Friday, March 29, 2013

Emerging CF Pathogen Is Transmissible

A bacterial species increasingly responsible for lung infections in cystic fibrosis patients can be transmitted from person to person, although probably not directly, researchers said.
Genomic analysis of Mycobacterium abscessus isolates taken from clusters of infected CF patients found almost no sequence differences -- in fact, less than is normally found in isolates taken from a single individual -- "strongly indicating between-patient transmission," according to Julian Parkhill, PhD, of the Wellcome Trust Sanger Institute in Hinxton, England, and colleagues.
"Comprehensive environmental sampling" in the hospitals where these patients were housed failed to identify a source for these nontuberculous mycobacteria, whereas the patients had "numerous opportunities for within-hospital transmission from other individuals," Parkhill and colleagues wrote online in The Lancet.
"Although the exact transmission route is yet to be established, our epidemiological analysis suggests that it could be indirect," they added.
M. abscessus has recently been identified as a major cause of illness in CF patients, whose sticky lung secretions create a favorable environment for bacteria to flourish. Parkhill and colleagues noted that M. abscessus is hard to eradicate, requiring long treatment with toxic antibiotic combinations that often ultimately fail.
Some 3% to 10% of CF patients in the U.S. and Europe are currently infected with the organism, which has also been linked to dermal infections from tattoo inks and equipment.
In the case of CF patients, reasons for the pathogen's rapid emergence have been unclear. Possible factors include greater infestation in shower heads and the unintended consequences of chronic antibiotic therapy in these patients. Eliminating other bacteria may provide a previously unavailable foothold for mycobacteria, and some antibiotics may impair normal host-defense mechanisms.
In addition, person-to-person transmission has been suspected but never proven, Parkhill and colleagues indicated. Their current study aimed to find evidence that it contributes to the organism's spread.
They obtained 168 M. abscessus isolates from 31 patients seen from 2007 to 2011 at a CF treatment clinic housed at Papworth Hospital in Cambridge, England, and performed whole-genome sequence analyses as well as antimicrobial susceptibility tests.
The genomic analyses indicated that some of the isolates were virtually identical, differing by only 10 base pairs or less. It appeared that these isolates had infected a total of 11 patients in two separate outbreaks.
As an example, Parkhill and colleagues cited the case of one patient, whose isolates had genetic diversity that "was entirely encompassed within that of [another patient], indicating immediate relatedness by direct descent."
These isolates were of the subspecies massiliense, one of the three major subspecies of M. abscessus previously identified.
The researchers also examined patterns of antimicrobial susceptibility as a clue to the organism's recent genetic evolution. They found that several patients whose records indicated no previous exposure to long-term macrolides or aminoglycosides nevertheless carried M. abscessus isolates that resisted amikacin and clarithromycin.
These findings, too, suggested transmission between individuals. Parkhill and colleagues suggested that it was likely that these mycobacterial strains had picked up resistance elements as a result of coinfection with resistant organisms in some individual.
Parkhill and colleagues sought to exclude the possibility that the outbreaks originated with environmental contamination either at Papworth Hospital or elsewhere in the community. They determined that patients within the outbreak clusters did not live near each other or share water supplies, and tests of the hospital's water supply and equipment (including shower heads, bronchoscopes, and dishwashers) were all negative.
On the other hand, they found that, prior to becoming infected, each of the outbreak patients had been at the clinic simultaneously with a patient who was infected at the time. The exceptions, of course, were the initial cases in each outbreak cluster, whose route of acquisition of M. abscessusremains a mystery.
Finally, the researchers estimated mutation rates for the isolates, which indicated that the outbreak strains shared a common ancestor during "the period when opportunities existed for hospital-associated transmission." Other isolates not associated with the outbreaks were likely to have been genetically distinct for several decades.
But Parkhill and colleagues argued that transmission from close patient-to-patient contact was unlikely because of strict patient segregation policies in place at the Papworth clinic. "Patients are advised not to meet socially and are cared for in individual rooms," they wrote.
They suggested that "fomite contamination" -- in which the organism moves from person to another via an inanimate object -- was a more probable route of transmission. M. abscessus can survive severe physical and chemical assaults as well as dessication, they noted.
Another possibility is that aerosol generation during physiotherapy and lung function testing and other procedures in CF patients produce contaminated aerosols that subsequent patients breathe in.
The researchers added that, as a result of their findings, infection control procedures have been strengthened at Papworth. Steps taken include continuous sputum screening of all patients for nontuberculous mycobacteria, treating infected outpatients in a dedicated clinic with single-use rooms, and negative air pressure in inpatient rooms.
They indicated that it was too early to say whether these measures had reduced mycobacterial infections.