APA Policy on Antibiotic Resistant

APA POLICY on CLINICAL and ENVIRONMENTAL FACTORS
CONTRIBUTING TO ANTIBIOTIC RESISTANT BACTERIA
by Kathi J Kemper MD, MPH and
The APA Standing Committee on Public Policy and Advocacy
(Chair, Charles N. Oberg, MD, MPH)


ABSTRACT


The emergence, growth and spread of bacteria with increasing resistance to antibiotics represents a significant health risk to children, particularly those children at greatest risk of serious infectious diseases (premature infants, hospitalized children, children who are dependent on immunosuppressive medications and those with compromised immune systems). Although antibiotics can provide life-saving benefits in the case of bacterial disease, the overuse of antibiotics contributes to the development and spread of resistant organisms as well as the transfer of resistant genes among pathogenic and non-pathogenic organisms. Two examples of such overuse include the use of antibiotics to treat children with non-bacterial infections and treating healthy livestock with antibiotics that are identical to or closely related to antibiotics used in human medicine.

Prestigious medical and public health authorities such as the Centers for Disease Control and Prevention (CDC), Institute of Medicine (IOM), Food and Drug Administration (FDA), World Health Organization (WHO), and the American Public Health Association (APHA) have cited bacterial resistance as an increasingly serious and costly medical and public health threat in need of much greater attention and action, including more education, research, and regulation. It is becoming increasingly more evident that the spread of bacterial resistance arises not only from overuse in human medicine, but also from overuse in animal agriculture, and that resistance developed in animals is spreading to human pathogens. Consistent with these positions, the Ambulatory Pediatric Association (its Board, Standing Committees and pertinent Special Interest Groups) proposes to raise awareness among pediatricians, families, public health programs and policy-makers of the environmental factors contributing to antibiotic resistant bacteria as well as develop strategies to reduce or eliminate the further growth and serious sequelae of antibiotic resistant bacteria. These strategies should include:

  • Health care providers should discourage the overuse of antibiotics in children and adolescents and encourage the prudent, responsible and sustainable use of antibiotics.
  • Families should be informed of the public health risks of the practice of using antibiotics which are identical to or closely related to those used in human medicine in order to treat or promote the growth of healthy livestock so that families may make informed decisions when purchasing meat products.
  • Pediatric education of medical students, residents, fellows, and ongoing continuing medical education of health professionals who care for children should include information on the clinical and public health risks of inappropriate antibiotic use.
  • Pediatric health services research should prioritize the evaluation of effective strategies to monitor and improve clinician antibiotic prescribing behavior with regard to appropriate use of antibiotics in infants, children and adolescents. In addition, this should include the clinical impact and health care costs associated with the agricultural use of antibiotics as growth promoters in livestock production.
  • The Ambulatory Pediatric Association (APA) should be active in coalitions advocating for responsible and sustainable clinical and agricultural use of antibiotics in humans and in livestock.

STATEMENT OF THE PROBLEM:



  • The development and spread of antibiotic resistant organisms represents a significant health risk to children and adolescents.

    Antibiotics represent an important scientific advance of the 20 th century and a valuable resource in combating serious infectious diseases among infants, children and adolescents. Factors that limit the effectiveness of antibiotics, such as those that promote bacterial resistance to antibiotics, jeopardize current and future pediatric care. Resistance of
  • E. coli to penicillin was first described in 1940 and the transfer of genetic material coding for resistance was described in 1952. It is now known that pathogenic bacteria, such as E. coli, can transfer DNA from other bacteria, including genes coding for antibiotic resistance. These transfers can occur in livestock and in the human gastrointestinal tract. Bacteria can also transfer DNA coding for virulent toxins such as Shig a toxins 1 .

    The rate of penicillin resistance increased by more than 300% and cefotaxime resistance increased by more than 1000% over a recent 5-year period 2. Erythromycin resistance has increased from 1% in 1992 to 44% of Strep pneumoniae ; resistance to trimethoprim-sulfamethoxazole has increased to 48% and resistance to penicillin has increased from 6% in 1992 to 42% in 2000 at the Children's Hospital in Columbus, Ohio. Antimicrobial resistance is also a substantial problem in treating Staphylococcal, E. coli, Salmonella, Campylobacter, Pseudomonas and other bacterial infections.

    The emergence of methicillin resistant Staphylococcal aureus (MRSA) infections in hospitals in the US has been a major public health concern. Soon after methicillin resistance was established, clinicians turned to other antibiotics, such as ciprofloxacin; however, within a few years 85% of isolates were also resistant to ciprofloxacin 3. Infections with MRSA have occurred even in children without identifiable predisposing risk factors 4, and pediatric deaths have been attributed to community-acquired methicillin resistant bacteria 5 . According to the US CDC, between 1990 and 1997, MRSA rates increased 260% in hospitals participating in the international monitoring programs. (http://www.cdc.gov/ncidod/focus/vol9no3/s_aureus.htm).

    The number of bacteria resistant to multiple antibiotics is also increasing, posing a serious threat to hospitalized children. For example, the prevalence of resistance to five antibiotics among certain strains of Salmonella has increased from 0.6% in 1979 to 34% in 1996 6 . The prevalence of drug resistant Streptococcal pneumonia is also increasing and appears to be directly linked with widespread use of antibiotics 7, 8, 9.
  • The inappropriate uses of antibiotics in both human medicine and livestock production contribute to the development and spread of antibiotic resistance.
    The US Centers for Disease Control and Prevention recommends against prescribing antibiotics for children with many common conditions including; otitis media with effusion lasting less than 3 months, 11 non-strep, non-gonococcal pharyngitis, 12 non-specific upper respiratory tract infection or the common cold 13 , 14 cough or bronchitis. 15 Inappropriate use of antibiotics remains common, both because of families' expectations and demands for antibiotics and because of physician practices 16 , 17 , 18 , 19 , 20 . In a survey of 531 pediatric office visits, antibiotics were prescribed for 44% of visits for a cold, 46% of non-specific upper respiratory infections and 75% of visits for bronchitis 21 . The available evidence suggests that the more antibiotics are used, the greater the selective pressure to develop antibiotic resistance and the faster resistance emerges. Further, there is evidence that this widespread, clinically unnecessary use of antibiotics has contributed to an increase and spread of resistant organisms. Yet it is evident that reductions in antibiotic use can lower the prevalence of antibiotic resistant organisms as has been demonstrated among children in day care centers 22 , 23 .

    Agricultural use of antibiotics is also a factor in the spread of resistant bacterial that causes human disease. Livestock consume a substantial proportion of the antibiotics used in the US. Many of these antibiotics are identical to or closely related to antibiotics used to treat human disease. Approximately 40% - 70% of all antibiotics used in the US are given to apparently healthy animals to enhance growth and prevent infections; this accounts for approximately 75% - 90% of all animal use of antibiotics 24. When used to promote growth (as opposed to treat specific diseases) antibiotics are given to large numbers of animals at sub-therapeutic doses (eg. 10 - 100 ppm per kg of feed). These are the perfect theoretic conditions to promote antibiotic resistance. Antibiotic use in animals selects for antibiotic resistant non-typhoid Salmonella serotypes which can be transferred to humans. Up to 80% of antibiotics fed to animals will be discharged into liquid or solid animal waste, and may contaminate nearby soil and ground water 25. These are the perfect theoretic conditions to promote antibiotic resistance in humans, and there is evidence to indicate that this does occur.

    Sub-therapeutic use of antibiotics in cattle has been linked to outbreaks of antibiotic resistant Salmonella infections in people who ate hamburger, including resistance to ceftriaxone 26 , 27. With the advent of the use of fluoroquinolones given prophylactically to healthy chickens and turkeys starting in 1996, the prevalence of fluoroquinolone resistance appeared in Campylobacter in chickens (reaching 18% by 1999). The FDA has recently proposed to bar the use of quinolone antibiotics in poultry raising operations due to the rapid emergency of quinolone-resistant bacteria in flocks treated with these antibiotics 28.

    Based on this information, the National Anti-microbial Resistance Monitoring System of the US Centers for Disease Control reports that antimicrobial resistant Salmonella result from the use of antimicrobial agents in food animals, and these antimicrobial resistant Salmonella are subsequently transmitted to humans through the food supply. Further, it urges non-antimicrobial infection control strategies in animals and the establishment of public health safeguards to minimize the development and dissemination of antimicrobial resistance 29. See the Internet site maintained by the CDC's International Network for the Study and Prevention of Emerging Antimicrobial Resistance (INSPEAR): http://www.cdc.gov/ncidod/hip/SURVEILL/inspear.HTM

Current Policy & Advocacy Activities to Reduce Disease Due to Resistant Bacteria:

Many groups have begun to develop information, policies and advocacy campaigns to address the overuse of antibiotics both in human medicine and among livestock. The California Medical Association has recognized that "the spread of bacterial resistance arises not only from overuse in human medicine, but also from massive use in animal agriculture, with increasing evidence that resistance developed in animals is spreading to human pathogens." The World Health Organization has recommended banning use of medically important antibiotics as growth promoters for livestock 31 . The European Union has banned the use of antibiotics for growth promotion in livestock 30 . In 1999, the Center for Science in the Public Interest (CSPI), Environmental Defense Fund (EDF) and Union of Concerned Scientists (UCS) petitioned the US FDA to rescind approvals for sub-therapeutic uses in livestock of any antibiotic identical to or closely related to those used in human medicine - including penicillin, tetracyclines and erythromycin. The National Academy of Sciences National Research Council reports that agricultural uses of antibiotics pose a risk to human health 32 . An American inter-agency Task Force on Antimicrobial Resistance was created in 1999. The Task Force is co-chaired by the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health. Participants also include the Agency for Healthcare Research and Quality, the Health Care Financing Administration, the Health Resources and Services Administration, the Department of Agriculture, the Department of Defense, the Department of Veterans Affairs, and the Environmental Protection Agency. These groups are consistent in their recommendations to evaluate, communicate and advocate on the need to reduce the increasing prevalence of resistance through the clinically and agriculturally appropriate use of antibiotics.
http://www.cdc.gov/drugresistance/index.htm. See also
http://www.cdc.gov/ncidod/dbmd/antibioticresistance/default.htm.

CONCLUSION:

The inappropriate use of antibiotics in clinical medicine and in raising livestock contributes to the development and spread of antibiotic resistant organisms. These organisms represent a serious threat to children and adolescents. The Ambulatory Pediatric Association proposes to raise awareness among pediatricians, families, public health programs and policy-makers of the problem of environmental factors contributing to antibiotics and develop strategies to reduce or eliminate the further growth and serious sequelae of antibiotic resistant bacteria. It proposes to do this via the work of its Board, Standing Committees and pertinent Special Interest Groups.

RECOMMENDATIONS:


The APA will support and encourage quality health services programs that:

  • Discourage the overuse of antibiotics in children and adolescents and encourage the prudent, responsible and sustainable use of antibiotics.
  • Inform families about the public health risks of the practice of using antibiotics which are identical to or closely related to those used in human medicine to treat animals.
  • Inform families regarding the public health risk of using any kind of antibiotics to promote the growth of healthy livestock.
  • Provide information to families regarding the selection of meat products from livestock raised without the use of antibiotics.

The APA will encourage and support the development of curricular materials so that medical students, residents, fellows, and the ongoing continuing medical education of health professionals who care for children are aware of the practices, costs and risks of and effective of methods of reducing;

  • the overuse of antibiotics for infants, children and adolescents;
  • the use of antibiotics that are identical to or closely related to those used in human medicine to treat illnesses in livestock;
  • the use of antibiotics to as growth promoters in otherwise healthy livestock.

The APA will support and encourage pediatric research focused on:

  • effective strategies to monitor and improve clinician behavior with regard to appropriate use of antibiotics in children;
  • assessing and monitoring the clinical impact and health care associated with using antibiotics in livestock;
  • the public health and environmental effects of antibiotic use in livestock production;
  • the impact of changing clinical and animal husbandry practices on antibiotic resistance.

The APA will participate and collaborate with other health and environmentally focused groups advocating for responsible and sustainable use of antibiotics in humans and in livestock, including (but not limited to)

  • American College of Preventive Medicine
  • American Medical Association
  • American Public Health Association
  • Canadian Association of Physicians for the Environment
  • Center for Science in the Public Interest
  • Environmental Defense Fund
  • Institute for Agricultural and Trade Policy
  • Tufts University-affiliated Alliance for the Prudent Use of Antibiotics
  • Union of Concerned Scientists
  • World Health Organization
  • American Society for Microbiology

The APA will publish articles and news about this issue in APA publications.

IMPLEMENTATION:

The Ambulatory Pediatric Association will undertake these efforts through the utilization of the Board and its relevant Standing Committees and/or Special Interest Groups over the next three years, at which time this policy shall be reviewed and amended as necessary.


REFERENCES:

1 Shoemaker NB, et al. Evidence for extensive resistance gene transfer among Bacteroides spp and among Bacteroides and other genera in the human colon. A ppl Envir Microbiol , 2001;67: 561-68

2 Dowell SF, et al. Acute otitis media: management and surveillance in an era of pneumococcal resistance - a report from the drug-resistant Streptococcus Pneumoniae therapeutic working group. Pediatr Infect Dis J , 1999;18:1-9

3 Coronado VG, et al. Ciprofloxacin resistance among nosocomial Pseudomonas aeruginosa and Staphylococcal aureus in the US. Infect Control Hosp Epid , 1995;16: 71-75

4 Herold BC, Immergluck LC, Maranan MC, et al. Community acquired methicillin-resistant Staphylococcus aureus in children without identified predisposing risk. JAMA , 1998;279:593-8

5 Center for Disease Control and Prevention. Four pediatric deaths from community-acquired methicillin resistant Staphylococcus aureus-Minnesota and North Dakota, 1979-99. MMWR , 1999;48:707-10

6 Dunne EF, Fey PD, Kludt P, et al. Emergence of domestically acquired ceftriaxone-resistant Salmonella infections associated with amp c beta-lactamase. JAMA , 2000;284: 3151-6

7 Arnold KE, Leggiadara RJ, Breiman RF, et al. Risk factors for carriage of drug-resistant Streptococcus pneumonia among children in Memphis, Tennessee. J Pediatr , 1996;128:757-64

8 Block SL, Harrison CJ, Hedrick JA, et al. Penicillin-resistant Streptococcus pneumonia in acute otitis media: risk factors, susceptibility patters and antimicrobial management. Pediatr Infect Dis J , 1995;14:751-9

9 Tan TQ, Mason EO, Kaplan SL. Penicillin-resistant systemic pneumococcal infections in children - a retrospective case control study. Pediatrics , 1993;92:761-7

10 Centers for Disease Control and Prevention. Careful antibiotic use . Atlanta, GA: CDC, 1998

11 Dowell SF, et al. Otitis media - principles of judicious use of antimicrobial agents. Pediatrics , 1998;101(1): 165-71

12 Schwartz B, et al. Pharyngitis - principles of judicious use of antimicrobial agents. Pediatrics , 1998;101(1): 171-4

13 O'Brien, et al. Cough illlness/bronchitis - principles of judicious use of antimicrobial agents. Pediatrics , 1998;101(1): 178-81

14 Rosenstein N, et al. The common cold - principles of judicious use of antimicrobial agents. Pediatrics , 1998;101(1): 181-84

15 Gadomski AM. Potential interventions for preventing pneumonia among young children: lack of effect of antibiotic treatment for upper respiratory infections. Pediatr Infect Dis J , 1993;12(2): 115-20

16 McCraig LF, Hughes JM. Trends in antimicrobial drug prescribing among office-based physicians in the United States. JAMA , 1995;273:214-9

17 Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for adults with colds, upper respiratory tract infections, and bronchitis by ambulatory care physicians. JAMA 1997; 278:901-4

18 Watson RL, Dowell SF, Jayaraman M, Keyserling H, Kolczack M, Schwartz B. Antimicrobial use for pediatric upper respiratory infections: reported practice, actual practice, and parent beliefs. Pediatrics 1999; 104:1251-7.

19 Bauchner H, Pelton S, Klein J. Parents, physicians, and antibiotic use. Pediatrics , 1999; 103: 395-401

20 Palmer D, Bauchner H. Parents' and physicians views on antibiotics. Pediatrics , 1997; 99:1-5

21 Nyquiest A-C, et al. Antibiotic prescribing for children with colds, upper respiratory tract infections and bronchitis. JAMA , 1998;279(11): 875-8

22 Stephenson J. Icelandic researchers are showing the way to bring down rates of antibiotic-resistant bacteria. JAMA ,1996;275(3): 175

23 Boken, et al. Colonization with penicillin-resistant Streptococcus pneumoniae in a child-care center. Pediatr Infect Dis J , 1993;12(2): 115-20

24 URL: http://www.ucsusa.org/release/01-08-01.html

25 Meyer M, et al. Occurrence of antibiotics in surface and ground water near confined animal feeding operations and waste water treatment plants using radioimmunoassay and liquid chromatography/electrospray mass spectrometry. Am Chem Soc Mtg. 3.27.2000. San Francisco, CA

26 Holmberg SD, et al. Drug-resistant Salmonella from animals fed antimicrobials. N Engl J Med , 1984;311: 617-22

27 Fey PD, et al. Ceftriaxone-Resistant Salmonella Infection Acquired by a Child from Cattle. N Engl J Med , 2000;342(17)

28 URL: http://www.fda.gov/oc/antimicrobial/taskforce2000.html

29 URL: http://www.cdc.gov/ncidod/dbmd/narms/pub/publications/angulo_f/angulo_f.htm

30 URL: http://www.who.int/emc-documents/zoonoses/whocdscsraph20004c.html

31 Falkow S, Kennedy D. Antibiotics, animals and people - again. Science magazine , 2001: Jan 19

32 National Research Council. The use of drugs in food animals: benefits and risks . Washington, DC; National Academy Press; 1998



 

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