In vitro effects of the new oral ß-lactamase inhibitor xeruborbactam in combination with oral ß-lactams against clinical Mycobacterium abscessus isolates.

Non-tuberculosis mycobacteria (NTM), particularly Mycobacterium abscessus subsp. abscessus (M. abscessus), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics, including ß-lactams. M. abscessus produces a class A ß-lactamase, whose activity is inhibited by cyclic boronic acid ß-lactamase inhibitors. We aimed to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid ß-lactamase inhibitor, against M. abscessus when combined with five ß-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). The drug susceptibilities of 43 M. abscessus clinical isolates obtained from 43 patients between August 2005 and May 2014 were tested. The MIC results for each ß-lactam with or without 4 µg/mL xeruborbactam were examined. Xeruborbactam lowered the MIC90 values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC90 values of cefoxitin without xeruborbactam were 32 µg/mL and did not change upon the addition of xeruborbactam. The lowest MIC90 value was obtained for tebipenem with xeruborbactam. Almost all isolates had an MIC of 4 µg/mL; one isolate had an MIC of 2 µg/mL. With respect to the susceptibility to the same family drug, the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%) for tebipenem with xeruborbactam. Combining tebipenem and xeruborbactam could be considered an effective all-oral regimen that benefits outpatient treatment of M. abscessus pulmonary disease. IMPORTANCE: Mycobacterium abscessus subsp. abscessus (M. abscessus) disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for M. abscessus infection, especially in the continuation phase. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid ß-lactamase inhibitor capable of inhibiting the class A ß-lactamase produced by M. abscessus, against 43 M. abscessus clinical isolates when combined with five ß-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of M. abscessus pulmonary disease.

Treatment strategy for older patients with pneumonia independent of the risk of drug resistance in the world's top country for longevity.

The number of older people with impaired swallowing function increases with aging population. Aspiration pneumonia is one of the most cases of pneumonia developing among older people. As aspiration pneumonia may develop as a result of age-related deterioration, it is crucial to consider it as an unavoidable event with aging. While pneumonia is diagnosed based on respiratory symptoms and radiological features, the lung involvement of aspiration pneumonia may be undetectable via a frontal chest radiograph in some cases. Bacterial profiles show the predominance of drug-resistant bacteria, such as Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA), but isolated bacteria from respiratory samples do not necessarily indicate causative pathogens. Furthermore, there is no evidence regarding treatment superiority using broad-spectrum antibiotics compared with narrow-spectrum antibiotics. Even if isolated pathogens are a causative factor for pneumonia among older patients, the use of broad-spectrum antibiotics covering the bacteria may not improve their outcomes. Therefore, we propose a treatment strategy independent of the risk of drug resistance focusing on the discrimination of patients who are unlikely to respond to broad-spectrum antibiotics. An aspiration risk is associated with increased in-hospital mortality in patients with pneumonia, which could also lead to a greater risk of poor long-term outcomes with increased 1-year mortality. Advance care planning is now recognized as a process for communication and medical decision-making across the life course. This approach would be widely recommended for older people with aspiration risk.

Acute eosinophilic pneumonia in twins.

The pathogenesis of eosinophilic pneumonia is currently poorly understood, and this disease has not been reported in twins since 1983. Herein, we report a case of acute eosinophilic pneumonia in twins, which appeared to be triggered by initial smoking at different times by both patients. One patient resumed smoking after recovering from eosinophilic pneumonia, with no observed recurrence. This study discussed the possibility of an association between susceptibility to eosinophilic pneumonia and genetic factors in twins.

Correlation between tuberculosis-specific interferon-γ release assay and intrathoracic calcification: A cross-sectional study.

BACKGROUND: Although persistent tuberculosis (TB) infection is known to cause calcification in the lungs, the relationship between intrathoracic calcification and the results of the interferon-γ release assay (IGRA) has not been fully elucidated. This study aimed to assess the association between intrathoracic calcification and IGRA results. METHODS: We retrospectively included consecutive patients who concurrently underwent chest X-ray, chest computed tomography (CT), and an IGRA. Patients with a current diagnosis of active TB or treatment history of active TB or latent tuberculosis infection (LTBI) were excluded. The association between calcification according to the chest X-ray or CT and IGRA results were analyzed using binomial logistic regression. RESULTS: This study included 574 patients, and 38 (7%) patients had a positive IGRA result. Patients with a positive result were significantly older and had a higher proportion of comorbidities, and history of tuberculosis exposure compared to those with a negative result. Calcification of the lung field and mediastinal lymph nodes according to chest CT was more frequently observed in patients with a positive IGRA result, whereas no significant difference was observed concerning the proportion of lung field calcification on chest X-ray between patients with positive and negative IGRA results. In multivariate analysis, calcification of mediastinal lymph nodes alone (adjusted odds ratio [OR] = 3.82, 95% confidence interval [CI] = 1.76-8.26) and the combination of lung field and mediastinal lymph node calcification (adjusted OR = 4.12, 95% CI = 1.51-11.76) on chest CT was independently associated with positive IGRA results. CONCLUSIONS: The finding of mediastinal lymph node calcification, with or without lung field calcification, on chest CT was associated with positive IGRA results independent of TB exposure history. Previous TB infection including eliminated TB infection and LTBI can be suspected when calcified lymph nodes in are observed the mediastinum on chest CT.