To print: Select File and then Print from your browser's menu --------------------------------------------------------------------------------------- Title: Resistance Increasing in Gram-Positive Bacteria URL: http://www.pslgroup.com/dg/C646.htm Doctor's Guide September 16, 1996
NEW ORLEANS, Sept. 16, 1996 -- Unless swift action is taken, antibiotic-resistant bacteria will become an increasing issue in U.S. hospitals and communities, according to experts presenting at a satellite symposium prior to the 36th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Researchers reported increasing resistance among several types of Gram-positive bacteria associated with common and potentially life-threatening infections. These pathogens -- penicillin-resistant Streptococcus pneumoniae (DRSP), methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) -- complicate the treatment of serious infections and have been linked to extended hospitalizations, higher medical costs and high mortality rates. However, researchers noted several new investigational agents with potent bactericidal activity as cause for hope. "Bacteria are remarkably agile in developing or acquiring new ways to outsmart antimicrobial agents," said Robert C. Moellering, M.D., Chairman, Department of Medicine, New England Deaconess Hospital in Boston. "While resistance was once found primarily in the hospital setting, we're beginning to see more and more evidence of resistant pathogens in the community." Drug-resistant Streptococcus pneumoniae (DRSP) poses a growing threat to people in places where they live and work, noted G. Douglas Campbell, Jr., M.D., Professor of Medicine and Chief of the Division of Pulmonary and Critical Care Medicine at Louisiana State Medical School in Shreveport. Streptococcus pneumoniae infections -- including pneumonia, sinusitis, meningitis and otitis media -- are among the leading causes of death and illness among the elderly, young children and persons with underlying medical conditions. DRSP often strikes vulnerable patient populations in daycare settings, nursing homes and prisons. Resistance to penicillin, the most common agent used to treat S. pneumoniae, now approaches 40 percent. Additional resistance has been reported against cephalosporins and non-beta-lactam agents, and scientists estimate that nearly half of these strains can be classified as highly resistant. "While high-dose penicillin and cephalosporins are first-line therapies, a broader range of agents is needed," said Dr. Campbell. "Vancomycin, the next generation of fluoroquinolones with agents such as sparfloxacin, the new streptogramin class, and combination therapies will help physicians stay one step ahead of resistant pneumococci." Staphylococcus aureus, the most common cause of more than a dozen conditions in both hospitals and communities, can be considered the "ultimate pathogen," according to Gordon L. Archer, M.D., Professor of Medicine and Chairman, Division of Infectious Diseases, Medical College of Virginia, Virginia Commonwealth University. S. aureus often colonizes without any signs of infection, and then from this reservoir gains access to skin and deep tissue, where it subverts the immune system. Staphylococcal infections range from local skin infections to endocarditis (heart valve infection), osteomyelitis (bone infection) and sepsis (blood stream infection). Methicillin-resistant S. aureus (MRSA) first emerged in the United Kingdom in the early 1960s. Since then, researchers have observed that several strains of S. aureus can outmaneuver a wide variety of currently available antibiotics, including penicillins, macrolides, fluoroquinolones and lincosamides. "With the dramatic increase in multidrug- resistant staphylococci, we must work harder than ever to help patients stay healthy," said Dr. Archer. In the same bacteria family, multidrug-resistant Staphylococcus epidermidis also compromises patient health. This coagulase-negative bacteria found primarily in skin tissue was once considered a non-threatening contaminant. Now, it has been established as a leading cause of hospital- acquired bloodstream infections. More than 80 percent of S. epidermidis isolates in U.S. hospitals are methicillin resistant, and recent studies have found resistance to quinolones, cephalosporins and vancomycin. "The emergence of Staphylococcus epidermidis as a pathogen has been fueled by the widespread use of catheters, prosthetic joints, valves and other invasive medical devices, and is a growing concern, particularly for immunocompromised cancer patients," said Issam Raad, M.D., Aassociate Professor of Medicine and Chief, Section of Infection Control at the University of Texas M.D. Anderson Cancer Center. "These patients desperately need new effective agents with high activity against this pathogen." Vancomycin-resistant enterococci (VRE) -- an increasingly frequent cause of hospital-acquired infections in the United States -- are resistant to virtually all currently available antibiotics including vancomycin, considered the agent of last resort for Gram-positive infections. Vancomycin use is prevalent, particularly in hematology, neurosurgery and cardiovascular surgery patients, and dosing for these patients is often inappropriate, according to William R. Jarvis, M.D., head of the Investigation and Prevention Branch of the Hospital Infection Program at the Centers for Disease Control and Prevention (CDC) in Atlanta. "It is imperative that clinicians adhere to the federal recommendations for vancomycin use," said Dr. Jarvis. "The first step is to generate pharmacy data for specific service areas, such as surgery, neonatal or transplant units. Data on antimicrobial use patterns can be enormously helpful in targeting clinician education programs to improve use patterns." New Treatments Offer Hope Two investigational antibiotics developed by Rhone-Poulenc Rorer are among those that have shown promise in treating serious and sometimes fatal infections. Synercid(R) (quinupristin/dalfopristin) an investigational compound not yet approved by the U.S. Food and Drug Administration (FDA), is a novel, injectable streptogramin antibiotic made of two molecules, quinupristin and dalfopristin. When combined, they appear to create a synergistic bactericidal agent that may have the power to kill bacteria by inhibiting protein synthesis. In laboratory tests, Synercid has been shown to be active against the major Gram-positive strains of Enterococcus faecium, Staphylococcus aureus, Staphylococcus epidermis and Streptococcus pneumoniae, including multidrug-resistant strains. Phase III clinical trials of Synercid are complete. New Drug Application filing is anticipated by the end of the year. Zagam(R) (sparfloxacin), currently under review by the FDA, is an oral antibiotic which appears to provide comprehensive coverage of community acquired infections, especially those of the respiratory tract. The agent is believed to be effective against Gram-negative (such as Haemophilus influenzae and Moraxella catarrhalis) and Gram-positive (such as Streptococcus pneumoniae and Staphylococcus aureus) pathogens, including penicillin-resistant Streptococcus pneumoniae. Additionally, it has demonstrated activity against the atypical pathogens (such as Mycoplasma pneumoniae, Legionella pneumophilia and Chlamydia pneumoniae). Like other quinolones, sparfloxacin is associated with photosensitivity reaction. Sparfloxacin exerts its antibacterial activity by inhibiting DNA gyrase, an enzyme which assists in DNA replication, deactivation and transcription. A New Drug Application for the product was filed with the FDA in December of 1995. "Based on extensive clinical trials, Synercid and sparfloxacin show promise in treating several important antibiotic resistant strains," said Dr. Moellering. "New agents, combined with infection control measures and judicious antibiotic use, will help us win the war against microbes." The symposium was made possible by an unrestricted grant from Rhone-Poulenc Rorer, Inc. (NYSE: RPR), a global pharmaceutical company dedicated to improving human health. --------------------------------------------------------------------------------------------- Copyright © 1999 P\S\L Consulting Group Inc. All rights reserved. Republication or redistribution of P\S\L content is expressly prohibited without the prior written consent of P\S\L. 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