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April 2000 Bruce H. Woolley, Pharm.D., Editor Vol. 7, No. 4
Kenneth J. Hunt, Associate Editor

Antibiotic Resistance in Streptococcus pneumoniae

A major problem facing medicine today is the increasing incidence of microbial resistance to antibiotics. More than ten years ago, most clinical isolates of Streptococcus pneumoniae in the United States were susceptible to a variety of anti-microbial drugs, including penicillin. In the early 1990s, however, antimicrobial resistance began to emerge, and ▀-lactam resistance began to be recognized. Resistance to non-▀-lactam drugs, such as the macrolides, clindamycin, tetracycline, and chloramphenicol also began to increase. A recently published CDC study demonstrated the increasing development of antimicrobial resistance with Strep pneumonia.

The investigators obtained 1,601 Streptococcus pneumoniae clinical isolates from 34 U.S. medical centers. Almost 30% of the strains were resistant to penicillin. Approximately 16% of the isolates displayed multi-drug resistance, which is defined as a lack of susceptibility to penicillin and at least two other non-▀-lactam classes of

antimicrobial drugs. Resistance to ten ▀-lactam drugs was examined in this study; findings demonstrated that resistance was directly related to the level of penicillin resistance.

Twenty-four of the 34 medical centers participating in this study had participated in a similar study 3 years before. In 80% of these centers, penicillin resistance rates increased between 3% and 39%. Similar increases were observed with rates of resistance to other anti-microbial drugs. Multi-drug resistance had increased from 9.1% to 16% since the previous study. The explanation offered by the investigators was an increasing clonal spread of multi-drug resistant organisms. Under this explanation, multi-drug resistant organisms may become more prevalent.

Clinically, this problem will only get worse as time goes on. The idea of clonal spreading should and undoubtedly will be studied further so that clonal relationships among multiple geographically distinct organisms can be established. The idea of drug resistance also reinforces the importance of cautious use of antibiotics and development of more powerful anti-microbial measures.

(1) Doern GV, et al Emerging Infectious Diseases 5(6), 1999 & Centers for Disease Control

(2) Woolley BH, et al. J of Collegium Aesculapium, Fall 1999; vol 17(1)  p 23-31

Osteoporosis in Men

As the population gets older, osteoporosis in men is beginning to represent a prominent public health issue. Though osteoporotic fractures are certainly fewer in men than in women, they remain remarkably common. A recent osteoporosis study involving men suggested that risk of a low trauma fracture is almost 25% over the lifetime of an average 60-year-old man. Fractures in men make up about 20% of the economic burden of osteoporosis. Still, this problem has been largely overshadowed by the larger problem that exists in women.

There are no well-established pharmacologic therapies for osteoporosis in men, nor are there any large, well-controlled trials of the efficacy of any therapy in prevention of fractures in men The FDA has not approved any therapies for osteoporosis in men. Most approaches, therefore, to males with the disease have been based on data derived primarily in women. In the absence of more specific data, prevention of osteoporosis in men should follow the same guidelines as in women.

Clinicians should become aware of the risks and symptoms of osteoporosis in men. Routine health maintenance recommendations should include measures to prevent fracture. Adequate calcium and vitamin D nutrition has been demonstrated as useful in maintaining bone mass and preventing fractures in older men. Recommendations are currently 1200 mg calcium and 600 to 800 IU of vitamin D daily in adult men. Weight- bearing exercise is useful for the maintenance of bone mass and the prevention of falls.

Fortunately, most lifestyle improvements that are beneficial in the prevention of osteoporosis are also recommended for general health. Avoiding lifestyles that contribute to bone loss or fractures, such as tobacco, alcohol abuse, or inactivity should be discouraged. The impact of medications or medical conditions associated with osteoporosis should be reviewed with patients and minimized with appropriate preventive strategies. As the population ages, women will not be the only victims of osteoporosis. Considerable work must still be performed so that appropriate roles of therapeutic approaches to osteoporosis in men may be identified.

Thanks to Orwoll ES New Dimensions in Osteoporosis 1(5):2-8, 12, 1999.

Proposal For Online Pharmacies

Recent growth of the Internet has created countless opportunities for patients to access health-related information, products, and services. Patients are now using the Internet to purchase medical products, including prescription drugs. This is a valuable tool for consumers, adding ease and convenience to medication purchases, and many online pharmacies operate within the legal framework set for the by the government. Unfortunately, several fraudulent websites are selling prescription drugs illegally.

Some of these sites are selling unapproved new and counterfeit drugs; others are not properly licensed to sell or dispense medications. Some do not even require a prescription at all. Patients obtaining medications from such websites are at risk of receiving a product that is unsafe, ineffective, or counterfeit. These problems are worsened because it is not always obvious whether an Internet pharmacy is legitimate. It is further difficult for governing bodies to determine the legitimacy of a web site, especially given that the Internet allows sellers to reach across the globe and remain anonymous.

Jane Henney, MD, the commissioner of the FDA, recently issued a report on the proposal by the Clinton administration aimed at protecting consumers from fraudulent online pharmacies. The proposal allocated ten million dollars to enable FDA to better identify, investigate, and prosecute Web sites that are selling illegal drug products. The proposal will also help ensure that patients purchasing prescription drugs over the Internet have the same safeguards as patients who walk into a pharmacy, and to help ensure that state and federal authorities have adequate tools to investigate and prosecute illegitimate Web sites.

The proposal is aimed at ensuring that online pharmacies are operating legally and enabling consumers and governmental bodies to clearly distinguish legitimate from illegitimate Web sites. There would be enhanced penalties for the illegal sale of prescription drugs over the Internet. New penalties could take the form of civil money penalties of up to $500,000 for failure to state and federal requirements, or for the sale of prescription drugs without a valid prescription. The FDA would also have administrative subpoena authority so they can efficiently obtain records for sites under investigation. FDA must currently go through a grand jury to obtain subpoenas for such records.

Online prescription drug sales that circumvent the regulations created by the federal and state governments place the health of the American public at risk. This recent proposal would maintain safety for Internet drug consumers. The ultimate goal is equal protection of patients who have their prescriptions filled by a traditional pharmacy and those patients who sign onto the Internet to purchase prescription drugs. By promoting consumer confidence and trust, the proposal will support the growth of legitimate online pharmacies while protecting patients who use the Internet to purchase prescription drugs.

Thanks to Henney, JE

Chromium and Zinc in Parenteral Nutrition

Concern over the potential adverse effects of long-term parenteral nutrition use in children was recently examined. The study evaluated the potential accumulation of chromium and zinc in children who had received parenteral nutrition for at least two months. Serum and urine concentrations of the two minerals were higher than recommended in the eleven children receiving treatment. The authors concluded that parenteral nutrition solutions for children frequently provide excessive amounts of chromium and zinc. They suggest that chromium be eliminated as a routine supplement for parenteral nutrition solutions and that zinc supplementation be further studied. Perhaps reducing chromium levels in parenteral solutions should be considered.

Mouser JF, et al Am J Health-Syst Pharm 1999;56:1950-6.

Recent FDA Actions

Caffeine citrate The need for an injectable form of caffeine citrate was recently filled with the recent FDA approval of Cafcit (Roxane Laboratories) for short-term use in neonates with apnea of prematurity. Caffeine citrate offers a wider therapeutic range than aminophylline and once daily dosing. Previous injectable forms contained caffeine benzyl alcohol and were inappropriate for use in neonates and use in the treatment of anemia in children with chronic renal failure who are undergoing dialysis. Epoetin administration has been shown to decrease the need for transfusions in patients receiving dialysis.

Mometasone An intranasal dosage formulation of mometasone (Nasonex«, Schering-Plough) has been approved for use in children 3 years of age and older. Intranasal mometasone is indicated for the treatment of seasonal and allergic rhinitis. The use of inhaled mometasone has not been associated with significant growth inhibition in pediatric patients.

Pneumococcus vaccine Last month, Wyeth-Lederle's 7-valent conjugate pneumococcus vaccine received a recommendation for approval from the Vaccines and Related Biological Products Advisory Committee of the FDA. The vaccine will be marketed as Prevenar«, and is recommended for immunization of all children under 5 years of age.

Poractant alfa Poractant alfa (Curosurf«, Dey) is a surfactant approved for treatment of respiratory distress syndrome (RDS) in premature infants. This product has been tested extensively in Europe and is already on the market in several foreign countries. Approval in the U.S. was delayed due to FDA concerns about the European prophylaxis trials. Thus, poractant alfa is only approved for treatment of RDS, rather than both prophylaxis and treatment.

Topiramate Topiramate (Topamax«, Ortho-McNeil) has received an additional indication from the FDA as adjunctive therapy for primary generalized seizures in children ages 2 to 16 years. This product has been used under protocol at the University of Virginia for several years in children with refractory mixed seizure disorders.

Zafirlukast Leukotriene receptor antagonists have made a significant contribution to the management of asthma in children and adults. Zafirlukast (Accolate«, AstraZeneca) is now available in a 10 mg unflavored mini-tablet for use in children years and older.

The information and opinions expressed in the Therapeutics Letter do not necessarily reflect the official policy of the sponsoring organizations