Tuesday, February 27, 2007

Pre- and probiotics

Pre- and probiotics
Ther Umsch. 2007 Mar

Meier R,
Lochs H.
Medizinische Universitatsklinik, Abteilung fur Gastroenterologie, Hepatologie und Ernahrung, Kantonsspital, Liestal.

Nowadays, the regular consumption of pre- and probiotics is recommended to provide various positive health benefits. The in vitro and in vivo demonstrated actions on the intestinal microflora, the mucosal barrier and the immunological system are very interesting to propose beneficial health effects, but the scientific proof in humans is not demonstrated yet. Pre- and probiotics are very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanism.

Prebiotics stimulates the growth of apathogen bacteria and increase the short chain fatty acid concentration by fermentation. Short chain fatty acids are necessary substrates for a healthy gut. Probiotics inhibit the growth of pathogen bacteria, reduce the translocation of bacteria and toxins and modulate the intestinal immune system. For some specific clinical diseases (ulcerative colitis, pouchitis, diarrhoea) a therapeutic and prophylactic effect with pre- and probiotics was shown.

In the near future more indications for pre- and probiotics (used as a single strain or as in a combination) will be added. Promising results are already shown in irritable bowel syndrome, prevention of antibiotic induced diarrhoea, in surgical and in intensive care patients.

Future studies should focus to determine the characteristics of a healthy gut and the evaluation of specific health benefits by well-designed, controlled human studies of adequate duration.

PMID: 17323288
[PubMed - in process]

Tuesday, February 20, 2007

Strategies in the treatment of infections with antibiotics in intensive care medicine.

Strategies in the treatment of infections with antibiotics in intensive care medicine.

Anasthesiol Intensivmed Notfallmed Schmerzther. 2007 Feb

Deja M,
Nachtigall I,
Halle E,
Kastrup M,
Guill MM,
Spies CD.


The treatment of infections is one of the central elements in post-operative intensive care and contributes significantly to outcome. Measures of quality of antibiotic therapy include survival, duration of ICU or in-atient stay and rates of organ failure, antibiotic resistance or nosocomial infection. The pre-requisites for antibiotic prescribing in the intensive care unit are as follows: the treatment has to be started early, the antibiotic must be effective against probable causative organisms, the patient's risk factors for infection with multi-drug resistant organisms must be taken into account, local patterns of resistance must be known, an effective dosage must be used and the duration of therapy should be adjusted to the patient's risk factors and probable causative organisms. The multiplicity of factors which must be taken into account when determining timely empirical therapy and the fact that this must be possible at any time of the day, make local standard operating procedures for antibiotic prescribing imperative. These standards should reflect local resistance patterns and should be regularly reviewed. The aim of this educational article is to portray a selection of the pre-requisites and strategies available in the treatment of infections with antibiotics in intensive care medicine.

PMID: 17309018 [PubMed - as supplied by publisher]

Wednesday, February 14, 2007

New Rules for Usage of Ketek by FDA

FDA Curbs Use of Ketek - 2 of 3 Indications Taken Away, New Warning Added

By Todd Zwillich

WebMD Medical News

Reviewed By Louise Chang, MD on Monday, February 12, 2007

Feb. 12, 2007 -- Federal regulators Monday narrowed the approved uses of the controversial antibiotic Ketek, and said they will add new safety warnings for the drug.

The move is the latest in years of maneuvering over Ketek, which has been the subject of a pair of FDA reviews and a U.S. Senate investigation.

Agency officials said Ketek will no longer be approved to treat bacterial sinus infection and bacterial exacerbations of chronic bronchitis bronchitis, two generally safe upper respiratory tract infections.

It will remain an option for the treatment of community-acquired pneumonia pneumonia of mild to moderate severity.

John Jenkins, MD, head of the FDA's office of new drugs, said the agency's decision was "the result of a comprehensive analysis of risks and benefits" of Ketek.

Those risks include liver toxicity, a side effect that has increasingly concerned FDA scientists and industry watchdogs since Ketek gained U.S. approval in April 2004.

An analysis commissioned by the agency late last year found 35 cases of severe injuries that analysts say were likely attributable to Ketek.

Doctors have written an estimated 6 million prescriptions for Ketek since its approval.
But scientists have worried that the risk of liver problems, while rare, may not be worth Ketek's limited benefits.

The drug was never shown to be better than other antibiotics at curing bacterial infections, but was approved under FDA regulations that seek to speed newer agents to market in an effort to combat drug resistance.

Ketek's label was changed in June 2006 to add the warning that it carries a risk of liver damage.

New Ketek Warning

Now, a new boxed warning in Ketek's labeling will warn doctors and consumers that the drug should not be used in patients with myasthenia gravismyasthenia gravis, a chronic condition that causes muscle to tire and weaken, the agency said.

Sanofi-Aventis, Ketek's manufacturer, said it will alert doctors to the changes and begin distributing patient information guides. Sanofi-Aventis is a WebMD sponsor.

In a statement, the France-based company said Ketek remains "an important option" for doctors.

Senate Scrutiny

The FDA has come under scrutiny from Congress over Ketek.

A U.S. Senate committee report in December 2006 concluded the agency had failed to inform expert advisors reviewing Ketek that a large safety study was flawed by researcher misconduct.
And the agency's handling of Ketek is likely to be a key focus of hearings on the agency's practices scheduled for Tuesday in the U.S. House of Representatives.

Jenkins referred to the 2006 episode Monday as "a learning experience for us." If the agency encounters a similar situation in the future, "it's possible we would take a different decision at that point," he said.

Sen. Charles E. Grassley (R-Iowa), whose staff issued the Senate report, said the FDA has been held accountable for its questionable approval of Ketek.

"Now the uses for Ketek are limited, and the public is safer and better informed," Grassley said.
Sanofi-Aventis posted $58.3 million in Ketek sales in the first nine months of 2006, company spokesman Melissa Feltmann tells WebMD.

"I think it's premature to speculate on the exact impact" of Monday's announcement, she says.
SOURCES: John Jenkins, MD, director, Office of New Drugs, FDA. News release, Sanofi-Aventis. Sen. Charles E. Grassley (R-Iowa). Melissa Feltmann, spokesman, Sanofi-Aventis.

Webb MD

Friday, February 09, 2007

Linezolid: a new antibiotic for newborns and children?

Linezolid: a new antibiotic for newborns and children?
J Chemother. 2006 Dec

Cuzzolin L,
Fanos V.

Department of Medicine & Public Health, University of Verona, Italy.

Staphylococcus aureus remains one of the most common and troublesome microorganisms causing disease in humans, despite the development of effective antibiotics. Linezolid is a member of a new class of synthetic antibiotics called oxazolidinones, introduced into therapy due to the increasing resistance of Gram-positive pathogens to traditional antibiotics. Information about the pharmacokinetics and tolerability profile of linezolid in the pediatric population mostly derive from adult studies and especially in the neonatal field relatively few data are available. Here we summarize linezolid's characteristics and report data available in the literature regarding linezolid use in newborns and children. For this purpose, a Medline search was performed between 1990 and 2006 involving the term "linezolid" combined with the terms "newborn", "infant", "child", "pediatrics". Additional information was obtained from Reactions Weekly.

PMID: 17267334 [PubMed - in process]

Related Article:

Use of linezolid in children: an overview of recent advances.

Expert Rev Anti Infect Ther. 2006 Dec

Velissariou IM.
P and A Kyriakou Children's Hospital, Amphitritis, Street 3, 17561, Palio Faliro, Athens, Greece.

Linezolid is the first member of a new generation of antibiotics, the synthetic oxazolidinones, to become available, with a broad spectrum of in vitro activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and vancomycin-resistant E. faecium. Linezolid is showing great promise currently for the treatment of multiresistant gram-positive bacterial infections, especially complicated skin infections, catheter-induced bacteremia or nosocomial pneumonia both in the community and in a hospital setting, in children and in adults. Although most recent reports are favorable and anticipatory of a more extensive use of linezolid in appropriately selected pediatric population groups in the near future, following treatment failure of conventional antimicrobial agents, more clinical trials are, however, required to investigate the safety profile and tolerability of this new antibiotic in the pediatric population.

Full Text Article

Tuesday, February 06, 2007

The antibiotic resistome: the nexus of chemical and genetic diversity.

The antibiotic resistome: the nexus of chemical and genetic diversity.

Nat Rev Microbiol. 2007 Feb 5;

Wright GD.
Antimicrobial Research Centre, Department of Biochemistry and Biomedical Sciences, DeGroote School of Medicine, McMaster University, 1200 Main Street West Hamilton, Ontario, L8N 3Z5, Canada.

Over the millennia, microorganisms have evolved evasion strategies to overcome a myriad of chemical and environmental challenges, including antimicrobial drugs. Even before the first clinical use of antibiotics more than 60 years ago, resistant organisms had been isolated. Moreover, the potential problem of the widespread distribution of antibiotic resistant bacteria was recognized by scientists and healthcare specialists from the initial use of these drugs. Why is resistance inevitable and where does it come from? Understanding the molecular diversity that underlies resistance will inform our use of these drugs and guide efforts to develop new efficacious antibiotics.

PMID: 17277795 [PubMed - as supplied by publisher]