anti-HIV therapy, or the onset of AIDS-indicator diseases. Information was retrospectively collected from medical records. RESULTS: Subjects included 210 patients: 91 in the symptomatic acute group, 72 in the symptomatic recent group, and 47 in the asymptomatic recent group. In the symptomatic acute (0.8 years) and symptomatic recent (2.2 years) groups, the Kaplan-Meier estimate of median interval until disease progression was significantly shorter than that in the asymptomatic recent group (2.9 years). Multivariate analysis by Cox's proportional hazards test showed that the symptomatic acute group (vs. asymptomatic recent group: hazard ratio: 1.93; 95% confidence interval: 1.14-3.36; p = 0.0140) and a baseline CD4 count of <400 cells/microL (hazard ratio: 3.88; 95% confidence interval: 2.57-5.96; p < 0.0001) were independent prognostic factors associated with early disease progression. CONCLUSIONS: Symptomatic seroconversion was associated with early disease progression. Furthermore, the estimated median interval until the CD4 count was <350 cells/microL was only 2.9 years even in patients with asymptomatic seroconversion. These results suggest the importance of early diagnosis in early seroconverters.

Correlation between UGT1A1 polymorphisms and raltegravir plasma trough concentrations in Japanese HIV-1-infected patients.

Raltegravir (RAL), an HIV integrase inhibitor, is metabolized mainly by UDP-glucuronosyltransferase 1A1 (UGT1A1). Polymorphisms in UGT1A1 may cause alterations in the pharmacodynamics of RAL, which is taken twice daily with no dietary restrictions. We compared the effect of two polymorphic alleles in this gene, UGT1A1*6 and UGT1A1*28 on plasma RAL concentrations in Japanese HIV-1-infected patients. Of 114 Japanese HIV-1-infected patients who received RAL, the frequencies of UGT1A1*6 and UGT1A1*28 were 18% and 13%, respectively. The percentage of homozygotes for UGT1A1*6 and UGT1A1*28 was 6% and 4%, respectively, the percentage of compound heterozygotes for UGT1A1*6 and UGT1A1*28 was 2%, and that of heterozygotes for UGT1A1*6 and UGT1A1*28 was 22% and 17%, respectively. RAL plasma trough concentrations were compared for each polymorphism. Significantly higher levels of RAL were observed with patients who were homozygous for UGT1A1*6 (median: 1.0 µg/mL) than for the normal allele (median: 0.11 µg/mL; p = 0.021). Multivariate logistic regression analysis showed that the presence of one or two alleles of UGT1A1*6 or two alleles of UGT1A1*28 were independent factors associated with high RAL plasma trough concentrations (≥ 0.17 µg/mL). These results indicated that UGT1A1*6 and UGT1A1*28 are both factors influencing the RAL plasma trough concentrations in Japanese HIV-1-infected patients.

[A Case of Disseminated Mycobacterium genavense Infection in an AIDS Patient. A Case Report and a Review of the Literature].

A 44-year-old male, who was HIV seropositive, developped weight loss, high grade fever, and multiple lymphadenopathies. Bone marrow biopsy revealed a granuloma lesion, and at the same part of the specimen, Ziehl Neelsen staining showed multiple mycobacterium diffusely arranged in the histocytes. The culture did not show positive after 6 to 8 weeks. Finally we diagnosed disseminated Mycobacterium genavense using a house-keeping gene analysis including 16S rRNA sequencing of lymph punctate with fine needle aspiration and the specimen from the biopsy of the lymph node. If a specimen tests positive for Ziehl Neelsen staining smear positive, culture negative, and PCR negative for tuberculosis and Mycobacterium avium complex, we should consider M. genavense infection as one of the differential diagnoses.

Retrospective analysis of eltrombopag for the treatment of refractory primary immune thrombocytopenia in Japan.

Eltrombopag, an oral thrombopoietin receptor agonist, is a novel drug that can be used in cases with previously-treated primary immune thrombocytopenia (ITP). In this study, we retrospectively analyzed 22 Japanese ITP patients treated in four hospitals. A responder was defined as a patient achieving a platelet count between 50,000/µl and 400,000/µl, at 75% or more of on-treatment assessments. Excluding 2 patients whose treatments were interrupted at their request, 13 of 20 patients (65%) were responders. Ten of the 13 responders had been taking more than 5 mg of a steroid preparation in the form of prednisolone or its equivalent. In 7 of these patients, the steroid dose could be tapered to 5 mg or less. Disappearance or amelioration of hemorrhagic symptoms was observed in 11 of 19 patients who had these symptoms prior to treatment (9 of 10 responders, 2 of 7 non-responders), and the improvement rate was greater in responders (p=0.018). No factors were identified as being related to efficacy. Reported adverse effects were fever (1), malaise (3), headache (2), and muscle pain (1). One severe adverse event, cerebral thromboembolism, was reported in 1 patient. Although eltrombopag is a useful therapeutic agent for refractory ITP, it is necessary to evaluate its position in the overall treatment strategy for ITP after assessing long-term complications as well as therapeutic effects.

[A case of POEMS syndrome responding to autologous peripheral blood stem cell transplantation].

The patient, a 44-year-old male, subjectively noticed edema in his lower legs in March, 2010. By June 2010, he could not walk, and was admitted to this hospital. Since multiple neuropathy, increased serum vascular endothelial growth factor-3, M-proteinemia, edema, pericardial effusions, papilledema, increased platelet count and skin lesions were detected in the complete examination, he was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-proteinemia and skin changes (POEMS) syndrome. Treatment with steroid and furosemide was initiated in September 2010. This markedly improved edema and brought about mild recovery of proximal lower-limb muscle strength. The patient, however, suffered prolonged difficulty in walking because his distal lower-limb muscle strength was not improved. In October 2010, he received treatment with high-dose cyclophosphamide, followed by peripheral blood stem cell sampling with granulocyte-colony stimulating factor. In November 2010, he underwent treatment with high-dose melphalan, followed by autologous peripheral blood stem cell transplantation. Recovery to neutrophils greater than 500 was achieved at 13 days after transplantation. He could walk without assistance in February 2011. M-protein was not identified by immunofixation electrophoresis in August 2011. Autologous peripheral blood stem cell transplantation is regarded as a useful treatment for POEMS syndrome.

[Human immunodeficiency virus-related non-hodgkin lymphoma: a clinical investigation at our hospital].

We investigated 8 cases of non-Hodgkin lymphoma(NHL)in human immunodeficiency virus(HIV)seropositive individuals who were diagnosed and treated at Osaka City General Hospital between April 2002 and October 2012. All patients were men, and the average age at the onset of NHL was 46 years(range: 30-61). Histological types were as follows: diffuse large B cell lymphoma in 4 patients, plasmablastic lymphoma in 2 patients, primary effusion lymphoma in 1 patient, and Burkitt lymphoma in 1 patient. In 3 cases, HIV infection was identified before the onset of NHL. Highly active anti-retroviral therapy (HAART)was initiated in 6 cases, and in 4 of these, we administered antineoplastic chemotherapy. Three patients who did not receive antineoplastic chemotherapy died within 1 month of diagnosis. Although 1 of the patients who received chemotherapy achieved complete remission, this patient died of BK virus nephritis. The remaining 3 patients achieved complete remission and are currently alive after 6 to 9 months. We believe that the combination of antineoplastic chemotherapy with HAART will lead to prognostic improvement in HIV-seropositive patients with NHL.

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.

Assessing recovery of renal function after tenofovir disoproxil fumarate discontinuation.

Impaired renal function caused by tenofovir disoproxil fumarate (TDF) is considered reversible by discontinuing TDF administration, but there are occasional cases of incomplete recovery. We investigated the recovery of renal function after the discontinuation of TDF. Subjects comprised patients who had been started on TDF but in whom it was later discontinued because of impaired renal function. We investigated renal function until 96 weeks after the discontinuation of TDF, and the duration of TDF administration, up to May 2010. TDF was discontinued because of impaired renal function in 21 of 766 patients (2.7%). Following discontinuation, a significant recovery was seen in eGFR (p = 0.003). The median duration of administration was 28 days (6-941 days) in 9 patients whose eGFR recovered to pre-administration levels, 405 days (250-1,379) in 7 patients in whom mild recovery was seen, and 1,110 days (421-1,470) in 5 patients in whom eGFR was much lower than at the time of discontinuation. A significant correlation was seen between the eGFR recovery rate and the duration of TDF administration. TDF administration was discontinued because of renal impairment in 2.7% of patients. The duration of TDF administration was short in patients whose renal function recovered to pre-administration levels, but patients in whom sufficient recovery was not seen after discontinuation had received TDF over long periods and included many whose renal function gradually declined, even after discontinuation. Recovery of renal function after discontinuation of TDF is likely affected by the duration of TDF administration.