Positive Mycobacterial Cultures Research Articles

Diagnostic Value of Targeted Next-generation Sequencing in Pulmonary Mycobacterial Infections.

This study aimed to explore the diagnostic value of novel technique-targeted next-generation sequencing (tNGS) of bronchoalveolar lavage fluid (BALF) in pulmonary mycobacterial infections. This retrospective study was conducted on patients who underwent bronchoscopy and tNGS, smear microscopy, and mycobacterial culture of BALF. Patients with positive Mycobacterium tuberculosis (MTB) culture or GeneXpert results were classified into the tuberculosis case group. Those diagnosed with nontuberculous mycobacteria (NTM)-pulmonary disease (NTM-PD) composed the case group of NTM-PD patients. The control group comprised patients without tuberculosis or NTM-PD. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance. For tuberculosis patients with positive mycobacterial culture results, the areas under the ROC curves (AUCs) for tNGS, GeneXpert, and smear microscopy were 0.975 (95% CI: 0.935, 1.000), 0.925 (95% CI: 0.859, 0.991), and 0.675 (95% CI: 0.563, 0.787), respectively. For tuberculosis patients with positive GeneXpert results, the AUCs of tNGS, culture, and smear microscopy were 0.970 (95% CI: 0.931, 1.000), 0.850 (95% CI: 0.770, 0.930), and 0.680 (95% CI: 0.579, 0.781), respectively. For NTM-PD, the AUCs of tNGS, culture, and smear-positive but GeneXpert-negative results were 0.987 (95% CI: 0.967, 1.000), 0.750 (95% CI: 0.622, 0.878), and 0.615 (95% CI: 0.479, 0.752), respectively. The sensitivity and specificity of tNGS in NTM-PD patients were 100% and 97.5%, respectively. tNGS demonstrated superior diagnostic efficacy in mycobacterial infection, indicating its potential for clinical application.

Increasing trends of non-tuberculous mycobacteria clinical isolates in Guangzhou, China

Non-tuberculous mycobacteria (NTM) are one of major public health concern. The current study aimed to find the prevalence trends of NTM in Guangzhou, China from January 2018 to December 2023. A total of 26,716 positive mycobacterial cultures were collected. Thirty-six specimens with incomplete personal information were excluded. The remaining 26,680 specimens were identified using a gene chip method. 16,709 isolates were Mycobacterium tuberculosis (MTB) (62.63 %), and 9,971 were NTM (37.37 %). 43.43 % (4,330/9,971) of NTM isolates were male, and 56.57 % (5,641/9,971) were female (χ2 = 24.36, P < 0.05), a male to female ratio of approximately 1:1.30. Infections in individuals with aged 40 years and above was higher (77.63 %) than below 40 years (22.37 %) (χ2 = 4.94, P = 0.026). The annual NTM isolation rates from 2018 to 2023 were 32.03 %, 34.00 %, 36.27 %, 38.58 %, 38.99 %, and 43.24 %, respectively, showing an increasing trend (χ2 for trend = 0.097, P < 0.05) (R = 0.097, P < 0.05). Out of 9,971 NTM isolates, 8,881 cases include only five common NTM species (MAC, M. abscessus/M. chelonae, M. kansasii, M. fortuitum, and M. gordonae). The overall NTM isolation rate was 37.37 %. The NTM isolation rate was significantly higher than the national average, showing an increasing trend over the last six years.

The diagnostic performance of Xpert MTB/RIF Ultra on Pericardial, Pleural and Ascitic cohort study fluids for diagnosis of extra-pulmonary Tuberculosis at a referral hospital in Malawi.

Extra-pulmonary tuberculosis (EPTB) accounts for 15% of the 1.4 million patients with TB notified in 2019. EPTB carries a high risk of mortality and so early diagnosis and treatment are important to reduce this risk. Diagnosis of EPTB in low- and middle-income countries is challenging. This study investigated the diagnostic performance of Xpert MTB Ultra for the diagnosis of EPTB (pericardial, pleural, and ascitic fluid) in adults at a referral hospital in Malawi. Adults with suspected extra-pulmonary TB were screened for evidence of extra-pulmonary fluid and tested for TB using Xpert MTB Ultra, mycobacterial culture, and a Focused Abdominal Sonography in HIV-associated TB (FASH scan). The diagnostic performance of the Xpert MTB Ultra was compared to mycobacterial culture and a composite reference standard defined as a positive FASH scan or a positive mycobacterial culture or a clinical TB diagnosis (constitutional symptoms not otherwise explained with response to empirical TB treatment). There were 174 patients recruited: 99/174 (57%) pleural, 70/174 (40%) ascitic and 5/174 (3%) pericardial. Overall, 10/174 (6%) had bacteriologically confirmed TB and 30/174 (17%) were started on TB treatment based on a positive FASH scan or a clinical TB diagnosis. The sensitivity and specificity of Xpert ultra compared to culture was 83% (95%CI:36%-100%) and 98% (95%CI:94%-99%), respectively. Compared to the composite reference standard, the sensitivity of Xpert Ultra was 17% (95%CI:7%-34%) and specificity was 98% (95%CI:94%-100%). Xpert MTB Ultra provides good diagnostic performance on pleural, pericardial and ascitic fluid with reference to mycobacterial culture. Improved EPTB diagnostic tests are required to improve patient outcomes. We recommend larger multi-centre studies to corroborate our findings.

134. Yield of Fungal and Mycobacterial Cultures for Operative Specimens in Orthopedic Procedures

Abstract Background Fungal and mycobacterial cultures are routinely sent on orthopedic operative specimens, but their impact on clinical care is not well established. Processing fungal and mycobacterial cultures is time and labor intensive, associated with significant healthcare costs, and may yield false-positive results due to contamination. The objective of this study was to determine the utility and diagnostic yield of fungal and mycobacterial cultures for orthopedic infections. Methods Patients undergoing surgery by the orthopedic or podiatry service that had operative specimens sent for fungal and mycobacterial cultures from January through December 2022 were included. Descriptive statistics were used to evaluate yield of fungal and mycobacterial cultures and incremental yield of fungal cultures over standard bacterial culture media. A random subset of patients was manually reviewed to determine whether microorganisms identified by fungal or mycobacterial cultures were considered clinically relevant and whether culture results changed management. Results Fungal and mycobacterial cultures were ordered on a total of 1148 operative specimens in 428 patients. A mean of 2.1 ± 1.4 specimens was collected per operative procedure. A microorganism was identified in 33 (2.8%) of fungal cultures and in no mycobacterial cultures. Fungal organisms included yeast (90.9%) and mold (9.1%). Of 50 randomly selected patients, a total of 249 operative specimens were collected (mean 5 per patient, 2.7 per operative procedure). A microorganism was identified by fungal culture in 5 (2%) specimens from 3 patients. All three patients were treated with antifungal agents indicating the fungi were deemed to be clinically relevant. However, the fungi also grew on the standard bacterial media from all 5 specimens suggesting there was no incremental benefit of the fungal cultures. There were no positive mycobacterial cultures, and no patients received mycobacterial treatment. Conclusion The diagnostic yield of fungal and mycobacterial cultures on operative specimens in orthopedic and podiatry surgery is very low and rarely results in a change in therapeutic management. The results of this study demonstrate an opportunity for diagnostic stewardship for these procedures. Disclosures Timothy C. Jenkins, MD, Basilea: Clinical events adjudication committee

Incidence of nontuberculous mycobacteria infections among persons with cystic fibrosis in the United States (2010–2019)

BackgroundNontuberculous mycobacteria (NTM) are ubiquitous, environmental bacteria that can cause chronic lung disease. Persons with cystic fibrosis (pwCF) are at high risk for NTM. Approximately 1 in 5 pwCF in the United States (U.S.) is affected by pathogenic NTM species, and incidence rates of NTM have been increasing among pwCF as well as in the general population. Prevalence of NTM pulmonary infections (PI) varies widely across the United States because of geographic variation in environmental exposures. This study will present updated region-level incidence of NTM infections in the cystic fibrosis (CF) population in the U.S.MethodsWe used the Cystic Fibrosis Foundation Patient Registry (CFFPR) data for the period 2010 through 2019. Our study population comprised persons with CF ≥ 12 years of age who had been tested for NTM PI. We included only registry participants with NTM culture results. We defined incident cases as persons with one positive mycobacterial culture preceded by ≥ two negative mycobacterial cultures. We defined non-cases as persons with ≥ two negative mycobacterial cultures. We estimated average annual NTM PI incidence by region. Using quasi-Poisson models, we calculated annual percent change in incidence by region.ResultsWe identified 3,771 incident NTM infections. Of these cases, 1,816 (48.2%) were Mycobacterium avium complex (MAC) infections and 960 (25.5%) were Mycobacterium abscessus infections. The average annual incidence of NTM PI among pwCF in the U.S. was 58.0 cases per 1,000 persons. The Northeast had the highest incidence of MAC (33.5/1,000 persons tested) and the South had the highest incidence of M. abscessus (20.3/1,000 persons tested). From 2010 to 2019, the annual incidence of total NTM PI increased significantly by 3.5% per year in the U.S.ConclusionsNTM PI incidence is increasing among pwCF. Identifying high risk areas and increasing trends is important for allocating public health and clinical resources as well as evaluating interventions.

Clinical manifestations, treatment and outcomes of patients infected with Mycobacterium haemophilum with a focus on immune reconstitution inflammatory syndrome: a retrospective multi-site study

Background Mycobacterium haemophilum is a nontuberculous mycobacterium with fastidious in vitro growth requirements and an increasingly reported cause of extrapulmonary disease. Timely diagnosis and management of M. haemophilum infections and the immune reconstitution inflammatory syndromes (IRIS) observed in a subset of patients during treatment remain challenging. Methods We conducted a retrospective chart review between January 1, 2010, and January 1, 2022 and identified 26 patients diagnosed with M. haemophilum infection at our institution. We describe their clinical presentation, diagnostic results, management, and outcomes. Results The majority of patients in our cohort had upper and/or lower extremity skin involvement, were immunosuppressed, and had generally favourable treatment outcomes. All tested M. haemophilum isolates were susceptible in vitro to clarithromycin and trimethoprim-sulfamethoxazole. Moreover, high rates of susceptibility were noted for ciprofloxacin (95%), linezolid (90%), and rifampin (85%). IRIS was identified in 31% of cases and should be considered in patients who develop worsening skin lesions or systemic symptoms following the initiation of effective antimicrobial therapy. Visualisation of acid-fast bacilli on initial tissue stains, a positive mycobacterial blood culture, and rapid de-escalation of tumour necrosis factor-α inhibitors and/or corticosteroids were more frequently encountered among patients in our cohort who developed IRIS. Conclusion M. haemophilum infection should be considered among patients receiving immunomodulatory therapy who develop discoloured or nodular skin lesions involving the extremities, worsening focal arthritis, tenosynovitis, or isolated adenopathy. A heightened awareness of this pathogen’s clinical and laboratory characteristics can lead to a timely diagnosis and favourable outcome.

Description, validation, and review of a decade of experience with a laboratory-developed PCR test for detection of Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens

Rapid detection of Mycobacterium tuberculosis complex directly from clinical specimens is critical for patient care. Mycobacterial culture requires days to weeks for results and therefore many laboratories employ rapid molecular methods for the diagnosis of tuberculosis. There are two FDA-cleared molecular assays for the detection of M. tuberculosis complex in the United States and both are cleared for testing of respiratory specimens only. The detection of M. tuberculosis complex in extrapulmonary specimens is often done using laboratory-developed PCR methods. In this work, the verification and subsequent validation of test performance over a decade is detailed for a laboratory-developed PCR assay (MTBRP) that detects M. tuberculosis complex from respiratory and non-respiratory specimens. The assay also provides information about potential isoniazid resistance. The performance of the MTBRP PCR assay was compared to the Cepheid Xpert MTB/RIF assay in acid-fast smear positive and smear negative specimens and mycobacterial culture for acid-fast smear positive specimens. The MTBRP assay demonstrated 99% correlation with the Xpert MTB/RIF assay using 499 respiratory specimens. The performance of the MTBRP PCR assay compared with mycobacterial culture for 867 AFB smear positive respiratory and non-respiratory specimens demonstrated a sensitivity of 100% and a specificity of 99.1%. This work provides longitudinal evidence using real-world clinical laboratory conditions and specimens to demonstrate that laboratory-developed PCR assays such as the MTBRP can provide a rapid and sensitive method for detection of pulmonary and extra-pulmonary tuberculosis from a wide-variety of smear positive specimen sources.

Prevalence of Culture-Confirmed Tuberculosis Among Patients with Nontuberculous Mycobacterial Disease.

BackgroundCurrently, the prevalence of nontuberculous mycobacteria (NTM) strains isolated from mycobacterial cultures has been well characterized. However, the data on the prevalence of tuberculosis (TB) in patients with NTM disease remain unclear.MethodsBetween January 2012 and August 2020, consecutive patients with positive mycobacterial cultures were included for analysis. The identification of Mycobacteria spp. was performed using the DNA array method or sequencing of 16S rDNA. NTM disease is diagnosed when the same infectious agent is identified in at least two sputum or is identified in sterile samples.ResultsA total of 997 strains were isolated from 828 inpatients. Of them, 261 inpatients (31.5%) were diagnosed as NTM disease. The mean age of the 261 patients was 55.7 ±15.5 years old and 64.0% (n = 167) of them were male. The prevalence of culture-confirmed TB patients among patients with NTM disease was estimated as 8.0% (21/261).ConclusionTB is common in NTM disease and caution should be taken when initiating the treatment of NTM disease.

Primary drug resistance among Mycobacterium tuberculosis isolates from treatment naïve and new pulmonary tuberculosis patients in relation to their socio-economic status

BACKGROUND: Multidrug-resistant Tuberculosis (TB) has become an area of growing concern throughout the World, despite the global efforts in eliminating TB. Detection of primary drug resistance in treatment naïve patients, either due to spontaneous mutation or due to transmission of drug-resistant strains is an important indicator of the presence of drug-resistant strains in the community.OBJECTIVES: The objective is to estimate the prevalence of primary drug resistance in treatment naïve pulmonary TB patients and to identify the socio-economic class of the resistant population.MATERIALS AND METHODS: A total of 272 treatment naïve presumptive TB patients were enrolled in the study from September 2018 to December 2020. The samples were subjected to GeneXpert, for detecting the presence of Mycobacterium TB (MTB) along with Rifampicin (RIF) resistance detection. Phenotypic drug susceptibility testing (DST) was performed on all positive mycobacterial cultures using the 1% proportion method against first-line anti-tuberculous drugs. Socioeconomic status of the patients was also assessed based on updated Kuppuswamy Socioeconomic scale (2018).RESULTS: Of the 272 samples subjected to GeneXpert MTB/RIF assay, MTB was detected in 193 (71%) samples and RIF resistance (rpoB gene) was detected in 25 (9%) samples. Phenotypic DST detected multidrug-resistant (MDR) in 22 (8%) samples. Majority of the MDR patients (55%) were belonging to the upper lower (IV) class of Kuppuswamy socio-economic scale.CONCLUSION: High prevalence of MDR-TB among treatment naïve pulmonary TB patients was noted in patients belonging to Class IV of Kuppuswamy socio-economic scale.

ЛЕГЕНЕВИЙ СИНДРОМ «ГАРЯЧОЇ ВАННИ»

HOT TUB LUNG Y. O. Dziublyk Abstract This review deals with current approaches to etiology, pathogenesis, clinical features and diagnostics of hot tub lung. The aim of the report is to extend the knowledge of practicing physicians in the area of interstitial lung diseases considering possible role of environmental exposures. Hot tub lung is a granulomatous lung disease, resulted in hyperreactive response of immune system to airborne exposure with nontuberculous mycobacteria (NTM). ATS diagnostic criteria for hot tub lung include the sub-acute onset of respiratory symptoms associated with hot tub exposure, positive mycobacterial cultures from respiratory and water samples, and characteristic radiographic findings. Treatment of this condition rests on avoidance of exposure with bacterial antigens and a trial of corticosteroid therapy. Better understanding of this pathology would help physician with sometimes difficult differential diagnosis of interstitial lung diseases. Key words: hot tub lung, nontuberculous mycobacteria, hypersensitivity pneumonitis. Ukr. Pulmonol. J. 2022;30(1):25–29.

Fungal and mycobacterial cultures should not be routinely obtained for diagnostic work-up of patients with suspected periprosthetic joint infections.

Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative. We performed a retrospective review of patients diagnosed with hip or knee PJI between 1 January 2010 and 31 December 2019, at the Mayo Clinic in Rochester, Minnesota, USA. We included patients aged 18 years or older who had fungal, mycobacterial, or both cultures performed together with bacterial cultures. Cases with positive fungal or mycobacterial cultures were reviewed using the electronic medical record to classify the microbiological findings as representing true infection or not. There were 2,067 episodes of PJI diagnosed within the study period. A total of 3,629 fungal cultures and 2,923 mycobacterial cultures were performed, with at least one of these performed in 56% of episodes (n = 1,157). Test positivity rates of fungal and mycobacterial cultures were 5% (n = 179) and 1.2% (n = 34), respectively. After a comprehensive review, there were 40 true fungal and eight true mycobacterial PJIs. BCB were 90% sensitive in diagnosing true fungal PJI and 100% sensitive in detecting rapidly growing mycobacteria (RGM). Fungal stains were performed in 27 true fungal PJI but were only positive in four episodes (14.8% sensitivity). None of the mycobacterial stains was positive. Routine fungal and mycobacterial stains and cultures should not be performed as they have little clinical utility in the diagnosis of PJI and are associated with significant costs. Candida species and RGM are readily recovered using BCB. More research is needed to predict rare non-Candida fungal and slowly growing mycobacterial PJI that warrant specialized cultures. Cite this article: Bone Joint J2022;104-B(1):53-58.

COMPARISON OF VALIDITY OF FNACAND ZIEHL–NEELSEN STAINS IN DIAGNOSING CERVICAL TUBERCULOUS LYMPHADENITIS

Objective: To compare the validity of FNAC &amp; ZN staining in diagnosing tuberculous lymphadenitis taking mycobacterial culture as gold standard.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Pathology department, Fauji Foundation Hospital Peshawar, from Oct 2019 to Sep 2020.&#x0D; Methodology: This study includes 100 patients with enlarged cervical lymph nodes who presented as outdoor patients. After routine baseline &amp; radiological investigations, FNAC &amp; ZN staining was carried out, followed by mycobacterial culture.&#x0D; Results: FNAC of tuberculous patients was positive in 56 (56%) patients while 24 (24%) patients revealed posi-tive mycobacterial culture. Inpatients with positive culture, 77 (77%) were FNAC positive and 23 (23%) were negative on cytology.&#x0D; Conclusion: Fine needle aspiration is more sensitive &amp; specific test than Ziehl-Neelsen staining.

Outcomes of adjunctive surgery for nontuberculous mycobacterial pulmonary disease

BackgroundOwing to the unsatisfactory results of antibiotic treatment alone, surgical resection is currently considered as adjunctive therapy in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). However, reports regarding the outcomes of surgery vary considerably by institution. Here, we investigated the surgical outcomes and risk factors associated with unfavorable outcomes after surgery.Methods We analyzed patients with NTM-PD who underwent pulmonary resection at Seoul National University Hospital between January 1, 2006, and December 31, 2020, and assessed the types of surgical procedures, complications, and long-term outcomes. Multivariate logistic regression analysis was used to identify the risk factors associated with treatment refractoriness or recurrence after surgery.ResultsAmong 67 patients who underwent surgery during the study period, the most common indication for surgery was persistent culture positivity despite rigorous medical treatment (80.6%), followed by longstanding cavitary lesions or radiographic aggravation (10.4%) and massive hemoptysis (4.5%). Among 53 patients with positive mycobacterial cultures at the time of surgery, 38 (71.7%) achieved initial negative culture conversion, 9 (17.0%) of whom experienced recurrence. Nine (13.4%) patients experienced postoperative complications, which were managed without lasting morbidity and mortality. Female sex (adjusted odds ratio [aOR] 6.63; 95% confidence interval [CI] 1.04–42.4; P = .046), preoperative positive mycobacterial culture (aOR 5.87; 95 %CI 1.04–33.08; P = .045), and residual lesions (aOR 6.86; 95 %CI 1.49–31.56; P = .013) were associated with refractoriness or recurrence.ConclusionsPulmonary resection is a reasonable treatment modality for patients with refractory NTM-PD or major complications such as massive hemoptysis. The potential risk factors associated with unfavorable outcomes included female sex, preoperative positive mycobacterial culture, and residual lesions after surgery.

Predictors and Trends of MDR/RR-TB in Shenzhen China: A Retrospective 2012-2020 Period Analysis.

PurposeWe analyzed the trends and predictors of multidrug-resistant (MDR) or rifampicin-resistant (RR) tuberculosis (TB) in culture-positive cases in Shenzhen during 2012–2020, after the implementation of improved strategies (scale-up molecular drug susceptibility testing [mDST], expansion of DST eligibility, and generous reimbursement of MDR-TB outpatient care costs).Materials and MethodsWe retrospectively extracted and analyzed data from the TB Information System on drug-resistant pulmonary tuberculosis diagnosed in Shenzhen during the 2012–2020 period. We analyzed trends in RR- and MDR-TB rates in new cases during 2012–2018 and 2018–2020 periods, and among previously-treated cases during 2012–2017 and 2017–2020 periods, using Cochran-Armitage tests. We generated multivariate logistic regression models to analyze demographic predictors of MDR/RR-TB rates.ResultsWe found 21,367 positive mycobacterial cultures in Shenzhen during the 2012–2020 period, and 19,951 (93.4%) were identified as Mycobacterium tuberculosis and had DST results (92.0% of those were mDST-based). Of these patients with DST results, 1630 (8.2%) were RR-TB, and 1142 (5.7%) were MDR-TB. Of the RR-TB, 70% were MDR-TB. The MDR/RR-TB rate in new TB cases increased significantly during the 2012–2018 period (Ptrend < 0.05), but it decreased in the 2018–2020 period (Ptrend > 0.05, with a significant trend for MDR-TB). Among previously treated cases, the temporal MDR/RR-TB rate trends did not differ significantly (Ptrend > 0.05). Our multivariate analysis showed that age younger than 30 years, housework service/unemployment, local residency, and previous TB treatment were all predictors of MDR/RR-TB. The percentage of patients with MDR-TB on treatment increased from 49.4% in 2012 to 70.5% in 2020. The treatment success rate of patients with MDR-TB during the 2012–2018 period was 71%.ConclusionDuring the study period in Shenzhen, the cases of MDR/RR-TB were detected, and the treatment enrollment increased and the MDR-TB rates decreased gradually after 2017. Decreasing trends may reflect the efficacy of improved strategies; however, their long-term impact on the MDR-TB burden remains to be investigated. The predictors of MDR-TB identified in our study should be considered when developing targeted MDR-TB control strategies.

Ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery

ObjectiveTo describe the ocular manifestations of disseminated Mycobacterium chimaera infection after cardiothoracic surgery. DesignRetrospective, observational case series. ParticipantsPatients with disseminated M. chimaera infection treated at the University of Alberta Hospital and Royal Alexandra Hospital in Edmonton, Alberta, Canada. MethodsSeven patients (14 eyes) with systemic M. chimaera infection after aortic graft and/or valvular surgeries were reviewed for ocular involvement. Cases were identified based on histopathologic analysis of cardiac tissue, repeat positive mycobacterial blood cultures, and cerebrospinal fluid analysis. Clinical ocular findings, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (SD-OCT), and autopsy results are described. ResultsThe mean age of our patients was 63 years (range, 22–76 years). Aortic graft and/or valvular surgeries were performed between June 2015 and April 2016. The mean duration from surgery to diagnosis of infection was 27 months (range, 19–36 months). All patients exhibited white-yellowish choroidal lesions. Bilateral, multifocal choroiditis was observed in 6 patients (12 eyes), who died of disseminated M. chimaera infection despite aggressive, multiagent antimicrobial therapy. One patient had a solitary, white-yellow choroidal lesion in the left eye only. Choroidal lesions were hyperfluorescent on late-phase fluorescein angiography and corresponded to localized choroidal thickening and retinal elevation on SD-OCT. ConclusionsM. chimaera infection after cardiothoracic surgery can cause life-threatening disease involving multiple organ systems. Ocular involvement is an important and possibly early clinical finding, with good correlation to systemic disease severity. Ophthalmological assessment and multimodal imaging may aid in early diagnosis and can be used to monitor disease progression.

Harnessing Big Data to Optimize an Algorithm for Rapid Diagnosis of Pulmonary Tuberculosis in a Real-World Setting.

BackgroundThe prompt diagnosis of pulmonary tuberculosis (PTB) remains a challenge in clinical practice. The present study aimed to optimize an algorithm for rapid diagnosis of PTB in a real-world setting.Methods28,171 adult inpatients suspected of having PTB in China were retrospectively analyzed. Bronchoalveolar lavage fluid (BALF) and/or sputum were used for acid-fast bacilli (AFB) smear, Xpert MTB/RIF (Xpert), and culture. A positive mycobacterial culture was used as the reference standard. Peripheral blood mononuclear cells (PBMC) were used for T-SPOT.TB. We analyzed specimen types’ effect on these assays’ performance, determined the number of smears for diagnosing PTB, and evaluated the ability of these assays performed alone, or in combination, to diagnose PTB and nontuberculous mycobacteria (NTM) infections.ResultsSputum and BALF showed moderate to substantial consistency when they were used for AFB smear or Xpert, with a higher positive detection rate by BALF. 3-4 smears had a higher sensitivity than 1-2 smears. Moreover, simultaneous combination of AFB and Xpert correctly identified 44/51 of AFB+/Xpert+ and 6/7 of AFB+/Xpert- cases as PTB and NTM, respectively. Lastly, when combined with AFB/Xpert sequentially, T-SPOT showed limited roles in patients that were either AFB+ or Xpert+. However, T-SPOTMDC (manufacturer-defined cut-off) showed a high negative predicative value (99.1%) and suboptimal sensitivity (74.4%), and TBAg/PHA (ratio of Mycobacterium tuberculosis-specific antigens to phytohaemagglutinin spot-forming cells, which is a modified method calculating T-SPOT.TB assay results) ≥0.3 demonstrated a high specificity (95.7%) and a relatively low sensitivity (16.3%) in AFB-/Xpert- patients.ConclusionsConcurrently performing AFB smear (at least 3 smears) and Xpert on sputum and/or BALF could aid in rapid diagnosis of PTB and NTM infections in a real-world high-burden setting. If available, BALF is preferred for both AFB smear and Xpert. Expanding this algorithm, PBMC T-SPOTMDC and TBAg/PHA ratios have a supplementary role for PTB diagnosis in AFB-/Xpert- patients (moderately ruling out PTB and ruling in PTB, respectively). Our findings may also inform policy makers’ decisions regarding prevention and control of TB in a high burden setting.

Comparison of MGIT 960 with Lowenstein Jensen Media for Recovery of Mycobacteria from Extrapulmonary Specimens in Southern India

Introduction: Prevalence of Extrapulmonary Tuberculosis (EPTB) due to Mycobacteriumtuberculosis and Non-Tuberculous Mycobacteria (NTM) are on the rise especially in a developing country like India. Smear Microscopy (SM) is commonly used for detection of mycobacteria. Due to the paucibacillary nature in the extrapulmonary specimens SM pose a problem in detection. Though molecular methods are increasingly used now-a-days but there are possibilities that these reactions may get inhibited due to the presence of inhibitors in the extrapulmonary specimens. Aim: To compare Mycobacterium Growth Indicator Tubes (MGIT 960) with Lowenstein Jensen (LJ) medium for the detection of mycobacteria. Materials and Methods: The current prospective study was conducted on 1879 extrapulmonary specimens collected from a tertiary care hospital during the study period from July 2018 to March 2020. Specimens were subjected to Ziehl Neelsen (ZN) staining and Auramine Phenol (AP) staining. Culture was done in both LJ media and MGIT 960 culture. Positive mycobacterial cultures were subjected to MPT64 Immunochromatographic Test (ICT). Data were analysed using the Statistical Package for Social Sciences (SPSS®) for Windows® release 21.0 (SPSS Inc., Chicago, IL, USA). Results: A total of 129 (6.9%) and 105 (5.6%) mycobacteria was isolated by MGIT 960 and by LJ culture respectively among 1879 extrapulmonary specimens. MGIT 960 identified 118 (91.5%) as Mycobacterium tuberculosis complex and 11 (8.5%) as NTM among the total mycobacteria isolated. Out of 105 mycobacteria grown by LJ culture, 95 (90.5%) and 10 (9.5%) were identified as Mycobacterium tuberculosis and NTM, respectively. The rate of contamination associated with MGIT 960 and LJ culture was 4.6% and 4.3% respectively. The Time to Detection (TTD) was found to be significantly shorter for isolation of Mycobacterium tuberculosis by MGIT 960 culture compared to LJ culture. Conclusion: In the current study, authors compared MGIT 960 with solid LJ culture for recovery of both Mycobacterium tuberculosisComplex and NTM from extrapulmonary specimens and authors found increased recovery by MGIT 960 compared to LJ culture and also shorter duration of detection for Mycobacterium tuberculosis by MGIT 960 with comparable contamination rates.

Feline mycobacterial disease in northern California: Epidemiology, clinical features, and antimicrobial susceptibility.

BackgroundMycobacterial infections in cats are challenging to treat and incompletely described.Hypothesis/objectivesTo describe the features of mycobacterial infections in cats from northern California.AnimalsNineteen cats, all with nontuberculous mycobacterial (NTM) infections; 4 with Mycobacterium avium infection, 15 with rapid‐growing mycobacterial (RGM) infection.MethodsRetrospective study. Cases with positive mycobacterial culture, species identification, and susceptibility testing were included. Descriptive statistics were used. Fisher's exact test and Mann‐Whitney U test were used for comparisons between M avium and RGM infections (P ≤ .05).ResultsRapid‐growing mycobacterial cases included Mycobacterium smegmatis (9), Mycobacterium fortuitum (4), Mycobacterium abscessus (1), and Mycobacterium thermoresistibile (1). Mycobacterium avium infections were more likely than RGM infections to be disseminated (3/4 vs 0/15; P = .004). Disease of the skin/subcutis (15/15 vs 0/4; P < .001) and outdoor access (14/15 vs 0/4; P = .001) were primary features of RGM infections. Resistance to fluoroquinolones and aminoglycosides was common among M avium isolates. A high prevalence of resistance to third‐ and fourth‐generation cephalosporins was noted in RGM species. Death/euthanasia was noted only in M avium cases (3/4). Twelve of 15 cats with RGM infection had available follow‐up; 4 of these cats achieved remission.Conclusions and Clinical ImportanceThe most prevalent RGM species isolated from cats from northern California are M smegmatis and M fortuitum. Susceptibility to prescribed antimicrobials does not appear to guarantee treatment success. Combination drug treatment is recommended. Repeat culture and susceptibility testing should be performed when disease is persistent/relapsing.

Combination of prealbumin and tuberculosis-specific antigen/phytohemagglutinin ratio for discriminating active tuberculosis from latent tuberculosis infection.

BackgroundGiven that there is no rapid and effective method for distinguishing active tuberculosis (ATB) from latent tuberculosis infection (LTBI), the discrimination between these two statuses remains challenging. This study sought to investigate the value of nutritional indexes and tuberculosis‐specific antigen/phytohemagglutinin ratio (TBAg/PHA ratio) for distinguishing ATB from LTBI.MethodsParticipants were consecutively recruited based on positive T‐SPOT.TB results between January 2018 and January 2020. ATB was diagnosed by positive mycobacterial culture and/or positive GeneXpert MTB/RIF, with clinical symptoms and radiological characteristics suggestive of ATB. Individuals with positive T‐SPOT.TB but without the evidence of ATB were defined as LTBI. Patients younger than 17 years and undergoing anti‐TB treatment were excluded.ResultsA total of 709 (312 ATB and 397 LTBI) and another 309 (120 ATB and 189 LTBI) subjects were respectively recruited from Tongji Hospital (Qiaokou cohort) and Sino‐French New City Hospital (Caidian cohort). The level of prealbumin was significantly lower in ATB than in LTBI. With a cut‐off value of 139 mg/L, the sensitivity and specificity of prealbumin in distinguishing ATB from LTBI were 50.96% (45.41%‐56.51%) and 91.69% (88.97%‐94.40%). Meanwhile, TBAg/PHA ratio was found statistically higher in ATB compared with LTBI. If using the threshold of 0.29, the sensitivity and specificity of TBAg/PHA ratio were 65.71% (60.44%‐70.97%) and 90.93% (88.11%‐93.76%), respectively. Moreover, the combination of prealbumin and TBAg/PHA ratio (obtaining by diagnostic model) yielded better specificity (90.18%, [87.25%‐93.10%]) and sensitivity (87.18%, [83.47%‐90.89%]), while the clinical utility index (CUI) positive and CUI negative were respectively 0.76 and 0.81. After anti‐TB treatment, TBAg/PHA ratio was declined while the level of prealbumin was restored (Wilcoxon test, P < 0.001). Furthermore, the performance of diagnostic model obtained in Qiaokou cohort was confirmed in Caidian cohort.ConclusionsThe diagnostic model based on combination of prealbumin and TBAg/PHA ratio is a rapid and accurate tool for discriminating ATB from LTBI.

Utility of Mycobacterium tuberculosis PCR in ruling out active disease and impact on isolation requirements in a low prevalence setting

ObjectiveTo analyze and interpret clinical microbiology data for specimens tested with the fluorochrome stain (AFB stain), mycobacterial culture and a laboratory-developed Mycobacterium tuberculosis (MTB) PCR in order to understand the performance of each test and to demonstrate the utility of MTB PCR to assist with decisions regarding discontinuation of airborne isolation. MethodsRetrospective cohort analysis of 2798 respiratory specimens from 2006 patients in the period between November 1st, 2011 and January 1st, 2018. Results53.7% were males, median age was 61 years, and 43 patients were HIV positive. Results demonstrated positive mycobacterial cultures for MTB in 52 specimens (1.9%) and for nontuberculous mycobacteria (NTM) or aerobic actinomycetes (eg., Nocardia spp.) in 435 specimens (16%). Using mycobacterial culture as the gold standard, AFB smear had a sensitivity of 48.1% while MTB PCR had a sensitivity of 96.0% in AFB smear positive specimens and an overall sensitivity of 57.7% with PPV of 94% and a NPV of 99%. ConclusionsThe combination of a positive AFB smear with a negative MTB PCR offers a rapid result to rule out active pulmonary MTB in a low prevalence setting. In this study, that combination reliably excluded active tuberculosis (NPV of 99.2%). The combination of a positive AFB smear with a negative MTB PCR indicated pulmonary NTM infection with the results available within 1 day. There was little benefit to pursuing collection and testing of more than 2 respiratory specimens in a low prevalence setting for both long term diagnostic or rapid isolation discontinuation purposes.