MONTREAL — The high mortality in community-acquired pneumonia caused by methicillin-resistant Staphylococcus aureus may be largely due to Panton-Valentine leukocidin toxin, according to Dr. Ian Gould, consultant microbiologist at the University of Aberdeen (Scotland).
Thus, efforts to control the infection should probably focus on the toxin as well as the bacteria, Dr. Gould said at an international conference on community-acquired pneumonia (CAP).
“Switching off toxin production is probably a major issue because it's mainly a toxin-induced disease,” he said in an interview at the meeting. “Even if the antibiotics can kill the bug, the toxin's still there and that's what's doing the damage.”
Panton-Valentine leukocidin (PVL) toxin is produced mostly by community-acquired, as opposed to hospital-acquired, strains of methicillin-resistant S. aureus (MRSA). And the prevalence is increasing, Dr. Gould said.
“Clearly, there have been big changes in the epidemiology of community-acquired MRSA, and now there are quite a few epidemic strains that produce PVL,” he said. In fact, according to a recent report from the Centers for Disease Control, the majority of reported community-acquired MRSA infections are PVL-producing strains (MMWR 2007;56:325–9; see accompanying story). However, although most of these infections involve skin and soft tissue and are “relatively mild,” according to Dr. Gould, “more and more commonly, we're seeing very severe respiratory disease associated with community-acquired MRSA PVL strains.” In the recent CDC report of 10 cases of MRSA-associated CAP, all isolates were positive for PVL toxin.
“This is an organism that causes severe pneumonia,” said Dr. Coleman Rotstein, who also presented at the meeting, which was sponsored by the International Society of Chemotherapy. The key features of CAP caused by MRSA are empyema and necrotizing pneumonia, said Dr. Rotstein, professor of medicine at McMaster University, Hamilton, Ont.
He and other experts at the meeting agreed that treatment options are limited.
“When it comes to treatment, we are standing in the dark, with a case mortality in the published literature of around 75%,” Dr. Gould said. “It's like going back to the influenza epidemic after the First World War, when there were no antibiotics.”
“For these new MRSA CAP etiologies, the present arsenal of antibiotics is unfortunately insufficient,” said Dr. Ethan Rubenstein, who also presented at the meeting. “Evidently, the β-lactams are useless, and vancomycin is associated with unfavorable clinical results even when used in higher doses,” said Dr. Rubenstein, professor and head of infectious diseases at the University of Manitoba, Winnipeg.
According to Dr. Gould, high-dose clindamycin or linezolid are good options not only for their antibacterial effects but also because of their potential ability to lower PVL production. “[Intravenous] immunoglobulin is also well recognized as an adjunct, but I don't know if there's much evidence for its effect—although there are PVL antibodies in it,” he said. In addition, gentamicin is indicated for patients who are bacteremic.
“We haven't seen the end of this story. This is a highly adaptable, rapidly developing organism … things are going to get worse here before they get better,” Dr. Gould said.