Controlling Antibiotic Resistance: Physician as Advocate for Cautious Use of Antibiotics

Tina Tan, MD

The problem of increasing antibiotic resistance is a serious concern to any physician treating children. The pediatric population has the highest prevalence of infection with common pathogens that are resistant to many antibiotics. Plus, a major driving force in the development of resistance is the overuse of antibiotics, and children receive courses of antibiotics more frequently than adults.^1–3 Although in recent years office-based pediatricians have reduced antibiotic use,⁴ the inappropriate prescribing of antibiotics continues to be a major problem. One study revealed that antibiotics were prescribed to children at 75% of office visits for bronchitis and at 44% of visits for the common cold.³ According to the latest study of the National Ambulatory Medical Care Survey data, visit-based prescribing rates for bronchitis have not changed.⁴

Too often, physicians prescribe unneeded antibiotics in response to parental pressure.⁵ To help control the rapid emergence of antibiotic resistance, physicians are urged to take the time to explain to concerned parents that antibiotics are not required for common colds and viral infections, and that unnecessary antibiotics can actually harm their child by making more germs resistant to antibiotics. Parents need to hear this message from their child’s doctor, particularly since antibiotic resistance is dangerously on the rise. Educating parents becomes an important role that physicians can play in an effort to curb antibiotic use and minimize the emergence of new strains of antibiotic-resistant bacteria.

Antibiotic resistance trends

Sharing with families the facts about the increasing antibiotic resistance, and the factors that contribute to it, may help parents appreciate the magnitude of this problem. Explaining the local resistance trends might further help parents realize that unless antibiotics are used wisely, their children might be left without effective treatments for common bacterial infections.

Streptococcus pneumoniae

S. pneumoniae is the major bacterial pathogen responsible for otitis media, pneumonia, meningitis, and other serious bacterial infections in children. Multidrug-resistant community-acquired strains of this pathogen have become increasingly prevalent in this country.¹ In the Chicago area, overall pneumococcal penicillin resistance rates for sterile site isolates are now close to 50%, compared to 12% in 1994, and 44% in 1998. Also in the Chicago area today, 40% to 45% of the isolates have some resistance to ceftriaxone, while 25% to 30% of the isolates have now become highly resistant to this agent. This trend is disturbing, considering that there were no ceftriaxone-resistant isolates found in 1994.

Staphylococcus aureus

S. aureus is another common pediatric pathogen in which antibiotic resistance has continued to develop rapidly. In the 1950s, appearance of penicillin-resistant S. aureus necessitated treatment with methicillin. When methicillin-resistant S. aureus (MRSA) emerged in the late 1970s, it was mainly a hospital-acquired pathogen, with community-acquired illnesses found only in patients with predisposing risk factors, such as chronic liver, lung, or vascular disease. In recent years, however, the prevalence of community-acquired MRSA infections has been increasing among children without identified risk factors. In Chicago, a few years ago, these cases tended to concentrate on the South side of the city. Now, these strains are becoming more prevalent on the North side of the city as well.

Even more worrisome is the first documented case of infection caused by vancomycin-resistant S. aureus (VRSA) that was found in June 2002 in a Michigan patient with diabetes mellitus, peripheral vascular disease and chronic renal failure.⁶ This patient had been treated for a prior MRSA infection with vancomycin, and had received multiple courses of antibiotics, including vancomycin, to treat chronic foot ulcer infections. VRSA and vancomycin-resistant enterococci (VRE) were discovered in a culture of the patient’s infected foot ulcer.

Increased use of vancomycin began shortly after MRSA appeared. In the 1980s, VRE emerged, causing serious concern that these organisms would exchange genetic material with other gram-positive bacteria, such as S. pneumoniae and S. aureus, resulting in resistance to vancomycin and other antibiotics, and eliminating an important antibiotic option for many common but serious infections. Analysis of the first VRSA isolate demonstrated the presence of an acquired vancomycin-resistant determinant from the patient’s VRE isolate, suggesting that transfer of genetic material to S. aureus did in fact occur. The predisposing factors for this type of infection include: prior MRSA and VRE infections, prior and prolonged courses of vancomycin, and renal insufficiency or failure.

And in October the second VRSA isolate⁷ was reported, which is a sobering indication that the extensive and unnecessary use of antibiotics has finally caught up to us. We may be witnessing the beginning of an era in which very common but extremely resistant organisms are the norm rather than the exception.

Preventative measures

The implications of recent antibiotic resistance trends are worrisome, underscoring the importance of preventative strategies. Parents need to be educated about the efficacy and limitations of immunization, as well as be informed about the appropriate indications for antibiotic use.

Vaccinations

Immunization is one of the most effective means to prevent systemic pneumococcal infections in young children, and thereby decrease the use of antibiotics and the development of antimicrobial resistance. The recently licensed heptavalent pneumococcal conjugate vaccine contains 80% to 90% of the pneumococcal serotypes responsible for systemic pneumococcal infections in children younger than five years of age.⁸

The conjugate vaccine demonstrated a 97% efficacy against invasive pneumococcal disease and a 73% efficacy in the prevention of consolidative pneumonia.^9,10 Even though the vaccine has proven efficacy against pneumococcal pneumonia, it is limited by the fact that it provides protection against only 7 pneumococcal serotypes. Over the past decade, the incidence of complicated pneumonia caused by S. pneumoniae has been increasing, with many of these cases caused by serotypes that are not currently included in the conjugate vaccine. A retrospective study of 8 children’s hospitals, including Children’s Memorial, found that hospitalizations for complicated pneumococcal pneumonia increased from 22.6% in 1994 to 53% in 1999. Only 56% of patients with complicated disease had serotypes included in the conjugate vaccine.¹¹

A 23-valent pneumococcal polysaccharide vaccine is also available, in addition to the heptavalent protein conjugate vaccine. However, this vaccine has limited efficacy and immunogenicity in children less than 2 years of age.¹²

Appropriate indications for antibiotic use.

In routine practice, physicians can focus on explaining to parents that the appropriate use of antibiotics can protect their children from future infection by resistant bacteria. The Centers for Disease Control (CDC) recommends that physicians share with parents the treatment guidelines for distinguishing conditions that call for antibiotic treatments and those that clearly do not.

The CDC has developed one-page summaries on appropriate antibiotic use in various clinical situations. These guidelines can be downloaded from the Internet and used in discussions with parents.¹³ The summaries are based on evidence-based principles published by a group from the CDC, the American Academy of Pediatrics, and the American Academy of Family Physicians. Included are treatment guidelines for otitis media (acute vs. with effusion), rhinitis and sinusitis, pharyngitis (group A streptococcal vs. non-streptococcal), as well as cough illness and bronchitis. See Table 1 for an overview.

TABLE 1 Overview of Guidelines for Antibiotic Use in Children¹³ Recommendations by Centers for Disease Control and American Academy of Pediatrics
Diagnosis	Principles of Appropriate Antibiotic Use
Otitis Media	Classify episodes as acute otitis media (AOM) or otitis media with effusion (OME). Only treat proven AOM with antibiotics. Diagnosis requires: documented middle ear infection and signs or symptoms of acute local or systemic illness
Rhinitis	Do not use antibiotics for viral rhinosinusitis. Do not use antibiotics to treat mucopurulent rhinitis that frequently accompanies viral rhinosinusitis unless it persists without improvement for more than 10-14 days.
Sinusitis	Diagnose as sinusitis only in the presence of: prolonged nonspecific upper respiratory signs and symptoms (e.g., rhynorrhea and cough without improvement for more than 10-14 days) or more severe upper respiratory tract signs and symptoms (e.g., fever over 39°C, facial swelling, facial pain) Use the most narrow-spectrum agent that is active against the likely pathogens as initial antibiotic treatment of acute sinusitis.
Pharyngitis	Diagnose as group A streptococcal pharyngitis using a laboratory test in conjunction with clinical and epidemiological findings. Do not give antibiotics to a child with pharyngitis in the absence of diagnosed group A streptococcal infection. Penicillin remains the drug of choice for treating group A streptococcal pharyngitis.
Cough Illness and Bronchitis	Cough illness/bronchitis in children rarely warrants antibiotic treatment. Antibiotic treatment for cough lasting more than 10 days may occasionally be warranted: Pertussis should be treated according to established recommendations. Mycoplasma pneumoniae infection may cause pneumonia and prolonged cough (usually in children older than 5 years). A macrolide agent (or tetracycline in children 8 years or older) may be used for treatment. Children with underlying chronic pulmonary disease (not including asthma) may occasionally benefit from antibiotic therapy for acute exacerbations.

Physicians can build cooperation and trust with parents by discussing the disturbing trends of antibiotic resistance, the available immunization options, and the relative risks and benefits of antibiotic use. By advocating cautious use of antibiotics, physicians create an alliance with parents, which is crucial to controlling the growing threat of antibiotic resistance.

REFERENCES

1. Whitney CG, et al. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States. N Engl J Med 2000;343: 1917-1924.

2. McCaig LF, et al. Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA 1995;273:214-219.

3. Nyquist AC, et al. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA 1998;279:875-877.

4. McCaig LF, et al. Trends in antimicrobial prescribing rates for children and adolescents. JAMA 2002;287(23):3096-3102.

5. Bauchner H, et al. Parents, physicians, and antibiotic use. Pediatrics 1999;103:395-401.

6. Sievert DM, et al. Staphylococcus aureus resistant to vancomycin—United States, 2002. CDC MMWR 2002;51(26):565-567.

7. Miller D, et al. Public health dispatch: vancomycin-resistant Staphylococcus aureus—Pennsylvania, 2002. CDC MMWR 2002;51(40):902.

8. Hausdorff WP, et al. The contribution of specific pneumococcal serogroups to different disease manifestations: implications for conjugate vaccine formulation and use, part II. Clin Infect Dis 2000;30:122-140.

9. Black S, et al. Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children. Pediatr Infect Dis J 2000;19:187-195.

10. Shinefield HR, Black S. Efficacy of pneumococcal conjugate vaccines in large scale field trials. Pediatr Infect Dis J 2000;19:394-397.

11. Tan TQ, et al. Clinical characteristics of children with complicated pneumonia caused by Streptococcus pneumoniae. Pediatrics 2002;110(1):1-6.

12. Tan TQ: Prevention of pneumococcal meningitis. Curr Infect Dis Rep 2002;4(4):317-323.

13. CDC Careful antibiotic use. Pediatric Academic Detailing Sheets. Available at: http://www.cdc.gov/drugresistance/factsheets/index.htm. Accessed November 29, 2002.

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