Diseases due to multidrug-resistant 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:
- 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.)
- 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.
- 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.
- Globally, studies using whole genome sequencing of Streptooccus pyogenes are increasingly reporting identification of ermA and ermB genes conferring macrolide resistance.
- Kimiko Ubukata, Takeaki Wajima, Miyuki Morozumi, Megumi Sakuma, Takeshi Tajima, Keita Matsubara, Koju Itahashi 5, Satoshi Iwata. Changes in Epidemiologic Characteristics and Antimicrobial Resistance of Streptococcus pyogenes Isolated Over 10 Years From Japanese Children With Pharyngotonsillitis. J Med Microbiol. 2020 Mar;69(3):443-450. doi: 10.1099/jmm.0.001158.
- Dharmapalan D, Inbanathan FY, Kharche S, et al. Whole genome shotgun sequences of Streptococcus pyogenes causing acute pharyngitis from India. Data Brief. 2018;18:1340‐1349. Published 2018 Apr 1. doi:10.1016/j.dib.2018.03.129
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.
- 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.
See the Antibiotic Resistance page for more information.