American Journal of Respiratory and Critical Care Medicine

To the Editor:

There has been no published report of direct or indirect patient-to-patient respiratory spread of nontuberculous mycobacteria (NTM) (15). We report an outbreak of Mycobacterium abscessus ss. massiliense in five patients with cystic fibrosis (CF). The index case was a 22-year-old man with an FEV1 of 28% predicted, ΔF508/1717–1G-A, who had M. abscessus ss. massiliense for 7 years before transfer to our practice, and was 4+ sputum smear–positive for acid-fast bacilli (AFB) at the time of entry into the clinic. Eight months after his transition, four additional patients, aged 27 to 38 years and with FEV1% of 27 to 44% predicted, all homozygous for ΔF508, were found to have M. abscessus ss. massiliense in their sputum. All four newly infected patients subsequently had multiple confirmatory positive AFB specimens. Historically all four patients had multiple (five to nine) annual screening mycobacterium sputum samples over the preceding decade. One patient had grown Mycobacterium avium complex 8 years previously, and all other samples from all patients had been AFB culture negative.

All patients had M. abscessus ss. massiliense isolates that were multidrug resistant, including mutational resistance to amikacin and the macrolides; repetitive unit-sequence based polymerase chain reaction pattern and pulsed–field gel electrophoresis analysis of isolates from the five patients were indistinguishable (Figure 1).

Clinical epidemiologic data included contact with medical providers, time and dates of CF clinic and lung transplant clinic visits including room number, radiology appointments including Dual Energy X-ray Absorptiometry (DEXA) scans, pulmonary function laboratory and audiometry visits, dates of hospital admissions, time of pulmonary function testing, and patient home address. None of the patients was acquainted or had any social interaction. All patients had different domestic water supplies.

Four of the five cases including the index case had overlapping CF clinic visit days, but no other shared space was determined. Once the outbreak was recognized, all patients with CF with M. abscessus were isolated in clinic by being placed in airborne isolation clinic rooms, and all clinic and equipment surfaces were cleaned twice between patients. No further cases occurred.

Environmental studies of the clinic rooms, toilets, and spirometers performed 8 months after the outbreak isolated M. avium complex and Mycobacterium gordonae from 13 water faucets, water supplies, or air samples. No environmental source of M. abscessus was found.

The index case died of overwhelming M. abscessus ss. massiliense infection 74 days after double lung transplant. Seven and eight months after initial recovery of M. abscessus in their sputum, two of the other four cases died with recalcitrant mycobacterial disease, despite intensive treatment with varying combinations of linezolid, meropenem, imipenem, azithromycin, ciprofloxacin, and cefoxitin. A third case was treated for 9 months with tigecycline, linezolid, and cefoxitin, which were discontinued because of side effects; subsequent sputum analysis failed to reveal growth of the organism. The fourth patient, with the highest lung function, had M. abscessus on three independent sputum samples, but subsequent sputum samples have been negative for mycobacterial growth.

We hypothesize that the high mycobacterial load in the sputum of the index case may have contaminated the clinic environment and facilitated patient-to-patient transmission of M. abscessus. Transmission could have occurred by patient-to-patient respiratory spread or by contamination of the clinic or some clinic equipment.

This is the first known outbreak of respiratory M. abscessus disease occurring in a population of patients with CF (611). We strongly advocate rigorous, diligent, repeated surface cleaning and consideration to use airborne isolation rooms when caring for patients whose sputum harbors this organism.

The authors thank Arjun Srinivasan, M.D., Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention for his assistance with this outbreak and his review of the letter; Carolyn Wallis and Susan Stiglich for assistance with mycobacterial culturing and sending isolates to UTHSCT; Nancy Whittington, RN, for her assistance with the environmental studies; Linda Bridge and Ravikiran Vasireddy, who performed the molecular analysis; and Kimberly Kriel and Michael Dillon, who performed susceptibility testing at UTHSCT.

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Author Contributions: M.L.A. initiated the investigation of the outbreak, promoted increased infection control, and wrote the manuscript with assistance from co-authors. B.A.B.-E., R.J.W., S.M., and their laboratory personnel performed the antibiotic susceptibility testing, molecular identification, and performed the PFGE. They also performed the rRNA gene sequencing for mutational resistance. They reviewed the manuscript and assisted in writing the manuscript. G.A.C. and M.A.D. performed the rep-PCR analysis, assisted with the UWMC Infection Control, and reviewed and assisted in writing the manuscript. K.N.O. assisted in the design of the report to identify and characterize the genetics of the isolates. He reviewed and assisted in writing the manuscript. A.L. and P.P. assisted in Infection Control and clinical management at the UWMC, assisted in review of the literature regarding this material, and in the selection of clinical antibiotics. They reviewed the manuscript and assisted in writing the manuscript. C.H.G. and M.R.T. assisted in environmental control issues, selection of antibiotics, and reviewed and assisted writing the manuscript. E.W. took the lead role in Infection Control and in facilitating the Environmental Cultures at the UWMC. She also reviewed and assisted in writing the manuscript.

Ethical Review Statement: The Human Subjects Division of the University of Washington (UW) approved clinical information retrieval. A Material Transfer agreement for the mycobacterial isolates was obtained between the UW and the University of Texas Health Science Center at Tyler, Texas (UTHSCT).

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