Negative Sputum Cultures Research Articles

Prior tuberculosis, radiographic lung abnormalities and prevalent diabetes in rural South Africa

BackgroundGrowing evidence suggests that chronic inflammation caused by tuberculosis (TB) may increase the incidence of diabetes. However, the relationship between post-TB pulmonary abnormalities and diabetes has not been well characterized.MethodsWe analyzed data from a cross-sectional study in KwaZulu-Natal, South Africa, of people 15 years and older who underwent chest X-ray and diabetes screening with hemoglobin A1c testing. The analytic sample was restricted to persons with prior TB, defined by either (1) a self-reported history of TB treatment, (2) radiologist-confirmed prior TB on chest radiography, and (3) a negative sputum culture and GeneXpert. Chest X-rays of all participants were evaluated by the study radiologist to determine the presence of TB lung abnormalities. To assess the relationships between our outcome of interest, prevalent diabetes (HBA1c ≥6.5%), and our exposure of interest, chest X-ray abnormalities, we fitted logistic regression models adjusted for potential clinical and demographic confounders. In secondary analyses, we used the computer-aided detection system CAD4TB, which scores X-rays from 10 to 100 for detection of TB disease, as our exposure interest, and repeated analyses with a comparator group that had no history of TB disease.ResultsIn the analytic cohort of people with prior TB (n = 3,276), approximately two-thirds (64.9%) were women, and the average age was 50.8 years (SD 17.4). The prevalence of diabetes was 10.9%, and 53.0% of people were living with HIV. In univariate analyses, there was no association between diabetes prevalence and radiologist chest X-ray abnormalities (OR 1.23, 95%CI 0.95–1.58). In multivariate analyses, the presence of pulmonary abnormalities was associated with an 29% reduction in the odds of prevalent diabetes (aOR 0.71, 95%CI 0.53–0.97, p = 0.030). A similar inverse relationship was observed for diabetes with each 10-unit increase in the CAD4TB chest X-ray scores among people with prior TB (aOR 0.92, 95%CI 0.87–0.97; p = 0.002), but this relationship was less pronounced in the no TB comparator group (aOR 0.96, 95%CI 0.94–0.99).ConclusionsAmong people with prior TB, pulmonary abnormalities on digital chest X-ray are inversely associated with prevalent diabetes. The severity of radiographic post-TB lung disease does not appear to be a determinant of diabetes in this South African population.

Characteristics of culture-negative subclinical pulmonarytuberculosis: a single-center observation.

Little is known about culture-negative subclinical pulmonary tuberculosis (TB), and its diagnosis remains challenging. Therefore, this study aimed to identify the characteristics and the extent of disease associated with culture-negative subclinical pulmonary TB. This retrospective cohort study was conducted on immunocompetent individuals with subclinical pulmonary TB at a university hospital in Thailand from January 2014 to December 2019. Subclinical pulmonary TB was diagnosed based on the presence of radiographic abnormalities consistent with TB in the absence of TB symptoms. All subjects demonstrated significant improvement or resolution of radiographic abnormalities following the completion of treatment. At least two negative sputum cultures were needed to fulfill the definition of culture-negative pulmonary TB. Data were analyzed using univariate and multiple logistic regression analyses to determine the characteristics of those with culture-negative subclinical pulmonary TB compared to culture-positive ones. Out of the 106 individuals identified with subclinical pulmonary TB, 84 met the criteria for inclusion in the analysis. The study found lower radiographic extent and increasing age were key attributes of culture-negative subclinical pulmonary TB. The odds ratios (95% confidence interval) were 7.18 (1.76 to 29.35) and 1.07 (1.01 to 1.13), respectively. They tend to have lower rates of bilateral involvement in both chest x-ray (8.5% vs. 32.0%, p=0.006) and computed tomography (15.4% vs. 42.9%, p=0.035). However, no other specific radiographic findings were identified. People with culture-negative subclinical pulmonary TB were likely to have less radiographic -severity, reflecting early disease. Nevertheless, no radiographic patterns, except for unilaterality, were related to culture-negative subclinical pulmonary TB.

Aspergilloma Mimicry of Lung Cancer: A Case Report

Background: Aspergilloma and lung cancer have similar risk factors, clinical features, and supporting features. Special supporting examinations are needed to rule out the differential diagnosis of aspergilloma. Case presentation: A 52-year-old male patient with coughing up blood and risk factors for smoking had a chest X-ray and computed tomography scan (CT scan) of the thorax and found a picture of a lung tumor. Bronchoscopy was carried out, and a bronchial lavage culture was carried out for the impression of Aspergillosis, given 1x150 mg of fluconazole for 6 months with improved clinical results and chest radiographs as well as negative sputum culture results. Conclusion: This patient showed the condition of aspergilloma mimicking lung cancer.

Study of Culture Conversion in Drug-Resistant Pulmonary Tuberculosis on All-Oral Longer Regimen at IGIMS, Patna

ABSTRACT Background: Multidrug-resistant tuberculosis (MDR-TB) refers to tuberculosis that resists at least two primary drugs, namely isoniazid and rifampicin. To assess the management of MDR-TB, sputum culture conversion is performed. This study aimed to determine the culture conversion status of MDR-TB patients undergoing an all-oral longer regimen. Methods: This research constitutes an observational and prospective study conducted within a hospital setting. The study was done at the Department of Microbiology, IGIMS, Patna, from October 2020 to March 2022. Culture conversion in multidrug resistance pulmonary tuberculosis on all-oral longer regimens took one spot and one morning sample of sputum as per standard protocol after completing two months of all-oral longer regimens and culturing it in liquid broth using Mycobacterium Growth Indicator Tube (MGIT) 960 System at two, four then six months till we got a negative result. Results: Maximum number of the cases, 77 (74.8%), belonged to 19–35 years of age group. Males were 68 (66.1%) and females were 35 (33.9%), respectively, with male to female ratio of 1.9:1. After 2 months of oral longer regimen treatment, out of 103 cases, we found 98 (95.1%) patients had sputum for culture positive and only five (4.2%) patients had sputum for culture negative. After 6 months of oral longer regimen treatment, out of 101 cases, we found 16 (15.8%) patients had sputum for culture positive and 85 (85.2%) patients had sputum for culture negative. Conclusion: In patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) who received an all-oral longer regimen, the introduction of bedaquiline led to positive outcomes as evidenced by a greater number of negative sputum cultures, a decrease in culture reversions, and a reduced risk of developing a more resistant form of MDR-TB.

Tuberculosis in United States-Bound Follow-to-Join Asylees, 2014-2019.

Persons may seek asylum in the United States or at a U.S. port of entry. Principal asylees are those who are granted asylum status. Their spouse and unmarried children under 21 years of age may be granted asylum if accompanying, or following to join, the principal asylees. U.S.-bound follow-to-join asylees must undergo an overseas medical examination that includes tuberculosis (TB) screening. Culture-based overseas TB screening in U.S.-bound follow-to-join asylees has not been evaluated. We evaluated data from overseas TB screening in 19,088 arrivals of follow-to-join asylees during 2014-2019 and assessed data from their postarrival evaluation, which is recommended for those at risk for TB. Of 19,088 arrivals of follow-to-join asylees, 29 (152 cases/100,000 persons) met criteria for class B0 TB (recent completion of TB treatment overseas) and 340 (1,781 cases/100,000 persons) met criteria for class B1 pulmonary TB (chest radiograph/clinical symptoms suggestive of TB but negative sputum cultures overseas). Of 6,847 persons aged 2 to 14 years from countries with a WHO-estimated TB incidence of ≥20 cases/100,000 population/year, 408 (6.0%) were classified as class B2 latent TB infection (LTBI). Postarrival evaluations were completed in 44.8%, 51.5%, and 40.4% of persons with class B0 TB, class B1 TB, and class B2 LTBI, respectively. In conclusion, culture-based overseas TB screening in U.S.-bound follow-to-join asylees is effective in identifying those with TB (class B0 TB) or those at risk for TB (class B1 TB and class B2 LTBI). Completion of postarrival evaluation for newly arrived follow-to-join asylees was less frequent than that reported for immigrants and refugees.

Identification and molecular characterization of Mycobacterium bovis DNA in GeneXpert® MTB/RIF ultra-positive, culture-negative sputum from a rural community in South Africa

This study investigated the presence of Mycobacterium bovis (M. bovis) DNA in archived human sputum samples previously collected from residents who reside adjacent to the M. bovis-endemic Hluhluwe-iMfolozi wildlife park, South Africa (SA). Sixty-eight sputum samples were GeneXpert MTB/RIF Ultra-positive for M. tuberculosis complex (MTBC) DNA but culture negative for M. tuberculosis. Amplification and Sanger sequencing of hsp65 and rpoB genes from DNA extracted from stored heat-inactivated sputum samples confirmed the presence of detectable amounts of MTBC from 20 out of the 68 sputum samples. Region of difference PCR, spoligotyping and gyrB long-read amplicon deep sequencing identified M. bovis (n = 10) and M. tuberculosis (n = 7). Notably, M. bovis spoligotypes SB0130 and SB1474 were identified in 4 samples, with SB0130 previously identified in local cattle and wildlife and SB1474 exclusively in African buffaloes in the adjacent park. M. bovis DNA in sputum, from people living near the park, underscores zoonotic transmission potential in SA. Identification of spoligotypes specifically associated with wildlife only and spoligotypes found in livestock as well as wildlife, highlights the complexity of TB epidemiology at wildlife-livestock-human interfaces. These findings support the need for integrated surveillance and control strategies to curb potential spillover and for the consideration of human M. bovis infection in SA patients with positive Ultra results.

Effect of multidrug therapy on the prognosis of Mycobacterium avium complex pulmonary disease

Multidrug therapy for Mycobacterium avium complex pulmonary disease (MAC-PD) results in negative sputum cultures. However, the prognostic value of this treatment approach remains unclear. This study aimed to clarify whether multidrug therapy reduces the incidence of events related to MAC-PD and improves the mortality rate. Patients who met the diagnostic criteria for MAC-PD at our hospital between 2003 and 2019 were retrospectively evaluated using medical records. Events related to MAC-PD were defined as hospitalisation for haemoptysis or respiratory infection and the development of chronic respiratory failure. There were 90 and 108 patients in the multidrug and observation groups, respectively. The median observation period was 86 months. Intergroup differences in body mass index, proportion of patients with cavities, and erythrocyte sedimentation rate were not significant. However, the observation group was older with a higher mean age (multidrug group: 62 years, observation group: 69 years; P < 0.001) and had a higher proportion of male patients (multidrug group: 13/90 [14.4%], observation group: 35/108 [32.4%]; P < 0.01). Furthermore, intergroup differences in the incidence of events related to MAC-PD (multidrug group: 26.69/1000 person-years, observation group: 25.49/1000 person-years), MAC-PD-associated mortality rate (multidrug group: 12.13/1000 person-years, observation group: 12.74/1000 person-years), and total mortality (multidrug group: 24.26/1000 person-years, observation group: 29.50/1000 person-years) were not significant. Many patients relapse even after multidrug therapy, and our findings suggest that multidrug therapy has no effect in preventing the onset of respiratory events or prolonging life expectancy.

Sudden Vision Loss: More than Just an Ophthalmic Diagnosis! A Case Report

Abstract A 66-year-old patient of asian background from the US was admitted with confusion and behavioral changes for the last 10 days. The patient was on rituximab for RA (Rheumatoid arthritis). He had a normal computed tomography (CT) head and blood tests showed hyponatremia and acute kidney injury. Cerebrospinal fluid (CSF) showed raised CSF pressure 30 cmH20, raised protein and considerably high lymphocyte count. Mycobacteria tuberculous was isolated from one of her sputum cultures after having several negative sputum cultures, and consequently, the patient was treated for tuberculous meningitis. During admission, he had worsening of GCS (Glasgow coma scale), and he was admitted to ITU (intensive care unit) where he developed acute ischaemic stroke. He was treated for acute infarct and TBM (tuberculous meningitis), and was discharged on anti-tuberculous medications. It was a unique presentation in an immunocompromised patient with sudden deterioration and confusion, however, without neck stiffness or typical meningitis features. His condition improved with the commencement of the anti-tuberculosis therapy and was discharged from the hospital, and the patient traveled back to the US (United States) following discharge. During his stay, he was started on anti-tuberculous therapy early on due to high suspicion of Tb. The positive sputum culture was reported only after he had traveled back to the US and the same was conveyed to the patient’s GP (general practitioner) in the US.

Changes in the airway microbiome in patients with bronchiectasis.

This study used metagenomic next-generation sequencing (mNGS) technology to explore the changes of the microbial characteristics in the lower respiratory tract in patients with acute exacerbations of bronchiectasis (noncystic fibrosis) to guide clinical treatment and improve patients' quality of life and prognosis. This prospective study included 54 patients with acute exacerbation and 46 clinically stable patients admitted to the Respiratory and Critical Care Medicine Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to July 2022. Sputum was subjected to routine microbiological tests, and bronchoalveolar lavage fluid (BALF) samples were subjected to microbiological tests and mNGS of BALF before empirical antibiotic therapy. Serum inflammatory markers (white blood cell count, interleukin-6, procalcitonin, and C-reactive protein) were measured. In addition, we evaluated the pathogen of mNGS and compared the airway microbiome composition of patients with acute exacerbation and control patients. The mean age of our cohort was 56 ± 15.2 years. Eighty-nine patients had positive results by mNGS. There was a significant difference in the detection of viruses between the groups (χ2 = 6.954, P < .01). The fungal species Candida albicans, Pneumocystis jirovecii, and Aspergillus fumigatus were significantly more common in patients with acute exacerbations (χ2 = 5.98, P = .014). The bacterial species Acinetobacter baumannii, Mycobacterium tuberculosis, Haemophilus influenzae, Haemophilus parahaemolyticus, Abiotrophia defectiva, and Micromonas micros were significantly more prevalent in patients with acute exacerbations (χ2 = 4.065, P = .044). The most common bacterial species isolated from the sputum and BALF samples of patients with acute exacerbation was A. baumannii. Chlamydia psittaci was found in 4 patients. In addition, of 77 patients with negative sputum culture, 66 had positive results by mNGS, demonstrating the increased sensitivity and accuracy of mNGS. Patients with acute exacerbation of bronchiectasis tend to have mixed infections in the lower respiratory tract. The frequency of viruses, fungi, and Mycoplasma was higher in these patients. Our findings suggest that mNGS could be used to identify pathogenic microorganisms in these patients, increasing the effectiveness of antibiotic therapy.

Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model.

Multidrug-resistant tuberculosis (MDR-TB) has a high mortality and is always one of the major challenges in global TB prevention and control. Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients. For follow-up data, the Cox proportional hazards regression model is an important multifactor analysis method. However, the method has significant limitations in its application, such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model. Therefore, Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy, and compare the differences between these 2 methods in their application. Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1, 2017 to March 31, 2021. Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors. Conventional and Bayesian Cox regression models were established to estimate the hazard ratios (HR) and their 95% confidence interval (95% CI) for the factors affecting the death of MDR-TB patients. The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable. The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. The median survival time (1st quartile, 3rd quartile) of the 388 MDR-TB patients included in the study was 10.18 (4.26, 18.13) months, with the longest survival time of 31.90 months. Among these patients, a total of 12 individuals died of MDR-TB and the mortality was 3.1%. The median survival time (1st quartile, 3rd quartile) for the deceased patients was 4.78(2.63, 6.93) months. The majority of deceased patients, accounting for 50%, experienced death within the first 5 months of anti-TB therapy, with the last mortality case occurring within the 13th month of therapy. The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications (HR=6.96, 95% CI 2.00 to 24.24, P=0.002) and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up (HR=0.19, 95% CI 0.05 to 0.77, P=0.020). In the results of Bayesian Cox regression model, the iterative history plot and Blue/Green/Red (BGR) plot for each parameter showed the good model convergence, and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture (HR=0.33, 95% CI 0.08 to 0.87). Additionally, compared to patients without complications, those with comorbidities had an approximately 6.80-fold increase in the risk of death (HR=7.80, 95% CI 1.90 to 21.91). Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up (HR=0.10, 95% CI 0.01 to 0.30). The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model, except for parameter standard deviations of receiving regular follow-up (Bayesian model was 0.77; conventional model was 0.72) and pulmonary cavities (Bayesian model was 0.73; conventional model was 0.73). The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients. Complications are the main risk factors of death in MDR-TB patients, while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death. For data with a small sample size and low incidence of outcome, the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

1883. Features and Outcomes of Tuberculosis in Documented versus Undocumented Migrants in Israel

Abstract Background In countries with low tuberculosis (TB) incidence, most TB cases are observed in foreign-born individuals, including permanent immigrants, and undocumented migrants. There is limited information regarding the differences within these groups. In Israel, where TB prevalence is &amp;lt; 2 cases/100,000 persons, 85% of TB cases occur in foreign-born people. We examined risk factors, clinical course, and outcomes between documented and undocumented immigrants hospitalized with active TB. Methods A retrospective analysis of medical records from foreign-born active TB patients admitted to a 700-bed hospital in the center of Israel between January 1st, 2019, to March 31st, 2023. We included patients who initiated TB treatment during hospitalization and were discharged by April 2023. Undocumented migrants were defined as non-Israeli citizens without medical insurance. We summarized their clinical characteristics, course, and outcomes. Results 48 patients were included, 21 (43.8%) were undocumented migrants. Undocumented migrants were younger (mean age 40.9 vs. 53.0 years, P&amp;lt; 0.001) and predominantly arrived from Africa (95.2% vs. 29.6%, P&amp;lt; 0.001). The prevalence of HIV was similar between both groups. Presenting symptoms, duration of symptoms before admission, rates of bilateral and cavitary pulmonary disease, and extrapulmonary disease were comparable. Multi-drug resistant TB was rare (0% vs. 11.5%, P=0.242). Among patients with positive sputum smears and follow-up, undocumented migrants experienced a longer time to achieve negative sputum cultures (76.0 days vs. 36.8 days, P=0.004), and hospitalizations lasting over 30 days were also more common among undocumented migrants (71.4% vs. 40.7%, P=0.045). Multivariate analysis identified undocumented migrant status, thrombocytosis, and bilateral and cavitary pulmonary disease as risk factors for prolonged hospitalization. Conclusion Although the clinical features of TB were similar between documented and undocumented migrants, the response to treatment was slower, and hospital stays were longer among undocumented migrants. This may be due to undocumented migrants presenting with more advanced disease or lack of suitable conditions for isolation and treatment at home. Disclosures Yasmin Maor, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Honoraria|Gilead: Honoraria|GSK: Honoraria|kamada: Honoraria|Medison: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria

Treatment for radiographically active, sputum culture-negative pulmonary tuberculosis: A systematic review and meta-analysis.

People with radiographic evidence for pulmonary tuberculosis (TB), but negative sputum cultures, have increased risk of developing culture-positive TB. Recent expansion of X-ray screening is leading to increased identification of this group. We set out to synthesise the evidence for treatment to prevent progression to culture-positive disease. We conducted a systematic review and meta-analysis. We searched for prospective trials evaluating the efficacy of TB regimens against placebo, observation, or alternative regimens, for the treatment of adults and children with radiographic evidence of TB but culture-negative respiratory samples. Databases were searched up to 18 Oct 2022. Study quality was assessed using ROB 2·0 and ROBINS-I. The primary outcome was progression to culture-positive TB. Meta-analysis with a random effects model was conducted to estimate pooled efficacy. This study was registered with PROSPERO (CRD42021248486). We included 13 trials (32,568 individuals) conducted between 1955 and 2018. Radiographic and bacteriological criteria for inclusion varied. 19·1% to 57·9% of participants with active x-ray changes and no treatment progressed to culture-positive disease. Progression was reduced with any treatment (6 studies, risk ratio [RR] 0·27, 95%CI 0·13-0·56), although multi-drug TB treatment (RR 0·11, 95%CI 0·05-0·23) was significantly more effective than isoniazid treatment (RR 0·63, 95%CI 0·35-1·13) (p = 0·0002). Multi-drug regimens were associated with significantly reduced risk of progression to TB disease for individuals with radiographically apparent, but culture-negative TB. However, most studies were old, conducted prior to the HIV epidemic and with outdated regimens. New clinical trials are required to identify the optimal treatment approach.

Spontaneous Cultural Conversion Rate of Mycobacterium avium Complex Pulmonary Disease Based on BACES Severity.

Only a few clinical factors can aid in predicting spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). In this study, we aimed to evaluate whether the rate of SCC varies according to the severity of the disease in MAC-PD patients. We retrospectively classified 373 MAC-PD patients who had undergone watchful waiting without antibiotics based on the severity assessment using the 'body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)' criteria. We evaluated the rate of SCC in MAC-PD patients based on BACES severity and analyzed the relevant factors. Results: Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severities of 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate BACES (hazard ratio [HR] = 0.63; 95% confidence interval [CI] 0.44-0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16-0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. Lower BACES severity may be associated with SCC in MAC-PD patients.

Treatment outcomes and relapse in patients with Mycobacterium avium-intracellulare complex pulmonary disease.

The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0-483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0-483), and the 1-year relapse rate was 17%.

Inhalation phage therapy as a new approach to preventing secondary bacterial pneumonia in patients with moderate to severe COVID-19: A double-blind clinical trial study.

Inhalation phage therapy is proposed as a replacement approach for antibiotics in the treatment of pulmonary bacterial infections. This study investigates phage therapy on bacterial pneumonia in patients with moderate to severe COVID-19 via the inhalation route. In this double-blind clinical trial, 60 patients with positive COVID-19 hospitalized in three central Mazandaran hospitals were chosen and randomly divided into two intervention and control groups. Standard country protocol drugs plus 10mL of phage suspension every 12h with a mesh nebulizer was prescribed for 7 days in the intervention group. The two groups were compared in terms of O2Sat, survival rate, severe secondary pulmonary bacterial infection and duration of hospitalization. Comparing the results between the intervention and control group, in terms of the trend of O2Sat change, negative sputum culture, no fever, no dyspnea, duration of hospitalization, duration of intubation and under ventilation, showed that the difference between these two groups was statistically different (P value<0.05). In conclusion, inhalation phage therapy may have a potential effect on secondary infection and in the outcome of COVID-19 patients. However, more clinical trials with control confounding factors are needed to further support this concept.

Concomitant Treatment of Tuberculosis and Hepatitis C Virus in Coinfected Patients Using Serum Drug Concentration Monitoring.

Concern for drug-drug interactions leading to treatment failure and drug-resistant strains have discouraged clinicians from attempting concomitant treatment of hepatitis C virus (HCV) and tuberculosis (TB). Increased metabolism of direct-acting antivirals (DAAs) by rifamycins has hindered concurrent use. Development of an assay for ledipasvir and sofosbuvir (LDV/SOF) serum concentrations for therapeutic drug monitoring (TDM) can ensure adequate therapy. We present the first cases of concomitant therapy of active TB and HCV with rifamycin-containing regimens and DAAs using TDM. Using TDM, we aim to determine whether concomitant therapy with rifamycin-containing regimens and DAAs is safe and effective for patients coinfected with TB and HCV. Five individuals with TB and HCV who experienced transaminitis before or during TB therapy were concomitantly treated with rifamycin-containing regimens and LDV/SOF. Therapeutic drug monitoring was performed for LDV, SOF, and rifabutin during therapy. Baseline laboratory tests and serial liver enzymes were performed. Hepatitis C virus viral load and mycobacterial sputum cultures were obtained upon completion of therapy to determine efficacy of therapy. All patients were found to have nondetectable HCV viral loads and negative mycobacterial sputum cultures upon completion of therapy. No clinically significant adverse effects were reported. These cases illustrate concomitant use of LDV/SOF and rifabutin in patients with HCV/TB coinfection. Utilizing serum drug concentration monitoring to guide dosing, correction of transaminitis were achieved, which allowed the use rifamycin-containing TB therapy. These findings suggest that concomitant therapy of TB/HCV is possible, safe, and effective.

Factors associated with adverse drug reactions or death in very elderly hospitalized patients with pulmonary tuberculosis

The aging of patients with tuberculosis and better therapeutic management for them are recent concerns. This study aimed to identify risk factors for adverse drug reactions (ADRs) or death in very elderly patients with pulmonary tuberculosis and to assess the association between the dosage of antituberculosis drugs and outcomes. We conducted a multicenter retrospective study at two hospitals. Hospitalized patients (≥ 80 years old) with pulmonary tuberculosis who were treated with antituberculosis drugs were enrolled. Multivariate analysis was performed to assess factors associated with ADRs or death within 60 days after treatment initiation. In total, 632 patients were included. The primary endpoint occurred in 268 patients (190 ADRs and 78 deaths). A serum albumin level < 2.5 g/dL, respiratory failure, and dependent activities of daily living were independent risk factors for ADRs or death. However, a low dosage (< 8 mg/kg/day) of rifampicin was associated with a lower risk of the primary outcomes. Delayed time to negative sputum culture conversion was not observed in the lower dosage of rifampicin group. Very elderly hospitalized tuberculosis patients with the aforementioned risk factors should be carefully monitored to receive safer treatment. Rifampicin dosage reduction may be considered for very elderly tuberculosis patients to prevent ADRs/death.

A Retrospective Assessment of Sputum Samples and Antimicrobial Resistance in COVID-19 Patients.

Data on bacterial or fungal pathogens and their impact on the mortality rates of Western Romanian COVID-19 patients are scarce. As a result, the purpose of this research was to determine the prevalence of bacterial and fungal co- and superinfections in Western Romanian adults with COVID-19, hospitalized in in-ward settings during the second half of the pandemic, and its distribution according to sociodemographic and clinical conditions. The unicentric retrospective observational study was conducted on 407 eligible patients. Expectorate sputum was selected as the sampling technique followed by routine microbiological investigations. A total of 31.5% of samples tested positive for Pseudomonas aeruginosa, followed by 26.2% having co-infections with Klebsiella pneumoniae among patients admitted with COVID-19. The third most common Pathogenic bacteria identified in the sputum samples was Escherichia coli, followed by Acinetobacter baumannii in 9.3% of samples. Commensal human pathogens caused respiratory infections in 67 patients, the most prevalent being Streptococcus penumoniae, followed by methicillin-sensitive and methicillin-resistant Staphylococcus aureus. A total of 53.4% of sputum samples tested positive for Candida spp., followed by 41.1% of samples with Aspergillus spp. growth. The three groups with positive microbial growth on sputum cultures had an equally proportional distribution of patients admitted to the ICU, with an average of 30%, compared with only 17.3% among hospitalized COVID-19 patients with negative sputum cultures (p = 0.003). More than 80% of all positive samples showed multidrug resistance. The high prevalence of bacterial and fungal co-infections and superinfections in COVID-19 patients mandates for strict and effective antimicrobial stewardship and infection control policies.

"It's Not Just Bacteria": A Cavitary Lung Lesion in a Patient Living in the Coachella Valley.

Cavitary pulmonary coccidioidomycosis is rare diagnosis with an incidence of 13% to 15% of pulmonary coccidioidomycosis cases. High clinical suspicion is necessary in the setting of geographical location endemicity. We present a 49-year-old male who has lived in the Coachella Valley of California for several years, with a medical history of uncontrolled type 2 diabetes who noted 1 week of right-sided chest pain with shortness of breath, fever, chills, night sweats, and weight loss. A chest X-ray revealed a 4- to 5-cm mass in the right lung. Initial workup revealed negative sputum cultures (aerobic/anaerobic, acid-fast bacilli). However, dedicated fungal cultures (samples from sputum, lymph nodes, lung right lower lobe bronchial swabs), bronchial washings, and surgical tissue biopsy of the right lower lobe revealed mold. The patient underwent right thoracotomy with right lower lobectomy and right mediastinal lymph node dissection for both diagnostic (lung specimen) and therapeutic (removing necrotic lung tissue, source control) purposes. Finally, serum Coccidioides antigens were positive and antibody titers were positive at 1:8; surgical biopsy of the right lower lobe grew mold that came back positive for Coccidioides posadasii. Targeted pharmacotherapy was commenced using intravenous fluconazole and then oral fluconazole for 3 months was prescribed upon discharge. The patient had gradual improvement of his shortness of breath and was instructed to follow-up at an infectious disease clinic.

Inhaled nitric oxide for adults with pulmonary non-tuberculous mycobacterial infection

QuestionThere is an increasing prevalence of nontuberculous mycobacteria pulmonary disease (NTM-PD) in the US. Treatment of NTM-PD typically requires multiple medications, which can be associated with unpleasant morbidity and eradication of infection is difficult. Therefore, there is a critical need for novel effective and well-tolerated therapies. Recent in vitro data and case reports have suggested that nitric oxide, inhaled as a gas (gNO), has antimicrobial activity against NTM. We sought to investigate the effect of gNO in patients with NTM-PD in an open-label proof of concept trial. MethodsEligible participants had NTM-PD with persistently positive respiratory cultures for NTM even if on antibiotic treatment. Participants were treated with gNO for 50 min three times daily, five days per week, for three weeks (total of 15 treatment days). ResultsTen participants, of whom nine were on long-term NTM antibiotic therapy, were enrolled. All participants completed the regimen without interruption or discontinuation. Small increases in methemoglobin were noted during treatment, and all resolved to baseline within 2 h. Four participants (40%) met the primary outcome measure of negative sputum cultures after three weeks of therapy. Following treatment discontinuation, three of these participants were again culture positive during the 3-month post-treatment monitoring period, although with measures suggesting low bacterial burden. AnswerPatients tolerated a 3-week regimen of gNO without safety concerns, and despite highly refractory disease four individuals completed the study with negative cultures, although three were again positive in subsequent months. These data support further investigation of gNO as a potential therapy for NTM-PD.