Antibiotic efflux pumps in Gram-negative bacteria: the inhibitor response strategy.
J Antimicrob Chemother. 2007 Jan 17
Mahamoud A,
Chevalier J,
Alibert-Franco S,
Kern WV,
Pages JM.
UMR-MD-1, Facultes de Medecine et de Pharmacie, Universite de la Mediterranee, 27 Boulevard Jean Moulin, F-13385 Marseille Cedex 05, France.
* Corresponding author. Tel.: +33-4-91-32-45-87; Fax: +33-4-91-32-46-06; E-mail: Jean-Marie.PAGES@medecine.univ-mrs.fr
After several decades of continuously successful antibiotic therapy against bacterial infections, we are now facing a worrying prospect: the accelerated evolution of antibiotic resistance to important human pathogens and the scarcity of new anti-infective drug families under development. Efflux is a general mechanism responsible for bacterial resistance to antibiotics. This active drug transport is involved in low intrinsic susceptibility, cross-resistance to chemically unrelated classes of molecules, and selection/acquisition of additional mechanisms of resistance.
Thus, inhibition of bacterial efflux mechanisms appears to be a promising target in order to (i) increase the intracellular concentration of antibiotics that are expelled by efflux pumps, (ii) restore the drug susceptibility of resistant clinical strains, and (iii) reduce the capability for acquired additional resistance. Structurally unrelated classes of efflux pump inhibitors (EPIs) have been described and tested in the last decade, including some analogues of antibiotic substrates and new chemical molecules. Among the current collection of EPIs, only a few compounds have been studied taking into account the structure-activity relationships and the spectrum of activity in terms of antibiotics, pumps and bacteria. While large efforts have characterized an increasing number of bacterial efflux pumps and generated several potentially active EPIs, they have not elucidated the molecular basis of efflux transport and inhibition.
Recent studies of pump-substrate complexes, the 3D resolution of the efflux pumps, the synthesis of novel compounds and molecular dynamic studies may generate new clues to decipher and select novel targets inside the efflux mechanisms and, finally, may result in a clinically useful molecule.
Key Words: antibiotic resistance , drug efflux pumps , efflux pump inhibitors
Oxford Journals
Monday, January 22, 2007
Tuesday, January 16, 2007
Modes and Modulations of Antibiotic Resistance Gene Expression.
Modes and Modulations of Antibiotic Resistance Gene Expression.
Clin Microbiol Rev. 2007 Jan;20
Depardieu F,
Podglajen I,
Leclercq R,
Collatz E,
Courvalin P.
Unite des Agents Antibacteriens, Institut Pasteur, 75724 Paris Cedex 15, France. pcourval@pasteur.fr.
Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment.
Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information.
PMID: 17223624 [PubMed - as supplied by publisher]
Related Article:
Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem.
Anim Biotechnol. 2006
Summers AO.
Department of Microbiology, University of Georgia, Athens, Georgia 30602, USA. summers@uga.edu
Bacteria carrying resistance genes for many antibiotics are moving beyond the clinic into the community, infecting otherwise healthy people with untreatable and frequently fatal infections. This state of affairs makes it increasingly important that we understand the sources of this problem in terms of bacterial biology and ecology and also that we find some new targets for drugs that will help control this growing epidemic.
This brief and eclectic review takes the perspective that we have too long thought about the problem in terms of treatment with or resistance to a single antibiotic at a time, assuming that dissemination of the resistance gene was affected by simple vertical inheritance. In reality antibiotic resistance genes are readily transferred horizontally, even to and from distantly related bacteria.
The common agents of bacterial gene transfer are described and also one of the processes whereby nonantibiotic chemicals, specifically toxic metals, in the environment can select for and enrich bacteria with antibiotic multiresistance. Lastly, some speculation is offered on broadening our perspective on this problem to include drugs directed at compromising the ability of the mobile elements themselves to replicate, transfer, and recombine, that is, the three "infrastructure" processes central to the movement of genes among bacteria.
Keywords:
Bacteriophage, Evolution, Integron, Plasmid, Toxic metal resistance, Transposon
Article
Clin Microbiol Rev. 2007 Jan;20
Depardieu F,
Podglajen I,
Leclercq R,
Collatz E,
Courvalin P.
Unite des Agents Antibacteriens, Institut Pasteur, 75724 Paris Cedex 15, France. pcourval@pasteur.fr.
Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment.
Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information.
PMID: 17223624 [PubMed - as supplied by publisher]
Related Article:
Genetic linkage and horizontal gene transfer, the roots of the antibiotic multi-resistance problem.
Anim Biotechnol. 2006
Summers AO.
Department of Microbiology, University of Georgia, Athens, Georgia 30602, USA. summers@uga.edu
Bacteria carrying resistance genes for many antibiotics are moving beyond the clinic into the community, infecting otherwise healthy people with untreatable and frequently fatal infections. This state of affairs makes it increasingly important that we understand the sources of this problem in terms of bacterial biology and ecology and also that we find some new targets for drugs that will help control this growing epidemic.
This brief and eclectic review takes the perspective that we have too long thought about the problem in terms of treatment with or resistance to a single antibiotic at a time, assuming that dissemination of the resistance gene was affected by simple vertical inheritance. In reality antibiotic resistance genes are readily transferred horizontally, even to and from distantly related bacteria.
The common agents of bacterial gene transfer are described and also one of the processes whereby nonantibiotic chemicals, specifically toxic metals, in the environment can select for and enrich bacteria with antibiotic multiresistance. Lastly, some speculation is offered on broadening our perspective on this problem to include drugs directed at compromising the ability of the mobile elements themselves to replicate, transfer, and recombine, that is, the three "infrastructure" processes central to the movement of genes among bacteria.
Keywords:
Bacteriophage, Evolution, Integron, Plasmid, Toxic metal resistance, Transposon
Article
Wednesday, January 10, 2007
Bronchitis and Antibiotics
Bronchitis and Antibiotics
Antibiotics Are Useless for Most Cases of BronchitisBut doctors keep prescribing them, contributing to bacterial resistance, study says
Healthday
Most people who go to a doctor with the raspy breathing problem called bronchitis get an antibiotic. Most of them shouldn't, a new study contends.
Two physicians at the Virginia Commonwealth University School of Medicine surveyed the world literature on bronchitis -- research studies, clinical trials and anything related to bronchitis and its treatment.
"Physicians should be encouraged to avoid antibiotics in most cases," said Dr. Richard P. Wenzel, chairman of the department of internal medicine at Virginia Commonwealth and one of the authors of the report.
The findings are published in the Nov. 16 issue of the New England Journal of Medicine.
The primary reason for over-prescription of antibiotics is that most cases of bronchitis, which is inflammation of the tiny airways of the lungs, "are caused by agents for which we have no therapy yet," meaning viruses, Wenzel said. Only a small percentage of acute bronchitis cases are caused by bacteria that doctors can treat, such as whooping cough, he said.
Yet doctors keep prescribing antibiotics, he said. He estimated that 70 percent to 80 percent of bronchitis patients are given a course of antibiotics lasting five to 10 days.
That's a lot of antibiotics. One of every 20 American adults will get bronchitis in a given year, Wenzel said. A first reason for them not taking antibiotics is that the drugs cost money, in an era when the mounting cost of health care is a major concern, he said.
"And all antibiotics have side effects, such as rash, diarrhea and abdominal pain," Wenzel said. Side effects are acceptable only when a medication helps the patient, he said.
"The third reason for not prescribing antibiotics is the impressive pressure it puts on organisms to select more resistant strains, so that the ones we use will no longer be effective," Wenzel said. While economists worry about medical costs, physicians worry about antibiotic-resistant strains of bacteria.
With all those arguments against the practice, why do doctors still write those prescriptions?
One reason is convenience, Wenzel said. "Think of all the patients we have to move through the office," he said. "I could take 15 minutes to explain why an antibiotic is not needed or write a prescription in 30 seconds."
And bronchitis tends to be overlooked as a subject of medical interest, Wenzel said. "It isn't considered very jazzy," he said. "It doesn't get highlights in medical journals or educational conferences. I can't remember in the past 10 years hearing a speaker discuss bronchitis at a medical meeting."
The information on bronchitis is there for any doctor who cares to look. The American Academy of Family Physicians notes that "because acute bronchitis is usually caused by viruses, antibiotics... usually do not help." The academy recommends getting lots of rest, drinking lots of non-caffeinated fluids, keeping the indoor humidity high and waiting for the condition to go away "after a few days or a week." If coughing and other symptoms persist, it could be a sign of a more serious condition, such as asthma or pneumonia.
One big reason for antibiotic prescriptions is patient demand, said Dr. Jeffrey Chapman, director of interstitial lung disease at the Cleveland Clinic.
"But patients are getting more savvy," he said. "They understand that a lot of infections are viral and that giving them an antibiotic places them at risk."
People with the bothersome symptoms of bronchitis shouldn't insist on a prescription, Chapman said. They should understand that "it may be the best course of treatment not to give an antibiotic."
"The message is getting out, a little bit at a time," he said. "There is a better understanding than there was, say, 10 years ago, that sometimes an antibiotic is not the better treatment."
Sinusitis and Antibiotics
Sinusitis and Antibiotics
Antibiotics Mostly Useless for SinusitisStudy only shows benefit with bacterial infections, which are minority of cases
(HealthDay News) -- If you develop a mild sinus infection this winter -- or even a moderately severe one -- antibiotics won't necessarily speed your recovery, new research shows.
"In the vast majority of cases, rhinosinusitis is a self-limiting disease," said Dr. An De Sutter, of Ghent University Hospital in Belgium. "It can last 10 days or longer, but antibiotics do not influence the course of the disease."
So, if you don't have signs of complications or severe infection, such as a high fever or extreme pain, your best bet is to forgo antibiotics, rely on symptomatic treatments and wait for a natural recovery, De Sutter said.
De Sutter estimates that 50 percent to 70 percent of sinusitis patients are prescribed antibiotics. Although the drugs can effectively treat patients who develop bacterial sinusitis, they are ineffective against viral sinusitis, which represents the majority of cases.
In the study, De Sutter and her colleagues looked at 300 patients with mild to moderately severe sinusitis, 218 of whom received sinus X-rays. They randomly assigned patients to receive either amoxicillin or a placebo, asked them to keep a symptom diary and observed them for 15 days.
The researchers found that neither typical sinusitis signs and symptoms nor abnormal X-rays had any value in predicting the course of the disease. They also found that the disease lasted as long in patients taking amoxicillin as it did in patients taking a placebo, and that 247 of the patients recovered within 15 days.
Only two subjective complaints -- a general feeling of illness and reduced productivity -- predicted a slower recovery from sinusitis. "In patients who feel ill or who do not feel able to work, recovery will take a few days longer," De Sutter said. "But antibiotic treatment does not speed recovery in these patients."
"We don't know for sure why antibiotic treatment seemed to have no effect on the duration of the illness," De Sutter said. "But there two possible explanations: Either the illness and X-ray abnormalities were not caused by a bacterial infection, or if they were, the patients' immune systems were able to overcome the infection just as quickly without antibiotics."
The results of the study are published in the November/December issue of the Annals of Family Medicine.
"We advise antibiotic treatment only when patients have severe symptoms such as high fever and bad pain or if they have impaired immune function," De Sutter said. "This is a very small minority of patients. For all others, we advise 'watchful waiting.' "
Instead of prescribing antibiotics, doctors should focus on symptom relief: paracetamol for pain relief and intranasal decongestants in case of a blocked nose, De Sutter suggested. "Some patients experience subjective relief by inhaling hot steam," she added.
In a similar study in the same journal, researchers found the desire for pain relief was one of the main reasons why sore-throat patients demand antibiotics. They concluded that it may be preferable to treat such patients with pain medications instead of antibiotics.
In most sinusitis cases, De Sutter believes that doctors should resist patient demand for antibiotics. "Doctors should explain to patients that antibiotics do not make a difference in the speed of recovery and can cause side effects," De Sutter said. "In our trial, diarrhea was more frequent with antibiotics. Other known side effects include nausea, oral or vaginal mold or yeast infection, allergic reactions and colitis."
The over-prescription of antibiotics, especially in children, also can cause the upper respiratory tract to become colonized with antibiotic-resistant bacteria such as S. pneumoniae, De Sutter said. "These resistant bacteria may cause infections that are more difficult to treat and may be passed on to other people."
"This is an interesting study because it looked at a large population of people with acute sinusitis," said Dr. David Sherris, chairman of otolaryngology at the University at Buffalo in New York.
"Most people do not need antibiotic therapy unless symptoms persist for more than seven to 10 days," Sherris said. "Plain X-rays of the sinuses add little or nothing to the diagnosis and treatment of acute sinusitis."
But that doesn't mean that imaging is of no value in sinusitis cases, he added. With prolonged or recurrent sinusitis or complications, computed tomography (CT) is the test of choice and works well, he noted.
"Early referral to an otolaryngologist is indicated in the most severe cases or where symptoms are out of proportion with findings," Sherris said. "The specialist can perform nasal endoscopy and accurately assess the most subtle CT scan findings."
Although the new study confirms some observations that Sherris has made during years of clinical practice, it would have been stronger if it had used the symptom system from the American Academy of Otolaryngology Head and Neck Surgery, Sherris said. "It is more complete than the one presented in this article, and though not infallible, is better to diagnose acute sinusitis."
Sherris also faulted the researchers' choice of antibiotics. "Amoxicillin, unless used in very high doses, is not a good first line antibiotic in acute sinusitis," he said. "Amoxicillin-clavulanate [augmentin] is a better choice, and is now generic in the United States. If there is an allergy to penicillin, physicians should consider azithromycin or a respiratory quinolone."
The danger of not taking all of your prescribed antibiotics
The danger of not taking all of your prescribed antibiotics
By Dr. Tom Gross Marin Independent Journal (California)Copyright 2007 Marin Independent Journal, a MediaNews Group publicationAll Rights Reserved Editor's note: Dr. Tom Gross is the emergency medical services director for the Novato Fire Protection District. His column appears every Monday.
I answered a telephone call the other day from a neighbor, who told me that she had a sinus infection. She wanted to know if it was OK for her to take some antibiotics. I asked her, "What antibiotics?"
She said, "Oh, I don't know, just something I have left over from my last infection." She described to me her symptoms, which included a sore throat, nasal congestion and sneezing; in other words, a common cold and not a sinus infection. She told me that whenever she gets those symptoms, she takes some leftover antibiotics from her medicine cabinet for a few days, but just until she feels better. Even though her cold would have resolved on its own, she thinks that the antibiotics are curing her illness.
There has been some doomsday press recently about strains of bacteria that are resistant to antibiotics. It is not difficult to create your own strain of antibiotic resistant bacteria. You can do it yourself at home. In fact, most people do.
Here is an experiment that you can try. All you need is some dishes of culture medium, easily available from any biological supply house, some cotton swabs, and your own vial of leftover antibiotics from the last time that you did not take your medication as prescribed.
First, take the cotton swab, wipe it along the back of your throat and rub it on a culture medium. Put the culture dish in a warm, dark place, like at the bottom of a laundry hamper and wait.
After a few days, the culture medium will be teeming with little white mounds of bacteria that look like cookie dough and smell like a laundry hamper.
Take another swab and transfer some of the bacteria to a new culture dish. Grind up a few of your leftover antibiotics and sprinkle them in the dish, close the lid and put it back in the bottom of the laundry hamper.
After a few days, examine your experiment again. The areas in the dish nearest to the antibiotic powder will be relatively free of bacterial culture; that is, no cookie dough.
However, the bacteria that have grown will have survived despite the presence of antibiotics. You will have just created your own strain of antibiotic-resistant bacteria, and you may now consider yourself to be a world-class WMD bioweapons manufacturer. You can go one step further, by repeating the experiment with another antibiotic, and you can make a bacterial culture that has multidrug resistance.
This type of experiment is known as "in vitro"; that is, your experiment was carried out "in glass." You can also perform this experiment "in vivo"; that is, in a living organism. In vivo experiments carry more scientific validity than in vitro experiments because their results are shown to be valid in actual patients rather than merely in a glass jar.
People who take their antibiotics for less than the prescribed period of time are performing in vivo experiments on themselves.
By taking antibiotics for only a few days, they are killing off the bacteria that are most susceptible, and leaving the most resistant behind to survive. They have participated in a living experiment that has demonstrated the validity of Darwin's theory of natural selection.
By exposing bacteria to intermittent small doses of antibiotics, they have killed off the bacteria that are most susceptible and have selected for those that are antibiotic resistant.
Having grown in their throats an antibiotic resistant strain of bacteria, then their next sinus infection will be truly resistant to antibiotics. These resistant bacteria can also spread to other people.
You may read in the paper about deadly strains of antibiotic resistant bacteria, such as MRSA (methicillin resistant staph aureus) or VRE (vancomycin resistant enterococcus). You may read about strains of tuberculosis bacillus that are resistant to all five antibiotics used to treat this disease.
This is no joke. This threat is real. The next time that you read about strains of antibiotic resistant bacteria, ask yourself if maybe you have been a part of this great experiment. Do you have antibiotics at home in your medicine cabinet left over from the last time that you did not take them as prescribed?
Please don't ask for stronger antibiotics. They have not been invented yet.
Article
By Dr. Tom Gross Marin Independent Journal (California)Copyright 2007 Marin Independent Journal, a MediaNews Group publicationAll Rights Reserved Editor's note: Dr. Tom Gross is the emergency medical services director for the Novato Fire Protection District. His column appears every Monday.
I answered a telephone call the other day from a neighbor, who told me that she had a sinus infection. She wanted to know if it was OK for her to take some antibiotics. I asked her, "What antibiotics?"
She said, "Oh, I don't know, just something I have left over from my last infection." She described to me her symptoms, which included a sore throat, nasal congestion and sneezing; in other words, a common cold and not a sinus infection. She told me that whenever she gets those symptoms, she takes some leftover antibiotics from her medicine cabinet for a few days, but just until she feels better. Even though her cold would have resolved on its own, she thinks that the antibiotics are curing her illness.
There has been some doomsday press recently about strains of bacteria that are resistant to antibiotics. It is not difficult to create your own strain of antibiotic resistant bacteria. You can do it yourself at home. In fact, most people do.
Here is an experiment that you can try. All you need is some dishes of culture medium, easily available from any biological supply house, some cotton swabs, and your own vial of leftover antibiotics from the last time that you did not take your medication as prescribed.
First, take the cotton swab, wipe it along the back of your throat and rub it on a culture medium. Put the culture dish in a warm, dark place, like at the bottom of a laundry hamper and wait.
After a few days, the culture medium will be teeming with little white mounds of bacteria that look like cookie dough and smell like a laundry hamper.
Take another swab and transfer some of the bacteria to a new culture dish. Grind up a few of your leftover antibiotics and sprinkle them in the dish, close the lid and put it back in the bottom of the laundry hamper.
After a few days, examine your experiment again. The areas in the dish nearest to the antibiotic powder will be relatively free of bacterial culture; that is, no cookie dough.
However, the bacteria that have grown will have survived despite the presence of antibiotics. You will have just created your own strain of antibiotic-resistant bacteria, and you may now consider yourself to be a world-class WMD bioweapons manufacturer. You can go one step further, by repeating the experiment with another antibiotic, and you can make a bacterial culture that has multidrug resistance.
This type of experiment is known as "in vitro"; that is, your experiment was carried out "in glass." You can also perform this experiment "in vivo"; that is, in a living organism. In vivo experiments carry more scientific validity than in vitro experiments because their results are shown to be valid in actual patients rather than merely in a glass jar.
People who take their antibiotics for less than the prescribed period of time are performing in vivo experiments on themselves.
By taking antibiotics for only a few days, they are killing off the bacteria that are most susceptible, and leaving the most resistant behind to survive. They have participated in a living experiment that has demonstrated the validity of Darwin's theory of natural selection.
By exposing bacteria to intermittent small doses of antibiotics, they have killed off the bacteria that are most susceptible and have selected for those that are antibiotic resistant.
Having grown in their throats an antibiotic resistant strain of bacteria, then their next sinus infection will be truly resistant to antibiotics. These resistant bacteria can also spread to other people.
You may read in the paper about deadly strains of antibiotic resistant bacteria, such as MRSA (methicillin resistant staph aureus) or VRE (vancomycin resistant enterococcus). You may read about strains of tuberculosis bacillus that are resistant to all five antibiotics used to treat this disease.
This is no joke. This threat is real. The next time that you read about strains of antibiotic resistant bacteria, ask yourself if maybe you have been a part of this great experiment. Do you have antibiotics at home in your medicine cabinet left over from the last time that you did not take them as prescribed?
Please don't ask for stronger antibiotics. They have not been invented yet.
Article
Friday, January 05, 2007
Elective penicillin skin testing in a pediatric outpatient setting.
Elective penicillin skin testing in a pediatric outpatient setting.
Dec 2006
Jost BC,
Wedner HJ,
Bloomberg GR.
Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
BACKGROUND: Adverse reactions associated with penicillin-type antibiotics are common in pediatric practice, leading to the subsequent unnecessary use of alternative antibiotics. IgE-mediated penicillin allergy represents only a fraction of these adverse reactions.
OBJECTIVES: To examine (1) the trend of penicillin skin test reactivity during a recent 10-year interval, (2) the relative distribution of specific reagents related to a positive skin test result, and (3) skin test reactivity as a function of reaction history.
METHODS: Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G, and sodium penicilloate (penicillin A)--was conducted in a prospective study of 359 consecutive patients referred to an outpatient pediatric allergy clinic between January 1, 1993, and May 31, 2003. We also retrospectively reviewed penicillin skin test results for 562 children previously tested between January 1, 1979, and December 31, 1992.
RESULTS: Between 1993 and 2003, the prevalence of penicillin skin test sensitivity markedly declined. Of all the positive skin test results between 1979 and 2002, either penicillin G or sodium penicilloate or both identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of positive skin test reactions was not significantly different between patients with vs without a history of suggestive IgE-mediated reactions.
CONCLUSIONS: A marked decline in penicillin skin test sensitivity in the pediatric age group is identified. The minor determinant reagents penicillin G and sodium penicilloate are both necessary for determining potential penicillin allergy. Relating history alone to potential penicillin sensitivity is unreliable in predicting the presence or absence of a positive skin test result.
PubMed
Dec 2006
Jost BC,
Wedner HJ,
Bloomberg GR.
Division of Allergy and Immunology, Department of Internal Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
BACKGROUND: Adverse reactions associated with penicillin-type antibiotics are common in pediatric practice, leading to the subsequent unnecessary use of alternative antibiotics. IgE-mediated penicillin allergy represents only a fraction of these adverse reactions.
OBJECTIVES: To examine (1) the trend of penicillin skin test reactivity during a recent 10-year interval, (2) the relative distribution of specific reagents related to a positive skin test result, and (3) skin test reactivity as a function of reaction history.
METHODS: Penicillin testing using 3 reagents--benzylpenicilloyl polylysine, penicillin G, and sodium penicilloate (penicillin A)--was conducted in a prospective study of 359 consecutive patients referred to an outpatient pediatric allergy clinic between January 1, 1993, and May 31, 2003. We also retrospectively reviewed penicillin skin test results for 562 children previously tested between January 1, 1979, and December 31, 1992.
RESULTS: Between 1993 and 2003, the prevalence of penicillin skin test sensitivity markedly declined. Of all the positive skin test results between 1979 and 2002, either penicillin G or sodium penicilloate or both identified 34%, with sodium penicilloate alone responsible for 8.5%. The rate of positive skin test reactions was not significantly different between patients with vs without a history of suggestive IgE-mediated reactions.
CONCLUSIONS: A marked decline in penicillin skin test sensitivity in the pediatric age group is identified. The minor determinant reagents penicillin G and sodium penicilloate are both necessary for determining potential penicillin allergy. Relating history alone to potential penicillin sensitivity is unreliable in predicting the presence or absence of a positive skin test result.
PubMed
Monday, January 01, 2007
Alternative to Antibiotics Developed at Technion-Isreal Institute of Technology
Alternative to Antibiotics Developed at Technion-Isreal Institute of Technology
December 2006
By JUDY SIEGEL-ITZKOVICH
Researchers at the Technion-Israel Institute of Technology have discovered a new way to create effective substitutes for antibiotics based on a combination of amino acids and fatty acids. Bacteria are not able to develop resistance to these substitutes, so this is their great advantage, as commonly used antibiotics are increasingly losing their effectiveness.
Prof. Amram Mor and students in his Haifa research team - Keren Marinka and Shahar Rotem of the biotechnology and food engineering faculty - found a way to preserve peptides in the body. Peptides are tiny proteins found in all organisms that constitute part of the immune system. They last only a short time, even minutes, but the Technion researchers found a way to stabilize and preserve them in the body for hours by creating a unique structure. Their study was published recently in the journal Chemistry and Biology.
"We found a way to shorten the natural molecule and thus reduce the cost of its production, while at the same time making it more efficient so it can successfully fight bacteria and other pathogens," said Mor.
"With help from Prof. Uri Kogan and Dr. Irina Fortania of our faculty, we added fatty acid to the short molecule, and its activity improved even more. We are also able to decide which bacterium to attack with our peptides."
The researchers show in the article how they use a fatty acid to activate the peptide so it acts specifically against Pseudonomas bacteria, which usually causes lung infections. It is important that the peptide function specifically against the bacterium so as not to harm healthy cells or beneficial bacteria that form the natural flora of the body. The team thus produced a pseudo-peptide that breaks the pathogenic bacteria down.
"This involves selective and specific construction against traditional pathogens and increasing the efficacy of treatment while significantly reducing toxicity and side effects," Mor explained.
Mor has been studying peptides for 20 years, during which he isolated a group of these proteins taken from frogs that live in trees. He found that these peptides were no less effective over time than antibiotics, which need to become 100 times bigger in their dosage to kill pathogens as time passes. There is no need, he said, to increase the dosage of the peptides.
The Jerusalem Post
December 2006
By JUDY SIEGEL-ITZKOVICH
Researchers at the Technion-Israel Institute of Technology have discovered a new way to create effective substitutes for antibiotics based on a combination of amino acids and fatty acids. Bacteria are not able to develop resistance to these substitutes, so this is their great advantage, as commonly used antibiotics are increasingly losing their effectiveness.
Prof. Amram Mor and students in his Haifa research team - Keren Marinka and Shahar Rotem of the biotechnology and food engineering faculty - found a way to preserve peptides in the body. Peptides are tiny proteins found in all organisms that constitute part of the immune system. They last only a short time, even minutes, but the Technion researchers found a way to stabilize and preserve them in the body for hours by creating a unique structure. Their study was published recently in the journal Chemistry and Biology.
"We found a way to shorten the natural molecule and thus reduce the cost of its production, while at the same time making it more efficient so it can successfully fight bacteria and other pathogens," said Mor.
"With help from Prof. Uri Kogan and Dr. Irina Fortania of our faculty, we added fatty acid to the short molecule, and its activity improved even more. We are also able to decide which bacterium to attack with our peptides."
The researchers show in the article how they use a fatty acid to activate the peptide so it acts specifically against Pseudonomas bacteria, which usually causes lung infections. It is important that the peptide function specifically against the bacterium so as not to harm healthy cells or beneficial bacteria that form the natural flora of the body. The team thus produced a pseudo-peptide that breaks the pathogenic bacteria down.
"This involves selective and specific construction against traditional pathogens and increasing the efficacy of treatment while significantly reducing toxicity and side effects," Mor explained.
Mor has been studying peptides for 20 years, during which he isolated a group of these proteins taken from frogs that live in trees. He found that these peptides were no less effective over time than antibiotics, which need to become 100 times bigger in their dosage to kill pathogens as time passes. There is no need, he said, to increase the dosage of the peptides.
The Jerusalem Post
Monday, December 25, 2006
The emergence of antibiotic resistance by mutation.
The emergence of antibiotic resistance by mutation.
Clin Microbiol Infect. 2007 Jan
Antibiotic Resistance Monitoring and Reference Laboratory, Centre for Infections, Health Protection Agency, London, UK.
The emergence of mutations in nucleic acids is one of the major factors underlying evolution, providing the working material for natural selection. Most bacteria are haploid for the vast majority of their genes and, coupled with typically short generation times, this allows mutations to emerge and accumulate rapidly, and to effect significant phenotypic changes in what is perceived to be real-time. Not least among these phenotypic changes are those associated with antibiotic resistance. Mechanisms of horizontal gene spread among bacterial strains or species are often considered to be the main mediators of antibiotic resistance. However, mutational resistance has been invaluable in studies of bacterial genetics, and also has primary clinical importance in certain bacterial species, such as Mycobacterium tuberculosis and Helicobacter pylori, or when considering resistance to particular antibiotics, especially to synthetic agents such as fluoroquinolones and oxazolidinones. In addition, mutation is essential for the continued evolution of acquired resistance genes and has, e.g., given rise to over 100 variants of the TEM family of beta-lactamases. Hypermutator strains of bacteria, which have mutations in genes affecting DNA repair and replication fidelity, have elevated mutation rates. Mutational resistance emerges de novo more readily in these hypermutable strains, and they also provide a suitable host background for the evolution of acquired resistance genes in vitro. In the clinical setting, hypermutator strains of Pseudomonas aeruginosa have been isolated from the lungs of cystic fibrosis patients, but a more general role for hypermutators in the emergence of clinically relevant antibiotic resistance in a wider variety of bacterial pathogens has not yet been proven.
PMID: 17184282 [PubMed - in process]
Sunday, December 10, 2006
Doctors Prescribing Antibiotics Without Patient Examination
Study: Doctors call in more antibiotics without exams
By Rita Rubin, USA TODAY
Created: 12/6/2006 10:56:47 AM
Updated: 12/6/2006 10:57:58 AMPrescribing antibiotics has become so common that many doctors literally are just phoning it in, a new analysis of insurance claims suggests.
Prescribing antibiotics has become so common that many doctors literally are just phoning it in, a new analysis of insurance claims suggests.
Researchers found that 40% of people who filled an antibiotic prescription had not seen a doctor in at least a month, raising the possibility that their symptoms were the result of a viral infection, which doesn't respond to antibiotics, instead of a bacterial infection, which does.
Though antibiotics generally are benign, overprescribing has helped produce drug-resistant "superbugs."
"The study is just a broad indicator of too great a willingness to prescribe," says author William Marder, senior vice president and general manager of Thomson Medstat, a health care information company based in Ann Arbor, Mich.
Thomson Medstat analyzed 1.5 million insurance claims for antibiotic prescriptions in 2004 - the most recent information available - for children and adults under 65 covered by an employer health plan.
Marder called for new treatment guidelines for doctors who increasingly are likely to evaluate patients by phone and the Internet. "It will be critical for physicians to develop the skills necessary to communicate effectively with patients" they can't examine, he writes.
Already, though, says Dartmouth pediatrics professor James Sargent, there are many situations where doctors call in antibiotic prescriptions and refills "without cause for alarm."
For example, Sargent said via e-mail, his practice often calls in prescriptions for antibiotic drops for pinkeye and pills for sore throats in people who have a family member diagnosed with strep throat.
Randall Stafford, associate professor at Stanford's Prevention Research Center, acknowledges that phoned-in antibiotic prescriptions are OK in some situations, such as for women with a repeat urinary tract infection. Still, he called Marder's findings "concerning."
"The standard of care is to have adequate information to make reliable decisions," Stafford says. "Usually, that requires a physical exam."
Article
By Rita Rubin, USA TODAY
Created: 12/6/2006 10:56:47 AM
Updated: 12/6/2006 10:57:58 AMPrescribing antibiotics has become so common that many doctors literally are just phoning it in, a new analysis of insurance claims suggests.
Prescribing antibiotics has become so common that many doctors literally are just phoning it in, a new analysis of insurance claims suggests.
Researchers found that 40% of people who filled an antibiotic prescription had not seen a doctor in at least a month, raising the possibility that their symptoms were the result of a viral infection, which doesn't respond to antibiotics, instead of a bacterial infection, which does.
Though antibiotics generally are benign, overprescribing has helped produce drug-resistant "superbugs."
"The study is just a broad indicator of too great a willingness to prescribe," says author William Marder, senior vice president and general manager of Thomson Medstat, a health care information company based in Ann Arbor, Mich.
Thomson Medstat analyzed 1.5 million insurance claims for antibiotic prescriptions in 2004 - the most recent information available - for children and adults under 65 covered by an employer health plan.
Marder called for new treatment guidelines for doctors who increasingly are likely to evaluate patients by phone and the Internet. "It will be critical for physicians to develop the skills necessary to communicate effectively with patients" they can't examine, he writes.
Already, though, says Dartmouth pediatrics professor James Sargent, there are many situations where doctors call in antibiotic prescriptions and refills "without cause for alarm."
For example, Sargent said via e-mail, his practice often calls in prescriptions for antibiotic drops for pinkeye and pills for sore throats in people who have a family member diagnosed with strep throat.
Randall Stafford, associate professor at Stanford's Prevention Research Center, acknowledges that phoned-in antibiotic prescriptions are OK in some situations, such as for women with a repeat urinary tract infection. Still, he called Marder's findings "concerning."
"The standard of care is to have adequate information to make reliable decisions," Stafford says. "Usually, that requires a physical exam."
Article
Monday, December 04, 2006
Cefazolin Sodium Injection
Cefazolin Sodium Injection
About your treatment
Your doctor has ordered cefazolin, an antibiotic, to help treat your infection. The drug will be either injected into a large muscle (such as your buttock or hip) or added to an intravenous fluid that will drip through a needle or catheter placed in your vein for 30 minutes, two to four times a day.
Cefazolin eliminates bacteria that cause many kinds of infections, including lung, skin, bone, joint, stomach, blood, heart valve, and urinary tract infections. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
Your health care provider (doctor, nurse, or pharmacist) may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments with your doctor and the laboratory. The length of treatment depends on how your infection and symptoms respond to the medication.
Precautions
Before administering cefazolin:
tell your doctor and pharmacist if you are allergic to cefazolin, any other cephalosporin [e.g., cefaclor (Ceclor), cefadroxil (Duricef), or cephalexin (Keflex)], penicillins, or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially other antibiotics, probenecid (Benemid), and vitamins.
tell your doctor if you have or have ever had kidney, liver, or gastrointestinal disease (especially colitis).
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking cefazolin, call your doctor.
if you have diabetes and regularly check your urine for sugar, use Clinistix or TesTape. Do not use Clinitest tablets because cefazolin may cause false positive results.
Administering your medication
Before you administer cefazolin, look at the solution closely. It should be clear and free of floating material. Gently squeeze the bag or observe the solution container to make sure there are no leaks. Do not use the solution if it is discolored, if it contains particles, or if the bag or container leaks. Use a new solution, but show the damaged one to your health care provider.
It is important that you use your medication exactly as directed. Do not stop your therapy on your own for any reason because your infection could worsen and result in hospitalization. Do not change your dosing schedule without talking to your health care provider. Your health care provider may tell you to stop your infusion if you have a mechanical problem (such as a blockage in the tubing, needle, or catheter); if you have to stop an infusion, call your health care provider immediately so your therapy can continue.
Side effect
Cefazolin may cause side effects. If you are administering cefazolin into a muscle, it may be mixed with lidocaine (Xylocaine) to reduce pain at the injection site. Tell your health care provider if any of these symptoms are severe or do not go away:
diarrhea
stomach pain
upset stomach
vomiting
If you experience any of the following symptoms, call your health care provider immediately:
skin rash
itching
hives
unusual bleeding or bruising
difficulty breathing
sore mouth or throat
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online
or by phone [1-800-332-1088].
Storing your medication
Your health care provider probably will give you a several-day supply of cefazolin at a time. If you are receiving cefazolin intravenously (in your vein), you probably will be told to store it in the refrigerator or freezer.
Take your next dose from the refrigerator 1 hour before using it; place it in a clean, dry area to allow it to warm to room temperature.
If you are told to store additional cefazolin in the freezer, always move a 24-hour supply to the refrigerator for the next day's use.
Do not refreeze medications.
If you are receiving cefazolin intramuscularly (in your muscle), your health care provider will tell you how to store it properly.
Store your medication only as directed. Make sure you understand what you need to store your medication properly.
Keep your supplies in a clean, dry place when you are not using them, and keep all medications and supplies out of reach of children. Your health care provider will tell you how to throw away used needles, syringes, tubing, and containers to avoid accidental injury.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Signs of infection
If you are receiving cefazolin in your vein or under your skin, you need to know the symptoms of a catheter-related infection (an infection where the needle enters your vein or skin). If you experience any of these effects near your intravenous catheter, tell your health care provider as soon as possible:
tenderness
warmth
irritation
drainage
redness
swelling
pain
Brand names
Ancef®
Last Revised - 08/01/2006
Medline Plus
* * * * * *
CEFAZOLIN SODIUM USP
Action And Clinical Pharmacology: Cefazolin is a cephalosporin antibiotic for parenteral administration. Cefazolin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. Cefazolin is about 85% bound to serum protein. The peak level in serum is approximately 32 to 42 mg/mL after an i.m. injection of 500 mg. Over 80% of injected cefazolin is excreted in the urine during the first 24 hours after i.m. injection; most is excreted during the first 4 to 6 hours. tag_Indications
Indications Indications And Clinical Uses: In the treatment of the following infections when caused by susceptible strains of the listed organisms: Respiratory tract infections caused by S. pneumoniae, K. pneumoniae, H. influenzae, S. aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci.
Urinary tract infections caused by E. coli, P. mirabilis, K. pneumoniae and some strains of enterobacter, and enterococci. See Note below.
Skin and soft tissue infections caused by S. aureus (penicillin-sensitive and penicillin-resistant), group A beta-hemolytic streptococci and other strains of streptococci.
Bone and joint infections caused by S. aureus. Septicemia caused by S. pneumoniae, S. aureus (penicillin-sensitive and penicillin-resistant), P. mirabilis, E. coli and K. pneumoniae. See Note below.
Endocarditis caused by S. aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci. Determine susceptibility of the causative organism to cefazolin by performing appropriate culture and susceptibility studies. Note: Most strains of Enterococci, indole positive Proteus (P. vulgaris).
E. cloacae, M. morganii, P. rettgeri and methicillin-resistant Staphylococci are resistant.
Serratia, Pseudomonas and A. calcoaceticus (formerly Mima and Herellea species) are almost uniformly resistant to cefazolin.
Perioperative Prophylaxis: In patients undergoing potentially contaminated surgical procedures, and in patients in whom infection would pose a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty), the preoperative, intraoperative and postoperative administration of cefazolin may reduce the incidence of certain postoperative infections. Identification of the causative organisms should be made by culture should signs of infection occur, so that appropriate therapy may be instituted.
Contra-Indications: In patients with known allergy to the cephalosporin group of antibiotics. tag_Warning
Warnings Manufacturers' Warnings In Clinical States: Use with caution in penicillin-allergic patients. There is clinical evidence of partial cross-allergenicity of the penicillins and the cephalosporins. There are instances of patients who have had reactions to both penicillins and cephalosporins (including fatal anaphylaxis after parenteral use). Clinical and laboratory evidence of partial cross-allergenicity of the 2 drug classes exists.
Cefazolin should be administered cautiously and then only when absolutely necessary to any patient who has demonstrated allergy, particularly to drugs. Immediate emergency treatment with epinephrine is indicated for serious anaphylactoid reactions. As indicated, oxygen, i.v. steroids, and airway management, including intubation, should also be employed.
There have been reports of pseudomembranous colitis with the use of cephalosporins. It is therefore important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use.
Precautions: The overgrowth of nonsusceptible organisms may result from the prolonged use of cefazolin. It is essential that the patient be carefully observed.
In patients with a history of lower gastrointestinal disease, particularly colitis, cefazolin should be prescribed with caution. Clinitest tablets solution, but not enzyme-based tests such as Clinistix and Tes-Tape, may falsely indicate glucose in the urine of patients on cefazolin.
Positive direct and indirect Coombs' tests have been reported during treatment with cefazolin. These may also occur in neonates whose mothers received cephalosporins before delivery. The clinical significance of this effect has not been established.
Renal Impairment: Caution should be exercised in treating patients with pre-existing renal damage although cefazolin has not shown evidence of nephrotoxicity.
Patients with low urinary output due to impaired renal function should be administered reduced daily dosages of cefazolin. (See Dosage, Patients with Reduced Renal Function.) Blood levels of cefazolin in dialysis patients remain fairly high and should be monitored.
Probenecid may decrease renal tubular secretion of cefazolin when used concurrently with cefazolin, resulting in increased and prolonged cefazolin blood levels.
In beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days, to minimize possible complications associated with the disease.
Pregnancy: The safety of the use of cefazolin during pregnancy has not been established.
Lactation: Very low concentrations of cefazolin are found in the milk of nursing mothers. Cefazolin should be administered with caution to a nursing woman.
Children: The safety of the use of cefazolin in prematures and infants under 1 month of age has not been established.
Drug Interactions: The renal tubular secretion of cefazolin may be decreased when probenecid is used concurrently, resulting in increased and prolonged cefazolin blood levels.
Adverse Reactions: The following reactions have been reported: Gastrointestinal: diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia. During antibiotic treatment symptoms of pseudomembranous colitis can appear. There have been rare reports of nausea and vomiting.
Allergic: Allergic reactions occur infrequently and include: anaphylaxis, eosinophilia, itching, drug fever, skin rash. Hematologic: neutropenia, anemia, leukopenia, thrombocythemia, positive direct and indirect antiglobulin (Coombs') tests.
Hepatic and Renal: Without clinical evidence of renal or hepatic impairment transient increases in AST, ALT, BUN and alkaline phosphatase levels have been observed. Transient hepatitis and cholestatic jaundice have been reported rarely, as with some penicillins and some other cephalosporins. Local: Phlebitis at the site of injection has occurred rarely. Infrequently there is pain at the site of injection following i.m. injection. Some induration has been reported. Other: vulvar pruritus, genital moniliasis, vaginitis and anal pruritus.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: There is a lack of experience with acute cefazolin overdosage. Supportive therapy should be instituted according to symptoms in cases of suspected overdosage. tag_DosageDosage
Dosage And Administration: After reconstitution cefazolin may be administered either i.m. or i.v. In both cases total daily dosages are the same. Cefazolin has been administered in dosages of 6 g/day in serious infections such as endocarditis. Treatment should be continued for at least 10 days in beta-hemolytic streptococcal infections to minimize possible complications associated with the disease.
Patients with Reduced Renal Function: After an initial loading dose appropriate to the severity of the infection, the following reduced dosage schedule is recommended (see Table II).
Perioperative Prophylactic Use: The recommended dosage regimen to prevent postoperative infection in contaminated or potentially contaminated surgery is: a) 1 g i.v. or i.m. administered 1/2 hour to 1 hour prior to the start of surgery so that at the time of the initial surgical incision adequate antibiotic levels are present in the serum and tissues. b) For lengthy operative procedures (e.g., 2 hours or more) 0.5 to 1 g administered i.v. or i.m. during surgery.
(Administration should be modified according to the duration of the operative procedure and the time of greatest exposure to infective organisms.) c) Postoperatively, 0.5 to 1 g i.v. or i.m. every 6 to 8 hours for 24 hours postoperatively. The prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery in which the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic athroplasty).
Children: A total daily dosage of 25 to 50 mg/kg of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections in children. For severe infections total daily dosage may be increased to 100 mg/kg of body weight. The use of cefazolin in prematures and in infants under 1 month is not recommended since the safety for use in these patients has not been established.
Pediatric Dosage Guide: See Tables III and IV. Treatment with 60% of the normal daily dose may be administered in divided doses every 12 hours to children with mild to moderate renal impairment (Ccr 0.67 to 1.17 mL/s). Children with moderate to severe renal impairment (Ccr 0.33 to 0.87 mL/s) should be given 25% of the normal daily dose in equally divided doses every 12 hours, and children with severe renal impairment (Ccr 0.08 to 0.33 mL/s) should receive 10% of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.
Administration:
Note: See Reconstitution and Dilution directions below: I.M.: Inject the reconstituted solution into a large muscle mass. Pain on injection of cefazolin occurs infrequently.
I.V.: Direct (bolus) Injection: Inject the appropriately diluted reconstituted solution slowly over 3 to 5 minutes directly into a vein or through tubing for patients receiving parenteral fluids. (See list of solutions for i.v. infusion.)
Intermittent or Continuous Infusion: The reconstituted solution can be administered along with primary i.v. fluid management programs in a volume control set or in a separate secondary i.v. bottle. (See list of solutions for i.v. infusion.)
Reconstituted Solutions: Parenteral drug products should be shaken well when reconstituted, and inspected visually for particulate matter prior to administration. The drug solutions should be discarded if particulate matter is evident in reconstituted fluids. Reconstituted solutions may range in color from pale yellow to yellow without a change in potency. Reconstituted cefazolin may be stored for 24 hours at controlled room temperature not exceeding 25°C, or for 72 hours under refrigeration (2 to 8°C), protected from light. Cefazolin solution reconstituted with bacteriostatic diluent and used for i.m. administration as multiple-dose containers should be used within 6 days when stored under refrigeration. The pharmacy bulk vial is intended for multiple dispensing for i.v. use only, employing a single puncture. Following reconstitution, the solution should be dispensed and diluted for use within 8 hours. Any unused reconstituted solution should be discarded after 8 hours.
I.M. Injection: Single Dose Vials: Reconstitute according to Table V. Shake well.
Direct I.V. (bolus) Injection: Single Dose Vial: Reconstitute as directed above. Shake well. A minimum of 10 mL of Sterile Water for Injection should be used to dilute the reconstituted solution.
Pharmacy Bulk Vial: Pharmacy Bulk Vials should be used for i.v. use only. Add, according to Table VI, Sterile Water for Injection, Bacteriostatic Water for Injection, or Sodium Chloride Injection. Shake well. The vial is intended for single puncture and multiple dispensing, and the vial contents should be used within 8 hours.
Intermittent or continous i.v. infusion, reconstituted cefazolin may be further diluted as follows: Single Dose Vials: Reconstitute according to Table V. Shake well.
Further dilute the reconstituted cefazolin in 50 to 100 mL of Sterile Water for Injection or 50 to 100 mL of one of the following solutions: Sodium Chloride Injection 0.9%, Dextrose Injection 5% or 10%, Dextrose 5% in Lactated Ringer's Injection, Dextrose 5% and Sodium Chloride Injection 0.9% (also may be used with Dextrose 5% and Sodium Chloride Injection 0.45% or 0.2%), Lactated Ringer's Injection, Ringer's Injection, Sodium Bicarbonate 5% in Sterile Water for Injection. Pharmacy Bulk Vial: Reconstitute according to Table VI. Shake well.
Further dilute aliquots in 50 to 100 mL of Sterile Water for Injection or one of the solutions listed above. The further diluted solutions above should be used within 24 hours at room temperature or 72 hours under refrigeration from the time of initial puncture.
Extended Use of I.V. Admixtures: Although i.v. admixtures may often be physically and chemically stable for longer periods, due to microbiological considerations, they are usually recommended for use within the maximum of 24 hours at room temperature or 72 hours when refrigerated (2 to 8°C). Hospitals and institutions, that have recognized admixture programs and use validated aseptic techniques for preparation of i.v. solutions, may extend the storage times for cefazolin in admixtures with 5% Dextrose Injection or 0.9% Sodium Chloride Injection in Viaflex bags in 80 mg/mL concentrations to 30 days when stored under refrigeration (2 to 8°C) and in 5 mg/mL concentrations to 72 hours when stored under refrigeration (2 to 8°C).
Availability And Storage: 500 mg: Each clear glass vial of sterile powder contains: cefazolin 500 mg. Preservative-free. 1 g: Each clear glass vial of sterile powder contains: cefazolin 1 g.
Preservative-free. 10 g: Each pharmacy bulk vial of sterile powder contains: cefazolin 10 g.
Preservative-free. The availability of the pharmacy bulk vial is intended for hospitals with a recognized i.v. admixture program. Store between 15 and 25°C, protect from light.
RxMed
About your treatment
Your doctor has ordered cefazolin, an antibiotic, to help treat your infection. The drug will be either injected into a large muscle (such as your buttock or hip) or added to an intravenous fluid that will drip through a needle or catheter placed in your vein for 30 minutes, two to four times a day.
Cefazolin eliminates bacteria that cause many kinds of infections, including lung, skin, bone, joint, stomach, blood, heart valve, and urinary tract infections. This medication is sometimes prescribed for other uses; ask your doctor or pharmacist for more information.
Your health care provider (doctor, nurse, or pharmacist) may measure the effectiveness and side effects of your treatment using laboratory tests and physical examinations. It is important to keep all appointments with your doctor and the laboratory. The length of treatment depends on how your infection and symptoms respond to the medication.
Precautions
Before administering cefazolin:
tell your doctor and pharmacist if you are allergic to cefazolin, any other cephalosporin [e.g., cefaclor (Ceclor), cefadroxil (Duricef), or cephalexin (Keflex)], penicillins, or any other drugs.
tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially other antibiotics, probenecid (Benemid), and vitamins.
tell your doctor if you have or have ever had kidney, liver, or gastrointestinal disease (especially colitis).
tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking cefazolin, call your doctor.
if you have diabetes and regularly check your urine for sugar, use Clinistix or TesTape. Do not use Clinitest tablets because cefazolin may cause false positive results.
Administering your medication
Before you administer cefazolin, look at the solution closely. It should be clear and free of floating material. Gently squeeze the bag or observe the solution container to make sure there are no leaks. Do not use the solution if it is discolored, if it contains particles, or if the bag or container leaks. Use a new solution, but show the damaged one to your health care provider.
It is important that you use your medication exactly as directed. Do not stop your therapy on your own for any reason because your infection could worsen and result in hospitalization. Do not change your dosing schedule without talking to your health care provider. Your health care provider may tell you to stop your infusion if you have a mechanical problem (such as a blockage in the tubing, needle, or catheter); if you have to stop an infusion, call your health care provider immediately so your therapy can continue.
Side effect
Cefazolin may cause side effects. If you are administering cefazolin into a muscle, it may be mixed with lidocaine (Xylocaine) to reduce pain at the injection site. Tell your health care provider if any of these symptoms are severe or do not go away:
diarrhea
stomach pain
upset stomach
vomiting
If you experience any of the following symptoms, call your health care provider immediately:
skin rash
itching
hives
unusual bleeding or bruising
difficulty breathing
sore mouth or throat
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online
or by phone [1-800-332-1088].
Storing your medication
Your health care provider probably will give you a several-day supply of cefazolin at a time. If you are receiving cefazolin intravenously (in your vein), you probably will be told to store it in the refrigerator or freezer.
Take your next dose from the refrigerator 1 hour before using it; place it in a clean, dry area to allow it to warm to room temperature.
If you are told to store additional cefazolin in the freezer, always move a 24-hour supply to the refrigerator for the next day's use.
Do not refreeze medications.
If you are receiving cefazolin intramuscularly (in your muscle), your health care provider will tell you how to store it properly.
Store your medication only as directed. Make sure you understand what you need to store your medication properly.
Keep your supplies in a clean, dry place when you are not using them, and keep all medications and supplies out of reach of children. Your health care provider will tell you how to throw away used needles, syringes, tubing, and containers to avoid accidental injury.
In case of emergency/overdose
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Signs of infection
If you are receiving cefazolin in your vein or under your skin, you need to know the symptoms of a catheter-related infection (an infection where the needle enters your vein or skin). If you experience any of these effects near your intravenous catheter, tell your health care provider as soon as possible:
tenderness
warmth
irritation
drainage
redness
swelling
pain
Brand names
Ancef®
Last Revised - 08/01/2006
Medline Plus
* * * * * *
CEFAZOLIN SODIUM USP
Action And Clinical Pharmacology: Cefazolin is a cephalosporin antibiotic for parenteral administration. Cefazolin exerts its bactericidal effect by inhibiting bacterial cell wall synthesis. Cefazolin is about 85% bound to serum protein. The peak level in serum is approximately 32 to 42 mg/mL after an i.m. injection of 500 mg. Over 80% of injected cefazolin is excreted in the urine during the first 24 hours after i.m. injection; most is excreted during the first 4 to 6 hours. tag_Indications
Indications Indications And Clinical Uses: In the treatment of the following infections when caused by susceptible strains of the listed organisms: Respiratory tract infections caused by S. pneumoniae, K. pneumoniae, H. influenzae, S. aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci.
Urinary tract infections caused by E. coli, P. mirabilis, K. pneumoniae and some strains of enterobacter, and enterococci. See Note below.
Skin and soft tissue infections caused by S. aureus (penicillin-sensitive and penicillin-resistant), group A beta-hemolytic streptococci and other strains of streptococci.
Bone and joint infections caused by S. aureus. Septicemia caused by S. pneumoniae, S. aureus (penicillin-sensitive and penicillin-resistant), P. mirabilis, E. coli and K. pneumoniae. See Note below.
Endocarditis caused by S. aureus (penicillin-sensitive and penicillin-resistant) and group A beta-hemolytic streptococci. Determine susceptibility of the causative organism to cefazolin by performing appropriate culture and susceptibility studies. Note: Most strains of Enterococci, indole positive Proteus (P. vulgaris).
E. cloacae, M. morganii, P. rettgeri and methicillin-resistant Staphylococci are resistant.
Serratia, Pseudomonas and A. calcoaceticus (formerly Mima and Herellea species) are almost uniformly resistant to cefazolin.
Perioperative Prophylaxis: In patients undergoing potentially contaminated surgical procedures, and in patients in whom infection would pose a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty), the preoperative, intraoperative and postoperative administration of cefazolin may reduce the incidence of certain postoperative infections. Identification of the causative organisms should be made by culture should signs of infection occur, so that appropriate therapy may be instituted.
Contra-Indications: In patients with known allergy to the cephalosporin group of antibiotics. tag_Warning
Warnings Manufacturers' Warnings In Clinical States: Use with caution in penicillin-allergic patients. There is clinical evidence of partial cross-allergenicity of the penicillins and the cephalosporins. There are instances of patients who have had reactions to both penicillins and cephalosporins (including fatal anaphylaxis after parenteral use). Clinical and laboratory evidence of partial cross-allergenicity of the 2 drug classes exists.
Cefazolin should be administered cautiously and then only when absolutely necessary to any patient who has demonstrated allergy, particularly to drugs. Immediate emergency treatment with epinephrine is indicated for serious anaphylactoid reactions. As indicated, oxygen, i.v. steroids, and airway management, including intubation, should also be employed.
There have been reports of pseudomembranous colitis with the use of cephalosporins. It is therefore important to consider its diagnosis in patients who develop diarrhea in association with antibiotic use.
Precautions: The overgrowth of nonsusceptible organisms may result from the prolonged use of cefazolin. It is essential that the patient be carefully observed.
In patients with a history of lower gastrointestinal disease, particularly colitis, cefazolin should be prescribed with caution. Clinitest tablets solution, but not enzyme-based tests such as Clinistix and Tes-Tape, may falsely indicate glucose in the urine of patients on cefazolin.
Positive direct and indirect Coombs' tests have been reported during treatment with cefazolin. These may also occur in neonates whose mothers received cephalosporins before delivery. The clinical significance of this effect has not been established.
Renal Impairment: Caution should be exercised in treating patients with pre-existing renal damage although cefazolin has not shown evidence of nephrotoxicity.
Patients with low urinary output due to impaired renal function should be administered reduced daily dosages of cefazolin. (See Dosage, Patients with Reduced Renal Function.) Blood levels of cefazolin in dialysis patients remain fairly high and should be monitored.
Probenecid may decrease renal tubular secretion of cefazolin when used concurrently with cefazolin, resulting in increased and prolonged cefazolin blood levels.
In beta-hemolytic streptococcal infections, treatment should be continued for at least 10 days, to minimize possible complications associated with the disease.
Pregnancy: The safety of the use of cefazolin during pregnancy has not been established.
Lactation: Very low concentrations of cefazolin are found in the milk of nursing mothers. Cefazolin should be administered with caution to a nursing woman.
Children: The safety of the use of cefazolin in prematures and infants under 1 month of age has not been established.
Drug Interactions: The renal tubular secretion of cefazolin may be decreased when probenecid is used concurrently, resulting in increased and prolonged cefazolin blood levels.
Adverse Reactions: The following reactions have been reported: Gastrointestinal: diarrhea, oral candidiasis (oral thrush), vomiting, nausea, stomach cramps, anorexia. During antibiotic treatment symptoms of pseudomembranous colitis can appear. There have been rare reports of nausea and vomiting.
Allergic: Allergic reactions occur infrequently and include: anaphylaxis, eosinophilia, itching, drug fever, skin rash. Hematologic: neutropenia, anemia, leukopenia, thrombocythemia, positive direct and indirect antiglobulin (Coombs') tests.
Hepatic and Renal: Without clinical evidence of renal or hepatic impairment transient increases in AST, ALT, BUN and alkaline phosphatase levels have been observed. Transient hepatitis and cholestatic jaundice have been reported rarely, as with some penicillins and some other cephalosporins. Local: Phlebitis at the site of injection has occurred rarely. Infrequently there is pain at the site of injection following i.m. injection. Some induration has been reported. Other: vulvar pruritus, genital moniliasis, vaginitis and anal pruritus.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: There is a lack of experience with acute cefazolin overdosage. Supportive therapy should be instituted according to symptoms in cases of suspected overdosage. tag_DosageDosage
Dosage And Administration: After reconstitution cefazolin may be administered either i.m. or i.v. In both cases total daily dosages are the same. Cefazolin has been administered in dosages of 6 g/day in serious infections such as endocarditis. Treatment should be continued for at least 10 days in beta-hemolytic streptococcal infections to minimize possible complications associated with the disease.
Patients with Reduced Renal Function: After an initial loading dose appropriate to the severity of the infection, the following reduced dosage schedule is recommended (see Table II).
Perioperative Prophylactic Use: The recommended dosage regimen to prevent postoperative infection in contaminated or potentially contaminated surgery is: a) 1 g i.v. or i.m. administered 1/2 hour to 1 hour prior to the start of surgery so that at the time of the initial surgical incision adequate antibiotic levels are present in the serum and tissues. b) For lengthy operative procedures (e.g., 2 hours or more) 0.5 to 1 g administered i.v. or i.m. during surgery.
(Administration should be modified according to the duration of the operative procedure and the time of greatest exposure to infective organisms.) c) Postoperatively, 0.5 to 1 g i.v. or i.m. every 6 to 8 hours for 24 hours postoperatively. The prophylactic administration of cefazolin may be continued for 3 to 5 days following the completion of surgery in which the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic athroplasty).
Children: A total daily dosage of 25 to 50 mg/kg of body weight, divided into 3 or 4 equal doses, is effective for most mild to moderately severe infections in children. For severe infections total daily dosage may be increased to 100 mg/kg of body weight. The use of cefazolin in prematures and in infants under 1 month is not recommended since the safety for use in these patients has not been established.
Pediatric Dosage Guide: See Tables III and IV. Treatment with 60% of the normal daily dose may be administered in divided doses every 12 hours to children with mild to moderate renal impairment (Ccr 0.67 to 1.17 mL/s). Children with moderate to severe renal impairment (Ccr 0.33 to 0.87 mL/s) should be given 25% of the normal daily dose in equally divided doses every 12 hours, and children with severe renal impairment (Ccr 0.08 to 0.33 mL/s) should receive 10% of the normal daily dose every 24 hours. All dosage recommendations apply after an initial loading dose.
Administration:
Note: See Reconstitution and Dilution directions below: I.M.: Inject the reconstituted solution into a large muscle mass. Pain on injection of cefazolin occurs infrequently.
I.V.: Direct (bolus) Injection: Inject the appropriately diluted reconstituted solution slowly over 3 to 5 minutes directly into a vein or through tubing for patients receiving parenteral fluids. (See list of solutions for i.v. infusion.)
Intermittent or Continuous Infusion: The reconstituted solution can be administered along with primary i.v. fluid management programs in a volume control set or in a separate secondary i.v. bottle. (See list of solutions for i.v. infusion.)
Reconstituted Solutions: Parenteral drug products should be shaken well when reconstituted, and inspected visually for particulate matter prior to administration. The drug solutions should be discarded if particulate matter is evident in reconstituted fluids. Reconstituted solutions may range in color from pale yellow to yellow without a change in potency. Reconstituted cefazolin may be stored for 24 hours at controlled room temperature not exceeding 25°C, or for 72 hours under refrigeration (2 to 8°C), protected from light. Cefazolin solution reconstituted with bacteriostatic diluent and used for i.m. administration as multiple-dose containers should be used within 6 days when stored under refrigeration. The pharmacy bulk vial is intended for multiple dispensing for i.v. use only, employing a single puncture. Following reconstitution, the solution should be dispensed and diluted for use within 8 hours. Any unused reconstituted solution should be discarded after 8 hours.
I.M. Injection: Single Dose Vials: Reconstitute according to Table V. Shake well.
Direct I.V. (bolus) Injection: Single Dose Vial: Reconstitute as directed above. Shake well. A minimum of 10 mL of Sterile Water for Injection should be used to dilute the reconstituted solution.
Pharmacy Bulk Vial: Pharmacy Bulk Vials should be used for i.v. use only. Add, according to Table VI, Sterile Water for Injection, Bacteriostatic Water for Injection, or Sodium Chloride Injection. Shake well. The vial is intended for single puncture and multiple dispensing, and the vial contents should be used within 8 hours.
Intermittent or continous i.v. infusion, reconstituted cefazolin may be further diluted as follows: Single Dose Vials: Reconstitute according to Table V. Shake well.
Further dilute the reconstituted cefazolin in 50 to 100 mL of Sterile Water for Injection or 50 to 100 mL of one of the following solutions: Sodium Chloride Injection 0.9%, Dextrose Injection 5% or 10%, Dextrose 5% in Lactated Ringer's Injection, Dextrose 5% and Sodium Chloride Injection 0.9% (also may be used with Dextrose 5% and Sodium Chloride Injection 0.45% or 0.2%), Lactated Ringer's Injection, Ringer's Injection, Sodium Bicarbonate 5% in Sterile Water for Injection. Pharmacy Bulk Vial: Reconstitute according to Table VI. Shake well.
Further dilute aliquots in 50 to 100 mL of Sterile Water for Injection or one of the solutions listed above. The further diluted solutions above should be used within 24 hours at room temperature or 72 hours under refrigeration from the time of initial puncture.
Extended Use of I.V. Admixtures: Although i.v. admixtures may often be physically and chemically stable for longer periods, due to microbiological considerations, they are usually recommended for use within the maximum of 24 hours at room temperature or 72 hours when refrigerated (2 to 8°C). Hospitals and institutions, that have recognized admixture programs and use validated aseptic techniques for preparation of i.v. solutions, may extend the storage times for cefazolin in admixtures with 5% Dextrose Injection or 0.9% Sodium Chloride Injection in Viaflex bags in 80 mg/mL concentrations to 30 days when stored under refrigeration (2 to 8°C) and in 5 mg/mL concentrations to 72 hours when stored under refrigeration (2 to 8°C).
Availability And Storage: 500 mg: Each clear glass vial of sterile powder contains: cefazolin 500 mg. Preservative-free. 1 g: Each clear glass vial of sterile powder contains: cefazolin 1 g.
Preservative-free. 10 g: Each pharmacy bulk vial of sterile powder contains: cefazolin 10 g.
Preservative-free. The availability of the pharmacy bulk vial is intended for hospitals with a recognized i.v. admixture program. Store between 15 and 25°C, protect from light.
RxMed
Tuesday, November 28, 2006
Single Dose Of Antibiotics Before Surgery
Single Dose Of Antibiotics Before Surgery Sufficient To Help Prevent Infection
Main Category: Infectious Diseases / Bacteria / Viruses News
Article Date: 26 Nov 2006 - 23:00pm (PST)
A single dose of antibiotics prior to surgery appears to prevent infections occurring at the surgical site as effectively as a 24-hour dosing regimen, and with reduced antibiotic costs, according to an article in the November issue of Archives of Surgery, one of the JAMA/Archives journals. Infections remain an important complication of surgical procedures despite increased knowledge about prevention and technological advances in modern surgery, according to background information in the article.
Prophylactic antibiotics--preventive antibiotics given before surgery--have been shown to decrease the occurrence of infection at the site of the surgery. However, due to rising health care costs and concerns about antimicrobial resistance, hospitals have been under pressure to use fewer antibiotics. Most guidelines for the use of prophylactic antibiotics recommend using only one dose prior to surgery; however, surgeons might not comply with this recommendation, sometimes giving patients more than one dose or using broad-spectrum (targeting many types of bacteria) rather than the recommended narrow-spectrum drugs. Silvia Nunes Szente Fonseca, M.D., M.P.H., Hospital Sao Francisco, Ribeirao Preto, Sao Paolo, Brazil, and colleagues studied infection rates before and after the implementation of a one-dose prophylactic antibiotic protocol at a local hospital. "We previously described the successful implementation of an antibiotic prophylaxis program in our hospital, discontinuing prophylactic antibiotic usage after 24 hours and correcting the timing of the first dosage," the authors write. "We decided to reduce all antibiotic prophylaxis to one dose because this measure could safely promote savings for our institution."
Under the new protocol, for most procedures, patients are given one 1-gram dose of the antibiotic cephazolin at the same time anesthesia is administered. The protocol was approved by surgeons prior to implementation; education was provided to surgical and medical staff. To assess the effectiveness of this approach, the researchers examined infection rates and costs for 6,140 consecutive patients who had surgery between February 2002 and October 2002 and 6,159 consecutive patients who had surgery between December 2002 and August 2003, following the implementation of the one-dose protocol.
The correct protocol was followed in 6,123 (99 percent) of the surgeries performed after the new guidelines were implemented. Surgical site infections occurred in 127 (2 percent) of surgeries performed under the 24-hour protocol and 133 (2.1 percent) performed under the one-dose protocol. The number of vials of cephazolin purchased decreased from 1,259 in the first time period to 467 in the second, a 63 percent decline that represented a monthly cost savings of $1,980 for this drug alone. The cooperation and encouragement of hospital administration and clinical staff, as well as educational efforts, contributed to the success of the new protocol, the authors write. "We were able to demonstrate that one-dose prophylaxis is feasible," they conclude. "In this era of restricted hospital budgets and increased bacterial resistance, one-dose prophylaxis may provide a way to improve performance by lowering costs." ### (Arch Surg. 2006;141:1109-1113.)
This study was supported by the Waldemar Barnsley Pessoa Foundation and Maternidade Sinha Junqueira Foundation.
Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Contact: Silvia Nunes Szente Fonseca
JAMA and Archives Journals
Main Category: Infectious Diseases / Bacteria / Viruses News
Article Date: 26 Nov 2006 - 23:00pm (PST)
A single dose of antibiotics prior to surgery appears to prevent infections occurring at the surgical site as effectively as a 24-hour dosing regimen, and with reduced antibiotic costs, according to an article in the November issue of Archives of Surgery, one of the JAMA/Archives journals. Infections remain an important complication of surgical procedures despite increased knowledge about prevention and technological advances in modern surgery, according to background information in the article.
Prophylactic antibiotics--preventive antibiotics given before surgery--have been shown to decrease the occurrence of infection at the site of the surgery. However, due to rising health care costs and concerns about antimicrobial resistance, hospitals have been under pressure to use fewer antibiotics. Most guidelines for the use of prophylactic antibiotics recommend using only one dose prior to surgery; however, surgeons might not comply with this recommendation, sometimes giving patients more than one dose or using broad-spectrum (targeting many types of bacteria) rather than the recommended narrow-spectrum drugs. Silvia Nunes Szente Fonseca, M.D., M.P.H., Hospital Sao Francisco, Ribeirao Preto, Sao Paolo, Brazil, and colleagues studied infection rates before and after the implementation of a one-dose prophylactic antibiotic protocol at a local hospital. "We previously described the successful implementation of an antibiotic prophylaxis program in our hospital, discontinuing prophylactic antibiotic usage after 24 hours and correcting the timing of the first dosage," the authors write. "We decided to reduce all antibiotic prophylaxis to one dose because this measure could safely promote savings for our institution."
Under the new protocol, for most procedures, patients are given one 1-gram dose of the antibiotic cephazolin at the same time anesthesia is administered. The protocol was approved by surgeons prior to implementation; education was provided to surgical and medical staff. To assess the effectiveness of this approach, the researchers examined infection rates and costs for 6,140 consecutive patients who had surgery between February 2002 and October 2002 and 6,159 consecutive patients who had surgery between December 2002 and August 2003, following the implementation of the one-dose protocol.
The correct protocol was followed in 6,123 (99 percent) of the surgeries performed after the new guidelines were implemented. Surgical site infections occurred in 127 (2 percent) of surgeries performed under the 24-hour protocol and 133 (2.1 percent) performed under the one-dose protocol. The number of vials of cephazolin purchased decreased from 1,259 in the first time period to 467 in the second, a 63 percent decline that represented a monthly cost savings of $1,980 for this drug alone. The cooperation and encouragement of hospital administration and clinical staff, as well as educational efforts, contributed to the success of the new protocol, the authors write. "We were able to demonstrate that one-dose prophylaxis is feasible," they conclude. "In this era of restricted hospital budgets and increased bacterial resistance, one-dose prophylaxis may provide a way to improve performance by lowering costs." ### (Arch Surg. 2006;141:1109-1113.)
This study was supported by the Waldemar Barnsley Pessoa Foundation and Maternidade Sinha Junqueira Foundation.
Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc. Contact: Silvia Nunes Szente Fonseca
JAMA and Archives Journals
Tuesday, November 07, 2006
Dalbavancin: A review for dermatologists.
Dalbavancin: A review for dermatologists.
1: Dermatol Online J. 2006 May 30;12(4):6.
Scheinfeld N.
Department of Dermatology, St Lukes Roosevelt Hospital, New York.
Most complicated skin and skin structure infections (cSSSI) are caused by Staphylococcus aurens (SA) and streptococcus (SC). More and more isolates of SA and SC are resistant to methicillin (MRSA) and there are concerns that SA will become resistant to vancomycin (VRSA), the current standard of treatment. Dalbavancin (BI397) is a novel semisynthetic lipoglycopeptide that was designed to improve uon the natural glycopeptides currently available, vancomycin and teicoplanin. Phase-III clinical trials comprising more than 1,500 patients evaluating once-weekly dalbavancin in skin and soft tissue infections (SSTIs) associated with Gram-positive bacteria met the primary endpoint of non-inferiority in patients whose clinical response was evaluated at 2 weeks following therapy when compared to linezolid, cefazolin, or vancomycin, the three most widely administered standard-of-care agents for SSTIs. The side effect profile of dalbavancin is mild, with headache and pyrexia being the most adverse effects.
Once-a-week dosing with dalbavancin may obviate the need for the continued presence of IV lines in some patients, which could translate into fewer local infections and blood stream infections and which could facilitate transfer of the patients to skilled nursing facilities. Unlike other new antibiotics, such as oritavancin and tigecycline, dalbavancin is not active against vancomycin-resistant enterococcus or VRSA. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred other newer agents such as linezolid.
1: Dermatol Online J. 2006 May 30;12(4):6.
Scheinfeld N.
Department of Dermatology, St Lukes Roosevelt Hospital, New York.
Most complicated skin and skin structure infections (cSSSI) are caused by Staphylococcus aurens (SA) and streptococcus (SC). More and more isolates of SA and SC are resistant to methicillin (MRSA) and there are concerns that SA will become resistant to vancomycin (VRSA), the current standard of treatment. Dalbavancin (BI397) is a novel semisynthetic lipoglycopeptide that was designed to improve uon the natural glycopeptides currently available, vancomycin and teicoplanin. Phase-III clinical trials comprising more than 1,500 patients evaluating once-weekly dalbavancin in skin and soft tissue infections (SSTIs) associated with Gram-positive bacteria met the primary endpoint of non-inferiority in patients whose clinical response was evaluated at 2 weeks following therapy when compared to linezolid, cefazolin, or vancomycin, the three most widely administered standard-of-care agents for SSTIs. The side effect profile of dalbavancin is mild, with headache and pyrexia being the most adverse effects.
Once-a-week dosing with dalbavancin may obviate the need for the continued presence of IV lines in some patients, which could translate into fewer local infections and blood stream infections and which could facilitate transfer of the patients to skilled nursing facilities. Unlike other new antibiotics, such as oritavancin and tigecycline, dalbavancin is not active against vancomycin-resistant enterococcus or VRSA. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred other newer agents such as linezolid.
PMID: 17083861 [PubMed - in process]
* * * * * *
Dalbavancin: a new option for the treatment of gram-positive infections.
1: Ann Pharmacother. 2006 Mar;40(3):449-60. Epub 2006 Feb 28
NEW DRUG DEVELOPMENTS
Dalbavancin: A New Option for the Treatment of Gram-Positive Infections Shu-Wen Lin, MS PharmD
at time of writing, Specialty Resident in Infectious Diseases, Department of Pharmacy Services, University of Michigan Health System; Clinical Instructor, Department of Clinical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI; now, Clinical Pharmacist, Infectious Diseases, Department of Pharmacy Services, Hahnemann University Hospital, Philadelphia, PA
Peggy L Carver, PharmD
Clinical Pharmacist in Infectious Diseases, Department of Pharmacy Services, University of Michigan Health System; Associate Professor, Department of Clinical Sciences, College of Pharmacy, University of Michigan
Daryl D DePestel, PharmD
Clinical Pharmacist in Infectious Diseases, Department of Pharmacy Services, University of Michigan Health System; Clinical Assistant Professor, Department of Clinical Sciences, College of Pharmacy, University of Michigan
Reprints: Dr. DePestel, Departments of Pharmacy Services and Clinical Sciences, University of Michigan Health System, UH B2D 301/0008, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0008, fax 734/936-7027, daryldd@umich.edu
OBJECTIVE:
To review the pharmacology, microbiology, chemistry, in vitro susceptibility, pharmacokinetics, clinical efficacy, safety, tolerability, dosage, and administration of dalbavancin, a new semisynthetic lipoglycopeptide.
DATA SOURCES:
A MEDLINE search, restricted to the English language, was conducted from 1966 through January 2006. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society of Microbiology, and the Infectious Diseases Society of America from 2000 to 2005 and information available from the manufacturer's Web site.
STUDY SELECTION AND DATA EXTRACTION:
In vitro and preclinical studies, as well as Phase I, II, and III clinical trials, were evaluated to summarize the microbiology, pharmacology, clinical efficacy, and safety of dalbavancin. All published trials and abstracts citing dalbavancin were selected.
DATA SYNTHESIS:
Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of gram-positive organisms, but no activity against gram-negative or vancomycin-resistant enterococci that possess VanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events are mild and limited; the most common include pyrexia, headache, nausea, oral candidiasis, diarrhea, and constipation.
CONCLUSIONS:
Dalbavancin appears to be a promising antimicrobial agent for the treatment of gram-positive infections. A new drug application was filed with the Food and Drug Administration (FDA) in December 2004. The FDA issued an approvable letter in 2005 for dalbavancin. If approved, dalbavancin is expected to be launched in the first quarter of 2006.
Key Words: BI397, dalbavancin, glycopeptide, gram-positive
Published Online, February 28, 2006. DOI 10.1345/aph.1G158
* * * * * *Dalbavancin activity against selected populations of antimicrobial-resistant Gram-positive pathogens.
Diagn Microbiol Infect Dis. 2005 Dec;53(4):307-10.
Streit JM,
Sader HS,
Fritsche TR,
Jones RN.
The JONES Group/JMI Laboratories, North Liberty, IA 52317, USA.
Dalbavancin, a dimethylaminepropyl amide derivative of the lipoglycopeptide A40926, was tested against 375 antimicrobial-resistant Gram-positive pathogens collected worldwide during 2001-2003. The isolates were tested by reference and Clinical Laboratory Standards Institute broth microdilution susceptibility methods, and dalbavancin was compared with over 20 other antimicrobials. Vancomycin resistance determinants among enterococci were identified using PCR primer sets for vanA and vanB. Dalbavancin was generally more potent than vancomycin or teicoplanin. Dalbavancin was highly active against penicillin- and ceftriaxone-resistant Streptococcus pneumoniae strains (MIC(90), < or =" 0.016">
PMID: 15922534 [PubMed - indexed for MEDLINE]
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