Since the 1980s, antibiotic-resistant infections have become increasingly common. 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 (CDC. Antibiotic Resistance Threats in the United States, 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf) A 2014 UK government report projected that the number of annual deaths attributable to antimicrobial resistance would surpass 10 million by the year 2050 if no meaningful interventions occur, possibly surpassing 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. Providers must remember that every antibiotic course exposes each patient’s entire microbiome to that drug and strive to use antibiotics only when needed and to use the narrowest spectrum and shortest duration needed for the patient’s infection.
Prominent examples of increasing antibiotic resistance threats commonly encountered in the outpatient pediatrics setting include:
Streptococcus pneumoniae
- S. pneumoniae is a common cause of acute otitis media, community-acquired pneumonia, and sinusitis in children.
- Drug resistant S. pneumoniae is considered a serious by the CDC, with an estimated 2 million infections each year. In more than 30% of infections, the isolate will be resistant to one or more clinically useful antibiotics (CDC, Antibiotic Resistance Threat Report, 2019.)
- The nationwide Active Bacterial Core pneumococcal surveillance report from 2018 found that 4.7% of invasive pneumococcal isolates were resistant or intermediate to penicillin and 2.6% were resistant or intermediate to cefotaxime. However, resistance rates were alarmingly high to erythromycin (28.2%) and tetracycline (10.3%). (Centers for Disease Control and Prevention. 2018. Active Bacterial Core Surveillance Report, Emerging Infections Program Network, Streptococcus pneumoniae, 2018.)
Staphylococcus aureus
S. aureus is one of the most important pathogens in medicine. The rise of community-acquired methicillin-resistant S. aureus (CA-MRSA) in the late 1990s and early 2000s drove significant increases in use of anti-MRSA antibiotics, such as clindamycin. Since the mid-2010s, there has been a rise in clindamycin resistance in Staphylococcus aureus. Fortunately, MSSA has risen in prevalence over the same time.
- Sutter DE, Milburn E, Chukwuma U, Dzialowy N, Maranich AM, Hospenthal DR. Changing Susceptibility of Staphylococcus aureus in a US Pediatric Population. Pediatrics. 2016;137(4). doi:10.1542/peds.2015-3099
- In this US-wide study, oxacillin susceptibility rose while clindamycin susceptibility fell over time.
- Vicetti M, Mejias A, Leber A, Sanchez PJ. A decade of antimicrobial resistance in Staphylococcus aureus: A single center experience. PLoS One. 2019 Feb 12;14(2):e0212029.
- Retrospective review of >40,000 S. aureus isolates identified from inpatient and outpatient settings in a large children’s hospital demonstrated resistance to clindamycin and TMP-SMX increased among outpatient isolates between 2005-2014.
Group A Streptococcus
- While Streptococcus pyogenes remains highly susceptible to beta-lactam antibiotics, over the past decade increasing prevalence of clindamycin and macrolide resistance are being reported worldwide.
ESBL-Producing Enterobacteriaceae in Children
Some of the most worrisome antibiotic-resistant bacteria are MDR Enterobacterales, which includes species like E. coli and Klebsiella pneumoniae. These species may gain extended-spectrum beta-lactamase (ESBL) enzymes, which confer resistance to almost all beta-lactams except carbapenems, or carbapenemases, which make them resistant to carbapenems. Antibiotic exposure allows these highly resistant bacteria to flourish. These represent a significant threat to human health. They most often occur in patients with significant antibiotic and healthcare exposure, but they may occur in previously healthy patients, including children, as well.
- 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.
- Kaarme J, Riedel H, et al. Rapid Increase in Carriage Rates of Enterobacteriaceae Producing Extended-Spectrum β Lactamases in Healthy Preschool Children, Sweden. 2018 Oct;24(10):1874-1881.
- Healthy preschool children in Sweden had high prevalence of ESBL-producing Enterobacteriaceae stool carriage.
- Islam S, Selvarangan R, et al. Intestinal Carriage of Third-Generation Cephalosporin-Resistant and Extended-Spectrum β-Lactamase-Producing Enterobacteriaceae in Healthy US Children. 2018 Aug 17;7(3):234-240.
- Five percent of healthy US children had intestinal carriage of 3rd generation cephalosporin-resistant Enterobacteriaceae among 519 subjects between 14 days and 14 years old enrolled from 3 US sites 2013-2015.
- Logan LK, Weinstein RA. The Epidemiology of Carbapenem-Resistant Enterobacteriaceae: The Impact and Evolution of a Global Menace. The Journal of Infectious Diseases. 2017;215(suppl_1):S28-S36. doi:10.1093/infdis/jiw282
- A review of CRE epidemiology, including trends in pediatric patients.
See the Antibiotic Resistance page for more information.
