Antibiotic, supplement may aid Parkinson’s

Government study suggests minocycline, creatine slow worsening of disease

Associated Press
Updated: 2:42 p.m. ET Feb. 23, 2006

WASHINGTON - An antibiotic and a muscle-related compound are leading candidates for a major government study of whether certain compounds could slow the worsening of Parkinson’s disease.

A pilot study, unveiled Thursday, suggests the two — the antibiotic minocycline and creatine, a substance produced in muscle tissue — may have some benefit.
“We are not concluding that these agents are useful, just that they are not useless,” cautioned Dr. Karl Kieburtz of the University of Rochester, who led the study.

It’s far too early for patients to seek the pills, stressed Dr. Diane Murphy, who oversees Parkinson’s research at the National Institutes of Health, which funded the work.

But in the study of 200 patients in the earliest stages of the disease—they didn’t yet require medication for its symptoms—those who took either of the two pills didn’t seem to decline quite as rapidly as those given a dummy pill, scientists said Thursday at Parkinson’s meeting in Washington.

The compounds are thought to lessen a type of cellular stress or fight inflammation that may damage cells.

About 1.5 million Americans have Parkinson’s disease, which gradually destroys brain cells that produce dopamine, a chemical crucial for the cellular communication that controls muscle movement. As dopamine levels drop, symptoms increase: tremors in the arms, legs and face; periodically stiff or frozen limbs; slow movement; impaired balance and coordination.
Standard treatments are to replace lost dopamine with the drug levodopa, and a brain implant to control tremors. Both work for a while, but can’t stop the disease’s inevitable march.

Who gets Parkinson's Disease?

So NIH’s National Institute of Neurological Disorders and Stroke is on a hunt for drugs that might protect patients’ remaining dopamine-producing cells, a so-called neuroprotector. The holy grail would be a simple, easy-to-take pill that would lower the risk of worsening Parkinson’s much like an aspirin a day can lower people’s risk of heart attacks.

“We’re looking for the aspirin of Parkinson’s disease,” is how Murphy puts it. “We don’t have a drug like that right now, and we don’t know of such a drug,” she cautions.

That’s where the pilot study comes in. NIH asked Parkinson’s specialists for a list of potential neuroprotective compounds — substances that could enter the brain and seemed promising in animal studies. From an initial list of 60, they settled on four to pilot-test. The minocycline and creatine results are first in, published in the journal Neurology online this week and announced Thursday at the World Parkinson Congress. Now being analyzed is a similar study on the dietary supplement coenzyme Q-10 or CoQ10 and an experimental drug thought to help repair damaged nerves.

Next up, NIH plans to test the top candidates in a large study to prove whether any of them truly work.

Minocycline is a prescription-only antibiotic, but creatine is available in dietary supplements. Murphy cautioned that over-the-counter preparations of creatine or CoQ10 may not be the same strengths as are under study.

Article

Vancomycin: can we teach the mainstay of therapy for gram-positives new tricks?

Infectious Disease News

February 2006

Future studies will examine the role of vancomycin therapeutic drug monitoring in treating gram-positive infections.

by Megan Goodwin, PharmD, and Elizabeth Dodds Ashley, PharmD, BCPSSpecial to Infectious Disease News

Vancomycin, the only available glycopeptide antibiotic in the United States, continues to be a mainstay of therapy for gram-positive infections, especially methicillin-resistant Staphylococcus aureus (MRSA). With the incidence of MRSA exceeding 50% at many institutions, vancomycin is frequently used as part of empiric regimens as well as for treatment of documented infections.
Optimizing therapy with vancomycin is a challenge for clinicians due to several factors, including interpatient variability in pharmacokinetics. Therefore, serum concentration monitoring is often performed to ensure efficacy while preventing toxicity. One large problem, however, remains for vancomycin: the lack of standardized targets for serum concentration monitoring.

It has been historically believed that both the nephrotoxicities and ototoxicities associated with vancomycin occur as a result of elevated serum concentrations. Evidence, however, confirming causality of this theory is lacking. Most vancomycin-induced toxicity initially described was a result of older, impure formulations. The new, cleaner preparations are associated with a much lower incidence of these reactions. It is known that concomitant medications as well as underlying disease states have been and remain important risk factors for these adverse events. Still, it is generally believed that serum concentrations between 80 and 100 µg/mL may be linked to vancomycin toxicity.

Determining the appropriate target for efficacy is an even more challenging decision. Owing to the time-dependent killing properties of vancomycin, serum trough concentrations are the kinetic parameter most closely related with efficacy. Historically, a trough concentration in the range of 5 to 10 µg/mL was desired. This would easily achieve the goal concentration at two to four times the minimum inhibitory concentration (MIC) for commonly encountered organisms.
More recently, however, this target is being re-evaluated due to increasing vancomycin MICs and the growing number of vancomycin therapeutic fail ures. Some investigators have shown that MICs for Staphylococcus sp. to vancomycin have not been increasing in recent years.

Rather, perhaps “underdosing” of vancomycin is not new and has been associated with failures for decades. Independent of the reason, many clinicians are now targeting higher troughs for vancomycin (from 15 to 20 µg/mL), especially when treating more deep-seated infections (ie, meningitis, endocarditis, osteomyelitis), in which vancomycin penetration may also be an issue.

In 2005, the publication of two new sets of treatment guidelines gave clinicians published target vancomycin monitoring parameters for the first time. These recommendations are based on expert opinion, however, and remain somewhat controversial.

Pneumonia guidelines

The recent pneumonia guidelines, a joint publication from the American Thoracic Society and the Infectious Diseases Society of America (IDSA), advocate targeting higher vancomycin trough concentrations. Vancomycin is a large molecule, and we have known for sometime that penetration into the lung and other infection sites may be difficult. Therefore, increasing the target trough serum concentrations may result in higher pulmonary drug concentrations.

The recommended target vancomycin trough in these guidelines is 15 to 20 µg/mL. However, there are no specific data to say that troughs more than 15 µg/mL are associated with improved outcomes over trough levels more than 5 or 10 µg/mL. Two recent studies that compared linezolid (Zyvox, Pfizer) with vancomycin for nosocomial pneumonia were not able to find a difference between the two medications regarding treatment outcomes. However, a post hoc analysis of the combined results of the two trials showed that in patients with confirmed MRSA pneumonia, linezolid was associated with better survival and clinical cure rates. When these two studies are analyzed, one has to consider vancomycin dosing and monitoring. It appears that most patients received 1 g of vancomycin every 12 hours (a standard, nonpatient-specific dose), and plasma concentrations were not documented nor specifically targeted. For this reason, many believe that the only reason linezolid appears superior in this retrospective analysis is that vancomycin was not appropriately dosed in each patient. Hence, the recommendation in the new guidelines is higher than more traditional regimens. We hope future studies will be designed to compare clinical outcomes in patients treated with “properly dosed” vancomycin and other antimicrobials with anti-MRSA activity.

Endocarditis guidelines

Similarly, the American Heart Association in conjunction with the IDSA revised treatment recommendations for endocarditis in June 2005. The recently published endocarditis guidelines also recommend specific target concentrations for vancomycin.

Because many clinicians consider the vegetations involved in endocarditis to be relatively difficult to penetrate, the traditional target troughs were 15 to 20 µg/mL for this infection. The recent guidelines, however, recommend a lower trough concentration of 10 to 15 µg/mL. As with the pneumonia guidelines, these targets reflect the opinion of the expert panel in the absence of data to document the ideal target. As endocarditis typically presents with positive blood cultures and the location of the infection is actually inside the vascular system, the target trough of 10 to 15 µg/mL is likely reasonable. Endocarditis is also treated for a relatively long time depending on the cause and type of infection. Therefore, IV antibiotics, including vancomycin, may be continued for two to six weeks. In this situation, the targeting of vancomycin troughs of 10 to 15 µg/mL may help reduce the incidence of vancomycin toxicity.

The inclusion of peak concentration monitoring in these guidelines is intriguing. The expert panel recommended a target peak concentration of 30 to 45 µg/mL. Most clinicians rely solely on trough concentration monitoring given the predictable intrapatient kinetics of this agent and the lack of strong association for efficacy or toxicity with peak concentrations. There are specific instances in which measurement of vancomycin peak concentrations has historically been considered clinically important. These include infections located in sites that are difficult to penetrate and include central nervous system (CNS) infections, bone and joint infections and pneumonia. However, the clinical relevance or correlation of improved outcomes and specific peak concentrations has not been proven.

Therapy for resistant gram-positive infections remains challenging. Treatment strategies for these infections are evolving given the availability of new drugs and an increasing understanding of the appropriate administration for older agents. One such example is vancomycin, in which treatment regimens remain suboptimal and ill defined despite more than 50 years of use. These two recent publications are the first to document targets for vancomycin therapeutic drug monitoring. Hopefully, this will aid clinicians in maximizing efficacy of vancomycin therapy. Future studies will document the appropriateness of these recommendations and the role of vancomycin therapeutic drug monitoring in treating these infections.

For more information:

American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416.

Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anethesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111:3167-3184.

Elizabeth Dodds Ashley, PharmD, is a clinical pharmacist in Infectious Disease, and Megan Goodwin, PharmD, is a pharmacy practice resident, at Duke University in Durham, N.C.

Anxious About Antibiotics? Read This

FEBRUARY 20, 2006 03:01

by Jin-Han Lee (likeday@donga.com)
Korea News

In order to prevent the misuse of antibiotics, the government recently revealed a list of hospitals and clinics that prescribe high amounts of antibiotics.

The most commonly prescribed antibiotics, "-mycins," have played a great role in prolonging human life expectancies by eliminating germs. However, overuse of antibiotics will cause germs to gain resistance, and a vicious cycle where stronger antibiotics are used to kill stronger germs is being repeated. But we cannot afford to renounce antibiotics, either.

Professor Baek Gyeong-ran of Seoul Samsung Hospital’s Infectious Diseases Department says, “The abuse and overuse of antibiotics gives people the misconception that avoiding or taking small amounts of antibiotics is good. But reducing the amount or period of antibiotic treatments causes germs to become more tolerant.”

Let’s look at some common illnesses that require antibiotics and find out how to correctly take them.

Cases Where Antibiotics are Unnecessary—

About 90 percent of enteritis cases, otherwise known as viral or bacterial intestinal infections, in children are caused by viruses like rotaviruses and adenoviruses. These viral intestinal infections cause problems in the upper digestive organs, such as the small intestine and the stomach, and often lead to vomiting, diarrhea, and severe stomachaches.

Kang Jin-han, a pediatrician at the Catholic University of Korea’s Our Lady of Mercy Hospital says, “Rather than using antibiotics, symptoms of viral intestinal infections should be alleviated by antipyretics and pain killers.”

On the other hand, bacterial infections are caused by bacteria in the intestines, leading to liquid or hema feces, and this is when antibiotics are prescribed.

In addition, epidemic keratoconjunctivitis, or “pink eye”-type ocular infections that cause neck pain, bloody eyes, and fever do not call for antibiotics in principle. That is because the condition is naturally cured in about one to two weeks. Ocular medicine, pain relievers, and antichloristic medicines are used to reduce inflammation and pain, instead.

Antibiotics are Absolutely Necessary in the Following Cases—

Urinary infections, such as bladder and urethra infections are commonly caused by germs rather than viruses. Hence, antibiotics are more effective in such cases than other diseases.
Even common colds, if they involve secondary bacterial infections, call for the prescription of antibiotics. The most common illnesses that accompany colds are laryngitis, bronchitis, pneumonia, tympanitis, paranasal sinusitis, and tonsillitis.

In particular, bacterial paranasal sinusitis causes high fever and yellowish nasal mucus. Symptoms of bacterial laryngitis include fever and sore throat, but in the initial stages, it is often mistaken for a common cold. However, when there is no runny nose or coughing, and only high fever and a sore throat, chances are that there will be a white mucus crust inside the throat.

Common cold patients that are highly susceptible to other bacterial infections, such as pneumonia and sinusitis, are also prescribed antibiotics as precautionary measures. That is the reason why 30 to 40 percent of cold patients are prescribed antibiotics.

Varicella, or chicken pox, is also a viral disease that doesn’t need antibiotics. The blisters on the skin caused by it can become infected, however. Antibiotics are used to prevent that from happening.

On the other hand, eye sty cases are mostly bacterial infections, calling for ocular antibiotic ointments and ingested antibiotics.

The Correct Way to Take Antibiotics—

Time is very important when taking antibiotics. One should take antibiotics at regularly timed intervals. For example, if a patient is taking antibiotics three times a day, it is better to take them at eight-hour intervals rather than after meals. If the timing of antibiotic ingestion is irregular, the antibiotic-levels in the blood will fall below an effective level, and the dying germs will once again attack the body. That is why it is critical to take them regularly, even though it can be bothersome.

If the patient thinks that his or her condition has improved and stops taking antibiotics, then the illness is likely to recur. If the germs grow tolerant to the antibiotic, then treatments will have to start using another antibiotic, which will result in more antibiotics being taken.

If prescribed drugs don’t seem to be curing a problem, going to other doctors and getting more antibiotic prescriptions is not the answer. It is very likely to increase the germ-tolerance of the antibiotics being taken. The strengths and types of antibiotics are all different, and are used at different stages of illnesses. When these stages are ignored, germs grow more resistant. If one changes doctors, one should tell his or her new doctor about the antibiotics that were previously prescribed.

A side effect of taking excessive doses of antibiotics is damage to the liver and kidneys. If yellow eyes or a reduction in the amount of urine develop while taking antibiotics, consider the possibility of antibiotic side effects.

Diarrhea, fatigue, nausea, vomiting, and rashes are other side effects of antibiotics. Most of them are temporary and will stop after an antibiotic treatment ends.

Article

How Bacteria Persist Despite Antibiotics

Persistence pays off – for bacteria as well as people. Researchers at the Hebrew University of Jerusalem and Rockefeller University in New York have demonstrated the constant presence of antibiotic-tolerant “persistent cells” within bacteria colonies and have shown, through mathematical modeling, how these cells develop into “normal” cells following their survival of even heavy dosages of antibiotics.

The findings have consequences for development of new tactics for overcoming the common problem of resistance by bacteria to medicinal treatment.

It has been known for some time that when an antibiotic is administered to counteract a specific bacterium, not all of the bacterial cells may die. Persistent cells can remain that will reinfect the patient later – the condition we commonly refer to as relapse. What was not known was the exact nature of these persistent cells nor how they function.

In their research with E. coli bacteria, the Hebrew University and Rockefeller University researchers discovered that persistent cells are a kind of reserve population that is constantly being produced within bacteria, regardless of whether the bacteria are being attacked by an antibiotic or not. These cells are slow-growing and – apparently because of their “retarded” or “non-mature” state – are not susceptible to antibiotics.

Translating their observations into a mathematical model, the researchers have shown how these persistent cells slowly but surely continue growing until they reach a “normal” growth stage. At that point, the former persistent cells are now themselves susceptible to antibiotic attack.

The work of the researchers – Prof. Nathalie Questembert-Balaban, head of the biophysics laboratories at the HU Racah Institute of Physics; Prof. Stanislas Leibler of Rockefeller University; and his students Jack Merrin, Remy Chait and Lukasz Kowalik – appeared in a recent issue of Science magazine.

Prof. Balaban observes that if the timing could be worked out so that the persistent cells could be “hit” with antibiotics at the point that they reach a normal growth stage, then perhaps the problem of relapse could be overcome. Alternatively, perhaps further study of the nature of the persistent cells could lead to drugs that would take direct action against them in their initial state.

The discoveries by the Hebrew and Rockefeller universities scientists might also point in the direction of overcoming the problem of reoccurrence of cancer in patients who have undergone earlier, successful remission.

Slow-growing bacteria cells that are resistant to antibiotic drugs are shown in the magnified illustration at left among the other “normal” bacterial cells, and again at right showing how they have survived after the other bacterial cells have been destroyed by antibiotics. (Illustration courtesy of the Hebrew University of Jerusalem)

Hebrew University of Jerusalem

Taking Generic Form of Drug Boosts Regimen Adherence

HealthDay
By Robert Preidt
Tuesday, February 14, 2006

TUESDAY, Feb. 14 (HealthDay News) -- Patients who take generic prescription drugs are more likely to adhere to their doctor's prescribed therapy plan than patients who take brand-name drugs, a new study finds.

The findings are another reason why "generic drugs should be prescribed for patients beginning chronic therapy, as long as there are no specific clinical reasons why a branded drug may be more appropriate," researcher Dr. William Shrank, of Brigham and Women's Hospital and Harvard Medical School in Boston, said in a prepared statement.

The findings appear in the Feb. 13 issue of the journal Archives of Internal Medicine.
Shrank's group analyzed how well 6,755 patients enrolled in a three-tier pharmacy benefit structure stuck to their drug regimens. Under their benefit plan, the patients had to pay the highest co-payment for non-preferred brand-name drugs (third tier), smaller co-payments for preferred brand-name drugs (second tier), and smallest or no co-payment for generic drugs. The group received a total of 7,532 new prescriptions during the study period.

There were six classes of drugs included in the study: cholesterol-lowering statins; oral contraceptives; orally inhaled corticosteroids (asthma); and three antihypertensives (calcium-channel blockers, angiotensin receptor blockers and angiotensin converting enzyme inhibitors).

Patients who took generic drugs showed a 12.6 percent increase in therapy adherence, compared to patients who took brand-name third-tier drugs, the study found. Patients who took second-tier drugs had an 8 percent increase in adherence compared to those who used third-tier drugs.

Other findings:

Patients who took a generic drug had a 62 percent better chance of achieving adequate adherence and those who took a brand-name second-tier drug had a 30 percent better chance than those who took third-tier drugs.

Patients who were initially prescribed third-tier brand-name drugs were 2.1 times more likely to switch to a drug in another tier than patients initially prescribed generic drugs.

Patients who switched from their initial prescription were 2.8 times more likely to switch to a less-expensive, lower-tier brand-name or generic than to a higher-tier drug.

Patients who initially received generic drugs switched at less than half the rate of those who received third-tier drugs.

"Physicians commonly prescribe chronic medications for important medical problems. Both physicians and patients should be aware of how the medication choice directly influences the patient's ability to follow the prescribed treatment," Shrank said.

Copyright © 2006 ScoutNews LLC

Minocycline

mih noe SYE kleen)

Dynacin, Minocin, Vectrin

What is the most important information I should know about minocycline?

Take all of the minocycline that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated.

Children younger than 8 years of age should not take minocycline. It can cause permanent tooth discoloration, and it can affect growth.

Avoid taking multivitamins, iron supplements, antacids, and laxatives within 2 hours of taking minocycline. These products may decrease the effectiveness of minocycline.

Minocycline may decrease the effectiveness of birth control pills. Use a second method of birth control to prevent pregnancy while taking minocycline.

Avoid prolonged exposure to sunlight. Minocycline may increase the sensitivity of your skin to sunlight. Use a sunscreen and wear protective clothing when exposure to the sun is unavoidable.

What is minocycline?

Minocycline is a tetracycline antibiotic. It fights bacteria in your body.

Minocycline is used to treat many different bacterial infections, such as urinary tract infections, acne, gonorrhea, and chlamydia, among others.

Minocycline may also be used for purposes other than those listed in this medication guide.
Who should not take minocycline?

Before taking minocycline, tell your doctor if you have kidney or liver disease. You may not be able to take minocycline, or you may require a dosage adjustment or special monitoring during therapy.

Minocycline is in the FDA pregnancy category D. This means that it is known to harm an unborn baby. Minocycline may affect bone and tooth development in the developing baby. Do not take this medication without first talking to your doctor if you are pregnant.

Minocycline passes into breast milk and may affect bone and tooth development in a nursing infant. Do not take this medication without first talking to your doctor if you are breast-feeding a baby.

Children younger than 8 years of age should not take minocycline. It can cause permanent tooth discoloration, and it can affect growth.

How should I take minocycline?

Take minocycline exactly as directed by your doctor. If you do not understand these instructions, ask your pharmacist, nurse, or doctor to explain them to you.

Take each dose with a full glass of water (8 ounces).

Minocycline may be taken on an empty stomach or with food or milk.

Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours of taking minocycline. These products may reduce the effectiveness of minocycline.

Take all of the minocycline that has been prescribed for you even if you begin to feel better. Your symptoms may start to improve before the infection is completely treated.

Throw away any unused minocycline when it expires or when it is no longer needed. Do not take any minocycline after the expiration date printed on the bottle. Expired minocycline can cause a dangerous syndrome resulting in damage to the kidneys.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and take only your next regularly scheduled dose. Do not take a double dose of this medication unless otherwise directed by your doctor.
What happens if I overdose?

Seek emergency medical attention.

Symptoms of a minocycline overdose include nausea, vomiting, and diarrhea.

What should I avoid while taking minocycline?

Avoid prolonged exposure to sunlight. Minocycline increases the sensitivity of your skin to sunlight, and severe burning may result. Wear protective clothing and sunscreen if exposure to the sun is unavoidable.

Do not take iron supplements, multivitamins, calcium supplements, antacids, or laxatives within 2 hours of taking minocycline. These products may reduce the effectiveness of minocycline.

Throw away any unused minocycline when it expires or when it is no longer needed. Do not take any minocycline after the expiration date printed on the bottle. Expired minocycline can cause a dangerous syndrome resulting in damage to the kidneys.

What are the possible side effects of minocycline?

If you experience any of the following serious side effects, stop taking minocycline and seek emergency medical attention:

·an allergic reaction (swelling of your lips, face, or tongue, difficulty breathing);
·a severe headache;
·vision changes;
·confusion;
·liver damage (yellowing of the skin or eyes, nausea, abdominal pain or discomfort, unusual bleeding or bruising, severe fatigue);
·blood problems (fever, fatigue, easy bruising or bleeding); or
·genital sores or itching.

If you experience any of the following less serious side effects, continue to take minocycline and talk to your doctor:

·nausea, vomiting, diarrhea, or decreased appetite;
·dizziness or lightheadedness;
·sensitivity to the sun;
·dark "furry" tongue, black tongue, or swollen tongue; or
·vaginal yeast infection.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

What other drugs will affect minocycline?

Do not take the following drugs within 2 hours of taking minocycline because they may decrease its effectiveness:

·cholestyramine (Questran) or colestipol (Colestid);
·antacids that contain aluminum or magnesium such as Tums or Rolaids;
·bismuth subsalicylate in products such as Pepto-Bismol; or
·minerals such as iron, zinc, calcium, and magnesium, which are found in dairy products (milk, cheese, etc.), and over-the-counter vitamin and mineral supplements.

Before taking minocycline, tell your doctor if you are taking any of the following medicines:
·an anticoagulant such as warfarin (Coumadin); or
·another antibiotic.

You may not be able to take minocycline, or you may require a dosage adjustment or special monitoring during treatment if you are taking any of the medicines listed above.

Minocycline may decrease the effectiveness of birth control pills. Use a second method of birth control to prevent pregnancy while taking minocycline.

Drugs other than those listed here may also interact with minocycline. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

Where can I get more information?

Your pharmacist has additional information about minocycline written for health professionals that you may read.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2003 Cerner Multum, Inc. Version: 6.02. Revision Date: 2/14/03.

........

Medline Plus: Minocycline Oral

Medline Plus: Minocycline Dental

Minocycline - Patient Education

Marinomycins a-d, antitumor-antibiotics of a new structure class

Marinomycins a-d, antitumor-antibiotics of a new structure class from a marine actinomycete of the recently discovered genus "marinispora".

Research Abstract

Kwon HC, Kauffman CA, Jensen PR, Fenical W.

Contribution from the Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093-0204.

Four antitumor-antibiotics of a new structure class, the marinomycins A-D (1-4), were isolated from the saline culture of a new group of marine actinomycetes, for which we have proposed the name "Marinispora". The structures of the marinomycins, which are unusual macrodiolides composed of dimeric 2-hydroxy-6-alkenyl-benzoic acid lactones with conjugated tetraene-pentahydroxy polyketide chains, were assigned by combined spectral and chemical methods. In room light, marinomycin A slowly isomerizes to its geometrical isomers marinomycins B and C. Marinomycins A-D show significant antimicrobial activities against drug resistant bacterial pathogens and demonstrate impressive and selective cancer cell cytotoxicities against six of the eight melanoma cell lines in the National Cancer Institute's 60 cell line panel. The discovery of these new compounds from a new, chemically rich genus further documents that marine actinomycetes are a significant resource for drug discovery.

PMID: 16448135

[PubMed - in process]

Treatment of plague with gentamicin or doxycycline in a randomized clinical trial in Tanzania.

Mwengee W, Butler T, Mgema S, Mhina G, Almasi Y, Bradley C, Formanik JB, Rochester CG.

Regional Medical Office, Tanga, Tanzania.

trigsby@jhmi.edu.

Background.

Over the past 50 years, antibiotics of choice for treatment of plague, including streptomycin, chloramphenicol, and tetracycline, have mostly become outdated or unavailable. To test gentamicin in the treatment of naturally occurring plague and the implications of its use in the treatment of bioterrorist plague, a randomized, comparative, open-label, clinical trial comparing monotherapy with gentamicin or doxycycline was conducted in Tanzania.

Methods.

Sixty-five adults and children with symptoms of bubonic, septicemic, or pneumonic plague of duration were enrolled in the study. Bubo aspirates and blood were cultured for Yersinia pestis. Acute-phase and convalescent-phase serum samples were tested for antibody against fraction 1 antigen of Y. pestis. Thirty-five patients were randomized to receive gentamicin (2.5 mg/kg intramuscularly every 12 h for 7 days), and 30 patients were randomized to receive doxycycline (100 mg [adults] and 2.2 mg/kg [children] orally every 12 h for 7 days). Serum creatinine concentrations were measured before and after treatment, and peak and trough concentrations of antibiotics were measured.

Results.

Three patients, 2 of whom were treated with gentamicin and 1 of whom was treated with doxycycline, died on the first or second day of treatment, and these deaths were attributed to advanced disease and complications including pneumonia, septicemia, hemorrhage, and renal failure at the start of therapy. All other patients experienced cure or an improved condition after receiving therapy, resulting in favorable response rates of 94% for gentamicin (95% CI, 81.1%-99.0%) and 97% for doxycycline (95% CI, 83.4%-99.8%). Y. pestis isolates obtained from 30 patients belonged to biotype antigua and were susceptible to gentamicin and doxycycline, which had MICs of 0.13 mg/L and 0.25-0.5 mg/L, respectively. Serum concentrations of antibiotics were within therapeutic ranges, and adverse events were infrequent. Patients treated with gentamicin demonstrated a modest increase in the mean serum creatinine concentration after treatment (P<.05, by paired t test).Conclusions. Both gentamicin and doxycycline were effective therapies for adult and pediatric plague, with high rates of favorable responses and low rates of adverse events.

PMID: 16447105

[PubMed - in process]