Identification rate of Legionella species in non-purulent sputum culture is comparable to that in purulent sputum culture in Legionella pneumonia.

Many Legionella pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of Legionella species. This study aimed to evaluate the identification rate of Legionella species based on sputum quality and the factors predictive of Legionella infection. This study included Legionella pneumonia patients at Kurashiki Central Hospital from November 2000 to December 2022. Sputum quality, based on gram staining, was classified as the following: Geckler 1/2, 3/6 and 4/5. Geckler 4/5 was defined as purulent sputum. The sputa of 104 of 124 Legionella pneumonia patients were cultured. Fifty-four patients (51.9%) were identified with Legionella species, most of which were Legionella pneumophila serogroup 1 (81.5%). The identification rates of Legionella species according to sputum quality were 57.1% (16/28) in Geckler 1/2 sputum, 50.0% (34/68) in Geckler 3/6 sputum, and 50.0% (4/8) in Geckler 4/5 sputum, which were not significantly different (P = 0.86). On multivariate analysis, pre-culture treatment with anti-Legionella antimicrobials (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.06-0.91), Pneumonia Severity Index class ≥IV (OR 2.57 [95% CI 1.02-6.71]), and intensive care unit admission (OR 3.08, 95% CI 1.06-10.09) correlated with the ability to identify Legionella species, but sputum quality did not (OR 0.88, 95% CI 0.17-4.41). The identification rate of Legionella species in non-purulent sputum was similar to that in purulent sputum. For the diagnosis of Legionella pneumonia, sputum should be collected before administering anti-Legionella antibiotics and cultured regardless of sputum quality.

Time to sputum culture conversion and its associated factors among drug-resistant tuberculosis patients: a systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors. METHODS: PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software. RESULTS: A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1+) (aHR = 0.87,95%CI:0.77,0.99), (grade 2+) (aHR = 0.81,95%CI:0.69,0.95), (grade 3+) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB. CONCLUSION: Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m2, lung cavity, sputum smear grading at baseline (Positive, grade 1+, grade 2+, grade 3+) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746.

Ceftriaxone efficacy for Mycobacterium avium complex lung disease in the hollow fiber and translation to sustained sputum culture conversion in patients.

BACKGROUND: Only 35.6%-50.8% of patients with Mycobacterium avium complex (MAC) pulmonary disease achieve sustained sputum culture conversion (SSCC) on treatment with the azithromycin-ethambutol-rifabutin standard of care (SOC). We tested the efficacy of ceftriaxone, a ß-lactam with a lung penetration ratio of 12.18-fold. METHODS: We mimicked lung concentration-time profiles of seven ceftriaxone once-daily doses for 28 days in the hollow fiber system model of intracellular MAC (HFS- MAC). Monte Carlo experiments were used for dose selection.We also compared the once-daily ceftriaxone monotherapy to three-drug SOC against five MAC clinical isolates in HFS-MAC using γ (kill)-slopes. Results were translated to SSCC rates. RESULTS: Ceftriaxone killed 1.02-3.82 log10 cfu/mL in dose-response studies. Ceftriaxone 2G once-daily was identified as the optimal dose. Ceftriaxone killed all five strains below day 0 versus 2/5 for SOC. The median γ (95% confidence interval) was 0.49(0.47-0.52) log10 cfu/mL/day for ceftriaxone and 0.38(0.34-0.43) log10 cfu/mL/day for SOC. In patients, the SOC was predicted to achieve SSCC rates of 39.3%(36%-42%) at 6 months (similar to meta-analyses results). The SOC SSCC was 50% at 8.18(3.64-27.66) months versus 3.58(2.20-7.23) months for ceftriaxone. Thus, ceftriaxone shortened time-to-SSCC 2.35-fold compared to SOC. CONCLUSION: Ceftriaxone is a promising agent for creation of short-course chemotherapy.

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study.

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

Time for culture conversion and its associated factors in multidrug-resistant tuberculosis patients at a tertiary level hospital in Peshawar, Pakistan.

Objectives: This study aimed to assess the time to sputum culture conversion (SCC) and its determinants among multidrug-resistant tuberculosis (MDR-TB) patients. Methods: This cross-sectional study was conducted from January 2019 to January 2020. A total of 252 MDR-TB patients presenting at a tertiary level teaching hospital in Peshawar, Khyber Pakhtunkhwa (KP), were included. The patient's demographic and clinical data were collected using a structured questionnaire. Time to SCC was calculated from the initiation of treatment till the patient had two consecutive negative cultures. The Cox proportional-hazards analysis was performed to check strength and association between the determinants and time for SCC. Results: Out of 252 MDR-TB patients enrolled, sputum culture conversion was observed in 76.6% of the patients by the end of six months. While, 19.0% of the patients failed to achieve negative culture and remained positive after interim report of their treatment. Age > 45 years (HR = 15.22; 95% CI: 7.27-31.83; p<0.001), female gender (6.22; 2.90-13.36; p<0.001), BMI < 18.5 kg/m2 (10.28; 5.25-20.11; p<0.001), weight loss (0.03; 0.01-0.06; p<0.001), smoking (0.10; 0.05-0.21; p<0.001), diabetes mellitus (0.02; 0.00-0.04 p<0.001) and disease severity on chest X-ray (CXR) (0.03; 0.01-0.09; p<0.001) were the significant determinants of delayed sputum culture conversion. Conclusion: MDR-TB patients with older age, low BMI, weight loss, diabetes, smokers and those with disease severity on CXR are less likely to respond to treatment as they displayed delayed SCC. Therefore, such patients should be meticulously followed up for successful management.

An Evaluation of The Diagnostic Value of Sputum Smears Microscopy and Pcr Relative to Sputum Culture in The Diagnosis of Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis in Iran.

Background: Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In many parts of the world, including Iran, the diagnosis of tuberculosis is based on the detection of acid-fast bacillus in sputum smear microscopy and PCR. this study aimed to synthesize evidence on the diagnostic accuracy of sputum smear and PCR compared to sputum culture for the diagnosis of PT in Iranian patients. Methods: This systematic review and meta-analysis was conducted based on PRISMA guideline for systematic review and meta-analysis. Eligible studies were cross-sectional original diagnostic studies published in English and Persian in Iran which examined the sensitivity or specificity(study outcome) of sputum smear microscopy or PCR( as the test) relative to sputum culture (as the gold standard/comparator) among Iranian patients suspected of having tuberculosis( study population). Studies whose data were not complete or extractable were excluded. Results: A total of 3518 subjects were evaluated from 15 eligible studies. The pooled sensitivity of sputum smear and PCR was 75.12 (95% CI: 66.68-83.56) and 88.02 (95% CI: 82.87-93.27), respectively. The specificity for sputum smear and PCR was 93.94 (95% CI: 91.26-96.63) and 91.82 (95% CI: 87.29-96.35) respectively. The sensitivity of both sputum smears was higher in studies published after 2010, and had higher quality. The specificity of sputum smear was a bit lower in studies published after2010 but higher in studies with higher quality. The specificity of PCR was higher in studies published after 2010 but higher in studies with higher quality. Conclusion:The increased sensitivity of sputum smear and PCR during recent years suggests the improvement of preparation and laboratory methods in recent years. However, the imperfect sensitivity of these tests highlights the need for a more accurate diagnostic method for the detection of pulmonary tuberculosis in Iran.

Bacterial and fungal growth in sputum cultures from 165 COVID-19 pneumonia patients requiring intubation: evidence for antimicrobial resistance development and analysis of risk factors.

BACKGROUND: Coronavirus SARS-CoV-2 causes COVID-19 illness which can progress to severe pneumonia. Empiric antibacterials are often employed though frequency of bacterial coinfection superinfection is debated and concerns raised about selection of bacterial antimicrobial resistance. We evaluated sputum bacterial and fungal growth from 165 intubated COVID-19 pneumonia patients. Objectives were to determine frequency of culture positivity, risk factors for and outcomes of positive cultures, and timing of antimicrobial resistance development. METHODS: Retrospective reviews were conducted of COVID-19 pneumonia patients requiring intubation admitted to a 1058-bed four community hospital system on the east coast United States, March 1 to May 1, 2020. Length of stay (LOS) was expressed as mean (standard deviation); 95% confidence interval (95% CI) was computed for overall mortality rate using the exact binomial method, and overall mortality was compared across each level of a potential risk factor using a Chi-Square Test of Independence. All tests were two-sided, and significance level was set to 0.05. RESULTS: Average patient age was 68.7 years and LOS 19.9 days. Eighty-three patients (50.3% of total) originated from home, 10 from group homes (6.1% of total), and 72 from nursing facilities (43.6% of total). Mortality was 62.4%, highest for nursing home residents (80.6%). Findings from 253 sputum cultures overall did not suggest acute bacterial or fungal infection in 73 (45%) of 165 individuals sampled within 24 h of intubation. Cultures ≥ 1 week following intubation did grow potential pathogens in 72 (64.9%) of 111 cases with 70.8% consistent with late pneumonia and 29.2% suggesting colonization. Twelve (10.8% of total) of these late post-intubation cultures revealed worsened antimicrobial resistance predominantly in Pseudomonas, Enterobacter, or Staphylococcus aureus. CONCLUSIONS: In severe COVID-19 pneumonia, a radiographic ground glass interstitial pattern and lack of purulent sputum prior to/around the time of intubation correlated with no culture growth or recovery of normal oral flora ± yeast. Discontinuation of empiric antibacterials should be considered in these patients aided by other clinical findings, history of prior antimicrobials, laboratory testing, and overall clinical course. Continuing longterm hospitalisation and antibiotics are associated with sputum cultures reflective of hospital-acquired microbes and increasing antimicrobial resistance. TRIAL REGISTRATION: Not applicable as this was a retrospective chart review study without interventional arm.

Risk factors associated with methicillin-resistant Staphylococcus aureus isolation from serially collected sputum samples of patients hospitalized with pneumonia.

INTRODUCTION: Risk factors associated with the new detection of methicillin-resistant Staphylococcus aureus (MRSA) during hospitalization remain unclear. This study aimed to identify risk factors associated with MRSA isolation from the sputum of patients admitted with pneumonia, during their hospitalization. METHODS: Patients were prospectively enrolled from 2003 to 2012. Sputum samples were collected for bacterial cultures on days 1, 4, 7, 11, and 14 of hospitalization and thereafter. Cases of MRSA first isolated from sputum obtained before day 4 were defined as "carriage on admission." Cases of MRSA first isolated on day 4 and thereafter, were defined as "new detection after admission." Statistical analysis was used to investigate the risk factors associated with MRSA isolation. RESULTS: MRSA was isolated from 167 of 1,008 patients (carriage: 47; new detection: 120). Multivariate analysis revealed that the risk factors for MRSA carriage were activities of daily living (ADL) disability prior to admission (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.37-6.22) and hospitalization within the previous 90 days (OR, 3.75; 95% CI, 1.90-7.41). ADL disability prior to admission (risk ratio [RR], 1.82; 95% CI, 1.17-2.84) and a high pneumonia severity index score upon admission (RR, 2.20; 95% CI, 1.37-3.65) were risk factors for new detection of MRSA. CONCLUSIONS: Several risk factors were found to be associated with MRSA carriage and/or its new detection, based on the sputum samples from patients admitted with pneumonia. These factors may be indicators for selective surveillance and the early implementation of infection control measures.

Depression and recovery of IL-17A secretion in mitogen responses in patients with active tuberculosis-a prospective observational study.

BACKGROUND/PURPOSE: T-helper cell 17 (Th17) is a distinct subset of CD4+ T lymphocytes that is important in the pathogenesis of Mycobacterium tuberculosis infection. This study aims to investigate the characteristics of interleukin (IL)-17A and Th17-related cytokines after stimulation with phytohemagglutinin in patients with active tuberculosis (TB). METHODS: This prospective cohort study enrolled patients with culture-confirmed active TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was performed upon TB diagnosis and at 2 months after TB treatment. Their non-TB-specific secretion of IL-17A and Th17-related cytokines were measured in supernatants of mitogen tubes in QFT-GIT and compared to those of active TB contacts with or without latent TB infection. We analyzed the association between IL-17A secretions and TB presentation and treatment outcomes. RESULTS: A total of 108 patients with TB and 64 non-TB cases were enrolled. The secretion of IL-17A, IL-21, IL-23, and IL-6 were lower in active TB patients upon TB diagnosis. In active TB patients, lower IL-17A secretions were associated with higher grades of sputum smear. In the multivariate analysis, lower IL-17A secretions served as an independent factor associated with 2-month culture non-conversion (odds ratio 23.04, 95% confidence interval [CI] 1.69-84.78) and on-treatment mortality (hazard ratio 28.54, 95% CI 1.30-99.25). The levels of IL-23, and IL-6 significantly increased after 2 months of anti-TB treatment. CONCLUSION: The non-TB-specific IL-17A secretions were lower in active TB patients upon TB diagnosis and associated with higher disease severity and worse treatment outcomes. Trend of recovery of the depressed Th17-related cytokines was noted after effective anti-TB treatment.

Blind Spots of Traditional Microbiological Tests for Severe Community-Acquired Pneumonia in Adults and Availability of Nonculture Techniques: A Nationwide Survey of Physicians in China.

BACKGROUND: In China, no national survey has been conducted to evaluate physicians' attitudes and compliance with guidelines in the management of adult patients with community-acquired pneumonia (CAP). Therefore, this study aimed to evaluate physicians' awareness of the use of microbiological tests in the management of severe CAP (SCAP) and to investigate the availability of nonculture tests in China. METHODS: A nationwide electronic questionnaire survey was conducted among Chinese physicians between March and July 2018, which assessed their viewpoints concerning the issues in the management of SCAP. RESULTS: A total of 6333 physicians completed this survey, evenly covering all career stages. Among these, 3208 (50.6%) and 1936 (30.6%) had blind spots in the application of blood and sputum cultures in the management of SCAP, respectively. Nonteaching hospital, nonrespirologists, and junior career stage were independently associated with misunderstandings. Regarding nonculture methods, 52.7% of the facilities had no access to polymerase chain reaction-based pathogen detection tests. The accessibility of urinary antigen tests for Streptococcus pneumoniae (42.5%) and Legionella pneumophila (38.5%) was also low. The main barriers were inland and remote region, lower hospital level, and nonteaching hospital. CONCLUSIONS: Insufficient use of sputum and blood cultures, together with low accessibility of major nonculture techniques, were noticeable barriers to achieving microbiological diagnosis of SCAP in China. To help curb the overuse of broad-spectrum antibiotics, further measures should be taken to raise awareness among nonspecialists and promote rapid nonculture tests, especially in nonteaching hospitals and developing regions.

Clinical usefulness of sputum culture on the first postoperative day to predict early postoperative pneumonia after esophagectomy for esophageal cancer.

BACKGROUND: Postoperative pneumonia is a serious prognostic problem that can appear after esophagectomy in patients with esophageal cancer. The past reports have considered the usefulness of perioperative culture examinations for predicting postoperative pneumonia; however, the direct relationship between these examinations and postoperative complications remains unclear. METHODS: This study retrospectively analyzed esophageal cancer patients who underwent esophagectomy followed by sputum culture on the first postoperative day. The bacterial species that frequently cause hospital-acquired pneumonia were chosen as the target species in this study. The relationship between culture examination and postoperative pneumonia within one week (7 days) after esophagectomy was investigated. RESULTS: Sputum cultures on the first postoperative day were investigated in 238 patients who underwent esophagectomy for esophageal cancer. Forty-one patients developed pneumonia within one week after surgery. The target bacterial species were detected in 26 of 238 sputum cultures (10.9%). In the univariate analysis, a Brinkman index, detection of target bacterial species, detection of Gram-positive cocci, and Gram-negative rods were significantly associated with postoperative pneumonia. In the three independent multivariate analyses, the target bacterial species, Gram-positive cocci, and Gram-negative rods (p = 0.001, 0.042, and < 0.001) were individually identified as independent risk factors of postoperative pneumonia in addition to a Brinkman index. CONCLUSIONS: Detection of target bacterial species by sputum culture on the first postoperative day after esophagectomy was an independent risk factor of postoperative pneumonia within 7 days after surgery. Prospective studies for the prevention of early postoperative pneumonia using sputum culture on the first postoperative day can be considered.

Understanding the drug exposure-response relationship of bedaquiline to predict efficacy for novel dosing regimens in the treatment of multidrug-resistant tuberculosis.

AIMS: To externally validate an earlier characterized relationship between bedaquiline exposure and decline in bacterial load in a more difficult-to-treat patient population, and to explore the performances of alternative dosing regimens through simulations. METHODS: The bedaquiline exposure-response relationship was validated using time-to-positivity data from 233 newly diagnosed or treatment-experienced patients with drug-resistant tuberculosis from the C209 open-label study. The significance of the exposure-response relationship on the bacterial clearance was compared to a constant drug effect model. Tuberculosis resistance type and the presence and duration of antituberculosis pre-treatment were evaluated as additional covariates. Alternative dosing regimens were simulated for tuberculosis patients with different types of drug resistance. RESULTS: High bedaquiline concentrations were confirmed to be associated with faster bacterial load decline in patients, given that the exposure-effect relationship provided a significantly better fit than the constant drug effect (relative likelihood = 0.0003). The half-life of bacterial clearance was identified to be 22% longer in patients with pre-extensively drug-resistant (pre-XDR) tuberculosis (TB) and 86% longer in patients with extensively drug-resistant (XDR) TB, compared to patients with multidrug-resistant (MDR) TB. Achievement of the same treatment response for (pre-)XDR TB patients as for MDR TB patients would be possible by adjusting the dose and dosing frequency. Furthermore, daily bedaquiline administration as in the ZeNix regimen, was predicted to be as effective as the approved regimen. CONCLUSION: The confirmed bedaquiline exposure-response relationship offers the possibility to predict efficacy under alternative dosing regimens, and provides a useful tool for potential treatment optimization.

Slow radiological improvement and persistent low-grade inflammation after chemotherapy in tuberculosis patients with type 2 diabetes.

BACKGROUND: Diabetes mellitus type 2 (DM) may impede immune responses in tuberculosis (TB) and thus contribute to enhanced disease severity. In this study, we aimed to evaluate DM-mediated alterations in clinical, radiological and immunological outcomes in TB disease. METHODS: Newly diagnosed pulmonary TB patients with or without DM (TB n = 40; TB-DM n = 40) were recruited in Dhaka, Bangladesh. Clinical symptoms, sputum smear and culture conversion as well as chest radiography were assessed. Peripheral blood and sputum samples were collected at the time of diagnosis (baseline) and after 1, 2 and 6 months of standard anti-TB treatment. Blood samples were also obtained from healthy controls (n = 20). mRNA expression of inflammatory markers in blood and sputum samples were quantified using real-time PCR. RESULTS: The majority of TB-DM patients had poor glycemic control (HbA1c > 8%) and displayed elevated pulmonary pathology (P = 0.039) particularly in the middle (P < 0.004) and lower lung zones (P < 0.02) throughout the treatment period. However, reduction of clinical symptoms and time to sputum smear and culture conversion did not differ between the groups. Transcripts levels of the pro-inflammatory cytokines IL-1ß (P = 0.003 at month-1 and P = 0.045 at month-2) and TNF-α (P = 0.005 at month-1) and the anti-inflammatory cytokine IL-10 (P = 0.005 at month-2) were higher in peripheral blood after anti-TB treatment in TB-DM compared to TB patients. Conversely in sputum, TB-DM patients had reduced CD4 (P < 0.009 at month-1) and IL-10 (P = 0.005 at month-1 and P = 0.006 at month-2) transcripts, whereas CD8 was elevated (P = 0.016 at month-2). At 1- and 2-month post-treatment, sputum IL-10 transcripts were inversely correlated with fasting blood glucose and HbA1c levels in all patients. CONCLUSION: Insufficient up-regulation of IL-10 in the lung may fuel persistent local inflammation thereby promoting lung pathology in TB-DM patients with poorly controlled DM.

Bronchiectasis in Severe Asthma: Does It Make a Difference?

BACKGROUND: Asthma and bronchiectasis are 2 heterogeneous diseases that frequently coexist, particularly in severe asthma. Recognition of this co-diagnosis may importantly affect treatment decisions and outcome. Previous studies in asthma with bronchiectasis show inconsistent outcomes, probably due to the heterogeneity of the included asthma cohorts. OBJECTIVES: We hypothesized that bronchiectasis contributes to asthma severity and that patients with severe asthma and bronchiectasis present with distinct characteristics resulting in different treatable traits. In addition, we explored whether bronchiectasis in severe asthma is more common in a specific phenotype. METHODS: This is a single-center study consecutively including patients with severe asthma from a tertiary referral center. Severe asthma was diagnosed according to the ATS/ERS guidelines. Asthma and infectious exacerbations were defined by the attending specialist as respiratory symptoms requiring treatment with systemic steroids or antibiotics, respectively. Two independent blinded radiologists evaluated each CT. RESULTS: 19% of patients with severe asthma showed bronchiectasis on CT. Patients with bronchiectasis had a lower FEV1% predicted (p = 0.02) and FEV1/FVC (p = 0.004) and more infectious exacerbations (p = 0.003) compared to patients without bronchiectasis. Bronchiectasis is more common in patients with a longer duration of asthma, sensitization to A. fumigatus or a positive sputum culture. Sputum cultures of patients with severe asthma and bronchiectasis revealed more P. aeruginosa, S. maltophilia, H. parainfluenzae, and A. fumigates compared to the non-bronchiectasis group. The adult-onset, eosinophilic asthma phenotype showed the highest prevalence of bronchiectasis (29.4%). CONCLUSIONS: Patients with severe asthma and coexisting bronchiectasis were found to represent a distinct group, in terms of disease severity, microbiology, and asthma phenotype. Performing (HR)CT and sputum cultures can help to identify these patients. These results can possibly contribute to early recognition and targeted treatment of this patient group.

Aerosol Transmission of Aspergillus fumigatus in Cystic Fibrosis Patients in the Netherlands.

We collected sputum samples and cough plates from 15 cystic fibrosis patients in the Netherlands who were colonized with Aspergillus fumigatus; we recovered A. fumigatus of the same genotype in cough aerosols and sputum samples from 2 patients. The belief that transmission of A. fumigatus from cystic fibrosis patients does not occur should be reconsidered.

Accuracy of High-Throughput Nanofluidic PCR-Based Pneumococcal Serotyping and Quantification Assays Using Sputum Samples for Diagnosing Vaccine Serotype Pneumococcal Pneumonia: Analyses by Composite Diagnostic Standards and Bayesian Latent Class Models.

The lack of reliable diagnostic tests for detecting vaccine serotype pneumococcal pneumonia (VTPP) remains a challenging issue in pneumococcal vaccine studies. This study assessed the performances of high-throughput nanofluidic PCR-based pneumococcal serotyping and quantification assay methods using sputum samples (the nanofluidic sputum quantitative PCR [Sp-qPCR] assay) to diagnose 13-valent pneumococcal conjugate VTPP compared with the performance of the serotype-specific urinary antigen detection (UAD) assay using urine samples. Adult pneumonia patients from Japan were enrolled in this study between September 2012 and August 2014. Sputum samples were subjected to the nanofluidic Sp-qPCR assay, quantitatively cultured, and serotyped by the Quellung reaction (SpQt). Urine samples were tested by the UAD method. The diagnostic performances of these tests were assessed using composite reference standards and Bayesian latent class models (BLCMs). Among 244 total patients, 27 (11.1%) tested positive with the UAD assay, while 16 (6.6%) and 34 (13.9%) tested positive with the SpQt and nanofluidic Sp-qPCR assays, respectively, with a cutoff value of ≥104 DNA copies/ml, which showed the maximum value of the Youden index. Using BLCMs, the estimated prevalence for VTPP was 12.9%, and the nanofluidic Sp-qPCR assay demonstrated the best performance (sensitivity, 90.2%; specificity, 96.9%), followed by UAD (sensitivity, 75.6%; specificity, 97.9%) and SpQt (sensitivity, 45.8%; specificity, 99.5%). However, when a higher cutoff value of ≥107 DNA copies/ml was applied, the performance of UAD became comparable to that of Sp-qPCR. The vaccine serotype-specific pneumococcal DNA load in sputum among UAD-positive patients was 3 logs higher than that among UAD-negative patients (P = 0.036). The nanofluidic Sp-qPCR assay may be accurate and useful for detecting VTPP among adults.

Factors affecting time to sputum culture conversion and treatment outcome of patients with multidrug-resistant tuberculosis in China.

BACKGROUND: Few prospective cohort studies, none in China, have investigated the relationship between treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients and sputum culture conversion. Factors affecting the time of the culture conversion throughout the whole course of the treatment have rarely been investigated. METHODS: This study was performed in four cities in Jiangsu province, China. MDR-TB patients were consecutively enrolled between December 2011 and March 2014. Rates of sputum culture conversion were calculated and Cox proportional-hazards model was performed. Factors contributing to sputum culture conversion were investigated. RESULTS: In all, 139 MDR-TB patients with treatment outcomes were enrolled. Median time to culture conversion among those who converted was 91.5 days (interquartile range, 34.0-110.8 days). After multivariable analysis, smoking (HR = 0.44; 95% CI: 0.23-0.83), drinking (HR = 0.41; 95% CI: 0.21-0.81), ofloxacin resistance (HR = 0.43; 95% CI: 0.24-0.76) and sputum smear grade > 1 (HR = 0.51; 95% CI: 0.31-0.83) were less likely to have culture conversion. CONCLUSIONS: MDR-TB patients who smoke, drink, have ofloxacin resistance, or a high smear grade are less likely to respond to treatment and should be meticulously followed up.

Time to Sputum Culture Conversion and Treatment Outcomes Among Patients with Isoniazid-Resistant Tuberculosis in Atlanta, Georgia.

BACKGROUND: Although isoniazid-resistant tuberculosis is more common than multidrug-resistant tuberculosis, it has been much less studied. We examined the impact of isoniazid resistance and treatment regimen, including use of a fluoroquinolone, on clinical outcomes. METHODS: A retrospective cohort study among patients with sputum culture-positive tuberculosis was performed. Early fluoroquinolone (FQ) use was defined as receiving ≥5 doses during the first month of treatment. The primary outcome was time to sputum culture conversion (tSCC). A multivariate proportional hazards model was used to determine the association of isoniazid resistance with tSCC. RESULTS: Among 236 patients with pulmonary tuberculosis, 59 (25%) had isoniazid resistance. The median tSCC was similar for isoniazid-resistant and -susceptible cases (35 vs 29 days; P = .39), and isoniazid resistance was not associated with tSCC in multivariate analysis (adjusted hazard ratio = 0.83; 95% confidence interval [CI], .59-1.17). Early FQ use was higher in isoniazid-resistant than -susceptible cases (20% vs 10%; P = .05); however, it was not significantly associated with tSCC in univariate analysis (hazard ratio = 1.48; 95% CI, .95-2.28). Patients with isoniazid-resistant tuberculosis were treated with regimens containing rifampin, pyrazinamide, and ethambutol +/- a FQ for a median of 9.7 months. Overall, 191 (83%) patients were cured. There was no difference in initial treatment outcomes; however, all cases of acquired-drug resistance (n = 1) and recurrence (n = 3) occurred among patients with isoniazid-resistant tuberculosis. CONCLUSIONS: There was no significant association with isoniazid resistance and tSCC or initial treatment outcomes. Although patients with isoniazid-resistant tuberculosis had a high cure rate, the cases of recurrence and acquired drug resistance are concerning and highlight the need for longer-term follow-up studies.

Comparison of Sputum-Culture Conversion for Mycobacterium bovis and M. tuberculosis.

Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden.

Early interventions for diabetes related tuberculosis associate with hastened sputum microbiological clearance in Virginia, USA.

BACKGROUND: Diabetes complicates tuberculosis (TB) treatment including a prolonged time of sputum culture conversion to negative growth. Since 2013 in Virginia, interventions early in the treatment course have used therapeutic drug monitoring and dose correction for isoniazid and rifampin after 2 weeks of TB treatment in patients with diabetes along with nurse manager initiated diabetes education and linkage to care. METHODS: A retrospective cohort study of the state TB registry was performed for patients initiating drug-susceptible pulmonary TB treatment that were matched for age, gender, chest imaging and sputum smear status to compare time to sputum culture conversion and other clinical outcomes in the pre-and post-intervention groups. RESULTS: Three hundred sixty-three patients had documented time to sputum culture conversion in the pre-and post-intervention periods, including 56 (15%) with diabetes. Seventy-four (57%) of all patients with diabetes were ≥60 years of age at treatment initiation. Twenty-six patients with diabetes were matched in each group. Mean time to sputum culture conversion in the post-intervention group was 42 ± 22 days compared to the pre-intervention group of 62 ± 31 days (p = 0.01). In the post-intervention group 21 (80%) of patients with diabetes had culture conversion by 2 months compared to 13 (50%) in the pre-intervention group (p = 0.04). CONCLUSIONS: Early interventions for diabetes related TB in the programmatic setting may hasten sputum culture conversion.