What can we do to decrease antibiotic resistance?

November 2006

To coincide with the November special issue on antimicrobial resistance, this month’s Pharmacology Consult column reviews the problem of resistance with an emphasis on methods community clinicians can employ to minimize or lessen the impact of antibiotic resistance.

Antibiotic use is a very important factor in the development of antibiotic resistance by bacteria, which is well supported by published data. However, other factors, like the presence and transfer of resistance-causing genes, or the non-therapeutic use of antibiotics in animal agriculture, are additionally important, resulting in a complex relationship between bacterial resistance development and the use of antibiotics. Yet, the role and use of antibiotics in the therapy of ill children remains a major means by which clinicians can affect the development of antibiotic resistance.

Rates of antibiotic use

The effect and importance of antibiotic resistance has become a widely discussed topic in both professional medical literature and mainstream press in recent years. There have been numerous efforts to promote the appropriate antibiotic use in children, which target clinicians and caregivers of children. Recently published studies have shown that clinicians, including pediatricians, appear to be prescribing fewer courses of antibiotics. Nyquist evaluated data from the 1992 National Ambulatory Medical Care Survey and found that office-based physicians prescribed antibiotics to 44%, 46%, and 75% of children with a diagnosis of common cold, upper respiratory infection and bronchitis, respectively. Pediatricians were less likely than other physicians to prescribe antibiotics (OR=0.57). Studies of antimicrobial prescribing rates by office-based physicians revealed a 48% increase in antibiotic use in children between 1980 and 1992.

Fortunately, antibiotic use rates have decreased more recently. Analysis of the National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey (hospital emergency and outpatient department physicians) from 1992 to 2000 revealed that population-based and visit-based antimicrobial prescribing rates decreased by 23% and 25%, respectively, for adults and children in total. Antibiotic prescribing rates decreased by 34% in physicians’ offices overall for children younger than 15 years (P<.05), and by 33% in pediatricians’ offices (P<.05).

Efforts by medical professional societies, state and local agencies and federal agencies, beginning in the mid-1990s, are in large part responsible for this reduction in antibiotic use. In 1995 the CDC launched the National Campaign for Appropriate Antibiotic Use with the objective of reducing inappropriate antibiotic use and the spread of antibiotic resistance. An important component of this campaign includes directing information to clinicians that describes when the use of antibiotics is most appropriate, and directing information to caregivers about the risks of inappropriate antibiotic use. According to the CDC, key components of appropriate antibiotic use include: 1) prescribing antibiotics only when they are likely to be beneficial to the patient; 2) use of an antibiotic that targets the likely pathogens; and 3) using the antibiotic for the appropriate dose and duration.

Many published studies have provided data describing a relationship between antibiotic use and the development of resistance to antibiotics. The importance of the increasing antibiotic resistance by Streptococcus pneumoniae is all too familiar to pediatric clinicians. For example, a child who has received a recent antibiotic is up to seven times more likely to be colonized with a drug-resistant strain than a child who has not recently taken an antibiotic. Unfortunately, fewer data exist that describe the relationship between reducing antibiotic use and a resulting reduction in antibiotic resistance, especially in the community setting.

However, some encouraging information is available. The Finnish Study Group for Antimicrobial Resistance evaluated the effects of a nationwide recommendation to reduce macrolide antibiotic use in response to increasing resistance to erythromycin by group A streptococci (Seppala). Information provided to prescribing physicians nationally resulted in a reduction in macrolide use; the use of other antibiotics increased, however, as the total rate of antibiotic use did not change. A reduction in macrolide use from 2.4 to 1.38 defined daily doses per day per 1,000 inhabitants was associated with in a decrease of group A streptococci erythromycin resistance from 16.5% to 8.6%. This resistance reduction was seen relatively quickly (within four years) after reduced macrolide use. Although this temporal relationship does not prove causality, it does provide encouraging information about the potential benefits of reducing antibiotic use.

Factors affecting antibiotic use

The dynamics of the process leading to prescribing an antibiotic to a child in the community office setting are complex. Several published studies reveal interesting data about this process. Bauchner evaluated surveys from 610 pediatricians, which describe the influence parents have upon their antibiotic prescribing habits. Forty percent of these pediatricians indicated that there were 10 or more parental requests for antibiotics, when the pediatrician determined that an antibiotic was not needed. Similarly, 48% of pediatricians responded that parents frequently pressured them to prescribe an antibiotic when not needed. When this occurs, 30% of pediatricians respond to parents’ requests (defined as occasionally or more often).

Those results indicate that educating parents on the appropriate use of antibiotics may be beneficial. Mangione-Smith evaluated the relationship between parental pre-visit expectations, pediatrician perception of parental expectations and inappropriate antibiotic prescribing. Ten pediatricians and 306 parents were surveyed. Multivariate analysis of the survey responses revealed interesting findings: When pediatricians believed a parent wanted an antibiotic, an antibiotic was prescribed in 62% of cases, compared with 7% of cases in which an antibiotic was prescribed and the pediatrician did not believe the parent wanted an antibiotic. When the pediatrician believed the parent wanted an antibiotic, a bacterial diagnosis was more common (70% vs. 31%). Actual parental expectations for antibiotics, however, were not a significant predictor of inappropriate antibiotic use. Several factors were evaluated for meeting parental satisfaction, and only failure to meet parental expectations for communication events was found to be statistically significant. This study, although small, suggests that inappropriate antibiotic use may be reduced by using adequate time to communicate with parents about when antibiotics may or may not be useful.

Trepka evaluated the effect of educating parents about antibiotic resistance and the appropriate uses of antibiotics upon parental knowledge. This study compared an intervention and control area in Wisconsin (n=361), using pre-intervention and post-intervention surveys. Parents in the intervention group received material in various community settings about the appropriate use of antibiotics and risks of resistance. Physicians in the intervention area also received education on appropriate antibiotic use. More parents in the intervention group were exposed to local educational messages on antibiotic use and resistance than in the control group (53% vs. 23%) during this year-long study. Knowledge on antibiotic resistance increased more in the intervention group (58% to 73%) than in the control group (60% to 65%). This study suggests that education of parents on the potential risks of antibiotic use and resistance may be beneficial.

Several trials have evaluated methods to increase appropriate antibiotic use in children in ambulatory settings. Finkelstein evaluated the effect of physician and parent education about appropriate antibiotic use on the rate of antibiotic courses dispensed to children younger than 6. Twelve community practices associated with two managed care organizations in Massachusetts and Washington state were studied for two years. The practices were randomized to intervention and control groups. Physicians in the intervention group received education about judicious antibiotic use, from CDC materials. Parents also received CDC-produced information. Antibiotics dispensed were evaluated from automated pharmacy claims data for 8,815 children. Antibiotic prescribing decreased more in the intervention group, compared with the control group (P<.05): 18.6% reduction vs. 11.5% reduction, respectively, for children aged 3 to 35 months, and 15% reduction vs. 9.8% reduction, respectively, for children aged 36 to 71 months. Reductions in antibiotic use in the control group may have reflected reductions in antibiotic use from generalized national attention on antibiotics.

Belongia assessed the effect of pediatrician and parent education on antibiotic prescribing and carriage of penicillin-nonsusceptible Streptococcus pneumoniae in childcare facilities in Wisconsin within a one-year study period. Clinicians (n=151) in the intervention group were educated about appropriate antibiotic use by presentations, academic detailing and CDC-produced materials. Community education in the intervention group targeted parents, childcare providers, and community groups, using CDC-produced pamphlets and readings. Antibiotic prescribing was based on clinician-specific prescribing data (solid and liquid dosage forms). Solid dosage form prescribing per clinician decreased by 19% and 8% in the intervention and control groups, respectively (P<.05). Liquid dosage form prescribing per clinician decreased by 11% in the intervention group and increased by 12% in the control group (P<.05). Among children attending childcare facilities, there were no differences in antibiotic use or carriage of penicillin nonsusceptible S. pneumoniae colonization between the intervention and control groups.

Perz also assessed the effect of a one-year education intervention program on appropriate antibiotic use by clinicians (250 pediatricians and family practitioners) and caregivers, and antibiotic prescribing in Tennessee. Children younger than 15 years enrolled in Tennessee’s Medicaid Managed Care Program in one county were included in the study. One county served as the intervention and three other counties served as the control. Children in the county receiving intervention were chosen because of high S. pneumoniae penicillin resistance rates. Clinicians received education about appropriate antibiotic use by expert peer presentations and distribution of printed materials. Caregivers received printed materials through the offices of the 250 targeted clinicians, day care, and schools. Printed materials were also distributed to the general public through the local media and health care provider offices (including dental and pharmacies). Oral antibiotic prescription use, determined from automated Medicaid files, was the primary outcome measure. Within three years of evaluation (one year each for pre-intervention, intervention and post-intervention), antibiotic prescription rates decreased 19% and 8% for the intervention and control counties, respectively (P<.05). Although not evaluated as an outcome measure, penicillin resistance rates of invasive S. pneumoniae remained high throughout the three study years.

Hennessy evaluated the effects of clinician and community education on antibiotic use and nasopharyngeal S. pneumoniae carriage in a controlled study of 13 remote Alaskan villages (n=3326) for three years. Nasopharyngeal specimens were taken from village residents of all ages who agreed to be cultured (31% of the population), and clinic records of all village residents were reviewed for antibiotic use. Education of health care providers and village residents about appropriate antibiotic use occurred in one of three regions initially, and was later expanded to all three regions. Antibiotic use decreased by 31% initially in the intervention region, and by 35% in the other regions that subsequently received community education (P<.05). Overall, there was no sustained decrease in carriage of penicillin nonsusceptible S. pneumoniae in the intervention regions. However, a significant correlation was observed between antibiotic use and risk of carriage of nonsusceptible S. pneumoniae (ie, increased antibiotic use was associated with increased likelihood of nonsusceptible S. pneumoniae carriage). Further analysis of this relationship using a generalized linear model revealed that antibiotic use and bacterial serotype accounted for 7% and 81%, respectively, of the model variance in bacterial sensitivity.

Conclusions

The studies discussed here provide encouraging information about antibiotic use in children. However, more data are needed to better define and describe the relationship between reducing antibiotic use and changes in bacterial pathogen antibiotic sensitivities. Several studies have suggested that educating clinicians and parents may be helpful in aiding appropriate antibiotic use. Communication between caregivers or patients and clinicians should be given adequate time to address the role of antibiotics and their risks. Accurate diagnosis and differentiation of viral and bacterial infections are also important. Although appropriate antibiotic use remains a goal, the use of active immunization may have a larger effect on reducing the prevalence of resistant pathogens, as suggested by one study. What can community practitioners do to affect antibiotic resistance? Take advantage of the numerous pamphlets the CDC offers to clinicians and caregivers, including diagnostic guidelines for clinicians.

The CDC offers printed materials targeted toward parents, caregivers, and clinicians. Several styles and themes of pamphlets targeting parents on viral infections and lack of benefit of antibiotics are available from the CDC Web address, usually free of charge. Pamphlets directed at day care institutions, discussing why antibiotics are not always necessary for ill children, are also available. Other useful printed materials, which can easily be downloaded, include academic detailing information sheets useful for clinicians and office staff. These materials describe the role of antibiotics for common pediatric ambulatory infectious diseases, including cough illness, otitis media, and the common cold. They also summarize useful diagnostic recommendations for these and other common illnesses. Communicate with caregivers and patients about their expectations, the role of antibiotics, the pathophysiology of the infectious illness, and the potential benefits of non-antibiotic therapy. These efforts, as alluded to above, may prove beneficial to your patients.

For more information:

• Edward A. Bell, PharmD, BCPS, is an Associate Professor of Pharmacy Practice at Drake University College of Pharmacy and a Clinical Specialist at Blank Children’s Hospital, Des Moines, Iowa.
• For more information on the CDC pamphlets visit www.cdc.gov/drugresistance/community/campaign.htm.
• Bauchner H. Parents, physicians, and antibiotic use. Pediatrics. 1999;103:395-401.
• Belongia EA. A community intervention trial to promote judicious antibiotic use and reduce penicillin-resistant Streptococcus pneumoniae carriage in children. Pediatrics. 2001;108:575-583.
• Finkelstein JA. Reducing antibiotic use in children: a randomized trial in 12 practices. Pediatrics. 2001;108:1-7.
• Hennessy TW. Changes in antibiotic-prescribing practices and carriage of penicillin-resistant Streptococcus pneumoniae: a controlled intervention trial in rural Alaska. Clin Infect Dis. 2002;34:1543-1550.
• Heppala H. The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. N Engl J Med. 1997;337:441-446.
• Mangione-Smith R. The relationship between perceived parental expectations and pediatrician antimicrobial prescribing behavior. Pediatrics. 1999;103:711-718.
• McCaig LF. Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA. 1995;273:214-219.
• Nyquist AC. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279:875-882.
• Perz JF. Changes in antibiotic prescribing for children after a community-wide campaign. JAMA. 2002;287:3103-3109.
• Trepka MJ. The effect of a community intervention trial on parental knowledge and awareness of antibiotic resistance and appropriate antibiotic use in children. Pediatrics. 2001;107:e6
• Weissman J. Promoting appropriate antibiotic use for pediatric patients: a social ecological framework. Semin Pediatr Infect Dis. 2004;15:41-51.