Cases

A total of 6 male patients with M. chimaera met our case definition. Patient characteristics are shown in Table 1. All had undergone open-chest heart surgery involving implants at the University Hospital of Zurich between 2008 and 2012. Latency between surgery and manifest infection ranged between 1.5 and 3.6 years (Figure 1). In all cases except 1 patient with sustained M. chimaerabacteremia, the cardiac implant showed echocardiographic signs of endocarditis. Accompanying symptoms, signs, and disorders were fatigue, fever, hepatitis, renal insufficiency, splenomegaly, and pancytopenia. Host defense was compromised in 2 patients. One patient had lowered CD4 cell counts for no obvious reason, and 1 had received steroid medication for a supposed granulomatous autoimmune disease. As prosthetic valves and aortic grafts differed in type, manufacturer, and lot, a production-related contamination cause appeared highly unlikely (Table 1). No potential common exposure sources outside the hospital could be identified among patients. RAPD-PCR analysis of isolates of the 6 cases repeatedly revealed 2 clusters with similar patterns involving 2 patients and 3 patients each (Figure 2). The isolate of 1 patient had a unique RAPD-PCR pattern.

Targeted antibiotic therapy consisted of a prolonged combination of clarithromycin, rifabutin, and ethambutol, combined with either amikacin or moxifloxacin. Three patients experienced breakthrough infections with splenic embolus, pacemaker pocket infection, and progressive mitral valve endocarditis, respectively. Three patients underwent valve replacement surgery; 1 patient required repeated surgical debridement. Two other patients died, despite antibiotic treatment [11].

Observations

We identified 2 sources of stagnant nonsterile water in the operating room consisting of a heater-cooler unit connected to the extracorporeal circuit, and a separate device providing warm water to patient warming blankets. Patients received water from a drinking water fountain in the ICU, and they were exposed to showers and tap water on floor wards. Additional water used in the operating room was sterile.

During open-chest heart surgery, heater-cooler units are generally used for the dual purpose of warming patients and cooling of the cardioplegia solution [16]. These are stand-alone units on wheels placed inside the operating room with reservoirs of tap water as a thermic transfer medium. The heater-cooler model used in the investigated period consists of a water tank with different compartments containing heating and cooling aggregates, all housed in a stainless steel case. Water from a 6-liter tank is pumped through a silicone tube to the heart–lung machine where it runs through the water phase of a single-use heat exchanger against the blood phase, separated by highly heat-conductive material. A second circuit, designed to feed a warming blanket, was never used. A third circuit delivers cold water from two 3-liter tanks to the single-use heat exchange unit for the cardioplegia solution. Temperature in the tanks may range between 2°C and 41°C during operation, returning to room temperature on standby. The tanks are not airtight due to overflow tubes, and multiple probes and stirring devices are inserted in their roof. Below the tank, a fan forces air through a heat exchanger for cooling. Heater-cooler units are usually located 1–2 m from the surgical sterile field.

Heater-cooler unit employment and water changes were not documented in the past. In 2012, the manufacturer (Sorin Group, Milan, Italy) issued a maintenance protocol. Recommendations were to change the water every second week using a bacteria filter with 0.2-µm pores, initially adding 100 mL of 3% w/v hydrogen peroxide as disinfectant, then 50 mL every 5 days. Every 3 months, a 15-minute extra disinfection cycle had to be run by adding 200 mL of 5% w/v Clorox Regular Bleach. The manual states to use decalcified water exclusively. During the operation, water tanks must be refilled occasionally. Spilling is common. The 2 single-use heat exchangers are tested for airtightness during assembly of the heart–lung machine by applying 250 mm Hg of pressure during 30 seconds.

The second nonsterile water source in the operating room concerned a body temperature regulation system (Blanketrol III, Cincinnati Sub-Zero Medical, Cincinnati, Ohio), a standalone device featuring a water tank with tubes feeding warm water to a blanket placed beneath the patient during surgery.

Sterile conditioned water is used to rinse the surgical site. In addition, we identified no risk of contamination related to handling or storage of prostheses at the hospital.

Environmental Cultures

Mycobacterium chimaera was cultured from 5 heater-cooler units and characterized by RAPD-PCR. Similar RAPD-PCR patterns were observed for M. chimaera isolates from heater-cooler unit no. 1 and an air sample associated with the same heater-cooler unit (Figure 2). Different RAPD-PCR patterns were observed for M. chimaera isolates sampled from the different heater-cooler units (Figure 2), indicating a wide diversity of M. chimaera strains in the different units. An exact match of RAPD-PCR patterns between M. chimaera strains from the environment and M. chimaera strains isolated from infected patients could not be established (Figure 2). Ten cultures from warming blanket devices remained negative (Supplementary Table). All drinking water fountains in the hospital ICUs tested positive for M. chimaera, whereas all samples taken from taps in the operating room, ICUs, and surgical wards remained negative (Figure 3;Supplementary Table). Water from showers on wards also tested negative.

Preventive Measures

In parallel with accumulating evidence for the transmission pathway, preventive actions and notification to the national regulatory bodies and the manufacturer of the heater-cooler units were undertaken to minimize the infectious risk of patients undergoing open-chest heart surgery at the Zurich Heart Centre and elsewhere (Figure 1). We use only factory-new, heater-cooler units with daily water changes over 0.2-µm bacteria filters and perform regular water and air surveillance cultures. Since March 2014, heater-cooler unit water and operating room air samples have remained negative for M. chimaera. However, in September 2014, it grew again from 1 heater-cooler unit sample. The construction of custom-built containers with high-efficiency particulate air filters to house heater-cooler units that cannot be placed outside the operating room is now under way.