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PUBLIC HEALTH Forecasting Method Predicts Floods of Drug-resistant BacteriaMultidrug-resistant strains of Streptococcus pneumoniae may rise at a shockingly fast rate in the next two years. The grim forecast comes from a mathematical model explaining the jumps and dips in antimicrobial resistance from state to state, reported in the April 2003 Nature Medicine (online March 10) by HSPH graduate student Alethea McCormick and colleagues. Further calculations suggest that local antibiotic use is to blame, rather than a few resistant clones that spread and thrive in many areas.
Strains of Streptococcus pneumoniae resistant to two common antibiotics may rise to 41 percent by next summer, predicts a mathematical model by Marc Lipsitch (left), Alethea McCormick, and colleagues. (Lipsitch photo by Graham Ramsay. McCormick photo by Jeff Cleary) "It's like a weather forecast: we may well be wrong," said senior author Marc Lipsitch, HSPH assistant professor of epidemiology. "But even if it's not quantitatively correct, the clear trend is that strains resistant to one of the two drugs are declining in frequency, while strains resistant to both are increasing. The message from this is to avoid overprescribing antibiotics."
Streptococcus pneumoniae is the leading cause of pneumonia, meningitis, and middle-ear infections in the developed world and may cause more than 1 million childhood deaths a year in developing countries. Drug resistance is a continuum, Lipsitch said. So far, penicillin resistance makes treatment harder and more expensive, but not completely ineffective. "No one is going to bet their life on real numbers, but there is no question resistance will rise," said Stuart Levy, director of the Center for Adaptation Genetics and Drug Resistance at Tufts University School of Medicine. "It doesn't surprise me. This is how bad it could be if we don't do anything." The four-year data set for the model came from a surveillance network of eight U.S. geographic regions of counties, cities, or states, covering approximately 21 million people, coordinated by the U.S. Centers for Disease Control and Prevention (CDC) in collaboration with several health departments and universities. All of the pneumococci samples collected at the sites were tested for antimicrobial resistance and, since 1998, serotyped. Resistance Is LocalWorldwide, antibiotic use and resistance vary greatly from country to country. In the U.S., the proportion of penicillin resistance in 1998 varied among the surveillance sites from 14.7 percent in New York state to 35.1 percent in Tennessee. The sites showed similar variation in erythromycin and dually resistant pneumococci samples. Resistance to penicillin and erythromycin is largely confined to about seven of the 90 serotypes."We didn't have antibiotic use data, but we had resistance data," McCormick said. "Using mathematical techniques, we showed it is likely that antibiotic use patterns are pushing resistance rather than one or two different strains taking off." Local selection won out as a dominant force for evolution of resistance based on their calculations. If a state had high drug resistance in one serotype, it also had high resistance in other serotypes. McCormick then adapted a mathematical model originally developed by Lipsitch to predict trends in single-drug resistance. By July 1, 2004, the model predicts, 41 percent of pneumococci in all the sites will be dually resistant, with 5 percent resistant to penicillin only and 5 percent to erythromycin only. That may be an overestimate, because the model ignores the heptavalent pneumococcal conjugate vaccine (PCV), approved for U.S. use in February 2000. The vaccine targets the most common strains, which also happen to have the highest resistance. Fewer people may be infected, and the infection is less likely to be resistant. But those infected with a vaccine-type strain will have more than a 50 percent chance of dually resistant infection, based on longer-term serotype data from two states. "Those figures will be the best test of the predictive model," Lipsitch said. Putting a Lid OnThis chilling prediction emphasizes the need for immediate action, according to an accompanying commentary by microbiologists Allison McGeer and Donald Low at Mount Sinai Hospital in Toronto. They note that Scandinavia has among the lowest per capita antibiotic use in the world without suffering poorer outcomes or more infections than other regions. Other strategies include pneumococcal vaccines, influenza vaccines to reduce inappropriate antibiotic use, and hand washing in schools to lower transmission of respiratory illness, for which most antibiotics are prescribed.According to the CDC, half of the 100 million antibiotic prescriptions a year written by office-based physicians are unnecessary, because they are prescribed for the common cold and other viral infections, against which antibiotics are not active. Unnecessary use of antibiotics in hospitals is also reportedly common. In February, the U.S. Food and Drug Administration posted new drug-labeling regulations designed to help reduce the development of drug-resistant bacterial strains. The FDA's action is part of a multi-agency effort to reduce the inappropriate prescription of antibiotics for common ailments such as ear infections and chronic coughs. "Antimicrobial resistance is not one problem, but rather an array of problems resulting from the evolution of bacterial populations in the presence of antimicrobials," McGeer and Low write. "In such a complex situation, mathematical modeling can improve our insight into the potential impact of different control strategies and create testable hypotheses at a population level." --Carol Cruzan Morton |
