By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Lau and colleagues describe a novel infectious problem — diffuse granulomatous encephalitis due to Mycobacterium chimaera infection occurring after cardiac surgery.

SOURCE: Lau D, Cooper R, Chen J, et al. Mycobacterium chimaera encephalitis post-cardiac surgery: A new syndrome. Clin Infect Dis 2019 Jun 18. doi: 10.1093/cid/ciz497. [Epub ahead of print].

Lau and colleagues at the University of Alberta described three patients who developed diffuse granulomatous encephalitis due to disseminated Mycobacterium chimaera infection that occurred after cardiac surgery, presumably as the result of contamination from a heater-cooler system used during cardiopulmonary bypass.

Two patients each presented 15 months after cardiac surgery with constitutional symptoms, pancytopenia, lymphadenopathy, hypercalcemia, and choroidal nodules. M. chimaera was recovered in blood cultures from each patient, and therapy was initiated with azithromycin, rifabutin, ethambutol, and amikacin. Clearance of mycobacteremia occurred after 18 days and 24 days, respectively. Nonetheless, each patient experienced progressive and profound neurocognitive decline. Brain imaging was limited because of the presence of acute kidney injury, precluding the use of contrast agents. PET-CT showed no brain abnormalities, while non-contrast MRI performed in one patient showed T2 white matter hyperintensities without restricted diffusion. Both patients died.

Although the third patient developed constitutional symptoms just four months after aortic valve and root replacement, the etiology was not determined until 12 months later with the recovery of M. chimaera in blood cultures. By the time of diagnosis, the patient was bed-bound. Choroidal nodules were detected on ophthalmological examination. Four-drug treatment was initiated with subsequent clearance of bacteremia, but with continued neurocognitive decline. Non-contrast MRI revealed multifocal T2 white matter hyperintensities, while gadolinium administration allowed detection of punctate lesions that enhanced and were thought to be consistent with granulomas. Despite the use of additional antimycobacterial agents, the patient experienced progressive neurological decline, leading to death.

Postmortem examination performed on all three patients revealed granulomatous inflammation in the brain as well as in multiple other organs and the cardiac bioprostheses. However, no brain specimens were submitted for culture. In the third patient, multiple acid fast bacilli were visualized in temporal lobe tissue.

COMMENTARY

The authors of a recently published review pointed out that two characteristics of M. chimaera infections after cardiopulmonary bypass are their prolonged latency and their high mortality, characteristics also found with other outbreaks of infection with nontuberculous mycobacteria.1 Some delay in diagnosis is inevitable, even when the diagnosis is suspected, because the organism takes two to eight weeks before it becomes detectable in blood cultures. The investigators also pointed out that chorioretinal lesions are frequently observed, as they were in the three patients described by Lau and colleagues, and recommended that all patients with suspected post-bypass M. chimaera infection undergo a careful retinal examination.

Treatment of M. chimaera infections generally has been based on regimens that are used in patients with infection with the very closely related Mycobacterium avium or Mycobacterium intracellulare. A recent study performed in Ireland found that none of 88 clinical and environmental M. chimaera isolates tested were resistant to clarithromycin or amikacin, while resistance to moxifloxacin and linezolid was detected in 52% and 39%, respectively, tested using Clinical Laboratory Standards Institute (CLSI) breakpoints.2 Using tentative epidemiological cutoffs, 1% were resistant to streptomycin and 2% to rifabutin, while rifampicin and ethambutol resistance was detected in 18% and 11%, respectively, based on their pharmacokinetics and pharmacodynamics. Of note, the CDC recommends that only clarithromycin susceptibility testing be performed (many would also test amikacin) because of a lack of data demonstrating a correlation between presumed susceptibility or resistance and clinical therapeutic outcomes.

Meanwhile, clinicians must remain alert to the possibility of late-onset M. chimaera infections in patients who have previously undergone cardiopulmonary bypass. Among the syndromic presentations of which they must be aware that can be caused by this organism is a chronic progressive granulomatous encephalitis described by Lau et al.

REFERENCES

  1. Kasperbauer SH, Daley CL. Mycobacterium chimaera infections related to the heater-cooler unit outbreak: A guide to diagnosis and management. Clin Infect Dis 2019;68:1244-1250. Erratum in: Clin Infect Dis 2019;69:195.
  2. Mok S, Hannan MM, Nölke L, et al. Antimicrobial susceptibility of clinical and environmental Mycobacterium chimaera isolates. Antimicrob Agents Chemother 2019 Jul 1. doi: 10.1128/AAC.00755-19. [Epub ahead of print].