• M. chimaera
• ELITe InGenius® platform
• Heater-cooler units
• Medical device water samples
• Nontuberculous mycobacteria
• Real-time PCR

• Real-Time Polymerase Chain Reaction/methods
• Mycobacterium/genetics
• Mycobacterium/isolation & purification
• Water Microbiology
• Limit of Detection
• Sensitivity and Specificity
• Italy
• Equipment and Supplies/microbiology
• Humans

• Aquarium fish
• Heat shock protein 65 kD gene
• Non-tuberculous mycobacteria

• Mycobacterium abscessus complex
• Mycobacterium avium complex
• Mycobacterium kansasii
• Sub-Saharan Africa
• long-term outcomes
• non-tuberculous mycobacteria

• Mycobacterium chimaera
• cardiac surgery
• causal link
• healthcare-associated infections

• Fondazione GVM per la Ricerca Scientifica onlus Lugo RA Italy

• Mycobacterium avium complex pulmonary disease
• Disease progression
• Immune profile
• Single-cell RNA sequencing
• Treatment outcome

• Humans
• Male
• Female
• Mycobacterium avium-intracellulare Infection/microbiology
• Aged
• Transcriptome
• Mycobacterium avium Complex/genetics
• Middle Aged
• Single-Cell Analysis/methods
• Leukocytes, Mononuclear/metabolism
• Leukocytes, Mononuclear/microbiology
• Lung Diseases/microbiology
• Lung Diseases/genetics
• Gene Expression Profiling
• Disease Progression
• Monocytes/metabolism
• Monocytes/immunology

• 2022R1A2C2003487 Ministry of Science and ICT, South Korea
• HI20C0017 Ministry of Health and Welfare

• Building size
• Hot water plumbing
• Mycobacterium abscessus
• Mycobacterium avium complex
• Square footage and disinfectant type
• Survey

• Disinfectants/analysis
• Water Microbiology
• Nontuberculous Mycobacteria
• Mycobacterium
• Environmental Monitoring/methods
• United States

• EPA999999 Intramural EPA

• BPC
• MIC
• Mycobacterium abscessus
• Mycobacterium avium
• biofilm prevention
• clarithromycin
• nontuberculous mycobacteria

• Clarithromycin/pharmacology
• Biofilms/drug effects
• Anti-Bacterial Agents/pharmacology
• Nontuberculous Mycobacteria/drug effects
• Humans
• Microbial Sensitivity Tests
• Mycobacterium Infections, Nontuberculous/microbiology
• Mycobacterium Infections, Nontuberculous/drug therapy
• Mycobacterium Infections, Nontuberculous/prevention & control
• Mycobacterium avium Complex/drug effects
• Mycobacterium abscessus/drug effects

• IR-Biotyper
• Mycobacterium chimaera
• absolute filter
• heater-cooler units
• nontuberculous Mycobacteria
• whole-genome sequencing

• Humans
• Mycobacterium Infections/epidemiology
• Mycobacterium Infections/microbiology
• Mycobacterium Infections/prevention & control
• Spectroscopy, Fourier Transform Infrared
• Mycobacterium/genetics
• Mycobacterium avium Complex
• Equipment Contamination
• Mycobacterium Infections, Nontuberculous/microbiology

• Biofilm infection
• Cystic fibrosis
• MAC

• Mycobacterium avium complex
• host-directed therapy
• innate immunity
• macrophage
• nontuberculous mycobacteria

• Culture
• Drinking water
• M. avium
• M. intracellulare
• Mycobacterium avium complex
• Water quality
• qPCR

• Environmental samples
• Heater cooler
• Membrane filtration
• Mycobacteria

• Antibiofilm
• Juniperus communis
• biofilm
• nontuberculous mycobacteria

• Biofilms
• Juniperus
• Mycobacterium avium
• Mycobacterium avium Complex
• Oils, Volatile/pharmacology
• Polystyrenes
• Temperature

Mycobacterium avium complex (MAC) species constitute most mycobacteria infections in persons with cystic fibrosis (CF) in the United States, but little is known about their genomic diversity or transmission. During 2016–2020, we performed whole-genome sequencing on 364 MAC isolates from 186 persons with CF from 42 cystic fibrosis care centers (CFCCs) across 23 states. We compared isolate genomes to identify instances of shared strains between persons with CF. Among persons with multiple isolates sequenced, 15/56 (27%) had >1 MAC strain type. Genomic comparisons revealed 18 clusters of highly similar isolates; 8 of these clusters had patients who shared CFCCs, which included 27/186 (15%) persons with CF. We provide genomic evidence of highly similar MAC strains shared among patients at the same CFCCs. Polyclonal infections and high genetic similarity between MAC isolates are consistent with multiple modes of acquisition for persons with CF to acquire MAC infections.

• Mycobacterium avium complex
• Mycobacterium intracellulare subsp. chimaera
• Mycobacterium intracellulare subsp. intracellulare
• United States
• bacteria
• clusters
• cystic fibrosis
• nontuberculous mycobacteria
• phylogenomics
• transmission
• tuberculosis and other mycobacteria
• whole-genome sequencing

• Cystic Fibrosis/complications
• Cystic Fibrosis/epidemiology
• Genomics
• Humans
• Metagenomics
• Mycobacterium avium Complex/genetics
• Mycobacterium avium-intracellulare Infection/epidemiology
• United States/epidemiology

• K01 AI125726 NIAID NIH HHS

Mycobacterium chimaera is the newly described species belonging to Mycobacterium avium complex (MAC), with morphology and growth characteristics closely related to Mycobacterium intracellulare. The aim of this retrospective study was to analyze the frequency and clinical significance of M. chimaera identification in the population of patients with previous positive respiratory cultures for M. intracellulare or MAC. 200 strains of M. intracellulare or MAC, isolated from respiratory specimens of patients hospitalized in pulmonary wards, between 2011 and 2020, were retrospectively analyzed with GenoType NTM-DR test. 88 (44%) of strains were re-classified to M. chimaera species. Analysis of clinical data in 30 patients with positive M. chimaera isolates revealed that they were diagnosed with chronic obstructive pulmonary disease (COPD) – 27%, past tuberculosis – 20%, or interstitial lung diseases – 17%, respectively. Non-tuberculous mycobacterial lung disease (NTMLD) caused by M. chimaera has been recognized in 53% of patients, most often in those presenting with post-tuberculous lung lesions. M. chimaera was almost exclusively isolated from respiratory specimens of patients with underlying lung diseases, especially those with COPD and/or past tuberculosis. NTMLD due to M. chimaera was diagnosed predominantly in patients with past tuberculosis.

• Mycobacterium chimaera
• chronic obstructive lung disease
• cystic fibrosis
• mycobacteriosis
• tuberculosis

• Nontuberculous mycobacteria
• environmental exposure
• nontuberculous mycobacterium infection

• Aged
• Female
• Humans
• Lung Diseases/epidemiology
• Middle Aged
• Mycobacterium avium Complex
• Nontuberculous Mycobacteria
• Republic of Korea/epidemiology
• Risk Factors
• Seoul

• Yonsei University College of Medicine

• M. avium
• M. intracellulare
• MIC distributions
• clinical characteristics
• infection

• culture media
• limit of detection
• non-tuberculous mycobacteria
• real-time polymerase chain reaction

Non-tuberculous mycobacteria (NTM) are widespread in the environment and are a public health concern due to their resistance to antimicrobial agents. The colonization of surgical heater-cooler devices (HCDs) by the slow-growing NTM species Mycobacterium chimaera has recently been linked to multiple invasive infections in patients worldwide. The resistance of M. chimaera to antimicrobials may be aided by a protective biofilm matrix of extracellular polymeric substances (EPS). This study explored the hypothesis that M. chimaera can form biofilms on medically relevant materials. Several M. chimaera strains, including two HCD isolates, were used to inoculate a panel of medical device materials. M. chimaera colonization of the surfaces was monitored for 6 weeks. M. chimaera formed a robust biofilm at the air-liquid interface of borosilicate glass tubes, which increased in mass over time. M. chimaera was observed by 3D Laser Scanning Microscopy to have motility during colonization, and form biofilms on stainless steel, titanium, silicone and polystyrene surfaces during the first week of inoculation. Scanning electron microscopy (SEM) of M. chimaera biofilms after 4 weeks of inoculation showed that M. chimaera cells were enclosed entirely in extracellular material, while cryo-preserved SEM samples further revealed that an ultrastructural component of the EPS matrix was a tangled mesh of 3D fiber-like projections connecting cells. Considering that slow-growing M. chimaera typically has culture times on the order of weeks, the microscopically observed ability to rapidly colonize stainless steel and titanium surfaces in as little as 24 h after inoculation is uncharacteristic. The insights that this study provides into M. chimaera colonization and biofilm formation of medical device materials are a significant advance in our fundamental understanding of M. chimaera surface interactions and have important implications for research into novel antimicrobial materials, designs and other approaches to help reduce the risk of infection.

• HCDS
• Mycobacterium chimaera
• NTM
• biofilm
• heater-cooler devices

Background: Mycobacterium chimaera (MC) is of recent origin and belongs to the large family of non-tuberculous mycobacteria. In recent years, it has shown a high infectious capacity via the aerosol produced by operating room equipment, such as heater–cooler units (HCU). The infection has a long latent period and high mortality rate. Genetic and epidemiological studies have shown that there is a clear link between the infection and a specific HCU model manufactured by LivaNova/Sorin. There is, therefore, a strong possibility that contamination occurs during device construction. The objective of this article is to describe the characteristics of this particular infection in view of the medico–legal implications on professional liability, specifically focusing on current evidence regarding contamination prevention. Methods: we have analyzed the clinical characteristics and data from the autopsic investigations performed on a patient who died as a result of MC infection, in addition to analyzing all pertinent recommendation documents available internationally. We searched for all articles in the literature available on MEDLINE between 1995 and 30 July 2020, using the search words “Mycobacterium chimaera”. We then analyzed those articles and reported only those that provide useful information regarding prevention techniques for containing dissemination and contamination. Results: the literature review produced 169 results that highlight the need to develop systems to mitigate and eliminate the risk of MC infection in operating rooms such as physical containment measures, e.g. device replacement, use of safe water, providing patients with information, and training healthcare professionals. Conclusions: from a medico–legal viewpoint, this particular situation represents a new frontier of professional liability, which includes manufacturers of electromedical equipment. In order to comprehend the true extent of this silent global epidemic, the development of an organic, preventative monitoring system is essential.

• Mycobacterium chimaera
• clinical risk management.
• informed consent
• medico legal assessment
• professional liability

• Cross Infection
• Equipment Contamination
• Humans
• Liability, Legal
• Mycobacterium
• Mycobacterium Infections/transmission
• Risk Management

Invasive cardiovascular infections by Mycobacterium chimaera associated with open-heart surgery have been reported worldwide since 2013. Here, we report a case of a 61 year old man, without any other particular medical background, who underwent cardiac surgery for replacing part of the ascending aorta by a bio-prosthetic graft. Eighteen months later, the patient was painful at the lower back with fever. A pyogenic vertebral osteomyelitis due to M. chimaera associated to graft infection was diagnosed after 6 months of sub-acute infection. The patient presented a disseminated disease with cerebral lesions, chorioretinitis, and chronic renal failure. Despite adequate antimicrobial treatment and graft explantation, the patient died after 6 years. We reviewed the literature on M. chimaera infections associated with open-heart surgery. The worldwide outbreak has been explained by airborne bioaerosol generated by the 3T heater–cooler unit (HCU) used during cardiac by-pass surgical procedures. These infections are difficult to diagnose because of a long latency period (up to several years), with no specific symptoms and a highly specialized microbiological diagnosis. The treatment is based on antibiotics and surgery. These infections are also difficult to treat, since the mortality rate is high around 50%. Prevention is necessary by modifying the use of HCUs in operating rooms.

• HCU
• NTM
• cardiac surgery
• non-tuberculous mycobacteria
• spondylodiscitis

• Mycobacterium chimaera
• dissemination
• endocarditis
• heater–cooler unit
• outbreak

• Disease progression
• Mycobacterium aviumcomplex (MAC)
• Non-tuberculous Mycobacterium(NTM)
• Prediction
• Subspecies identification

• Mycobacterium avium complex (MAC)
• culture conversion
• recurrence
• treatment duration

• Infection
• Mycobacterium chimaera
• Review
• Update

• Anti-Bacterial Agents/pharmacology
• Anti-Bacterial Agents/therapeutic use
• Humans
• Microbial Sensitivity Tests
• Mycobacterium
• Mycobacterium Infections
• Postoperative Complications
• Thoracic Surgical Procedures/adverse effects

• Heater–cooler unit
• Mycobacterium chimaera
• Sampling
• Sodium thiosulfate

• Cardiopulmonary bypass
• Disseminated
• Guidelines
• Heater-cooler device
• ISCVID
• Infection
• Mycobacterial
• Mycobacterium chimaera
• Outbreaks

• Cardiac surgery
• Disinfection
• Heater–cooler unit
• Microbiological monitoring
• Mycobacterium chimaera
• Polymerase chain reaction

The rapid identification of lineage remains a challenge in the genotyping of clinical isolates of recombinogenic pathogens. The chromosome of Mycobacterium avium subsp. hominissuis (MAH), an agent of Mycobacterium avium complex (MAC) lung disease, is often mosaic and is composed of chromosomal segments originating from different lineages. This makes it difficult to infer the MAH lineage in a simple experimental set-up. To overcome this difficulty, we sought to identify chromosomal marker genes containing lineage-specific alleles by genome data mining.

We conducted genetic population structure analysis, phylogenetic analysis, and a survey of historical recombination using data from 125 global MAH isolates. Six MAH lineages (EA1, EA2, SC1, SC2, SC3, and SC4) were identified in the current dataset. One P-450 gene (locus_tag MAH_0788/MAV_0940) in the recombination-cold region was found to have multiple alleles that could discriminate five lineages. By combining the information about allele type from one additional gene, the six MAH lineages as well as other M. avium subspecies were distinguishable. A recombination-cold region of 116 kb contains an insertion hotspot and is flanked by a mammalian cell-entry protein operon where allelic variants have previously been reported to occur. Hence, we speculate that the acquisition of lineage- or strain-specific insertions has introduced homology breaks in the chromosome, thereby reducing the chance of interlineage recombination.

The allele types of the newly identified marker genes can be used to predict major lineages of M. avium. The single nucleotide polymorphism typing approach targeting multiallelic loci in recombination-cold regions will facilitate the epidemiological study of MAC, and may also be useful for equivalent studies of other nontuberculous mycobacteria potentially carrying mosaic genomes.

• BAPS
• Genetic population structure
• Genotyping
• MAC
• MLVA
• Marker gene
• Mycobacterium
• NTM
• SNP
• VNTR

An epidemic of Mycobacterium chimaera (M. chimaera) infections following cardiac surgery is ongoing worldwide. The outbreak was first discovered in 2011, and it has been traced to a point source contamination of the LivaNova 3T heater-cooler unit, which is used also in Italy. International data are advocated to clarify the spectrum of clinical features of the disease as well as treatment options and outcome. We report a series of M. chimaera infections diagnosed in Treviso Hospital, including the first cases notified in Italy in 2016.

Since June 2016, we diagnosed a M. chimaera infection in nine patient who had undergone cardiac valve surgery between February 2011 and November 2016. The time between cardiac surgery and developing symptoms ranged from 6 to 97 mo. Unexplained fever, psychophysical decay, weight loss, and neurological symptoms were common complaints. The median duration of symptoms was 32 wk, and the longest was almost two years. A new cardiac murmur, splenomegaly, choroidoretinitis, anaemia or lymphopenia, abnormal liver function tests and hyponatremia were common findings. All the patients presented a prosthetic valve endocarditis, frequently associated to an ascending aortic pseudoneurysm or spondylodiscitis. M. chimaera was cultured from blood, bioprosthetic tissue, pericardial abscess, vertebral tissue, and bone marrow. Mortality is high in our series, reflecting the poor outcome observed in other reports. Three patients have undergone repeat cardiac surgery. Five patients are being treated with a targeted multidrug antimycobacterial regimen.

Patients who have undergone cardiac surgery in Italy and presenting with signs and symptoms of endocarditis must be tested for M. chimaera.

• Mycobacterium chimaera
• Prosthetic valve endocarditis
• Spondylodiscitis
• Cardiac surgery infections
• Case report

• Mycobacterium chimaera
• heater–cooler units
• microbiological surveillance
• non-tuberculous mycobacteria

• functions
• metagenome
• network interaction
• rhizosphere
• tradeoff

• CPB equipment
• cardiopulmonary bypass (CPB)
• heater–cooler
• hypothermia
• infection
• wound infection

• Cardiopulmonary Bypass
• Equipment Contamination
• Humans
• Infection Control
• Water Microbiology

• Anti-Bacterial Agents/therapeutic use
• Humans
• Mycobacterium Infections, Nontuberculous/diagnosis
• Mycobacterium Infections, Nontuberculous/drug therapy
• Mycobacterium Infections, Nontuberculous/prevention & control

• R21 AI099534 NIAID NIH HHS
• R21 AI142267 NIAID NIH HHS
• R01 AI125160 NIAID NIH HHS
• HHSN272201000009I NIAID NIH HHS
• U01 AI078054 NIAID NIH HHS
• HHSN272200800045C NIAID NIH HHS

• Mycobacterium talmoniae
• bronchiectasis
• cystic fibrosis

• Abcsessus
• MAC
• Mycobacteria
• NTM
• Nontuberculous

Bacteria thrive in showerheads and throughout household water distribution systems. While most of these bacteria are innocuous, some are potential pathogens, including members of the genus Mycobacterium that can cause nontuberculous mycobacterial (NTM) lung infection, an increasing threat to public health. We found that showerheads in households across the United States and Europe often harbor abundant mycobacterial communities that vary in composition depending on geographic location, water chemistry, and water source, with households receiving water treated with chlorine disinfectants having particularly high abundances of certain mycobacteria. The regions in the United States where NTM lung infections are most common were the same regions where pathogenic mycobacteria were most prevalent in showerheads, highlighting the important role of showerheads in the transmission of NTM infections.

Bacteria within the genus Mycobacterium can be abundant in showerheads, and the inhalation of aerosolized mycobacteria while showering has been implicated as a mode of transmission in nontuberculous mycobacterial (NTM) lung infections. Despite their importance, the diversity, distributions, and environmental predictors of showerhead-associated mycobacteria remain largely unresolved. To address these knowledge gaps, we worked with citizen scientists to collect showerhead biofilm samples and associated water chemistry data from 656 households located across the United States and Europe. Our cultivation-independent analyses revealed that the genus Mycobacterium was consistently the most abundant genus of bacteria detected in residential showerheads, and yet mycobacterial diversity and abundances were highly variable. Mycobacteria were far more abundant, on average, in showerheads receiving municipal water than in those receiving well water and in U.S. households than in European households, patterns that are likely driven by differences in the use of chlorine disinfectants. Moreover, we found that water source, water chemistry, and household location also influenced the prevalence of specific mycobacterial lineages detected in showerheads. We identified geographic regions within the United States where showerheads have particularly high abundances of potentially pathogenic lineages of mycobacteria, and these “hot spots” generally overlapped those regions where NTM lung disease is most prevalent. Together, these results emphasize the public health relevance of mycobacteria in showerhead biofilms. They further demonstrate that mycobacterial distributions in showerhead biofilms are often predictable from household location and water chemistry, knowledge that advances our understanding of NTM transmission dynamics and the development of strategies to reduce exposures to these emerging pathogens.

• Mycobacterium
• NTM lung disease
• nontuberculous mycobacterial infection
• plumbing biofilms

• Hawaii
• environments
• man-made
• natural
• nontuberculous mycobacteria

Mycobacterium avium complex (MAC) organisms are waterborne, opportunistic pathogens whose source is natural waters and soils and proliferates and persists in premise plumbing, for example household and hospital plumbing. M. avium complex and other environmental mycobacteria grow slowly, not because their metabolism is slow, but because they synthesize long chain (C₆₀–C₈₀) fatty acids that make up its hydrophobic and impermeable outer membrane. There are costs and benefits to the presence of that lipid-rich outer membrane. One benefit is that cell-surface hydrophobicity drives M. avium complex cells to adhere to surfaces to reduce their interaction with charged ions in suspension; they are likely “biofilm pioneers”, adhering to a wide variety of surface materials. The result is that the slow-growing M. avium complex cells (1 gen/day at 37 °C) will not be washed out of any flowing system, whether a stream or plumbing in the built environment. Although the slow permeation of nutrients in M. avium complex organisms limits growth, they are also resistant to disinfectants, thus increasing their survival in water distribution systems, premise plumbing, and medical equipment. There are three components to the antimicrobial resistance of M. avium complex in biofilms: (1) innate resistance due to the hydrophobic, impermeable outer membrane, (2) residence in a matrix of extracellular polysaccharide, lipid, DNA, and protein that prevents access of antimicrobials to M. avium cells, and (3) an adaptive and transient increased resistance of biofilm-grown M. avium cells grown in biofilms. As expected M. avium in biofilms will display neutral, antagonistic, or beneficial interactions with other biofilm inhabitants. Methylobacterium spp., the common pink-pigmented, waterborne bacteria compete with M. avium for surface binding, suggested an approach to reducing M. avium biofilm formation and hence persistence in premise plumbing.

• M. avium complex
• MAC
• adherence
• antibiotic
• biofilm
• disinfectant
• hydrophobic
• methylobacteria
• mycobacteria