Multidrug-Resistant Mycobacteria Transmitted Among Patients

Laurie Barclay, MD

March 29, 2013

Despite conventional cross-infection measures, multidrug-resistant (MDR) Mycobacterium abscessus often spreads indirectly among patients with cystic fibrosis, according to a retrospective cohort study published online March 29 in the Lancet. The findings raise red flags regarding the adequacy of current infection control measures for hospitalized patients with cystic fibrosis as well as other hospitalized patient groups.

In the United States and Europe, prevalence of MDR M abscessus among patients with cystic fibrosis is about 3% to 10% and is increasing. Morbidity includes progressive pulmonary disease refractory to treatment.

"The clinical implication of this study is the confirmation of person-to-person transmission of M abscessus in patients with cystic fibrosis, by using whole-genome sequencing analyses," Toshiyuki Harada, MD, PhD, told Medscape Medical News in an email interview. Dr. Harada, who was not involved with the study, is chief doctor, Center for Respiratory Diseases, Hokkaido Social Insurance Hospital in Sapporo, Japan.

Between 2007 and 2011, 31 patients with cystic fibrosis who were seen at the Cambridge Centre for Lung Infection at PapworthHospital, in Cambridge, United Kingdom, had M abscessus infection in 2 clustered outbreaks. Antimicrobial susceptibility testing of 168 consecutive isolates showed considerable multidrug resistance. Whole-genome sequencing identified genetically identical or near-identical strains of M abscessus subspecies massiliense (from 11 patients) that differed by fewer than 10 base pairs.

"Isolates from these 11 patients were often more closely related to each other than to other samples from the same individual, strongly suggesting that cross-infection has occurred widely between patients," senior author R. Andres Floto, PhD, from the University of Cambridge, Cambridge, United Kingdom, said in a news release.

Environmental testing ruled out obvious potential sources of infection, including bronchoscopes and tap water. Social network analysis allowed comparison of opportunities for cross-infection between patients carrying genetically clustered and unclustered cases.

"This group of patients had numerous opportunities for within-hospital transmission from other individuals, while widespread environmental sampling failed to detect any specific source of exposure to [nontuberculous mycobacteria] infection," Dr. Floto said. "[T]he exact mechanism of cross-infection remains to be established. Because of strict infection control policies, we believe that transmission probably occurred indirectly, for example via fomite (eg, hair, clothing, and bedding) contamination or aerosol-generating procedures such as lung function testing."

Within the clusters of M abscessus subspecies massiliense, additional evidence for cross-infection was the transmission of mutations acquired during infection of an individual to other patients. Furthermore, several patients with no history of long-term use of amikacin and clarithromycin had bacterial isolates resistant to these antibiotics.

"The increased resolution provided by whole-genome sequencing over previous typing techniques allowed us to clearly identify the existence, and in some cases the direction, of patient-to-patient transmission, something that would not previously have been possible," said coauthor Julian Parkhill, PhD, from the Sanger Institute, Hinxton, United Kingdom.

"Further research should include whole-genome sequencing to identify transmission between patients in other nontuberculous mycobacterium species or in Mycobacterium abscessus without cystic fibrosis," Dr. Harada said. "Examination of the exact transmission route is needed to prove the mechanism — is it direct or indirect?"

The Wellcome Trust, Papworth Hospital, NIHR Cambridge Biomedical Research Centre, UK Health Protection Agency, Medical Research Council, and the UKCRC Translational Infection Research Initiative funded this study. One of the study authors (Dr. Parkhill) received funding for conference travel and accommodation from Illumina Inc. The other study authors and Dr. Harada have disclosed no relevant financial relationships.

Lancet . Published online March 29, 2013. Abstract