There are many strategies that antimicrobial stewardship programs may use to encourage appropriate antibiotic prescribing. On this page we will highlight several of the most important, based on guidelines from CDC and IDSA/SHEA.
Prospective Audit and Feedback (PAF)
PAF allows clinicians to order antibiotics and then the ASP team reviews the use of this antibiotic and when an PAF allows clinicians to order antibiotics and then the ASP team reviews the use of this antibiotic and when an opportunity for antibiotic optimization is identified, the stewardship team contacts the prescribing team to provide recommendations. Depending on the institution, recommendations may be documented in the medical record. Some programs have successfully augmented the recommendation process by delivering recommendations face-to-face on “stewardship rounds,” a practice known as “Handshake Stewardship.”
References
- Key Publications
- Di Pentima MC, Chan S, Hossain J. Benefits of a pediatric Antibiotic stewardship program at a children’s hospital. Pediatrics. 2011;128(6):1062-1070. doi:10.1542/peds.2010-3589.
- Newland JG, Stach LM, Lurgio SAD, et al. Impact of a Prospective-Audit-With-Feedback Antibiotic Stewardship Program at a Children’s Hospital. J Ped Infect Dis. 2012;1(3):179-186. doi:10.1093/jpids/pis054.
- Hurst AL, Child J, Pearce K, Palmer C, Todd JK, Parker SK. Handshake Stewardship: A Highly Effective Rounding-Based Antibiotic Optimization Service. Pediatr Infect Dis J. May 2016. doi:10.1097/INF.0000000000001245.
- MacBrayne CE, Williams MC, Levek C, et al. Sustainability of Handshake Stewardship: Extending a Hand Is Effective Years Later. Clin Infect Dis. 2020;70(11):2325-2332. doi:10.1093/cid/ciz650
- Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2013;4:CD003543. doi:10.1002/14651858.CD003543.pub3.
- Stach LM, Hedican EB, Herigon JC, Jackson MA, Newland JG. Clinicians’ Attitudes Towards an Antibiotic Stewardship Program at a Children’s Hospital. J Ped Infect Dis. 2012;1(3):190-197. doi:10.1093/jpids/pis045.
Prior Approval
“Prior approval” or “preauthorization” refers to policies in which antibiotic orders must be approved by the stewardship program before the pharmacy will fill the order. So-called “restrictive policies” are highly effective in producing an immediate decline in utilization of targeted antibiotics (Davey et al, 2013). Prior approval encourages careful consideration of each case at the time of initial ordering, potentially preventing any unnecessary exposure to the targeted agent.
References:
- Davey P, Brown E, Charani E, et al. Interventions to improve antibiotic prescribing practices for hospital inpatients. Cochrane Database Syst Rev. 2013;4:CD003543. doi:10.1002/14651858.CD003543.pub3.
- LaRosa LA, Fishman NO, Lautenbach E, Koppel RJ, Morales KH, Linkin DR. Evaluation of Antibiotic therapy orders circumventing an Antibiotic stewardship program: investigating the strategy of “stealth dosing”. Infect Control Hosp Epidemiol. 2007;28(5):551-556. doi:10.1086/513535.
- Metjian TA, Prasad PA, Kogon A, Coffin SE, Zaoutis TE. Evaluation of an Antibiotic stewardship program at a pediatric teaching hospital. Pediatr Infect Dis J. 2008;27(2):106-111. doi:10.1097/INF.0b013e318158603a.
- Pakyz AL, Oinonen M, Polk RE. Relationship of carbapenem restriction in 22 university teaching hospitals to carbapenem use and carbapenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53(5):1983-1986. doi:10.1128/AAC.01535-08.
- Rahal JJ, Urban C, Horn D, et al. Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella. JAMA. 1998;280(14):1233-1237.
Clinical Guidelines / Protocols / Care Process Models
Standardization of care for common conditions has been an effective strategy to improve antibiotic use. Clinical guidelines/protocols/care process models are based on existing national or international practice guidelines and can be used to enhance guideline adherence. These guidelines can be adapted to best fit the particular settings and microbiologic patterns of the institutions that will utilize them. Examples of conditions that can be targeted by clinical practice guidelines (CPGs) include community-acquired pneumonia, acute hematogenous osteomyelitis, acute appendicitis, urinary tract infections, sepsis, and many others. Clinical pathways should be reviewed and updated as needed every three years.
References:
- Publications
- Smith MJ, Kong M, Cambon A, Woods CR. Effectiveness of Antibiotic guidelines for community-acquired pneumonia in children. Pediatrics. 2012;129(5):e1326-1333. doi:10.1542/peds.2011-2412.
- Willis ZI, Duggan EM, Bucher BT, et al. Effect of a Clinical Practice Guideline for Pediatric Complicated Appendicitis. JAMA Surg. 2016:e160194. doi:10.1001/jamasurg.2016.0194.
- Newman RE, Hedican EB, Herigon JC, Williams DD, Williams AR, Newland JG. Impact of a Guideline on Management of Children Hospitalized With Community-Acquired Pneumonia. Pediatrics. 2012;129(3):e597-e604. doi:10.1542/peds.2011-1533.
- Ambroggio L, Thomson J, Kurowski EM, et al. Quality Improvement Methods Increase Appropriate Antibiotic Prescribing for Childhood Pneumonia. Pediatrics. 2013;131(5):e1623-e1631. doi:10.1542/peds.2012-2635.
- Urinary Tract Infection: Clinical Practice Guideline for the Diagnosis and Management of the Initial UTI in Febrile Infants and Children 2 to 24 Months. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Pediatrics. 2011;128(3):595-610. doi: 10.1542/peds.2011-1330.
- Published and Publicly Available CPGs
Neonatal Specific Guidelines/Resources:
The care of neonates is highly specialized, and neonatal patients are vulnerable to a unique set of infections, such as early-onset sepsis, meningitis, and necrotizing enterocolitis. The highest-risk neonates are also at risk of nosocomial infectious complications, such as catheter-related bloodstream infection. The usual principles of antimicrobial stewardship apply, but strategies specific to this setting should be implemented.
Early-Onset Neonatal Sepsis
Puopolo KM, Benitz WE, Zaoutis TE, Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of Neonates Born at ≥35 0/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. December 2018, 142 (6) e20182894.
Puopolo KM, Benitz WE, Zaoutis TE, Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of Neonates Born at ≤34 6/7 Weeks’ Gestation With Suspected or Proven Early-Onset Bacterial Sepsis. Pediatrics. December 2018, 142 (6) e20182896.
Neonatal Early-Onset Sepsis Calculator (https://neonatalsepsiscalculator.kaiserpermanente.org/)
Puopolo KM, Lynfield R, Cummings JJ, Committee on Fetus and Newborn, Committee on Infectious Diseases. Management of Infants at Risk for Group B Streptococcal Disease. Pediatrics. August 2019, 144 (2) e20191881.
American College of Obstetrics and Gynecology Committee Opinion No. 797: Prevention of Group B Streptococcal Early-Onset Disease in Newborns: Correction. Obstet Gynecol. 2020. PMID: 32217968 https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/02/prevention-of-group-b-streptococcal-early-onset-disease-in-newborns
Role of serial physical Exams in reducing antibiotic use in neonates at risk for EOS
- Vatne A, Klingenberg C, Øymar K, Rønnestad AE, Manzoni P, Rettedal S. Reduced Antibiotic Exposure by Serial Physical Examinations in Term Neonates at Risk of Early-onset Sepsis. Pediatr Infect Dis J. 2020 May;39(5):438-443. doi: 10.1097/INF.0000000000002590. PMID: 32301920.
- Joshi NS, Gupta A, Allan JM, Cohen RS, Aby JL, Kim JL, Benitz WE, Frymoyer A. Management of Chorioamnionitis-Exposed Infants in the Newborn Nursery Using a Clinical Examination-Based Approach. Hosp Pediatr. 2019 Apr;9(4):227-233. doi: 10.1542/hpeds.2018-0201. Epub 2019 Mar 4. PMID: 30833294.
Late-Onset Neonatal Sepsis
There is a lack of consensus on the most appropriate antibiotic regimen to treat suspected late-onset neonatal sepsis. Empiric antibiotic regimens should be based on the most likely organisms for a particular unit and the clinical situation. Antibiotic choices should be guided by local susceptibility patterns and once an organism is identified, therapy should be tailored appropriately.
Necrotizing Enterocolitis
There is a lack of consensus of the most appropriate antibiotic regimen to treat suspected and/or confirmed necrotizing enterocolitis. In general, regimens should provide coverage for pathogens that cause late-onset sepsis and the addition of anaerobic coverage should be considered, although there is inadequate evidence to support a specific regimen. Antibiotic choices should be guided by local susceptibility patterns, and if an organism is identified, therapy should be tailored appropriately.
Health Care-Associated Infections in the NICU
Polin RA, Denson S, Brady MT, Committee on Fetus and Newborn, Committee on Infectious Diseases. Strategies for Prevention of Health Care–Associated Infections in the NICU. Pediatrics. May 2016, 137 (5) e20160592.
Polin RA, Denson S, Brady MT, Committee on Fetus and Newborn, Committee on Infectious Diseases. Epidemiology and Diagnosis of Health Care–Associated Infections in the NICU. Pediatrics. May 2016, 137 (5) e20160592.
Antibiotic Stewardship in Neonatal Intensive Care Units
Cantey SB, Patel SJ. Antimicrobial stewardship in the NICU. Infect Dis Clin North Am. 2014 Jun;28(2):247-61.
Mukhopadhyay S, Sengupta S, Puopolo KM. Challenges and opportunities for antibiotic stewardship among preterm infants. Arch Dis Child Fetal Neonatal Ed. 2019;104:F327–F332.
Willis Z, de St. Maurice A. Strategies to improve antibiotic use in the neonatal ICU. Current Opinion in Pediatrics. 2019;31(1):127. doi:10.1097/MOP.0000000000000716
Utilization of Rapid Diagnostics
The implementation of rapid diagnostic tools have had the greatest success in improving antibiotic use and patient outcomes when an ASP is involved. Examples include:
- Matrix-Assisted Laser Desorption and Ionization Time-of-Flight (MALDI-TOF)
- Decreased duration of unnecessary antibiotic therapy for coagulase-negative staphylococcal bloodstream contaminants
- Marked reduction (approximately 2.5 – 4 days) in duration of time prior to initiation of optimal antibiotic therapy for gram negative bacteria
- Reduction in overall length of inpatient hospital stay by 2-3 days
- Hospital cost savings of ~$20,000 – $30,000 per patient diagnosed with gram-negative sepsis
- Multiplex Polymerase Chain Reaction (PCR)/Nucleic Acid Assays
- Reduction in duration of therapy for blood culture contaminants
- Decreased overall length of inpatient hospital stay
- More rapid implementation of effective therapy aimed at treatment of multidrug-resistant pathogens
- Hospital cost savings of ~$20,000 per patient diagnosed with Staphylococcus aureus bacteremia
References:
- Willis ZI, de St. Maurice A. A Piece of the Puzzle: The Role of Molecular Testing in Antimicrobial Stewardship. J Pediatric Infect Dis Soc. 2021;, piab037, https://doi.org/10.1093/jpids/piab037
- Banerjee R, Teng CB, Cunningham SA et al. Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis. 2015 Oct 1;61(7):1071-80.
- Nagel JL, Huang AM, Kunapuli A, et al. Impact of Antibiotic Stewardship Intervention on Coagulase-Negative Staphylococcus Blood Cultures in Conjunction with Rapid Diagnostic Testing. J Clin Microbiol. 2014; 52: 2849-54.
- Perez KK, Olsen RJ, Musick WL, et al. Integrating Rapid Diagnostics and Antibiotic Stewardship Improves Outcomes in Patients with Antibiotic-resistant Gram-negative Bacteremia. J Infect. 2014; 69: 216-25.
- Malcolmson C, Ng K, Hughes S, et al. Impact of Matrix-Assisted Laser Desorption and Ionization Time-of-Flight and Antibiotic Stewardship Intervention on Treatment of Bloodstream Infections in Hospitalized Children. (2012). J Pediatric Infect Dis Soc. Advance online publication. doi: 10.1093/jpids/piw033
- Avdic E, Carroll KC. The Role of the Microbiology Laboratory in Antibiotic Stewardship Programs. Infect Dis Clin North Am. 2014; 28: 215-35
- Bauer KA, Perez KK, Forrest GN, Goff DA. Review of Rapid Diagnostic Tests Used by Antibiotic Stewardship Programs. Clin Infect Dis. 2014; 59 (S3): S134-45
- Box MJ, Sullivan EL, Ortwine KN, et al. Outcomes of Rapid Identification for Gram-Positive Bacteremia in Combination with Antibiotic Stewardship at a Community-Based Hospital System. Pharmacotherapy. 2015; 35: 269-76
- Bauer KA, West JE, Balada-Llasat J, Pancholi P, Stevenson KB, Goff DA. An Antibiotic Stewardship Program’s Impact with Rapid Polymerase Chain Reaction Methicillin-Reistant Staphylococcus aureus/S. aureus Blood Culture Test in Patients with S. aureus Bacteremia. Clin Infect Dis. 2010; 51: 1074-80
- Walker T, Dumadag S, Lee CJ, et al. Clinical Impact of Laboratory Implementation of Verigene GC-GN Microarray-Based Assay for Detection of Gram-Negative Bacteria in Positive Blood Cultures. J Clin Microbiol. 2016; 54: 1789-96
- Nelson MU, Bizzarro MJ, Baltimore RS, Dembry LM, Gallagher PG. Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in a Neonatal Intensive Care Unit in the Decade Following Implementation of an Active Detection and Isolation Program. J Clin Microbiol. 2015; 53: 2492-2501.
Cascading Antimicrobial Susceptibility Reports
The Clinical Microbiology lab can provide “cascading” antimicrobial susceptibility results. In this approach, the lab reports only susceptibilities for the narrowest effective member of a class and/or excluding classes when superior alternatives exist. For example, when a patient’s urine culture grows E. coli, the lab will likely test susceptibility to carbapenems. If, however, the isolate is susceptible to ceftriaxone, the lab should not report the carbapenem result. If needed, providers can request the carbapenem result. This strategy encourages use of narrower-spectrum effective antibiotics. The design of such algorithms requires significant input from infectious diseases clinical experts, which the ASP can provide.
References
- Vissichelli NC, Orndahl CM, Cecil JA, et al. Impact of cascade reporting of antimicrobial susceptibility on fluoroquinolone and meropenem consumption at a Veterans’ Affairs medical center. Infect Control Hosp Epidemiol. Published online April 6, 2021:1-6. doi:10.1017/ice.2021.83
- Liao S, Rhodes J, Jandarov R, DeVore Z, Sopirala MM. Out of Sight-Out of Mind: Impact of Cascade Reporting on Antimicrobial Usage. Open Forum Infect Dis. 2020;7(2):ofaa002. doi:10.1093/ofid/ofaa002
Penicillin Allergy Testing
Up to 10% of the US population reports a beta-lactam allergy, but the majority do not have a clinically significant allergy or hypersensitivity. Beta-lactams are frequently the most effective and safest antibiotic options for infections in both the inpatient and ambulatory setting; inaccurate beta-lactam allergy reporting results in use of antibiotics that are less safe, less effective, and/or more expensive. For example, a patient with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia who reports a beta-lactam allergy may receive treatment with vancomycin, which is less effective and more toxic than a penicillin or first-generation cephalosporin. There have been significant advances in the assessment of reported beta-lactam allergies, with many patients able to be de-labeled using protocols that combine history, skin testing, and/or oral challenges.
Jones TW, Fino N, Olson J, Hersh AL. The impact of beta-lactam allergy labels on hospitalized children. Infect Control Hosp Epidemiol. 2021;42(3):318-324. doi:10.1017/ice.2020.424
Vyles D, Antoon JW, Norton A, et al. Children with reported penicillin allergy: Public health impact and safety of delabeling. Ann Allergy Asthma Immunol. 2020;124(6):558-565. doi:10.1016/j.anai.2020.03.012
Shenoy ES, Macy E, Rowe T, Blumenthal KG. Evaluation and Management of Penicillin Allergy: A Review. JAMA. 2019;321(2):188-199. doi:10.1001/jama.2018.19283