Baseline Predictors of Sputum Culture Conversion in Pulmonary Tuberculosis: Importance of Cavities, Smoking, Time to Detection and W-Beijing Genotype

Background: Time to detection (TTD) on automated liquid mycobacterial cultures is an emerging biomarker of tuberculosis outcomes. The M. tuberculosis W-Beijing genotype is spreading globally, indicating a selective advantage. There is a paucity of data on the association between baseline TTD and W-Beijing genotype and tuberculosis outcomes. Aim: To assess baseline predictors of failure of sputum culture conversion, within the first 2 months of antitubercular therapy, in participants with pulmonary tuberculosis. Design: Between May 2005 and August 2008 we conducted a prospective cohort study of time to sputum culture conversion in ambulatory participants with first episodes of smear and culture positive pulmonary tuberculosis attending two primary care clinics in Cape Town, South Africa. Rifampicin resistance (diagnosed on phenotypic susceptibility testing) was an exclusion criterion. Sputum was collected weekly for 8 weeks for mycobacterial culture on liquid media (BACTEC MGIT 960). Due to missing data, multiple imputation was performed. Time to sputum culture conversion was analysed using a Cox-proportional hazards model. Bayesian model averaging determined the posterior effect probability for each variable. Results: 113 participants were enrolled (30.1% female, 10.5% HIV-infected, 44.2% W-Beijing genotype, and 89% cavities). On Kaplan Meier analysis 50.4% of participants underwent sputum culture conversion by 8 weeks. The following baseline factors were associated with slower sputum culture conversion: TTD (adjusted hazard ratio (aHR) = 1.11, 95% CI 1.02; 1.2), lung cavities (aHR = 0.13, 95% CI 0.02; 0.95), ever smoking (aHR = 0.32, 95% CI 0.1; 1.02) and the W-Beijing genotype (aHR = 0.51, 95% CI 0.25; 1.07). On Bayesian model averaging, posterior probability effects were strong for TTD, lung cavitation and smoking and moderate for W-Beijing genotype. Conclusion: We found that baseline TTD, smoking, cavities and W-Beijing genotype were associated with delayed 2 month sputum culture. Larger studies are needed to confirm the relationship between the W-Beijing genotype and sputum culture conversion.Publisher's versio

Achilles tendon disease in lung transplant recipients: association with ciprofloxacin

Achilles tendonitis or rupture are uncommon complications following the use of fluoroquinolones, with a reported incidence in the general population of 0.4%. The aims of the current study were to determine the incidence of Achilles tendon disease (ATD) in lung transplant recipients (LTR) and to identify risk factors

Risk factors and management of bleeding associated with transbronchial lung biopsy in lung transplant recipients

The aim of this study was to assess specific risk factors associated with bleeding during transbronchial biopsy (TBBx) in lung transplant recipients. Risk factors analyzed included gender, type of transplant, acute rejection, bronchiolitis obliterans syndrome (BOS) status, infections, number of biopsies obtained per procedures, serum creatinine level and post-operative day since transplantation. The bronchoscope was not wedged to obtain TBBx and associated bleeding was managed using the "back-and-forth" technique. The severity of bleeding is shown to be independent of any specific risk factor and the back-and-forth technique described herein can be safely employed in lung transplant recipients to manage bleeding associated with TBBx performed without wedging of the bronchoscope

Indirect fluorescent antibody testing of nasopharyngeal swabs for influenza diagnosis in lung transplant recipients

Background: Rapid and reliable diagnosis of respiratory viral infections (RVI) in lung transplant recipients is essential to direct therapy of acute graft dysfunction and identify epidemic trends. Traditional techniques of serology and viral culture are limited by the lack of antibody response and delay in diagnosis

Prospective analysis of 1,235 transbronchial lung biopsies in lung transplant recipients

Objective:. Fiber-optic bronchoscopy with multiple transbronchial lung biopsies (TBB) is the gold standard of evaluation of the pulmonary allograft post-lung transplantation (LT). However controversy exists regarding the need for surveillance procedures and number. of biopsy specimens required for satisfactory yield. The potential morbidity in obtaining multiple TBB specimens remains poorly described. We report the largest series of TBB in LT recipients to date, highlighting the occurrence of acute rejection and infection for surveillance and diagnostic procedures. The safety of TBB is analyzed and a biopsy schedule proposed

Identification of miR-93 as a suitable miR for normalizing miRNA in plasma of tuberculosis patients

© 2015 The Authors. Tuberculosis (TB) remains a major public health issue. New tests to aid diagnoses and monitor the response to therapy are urgently required. There is growing interest in the use of microRNA (miRNA) profiles as diagnostic, prognostic or predictive markers in a range of clinical and infectious diseases, including Mycobacterium tuberculosis infection, however, challenges exist to accurately normalise miRNA levels in cohorts. This study examined the appropriateness of 12 miRs and RNU6B to normalise circulating plasma miRNA levels in individuals with active TB from 2 different geographical and ethnic regions. Twelve miRs (let-7, miR-16, miR-22, miR-26, miR-93, miR-103, miR-191, miR-192, miR-221, miR-423, miR-425 and miR-451) and RNU6B were selected based on their reported production by lung cells, expression in blood and previous use as a reference miRNA. Expression levels were analysed in the plasma of newly diagnosed TB patients from Australia and China compared with individuals with latent TB infection and healthy volunteers. Analysis with both geNorm and NormFinder software identified miR-93 as the most suitable reference miR in both cohorts, either when analysed separately or collectively. Interestingly, there were large variations in the expression levels of some miRs, in particular miR-192 and let-7, between the two cohorts, independent of disease status. These data identify miR-93 is a suitable reference miR for normalizing miRNA levels in TB patients, and highlight how environmental, and possibly ethnic, factors influence miRNA expression levels, demonstrating the necessity of assessing the suitability of reference miRs within the study population

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

PURPOSE: Respiratory Syncytial Virus (RSV) infection after lung transplantation (LTx) has been associated with acute and chronic allograft dysfunction. A previous study at our center demonstrated an IV loading regimen followed by oral therapy was an effective and cost-efficient treatment for RSV infection after LTx. This study evaluates efficacy, safety, and cost-efficiency of an entirely oral ribavirin regimen for treatment of RSV infection after LTx. METHODS: We performed a single center retrospective analysis of 49 consecutive LTx recipients from Aug-2016 to Aug-2019. RSV was diagnosed by PCR from nasopharyngeal swab or bronchoalveolar lavage fluid. Patients were followed for 3 months post RSV treatment. Data collected included longitudinal spirometry, hemoglobin and drug cost. RESULTS: Forty-nine patients (mean age 47±15, male:female ratio 25:24), presented with 52 episodes of clinically symptomatic RSV. Complete spirometry data was available for 33 episodes. Mean FEV1 fell from baseline 2.33±0.69 to 2.06±0.71 (p<0.001) at presentation. All patients received an oral loading dose of ribavirin (33mg/kg in 3 divided doses) followed by 20mg/kg orally in 2 divided doses from day 2 (adjusted for renal function). Median duration of therapy was 7 days (6-21). Patients also received prednisolone 1mg/kg/day weaned by 5mg second daily to usual baseline dose, and antibiotic cover. Adverse events included worsening anemia in 3/24 patients with existing anemia and new-onset anemia in 4/21. Mean hemoglobin fell from 121±20 to 117±19 (p=0.042). Two patients required a transfusion for anemia associated with prolonged ribavirin therapy. Mean FEV1 recovered to 2.20±0.76 after completion of therapy and to 2.26±0.74 within 3 months (p<0.001 compared to FEV1 at presentation). There were 3 deaths: one at 2 months post RSV (respiratory failure), and 2 late unrelated deaths. Compared to our center's previous regimen using IV ribavirin loading, mean drug cost reduced from US$1445 to US$60 per treatment course. Hospital admission was avoided in 36/52 (69%) patient episodes. CONCLUSION: An exclusively oral regimen of loading and maintenance dose ribavirin for treatment of RSV post LTx appears to be effective and well-tolerated. Furthermore, it carries a significant cost saving and completely avoids hospital admission in 69% of patient episodes