St.Jude - clindamycin and azithromycin are more effective than ampicillin in the treatment of pneumonia after influenza illness

[Giuseppe]

J Infect Dis. 2008 Dec 29. [Epub ahead of print]

Treatment with Protein Synthesis Inhibitors Improves Outcomes of Secondary Bacterial Pneumonia after Influenza.

Karlstr?m A, Boyd KL, English BK, McCullers JA. - 1Department of Infectious Diseases and the 2Veterinary Pathology Core, St. Jude Children's Research Hospital, 3Department of Pediatrics, Division of Infectious Diseases, Le Bonheur Children's Medical Center, Memphis, Tennessee.

Pneumonia occurring as a secondary infection after influenza is a major cause of excess morbidity and mortality, despite the availability and use of antibiotics active against Streptococcus pneumoniae.
We hypothesized that the use of a bacteriostatic protein synthesis inhibitor would improve outcomes by reducing the inflammatory response.
BALB/cJ mice infected with influenza virus and superinfected with S. pneumoniae were treated with either the cell-wall-active antibiotic ampicillin or the protein synthesis inhibitor clindamycin or azithromycin.
In the model, ampicillin therapy performed significantly worse (survival rate, 56%) than (1) clindamycin therapy used either alone (82%) or in combination with ampicillin (80%) and (2) azithromycin (92%).
Improved survival appeared to be mediated by decreased inflammation manifested as lower levels of inflammatory cells and proinflammatory cytokines in the lungs and by observation of less-severe histopathologic findings.
These data suggest that beta-lactam therapy may not be optimal as a first-line treatment for community-acquired pneumonia when it follows influenza.

PMID: 19113989 [PubMed - as supplied by publisher]
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[Shiloh]

St.Jude - clindamycin and azithromycin are more effective than ampicillin in the treatment of pneumonia after influenza illness

Source: http://www.eurekalert.org/pub_releas...-sfm010809.php

Public release date: 8-Jan-2009
Study finds more effective treatment for pneumonia following influenza
Results of St. Jude study could shape new treatments for secondary pneumonia

Scientists at St. Jude Children's Research Hospital have demonstrated a more effective treatment for bacterial pneumonia following influenza. They found that the antibiotics clindamycin and azithromycin, which kill bacteria by inhibiting their protein synthesis, are more effective than a standard first-line treatment with the "beta-lactam" antibiotic ampicillin, which causes the bacteria to lyse, or burst.

The finding is important because pneumonia, rather than the influenza itself, is a principal cause of death from influenza in children and the elderly. During pandemics?such as the one that may arise from avian influenza?up to 95 percent of influenza deaths are due to pneumonia. A bioterrorism attack using the influenza virus would likely result in the same high percentage of pneumonia deaths, according to the researchers.

The group, led by Jonathan McCullers, M.D., associate member of the St. Jude Infectious Diseases department, expect the new findings, currently demonstrated in mice, to be incorporated into standard clinical practice guidelines during the next few years.

McCullers and his colleagues published their findings in the advanced, online issue of the Journal of Infectious Diseases. The researchers based the new treatment on growing evidence that beta-lactams are relatively ineffective against secondary pneumonia because the drugs exacerbate inflammation caused by influenza.

"With severe secondary pneumonia, it has seemed that physicians do almost everything they can, and it doesn't work," McCullers said. "People still die despite treatment with antibiotics that can kill the bacteria. Our research is showing that the intense inflammatory response that is already there from the virus is amplified by the bacterial infection. And, treatment with beta-lactams releases bacterial components into the bloodstream that the immune system recognizes, triggering an inflammatory burst that can be deadly.

"Traditional first-line therapy has been based on the belief that the bacteria are bad, so we have to get rid of them as quickly as possible," McCullers said. "But what we are finding is that maybe it is the inflammation we need to worry about first, and the bacteria second. Protein synthesis inhibitors shut down the bacterial protein-making factory, and they can avoid the inflammatory burst by killing them over days instead of quickly lysing them."

In their experiments, the St. Jude researchers infected mice with a mild form of influenza that restricted itself to the lungs. After a week, the scientists infected the mice with pneumonia bacteria. This sequence mimics how humans with influenza would contract secondary pneumonia.

The researchers treated groups of the doubly infected mice with ampicillin, clindamycin, combined clindamycin and ampicillin, or azithromycin. They found that 56 percent of the mice survived with ampicillin treatment, 82 percent survived with clindamycin, 80 percent with clindamycin and ampicillin, and 92 percent with azithromycin. Significantly, while clindamycin and azithromycin both inhibit protein synthesis, azithromycin also has anti-inflammatory properties.

Ampicillin aggravated inflammation compared to clindamycin, the researchers confirmed in test tube studies. The investigators also found evidence of increased inflammation in lung cells of ampicillin-treated animals.

According to McCullers, lung tissue studies of ampicillin-treated animals also revealed the antibiotic's deleterious effects.

"We saw in those animals that, even though we were clearing their lungs of bacteria, the lungs looked just like those of animals in which the bacteria were continuing to multiply," McCullers said. "The damage process was continuing."

McCullers said he would like the new findings to influence treatment guidelines immediately for pneumonia secondary to influenza.

"The current guidelines still adhere to the theory that beta-lactams are the only drugs of choice, because it is necessary to kill the bacteria as fast as possible," he said. "However, our findings represent the first data showing that inflammation is important, and that alternative therapies such as protein synthesis inhibitors should be considered and incorporated into revised guidelines."

More broadly, McCullers said, the new findings support a growing body of evidence that treating severe pneumonia in general should take into account the inflammatory response and not just the rapid demise of bacteria.

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Other authors of this paper include ?sa Karlstr?m and Kelli Boyd (St. Jude); and B. Keith English (Le Bonheur Children's Medical Center). This research was supported in part by the U.S. Public Health Service and ALSAC.

St. Jude Children's Research Hospital

St. Jude Children's Research Hospital is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. Founded by late entertainer Danny Thomas and based in Memphis, Tenn., St. Jude freely shares its discoveries with scientific and medical communities around the world. No family ever pays for treatments not covered by insurance, and families without insurance are never asked to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.

Contact: Carrie Strehlau
carrie.strehlau@stjude.org
901-595-2295
St. Jude Children's Research Hospital

[mixin]

Re: Study finds more effective treatment for pneumonia following influenza

clindamycin and azithromycin

Seems like it would be good to remember these antibiotics.

I wonder how much there is in the pandemic stockpile?

[sharon sanders]

Re: St.Jude - clindamycin and azithromycin are more effective than ampicillin in the treatment of pneumonia after influenza illness

"Ampicillin aggravated inflammation compared to clindamycin, the researchers confirmed in test tube studies. The investigators also found evidence of increased inflammation in lung cells of ampicillin-treated animals.

According to McCullers, lung tissue studies of ampicillin-treated animals also revealed the antibiotic's deleterious effects. "

[mixin]

Re: St.Jude - clindamycin and azithromycin are more effective than ampicillin in the treatment of pneumonia after influenza illness

Ampicillin has been around for a long time; I'm not sure when it was approved for human use. Did no one ever wonder about the inflammation?

One good thing comming out fear of an influenza pandemic is all the research that's being done. Until AI, flu has been around for several hundred years (at least) and we've known so little about it.

IOH, those study titles are really hard for us non-science types to understand sometimes. Thanks for the link.