Development of a score model to predict long-term prognosis after community-onset pneumonia in older patients.

BACKGROUND AND OBJECTIVE: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model. METHODS: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected. RESULTS: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2. CONCLUSION: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered.

Efficacy and safety of lascufloxacin for nursing- and healthcare-associated pneumonia: A single-arm, open-label clinical trial.

BACKGROUND: Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. METHODS: In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. RESULT: During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. CONCLUSION: Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications.

Survey of Advance Care Planning Practices in Elderly COVID-19 Patients: A Multicenter Questionnaire Survey.

Objective Advance care planning (ACP) is a process in which the patient and family discuss end-of-life care in advance with healthcare providers in case decisional ability declines. Due to the rapid deterioration of symptoms and isolation for treatment, it is not easy for COVID-19 patients to discuss their end-of-life care with families and medical staff. We conducted a questionnaire survey to assess the current situation of ACP practices in hospitalized COVID-19 patients. Materials and methods Multicenter questionnaire surveys of hospitalized COVID-19 patients aged ≥60 years between January 2021 and August 2022 were conducted in two hospitals. The questionnaires assessed whether patients had discussed end-of-life medical treatment with their families and family physicians at the time of admission and their preferences for end-of-life medical treatments. Results A total of 109 patients aged 60-99 years (median 75.0 years) were enrolled. Only eight patients (7.3%) had practiced ACP at the time of admission. Age was a significant factor related to ACP practices (p=0.035). Although there was no significant difference between the ACP and non-ACP practiced groups for each end-of-life care, all eight patients in the ACP-practiced group were able to make decisions for all the end-of-life medical treatment, while 40 patients (33.0%) in the non-ACP-practiced group did not, showing a significant difference (p=0.026). Conclusion In hospitalized COVID-19 patients, the rate of ACP practice was as low as 7.3%. Awareness of ACP practice is necessary, especially for elderly patients with underlying diseases.

Clinical significance of a positive Clostridioides difficile glutamate dehydrogenase test on the outcomes of hospitalized older patients.

AIM: Clostridioides difficile infection worsens the outcome of older hospitalized patients; thus, its diagnosis is necessary for the nosocomial infection control. The standard diagnostic test's limited sensitivity for Clostridioides difficile infection, an enzyme immunoassay for Clostridioides difficile toxins, is of clinical concern. Glutamate dehydrogenase detection is usually tested combined with Clostridioides difficile toxins. However, the clinical significance of a positive glutamate dehydrogenase result is unclear. We evaluated the association between positive glutamate dehydrogenase results, in-hospital mortality and hospital stay length among older patients with suspected Clostridioides difficile infection. METHODS: In this retrospective cohort study, we examined the data of patients who received antibiotics (except for Clostridioides difficile infection treatment) after admission and tested for Clostridioides difficile infection using an enzyme immunoassay for Clostridioides difficile toxins and glutamate dehydrogenase in a secondary care hospital located in a rural region with high aging rate, between 2015 and 2018. RESULTS: In total, 188 patients were included (83.5% of them aged >75 years). Glutamate dehydrogenase positivity was independently associated with in-hospital mortality (adjusted odds ratio 2.19, 95% confidence interval 1.14-4.21) and hospital stay length (regression coefficient 16.0, 95% confidence interval 5.15-26.9). Clostridioides difficile toxin positivity was independently associated with hospital stay duration (regression coefficient 14.5, 95% confidence interval 0.04-29.1), unlike in-hospital mortality. CONCLUSIONS: Glutamate dehydrogenase was closely related to in-hospital mortality and prolonged hospitalization compared with Clostridioides difficile toxin. Clinicians should not neglect glutamate dehydrogenase-positive patients, even when they are Clostridioides difficile toxin-negative, and consider them as having poor prognostic potential. Geriatr Gerontol Int 2020; 20: 1138-1144.

Efficacy and safety of cefditoren pivoxil for exacerbations of chronic obstructive pulmonary disease: A prospective multicenter interventional study.

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

Intraabdominal abscess caused by Stenotrophomonas maltophilia: A case report.

INTRODUCTION: Stenotrophomonas maltophilia usually causes nosocomial infections, but intraabdominal abscesses or organ/space surgical site infection (SSI) secondary to this organism has been rarely reported. Here, we reported a rare case of SSI that presented as intraabdominal abscess caused by S. maltophilia. PRESENTATION OF CASE: A 68-year-old woman presented to our hospital with transverse colon cancer. Further work up with abdominal computed tomography (CT) revealed left renal cell carcinoma. Transverse colon resection and left kidney partial resection were performed. On post-operative day 10, she started to have fever at 38°C and repeat abdominal CT showed intraabdominal abscess. Empiric treatment with piperacillin/tazobactam (TAZ/PIPC) was initiated. However, fever persisted and the abscess size did not change despite 10 days of antibiotic. On post-operative day 20, drainage of intraabdominal abscess was performed. TAZ/PIPC was then shifted to meropenem (MEPM). After two days, S. maltophilia was identified in the culture of the abscess, and MEPM was shifted to minocycline (MINO). Fever disappeared after 7days of treatment and abdominal CT after 14 days showed almost complete resolution of the abscess. DISCUSSION: S. maltophilia is a multi-drug resistant, aerobic, non-glucose fermenting, non-sporulating, Gram-negative bacillus. S. maltophilia may cause a variety of infections, but intraabdominal abscesses as a manifestation of SSI due to this organism is relative rare. CONCLUSION: Although usually a non-pathogenic organism or colonizer, S. maltophilia can cause organ/space SSI in an immunocompromised host. Therefore, clinicians should be aware of the possibility that S. maltophilia may cause organ/space SSI.

Detection of high serum levels of ß-D-Glucan in disseminated nocardial infection: a case report.

BACKGROUND: ß-D-glucan (BDG) is a helpful diagnostic marker for many invasive fungal infections, but not for nocardiosis. Here, we reported the first case of nocardial infection with high serum level of BDG. CASE PRESENTATION: A 73-year-old man was hospitalized because of fever, headache, and appetite loss after 10 months of steroid and immunosuppressive therapy for cryptogenic organizing pneumonia. With a diagnosis of bacterial pneumonia, treatment with ampicillin/sulbactam was initiated. There was improvement on chest radiograph, but fever persisted. Further work-up revealed multiple brain abscesses on cranial magnetic resonance imaging (MRI). Serum galactomannan and BDG were elevated at 0.6 index and 94.7 pg/ml, respectively. Voriconazole was initiated for presumed aspergillus brain abscess. However, fever persisted and consciousness level deteriorated. Drainage of brain abscess was performed; based on the Gram stain and Kinyoun acid-fast stain, disseminated nocardiosis was diagnosed. Voriconazole was then shifter to trimethoprim/sulfamethoxazole. The presence of Nocardia farcinica was confirmed by the 16S rRNA gene sequence. Treatment course was continued; BDG level normalized after 1 month and cranial MRI showed almost complete improvement after 2 months. CONCLUSION: BDG assay is widely used to diagnose invasive fungal infection; therefore, clinicians should be aware that Nocardia species may show cross-reactivity with BDG assay on serum.

Relapsed Pulmonary Cryptococcosis during Tumor Necrosis Factor α Inhibitor Treatment.

A 35-year-old non-HIV patient developed pulmonary cryptococcosis after the initiation of infliximab. He recovered by fluconazole treatment and completed the therapy for a total of 6 months. However, he experienced a relapse 16 months later during retreatment with infliximab, revealing an interesting clinical course contradicting retreatment. This case also represents the first case of relapsed pulmonary cryptococcosis suspected during treatment with a biologic agent. Both of these aspects generated important clinical questions about the length of pulmonary cryptococcosis treatment and the necessity of introducing a second prophylaxis for such patients.

[A Case of Influenza A (H1N1) pdm09 Pneumonia Occurring Out of the Influenza Season].

A 42-year-old woman was referred to our hospital with a diagnosis of influenza A and pneumonia out of the influenza season. Chest CT findings resembled interstitial pneumonia, but we initiated anti viral agents and antibiotics. Flexible fiberoptic bronchoscopy was performed on hospital day 3. Based on the results of an RT-PCR analysis of broncho-alveolar lavage, this patient was diagnosed as having influenza viral pneumonia. In the influenza season, we can easily suspect influenza as a differential diagnosis, even if the patient's chest CT findings resemble interstitial pneumonia. Out of the influenza season, clinicians should take into consideration influenza viral pneumonia as a differential diagnosis.

Epidemiology and clinical features of pulmonary nontuberculous mycobacteriosis in Nagasaki, Japan.

BACKGROUND AND OBJECTIVES: Recent reports indicate that the incidence of nontuberculous mycobacterial-lung disease (NTM-LD) is increasing. This study aimed to investigate the epidemiology and clinical features of NTM-LD patients in Nagasaki prefecture, Japan to identify the negative prognostic factors for NTM-LD in Japan. METHODS: The medical records of patients newly diagnosed with NTM-LD in eleven hospitals in Nagasaki prefecture between January 2001 and February 2010 were reviewed. Data regarding the annual population of each region and the incidence of all forms of tuberculosis were collected to assess geographic variations in NTM-LD incidence, isolates, and radiological features. RESULTS: A total 975 patients were diagnosed with NTM-LD. The incidence increased over the study period and reached 11.0 and 10.1 per 100,000 population in 2008 and 2009, respectively. M. intracellulare was the most common pathogen in the southern region, and M. avium most common in other regions. The most common radiographic pattern was the nodular-bronchiectatic pattern. Age >60 years, body mass index <18.5 kg/m2, underlying lung disease, and cavitary pattern were the negative prognostic factors at the 1-year follow-up. CONCLUSIONS: The incidence of NTM-LD has been increasing in Nagasaki prefecture. The isolates and radiographic features of patients vary markedly by region.

Autoimmune pulmonary alveolar proteinosis co-existing with breast cancer: a case report.

INTRODUCTION: Pulmonary alveolar proteinosis is a rare pulmonary disease characterized by excessive alveolar accumulation of surfactant due to defective alveolar clearance by macrophages. There are only a few published case reports of pulmonary alveolar proteinosis occurring in association with solid cancers. To the best of our knowledge, there are no previously reported cases of pulmonary alveolar proteinosis associated with breast cancer. CASE PRESENTATION: A 48-year-old Asian woman, a nonsmoker, presented to our institution with a right breast mass. Biopsy examination of the lesion revealed scirrhous carcinoma. A chest computed tomography scan for metastases showed abnormal shadows in both upper lung fields. As a result of flexible fiberscopic bronchoscopy, this patient was diagnosed as having pulmonary alveolar proteinosis. This case was categorized as autoimmune pulmonary alveolar proteinosis due to the positive anti-granulocyte-macrophage colony-stimulating factor antibody. Pulmonary alveolar proteinosis decreased gradually after mastectomy. CONCLUSIONS: The present case involved the coincident occurrence of autoimmune pulmonary alveolar proteinosis with breast cancer; breast cancer may be a factor during pulmonary alveolar proteinosis development.

A retrospective comparative study of recombinant human thrombomodulin and gabexate mesilate in sepsis-induced disseminated intravascular coagulation patients.

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

A case of community-acquired pneumonia due to influenza A virus and Nocardia farcinica co-infection.

Nocardia spp. has not been reported previously as a cause of post-influenza pneumonia. Here we present a first case of post-influenza bacterial pneumonia due to Nocardia farcinica. Initial reason for hospitalization of the 90 year old female patient was a pneumonia with the symptoms of fever and productive cough. A rapid test for influenza antigen was positive for influenza A virus. Treatment with Zanamivir and piperacillin was initiated. However, after 1 week of treatment, the infiltration shadows on chest X-ray had worsened. Because the expectorated sputum collected on admission for culture was found to be positive for Nocardia spp., piperacillin was replaced with trimethoprim/sulfamethoxazole, and a chest X-ray showed some improvement. Although pulmonary nocardiosis with co-infection with influenza A is extremely rare, clinicians should be alert to the possibility.

[A case of lung cancer pain relief and safe return home by strontium chloride].

Strontium chloride 89 (89Sr) is used as a systemic radiopharmaceutical therapy for the palliation of pain in patients with metastatic bone cancer. A 64-year-old man had previously undergone an operation to resect his right upper lobe of lung and sixth rib. He was diagnosed with lung cancer (large cell carcinoma, pT3N0M0, stage IIB). Three months later, he was treated with chemoradiotherapy for local recurrence. Ten months later, he could not sit up due to severe pain of the left ilium, although he had been treated with opiate analgesics. Fourteen months later, his hospital stay was prolonged and he was treated with 89Sr. One week after injection, the pain was almost completed relieved. Two weeks after injection, morphine infusion was stopped and a reduced dose of a fentanyl patch was used. He was also able to eat meals. Three weeks after injection, he started rehabilitation. Two months after the injection of 89Sr, he could return home from the hospital. Adverse events included grade 2 leukopenia, neutropenia and thrombocytopenia. These peaked 2 months after injection.

Genetic variants in antioxidant pathway: risk factors for hepatotoxicity in tuberculosis patients.

Tuberculosis (TB) treatment can cause serious sequelae including adverse effects such as anti-TB drug-induced hepatotoxicity (ATDH). We performed a candidate gene-based association study between single nucleotide polymorphisms (SNPs) in 10 genes in the antioxidant pathway and ATDH susceptibility. The subjects comprised 100 Japanese patients with pulmonary TB who received a treatment regimen including isoniazid and rifampicin. Out of them, 18 patients had ATDH. Thirty-four tag SNPs in 10 genes were analyzed by PCR-restriction fragment length polymorphism or PCR-direct DNA sequencing. The frequencies of alleles and genotypes between patients with and without ATDH were compared in three different genetic models. Statistical analyses revealed that a C/C genotype at rs11080344 in NOS2A, a C/C genotype at rs2070401 in BACH1, and a G/A or A/A genotype at rs4720833 in MAFK independently conferred ATDH susceptibility. Remarkably, the association of the latter two tag SNPs with ATDH susceptibility was highly statistically significant (P = 0.0006) with an odds ratio of 9.730. This study is the first report to demonstrate that NOS2A, BACH1, and MAFK appear to be genetic determinants of ATDH in Japanese patients with TB. Furthermore, a combination of BACH1 and MAFK polymorphisms may be useful as new biomarkers to identify high-risk Japanese TB patients for ATDH.

The first surgical treatment case of pulmonary Mycobacterium malmoense infection in Japan.

Mycobacterium malmoense is a very rare pathogen of pulmonary infectious disease in Japan. We encountered a case of M. malmoense infectious lung disease which could be cured by surgical operation without chemotherapy. M. malmoense strains were isolated in both the bronchial washing lavage and the removed lung specimen, and it were identified using 16S rRNA gene and rpoB gene sequencing. This case might indicate that pulmonary infectious disease caused by a rare non-tuberculous mycobacteria pathogen should be positively considered to be treated surgically as an initial therapy when the patient's condition is admissive, and also indicated the importance of identification of the causative pathogen from surgical specimens. In addition, this was the second report of M. malmoense infectious disease, and the first case of surgical treatment case of M. malmoense lung disease in Japan, as far as we could determine.

A patient with fulminant influenza-related bacterial pneumonia due to Streptococcus pneumoniae followed by Mycobacterium tuberculosis infection.

A 74-year-old man with poorly controlled diabetes mellitus was admitted to our hospital because of severe respiratory disturbance, fever, and sputum. We found massive consolidation of the right lung and nodular shadows on the left lung on chest X-ray, and detected influenza virus and Streptococcus pneumoniae antigen from a nasopharyngeal swab and urine sample, respectively. Co-infection with influenza virus and bacteria was suspected, and oseltamivir and biapenem were prescribed. Laboratory data improved after the addition of sivelestat sodium hydrate, an inhibitor of neutrophil-derived elastase; however, chest X-ray findings became worse on Day 8, and we administered 1 g methylprednisolone intravenously for two days. On Day 12, we detected Mycobacterium tuberculosis in the sputum, even though we did not previously detect any acid-fast bacilli, and started anti-tuberculosis drugs, such as isoniazid, rifampicin, ethambutol hydrochloride, and pyrazinamide; however, the patient died 12 days later. Severe influenza-related bacterial pneumonia with Streptococcus pneumoniae and subsequently secondary tuberculosis infection were finally suspected in this case. This was a very rare case in which additional tuberculosis infection was found in a patient with fulminant pneumonia due to co-infection of influenza virus and bacteria. It is necessary to observe patients with influenza carefully, especially when steroids are used, even if antibiotics are also administered.