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CERTs researchers are committed to learning more about the benefits, risks, and appropriate use of current medical therapies. The optimal use of medical therapies is a critical component in the improvement of health care. In this section, we discuss our latest findings on a number of topics, including the use of antibiotics, bacterial resistance, blood glucose monitoring in children, and the risks of side effects with commonly used medications.

CERTs researchers conduct many studies on the use of antibiotics to fight infectious diseases and the challenges that can result from the rising rates of bacterial resistance. Several of these studies examine how antibiotics should be used. Others evaluate how they are used. Still other studies evaluate approaches to reducing unnecessary use.

With the increasing incidence of infections caused by antibiotic-resistant organisms, concern is growing about the overuse of antibiotics. Very few studies have evaluated the long-term use of antibiotics in those who are relatively healthy. Acne is an illness of relatively healthy young adults, and long-term treatment with antibiotics such as tetracycline is common and accepted medical practice. Using a database in the United Kingdom, a CERTs research team identified more than 118,000 people diagnosed with acne between 1987 and 2002. Seventy-two percent received either topical or oral antibiotic treatment for more than 6 weeks.

The patients receiving antibiotics were twice as likely to develop an upper respiratory tract infection as patients not receiving antibiotics. It is not known why patients on antibiotics are more likely to develop an upper respiratory tract infection. However, it has been shown that these patients are more likely to be colonized by group A streptococcus. Antibiotics used for acne can be immune modulating and could affect the likelihood of infection. In addition, several studies have recently shown that changes in the prevalence of one microorganism can alter the infectivity of another. Additional studies are needed to more clearly differentiate these possible mechanisms. These results, carried widely by the news media, suggest that long-term use of antibiotics may be associated with increased risks of developing an infectious illness.

Intestinal bacterial flora plays a central role in the etiology of inflammatory bowel diseases. Antibiotic therapy alters bacterial flora, and as such, could influence the natural history of inflammatory bowel diseases, either increasing or decreasing the risk of exacerbation. One CERTs study examined historical data from patients with the inflammatory bowel diseases Crohn's disease and ulcerative colitis to examine the impact of antibiotic therapy on disease course.

The patients with Crohn's disease who had taken antibiotics within the past 60 days were less likely to start new inflammatory bowel disease therapies compared with patients who had not taken antibiotics during this interval, suggesting that new flares of Crohn's disease were less likely following a period of recent antibiotic therapy. Among patients suffering from ulcerative colitis, those who had taken antibiotics in the previous 60 days were neither more nor less likely to initiate new inflammatory bowel disease therapies. While this study does not justify the use of antibiotics as a primary treatment of Crohn's disease, it suggests that when used for other reasons, antibiotics are unlikely to exacerbate quiescent inflammatory bowel disease.

Several CERTs studies have focused on current trends in antibiotic use and the growing problem of antibiotic resistance in children and young adults.

CERTs researchers studied a group of college students to determine how many had throats colonized with bacteria that are often the cause of bacterial pharyngitis. They also wanted to determine if colonization was more likely in late winter and early spring, typically considered "prime time" for sore throats and other respiratory ailments. While they did not find significant seasonal differences, they did find an overall increase in the rate of colonization of Streptococcus pyogenes and Staphylococcus aureus when compared with previously reported rates. Colonization rates increased both in students who had symptoms of infection and in those who did not. In fact, the rate of colonization for Streptococcus pyogenes was higher than had been found in some previous studies of Streptococcus pyogenes infection (also called pharyngitis or Strep throat). In addition, most of these colonizing organisms were resistant to tetracycline antibiotics.

This study implies that it may be difficult to differentiate college students who are colonized with Streptococcus pyogenes from those having an infection needing antibiotics. Furthermore, the results of this study show that in college students the baseline rate of colonization by Streptococcus pyogenes is much higher than previously suspected. The results of this study are an important reference point for future studies that examine, for example, the impact of treating college students with antibiotics for a sore throat.

Children born with life-threatening heart disease often face surgery within the first few weeks of life. After surgery, a chest infection called mediastinitis can develop. While this complication is rare, it can be fatal. A CERTs research team designed a study to examine children, birth to 18 years of age, who develop mediastinitis and to find ways to reduce the risk of developing this infection.

The incidence of mediastinitis found in this study, about 1.4 percent, was similar to the rate in previous studies of adults. However, one-third of the infections were due to gram-negative bacilli (GNB), a higher percentage than previously found in studies of children. Researchers believe the higher number of GNB infections is due, at least in part, to the fact that the study included infants-a group often exposed to GNB immediately before or after birth. Sometimes surgeons do not close the patient's sternum immediately after surgery so that they can gain quick access to the area in case of internal complications. Researchers identified that this delay in closing the patient's sternum was associated with an increased risk of GNB infection.

This is concerning because GNB are frequently resistant to antibiotics. Results of this study provide important baseline information about the incidence, responsible microorganisms, and risk factors associated with mediastinitis in children. Researchers can use this information to design future studies of therapeutic interventions and prevention strategies.

Because antibiotic resistance is widespread in children and can make treatment of common infections more difficult, one CERTs study looked at the impact of antibiotic resistance on the management of childhood infections. Researchers tracked the frequency of antibiotic-resistant bacteria and antibiotic treatments in children with urinary tract infections. They found that resistant bacteria were quite common, that the frequency of resistance was affected by multiple factors, and that antibiotic resistance increased the risk of treatment failure. Additional studies on urinary tract infections and bacteria known to cause skin infections and diarrhea are underway.

Type 1 diabetes mellitus is a severe chronic disease in which the body does not produce insulin. It can occur at any age but is usually diagnosed in children and young adults. Type 1 diabetes accounts for about 3 percent of new cases of diabetes each year, with 1 new case diagnosed annually for every 7,000 children. Complications can be serious, including cardiovascular disease, blindness, and kidney disease. To avoid these complications, it is important to maintain good control of blood glucose by systematic and accurate monitoring of blood glucose levels.

A CERTs research team is conducting a study to establish the safety and efficacy of continuous blood glucose-monitoring devices in children with diabetes. Initial data suggest that continuous monitoring devices can improve control of their blood glucose levels. These results could be important in helping children with diabetes manage their condition well and increase their chances to live long, active, and healthy lives.

Some medications affect the rhythm of the heart by prolonging the QT interval, the time it takes for the electrical activity of the heart to return to baseline between each beat. This, in turn, can increase the risk of torsades de pointes, a rapid, irregular heartbeat that can be fatal.

Methadone is a synthetic narcotic medication that is less addictive than morphine or heroin. Physicians prescribe it as a substitute for other drugs in addictiontreatment programs and for chronic pain management. Methadone has been on the market for more than 45 years, and although it is safer to use than heroin, it can cause serious side effects, including death.

Physicians generally believed that methadone-related deaths are caused by overdoses, with death resulting from respiratory depression. However, now researchers know that methadone can cause irregularities in the rhythm of the heart. A CERTs research team examined data from the U.S. Food and Drug Administration (FDA) Adverse Events Reporting System to learn more about heart rhythm irregularities and deaths that occur during methadone use. Specifically, they looked at risk factors and methadone dosages in relation to QT-interval prolongation on the electrographic heart tracings and life-threatening episodes of torsades de pointes.

Although many serious heart rhythm abnormalities due to methadone occurred at high dosages, almost one-third of incidents occurred with recommended or low dosages. Additional risk factors reported for other medications known to cause torsades de pointes were also associated with the cases involving methadone. These factors include female sex, low levels of magnesium or potassium in the blood, and drugs known to block methadone metabolism. Given these results, more research is needed to fully understand the risks and how to prevent life-threatening heart rhythms in patients who are taking methadone.

Another CERTs study used a sample of 2 million health plan members from 10 health maintenance organizations (HMOs) to identify potential drug interactions involving QT-prolonging medications.

This study found that approximately 5 percent of patients taking a QT-prolonging medication also take either another QT-prolonging medication(s) or another medication that can cause an interaction between the two, thus raising the risk of a dangerous heart rhythm abnormality. Ninety percent of these drug interactions occurred in patients who had at least one other risk factor for this heart rhythm abnormality, making the risk of the drug interaction potentially even higher. Most of the potential drug interactions identified in this study involved amitriptyline (Elavil).

Educating physicians and developing automatic alerts or warning systems to target high-risk combinations might reduce the risks associated with QT-prolonging medications.

To learn more about medications that can affect the QT interval or cause torsades de pointes, visit www.qtdrugs.org

Churg-Strauss Syndrome (CSS) is a potentially lifethreatening disorder in which inflammation of the blood vessels can cause multi-organ damage, often in the presence of an unusually large number of eosinophils, a type of white blood cell. This rare syndrome can be associated with asthma, sinus infections, or allergic reactions to pollens or other allergens.

Previous research suggests a possible link between CSS and specific medications used to treat asthma; however, it is difficult to find enough cases of CSS to study because the disease is rare. The estimated annual incidence in the United States is 1 to 3 cases per 100,000 adults each year. One way of advancing CSS research is to identify cases through epidemiological reviews of large numbers of patients at risk of developing CSS.

CERTs researchers reviewed patient claims data from the HMO Research Network and figured out how to identify confirmed CSS cases. As a result of this study, researchers can make better use of existing data to learn more about the factors that trigger this rare condition.

Systemic lupus erythematosus (SLE), often referred to simply as lupus, is an autoimmune disease that leads to inflammation and damage to various bodily tissues. It is characterized by flare-ups of the disease followed by periods of wellness, or remission. When symptoms flare up, physicians typically prescribe various drugs to minimize lasting damage; however, several medications can themselves cause damage. For example, corticosteroids, often prescribed for lupus patients, have been associated with an increased risk of cataracts, osteoporosis, and strokes, among other conditions. We know that many more women than men have lupus. Lupus is three times more common in African American women than in Caucasian women and is also more common in women of Hispanic, Asian, and Native American descent.

A CERTs research team devised a study to investigate whether using hydroxychloroquine (HCQ), an antimalarial medication, was associated with less damage to the major body systems during a flare-up of SLE when compared with not treating with HCQ. They looked at 518 patients who had been suffering from SLE for 5 years or less, measured the damage they had accrued from the disease at the beginning of the study, and followed up on these assessments yearly.

Researchers divided patients into two groups-those who were taking HCQ at the beginning of the study and those who were not. The use of HCQ at baseline was associated with significantly less damage to the body during the study, but this benefit was limited only to patients who had no damage at the beginning of the study. Because HCQ can have other favorable effects on health, including possible protection against osteoporosis in some patients and reduction of blood cholesterol levels, physicians should consider HCQ for routine SLE treatment, especially for patients who have not sustained damage early in the course of the disease.

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