Reasons for Outpatient Antibiotic Stewardship

Diseases due to bacteria resistant to the antibiotics available are increasing at an alarming rate. Use of antibiotics by humans rose by 40% between 2000 and 2010, but the rate of new antibiotic development has slowed. Recent estimates of the burden of antimicrobial resistance suggest that there are approximately 700,000 deaths worldwide every year due to infections with antimicrobial resistant bacteria, with nearly 50,000 of these deaths occurring in the United States and Europe. A report led by economist Jim O’Neil on antimicrobial resistance commissioned by the British government in 2014 projected that the number of annual deaths attributable to antimicrobial resistance would surpass 10 million by the year 2050 if no meaningful interventions occur. These estimates suggests that death related to antimicrobial resistant infections will surpass cancer as the number one cause of mortality worldwide. (O’Neil, J. Review on Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations. (2014).)

Antibiotic treatment for a single outpatient infection has been shown to influence resistance patterns of future infections. (Paschke AA et al, “Previous antimicrobial exposure is associated with drug-resistant UTI in children”; Pediatrics 2010; 125: 664-672.); Kuster SP et al, “Previous Antibiotic Exposure and Antimicrobial Resistance in Invasive Pneumococcal Disease: Results From Prospective Surveillance,” Clin Infect Dis 2014; 59(7): 944-952.

Prominent examples of increasing antibiotic resistance threats commonly encountered in the outpatient pediatrics setting include:

Streptococcus pneumoniae

• S. pneumoniae is the most common cause of acute otitis media, community-acquired pneumonia, and sinusitis in children.
• Drug resistant Streptococcus pneumoniae is considered by the CDC to be a serious threat, with an estimated incidence of 1.2 million infections annually. (CDC. Antibiotic Resistance Threat Report, 2013.
• The nationwide Active Bacterial Core pneumococcal surveillance study from 2005-2013 found that 13.4% of invasive pneumococcal isolates obtained from children < 5 years of age were non-susceptible to macrolides, cephalosporins, tetracyclines or penicillins. (Centers for Disease Control and Prevention. 2013. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2013.)

Staphylococcus aureus

• (Tamma PD, Robinson GL, Gerber JS, Newland JG, DeLisle CM, Zaoutis TE, Milstone AM. Pediatric Antibiotic susceptibility trends across the United States. Infect Control Hosp Epidemiol. 2013 Dec;34(12):1244-51.)
  • A pooled pediatric antibiogram representing 200 pediatric healthcare institutions across the United States from 2005 and 2011 demonstrated that 50% of all Staphylococcus aureus isolates were methicillin-resistant and 21% of S. aureus isolates were resistant to clindamycin.

ESBL-Producing Enterobacteriaceae in Children

• Logan LK, Braykov NP, Weinstein RA, Laxminarayan R; CDC Epicenters Prevention Program. Extended-Spectrum β-Lactamase-Producing and Third-Generation Cephalosporin-Resistant Enterobacteriaceae in Children: Trends in the United States, 1999-2011. J Pediatric Infect Dis Soc. 2014 Dec;3(4):320-8.
  • National data from The Surveillance Network Database demonstrated an increase in prevalence of third generation cephalosporin-resistant and ESBL-producing Enterobacteriaceae, from 1.39% and 0.28% in 1999–2001 to 3% and 0.92% in 2010–2011 respectively.

See the Antibiotic Resistance page for more information.

• Overall, an estimated 1 in 3 outpatient prescriptions are inappropriate. (Fleming-Dutra K et al. Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011. JAMA. 2016 May 3;315(17):1864-73.) An estimated 49 million courses of antibiotics are prescribed annually in ambulatory pediatrics with 50% being broad spectrum antibiotics. (Hersh AL et al. Antibiotic prescribing in ambulatory pediatrics in the United States. Pediatrics. 2011 Dec;128(6):1053-61). The total number of excess prescriptions for acute respiratory illnesses is estimated to be 11.5 million. (Kronman M et al. Bacterial prevalence and Antibiotic prescribing trends for acute respiratory tract infections. Pediatrics. 2014 Oct;134(4):e956-65.)
• Proportion of broad-spectrum antibiotic prescribing increased from 2000 to 2010 among children and adolescents by 143%, more than in any other age group. (Lee GC, Reveles KR, Attridge RT, et al. Outpatient antibiotic prescribing in the United States: 2000 to 2010. BMC Med. 2014;12:96)
• For group A strep pharyngitis, up to 10,000 people are needed to be treated to prevent 1 case of acute rheumatic fever. (McMurray K, Garber M. Taking Chances with Strep Throat. Hosp Pediatr. 2015 Oct; 5(10): 552-4.)
• For every 14 children treated with an antibiotic for acute otitis media, one will experience an adverse drug reaction (eg. Vomiting, diarrhea, rash). (Venenkamp RP et al. Antibiotics for acute otitis media in children. Cochrane Database Syst Rev. 2015 Jun23;(6):CD000219.)

• In addition to risks to human health associated with handling and consuming meat products, the surrounding community is at higher risk of exposure to antibiotic residues and resistant bacteria via soil, water, and interaction with farm workers. While the existence of antibiotic residues in meat products is tightly regulated and not a topic of current concern, the U. S. Geological Survey (USGS) reported in March 2002 that antibiotics were present in 48 percent of the streams tested nationwide; and half of those tested were downstream from agricultural operations. (Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams, 1999−2000:  A National Reconnaissance. Dana W. Kolpin*, Edward T. Furlong, Michael T. Meyer, E. Michael Thurman, Steven D. Zaugg, Larry B. Barber, and Herbert T. Buxton Environmental Science & Technology 2002 36 (6), 1202-1211.)
• Multidrug-resistant pathogens have been associated with food-related illnesses. For example, a study dating back to April 1999 by the Government Accountability Office concluded that resistant strains of three microorganisms that cause foodborne illnesses in humans (Salmonella, Campylobacter, and E. coli) are linked to the use of antibiotics in animals.
• Soaps and household products (there are Antibiotics in products like toys and trays marketed specifically to children); see recent FDA ban on triclosan in soaps

• Antibiotics account for almost half of all ED visits for adverse drug events that result from systemic medication, (Lovegrove MC et al. US Emergency Department Visits for Adverse Drug Events From Antibiotics in Children, 2011–2015. J Pediatric Infect Dis Soc. 2018 Aug 23.)
• The frequency of adverse drug reactions related to trimethoprim-sulfamethoxazole in children has increased from 2000 to 2009, coincident with the increase in prescribing this drug for skin and soft tissue infections (Goldman JL, Jackson MA, Herigon JC, Hersh AL, Shapiro DJ, Leeder JS. Trends in adverse reactions to trimethoprim-sulfamethoxazole. Pediatrics. 2013 Jan;131(1):e103-8.)8

• The incidence of Clostridium difficile infections in children has increased over the past decade. Sammons JS, Toltzis P. Recent trends in the epidemiology and treatment of C. difficile infection in children. Curr Opin Pediatr. 2013 Feb;25(1):116-21.