Use of epigenetically modified bacteriophage and dual beta-lactams to treat a Mycobacterium abscessus sternal wound infection.

Nontuberculous mycobacterium (NTM) infections are challenging to manage and are frequently non-responsive to aggressive but poorly-tolerated antibiotic therapies. Immunosuppressed lung transplant patients are susceptible to NTM infections and poor patient outcomes are common. Bacteriophages present an alternative treatment option and are associated with favorable clinical outcomes.

activity of cefoxitin, imipenem, meropenem, and ceftaroline in combination with vaborbactam against .

(MAB) infections pose a growing public health threat. Here, we assessed the activity of the boronic acid-based β-lactamase inhibitor, vaborbactam, with different β-lactams against 100 clinical MAB isolates. Enhanced activity was observed with meropenem and ceftaroline with vaborbactam (1- and >4-fold MIC/ reduction).

activity of meropenem-vaborbactam plus aztreonam against metallo-β-lactamase-producing .

We evaluated the activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-β-lactamase (MBL)-producing isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.

The impact of COVID on bacterial sepsis.

Purpose: To identify the predictors of morbidity and mortality in matched COVID-19 positive and negative patients who were septic with Gram positive or Gram negative infections.

Methods: We conducted a retrospective review, from March to October 2020, of matched septic patients at five Hackensack Meridian Health hospitals who had bacteremia with Staphylococcus aureus, Klebsiella pneumoniae or Escherichia coli with and without COVID-19. We extracted patient demographics, comorbidities and clinical outcomes data using ICD-10 codes.

Ultrasensitive Detection of Multidrug-Resistant Using SuperSelective Primer-Based Real-Time PCR Assays.

The emergence of drug-resistant tuberculosis is a significant global health issue. The presence of heteroresistant is critical to developing fully drug-resistant tuberculosis cases. The currently available molecular techniques may detect one copy of mutant bacterial genomic DNA in the presence of about 1-1000 copies of wild-type DNA.

A Molecular-Beacon-Based Multiplex Real-Time PCR Assay To Distinguish Mycobacterium abscessus Subspecies and Determine Macrolide Susceptibility.

Mycobacterium abscessus is a rapidly growing nontuberculous mycobacterial species that comprises three subspecies: M. abscessus subsp. abscessus, M.

Apramycin resistance in epidemic carbapenem-resistant Klebsiella pneumoniae ST258 strains.

Background: Recent studies indicated that the monosubstituted deoxystreptamine aminoglycoside apramycin is a potent antibiotic against a wide range of MDR Gram-negative pathogens.

Objectives: To evaluate the in vitro activity of apramycin against carbapenem-resistant Klebsiella pneumoniae (CRKp) isolates from New York and New Jersey, and to explore mechanisms of apramycin resistance.

Methods: Apramycin MICs were determined by broth microdilution for 155 CRKp bloodstream isolates collected from 2013 to 2018.

Klebsiella pneumoniae ST307 with bla South Africa, 2014-2016.

Klebsiella pneumoniae sequence type (ST) 307 is an emerging global antimicrobial drug-resistant clone. We used whole-genome sequencing and PCR to characterize K. pneumoniae ST307 with oxacillinase (OXA) 181 carbapenemase across several private hospitals in South Africa during 2014-2016.

Colonization With Levofloxacin-resistant Extended-spectrum β-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients.

Background: Bacteremia caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae (ESBL-E) is associated with inadequate empirical therapy and substantial mortality in neutropenic patients. Strategies are needed to identify neutropenic patients at high risk of these infections.

Methods: From April 2014 to September 2016, we collected perianal swabs, both at admission and weekly thereafter, from patients undergoing hematopoietic stem cell transplantation (HSCT).

Genotypic characterisation of isolates from tuberculous meningitis patients at a tertiary neurocare centre in Southern India.

Aims: Specific genotypes of Mycobacterium tuberculosis (MTB) have been reported to cause outbreaks of pulmonary tuberculosis (TB) in geographical areas that are endemic to TB. However, since there is little epidemiological evidence on the association of particular genotypes that cause tuberculous meningitis (TBM), we sought to investigate the association of specific MTB strains with infection of the central nervous system (CNS).

Materials And Methods: We carried out a genetic characterisation of 89 MTB isolates from TBM patients at a Southern Indian tertiary neurocare centre and compared the genotypes with strains of pulmonary TB isolated from Indian immigrants in New York City.

Impact of and Mutations in Improving Detection of Second-Line-Drug Resistance among Mycobacterium tuberculosis Isolates from Georgia.

The country of Georgia has a high burden of multi- and extensively drug-resistant tuberculosis (XDR-TB). To evaluate whether mutations in and genes increased the sensitivity of detection of phenotypic resistance to ofloxacin and kanamycin or capreomycin compared to use of the first-generation MTBDR assay alone, which tests for mutations in and genes, a retrospective study of stored isolates was performed. All isolates underwent DNA sequencing of resistance-determining regions.

Strains of Mycobacterium tuberculosis transmitting infection in Brazilian households and those associated with community transmission of tuberculosis.

Molecular epidemiologic studies have shown that the dynamics of tuberculosis transmission varies geographically. We sought to determine which strains of Mycobacterium tuberculosis (MTB) were infecting household contacts (HHC), and which were causing clusters of tuberculosis (TB) disease in Vitoria-ES, Brazil. A total of 741 households contacts (445 TST +) and 139 index cases were characterized according to the proportion of contacts in each household that had a tuberculin skin test positive: low (LT) (≤40% TST+), high (HT) (≥70% TST+) and (40-70% TST+) intermediate (IT) transmission.

Mycobacterium tuberculosis Infection among Asian Elephants in Captivity.

Although awareness of tuberculosis among captive elephants is increasing, antituberculosis therapy for these animals is not standardized. We describe Mycobacterium tuberculosis transmission between captive elephants based on whole genome analysis and report a successful combination treatment. Infection control protocols and careful monitoring of treatment of captive elephants with tuberculosis are warranted.

pncA Gene Mutations Associated with Pyrazinamide Resistance in Drug-Resistant Tuberculosis, South Africa and Georgia.

Although pyrazinamide is commonly used for tuberculosis treatment, drug-susceptibility testing is not routinely available. We found polymorphisms in the pncA gene for 70% of multidrug-resistant and 96% of extensively drug-resistant Mycobacterium tuberculosis isolates from South Africa and Georgia. Assessment of pyrazinamide susceptibility may be prudent before using it in regimens for drug-resistant tuberculosis.

Exploring genotype concordance in epidemiologically linked cases of tuberculosis in New York City.

Comparing genotype results of tuberculosis (TB) isolates from individuals diagnosed with TB can support or refute transmission; however, these conclusions are based upon the criteria used to define a genotype match. We used a genotype-match definition which allowed for variation in IS6110 restriction fragment length polymorphism (RFLP) to support transmission between epidemiologically linked persons. Contacts of individuals with infectious TB (index cases) diagnosed in New York City from 1997 to 2003 who subsequently developed TB (contact cases) from 1997 to 2007 were identified.

MIC of Delamanid (OPC-67683) against Mycobacterium tuberculosis Clinical Isolates and a Proposed Critical Concentration.

The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients).

A Novel Molecular Strategy for Surveillance of Multidrug Resistant Tuberculosis in High Burden Settings.

Background: In South Africa and other high prevalence countries, transmission is a significant contributor to rising rates of multidrug resistant tuberculosis (MDR-TB). Thus, there is a need to develop an early detection system for transmission clusters suitable for high burden settings. We have evaluated the discriminatory power and clustering concordance of a novel and simple genotyping approach, combining spoligotyping with pncA sequencing (SpoNC), against two well-established methods: IS6110-RFLP and 24-loci MIRU-VNTR.

Confirming Mycobacterium tuberculosis transmission from a cadaver to an embalmer using molecular epidemiology.

Genotyping results and epidemiologic investigation were used to confirm tuberculosis transmission from a cadaver to an embalmer. This investigation highlights the utility of genotyping in identifying unsuspected epidemiologic links and unusual transmission settings. In addition, the investigation provides additional evidence for the occupational risk of tuberculosis among funeral service workers and indicates a need for education about tuberculosis risk and the importance of adhering to appropriate infection control measures among funeral service workers.

Risk for Tuberculosis Disease Among Contacts with Prior Positive Tuberculin Skin Test: A retrospective Cohort Study, New York City.

Background: Patients with prior positive tuberculin skin test (TST) results may benefit from prophylaxis after repeat exposure to infectious tuberculosis (TB).

Objective: To evaluate factors associated with active TB disease among persons with prior positive TST results named as contacts of persons with infectious TB.

Design: Population-based retrospective cohort study.

Molecular epidemiology of Mycobacterium tuberculosis among South African gold miners.

Rationale: HIV-associated tuberculosis remains a major health problem among the gold-mining workforce in South Africa. We postulate that high levels of recent transmission, indicated by strain clustering, are fueling the tuberculosis epidemic among gold miners.

Objectives: To combine molecular and epidemiologic data to describe Mycobacterium tuberculosis genetic diversity, estimate levels of transmission, and examine risk factors for clustering.

Transmission of tuberculosis in a South African community with a high prevalence of HIV infection.

Background: In settings of high tuberculosis transmission, little is known of the interaction between human immunodeficiency virus (HIV) positive and HIV-negative tuberculosis disease and of the impact of antiretroviral treatment (ART) programs on tuberculosis transmission dynamics.

Methods: Mycobacterium tuberculosis isolates were collected from patients with tuberculosis who resided in a South African township with a high burden of tuberculosis and HIV infection. Demographic and clinical data were extracted from clinic records.

Factors affecting tuberculosis strain success over 10 years in a high TB- and HIV-burdened community.

Background: Factors associated with Mycobacterium tuberculosis (Mtb) strain success over time in high burdened communities are unknown.

Methods: Mtb isolates collected over 10 years from sputum-positive tuberculosis (TB) patients resident in the study site underwent IS6110-based restriction fragment length polymorphism analysis. Clinical, demographic and social data were extracted from clinic records and interviewer-administered questionnaires.

Nosocomial transmission of extensively drug-resistant tuberculosis in a rural hospital in South Africa.

Background: Extensively drug-resistant tuberculosis (XDR-tuberculosis) is a global public health threat, but few data exist elucidating factors driving this epidemic. The initial XDR-tuberculosis report from South Africa suggested transmission is an important factor, but detailed epidemiologic and molecular analyses were not available for further characterization.

Methods: We performed a retrospective, observational study among XDR-tuberculosis patients to identify hospital-associated epidemiologic links.

Retreatment tuberculosis in a South African community: the role of re-infection, HIV and antiretroviral treatment.

Background: Limited data exist on the impact of human immunodeficiency virus (HIV) or antiretroviral treatment (ART) on retreatment tuberculosis (TB).

Methods: Retreatment TB episodes between 2001 and 2010 in a high HIV and TB burden community were linked to first-episode treatment outcomes, HIV status and ART use. Genotypic analysis of Mycobacterium tuberculosis isolates distinguished re-infection from reactivation TB.

Molecular epidemiology of HIV-associated tuberculosis in Dar es Salaam, Tanzania: strain predominance, clustering, and polyclonal disease.

Molecular typing of Mycobacterium tuberculosis can be used to elucidate the epidemiology of tuberculosis, including the rates of clustering, the frequency of polyclonal disease, and the distribution of genotypic families. We performed IS6110 typing and spoligotyping on M. tuberculosis strains isolated from HIV-infected subjects at baseline or during follow-up in the DarDar Trial in Tanzania and on selected community isolates.