Each year, 2 million Americans are infected with an antibiotic resistant infection. And for 23,000 Americans each year that infection will be fatal. These infections, which include Methicillin-resistant Staphylococcus aureus, Extended-Spectrum Beta-lactamase producing for gram negative infections, and Carbapenem-resistant Enterobacteriaceae strike both adults and children. For ESBL and CRE in particular, the group led by LaTonya Logan, published data demonstrating a dramatic increase in infections observed in children since 2005, 2006. Studies suggest that between 33% and 60% of children will receive at least one antibiotic while hospitalized. Studies have also shown that the biggest increase in antibiotic use is among our broad spectrum antibiotics. For example, Lanasalige use has increased over 200%. Furthermore, large variability in total use occurs when comparing free-standing children's hospitals, even when controlling for many factors associated with the severity of illness. The use in these hospitals range from 38 to 72 children receiving an antibiotic per 100 discharges. The majority of antibiotics, however, are used in the outpatient setting, with an estimated 49 million antibiotic prescriptions occurring in this setting in pediatrics. While antibiotics are important therapeutic agents, their use is often inappropriate. Among a group of four neonatal intensive care units, 806 of the 3,334 days of antibiotic, or 24% of the antibiotic days, were inappropriate. This resulted in 35% of these infants receiving inappropriate antibiotic use. These inappropriate uses included using too broad of a therapy when a narrower agent was available, treating colonization, and not stopping antibiotics when appropriate. A more recent study performed at a children's hospital observed that 11% of Vancomycin use and 6% of Cefepime use were inappropriate. The surgical services were the most likely groups to inappropriately use these antibiotics. Lack of de-escalation, or discontinuing, was the most common reason to be inappropriate. Antimicrobial stewardship programs, like the ones at the Children's Hospital of Philadelphia, improve the use of antibiotics in children's hospitals through the core strategies of pre-authorization, and or prospective audit with feedback. CHOP uses pre-authorization for most antibiotics, including vancomysin, meropenem, ceftriaxone, and many more. 20% of their interventions were targeting a known pathogen, and 18% were for an ID consult. They had a high compliance rate with these recommendations of up to 89%. The financial impact was a drug acquisition savings of $150,000. Importantly, their program led to better care, and the cost savings involved with making sure a child was dosed appropriately in the treatment of meningitis was not even determined. Prospective audit with feedback has also been a successful strategy in improving antibiotic use in children's hospitals. DuPont Children's Hospital in Wilmington, Delaware, demonstrated 21% decrease in doses of antibiotics with no changes to antibiotic resistance over the study period. At Children's Mercy Hospital in Kansas City, Missouri, a prospective audit with feedback program demonstrated an average monthly decrease in days of therapy per 1,000 patient days of 17% after the implementation of the program. Furthermore, the clinicians impacted by this program felt the program provided knowledge on appropriate antibiotic prescribing as well as improved the quality of care. Furthermore, the clinicians impacted by this program felt the program provided knowledge on appropriate antibiotic prescribing as well as improved the overall quality of care. Finally, a new study from Children's Hospital, Colorado, has shown the impact of a prospective audit with feedback program that involves daily rounding with all inpatient teams prescribing antibiotics. This method is termed handshake stewardship. In this model, the ASP team reviews all new antibiotics starts, and then does a daily rounding process where they meet with all medical and surgical teams to provide recommendations and to be available for questions. This program observed an overall decrease in antimicrobial use of 10%, and specifically absorbed a 22% and 25% decrease in meropenem and vancomycin use respectively. Pediatric specific clinical guidelines have been an effective strategy in improving the use of antibiotics in children. In a study performed by Dr. Ross Newman and colleagues from Children's Mercy Hospital in Kansas City, after the implementation of a community-acquired pneumonia clinical practice guideline, the use of ampicillin for hospitalized children with uncomplicated community-acquired pneumonia increased to over 60% of children receiving ampicillin after the implementation of the guideline. Furthermore, the use of amoxicillin also increased to over 90% of patients discharged, receiving this narrow spectrum antibiotics. Guidelines or care process models have also been effective in the treatment of a febrile infants in the first 90 days of life. Dr. Cary Buyington and colleagues demonstrated that after the implementation of their care process model that infants were more likely to receive the appropriate antibiotics and to have the antibiotics discontinued at 36 hours. Additionally, patients considered low risk were less likely to receive antibiotics. Finally, the total length of stay was decreased significantly without an increase in adverse events. Similar to adult ASPs, certain features should be in place to develop an effective pediatric ASP. Importantly, financial support for pharmacist and physicians is highly recommended. Adam Hersh and colleagues demonstrated that among a group of children's hospitals, those hospitals that provided financial support for these core providers saw the greatest decrease in antimicrobial use. The neonatal intensive care unit is a unique area for pediatric ASPs. Currently, the Vermont Oxford Network is conducting a quality improvement collaborative to improve the use of antibiotics in NICUs. Areas that hospitals have focused improving antibiotic use are early onset sepsis, necrotizing enterocolitis, and empiric treatment of late onset sepsis. For early onset sepsis in infants 34 weeks and older, a validated risk assessment took has been used to help clinicians know when it is safe to not prescribe antibiotics. This risk assessment tool uses the following factors. Highest maternal antipartum temperature, gestational age, length of time a mother's membranes were ruptured, group B streptococcal carriage status, and type of intrapartum antibiotics given. This data gives the estimated probability of culture-confirmed sepsis as risk per 1,000 live births. Additionally, by taking into account the clinical presentation, whether they are well, it's equivocal, or clinically sick, the provider can reliably determine if an antibiotic is needed. This tool has reliably determined 350 confirmed early onset sepsis among 608,014 live births. The author suggests the implementation of this tool could reduce the use of antibiotics in up to 240,000 US newborns each year. Other areas clinicians have been successful in improving antibiotic use in the NICU include standardizing the treatment recommendations involved with neonates NEC. This would include basing the use of anti-anaerobic antibiotics on whether perforation is present, and to only continue vancomycin when an ampicillin resistant has been cultured. Additionally, establishing areas of agreement of the duration of therapy for each Bell stage can be beneficial. Finally, the empiric treatment of late onset sepsis can be done, avoiding the use of vancomycin unless specific risk factors are present. Data has shown that the use of oxacillin or nafcillin has not been associated with worse outcomes, even in patients that are bacterimic with coagulase negative staphylococcus. Outpatient parenteral antimicrobial therapy is an important area for ASPs to intervene. A study from a free standing children's hospital observed that among OPAT episodes not having infectious diseases or ASP involvement, that up to 78% would have at least one recommendation. These recommendations include appropriate lab monitoring, dose and drug change, and reduction in treatment duration. Finally, up to 40% likely did not even need the OPAT therapy. A significant cost savings from this study was up to $4,000 per OPAT episode likely will occur from both the improved safety of the use of OPAT and the cost avoidance from eliminating its use. Finally, improving the use of antibiotics in the outpatient setting is paramount. Jeff Gerber published one of the initial seminal papers in the Journal of the American Medical Association in 2013. He performed a cluster randomized trial of outpatient practices in the suburban Philadelphia area. He divided the clinics into education only versus education plus audit and feedback. The audit and feedback group received quarterly antibiotic prescribing data on their use of broad spectrum antibiotics for acute otitis media, sinusitis, community acquired pneumonia, and group A streptococcal pharyngitis. They observed a 12.5% reduction in broad spectrum antibiotic prescribing for intervention practices, versus only a 5.8% for control practices. For community acquiring pneumonia and sinusitis, the difference in intervention versus control were 12 and 20% respectively. While these were impressive improvements in antibiotic use, when the quarterly reports were removed, the broad spectrum antibiotic use increased back to baseline. Additional work is needed to find the factors and strategies in the outpatient setting to improve antibiotic prescribing for children. So in summary, antibiotics are frequently used in children. Strategies in both the inpatient and outpatient setting have been successful in proving antibiotic use. More work is needed to assure that antimicrobial stewardship programs are implemented in all hospitals, and that children are included in the work of ASPs in all settings.
