Sputum Culture Research Articles

Active screening for tuberculosis among high-risk populations in high-burden areas in Zhejiang province, China

ObjectivesTuberculosis (TB) is a major global public health concern. Although the incidence of TB in China is declining, the country continues to face many challenges regarding TB control. This study aimed to develop an active case finding (ACF) strategy for high-risk populations in areas with high TB burden and evaluate the effectiveness of the ACF strategy for early TB detection in patients to reduce TB transmission. Study designThis was a descriptive study. MethodsFrom May to October 2019, active TB screening was conducted in Zhejiang Province, China. Overall, 24 high-burden townships were chosen as study sites. Residents aged ≥65 years, suffering from diabetes, diagnosed with HIV/AIDS, or with a history of TB were mobilized for screening. Chest radiography was performed for all participants in the community. Sputum specimens were collected for sputum smear tests and cultures at county-level TB-designed hospitals. A professional medical team performed the final diagnoses. ResultsOverall, 130,643 residents were included, accounting for 8.85% of the total population in the selected areas. After screening, 89 confirmed cases and 419 suspected cases were identified. The detection rates for suspected and confirmed cases were 320.72/100,000 and 68.12/100,000, respectively. Individuals with a history of TB accounted for a large proportion of detected cases, and the detection rate was higher among males than in females. This study identified 10.5% of reported cases in the selected areas in 2019. In Zhejiang province, compared with the previous year, the rates of TB notification in 2019 and 2020 declined by 7.0% and 7.4%, respectively, compared with the previous year. However, the TB notification rate in 2019 was almost the same as that in 2018 (a decline of 2.5%) but sharply declined in 2020 (14.4%) in the screened areas. ConclusionsOur findings suggest that the ACF strategy may have helped to maintain the downward trends in TB notification rates by detecting patients with TB and suspected cases in the short term.

The use of BPaL containing regimen in the MDR/PreXDR TB treatments in Thailand

The primary objective of this study was to evaluate the real-world effectiveness, side effects and challenges associated with the implementing of the groundbreaking BPaL-containing regimen in Thailand. Another aim was to investigate the characteristics and severity of the disease, the presence of abnormal extensive lesions in chest X-Rays and the influence of cavitation on sputum conversion. Material and method: The case series study included patients at TB clinic of Central chest institute of Thailand between August 2021-April 2023. All 28 Patients fullfilled the diagnostic criterial for MDR-TB by molecular tests and/or sputum culture. Sputum molecular test, utilizing GeneXpert MRB/XDR or Genotype MTBDRsl assay, was conducted. The 8 Pre-XDR patients who exhibited quinolone resistance and the 2 MDR-TB patients who encountered side effected from quinolone drugs were treated with BPaL regimen, while the remainder received BPaLM regimens. Results: Among the 28 patients, 23 (82.1 %) successfully completed the treatment with favorable outcomes. However, one patient from the BpaL regimen died due to severe destroy lung lesion, and four patients from the BpalM regimen discontinued treatment. The investigation into the correlation between extension lesion, cavitation lesions, and culture conversion unveiled that the group with extension lesions and cavitation ≥4 cm had a diminished probability of achieving sputum culture conversion within 8 weeks in comparison to the group without attributes. The associated risk ratio was 0.56 (95 % CI, 0.14–2.27), p = 0.14. Although the study report minimal side effects, 6 patients (22.2 %) experienced peripheral neuropathy and a notable adverse reaction identified was optic neuritis, affecting 2 cases (7.1 %). Summary: The administration of the BPaL-containing regimen resulted in rapid sputum conversion within 8 weeks and had minimal side effects.

Breakthrough of chemiluminescence-based LAM urine test beyond HIV-positive individuals: Clinical diagnostic value of pulmonary tuberculosis in the general population.

To investigate the diagnostic value of a novel high-sensitivity urine lipoarabinomannan (LAM) test (chemiluminescence-based) for active tuberculosis in the general population. A retrospective study was conducted on 250 clinical suspected tuberculosis patients who were HIV-negative and visited the Fourth People's Hospital of Foshan from January 2022 to December 2022. Among them, there were 135 cases of pulmonary tuberculosis, 34 cases of extrapulmonary tuberculosis, and 81 cases of non-tuberculosis. Urine samples were collected for LAM antigen detection before treatment, and laboratory data of sputum smear acid-fast staining (smear method), sputum culture, and GeneXpert method were collected. Using clinical diagnosis as the reference standard, the diagnostic efficacy of 4 methods for detecting active tuberculosis was evaluated. For the 135 cases of pulmonary tuberculosis, the sensitivity of sputum smears, sputm culture, sputm GeneXpert method, and urine LAM were 29.6% (40/135), 45.9% (62/135), 59.3% (80/135), and 51.9% (70/135), respectively. The combination of LAM + GeneXpert and LAM + culture had the highest sensitivity for detecting active pulmonary tuberculosis, which were 71.0% and 78.2%, respectively. For the detection of sputum culture-negative pulmonary tuberculosis, the positive rates of smear, GeneXpert, and LAM were 0.0% (0/73), 53.4% (39/73), and 52.1% (38/73), respectively. LAM + smear and LAM + Genexpert could detect 52.1% and 68.5% of sputum culture-negative patients, respectively. The high-sensitivity urine LAM test holds promise for tuberculosis diagnosis in the general population. It demonstrates high-sensitivity, enabling the detection of sputum culture-negative pulmonary tuberculosis patients. Furthermore, when combined with existing methods, it can enhance the overall detection rate.

Clinical profile of pulmonary tuberculosis patients in Oman from 2010 to 2014:A tertiary care hospital perspective

BackgroundDespite the efforts taken to improve the screening and treatment programs, Tuberculosis (TB) affects many people around the world. This descriptive retrospective study was conducted to explore the clinical profile of patients diagnosed with Pulmonary TB at a tertiary care hospital, Sultanate of Oman, during the period between 2010 and 2014. Methods.This is a cross-sectional study conducted in a tertiary care hospital in Sultanate of Oman during the period between 2010 and 2014. Clinical profile of pulmonary TB cases was investigated. The collected data included patient nationality, gender, age group, method of diagnosis, presenting symptoms, risk factors for TB and its complications. All data was gathered from electronic medical records. The data was analyzed by SPSS version 23. The study was ethically approved by the Ethical committee at the institute. ResultsOur study covered 239 patients with pulmonary and extra pulmonary TB. Pulmonary TB constituted 128 patients (54 %) of the total sample. More than half of the included patients were males and more than 70 % were Omanis. The mean age was 42.74±18.2 years. Half of the pulmonary TB patients fall within 25–50 years age range. Diabetes and hypertension were the most common risk factors reported at 24 patients (20 %) of the population each. While smoking was found to be one of the main risk factors to develop pulmonary TB, 23 patients (18 %) of the subject population were smokers and 13 patients (10 %) had a recent history of traveling along with 13 TB patients and 13 patients (10 %) had history of some kind of contact with TB patients. The main symptoms observed were cough in 86 patients (67 %), fever in 74 patients (58 %) associated with weight loss in 58 patients (45 %) and around 14 patients (11 %) were diagnosed incidentally. Out of the studied population, 22 patients were diagnosed with Ziehl–Neelsen (ZN) stain, followed by 25 patients with TB culture alone and 55 patients had both ZN and TB culture together. Pleural effusion and pneumothorax were the major complications experienced by the subject population, 13 (10.2 %) and 8 (6.3 %) patients respectively. However, 18 patients (14.1 %) died from pulmonary TB. ConclusionMost of the patients covered were of young to middle age, ranging between 25 and 50 years and most of them had pulmonary TB. Diabetes, hypertension, and smoking were found to be the main risk factors. The subject patients presented mainly suffered from cough, fever, and weight loss. ZN staining and sputum culture were the main methods of diagnosis. Pleural effusion and pneumothorax were the most common complications of pulmonary TB encountered in the subject population.

Ceftriaxone Efficacy for Mycobacterium avium Complex Lung Disease in the Hollow Fiber and Translation to Sustained Sputum Culture Conversion in Patients.

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 β-lactam with a lung-to-serum penetration ratio of 12.18-fold. We mimicked lung concentration-time profiles of 7 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 once-daily ceftriaxone monotherapy to 3-drug SOC against 5 MAC clinical isolates in HFS-MAC using γ (kill) slopes, and translated to SSCC rates. Ceftriaxone killed 1.02-3.82 log10 colony-forming units (CFU)/mL, at optimal dose of 2 g once-daily. Ceftriaxone killed all 5 strains below day 0 versus 2 of 5 for SOC. The median γ (95% confidence interval [CI]) was 0.49 (.47-.52) log10 CFU/mL/day for ceftriaxone and 0.38 (.34-.43) log10 CFU/mL/day for SOC. In patients, the SOC was predicted to achieve SSCC rates (CI) of 39.3% (36%-42%) at 6 months. The SOC SSCC was 50% at 8.18 (3.64-27.66) months versus 3.58 (2.20-7.23) months for ceftriaxone, shortening time to SSCC 2.35-fold. Ceftriaxone is a promising agent for creation of short-course chemotherapy.

Evaluating newly approved drugs in combination regimens for multidrug-resistant tuberculosis with fluoroquinolone resistance (endTB-Q): study protocol for a multi-country randomized controlled trial

BackgroundTreatment for fluoroquinolone-resistant multidrug-resistant/rifampicin-resistant tuberculosis (pre-XDR TB) often lasts longer than treatment for less resistant strains, yields worse efficacy results, and causes substantial toxicity. The newer anti-tuberculosis drugs, bedaquiline and delamanid, and repurposed drugs clofazimine and linezolid, show great promise for combination in shorter, less-toxic, and effective regimens. To date, there has been no randomized, internally and concurrently controlled trial of a shorter, all-oral regimen comprising these newer and repurposed drugs sufficiently powered to produce results for pre-XDR TB patients.MethodsendTB-Q is a phase III, multi-country, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of a treatment strategy for patients with pre-XDR TB. Study participants are randomized 2:1 to experimental or control arms, respectively. The experimental arm contains bedaquiline, linezolid, clofazimine, and delamanid. The control comprises the contemporaneous WHO standard of care for pre-XDR TB. Experimental arm duration is determined by a composite of smear microscopy and chest radiographic imaging at baseline and re-evaluated at 6 months using sputum culture results: participants with less extensive disease receive 6 months and participants with more extensive disease receive 9 months of treatment. Randomization is stratified by country and by participant extent-of-TB-disease phenotype defined according to screening/baseline characteristics. Study participation lasts up to 104 weeks post randomization. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 324 participants across 2 arms affords at least 80% power to show the non-inferiority, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per-protocol populations.DiscussionThis internally controlled study of shortened treatment for pre-XDR TB will provide urgently needed data and evidence for clinical and policy decision-making around the treatment of pre-XDR TB with a four-drug, all-oral, shortened regimen.Trial registrationClinicalTrials.Gov NCT03896685. Registered on 1 April 2018; the record was last updated for study protocol version 4.3 on 17 March 2023.

The levels of vitamins and cytokines in serum of elderly patients with community-acquired pneumonia: A case-control study.

The community acquired pneumonia (CAP) is a common disease with high incidence rate and mortality among the elderly. This study aims to explore the association between vitamins, cytokines, and CAP infected by different pathogens in Handan First Hospital. The subjects of this study were elderly patients with community-acquired pneumonia in Handan First Hospital and healthy elderly people in the community from February 2018 to December 2019. The study include 234 CAP patients and 180 healthy elderly people. The differences between the healthy and CAP groups were analyzed by blood routine test, urine routine test, Liquid chromatography tandem mass spectrometry (LC-MS/MS) detection of vitamin level, and Enzyme linked immunosorbent assay (ELISA) detection of cytokine level. Sputum culture was used to detect pathogens. According to our results, there was no significant difference in the contents of vitamin A, vitamin D, vitamin E, and vitamin C in serum between the healthy and CAP elderly. However, compared with the control group, the levels of serum cytokines of IL-2, IL-17, and TGF-β in the CAP patients were significantly increased. In addition, IL-17 was positively correlated with white blood cells, neutrophils, platelet/lymphocyte ratio and neutrophil/lymphocyte ratio of CAP patients, and negatively correlated with lymphocytes. The four pathogens with the highest positive rates were Streptococcus pneumoniae, Klebsiella pneumoniae, Mycoplasma pneumoniae and H. influenza. In patients with S. pneumoniae infection, the IL-2, IL-17, and TGF-β levels were significantly higher than the levels in the control group; IL-17 was also significantly increased in the serum of patients infected with M. pneumoniae, K. pneumoniae, and H. influenza. There is no direct association between vitamins in serum and community acquired pneumonia (CAP). However, the cytokines are closely related to the clinical indicators and pathogens of CAP patients, which can provide references for the diagnosis, prognosis and treatment of CAP patients.

Safety and Efficacy of Clofazimine as an Alternative for Rifampicin in Mycobacterium avium Complex Pulmonary Disease Treatment: Outcomes of a Randomized Trial

BackgroundRetrospective studies have suggested clofazimine as an alternative for rifampicin in MAC-PD treatment. Research questionIs a treatment regimen consisting of clofazimine-ethambutol-macrolide non inferior to the standard treatment regimen (rifampicin-ethambutol-macrolide) in the treatment of M.avium complex pulmonary disease? Study design and MethodsIn this single centre non-blinded clinical trial, we randomly assigned adult patients with MAC-PD in a 1:1 ratio to receive rifampicin or clofazimine as adjuncts to an ethambutol-macrolide backbone. The primary outcome was sputum culture conversion after six months of treatment. ResultsForty patients were assigned to receive either rifampicin (n=19) or clofazimine (n=21) ) next to ethambutol and a macrolide. After 6 months of treatment, both arms showed similar percentages of sputum culture conversion based on intention to treat analysis: 58% (11/19) for rifampicin; 62% (13/21) for clofazimine. Study discontinuation, mainly due to adverse events, was equal in both arms (26% vs 33%). Based on an on treatment analysis sputum culture conversion after 6 months of treatment was 79% in both groups.In the clofazimine arm, diarrhoea was more prevalent (76% vs 37%; p=0.012), while arthralgia was more frequent in the rifampicin arm (37% vs 5%; p=0.011). No difference in the frequency of QTc prolongation was seen between both groups. InterpretationA clofazimine-ethambutol-macrolide regimen showed similar results to the standard rifampicin-ethambutol-macrolide regimen and should be considered in the treatment of MAC-PD. The frequency of adverse events was similar in both arms, but their nature was different. Individual patients characteristics and possible drug-drug interactions should be taken into consideration when choosing an antibiotic regimen for MAC-PD.

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.

1107. Three Year Longitudinal Assessment of Pseudomonas aeruginosa (Pa) Antibiotic Susceptibility in Children with Cystic Fibrosis (CF) in the Era of Modulator Therapy

Abstract Background CF is a genetic disease characterized by chronic lung infection, often with Pseudomonas aeruginosa (Pa). It is widely accepted that increasing antibiotic resistance develops in Pa following repeated antibiotic exposure. With the advent of elexacaftor/tezacaftor/ivacaftor (ETI) modulator therapy, we wished to assess Pa antibiotic resistance to beta-lactam and fluoroquinolone (FQ) antibiotics in both children receiving ETI, and those not eligible for ETI (nonETI) who continue to experience recurrent pulmonary exacerbation (PEx) and require repeated antibiotic treatment. Methods We examined current patterns of antibiotic resistance over 3 years for a cohort of 11 children with CF having 5 or more positive sputum cultures for Pa between January 2020-December 2022 obtained from CF clinic and hospital PEx sputum samples. Chart review included: demographic data; dates of PEx/hospitalization; dates of CF clinic visits; dates and results of CF sputum cultures; and antibiotics used and dates for intravenous (IV) and oral (PO) treatment courses. Results Six males and 5 females were reviewed (6/11 [54%] were Hispanic), with 3/11 (27%) on ETI therapy (average age 14.6 yr), and 8/11 (73%) not on ETI therapy (average age 11.6 yr). Average age at acquisition of Pa was 10.2 yrs. The average number of cultures yielding Pa over 3 years was 11 for both ETI and nonETI subjects. Average number of IV antibiotic courses was 6 for nonETI, but 0 for ETI subjects, while the average number of oral (PO) FQ courses with ciprofloxacin/levofloxacin was 6 in nonETI, and only 1 in ETI subjects. No increase in antibiotic resistance was noted against any IV antibiotic over 3 years of observation (Table), but of the 9 subjects (both ETI and nonETI) who received PO FQ, 5 (55%) were documented to have at least one nonsusceptible isolate, as shown for one 16 year old nonETI subject (Figure). Conclusion Current antibiotic/pulmonary management of children with CF was not associated with an increased risk of IV antibiotic resistance over 3 years of observation despite repeated exposure for PEx (mean of 6 IV antibiotic courses per nonETI subject), but susceptibility to FQ decreased in 55% of those treated over 3 years following repeated FQ oral therapy courses. Disclosures All Authors: No reported disclosures

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 < 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< 0.001) and predominantly arrived from Africa (95.2% vs. 29.6%, P< 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

Association between sputum culture results and pulmonary changes in children with cystic fibrosis.

Despite the significant improvement in the prognosis of cystic fibrosis (CF), it is still regarded as the most common life-shortening genetic disease in Caucasian populations. This disease is the most important cause of chronic lung disease and exocrine pancreatic insufficiency in infancy and childhood. The aim of our study was to assess the potential association between bacterial colonization detected by sputum cultures and pulmonary structural and functional changes in Iranian children with CF. In this cross-sectional study, 76 CF children ≥6 years old registered in the CF Foundation of Children's Medical Center Hospital, Tehran, Iran, who underwent high resolution CT scan (HRCT), pulmonary function test, and sputum cultures within a month of each other during the study period were included. For each patient, demographic characteristics (age and sex), results of sputum cultures, forced expiratory volume in 1st second (FEV1), and chest HRCT findings based on the Bhalla scoring system were recorded in a check list. Sixty seven percent of the patients had positive sputum cultures, with the most commonly isolated microorganism being Pseudomonas aeruginosa (mucoid strain). Based on categorization of Bhalla scores, none of the patients had severe pulmonary involvement. FEV1 was mainly >70%. There was a statistically significant correlation between colonization with mucoid P. aeruginosa and lower Bhalla scores in children aged 14-16 years (P=0.001). Colonization with mucoid P. aeruginosa was also significantly associated with patient's age (P=0.020) and FEV-1 (P=0.001). Severity of lung involvement in CF children is clearly dependent to mucoid P. aeruginosa colonization in airways and this notorious bacterium is the most prevalent one in Iranian CF children. Prompt identification and eradication by proper nebulized and systemic antibiotics can have valueless effects on patients' quality of life and prevent lifelong destructive complications such as bronchiectasis. Timely lung CT scan wisely advised by expert CF treatment team can meticulously detect injuries and it seems to act more efficacious than -still helpful-clinical scores and pulmonary function tests.

Efficacy and safety of the all-oral bedaquiline-containing regimen as treatment for pediatric multidrug/rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study

ABSTRACT Objective The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China. Methods In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed. Results 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8–16} and 11 {9–15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred. Conclusions The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

Actinobacillus ureae may be a critical pathogen in patients with predispositions: A case report and review of the literature.

Actinobacillus ureae (A. ureae) is an unusual commensal of human respiratory flora, rarely causing human infection. The predisposing factors, identification, clinical features, and antibiotic therapy of A. ureae are seldomly reported. Herein, we present a case of 64-year-old man affected by A. ureae pneumonia after intracranial surgery. A 64-year-old male was admitted with vomiting, drowsiness, and a severe disturbance of consciousness and was later diagnosed with cerebral hemorrhage by computed tomography images. After a craniocerebral surgery, the patient suffered from intractable pneumonia, experiencing treatment failure with multiple anti-bacterial agents. Sputum culture yield pure colonies of A. ureae, confirmed by matrix-assisted laser desorption/ionization time of flight and 16S rRNA gene sequencing. Minocycline (100 mg p.o. per 12 hours) with a course of 15 days was administrated for this patient. The respiratory symptoms, presenting as intermittent coughing with purulent and yellowish sputum, were gone. A 3-month follow-up examination showed a complete resolution of radiological findings. Clinically, the actual incidence of A. ureae pneumonia may be higher than that we generally recognized, and clinicians should consider A. ureae as a possible etiologic agent in patients with predispositions. Currently, A. ureae may be susceptible to penicillin, ampicillin, and third-generation cephalosporins. Other antibacterial agents, such as tetracycline, amoxicillin/clavulanic acid, and aminoglycosides also respond well and can be a choice in the treatment of A. ureae infections.

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.

Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

A retrospective cohort analysis of treatment outcomes of patients with tuberculosis who used substances in Tel Aviv, Israel.

To outline the demographic, clinical, laboratory characteristics, and treatment outcomes of tuberculosis (TB) patients who used substances. This retrospective cohort study compared 50 TB patients who used substances with a matched random sample of 100 TB patients who did not use substances between 2007 and 2017. Treatment failure was defined as a sputum smear or culture that tested positive after 5months of treatment, loss to follow-up, unevaluated patients, or death. TB patients who used substances were typically younger, experienced homelessness, smokers, and had fewer chronic diseases than those who did not use substances. They also were hospitalized for longer periods, their treatment durations were longer, had higher rates of multidrug resistant strains, increased rates of treatment failure, and higher mortality. Individuals whose treatment failed predominantly originated from the former Soviet Union, experienced homelessness, and had chronic diseases compared with those whose treatment was successful. In the multivariate analysis, homelessness [odds ratios (OR) = 6.7], chronic diseases (OR = 12.4), and substance use (OR = 4.0) were predictors of treatment failures. TB patients who used substances were more likely to have treatment failure. Targeted interventions, including early diagnosis and enhanced support during treatment, are essential to achieve treatment success in this vulnerable population, in addition to TB-alcohol/drug collaborative activities.

Effect of multimodal diagnostic approach using deep learning-based automated detection algorithm for active pulmonary tuberculosis

In this study, we developed a model to predict culture test results for pulmonary tuberculosis (PTB) with a customized multimodal approach and evaluated its performance in different clinical settings. Moreover, we investigated potential performance improvements by combining this approach with deep learning-based automated detection algorithms (DLADs). This retrospective observational study enrolled patients over 18 years of age who consecutively visited the level 1 emergency department and underwent chest radiograph and sputum testing. The primary endpoint was positive sputum culture for PTB. We compared the performance of the diagnostic models by replacing radiologists’ interpretations of chest radiographs with screening scores calculated through DLAD. The optimal diagnostic model had an area under the receiver operating characteristic curve of 0.924 (95% CI 0.871–0.976) and an area under precision recall curve of 0.403 (95% CI 0.195–0.580) while maintaining a specificity of 81.4% when sensitivity was fixed at 90%. Multicomponent models showed improved performance for detecting PTB when chest radiography interpretation was replaced by DLAD. Multicomponent diagnostic models with DLAD customized for different clinical settings are more practical than traditional methods for detecting patients with PTB. This novel diagnostic approach may help prevent the spread of PTB and optimize healthcare resource utilization in resource-limited clinical settings.

Association of Pseudomonas aeruginosa incident infections with adherence to cystic fibrosis foundation care guidelines

BackgroundCare guidelines for cystic fibrosis (CF) have been developed to enhance consistent care and to improve health outcomes. We determined if adherence to CF care guidelines predicted P. aeruginosa incidence rates (Pa-IR) at U.S. CF centers in 2018. MethodsThis cross-sectional CF Foundation Patient Registry study included 82 adult and 132 pediatric centers. Adherence to 12 guidelines was defined categorically (guideline met) or as a continuous measure (proportion of patients being treated/evaluated per guideline). Association of adherence to individual guidelines with Pa-IR, accounted for center and patient characteristics relevant to Pa-IR and were modeled using random forests and weighted-least-squares (WLS) analyses. ResultsThe mean Pa-IR was 0.2 cases/patient-years at risk (SE 0.0074) for all centers combined. Guideline adherence was lowest for ≥4 bacterial cultures/year (54% of centers) and annual oral glucose tolerance test (OGTT) (48% of centers), and highest for annual non-tuberculous mycobacteria (NTM) sputum culture (98%). The mean number of guidelines met was 6.7 and higher for pediatric (7.3) than adult (5.6) centers, (p<0.001). The number of guidelines met correlated negatively with Pa-IR (β=-0.007, p = 0.043). Macrolide prescription and annual OGTT per guideline were associated with lower and higher Pa-IR, respectively. Centers with lower center-wide lung function, higher proportion of pwCF with low body-mass index, and location in the Southwest had higher Pa-IR. ConclusionOverall adherence to guidelines was high except for performing ≥4 bacterial cultures/year and OGTT. Higher Pa-IR was associated with center characteristics and lower guideline adherence. The lower Pa-IR with greater adherence to guidelines suggests that focusing on quality care can positively impact Pa-IR.