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Inappropriately high breakpoints have resulted in systematic false-susceptible AST results to anti-TB drugs. MIC, PK/PD and clinical outcome data should be combined when setting breakpoints to minimise the emergence and spread of antimicrobial resistance. https://bit.ly/3i43wb6

Nontuberculous mycobacteria (NTM) are ubiquitous microorganisms found in indoor and outdoor habitats, including water, soil, and dust. NTM can infect susceptible persons, including those with lung diseases such as cystic [...]

Mycobacterium chimaera is a species in the Mycobacterium avium complex (MAC) (1). MAC is the most frequently reported cause of nontuberculous mycobacterium (NTM) infection in the United States, although disseminated [...]

Background Nontuberculous mycobacteria (NTM) cause pulmonary (PNTM) and extrapulmonary (ENTM) disease. Infections are difficult to diagnose and treat, and exposures occur in healthcare and community settings. In the United States, NTM epidemiology has been described largely through analyses of microbiology data from health departments, electronic health records, and administrative data. We describe findings from a multisite pilot of active, laboratory- and population-based NTM surveillance. Methods The Centers for Disease Control and Prevention's Emerging Infections Program conducted NTM surveillance at 4 sites (Colorado, 5 counties; Minnesota, 2 counties; New York, 2 counties; and Oregon, 3 counties [PNTM] and statewide [ENTM]) from 1 October 2019 through 31 March 2020. PNTM cases were defined using published microbiologic criteria. ENTM cases required NTM isolation from a nonpulmonary specimen, excluding stool and rectal swabs. Patient data were collected via medical record review. Results Overall, 299 NTM cases were reported (PNTM: 231, 77%); Mycobacterium avium complex was the most common species group. Annualized prevalence was 7.5/100 000 population (PNTM: 6.1/100 000; ENTM: 1.4/100 000). Most patients had signs or symptoms in the 14 days before positive specimen collection (ENTM: 62, 91.2%; PNTM: 201, 87.0%). Of PNTM cases, 145 (62.8%) were female and 168 (72.7%) had underlying chronic lung disease. Among ENTM cases, 29 (42.6%) were female, 21 (30.9%) did not have documented underlying conditions, and 26 (38.2%) had infection at the site of a medical device or procedure. Conclusions Active, population-based NTM surveillance will provide data for monitoring the burden of disease and characterize affected populations to inform interventions. [ABSTRACT FROM AUTHOR]

Abstract Multidrug-resistant (MDR) strains of Mycobacterium tuberculosis have emerged worldwide. In many countries and regions, these resistant strains constitute a serious threat to the efficacy of tuberculosis control programs. An important element in gaining control of this epidemic is developing an understanding of the molecular basis of resistance to the most important antituberculosis drugs: isoniazid, rifampin, and pyrazinamide. On the basis of this information, more exacting laboratory testing, and ultimately more appropriate and timely treatment regimens, can be developed.

In 2001, New York City implemented genotyping to its tuberculosis (TB) control activities by using IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping to type isolates from culture-positive TB patients. [...]

Motivation Short-read whole-genome sequencing (WGS) is a vital tool for clinical applications and basic research. Genetic divergence from the reference genome, repetitive sequences and sequencing bias reduces the performance of variant calling using short-read alignment, but the loss in recall and specificity has not been adequately characterized. To benchmark short-read variant calling, we used 36 diverse clinical Mycobacterium tuberculosis (Mtb) isolates dually sequenced with Illumina short-reads and PacBio long-reads. We systematically studied the short-read variant calling accuracy and the influence of sequence uniqueness, reference bias and GC content. Results Reference-based Illumina variant calling demonstrated a maximum recall of 89.0% and minimum precision of 98.5% across parameters evaluated. The approach that maximized variant recall while still maintaining high precision (<99%) was tuning the mapping quality filtering threshold, i.e. confidence of the read mapping (recall = 85.8%, precision = 99.1%, MQ ≥ 40). Additional masking of repetitive sequence content is an alternative conservative approach to variant calling that increases precision at cost to recall (recall = 70.2%, precision = 99.6%, MQ ≥ 40). Of the genomic positions typically excluded for Mtb, 68% are accurately called using Illumina WGS including 52/168 PE/PPE genes (34.5%). From these results, we present a refined list of low confidence regions across the Mtb genome, which we found to frequently overlap with regions with structural variation, low sequence uniqueness and low sequencing coverage. Our benchmarking results have broad implications for the use of WGS in the study of Mtb biology, inference of transmission in public health surveillance systems and more generally for WGS applications in other organisms. Availability and implementation All relevant code is available at https://github.com/farhat-lab/mtb-illumina-wgs-evaluation. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Rationale:Mycobacterium abscessus is a significant threat to individuals with cystic fibrosis (CF) because of innate drug resistance and potential transmission between patients. Recent studies described global dominant circulating clones of M. abscessus, but detailed genomic surveys have not yet been described for the United States. Objectives: We examined the genetic diversity of respiratory M. abscessus isolates from U.S. patients with CF and evaluated the potential for transmission events within CF Care Centers. Methods: Whole-genome sequencing was performed on 558 M. abscessus isolates from 266 patients with CF attending 48 CF Care Centers in 28 U.S. states as part of a nationwide surveillance program. U.S. isolates were also compared with 64 isolate genomes from 13 previous studies to evaluate the prevalence of recently described dominant circulating clones. Results: More than half of study patients with CF and M. abscessus had isolates within four dominant clones; two clones of M. abscessus subspecies (subsp.) abscessus (MAB) and two clones of M. abscessus subsp. massiliense (MMAS). Acquired drug resistance mutations for aminoglycosides and macrolides were rare in the isolate population, and they were not significantly enriched in dominant clones compared with unclustered isolates. For a subset of 55 patients, there was no relationship between dominant clones and diagnosis of active lung disease (P = 1.0). Twenty-nine clusters of genetically similar MAB isolates and eight clusters of genetically similar MMAS isolates were identified. Overall, 28 of 204 (14%) patients with MAB and 15 of 64 (23%) patients with MMAS had genetically isolates similar to those of at least one other patient at the same CF Care Center. Genetically similar isolates were also found between 60 of 204 (29%) patients with MAB and 19 of 64 (30%) patients with MMAS from different geographic locations. Conclusions: Our study reveals the predominant genotypes of M. abscessus and frequency of shared strains between patients in U.S. CF Care Centers. Integrated epidemiological and environmental studies would help to explain the widespread presence of dominant clones in the United States, including the potential for broad distribution in the environment. Single site studies using systematic, evidence-based approaches will be needed to establish the contributions of health care-associated transmission versus shared environmental exposures. [ABSTRACT FROM AUTHOR]

In the article, the editors discuss developments in the diagnosis and treatment of patients with pulmonary nontuberculous mycobacteria (PNTM) across all age groups, particularly in the U.S., as of April 2021. Other topics include the study by the National Institute of Allergy and Infectious Diseases (NIAID), as well as the definitive diagnosis and proper management of infectious diseases like microbiologic culture and antimicrobial susceptibility testing.

There are many resources available to mycobacterial researchers, including culture collections around the world that distribute biomaterials to the general scientific community, genomic and clinical databases, and powerful bioinformatics tools. However, many of these resources may be unknown to the research community. This review article aims to summarize and publicize many of these resources, thus strengthening the quality and reproducibility of mycobacterial research by providing the scientific community access to authenticated and quality-controlled biomaterials and a wealth of information, analytical tools and research opportunities. [ABSTRACT FROM AUTHOR]

An adult female captive-born Atlantic guitarfish (Rhinobatos lentiginosus) was found acutely moribund on exhibit and died soon after presentation. Abnormalities on autopsy were focal cutaneous erythema on the tail, a small liver, many variably sized friable ovarian follicles, and coelomic effusion. Histologic examination revealed systemic bacterial embolization, and yolk coelomitis with minimal associated inflammation and some mineralization. Bacterial culture of blood and coelomic effusion grew a rapidly growing Mycobacterium species that was further identified as Mycobacterium chelonae by PCR amplification and sequencing of the RNA polymerase subunit beta (rpoB) gene of isolated genomic DNA. Concurrent reproductive disease may have caused immunosuppression, thus predisposing to the mycobacterial infection. At another institution, an adult male wild-caught Atlantic guitarfish was found dead on exhibit with no premonitory signs. Abnormalities on autopsy were a thin body condition, small liver, and coelomic effusion. Histologic examination revealed acute mycobacterial septicemia. M. chelonae was also identified in this fish by PCR amplification and sequencing. Mycobacteriosis has rarely been reported in captive elasmobranchs. Guitarfish may have greater susceptibility to mycobacteriosis than other elasmobranchs, and acute and chronic manifestations of the disease may exist in this species. [ABSTRACT FROM AUTHOR]

National Jewish Health Advanced Diagnostic Laboratories strives for excellence in the quality of its services. In an effort to foster continual quality improvement across the organization, the laboratory's management and staff sought to achieve and maintain compliance with the ISO 15189 standard. All laboratory sections of this highly esoteric reference laboratory participated in the initiative. A quality manual was developed and a robust quality management system deployed. A variety of tools were utilized to determine areas for improvement, including heat maps, metrics, quality reports, root cause analysis, internal auditing, action plans, customer satisfaction surveys and a Plan-Do-Survey-Act approach. Focused training was provided where indicated. Several different quality committees, consisting of staff of all levels, were formed to enable communication of ideas, foster collaboration and disseminate information. Leadership focused on fostering a culture of quality throughout the organization. An employee recognition program was established to positively reinforce this culture. Progress on initiatives was assessed through the ongoing utilization of heat maps, follow-up audits and committees, which culminated in March 2013 with a successful CAP 15189 surveillance inspection. Through the CAP 15189 accreditation process, the organization realized measurable improvement both financially and in the level of quality of laboratory services. [ABSTRACT FROM AUTHOR]

Summary: Setting: The WHO-recommended strategy of tuberculosis control (DOTS strategy) has been shown to be effective in reducing tuberculosis incidence in a variety of countries/ settings. Little evidence exists on the implementation, and effectiveness of DOTS in a transitional, post-war setting Objective: To describe the process of establishing a National Tuberculosis Control Program (NTP) and implementing DOTS throughout Kosovo, and the outcomes achieved by this international collaboration in a post-war transitional setting during 1999–2005. Methods: In 1999, as part of the re-organization of health services, a DOTS-based NTP was established and operationalized through a collaboration of several international partners in Kosovo. Five key steps supported these activities. Results: Kosovo has reached the World Health Assembly targets, having achieved 75% case detection rate (sputum smear-positive cases) and 93% treatment success rate. During 2000–2005, new smear-positive tuberculosis case notifications decreased by 44.5% (median annual decrease for all cases: 7.6%). Conclusions: Kosovo''s success story is a collaborative tale, each partner involved playing a unique role in supporting NTP activities. The Kosovo example provides yet another setting in which DOTS implementation has resulted in successful patient outcomes. The international TB control community would be well-served by formal guidelines for implementing DOTS and the new STOP TB Strategy in these settings. [Copyright &y& Elsevier]

The article focuses on the study which concentrates on mycobacterium tuberculosis. To know the reason of their worldwide spread and their frequent association with outbreaks, a number of multidrug-resistant strain-W isolates was examined by susceptibility testing for pyrazinamide (PZA). The results, which showed that all strains are susceptible to PZA, led to the conclusion that the current radiometric reference method cannot detect PZA resistance in patients infected with W-Beijing strains.

Focuses on the functions and capabilities of State Public Health Laboratories (SPHL) in the U.S. Role of SPHL in developing health policies; Importance of high quality laboratory services to health care systems; Information on the funding of SPHL; Details on the National Laboratory System.

In a double-blind study, 655 sputum specimens were obtained from individuals suspected of having tuberculosis and were analyzed for the presence of Mycobacterium tuberculosis and rifampin susceptibility with use of a polymerase chain reaction (PCR)-based universal heteroduplex generator assay (PCR/UHG-Rif). Of the specimens containing viable M. tuberculosis, 100% of the smearpositive (nn = 41) and 50% of the smear-negative (n = 6) specimens tested positive for the organism by PCR/UHG-Rif. Nineteen of 537 culture-negative specimens tested positive for M. tuberculosis by PCR/UHG-Rif and were from patients with confirmed tuberculosis who were receiving antituberculosis therapy at the time of specimen collection. Thirty-five specimens contained nontuberculous mycobacteria and were negative by PCR/UHG-Rif. Genotypic evidence of rifampin resistance in five of six culture-confirmed, rifampin-resistant isolates was obtained by PCR/UHG-Rif, yielding a sensitivity and specificity for the assay of 83% and 98.2%, respectively. These results demonstrate the feasibility of using a PCR-based assay directly on sputum specimens for simultaneous detection of M. tuberculosis and rifampin susceptibility, and they suggest that patients with smear-positive, untreated tuberculosis and those presenting with suspected drug-resistant tuberculosis are the most appropriate groups for testing by PCR/UHG-Rif. [ABSTRACT FROM PUBLISHER]

Mycobacterium malmoense is a potentially pathogenic species that was first described in 1977. During the past decade M. malmoense has been recognized with increasing frequency as a pulmonary pathogen. More than 180 cases of M. malmoense infection have been reported. Most of these infections affected a previously damaged lung. Other infection sites included the skin, lymph nodes, and bursae. Five cases of disseminated infection have been reported. The antituberculous drugs associated with the most favorable susceptibility patterns are rifampin and ethambutol. Because of the slow growth of M. malmoense on conventional, egg-based bacteriologic media, the incubation time should be >6 weeks; special solid and liquid media are recommended. We report a case of disseminated pulmonary and gastrointestinal infection due to M. malmoense in a patient with AIDS, who was treated successfully with a combination of rifabutin (ansamycin), clofazimine, and isoniazid. In addition, we review the characteristics of extrapulmonary and disseminated infections due to M. malmoense. [ABSTRACT FROM PUBLISHER]

Over the last decades, the rate of isolation of tubercle bacilli has declined in the developed countries, while the incidence of infection with nontuberculous mycobacteria (NTM) has increased. In a retrospective study, we analyzed all cases of patients negative for human immunodeficiency virus (HIV) and from whom NTM were isolated in the Zurich area of Switzerland from 1983 to 1988. During the 6-year study period, 513 patients infected with NTM were identified, 34 of whom had clinically significant disease. The presentation of mycobacteriosis was found to be lung disease in 23 cases, soft-tissue disease in 10 cases, and disseminated disease in one case. The highest attack rate of pulmonary mycobacteriosis was 0.49% and was found in the group of patients 41–50 years old. During the 6-year period, the incidence of tuberculosis declined from 16.2 to 13.2 per 100,000 population, while the incidence of mycobacteriosis increased from 0.4 to 0.9 per 100,000 population. Clinically nonsignificant NTM isolates were found more frequently in patients with chronic lung diseases (P < .01) and especially in patients with a history of tuberculosis (P < .001). [ABSTRACT FROM PUBLISHER]

In the spring of 2015, investigators in Switzerland reported a cluster of six patients with invasive infection with Mycobacterium chimaera, a species of nontuberculous mycobacterium ubiquitous in soil and water. The infected patients had undergone open-heart surgery that used contaminated heater-cooler devices during extracorporeal circulation (1). In July 2015, a Pennsylvania hospital also identified a cluster of invasive nontuberculous mycobacterial infections among open-heart surgery patients. Similar to the Swiss report, a field investigation by the Pennsylvania Department of Health, with assistance from CDC, used both epidemiologic and laboratory evidence to identify an association between invasive Mycobacterium avium complex, including M. chimaera, infections and exposure to contaminated Stöckert 3T heater-cooler devices, all manufactured by LivaNova PLC (formerly Sorin Group Deutschland GmbH) (2). M. chimaera was described as a distinct species of M. avium complex in 2004 (3). The results of the field investigation prompted notification of approximately 1,300 potentially exposed patients.* Although heater-cooler devices are used to regulate patients' blood temperature during cardiopulmonary bypass through water circuits that are closed, these reports suggest that aerosolized M. chimaera from the devices resulted in the invasive infections (1,2). The Food and Drug Administration (FDA) and CDC have issued alerts regarding the need to follow updated manufacturer's instructions for use of the devices, evaluate the devices for contamination, remain vigilant for new infections, and continue to monitor reports from the United States and overseas (2). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Twenty years of global surveillance of antituberculosis-drug resistance" by M. Zignol and colleagues which was published in the September 15, 2016 issue.

The article presents information on the report based from the Florida Department of Health on increase of tuberculosis (TB) cases of the Mycobacterium tuberculosis genotype in Duval County, Florida. It mentions inclusion of the people mainly from the homeless community with the disease. It highlights the combined work from the organization including Duval County Health Department, Florida Department of Health, and the U.S. Centers for Disease Control & Prevention (CDC) regarding the investigation among the TB patients, and informs the analysis results consisting of 99 cases related to matching genotype result and 48 cases of epidemiologic links.

The article reveals that the prevalence of Mycobacterium tuberculosis (TB) in Duval County, Florida from 2004 to 2012 is associated with homelessness. It describes the efforts of Duval County public health workers to identify and manage cases of active TB or latent TB infection. According to the authors, despite the decreasing incidence of TB in Florida and across the U.S. outbreaks still occur among homeless people.