Chimaera Infection Research Articles

OC46 MYCOBACTERIUM CHIMAERA INFECTIONS FOLLOWING CARDIAC SURGERY IN ITALY: RESULTS FROM A NATIONAL SURVEY ENDORSED BY SICCH

Background: A global outbreak of Mycobacterium Chimaera (MC) infections following cardiac surgery and linked to contaminated heater-cooler units (HCU) is currently ongoing. In 2017, since the status of this outbreak in Italy and the mitigation strategies adopted by adult cardiac surgery unit (ACSU) were not known, SICCH launched a national survey among Italian ACSUs. Methods: In Italy there are 90 ACSU across 20 regions. From May to Nov 2017 they were surveyed collecting data on a) patients diagnosed with MC infections b) ACSU workload c) used HCU models d) control measures adopted in theatres. Results: The response rate was 87.8%. The mean number of cardiac procedures at each ACSU was 508 ± 229/year and nationally the number of procedures/year exceeded 40k. In Italy 7 patients with MC infections following cardiac were reported since 2015: all had aortic or valve surgery as first procedure; the latency between first operation and infection was 2.8 ± 1.6 years. Mortality for patients requiring redo cardiac surgery was 50%. MC infections risk was 0.4–1 patient every 1000 cardiac procedures. The most common HCU model in Italy is the 3T HCU (70.9%). The most common control measures adopted were: implementing new HCU disinfection protocols, using sterile or filtrated water in the HCU and displacing HCU fans away from the patient: HCU replacement and microbiology testing were infrequent. Conclusions: In Italy the risk of contracting MC infections and the mortality reported are in line with other European countries; a significant heterogeneity exists on the mitigation strategies to prevent further MC inoculations.

Mycobacterium chimaera Infections Related to the Heater-Cooler Unit Outbreak: A Guide to Diagnosis and Management.

We are in the midst of a global outbreak of Mycobacterium chimaera infections related to a point source contamination of a widely used surgical device, the 3T heater-cooler unit. More than 250000 heart bypass procedures using heater-cooler devices are performed in the United States every year. It is estimated that 60% of these operations use the device associated with this outbreak. Most of the reported cases present with a disseminated infection that is striking in both the latency of presentation and the high mortality. The diagnosis can be elusive due to intermittent bacteremia and normal echocardiography. Therapy includes several months of antibiotics, and surgical intervention appears to be critical for successful outcomes. Here, we review diagnostic methods and treatment options to guide clinicians in the management of this complicated infection.

Fast update of undetected Mycobacterium chimaera infections to reveal unsuspected cases

Mycobacterium chimaera is involved in a worldwide alert due to contaminated heater-cooler units. A real-time polymerase chain reaction (RT-PCR)-based procedure was implemented tosurvey undetected cases of M.chimaera infection. PCR was negative in the 59 prosthetic heart valves from patients with PCR-16SrRNA-negative infective endocarditis. PCR identifiedM.chimaera in one of 15 clinically significant retrospective Mycobacterium avium-Mycobacterium intracellulare complex isolates, which corresponded to a patient who had undergone heart valve replacement in a different institution. Whole-genome sequencing demonstrated that he was the first case in Spain with involvement of the strain responsible for the global outbreak. These results highlight the relevance of retrospective tracking for undetected M.chimaera infections.

Responding to Mycobacterium chimaera heater-cooler unit contamination: international and national intersectoral collaboration coordinated in the state of Queensland, Australia

The index case of Mycobacterium chimaera infection in a patient following open cardiac surgery in the state of Queensland, Australia prompted a centralized coordinated response to mitigate the risk. To describe the public health response to M.chimaera contamination of heater-cooler units (HCUs) and patient infection. A public health sector strategy was developed with national and international consultation to respond to the threat of HCUs contaminated with M.chimaera. Data linkage of non-tuberculous mycobacterium notifications and selected procedures was undertaken where potential use of HCUs was identified through hospitalization records. Water sampling and testing protocols were standardized. Public disclosure and patient notification were undertaken. A single case of disseminated M.chimaera infection in a patient has been diagnosed to date in Queensland, Australia. Ten of 12 (83%) LivaNova Stockert 3T HCUs from five hospitals tested positive for M.chimaera. In total, 5650 patients were notified by post of their potential risk of exposure. Use of the telehealth call centre was modest. M.chimaera was also found in extracorporeal membrane oxygenation heater units produced by two other device manufacturers, four of which tested positive prior to commissioning for use. Rapid international collaboration optimized the Queensland Health response to potential M.chimaera exposure during cardiac surgery. State-wide collaboration ensured a transparent, consistent approach to contacting patients and informing the public of the potential risk. A framework for ongoing risk management, clinical awareness and laboratory diagnosis was established. No further cases of M.chimaera infection have been identified in Queensland.

Mycobacterium chimaera infections after cardiac surgery—lessons learned

Mycobacterium chimaera infections after cardiac surgery—lessons learned

Microbiological monitoring of heater-cooler unit to keep free of Mycobacterium chimaera infection.

The association of Mycobacterium chimaera infection in patients undergoing cardiopulmonary bypass (CPB) with the use of heater-cooler units (HCU) has been reported in various literature. We described microbiological monitoring and the extent of microbiological contamination of HCUs utilized in our centre and strategies employed to reduce the high microbial load. Since August 2016, we have been following the new Instructions for Use from the manufacturer for the cleaning and disinfection of three units of Stöckert 3T and four units of Stöckert 1T HCU at the National Heart Centre Singapore. Microbiological monitoring began in January 2017 and included acid-fast bacilli (AFB) culture, Pseudomonas aeruginosa, total colony and total coliform count. Methods, such as increasing disinfection frequency and making the HCU inactive by keeping it empty in storage, were used to reduce the high colony count. All three units of Stöckert 3T and two units of Stöckert 1T were contaminated with Mycobacterium chimaera. Pseudomonas aeruginosa and total coliform count were consistently <1 colony-forming unit (CFU)/100 mL in every water sample of each HCU. High colony counts were encountered initially in all units. Step-up frequency of disinfection was found to be not as effective as keeping the HCU inactive in bringing the total colony count to an acceptable level. All monitoring and maintenance measures of HCUs need to be established and maintained to mitigate potential infection risks to patients. Strict adherence to all cleaning and disinfection processes and keeping the HCU inactive maintained the water quality of the HCU at acceptable levels.

Management of Extrapulmonary Nontuberculous Mycobacterial Infections.

Extrapulmonary disease occurs in a minority of nontuberculous mycobacterial (NTM) infections. The pattern of disease tends to be multifocal in immunocompromised individuals and localized in the immunocompetent. There is increasing recognition of disseminated Mycobacterium chimaera infection, as a complication of cardiac surgery, and focal infections due to rapidly growing mycobacteria. Microbiologic diagnosis requires detection of NTM in blood or tissue samples by microscopy, culture, or molecular methods. Management of extrapulmonary NTM infection requires prolonged, targeted multiple-drug therapy and, in some cases, aggressive surgical intervention. The optimal treatment approach is often unknown. Despite combined medical and surgical therapy, outcomes may be poor. A high degree of clinical suspicion and early diagnosis are required to maximize chances of a positive outcome.

Different Types of Heater-Cooler Units and Their Risk of Transmission of Mycobacterium chimaera During Open-Heart Surgery: Clues From Device Design.

OBJECTIVEWorldwide, Mycobacterium chimaera infections have been linked to contaminated aerosols from heater-cooler units (HCUs) during open-heart surgery. These infections have mainly been associated with the 3T HCU (LivaNova, formerly Sorin). The reasons for this and the risk of transmission from other HCUs have not been systematically assessed.DESIGNProspective observational study.SETTINGUniversity Hospital Basel, Switzerland.METHODSContinuous microbiological surveillance of 3 types of HCUs in use (3T from LivaNova/Sorin and HCU30 and HCU40 from Maquet) was initiated in June 2014, coupled with an epidemiologic workup. Monthly water and air samples were taken. Construction design was analyzed, and exhausted airflow was measured.RESULTS Mycobacterium chimaera grew in 8 of 12 water samples (66%) and 22 of 24 air samples (91%) of initial 3T HCUs in use, and in 2 of 83 water samples (2%) and 0 of 41 (0%) air samples of new replacement 3T HCUs. Moreover, 7 of 12 water samples (58%) and 0 of 4 (0%) air samples from the HCU30 were positive, and 0 of 64 (0%) water samples and 0 of 50 (0%) air samples from the HCU40 were positive. We identified 4 relevant differences in HCU design compared to the 3T: air flow direction, location of cooling ventilators, continuous cooling of the water tank at 4°C, and an electronic alarm in the HCU40 reminding the user of the next disinfection cycle.CONCLUSIONSAll infected patients were associated with a 3T HCU. The individual HCU design may explain the different risk of disseminating M. chimaera into the air of the operating room. These observations can help the construction of improved devices to ensure patient safety during cardiac surgery.Infect Control Hosp Epidemiol 2018;834-840.

Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases

ObjectivesMycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater–cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases. MethodsCase note review was performed for cases identified retrospectively through outbreak investigations and prospectively through ongoing surveillance. Case definition was Mycobacterium chimaera detected in any clinical specimen, history of cardiothoracic surgery with cardiopulmonary bypass, and compatible clinical presentation. ResultsThirty patients were identified (28 with prosthetic material) exhibiting a spectrum of disease including prosthetic valve endocarditis (14/30), sternal wound infection (2/30), aortic graft infection (4/30) and disseminated (non-cardiac) disease (10/30). Patients presented a median of 14 months post surgery (maximum 5 years) most commonly complaining of fever and weight loss. Investigations frequently revealed lymphopenia, thrombocytopenia, liver cholestasis and non-necrotizing granulomatous inflammation. Diagnostic sensitivity for a single mycobacterial blood culture was 68% but increased if multiple samples were sent. In all, 27 patients started macrolide-based combination treatment and 14 had further surgery. To date, 18 patients have died (60%) a median of 30 months (interquartile range 20–39 months) after initial surgery. Survival analysis identified younger age, mitral valve surgery, mechanical valve replacement, higher serum sodium concentration and lower C-reactive protein as factors associated with better survival. ConclusionsMycobacterium chimaera infection following cardiac surgery is associated with a wide spectrum of disease. The diagnosis should be considered in all patients who develop an unexplained illness following cardiac surgery.

Global Health Estimate of Invasive Mycobacterium chimaera Infections Associated with Heater-Cooler Devices in Cardiac Surgery.

Investigations of a worldwide epidemic of invasive Mycobacterium chimaera associated with heater–cooler devices in cardiac surgery have been hampered by low clinical awareness and challenging diagnoses. Using data from Switzerland, we estimated the burden of invasive M. chimaera to be 156–282 cases/year in 10 major cardiac valve replacement market countries.

Response to Alert on Possible Infections with Mycobacterium chimaera From Contaminated Heater-Cooler Devices in Hospitals Participating in the Canadian Nosocomial Infection Surveillance Program (CNISP).

Canadian hospitals were made aware of the risk of Mycobacterium chimaera infection associated with heater-cooler units (HCUs) through alerts issued by the US food and Drug Administration (FDA) and the US Centers for Disease Control and Prevention (CDC). In response, most hospitals conducted retrospective reviews for infections, informed exposed patients, and initiated a requirement for informed consent with HCU use. Infect Control Hosp Epidemiol 2018;39:482-484.

Mycobacterium chimaera Infection After Aortic Valve Replacement Presenting With Aortic Dissection and Pseudoaneurysm.

We present a case of Mycobacterium chimaera infection presenting with aortic dissection and pseudoaneuysm in a 22-year-old man with a past history of aortic valve replacement. Clinicians should consider M. chimaera infection in those presenting with aortic dissection as a late complication of cardiovascular surgery.

Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series

A growing number of Mycobacterium chimaera infections after cardiosurgery have been reported by several countries. These potentially fatal infections were traced back to contaminated heater-cooler devices (HCDs), which use water as a heat transfer medium. Aerosolization of water contaminated with M.chimaera from HCDs enables airborne transmission to patients undergoing open chest surgery. Infection control teams test HCD water samples for mycobacterial growth to guide preventive measures. The detection limit of M.chimaera in water samples, however, has not previously been investigated. To determine the detection limit of M.chimaera in water samples using laboratory-based serial dilution tests. An M.chimaera strain representative of the international cardiosurgery-associated M.chimaera outbreak was used to generate a logarithmic dilution series. Two different water volumes, 50 and 1000mL, were inoculated, and, after identical processing (centrifugation, decantation, and decontamination), seeded on mycobacteria growth indicator tube (MGIT) and Middlebrook 7H11 solid media. MGIT consistently showed a lower detection limit than 7H11 solid media, corresponding to a detection limit of ≥1.44×104cfu/mL for 50mL and ≥2.4cfu/mL for 1000mL water samples. Solid media failed to detect M.chimaera in 50mL water samples. Depending on water volume and culture method, major differences exist in the detection limit of M.chimaera. In terms of sensitivity, 1000mL water samples in MGIT media performed best. Our results have important implications for infection prevention and control strategies in mitigation of the M.chimaera outbreak and healthcare water safety in general.

A patient notification exercise for Mycobacterium chimaera infection associated with cardiac bypass surgery: the Welsh perspective

A patient notification exercise for Mycobacterium chimaera infection associated with cardiac bypass surgery: the Welsh perspective

Mycobacterium chimaera Infections Associated With Contaminated Heater-Cooler Devices Among Open Cardiac Surgery Patients: A Global Outbreak

Mycobacterium chimaera Infections Associated With Contaminated Heater-Cooler Devices Among Open Cardiac Surgery Patients: A Global Outbreak

Mycobacterium chimaera infections associated with heater-cooler units in cardiac surgery.

Mycobacterium chimaera infections following cardiac surgery have been reported from an increasing number of countries. These infections are characterized by a poor prognosis with a case fatality rate around 50% despite treatment. Since the first description in 2013, our understanding has grown steadily. Several outbreak investigations, case series, and experiments with heater-cooler units (HCUs) have been published. This review summarizes the current knowledge. M. chimaera transmission occurs during cardiopulmonary bypass via bioaerosols emitted from contaminated HCU water systems. Manifestations of M. chimaera infection comprise endocarditis, vascular graft infections, surgical site infections, and dissemination. So far, all cases were exposed to a single HCU brand. Samples from the manufacturing site as well as clonality of M. chimaera strains isolated from HCUs and patients suggest a contamination already at time of delivery representing the main source for the outbreak. Nevertheless, HCU contamination in hospitals cannot be excluded. Improved awareness of physicians of M. chimaera infection is crucial to prompt adequate diagnostic workup in patients that have been exposed to HCU presenting with compatible symptoms. For risk mitigation, strict separation between the air volume in contact with HCUs and critical clinical areas such as operating rooms is essential.

Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study

Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater-cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease. We included 24 M chimaera isolates from 21 cardiac surgery-related patients in Switzerland, Germany, the Netherlands, and the UK, 218 M chimaera isolates from various types of HCUs in hospitals, from LivaNova (formerly Sorin; London, UK) and Maquet (Rastatt, Germany) brand HCU production sites, and unrelated environmental sources and patients, as well as eight Mycobacterium intracellulare isolates. Isolates were analysed by next-generation whole-genome sequencing using Illumina and Pacific Biosciences technologies, and compared with published M chimaera genomes. Phylogenetic analysis based on whole-genome sequencing of 250 isolates revealed two major M chimaera groups. Cardiac surgery-related patient isolates were all classified into group 1, in which all, except one, formed a distinct subgroup. This subgroup also comprised isolates from 11 cardiac surgery-related patients reported from the USA, most isolates from LivaNova HCUs, and one from their production site. Isolates from other HCUs and unrelated patients were more widely distributed in the phylogenetic tree. HCU contamination with M chimaera at the LivaNova factory seems a likely source for cardiothoracic surgery-related severe M chimaera infections diagnosed in Switzerland, Germany, the Netherlands, the UK, the USA, and Australia. Protective measures and heightened clinician awareness are essential to guarantee patient safety. Partly funded by the EU Horizon 2020 programme, its FP7 programme, the German Center for Infection Research (DZIF), the Swiss National Science Foundation, the Swiss Federal Office of Public Health, and National Institute of Health Research Oxford Health Protection Research Units on Healthcare Associated Infection and Antimicrobial Resistance.

A Year in the Life of a Contaminated Heater-Cooler Unit With Mycobacterium chimaera?

OBJECTIVE Heater-cooler units (HCUs) have been shown to be a source of Mycobacterium chimaera infections. For the past year, weekly water samples have been taken from HCUs used at University Hospitals Birmingham (UHB) NHS Foundation Trust. We report the microbial contamination of the HCUs over a year detailing the decontamination regimes applied at UHB to reduce the microbial load. DESIGN Observational study SETTING UHB is a tertiary referral teaching hospital in Birmingham, United Kingdom, that provides clinical services to nearly 1 million patients every year. The UHB Cardiac department is one of the largest in the United Kingdom and provides treatment for adult patients with a wide range of cardiac diseases. METHODS Water samples taken from HCUs used at UHB for cardiopulmonary bypass surgery were sampled over a year to determine the number of microorganisms by membrane filtration. Various decontamination processes were employed throughout the year. RESULTS Varying total viable counts containing a wide variety of microorganisms were obtained from water inside the HCUs. No M. chimaera were isolated after replacement of the HCU internal tubing. Stringent decontamination regimes resulted in degradation of the HCUs and increased TVCs after several months. CONCLUSION More work is required to ensure effective decontamination processes to reduce the microbial load within the HCUs. Our studies indicate that weekly water sampling for TVC will be required indefinitely to monitor the water quality in these units as well as regular replacement of the tubing to control the build-up of biofilm. Infect Control Hosp Epidemiol 2017;38:705-711.

Mycobacterium chimaera infections in post–operative patients exposed to heater–cooler devices: An overview

Mycobacterium chimaera infections in post–operative patients exposed to heater–cooler devices: An overview

Mycobacterium chimaera infections in post–operative patients exposed to heater–cooler devices: An overview

A multi-country outbreak of Mycobacterium chimaera infection associated with contaminated heater-cooler devices (HCDs) has been reported, with more than 70 cases in Europe and the United States and two cases in Canada to date. The epidemiological and microbiological characteristics of this outbreak provide evidence for common-source transmission of M. chimaera from the exhaust air of intrinsically contaminated HCDs to patients during cardiac surgery. To date, all reported cases have been associated with Stöckert 3T HCDs manufactured at one plant by LivaNova prior to September 2014. Implantation of prosthetic material increases the risk of infection. Infections usually present as prosthetic valve endocarditis, vascular graft infection or disseminated infection. Reported mortality rates have varied, but were often over 40%. Several measures are recommended to facilitate case-finding and mitigate risk of exposure. The feasibility of some risk mitigation measures and their effectiveness in reducing the risk of exposure are yet to be determined. Until HCDs are redesigned in a manner that prevents water contamination and aerosolization, separating the HCD exhaust air from the operating room air during surgery may be the most effective risk mitigation strategy. However, possible unintended consequences of this approach should be considered. This overview summarizes findings from peer-reviewed and other relevant national documents on key features of the outbreak, including the source, identified risk factors for infection, signs and symptoms of infection, burden of disease, risk mitigation measures, management challenges and knowledge gaps.