Two cases of Clostridium ramosum bacteremia with intestinal perforation: The antimicrobial susceptibility of clinical strains.

Clostridium ramosum is one of the obligate anaerobes that constitute the intestinal microbiota, and one of the rare Clostridia. With Clostridium ramosum, very few data have been reported to investigate antimicrobial susceptibility for clinical isolates that have caused bacteremia. Here, we report two cases of Clostridium ramosum bacteremia. The first case was a 54-year-old Japanese man with taking 20mg hydrocortisone for hypopituitarism. He presented to the emergency department for an unknown cause cardiopulmonary arrest. At the hospital day 36, he had fever and a drop in blood pressure. Abdomen computed tomography (CT) revealed free air around the ascending colon, we diagnosed with intestinal perforation, and peritonitis. Blood culture revealed Clostridium ramosum. We administered conservative management by 6-week of antibiotic treatment. The second case was a 78-year-old Japanese man with no significant medical history. He was referred to our hospital with fever and abdominal pain. Abdomen CT revealed perforated appendicitis, and blood cultures revealed Clostridium ramosum. We performed emergency surgery, and administered one-week course of antibiotic treatment. This report demonstrates two cases of Clostridium ramosum bacteremia with intestinal perforation, and the antimicrobial susceptibility of each clinical strain. For the future, it is necessary to accumulate data on the susceptibility of clinical isolates in order to find an appropriate treatment.

Invasive pulmonary aspergillosis caused by Aspergillus terreus diagnosed using virtual bronchoscopic navigation and endobronchial ultrasonography with guide sheath and successfully treated with liposomal amphotericin B.

Invasive aspergillosis is a significant cause of mortality in patients with hematological malignancy. Early diagnosis of invasive pulmonary aspergillosis (IPA) by bronchoscopy is recommended but is often difficult to perform because of small lesion size and bleeding risk due to thrombocytopenia. A 71-year-old woman had received initial induction therapy for acute myeloid leukemia. On day 22 of chemotherapy, she had a high fever, and the chest computed tomography scan revealed a 20-mm-sized nodule with a halo sign. Bronchoscopy assisted by virtual bronchoscopic navigation (VBN) and endobronchial ultrasonography with a guide sheath (EBUS-GS) was performed, and Aspergillus terreus was identified from the culture of obtained specimens. A. terreus is often resistant to amphotericin B; thus, voriconazole is usually recommended for treatment. However, the obtained A. terreus isolate showed minimal inhibitory concentrations of 2 µg/mL for voriconazole and 0.5 µg/mL for amphotericin B. Therefore, the patient was successfully treated with liposomal amphotericin B. For patients suspected of having IPA, early diagnosis and drug susceptibility testing are very important. This case suggests that bronchoscopy using VBN and EBUS-GS is helpful for accurate diagnosis and successful treatment even if the lesion is small and the patient has a bleeding risk.

Three-year epidemiological analysis of Clostridioides difficile infection and the value of hospital-infection control measures in a tertiary-care teaching hospital in Japan using PCR-based open-reading frame typing.

INTRODUCTION: Clostridioides difficile is an important causative pathogen in antibiotic-associated colitis and nosocomial infections. This study aimed to assess immunochromatographic test results for C. difficile infection and the utility of PCR-based open-reading frame typing (POT) for potentially controlling the intra-ward transmission of C. difficile. METHODS: We conducted a molecular epidemiological analysis using POT to investigate 102 inpatients who tested positive for the C. difficile toxin using immunochromatography in a tertiary-care teaching hospital in Japan between 2016 and 2018; isolates from the patients were obtained and cultured. RESULTS: The number of POT numbers detected in 2016, 2017, and 2018 were 27 (among 34 patients), 20 (among 31 patients), and 28 (among 37 patients), respectively. During this three-year period, there were seven cases whose bacterial strains with the same POT number was identified in the same ward within 6 months. The intra-ward transmission rate was the highest in 2017 (16.1%). Intra-ward transmission was identified at a higher rate in patients whose sample cultures tested toxin-positive than in patients whose sample cultures tested toxin- and glutamate-dehydrogenase-positive via immunochromatography (16% vs. 3%, p < 0.05). CONCLUSIONS: We conclude that the use of immunochromatographic tests for C. difficile diagnosis and epidemiological analyses via POT may be helpful for evaluating intra-ward transmission of C. difficile.

Incidental finding of neurosyphilis with intracranial hemorrhage and cerebral infarction: A case report.

Syphilis has recently increased in prevalence in Japan. Neurosyphilis is a special pathological condition of syphilis well known to cause cerebral vasculitis and ischemic stroke. Neurosyphilis in the meningovascular stage rarely causes caliber irregularity of the cerebral blood vessels or cerebral hemorrhage. We describe the case of a 49-year-old Japanese man with neurosyphilis. Cerebral hemorrhage, multiple cerebral infarctions, and caliber irregularity of the cerebral blood vessels were observed, the patient underwent surgery for cerebral hemorrhage on the day of admission, all of which were suspected to be caused by syphilis. He was started on an antibacterial treatment of penicillin on the day of admission and was diagnosed with neurosyphilis the following week based on his serum and spinal fluid test results. His condition improved, and he was transferred to another hospital after 4 weeks of treatment consisting of 3 weeks of infusion treatment with benzylpenicillin followed by oral treatment with amoxicillin. To the best of our knowledge, this is a rare case of neurosyphilis in conjunction with cerebral hemorrhage and cerebral infarction. Clinicians should consider syphilis in the differential diagnosis of cerebral hemorrhage and cerebral infarction and test patients for sexually transmitted diseases, in addition to cerebrospinal fluid testing, when cerebral hemorrhage occurs with an unknown cause. This is especially pertinent when patients present with cerebral infarction or caliber irregularity of the cerebral blood vessels.

Corynebacterium jeikeium-induced infective endocarditis and perivalvular abscess diagnosed by 16S ribosomal RNA sequence analysis: A case report.

INTRODUCTION: Corynebacterium jeikeium normally presents on human skin, and it is often judged as contamination when it is cultured from blood. C. jeikeium can cause infective endocarditis, especially, that associated with cardiac surgery and prosthetic valvular endocarditis. CASE REPORT: A 66-year-old Japanese male patient was diagnosed with C. jeikeium-induced infective endocarditis (IE) and perivalvular abscess after a coronary artery bypass grafting and aortic valve replacement with bioprosthesis; pyogenic spondylodiscitis was also observed. Patch repair for aortic valve annulus and re-Bentall procedure with bioprosthesis was performed for IE and perivalvular abscess. The causative bacterium was confirmed as C. jeikeium on 16S ribosomal RNA sequencing of surgical sample and positive blood culture. The patient underwent six weeks of intravenous antibacterial treatment with vancomycin and an additional two weeks of oral treatment with linezolid, following which, his condition improved. Corynebacterium jeikeium can cause infective endocarditis and perivalvular abscess, which is a more severe condition than IE. CONCLUSION: 16S ribosomal RNA sequencing is useful in diagnosing bacterial species that can cause contamination, such as Corynebacterium spp.

Congenital bronchial atresia complicated by a lung abscess due to Aspergillus fumigatus: a case report.

BACKGROUND: Congenital bronchial atresia is a rare pulmonary abnormality characterized by the disrupted communication between the central and the peripheral bronchus and is typically asymptomatic. Although it can be symptomatic especially when infections occur in the involved areas, fungal infections are rare complications in patients with bronchial atresia. We report a case of congenital bronchial atresia complicated by a fungal infection. CASE PRESENTATION: A 30-year-old man with no previous history of immune dysfunction was brought to a nearby hospital and diagnosed with a left lung abscess. Although antimicrobial treatment was administered, it was ineffective, and he was transferred to our hospital. Since diagnostic imaging findings and bronchoscopy suggested congenital bronchial atresia and a fungal infection, he was treated with voriconazole and surgical resection was subsequently performed. A tissue culture detected Aspergillus fumigatus and histopathological findings were compatible with bronchial atresia. After discharge, he remained well and voriconazole was discontinued 5 months after the initiation of therapy. CONCLUSION: Bronchial atresia is a rare disease that is seldom complicated by a fungal infection, which is also a rare complication; however, physicians should consider fungal infections in patients with bronchial atresia who present with infections resistant to antimicrobial treatment.

Disseminated Mycobacterium abscessus subsp. massiliense infection in a Good's syndrome patient negative for human immunodeficiency virus and anti-interferon-γ autoantibody: a case report.

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.

The effect of intervention by an antimicrobial stewardship team on anaerobic bacteremia.

The effect of antimicrobial stewardship (AS) on anaerobic bacteremia is uncertain. This study aimed to assess the effect of interventions by the AS team (AST) on clinical and microbiological outcomes and antimicrobial use. An AS program was introduced at Osaka City University Hospital in January 2014; an interdisciplinary AST was established. We enrolled patients with anaerobic bacteremia between January 2009 and December 2018. Patients were classified into the pre-intervention group (from January 2009 to December 2013) and the post-intervention group (from January 2014 to December 2018). A significant decrease in definitive carbapenem use (P = 0.0242) and an increase in empiric tazobactam/piperacillin use (P = 0.0262) were observed in the post-intervention group. The de-escalation rate increased significantly from 9.38% to 32.7% (P = 0.0316) in the post-intervention group. The susceptibility of Bacteroides species and 30-day mortality did not worsen in the post-intervention group. These results showed that interventions by an AST can reduce carbapenem use and increase the de-escalation rate without worsening patient outcomes.

The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan.

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.

Successful treatment of invasive pulmonary aspergillosis caused by Aspergillus felis, a cryptic species within the Aspergillus section Fumigati: A case report.

Aspergillus species are a major cause of life-threatening infections in immunocompromised hosts, and the most common pathogen of invasive aspergillosis is Aspergillus fumigatus. Recently, the development of molecular identification has revealed cryptic Aspergillus species, and A. felis is one such species within the Aspergillus section Fumigati reported in 2013. We describe a case of invasive pulmonary aspergillosis caused by A. felis in a 41-year-old Japanese woman diagnosed with myelodysplastic syndrome. She presented with fever 19 days after undergoing autologous peripheral blood stem cell transplantation and was clinically diagnosed with invasive pulmonary aspergillosis. Bronchoscopy and bronchoalveolar lavage were performed for definitive diagnosis. The ß-tubulin genes of the mold isolated from the bronchoalveolar lavage fluid, and sequenced directly from the PCR products using a primer pair were found to have 100% homology with A. felis. We successfully treated the patient with echinocandin following careful susceptibility testing. To the best of our knowledge, this is the first published case reporting the clinical course for diagnosis and successful treatment of invasive aspergillosis by A. felis.

The intervention by an antimicrobial stewardship team can improve clinical and microbiological outcomes of resistant gram-negative bacteria.

Antibiotic stewardship (AS) improves patient outcomes and rates of antibiotic susceptibilities. However, the long-term effect of AS programs (ASPs) on mortality is unclear. This study aimed to assess the impact of bedside interventions by an AS team (AST) on clinical and microbiological outcomes. This retrospective study enrolled patients with bloodstream infections (BSI) and long-term use of broad-spectrum antibiotics (more than 7 days). The main outcomes were 30-day and in-hospital mortality of patients with BSI. The secondary outcomes were the day of therapy (DOT) and susceptibility of antipseudomonal agents. Cases were classified into two groups: the pre-ASP group comprised cases between 2011 and 2013 and the post-ASP group, between 2014 and 2016. The outcomes were then compared between the two groups. Among the patients with all BSI (n = 1187), no significant differences in 30-day mortality were observed between those in the pre-ASP and post-ASP groups. However, in-hospital mortality was significantly lower in the post-ASP group than that in the pre-ASP group (24.8% vs. 18.0%; P = 0.004). Furthermore, the 30-day and in-hospital mortality of resistant gram-negative bacteraemia was significantly lower (20.4% vs.10.5%; P = 0.04 and 28.0% vs.16.1%; P = 0.03). The DOT of broad-spectrum antibiotics decreased except that of tazobactam/piperacillin. The susceptibilities of tazobactam/piperacillin, ceftazidime, cefepime, sulbactam/cefoperazone, gentamicin, ciprofloxacin levofloxacin, imipenem and meropenem were significantly better. Interventions by the AST can improve the clinical and microbiological outcomes, especially resistant gram-negative bacteria. Furthermore, this effect of our ASP can continue for a long term.

A case of allergic bronchopulmonary mycosis due to Schizophyllum commune with elevated serum carcinoembryonic antigen levels.

A 78-year-old Japanese woman without any history of asthma or smoking presented prolonged cough. Laboratory data showed elevated serum CEA levels and a chest CT revealed a mass with abnormal uptake in the left lower lobe. One month later, the mass spontaneously regressed, and CEA levels improved. However, the symptoms progressed during the observation period without treatment. Chest radiograph findings revealed collapse of the right middle lobe, and Schizophyllum commune was isolated from the mucous plugs; the patient was diagnosed with allergic bronchopulmonary mycosis (ABPM). Herein, we report the first case of ABPM caused by S. commune with elevated CEA levels and mimicking lung cancer.

Clinical analysis of 71 spontaneous pneumomediastinum cases: an observational study from a tertiary care hospital in Japan.

BACKGROUND: Spontaneous pneumomediastinum is characterized by the presence of interstitial air in the mediastinum without any underlying disease. Some cases of spontaneous pneumomediastinum have been reported in the past, although only few reports are available, and its management remains uncertain. This study reviewed our experience in the diagnosis and treatment of spontaneous pneumomediastinum. METHODS: A retrospective study of 71 cases treated for spontaneous pneumomediastinum at the Yodogawa Christian Hospital between April 2005 and March 2020 was conducted. RESULTS: The patients' mean age was 19.3 years (range, 7-48 years). A triggering event was noted in 69% of the cases. Seventy-six percent of the patients were admitted to the hospital, and 24% were outpatients. Treatment included analgesia, rest, antibiotics, and/or oxygen therapy. Thirty-six patients (51%) were treated with antibiotics. None of the cases presented any complications, including mediastinitis or worsening respiratory condition. Two patients (3%) had a recurrence of spontaneous pneumomediastinum. CONCLUSIONS: All the patients, with or without antimicrobial treatment and hospitalization, had favorable outcomes. We should therefore reconsider the need for hospitalization and antimicrobial therapy for patients with mediastinitis prophylaxis.

Risk factor analysis for piperacillin-tazobactam-resistant Enterobacter spp. bacteremia at a tertiary hospital.

This study aimed to analyze the risk factors for piperacillin-tazobactam (TZP1)-resistant Enterobacter spp. bacteremia. The medical records of 111 patients with Enterobacter spp. bacteremia divided into a TZP-susceptible group (minimum inhibitory concentrations [MICs2] ≤16 µg/mL) and TZP-resistant group (MICs >16 µg/mL) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, and infection site did not differ between the 2 groups. Multivariate analysis revealed that the independent predictor associated with TZP-resistant Enterobacter spp. bacteremia was the previous usage of third-generation cephalosporins (P = 0.036). In conclusion, TZP administration in cases of suspected Enterobacter spp. bacteremia previously treated with third-generation cephalosporin should be cautiously considered.

Isoniazid-induced Immune Thrombocytopenia.

Drug-induced thrombocytopenia occurs through immune-mediated platelet destruction, and its management is challenging during tuberculosis treatment. Although rifampicin is the most common drug causing thrombocytopenia, isoniazid can also cause thrombocytopenia. We herein report a 75-year-old man who developed thrombocytopenia during tuberculosis treatment. Platelet-associated immunoglobulin G and a drug-induced lymphocyte stimulation test for isoniazid were positive; no other causes of thrombocytopenia were identified. The patient was diagnosed with isoniazid-induced immune thrombocytopenia, and the platelet count normalized after isoniazid discontinuation. We describe the immunological mechanism of thrombocytosis due to isoniazid, an uncommon cause of thrombocytopenia that physicians should be aware exists.

A mouse model of rapidly progressive fatal haemorrhagic pneumonia caused by Stenotrophomonas maltophilia.

OBJECTIVES: Stenotrophomonas maltophilia causes severe haemorrhagic pneumonia with a reported mortality rate of 100%. However, currently there are no available mouse models of haemorrhagic pneumonia. In the present study, we generated a mouse model of haemorrhagic pneumonia and subjected the animals to treatment with levofloxacin and moxifloxacin to determine whether this model can be used to determine therapeutic effects. METHODS: Stenotrophomonas maltophilia was transtracheally administered to mice immunosuppressed with cyclophosphamide. We confirmed the pathological status of the S. maltophilia isolate and assessed whether the therapeutic effects of quinolone antibiotics could be studied using the model. Levofloxacin and moxifloxacin were administered to evaluate survival rate, bacterial load in the lungs and cardiac blood, as well as pathological changes in diseased lungs compared with those of the control group. RESULTS: Haemorrhagic pneumonia developed within 16-24 h after bacterial infection and was confirmed pathologically. Levofloxacin and moxifloxacin significantly improved survival rates, decreased the bacterial load in lungs and cardiac blood, and improved haemorrhagic pneumonia as indicated by pathological examination. CONCLUSIONS: We established a mouse model of rapidly progressive fatal haemorrhagic pneumonia caused by S. maltophilia that is useful for determining the therapeutic effect of various agents. We believe that this model will prove useful to further elucidate the mechanisms underlying haemorrhagic pneumonia as well as in the design and development of novel therapeutic modalities and targets.

Blood culture reports by infectious disease physicians can improve prognosis of bacteremia, including weekend-onset cases.

OBJECTIVES: Cases of positive blood cultures were previously reported by a microbiological technologist (MT) to an attending physician (AP), and the Antimicrobial Stewardship team provided medical assistance by grasping the situation at the morning meeting the next day. Since April 2018, MTs have reported positive blood cultures to an infectious disease physician (IDP), who proposes the management approach to the AP and provides weekend support. This study assessed the effectiveness of blood culture reports provided by IDPs to APs on outcomes of bacteremia, including weekend-onset cases. METHODS: Patient characteristics and prognoses before (October 2017 to March 2018) and after intervention (April to September 2018) were compared. RESULTS: The pre-intervention and post-intervention groups comprised 134 and 161 patients, respectively. Patients were more likely to be older (>65 years) in the post-intervention group (p < 0.05). There were no significant between-group differences in infection severity. The rate of de-escalation significantly increased from 38.1%-57.8% (p = 0.001). The rates of 28-day and in-hospital mortality reduced following the intervention (21.3% vs. 8.2% and 32.8% vs. 10.6%; p = 0.004 and p < 0.001, respectively). In-hospital mortality for weekend-onset cases also reduced following the intervention (33.3% vs. 12.9%, p = 0.01). Sepsis was a poor prognostic factor (OR 8.070, 95% CI 3.320-19.600, p < 0.001) and intervention was a good prognostic factor (OR 0.311, 95% CI 0.142-0.680, p = 0.003) affecting 28-day mortality in multivariate analysis. CONCLUSIONS: Changes to blood culture result reporting protocols can improve outcomes of bacteremia, including weekend-onset cases.

Clinical Characteristics of Rapidly Progressive Fatal Hemorrhagic Pneumonia Caused by Stenotrophomonas maltophilia.

Objective Hemorrhagic pneumonia due to Stenotrophomonas maltophilia (SM) in severely immunocompromised patients has a very poor prognosis. However, the risk factors for hemorrhagic pneumonia are not clear. Methods This study assessed the predictive factors of hemorrhagic pneumonia caused by SM. The medical records of patients admitted to Osaka City University Hospital with SM bacteremia between January 2008 and December 2017 were retrospectively reviewed. Patients All patients who had positive blood cultures for SM were included in this study. They were categorized into two groups: the SM bacteremia with hemorrhagic pneumonia group and the SM bacteremia without hemorrhagic pneumonia group. The clinical background characteristics and treatments were compared between these groups. Results The 35 patients with SM bacteremia included 4 with hemorrhagic pneumonia and 31 without hemorrhagic pneumonia. Hematologic malignancy (p=0.03) and thrombocytopenia (p=0.04) as well as the prior use of quinolone within 30 days (p=0.04) were more frequent in the SM bacteremia patients with hemorrhagic pneumonia than in those without hemorrhagic pneumonia. The mortality of the SM bacteremia patients with hemorrhagic pneumonia was higher than that of those without hemorrhagic pneumonia group (p=0.02). Conclusion Patients with SM bacteremia who have hematologic malignancy, thrombocytopenia, and a history of using quinolone within the past 30 days should be treated with deliberation.

Successful treatment with intravenous high-dose immunoglobulin for cardiomyopathy in dermatomyositis complicated with rapid progressive interstitial pneumonia.

Cardiomyopathy and rapid progressive interstitial pneumonia (IP) are potentially fatal complications in polymyositis/dermatomyositis. We experienced a dermatomyositis patient with multiple adverse prognostic factors, complicating rapid progressive IP, macrophage activation syndrome (MAS), and cardiomyopathy. IP and MAS improved with strong immunosuppressive therapy, despite which cardiomyopathy developed. Therefore, we applied intravenous high-dose immunoglobulin therapy (IVIg), and cardiac function improved dramatically. This is the first report to present the effectiveness of IVIg for cardiomyopathy in dermatomyositis.

Mortality caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia; a case control study: alert to Enterobacteriaceae strains with high minimum inhibitory concentrations of piperacillin/tazobactam.

This study aimed to assess the prognostic factors of patients with bacteremia due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) as well as the antimicrobial susceptibility, particularly to piperacillin/tazobactam (PTZ), among ESBL-PE strains. The medical records of 65 patients with ESBL-PE bacteremia divided into the survivor group (n = 52) and nonsurvivor group (n = 13) were retrospectively reviewed. The male-to-female ratio, age, underlying disease, leukocyte count, C-reactive protein level, and treatment did not differ between the 2 groups. Multivariate analysis showed that the independent predictors associated with hospital mortality of ESBL-PE bacteremia were sepsis (P = 0.047) and febrile neutropenia (P = 0.008); thus, early assessment of these conditions is important. Further, the minimum inhibitory concentration values of ESBL-PE isolates in nonsurvivors tended to be higher than those in survivors. PTZ should be used with caution in cases of ESBL-PE strains with low susceptibility to the drug.