How can we decrease antibiotic resistance?

January 2007

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 (eg, 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 therapy remain 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 the mainstream press in recent years. There have been numerous efforts to promote the appropriate antibiotic use in patients. Recently published studies have shown that clinicians appear to be prescribing fewer courses of antibiotics, particularly in pediatric patients.

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 pediatric patients 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 from 1980 to 1992.

Fortunately, antibiotic use rates have decreased more recently. Analysis of the National Ambulatory Medical Care Survey (office-based physicians) 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% for adults and children, respectively.

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 prescribing antibiotics only when they are likely to be beneficial to the patient, use of an antibiotic that targets the likely pathogens, and 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 many clinicians. For example, a patient who has received a recent antibiotic is up to seven times more likely to be colonized with a drug-resistant strain than a patient 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 (ie, not in the hospital 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 resulted 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 antibiotics

The dynamics of the process leading to prescribing an antibiotic to a patient in the community office setting are complex. Particularly in pediatric patients, this process can be influenced by several factors. 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 (private community practice- and university-based) 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.

Hennessy evaluated the effects of clinician and community education on antibiotic use and nasopharyngeal Streptococcus 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 Streptococcus pneumoniae in the intervention regions. However, a significant correlation was observed between antibiotic use and risk of carriage of nonsusceptible Streptococcus pneumoniae (ie, increased antibiotic use was associated with increased likelihood of nonsusceptible Streptococcus 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. 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 patients 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. 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 Universiity College of Pharmacy and a Clinical Specialist at Blank Children’s Hospital, Des Moines, Iowa.
• 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;108:575-83.
• 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;34:1543-50.
• 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;337:441-6.
• Mangione-Smith R. The relationship between perceived parental expectations and pediatrician antimicrobial prescribing behavior. Pediatrics 1999;103:711-18.
• Nyquist AC. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279:875-82.