Pediatric Annals

ANTIBIOTICS FOR THE PEDIATRICIAN 

Antibiotic Use and Abuse in Clinical Practice

Ann-Christine Nyquist, MD, MSPH

Abstract

To regard any form of life merely as slave or foe will one day be considered poor philosophy, for all living things constitute an integral part of the cosmic order bacterial resistance will cease to be a problem when microbes are no longer considered foes or slaves but instead maintained as indispensable links with life itself. (Dubos)1

Antibiotics may be considered the most important advance in the history of medicine. Since the introduction of sulfonamides 80 years ago, there has been a significant decrease in the morbidity and mortality of infectious diseases. We have a plethora of antimicrobials available in our armamentarium against bacterial infections as we approach the new millennium. Yet in 1999 we find many of Dubos's early premonitions about bacterial resistance fulfilled. Antibiotic resistance is a growing problem for a variety of pathogens. As a result of the extensive use and abuse of antibiotics, often for conditions for which antibiotics are neither effective nor indicated, there is increased development of drug-resistant bacteria.

Approximately half of the antibiotics used worldwide are used in agriculture and animal husbandry. Up to 80% of this use is for prophylaxis and growth promotion. Of the 25,000 tons of antibiotics produced every year in the United States, approximately 40% is given to animals, mostly as feed additives to promote growth. Although controversial, there is great concern that this questionable use of antibiotics in agriculture will translate to antibiotic-resistant bacterial strains in humans. Recent studies have found bacteria in chickens that are resistant to fluoroquinolones, the most recently approved class of antibiotics and one that scientists had been hoping would remain effective for a long time.

Antimicrobial drug use exerts selective pressure favoring the emergence of resistance. Until now, the primary response to the problem of bacterial resistance has been the development of new antibiotics. The discovery, development, and licensing of antibiotics has been driven by the continual emergence of bacterial resistance and a profitable market. We have come to expect development of new alternative antimicrobials if resistance develops to one agent.

The emergence of bacterial strains that are increasingly resistant to antimicrobial agents is a growing national and international concern. The spread of organisms such as vancomycin-resistant enterococci, multidrug-resistant tuberculosis, and methicillin-resistant Staphylococcus aureus, all essentially untreatable with routinely available antibiotics, has given credence to the concept of a "post-antimicrobial era."

The sense of urgency for the control of resistance in community-acquired pathogens has come in response to the recent dramatic emergence of illness caused by multidrug-resistant Streptococcus pneumoniae. In the United States, the pneumococcus was almost universally sensitive to penicillin until the early 1980s. However, in the past several years there has been a rapid increase in the number of strains resistant to penicillin, extended-spectrum cephalosporins, and many other antibiotics. Approximately one-third of all pneumococcal isolates from invasive infections in recent years are not susceptible to penicillin.

Addressing antimicrobial use and resistance is one of the most urgent priorities in confronting emerging infectious disease threats. Now is the time to act and change our ways. Widespread antibiotic use is the driving force behind this growing resistance pandemic. We have spent half of the century pronouncing antibiotics a panacea, but now the diseases and times are changing. The successes of antibiotics, whether fictional or real, have encouraged health care consumers to expect a "cure" for all of the common maladies that infect children. It is critical at this juncture to reeducate ourselves and our patients about the appropriate role that antibiotics play in the lives and the health of our children. Jernigan et al. eloquently stated the scenario: "Unless we act swiftly, we…

To regard any form of life merely as slave or foe will one day be considered poor philosophy, for all living things constitute an integral part of the cosmic order bacterial resistance will cease to be a problem when microbes are no longer considered foes or slaves but instead maintained as indispensable links with life itself. (Dubos)1

Antibiotics may be considered the most important advance in the history of medicine. Since the introduction of sulfonamides 80 years ago, there has been a significant decrease in the morbidity and mortality of infectious diseases. We have a plethora of antimicrobials available in our armamentarium against bacterial infections as we approach the new millennium. Yet in 1999 we find many of Dubos's early premonitions about bacterial resistance fulfilled. Antibiotic resistance is a growing problem for a variety of pathogens. As a result of the extensive use and abuse of antibiotics, often for conditions for which antibiotics are neither effective nor indicated, there is increased development of drug-resistant bacteria.

Approximately half of the antibiotics used worldwide are used in agriculture and animal husbandry. Up to 80% of this use is for prophylaxis and growth promotion. Of the 25,000 tons of antibiotics produced every year in the United States, approximately 40% is given to animals, mostly as feed additives to promote growth. Although controversial, there is great concern that this questionable use of antibiotics in agriculture will translate to antibiotic-resistant bacterial strains in humans. Recent studies have found bacteria in chickens that are resistant to fluoroquinolones, the most recently approved class of antibiotics and one that scientists had been hoping would remain effective for a long time.

Antimicrobial drug use exerts selective pressure favoring the emergence of resistance. Until now, the primary response to the problem of bacterial resistance has been the development of new antibiotics. The discovery, development, and licensing of antibiotics has been driven by the continual emergence of bacterial resistance and a profitable market. We have come to expect development of new alternative antimicrobials if resistance develops to one agent.

The emergence of bacterial strains that are increasingly resistant to antimicrobial agents is a growing national and international concern. The spread of organisms such as vancomycin-resistant enterococci, multidrug-resistant tuberculosis, and methicillin-resistant Staphylococcus aureus, all essentially untreatable with routinely available antibiotics, has given credence to the concept of a "post-antimicrobial era."

The sense of urgency for the control of resistance in community-acquired pathogens has come in response to the recent dramatic emergence of illness caused by multidrug-resistant Streptococcus pneumoniae. In the United States, the pneumococcus was almost universally sensitive to penicillin until the early 1980s. However, in the past several years there has been a rapid increase in the number of strains resistant to penicillin, extended-spectrum cephalosporins, and many other antibiotics. Approximately one-third of all pneumococcal isolates from invasive infections in recent years are not susceptible to penicillin.

Addressing antimicrobial use and resistance is one of the most urgent priorities in confronting emerging infectious disease threats. Now is the time to act and change our ways. Widespread antibiotic use is the driving force behind this growing resistance pandemic. We have spent half of the century pronouncing antibiotics a panacea, but now the diseases and times are changing. The successes of antibiotics, whether fictional or real, have encouraged health care consumers to expect a "cure" for all of the common maladies that infect children. It is critical at this juncture to reeducate ourselves and our patients about the appropriate role that antibiotics play in the lives and the health of our children. Jernigan et al. eloquently stated the scenario: "Unless we act swiftly, we risk entering a 'postantibiotic era' in which magic bullets become a useless arsenal against the rapid emergence of drug-resistant pathogens."2

EPIDEMIOLOGY OF ANTIBIOTIC USE

Antimicrobials are the second leading therapeutic category of drugs prescribed by officebased physicians in the United States each year. According to the 1996 National Ambulatory Medical Care Survey (NAMCS), antibiotic prescriptions reached 128 million doses compared with 86 million in 1980. From 1990 to 1992, almost one in six physician office visits resulted in an antimicrobial prescription. Upper respiratory infections (URIs) and bronchitis ranked second and third, respectively, among conditions associated with antimicrobial prescriptions.3

As evidenced by these numbers, millions of courses of unnecessary antibiotics are given each year. We treat infections that are predominantly viral in nature with antimicrobials. We use broadspectrum antibiotics when a less expensive, narrower spectrum antimicrobial will achieve the same result. In developing countries, antibiotics are often available over the counter. Throughout the world and among all types of health care providers, we overuse antibiotics.

Antibiotics not only treat individual patients but populations as well. Unnecessary antibiotic use not only changes the bacterial ecology of the community, but also increases the risk that individuals will be infected with a resistant organism. Curbing antimicrobial use benefits the community as a whole and decreases the individual's risk for infections caused by drug-resistant organisms.

CONSEQUENCES OF OVERUSE

S. pneumoniae is a leading cause of sepsis and meningitis in young children. Acute otitis media is the leading reason for antibiotic prescriptions in childhood.3 Approximately half of the cases of acute otitis media, as well as the cases least likely to resolve without treatment, are caused by S. pneumoniae. Overuse of antimicrobials exerts selective pressure on microbes and promotes survival of those with resistance traits. Multiple studies document strong association between the frequency and duration of antibiotic exposure, be it therapeutic or prophylactic, and the emergence and spread of resistant S. pneumoniae. In the United States, strains of S. pneumoniae that previously were uniformly susceptible to penicillin now have intermediate or high-level resistance to this drug in as many as 30% of isolates from respiratory sites.2

Pneumococci were isolated from nasopharyngeal cultures in children 6 years of age or younger presenting with URIs. Almost two-thirds of these isolates were not susceptible to at least one antibiotic and 40% were resistant to penicillin. Infection with penicillin-resistant strains of S. pneumoniae was associated with the use of antibiotics during the previous 3 months. White race, higher family income, and day care attendance were also associated with carriage of these penicillin-resistant strains.4

A working group of the Centers for Disease Control and Prevention proposed four major initiatives to address this growing concern about drug-resistant S. pneumoniae. They suggested implementing an electronic laboratorybased surveillance system to report invasive penicillin-resistant S. pneumoniae infections and to provide clinically relevant feedback to clinicians; identifying risk factors and outcomes of these infections; increasing pneumococcal vaccination; and promoting the judicious use of antimicrobials.2

WHO, WHAT, WHEN, WHERE, WHY?

Who are the culprits in this abuse of antimicrobials and why? Ambulatory prescriptions for antimicrobials account for more than 100 million prescriptions annually. Children receive a significant proportion of the antibiotics prescribed each year. Many prescriptions are written for conditions where antimicrobials are not indicated or have not proven to be of benefit. In 1992, more than 6.5 million prescriptions were written for children with a cold or a URI. Children represent an important target group for efforts aimed at reducing unnecessary antibiotic use.3

Nyquist et al. analyzed the 1992 NAMCS data to evaluate antibiotic-prescribing practices for children younger than 18 years by ambulatory physicians in the United States. Antibiotics were prescribed to 44% of patients with common colds, 46% with URIs, and 75% with bronchitis. Children ages 5 to 11 years were 1.94 times as likely to receive antibiotic prescriptions for physician office visits related to colds, URIs, and bronchitis as children age birth to 4 years. Additionally, pediatricians were 0.57 times less likely to prescribe antibiotics for these conditions than were non-pediatricians.5 A repeat analysis of the 1996 NAMCS database found some decrease in prescription rates for colds (34%), URIs (38%), and bronchitis (52%) in children compared with 1992. Family practitioners were 1.76 times more likely (95% confidence interval [Cl95], 1.1-2.9) and other non-pediatricians were 2.1 times more likely (CI95, 0.8-5.6) to prescribe antibiotics for colds, URIs, and bronchitis in children than were pediatricians.6

Mainous et al. examined Kentucky Medicaid data assessing primary care physician characteristics that were associated with prescribing antibiotics for pediatrie URIs. Antibiotics used to treat colds accounted for 23% of the total cost of managing URIs and added more than $11 to the cost of managing every URI episode in this study. High prescribers were farther from medical school graduation, managed more episodes of URI, and prescribed antimicrobials in 80% of URI episodes. Compared with pediatricians, the odds of being a high prescriber were 409 (CI , 29-7,276) for family practitioners and 318 (Q95, 17-6,125) for other primary care physicians.7

Purulent rhinitis has been another contestable diagnosis where antimicrobials are frequently requested by parents and often prescribed by physicians. Schwartz et al. surveyed pediatricians and family physicians and found that 97% have concerns about the spread of bacterial resistance caused by unwarranted antibiotic therapy. Yet, when presented with a case vignette, 71% of family physicians and 53% of pediatricians would prescribe a 1-day course of antibiotics for purulent rhinitis. The explanation for this practice related to concerns over the development of acute otitis media and persistent purulent nasal drainage. Additionally, physicians felt pressure from mothers to prescribe an antibiotic and wanted to allow employed parents to return to work earlier.8 When presented with the same case vignette, only 21.9% of board-certified pediatrie infectious disease specialists immediately prescribed antibiotics.9

WHY DO WE PRESCRIBE UHMECESSARY ANTIBIOTICS?

Physicians report many pressures to prescribe antibiotics. They prescribe antibiotics to shorten or reduce the severity of URIs, to prevent bacterial superinfection, to tackle their diagnostic uncertainty, and to meet their desire to "do something." But the reason physicians cite most often for prescribing unnecessary antibiotics is parents' unrealistic expectations. However, most parents do not acknowledge that they pressure their physicians for antibiotics.

Because the etiology of URIs is primarily viral, antibiotics do not have any significant effect on the URI episode itself but have been used in hopes of preventing bacterial complications after URI. Many studies that date back to 1950 fail to show any substantial alleviation of symptoms or reduction of complications such as pneumonia with the use of antimicrobials for the treatment of URIs. In 1984, Todd et al. performed a randomized, placebo-controlled trial of the bacteriology and treatment of purulent nasopharyngitis. Forty-six percent of the patients with purulent nasopharyngitis had positive results on culture for S. pneumoniae. Despite this high degree of colonization, they found no significant difference in the development of complications (eg, otitis media or more severe illness) with empirical antibiotic therapy compared with placebo treatments.10

Heikkinen et al. performed a randomized, double-blind, placebo-controlled study to determine whether acute otitis media could be prevented by antibiotic therapy initiated promptly after the appearance of URI. Children ages 1 to 4 years who had a history of three or more episodes of acute otitis media with at least one during the past 6 months received a 7-day course of amoxicillin-davulanate potassium or placebo. Acute otitis media developed in 9 of the 50 children (18%) receiving antibiotics and in 12 of the 54 children (22%) receiving placebo (P = .59). In this study, antimicrobial therapy initiated soon after the appearance of symptoms of URI did not prevent the development of acute otitis media.11 When physicians were asked why they prescribed antibiotics when they were not clinically indicated, they stated that parental expectations was the number one reason. They also cited concerns about complications, uncertain diagnoses, time pressures, and the fear of litigation. The role of day care in increasing the risk of infections and the need to get children back to day care was also noted by these physicians.12

The reasons why physicians are overprescribing antimicrobials also directly relate to their experience and their education. Family physicians may see fewer pediatrie patients, be less confident with their diagnostic skills for children, and be more accustomed to prescribing antibiotics for adults with similar clinical findings. Patients may have received antibiotics for a similar illness in the past and expect them again.

The underlying expectations and economic pressures of managed care - higher patient loads, less time per patient, and cost containment with fewer diagnostic tests for patients with respiratory infections - may have an adverse influence on antibiotic prescribing habits. Trying to "satisfy" the patient with a prescription may be important to some health care providers if managed care organizations tie compensation to patient satisfaction. This crisis in antibiotic resistance is occurring at the same time that managed care and capitated medical health care systems are becoming prominent forces in health care delivery. Consumer satisfaction is important; families may select practitioners who readily prescribe antibiotics and reject the services of those who are more rigid in their criteria for antibiotic use. There are increasing time constrictions on practitioners. It takes much less time to write a prescription versus communicating with patients so that they can better understand their illness.

HUtENTU. PRESSURE

Bauchner et al. found mat the major reason cited by 54% of pediatricians surveyed for inappropriate use of oral antibiotics was parental pressure. One-third of pediatricians reported at least occasionally dispensing an antibiotic when it was not indicated. More than three-fourths of these pediatricians believed that educating parents is required to promote appropriate antibiotic use.13

Are patients more satisfied with care if they leave with a prescription? A survey of physicians and patients by Harrtm et al. found that initially 65% of patients surveyed expected antibiotics for URIs. Physicians in this study inaccurately perceived their patients' expectations for antibiotics: they underestimated the proportion who expected antibiotics and were inaccurate in identifying which patients expected antibiotics. Patient satisfaction did not correlate with a prescription for antibiotics, but patients were more satisfied when they understood the illness and felt that the physician spent enough time with them.14

Another recent survey examined antibiotic prescription expectations and perceptions of parents and pediatricians. Physicians' perceptions of parental expectations for antimicrobials were the only significant predictor of prescribing antimicrobials for conditions of presumed viral etiology. Parental expectation for an antibiotic prescription was not associated with physician antimicrobial prescribing behavior. But if physicians thought a parent wanted an antimicrobial, they tried to "satisfy" him or her with an antimicrobial prescription 62% of the time versus 7% of the time when they did not think the parent wanted antimicrobials. The only significant predictor of parental satisfaction was communication with the care provider during the visit. Failure to provide antimicrobials did not affect satisfaction.15

Focus groups of parents with young children deny having expectations for antibiotics and are satisfied as long as they understand the reasons for the physician's choice of therapy.12 Surveys assessing parental knowledge show that parents often misunderstand appropriate indications for antibiotics. They feel that antibiotics are always or sometimes indicated for throat infections, colds, cough, and fever.16 Parents feel that antibiotics are needed for yellow or green nasal discharge and that antibiotics facilitate return to day care. These strong opinions of parents often influence the choice of treatment. Parents may pressure the pediatrician for an antibiotic for a diagnosis where it is not indicated or may even request a specific antibiotic or a different one than the pediatrician recommended because "that antibiotic doesn't work." Overall, they are misinformed and show a limited understanding of antimicrobial resistance.

Routinely giving antibiotics reinforces parental expectations that children will receive them in the future. Routine prescribing also fosters a feeling among parents that physicians who do not give antibiotics are not good physicians. A prescription for an antibiotic also sends parents the message that their child is really sick. With education, parents may pressure health care providers less to dispense antibiotics when they are not indicated. Some parents may even request waiting before prescribing antibiotics for an illness or may even question why antibiotics are being prescribed.

HOW TO CHANGE?

Educating patients is one goal, but physicians also need education. Physicians have individual and consistent patterns of prescribing antibiotics, and they often give diagnoses to justify treatment rather than the other way around. Re-education campaigns to reduce inappropriate oral antibiotic use must be balanced to include both patients and physicians.17 Various strategies for changing physicians' behavior include reminders, outreach visits, and education by opinion leaders. To be most effective, the intervention strategy must be patient mediated and the physician must be receptive to change.

These strategies have been successful around the world. In Japan, a striking 62% of group A streptococcal isolates were resistant to erythromycin in 1974, when macrolides accounted for 22% of all antibiotic use. By 1988, macrolides accounted for only 8% of antibiotic use, and less than 2% of group A streptococcal isolates were resistant to erythromycin.18 In Finland, nationwide recommendations for reductions in the use of macrolide antibiotics for respiratory and skin infections in outpatients resulted in reducing group A streptococcal isolates resistant to erythromycin from 16% to 8.6% (odds ratio, 0.5; CI , 0.4-0.5) by 1996.19 Similar observations have been reported for resistant pneumococci as well. With education and possible restriction of antimicrobials, we can make changes in resistance patterns. If unnecessary antibiotic use can be curtailed, the community as well as the individual patient will benefit.

Table

TABLETen Ways to Live Peacefully in a MIcrobial World

TABLE

Ten Ways to Live Peacefully in a MIcrobial World

WHAT CAN YOU DO?

Communicate and share the facts. An improved understanding by the general public as well as the recognition by physicians that patient satisfaction is not dependent on prescribing antibiotics will help principled physicians in their efforts to restrict antibiotic overuse. We need to explain to patients and to parents that unnecessary antibiotics can be harmful. We need to support national information campaigns to improve parental and patient awareness about antimicrobial resistance and unnecessary antibiotic use (Table).

Infection control practices such as immunization and hand washing go a long way in the battle. Providing education for health care professionals and parents and better infection control in day care centers will help to decrease some of the pressures to prescribe unnecessary antimicrobials. If antibiotics are indicated, the use of prophylaxis should be limited and as narrow a spectrum of antibiotic as possible should be used for as short of a course as clinically possible. All of these will help in the battle. We need to encourage immunizations. New protein conjugate vaccines for S. pneumoniae should become available within the next few years and may allow younger children to be successfully immunized.

The practical problems in the implementation of a strategy to promote judicious antimicrobial use are not insurmountable. We need to encourage all physicians to examine their own practices and to identify where they can decrease unnecessary antimicrobial use. We can improve diagnostic methods and communication with patients concerning lack of benefit, potential adverse effects, and development of resistance associated with unnecessary antibiotic therapy. It is important to develop a set of principles that are evidence based and promulgated in an effort to improve both patient care and public health, as opposed to containing costs or restricting care.

Globally we can advocate change in managed care policies to allow physicians to spend more time with patients and to ensure that managed care companies cover vaccination of their subscribers. As individuals, we can prevent bacterial resistance by supporting agricultural companies that do not use prophylactic antimicrobials in their animals or animal feed. We can make a difference if we have a united front.

Our goal of the next century will be to work in concert with bacteria and to leam the most important lesson of the antibiotic era - the microbe always wins.

REFERENCES

1. Dubos R. Pasteur in his time. In: McKeen TE, ed. The Pasteur Fermentation Centennial, 1857-1957. New York: Charles Pfizer; 1958.

2. Jernigan DB, Cetron MS, Breiman RF. Minimizing the impact of drug-resistant Streptococcus pneumoniae: a strategy from the DRSP Working Group. JAMA. 19%;275:206209.

3. McCaig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. /AAM. 1995;273:214-219.

4. Arnold KE, Leggiadro RJ, Breiman RF, et al. Risk factors for carriage of drug-resistant Streptococcus pneumonias among children in Memphis, Tennessee. / Pediatr. 1996;128:757-764.

5. Nyquist A-C, Gonzales R, Steiner J, Sande M. Antibiotic prescribing for children with colds, upper respiratory infections and bronchitis by ambulatory physicians in the United States. JAMA, 1998;279:875-877.

6. Nyquist A-C, Gonzales R, Steiner J, Sande M. Antibiotics for children with upper respiratory infections. JAMA. 1998;280:1401. Letter.

7. Mainous AG, Hueston WJ, Love MM. Antibiotics for colds in children: who are the high prescribers? Arch Pediatr Adolesc Med. 1998;152:349-352.

8. Schwartz RH, Freij BJ, Ziai M, Sheridan MJ. Antimicrobial prescribing for acute purulent rhinitis in children: a survey of pediatricians and family practitioners. Pediatr Infect Dis }. 1997;16:185-190.

9. Freij BJ, Schwartz RH, Sheridan MJ, Ziai M. The management of acute purulent rhinitis in children: contrasting the approaches of pediatrie infectious disease specialist and primary care physicians. In: Program and abstracts of the 36th annual IDSA meeting; Denver, Colorado; November 12-15, 1998. Abstract #734.

10. Todd JK, Todd N, Damato J, Todd WA. Bacteriology and treatment of purulent nasopharyngitis. Pediatr Infect Dis ]. 1984;3:226-232.

11. Heikkinen X Ruuskanen O, Ziegler T, Waris M, Puhakka H. Short-term use of amoxicillin-clavulanate during upper respiratory tract infection for prevention of acute otitis media. / Pediatr. 1995; 126:313-316.

12. Barden LS, Dowell SF, Schwartz B, Lackey C Current attitudes regarding use of antimicrobial agents: results from physicians' and parents' focus group discussions. Clin Pediatr. 1998^37:665-672.

13. Bauchner H, Pelton SI, Klein JO. Parents, physicians, and antibiotic use. Pediatrics. 1999;103:395-401.

14. Hamm RM, Hicks RJ, Bemben DA. Antibiotics and respiratory infections: are patients more satisfied when expectations are met? / Fam Pract. 1996;43:56-62.

15. Mangione-Smith R, McGlynn EA, Elliott MN, Krogstad P, Brook RH. The relationship between perceived parental expectations and pediatrician antimicrobial prescribing behavior. Pediatrics. 1999;103:711-718.

16. Palmer D, Bauchner H. Parents' and physicians' views on antibiotics. Pediatrics [serial online]. June 1997;99(6): E6. Available Internet: <http:/ /www.pediatrics.org/cgi/ content/full/99/6/e6/>.

17. Bauchner H, Philipp B. Reducing inappropriate oral antibiotic use: a prescription for change. Pediatrics. 1998;102: 142-145.

18. Fujita K, Murono K, Yoshikawa M, Murai T. Decline of erythromycin resistance of group A streptococci in Japan. Pediatr Infect Dis J. 1994;13: 1075-1078.

19. Seppälä H, Klaukka X Vuopio-Varkila J, et al. 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.

TABLE

Ten Ways to Live Peacefully in a MIcrobial World

10.3928/0090-4481-19990701-12

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