Positive Sputum Culture Research Articles

Predictors of early and interim culture un-conversion in multidrug-resistant/rifampicin-resistant tuberculosis: a retrospective multi-center cohort study in China

BackgroundWe aimed to evaluate the predictors for early and interim culture conversion within 2 months and 6 months of treatment in multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) patients in China.MethodsThis study included adult MDR/RR-TB patients with a positive baseline sputum culture from 8 institutions located in different cities in China from May 2018 to January 2022. We mainly used logistic regression model to derive possible predictors of early and interim culture conversion.ResultsA total of 813 patients were enrolled and 28.5% of them received multidrug-resistant treatment regimens containing bedaquiline. Of these, 362 (44.5%) patients experienced culture conversion within 2 months of treatment, and 649 (79.8%) within 6 months. The results of the multivariable logistic regression analysis revealed that acid-fast bacilli smear positive (adjusted odds ratio [aOR] = 1.637, 95% confidence interval [CI] = 1.197–2.238), cavities (aOR = 1.539, 95% CI = 1.132–2.092), bilateral disease (aOR = 1.638, 95% CI = 1.183–2.269), and viral hepatitis (aOR = 2.585, 95% CI = 1.189–5.622) were identified as risk factors for early culture un-conversion within 2 months of treatment. Additionally, smoking history (aOR = 2.197, 95% CI = 1.475–3.273), previous treatment for tuberculosis (aOR = 1.909, 95% CI = 1.282–2.844), bilateral disease (aOR = 2.201, 95% CI = 1.369–3.537), viral hepatitis (aOR = 2.329, 95% CI = 1.094–4.962) were identified as risk factors for interim culture un-conversion within 6 months of treatment, while patients with regimen containing bedaquiline (aOR = 0.310, 95% CI = 0.191–0.502) was a protective factor.ConclusionsA history of smoking, a baseline sputum AFB smear positive, lung cavities, bilateral disease, previous anti-tuberculosis treatment, or a comorbidity of viral hepatitis can be used as the predictors for early and interim culture un-conversion in MDR/RR-TB patients, while bedaquiline was a protective factor .

Critical assessment of infants born to mothers with drug resistant tuberculosis

There have been no detailed descriptions of infants born to mothers treated for drug resistant TB in pregnancy. Critical case history assessment is important to identify risks and guide clinical practice. In a cohort of pregnant women with multidrug or rifampicin resistant (MDR/RR)-TB enrolled between 1 January 2013 and 31 December 2022, we followed mother-infant pairs until the infant was 12 months old. We performed critical case history assessments to explore potential mechanisms of Mycobacterium tuberculosis transmission to the infant, and to describe the clinical presentation and disease trajectories observed in infants diagnosed with TB. Among 101 mother-infant pairs, 23 (23%) included infants diagnosed with TB disease; 16 were clinically diagnosed and seven had microbiological confirmation (five MDR/RR-TB, two drug-susceptible TB). A positive maternal sputum culture at the time of delivery was significantly associated with infant TB risk (p=0.023). Of the 12 infants diagnosed with TB in the first three months of life, seven (58%) of the mothers were culture positive at delivery; of whom four reported poor TB treatment adherence. However, health system failures, including failing to diagnose and treat maternal MDR/RR-TB, inadequate screening of newborns at birth, not providing appropriate TB preventive therapy (TPT), and M.tuberculosis transmission from non-maternal sources also contributed to TB development in infants. Infants born to mothers with MDR/RR-TB are at greatest risk if maternal adherence to MDR/RR-TB treatment or antiretroviral therapy (ART) is sub-optimal. In a high TB incidence setting, infants are also at risk of non-maternal household and community transmission. Ensuring maternal TB diagnosis and appropriate treatment, together with adequate TB screening and prevention in all babies born to mothers or households with TB will minimise the risk of infant TB disease development. South African Medical Research Council.

Bacterial Profile, Susceptibility Patterns, and Factors Associated with Culture-Positive Sputum Among HIV Patients Presenting with a Cough in Northern Uganda.

Sub-Saharan Africa bears the highest burden of HIV/AIDS infections and constitutes 72% and 69% of AIDS-related deaths and people living with HIV worldwide, respectively. Due to the relationship between pulmonary infections and HIV/AIDS, it is biologically plausible that the surge in morbidity and mortality among HIV/AIDS patients could be attributed to an increase in pulmonary infections among this cohort of patients. This study determined the bacterial profile, susceptibility patterns, and factors associated with culture-positive sputum among HIV patients presenting with cough at the Lira Infectious Disease Centre in Northern Uganda. This prospective cross-sectional study recruited 180 participants. Culture and sensitivity of the sputum samples were done to determine the causative organism and its susceptibility. Blood agar, MacConkey's agar, and Chocolate agar were deployed for the culture media. Antimicrobial susceptibility testing was done using the Kirby-Bauer disc diffusion test. Data were analyzed using SPSS version 26. Out of the 180 enrolled patients, 113 were females with a mean age of 45. Bacterial growth was seen in 56 of the 180 samples. The most common isolate was Staphylococcus aureus at 35.7% of the 56 growths. The minority that accounted for 1.8% each were Citrobacter freundii, Salmonella species and Acinetobacter baumanii, respectively. A combination of ceftriaxone and gentamicin was effective against most organisms isolated in this study. At the multivariate level of analysis, an unsuppressed viral load and low peripheral oxygen saturation were independently associated with a sputum culture-positive cough. HIV patients at LIDC who present with productive cough with low oxygen saturation and an unsuppressed viral load may be screened for Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia, Klebsiella pneumonia, and Enterobacter species infection. A combination of ceftriaxone and gentamicin may be used as empiric therapy before the culture and sensitivity results are available.

Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis.

Routine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design. The rationale of this trial is to investigate the utility of urine lipoarabinomannan (LAM) as a test to identify people with CF with a new positive NTM culture. We hypothesize that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value to identify individuals with a relatively low risk of having positive NTM sputum culture. This is a prospective, single-center, non-randomized observational study in adults with CF, 3 years of negative NTM cultures, and no known history of NTM positive cultures. Patients are followed for two year-long observational periods with the primary endpoint being a positive NTM sputum culture within a year of a positive urine LAM result and a secondary endpoint of a positive NTM sputum culture within 3 years of a positive urine LAM result. Study implementation includes remote consent and sample collection to accommodate changes from the COVID-19 pandemic. This report describes the study design of an observational study aimed at using a urine biomarker to assist in the diagnosis of NTM lung infection in pwCF. If successful, urine LAM could be used as an adjunct to traditional sputum cultures for routine NTM screening.

Resolution of tuberculosis blood RNA signatures fails to discriminate persistent sputum culture positivity after eight weeks of anti-tuberculous treatment.

Concerted efforts aim to reduce the burden of 6 months anti-tuberculous treatment for tuberculosis (TB). Treatment cessation at 8 weeks is effective for most but incurs increased risk of disease relapse. We tested the hypothesis that blood RNA signatures or C-reactive protein (CRP) measurements discriminate 8-week sputum culture status, as a prerequisite for a biomarker to stratify risk of relapse following treatment cessation at this time point. We identified blood RNA signatures of TB disease or cure by systematic review. We evaluated these signatures and CRP measurements in a pulmonary TB cohort, pre-treatment, at 2 and 8 weeks of treatment, and sustained cure after treatment completion. We tested biomarker discrimination of 8-week sputum culture status using area under the receiver operating characteristic curve (AUROC) analysis and, secondarily, assessed correlation of biomarker scores with time-to-culture positivity at 8 weeks of treatment. 12 blood RNA signatures were reproduced in the dataset from 44 individuals with sputum culture positive pulmonary TB. These normalised over time from TB treatment initiation. 11/44 cases with blood RNA, CRP and sputum culture results were sputum culture positive at 8 weeks of treatment. None of the contemporary blood RNA signatures discriminated sputum culture status at this time point or correlated with bacterial load. CRP achieved modest discrimination with AUROC of 0.69 (95% confidence interval 0.52-0.87). Selected TB blood RNA signatures and CRP do not provide biomarkers of microbiological clearance to support TB treatment cessation at 8 weeks. Resolution of blood transcriptional host-responses in sputum culture-positive individuals suggests Mycobacterium tuberculosis may colonise the respiratory tract without triggering a detectable immune response.

The impact of the COVID-19 pandemic on adult bronchiectasis patients and the relationship between clinical parameters and bronchiectasis severity.

Viral infections are an important cause of exacerbation in bronchiectasis patients. We aimed to determine the influence of the COVID-19 pandemic on adult bronchiectasis patients and whether there was a relationship between the clinical parameters and the COVID-19 infection. In this retrospective observational study, 547 bronchiectasis patients were included. Demographic characteristics, vaccination status, Bronchiectasis Severity Index (BSI), FACED and Reiff scores, and clinical and laboratory parameters during COVID-19 infection were evaluated. The median age was 56, and 49.2% of the patients were male. The COVID-19 infection rate was 27.6%. 431 (78.8%) patients had at least one dose of the COVID-19 vaccine. The patients were divided into two groups according to their COVID-19 infection status. Emergency admission was significantly higher in the COVID-19-infected group. There was no statistical difference with other clinical factors. The COVID-19-infected patients were divided into home treatment and hospital/intensive care unit (ICU) treatment groups. There was a statistically significant difference between the two groups regarding advanced age, male gender, presence of asthma, long-term oxygen therapy (LTOT) and non-invasive mechanic ventilator (NIMV) usage, sputum culture positivity, BSI and FACED scores, and multiple laboratory parameters (ferritin, C-reactive protein, eosinophil). In logistic regression analysis, BSI was found as a risk factor [OR 1.252 (1.077-1.456), p=0.004] and eosinophilia as a protective factor [OR 0.986 (0.973-0.999), p=0.030] for hospital/ICU admission. Frequent emergency visits might increase the risk of COVID-19 infection in bronchiectasis patients. BSI was found to be an independent risk factor, and blood eosinophilia could play a protective role in hospital/ICU admission for COVID-19 infection.

Distinct TB-antigen stimulated cytokine profiles as predictive biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain. This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, n = 27) in comparison to recurrence-free, microbiologically cured controls (n = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements. In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens. Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.

Effect of the intraoperative infusion of recombinant activated coagulation factor VII on short-term prognosis and thoracic complications after acute aortic coarctation

Purpose: To investigate the impact of intraoperative infusion of recombinant human-activated coagulation factor VII (rFVIIa) on postoperative outcomes in patients with acute aortic dissection (AAD). Methods: This study involved 120 individuals who underwent aortic coarctation surgery between January 1, 2020, and December 31, 2022 in the First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China. The participants were divided into control (receiving only conventional treatment) and study (receiving rFVIIa infusion in addition to conventional treatment) groups. Various parameters, including patient status, postoperative measures, and complications were evaluated. Results: There was no significant difference in age, gender distribution, duration of myocardial block, onset time, or surgery duration (p > 0.05) between both groups. However, the study group exhibited longer extracorporeal circulation duration (p < 0.05). The study group also demonstrated lower levels of chest drainage compared to the control group 12 and 24 h after surgery (p < 0.05). Moreover, fewer concentrated red blood cells and fresh frozen plasma transfusions were administered to study group (p < 0.05). Despite having longer stays in the ICU (p < 0.05), the study group required less postoperative mechanical ventilation (p < 0.05). There was a significant difference in the incidence of postoperative thrombosis cases, positive gram-negative bacilli sputum culture results, and deaths within the study group (p < 0.05). Conclusion: Intraoperative rFVIIа infusion in AAD patients enhances short-term prognosis, with elevated risk of chest complications. However, further studies with larger sample sizes is essential to comprehensively assess clinical advantages and drawbacks.

Effect of NAT2, GSTM1 and CYP2E1 genetic polymorphisms on plasma concentration of isoniazid and its metabolites in patients with tuberculosis, and the assessment of exposure-response relationships.

Objectives: Isoniazid is a key drug in the chemotherapy of tuberculosis (TB), however, interindividual variability in pharmacokinetic parameters and drug plasma levels may affect drug responses including drug induced hepatotoxicity. The current study investigated the relationships between isoniazid exposure and isoniazid metabolism-related genetic factors in the context of occurrence of drug induced hepatotoxicity and TB treatment outcomes. Methods: Demographic characteristics and clinical information were collected in a prospective TB cohort study in Latvia (N = 34). Time to sputum culture conversion (tSCC) was used as a treatment response marker. Blood plasma concentrations of isoniazid (INH) and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) were determined at three time points (pre-dose (0h), 2h and 6h after drug intake) using liquid chromatography-tandem mass spectrometry. Genetic variations of three key INH-metabolizing enzymes (NAT2, CYP2E1, and GSTM1) were investigated by application PCR- and Next-generation sequencing-based methods. Depending on variables, group comparisons were performed by Student's t-test, one-way ANOVA, Mann-Whitney-Wilcoxon, and Kruskal-Wallis tests. Pearson correlation coefficient was calculated for the pairs of normally distributed variables; model with rank transformations were used for non-normally distributed variables. Time-to-event analysis was performed to analyze the tSCC data. The cumulative probability of tSCC was obtained using Kaplan-Meier estimators. Cox proportional hazards models were fitted to estimate hazard rate ratios of successful tSCC. Results: High TB treatment success rate (94.1%) was achieved despite the variability in INH exposure. Clinical and demographic factors were not associated with either tSCC, hepatotoxicity, or INH pharmacokinetics parameters. Correlations between plasma concentrations of INH and its metabolites were NAT2 phenotype-dependent, while GSTM1 genetic variants did not showed any effects. CYP2E1*6 (T > A) allelic variant was associated with INH pharmacokinetic parameters. Decreased level of AcINH was associated with hepatotoxicity, while decreased values of INA/INH and AcINH/INH were associated with month two sputum culture positivity. Conclusion: Our findings suggest that CYP2E1, but not GSTM1, significantly affects the INH pharmacokinetics along with NAT2. AcINH plasma level could serve as a biomarker for INH-related hepatotoxicity, and the inclusion of INH metabolite screening in TB therapeutic drug monitoring could be beneficial in clinical studies for determination of optimal dosing strategies.

Acquired rifamycin resistance among patients with tuberculosis and HIV in new York City, 2001–2023

IntroductionAcquired rifamycin resistance (ARR) in tuberculosis (TB) has been associated with HIV infection and can necessitate complicated TB treatment regimens, particularly in people living with HIV (PLWH). This work examines clinical characteristics and treatment outcomes of PLWH who developed ARR from 2001 to 2023 in New York City (NYC) to inform best practices for treating these patients. MethodsPLWH who developed ARR 2001–2023 were identified from the NYC TB registry. ResultsSixteen PLWH developed ARR; 15 were diagnosed 2001–2009 and the 16th was diagnosed in 2017. Median CD4 count was 48/mm3. On initial presentation, 14 had positive sputum cultures; of these, 12 culture-converted prior to developing ARR. Ten patients completed a course of TB treatment but subsequently relapsed; in six of these cases, ARR was discovered upon relapse, triggering treatment with a non-rifamycin-containing regimen, while in the other four, ARR was discovered during a second round of rifamycin-containing treatment. Three patients were lost to follow-up during their initial course of TB treatment and later returned to care; after being restarted on a rifamycin-containing regimen, ARR was discovered. Finally, three patients culture-converted during their first course of treatment but subsequently had cultures that grew rifamycin-resistant Mycobacterium tuberculosis prior to treatment completion, leading to changes in their treatment regimens. Among the 16 patients, eight died before being cured of TB, seven successfully completed treatment, and one was lost to follow-up. ConclusionsPLWH should be monitored closely for the development of ARR during treatment for TB, and sputum culture conversion should be interpreted cautiously in this group. Collecting a final sputum sample may be especially important for PLWH, as treatment failure and relapse were common in this population. The decrease in the number of cases of ARR among PLWH during the study period may reflect the decrease in the total number of PLWH diagnosed with TB in NYC in recent years, improved immune status of PLWH due to increased uptake of antiretroviral drugs, and improvements in the way anti-TB regimens are designed for PLWH (such as recommending daily rather than intermittent rifamycin dosing).

Prevalence of subclinical pulmonary tuberculosis in adults in community settings: an individual participant data meta-analysis

Subclinical pulmonary tuberculosis, which presents without recognisable symptoms, is frequently detected in community screening. However, the disease category is poorly clinically defined. We explored the prevalence of subclinical pulmonary tuberculosis according to different case definitions. We did a one-stage individual participant data meta-analysis of nationally representative surveys that were conducted in countries with high incidence of tuberculosis between 2007 and 2020, that reported the prevalence of pulmonary tuberculosis based on chest x-ray and symptom screening in participants aged 15 years and older. Screening and diagnostic criteria were standardised across the surveys, and tuberculosis was defined by positive Mycobacterium tuberculosis sputum culture. We estimated proportions of subclinical tuberculosis for three case definitions: no persistent cough (ie, duration ≥2 weeks), no cough at all, and no symptoms (ie, absence of cough, fever, chest pain, night sweats, and weight loss), both unadjusted and adjusted for false-negative chest x-rays and uninterpretable culture results. We identified 34 surveys, of which 31 were eligible. Individual participant data were obtained and included for 12 surveys (620 682 participants) across eight countries in Africa and four in Asia. Data on 602 863 participants were analysed, of whom 1944 had tuberculosis. The unadjusted proportion of subclinical tuberculosis was 59·1% (n=1149/1944; 95% CI 55·8-62·3) for no persistent cough and 39·8% (773/1944; 36·6-43·0) for no cough of any duration. The adjusted proportions were 82·8% (95% CI 78·6-86·6) for no persistent cough and 62·5% (56·6-68·7) for no cough at all. In a subset of four surveys, the proportion of participants with tuberculosis but without any symptoms was 20·3% (n=111/547; 95% CI 15·5-25·1) before adjustment and 27·7% (95% CI 21·0-36·4) after adjustment. Tuberculosis without cough, irrespective of its duration, was more frequent among women (no persistent cough: adjusted odds ratio 0·79, 95% CI 0·63-0·97; no cough: adjusted odds ratio 0·76, 95% CI 0·62-0·93). Among participants with tuberculosis, 29·1% (95% CI 25·2-33·3) of those without persistent cough and 23·1% (18·8-27·4) of those without any cough had positive smear examinations. The majority of people in the community who have pulmonary tuberculosis do not report cough, a quarter report no tuberculosis-suggestive symptoms at all, and a quarter of those not reporting any cough have positive sputum smears, suggesting infectiousness. In high-incidence settings, subclinical tuberculosis could contribute considerably to the tuberculosis burden and to Mycobacterium tuberculosis transmission. Mr Willem Bakhuys Roozeboom Foundation.

Variables associated with antibiotic treatment tolerance in patients with Mycobacterium avium complex pulmonary disease

BackgroundTreatment of Mycobacterium avium complex pulmonary disease (MAC-PD) involves prolonged courses of multiple antibiotics that are variably tolerated and commonly cause adverse drug reactions (ADR). The purpose of this retrospective, single-center study was to identify demographic and disease-related variables associated with significant ADRs among patients treated with antibiotics against MAC-PD.MethodsWe reviewed all patients treated with antibiotic therapy for MAC-PD at a single center from 2000 to 2021. Patients were included if they met diagnostic criteria for MAC-PD, were prescribed targeted antibiotic therapy for any length of time and had their treatment course documented in their health record. We compared patients who completed antibiotics as originally prescribed (tolerant) with those whose antibiotic treatment course was modified or terminated secondary to an ADR (intolerant).ResultsOver the study period, 235 patients were prescribed antibiotic treatment with their clinical course documented in our center’s electronic health record, and 246 treatment courses were analyzed. One hundred forty-three (57%) tolerated therapy versus 108 (43%) experienced ADRs. Among the 108 intolerant courses, 67 (63%) required treatment modification and 49 (46%) required premature treatment termination. Treatment intolerance was associated more frequently with smear positive sputum cultures (34% vs. 20%, p = 0.009), a higher Charlson Comorbidity Index (CCI) (4 vs. 6, p = 0.007), and existing liver disease (7% vs. 1%, p = 0.03). There was no between-group difference in BMI (21 vs. 22), fibrocavitary disease (24 vs. 19%), or macrolide sensitivity (94 vs. 80%). The use of daily therapy was not associated with intolerance (77 vs. 79%). Intolerant patients were more likely to be culture positive after 6 months of treatment (44 vs. 25%).ConclusionsPatients prescribed antibiotic therapy for MAC-PD are more likely to experience ADRs if they have smear positive sputum cultures at diagnosis, a higher CCI, or existing liver disease. Our study’s rate of early treatment cessation due to ADR’s was similar to that of other studies (20%) but is the first of its kind to evaluate patient and disease factors associated with ADR’s. A systematic approach to classifying and addressing ADRs for patients undergoing treatment for MAC-PD is an area for further investigation.

Microbial variations in sputum cultures among hospitalized patients with community-acquired pneumonia: differences in sputum microbiota between asthma and COPD patients.

To assess differences in the sputum microbiota of community-acquired pneumonia (CAP) patients with either COPD or asthma, specifically focusing on a patient population in Turkey. This retrospective study included hospitalized patients > 18 years of age with a diagnosis of pneumonia between January of 2021 and January of 2023. Participants were recruited from two hospitals, and three patient groups were considered: CAP patients with asthma, CAP patients with COPD, and CAP patients without COPD or asthma. A total of 246 patients with CAP were included in the study, 184 (74.8%) and 62 (25.2%) being males and females, with a mean age of 66 ± 14 years. Among the participants, 52.9% had COPD, 14.2% had asthma, and 32.9% had CAP but no COPD or asthma. Upon analysis of sputum cultures, positive sputum culture growth was observed in 52.9% of patients. The most commonly isolated microorganisms were Pseudomonas aeruginosa (n = 40), Acinetobacter baumannii (n = 20), Klebsiella pneumoniae (n = 16), and Moraxella catarrhalis (n = 8). CAP patients with COPD were more likely to have a positive sputum culture (p = 0.038), a history of antibiotic use within the past three months (p = 0.03), utilization of long-term home oxygen therapy (p < 0.001), and use of noninvasive ventilation (p = 0.001) when compared with the other patient groups. Additionally, CAP patients with COPD had a higher CURB-65 score when compared with CAP patients with asthma (p = 0.004). This study demonstrates that CAP patients with COPD tend to have more severe presentations, while CAP patients with asthma show varied microbial profiles, underscoring the need for patient-specific management strategies in CAP.

Patient Characteristics Associated with Concurrent Klebsiella pneumoniae Infection and Severe Pulmonary Tuberculosis.

This study aims to investigate the clinical characteristics associated with concurrent Klebsiella pneu-moniae (K. pneumoniae) infection in hospitalized patients with severe pulmonary tuberculosis. A retrospective study was conducted on hospitalized severe pulmonary tuberculosis patients between January 2019 and December 2020. Among the 487 patients with severe pulmonary tuberculosis, a positive sputum culture for K. pneumoniae was reported in 76 patients (15.6%, 61 males and 15 females). Among these patients, 27 (35.5%) and 49 (64.5%) patients were with and without K. pneumoniae infection, respectively. Compared to patients without K. pneumoniae infection, patients with K. pneumoniae infection had higher mortality (16.3% vs. 40.7%, p = 0.02), and lower inhibitory/cytotoxic CD8 count (24.2 ± 9.9 vs. 17.8 ± 8.0, p = 0.02), complement C4 (0.3 ± 0.1 vs. 0.2 ± 0.1, p = 0.01), and retinol-binding protein level (32.2 ± 22.2 vs. 22.4 ± 11.8, p = 0.02). Furthermore, the acute Physiology and Chronic Health Evaluation II score was associated with the K. pneumoniae infection in severe pulmonary tuberculosis patients. It can be concluded that a significant number of severe pulmonary tuberculosis patients can have concurrent K. pneumoniae infection. Immunity, nutritional status, and disease severity are associated with the concurrent infection of K. pneumoniae in these patients.

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.

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

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.

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.

Prevalence of subclinical pulmonary tuberculosis and its association with HIV in household contacts of index tuberculosis patients in two South African provinces: a secondary, cross-sectional analysis of a cluster-randomised trial

BackgroundPeople with subclinical tuberculosis (TB) have microbiological evidence of disease caused by Mycobacterium tuberculosis, but either do not have or do not report TB symptoms. The relationship between human immunodeficiency virus (HIV) and subclinical TB is not yet well understood. We estimated the prevalence of subclinical pulmonary TB in household contacts of index TB patients in two South African provinces, and how this differed by HIV status.MethodsThis was a cross-sectional, secondary analysis of baseline data from the intervention arm of a household cluster randomised trial. Prevalence of subclinical TB was measured as the number of household contacts aged ≥ 5 years who had positive sputum TB microscopy, culture or nucleic acid amplification test (Xpert MTB/Rif or Xpert Ultra) results on a single sputum specimen and who did not report current cough, fever, weight loss or night sweats on direct questioning. Regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the association between HIV status and subclinical TB; adjusting for province, sex and age in household contacts; and HIV status in index patients.ResultsAmongst household contacts, microbiologically confirmed prevalent subclinical TB was over twice as common as symptomatic TB disease (48/2077, 2.3%, 95% CI 1.7–3.1% compared to 20/2077, 1.0%, 95% CI 0.6–1.5%). Subclinical TB prevalence was higher in people living with HIV (15/377, 4.0%, 95% CI 2.2–6.5%) compared to those who were HIV-negative (33/1696, 1.9%, 95% CI 1.3–2.7%; p = 0.018). In regression analysis, living with HIV (377/2077, 18.2%) was associated with a two-fold increase in prevalent subclinical TB with 95% confidence intervals consistent with no association through to a four-fold increase (adjusted OR 2.00, 95% CI 0.99–4.01, p = 0.052). Living with HIV was associated with a five-fold increase in prevalent symptomatic TB (adjusted OR 5.05, 95% CI 2.22–11.59, p < 0.001).ConclusionsMost (70.6%) pulmonary TB diagnosed in household contacts in this setting was subclinical. Living with HIV was likely associated with prevalent subclinical TB and was associated with prevalent symptomatic TB. Universal sputum testing with sensitive assays improves early TB diagnosis in subclinical household contacts.