Antibiotic Stewardship in Inpatient and Outpatient Settings in Pediatric Practice

1. Introduction and Definition

Antimicrobial resistance has been identified by the World Health Organization (WHO) as one of the top 10 threats to global human health. Antimicrobial Stewardship (AMS) is defined as a set of coordinated interventions designed to improve and optimize the use of antimicrobial agents. The core principles involve selecting the optimal antimicrobial drug regimen, including the correct dose, duration of therapy, and route of administration.

The primary goals of an Antimicrobial Stewardship Program (ASP) are:

1. Optimize Clinical Outcomes: Achieving the best possible recovery for the patient.
2. Minimize Unintended Consequences: Reducing the risk of adverse drug events, Clostridioides difficile infections (CDI), and the emergence of antimicrobial resistance.
3. Cost Effectiveness: Reducing healthcare costs associated with unnecessary therapy.

It is critical to recognize that the goal is not merely to reduce antibiotic use, but to optimize it; however, because inappropriate use is prevalent (estimated at 25–50% of prescriptions), optimization often leads to de-escalation or discontinuation of therapy.

2. Rationale for Stewardship in Pediatrics

The necessity for ASPs in pediatric practice stems from the high prevalence of antibiotic exposure and the associated harms.

2.1. Magnitude of Use and Misuse

• Antibiotics are the most common class of medications prescribed to pediatric outpatients.
• Over 50% of pediatric inpatients receive antibiotics during hospitalization.
• Approximately 25% to 50% of these prescriptions are inappropriate regarding drug choice, dose, or duration.
• Irrational Therapy: Common examples include using antibiotics for viral upper respiratory infections, prescribing broad-spectrum agents (e.g., carbapenems) for community-acquired infections, and using redundant combinations.

2.2. Harms of Overuse

• Adverse Drug Events (ADEs): 21% of antibiotic courses among pediatric inpatients are complicated by an ADE. Each additional day of therapy increases the odds of an ADE by 7%.
• Resistance: Overuse drives the selection of multidrug-resistant organisms (MDROs), such as Extended-Spectrum Beta-Lactamase (ESBL) producing Gram-negatives and Vancomycin-Resistant Enterococci (VRE).
• C. difficile Infection: While less common in children than adults, CDI is a serious complication of antibiotic exposure.
• Microbiome Dysbiosis: Emerging research links early childhood antibiotic exposure to long-term health issues like obesity, asthma, and allergic diseases.

3. Core Elements of Stewardship Programs

Successful ASPs, whether inpatient or outpatient, rely on a multidisciplinary team usually led by an infectious diseases physician and a clinical pharmacist. The CDC outlines core elements essential for these programs:

1. Leadership Commitment: Dedicating necessary human, financial, and IT resources.
2. Accountability: Appointing a leader responsible for program outcomes.
3. Drug Expertise: appointing a pharmacist leader to improve antibiotic use.
4. Action: Implementing interventions to improve prescribing.
5. Tracking: Monitoring antibiotic use and resistance patterns.
6. Reporting: Sharing data with prescribers and staff.
7. Education: Educating clinicians about resistance and optimal prescribing.

4. Inpatient Antimicrobial Stewardship

In the hospital setting, ASPs utilize specific strategies to influence prescribing behaviors. These are broadly categorized into "front-end" and "back-end" strategies.

4.1. Primary Strategies

A. Preauthorization ("Front-End")

• Definition: Clinicians must obtain approval from the ASP team (ID physician or pharmacist) before or shortly after prescribing restricted antimicrobials (usually broad-spectrum or expensive agents).
• Pros: Allows immediate optimization of therapy, prevents unnecessary initiation of broad-spectrum drugs, and prompts diagnostic counseling.
• Cons: Resource-intensive (requires real-time availability), potential delay in therapy, and perceived loss of prescriber autonomy.

B. Prospective Audit and Feedback (PAF) ("Back-End")

• Definition: The ASP team reviews antimicrobial orders after a set period (usually 48–72 hours). They then contact the prescriber to recommend de-escalation, discontinuation, or modification based on culture results and clinical status.
• Pros: Generally well-received by clinicians, preserves autonomy, allows review of more clinical data (cultures), and is flexible.
• "Handshake Stewardship": A specific form of PAF where recommendations are delivered face-to-face during rounds. This builds collaborative relationships and is highly effective.

4.2. Supplemental Inpatient Interventions

1. Antibiotic "Time-Outs": A clinician-led reassessment of antibiotic need after 48–72 hours. This prompts the team to ask: "Does this patient still need antibiotics? Can we narrow the spectrum?".
2. Facility-Specific Guidelines: Developing local clinical practice guidelines for common conditions (e.g., community-acquired pneumonia, febrile neutropenia) based on local antibiograms (susceptibility patterns).
3. IV to Oral Conversion: transitioning patients to oral therapy when clinically stable reduces hospital stay, costs, and line-associated complications.
4. Dose Optimization: Pharmacists ensure optimal dosing (e.g., extended infusions for beta-lactams) and therapeutic drug monitoring for vancomycin and aminoglycosides to ensure efficacy and minimize toxicity.
5. Diagnostic Stewardship: Utilizing rapid diagnostic tests (e.g., PCR panels for blood cultures) to identify pathogens quickly, allowing faster de-escalation.
6. Penicillin Allergy De-labeling: Many patients report penicillin allergies but are not truly allergic. Assessing and removing incorrect allergy labels allows the use of first-line, narrow-spectrum beta-lactams.

5. Outpatient Antimicrobial Stewardship

The majority of antibiotic use occurs in the outpatient setting, presenting unique challenges such as high patient volume and time constraints.

5.1. Commitment and Communication

• Public Commitment: Displaying posters in waiting rooms stating the clinic’s commitment to judicious antibiotic use can reduce unnecessary prescribing.
• Communication Training: Educating providers to provide "positive recommendations" (what to do for symptoms) alongside "negative recommendations" (why antibiotics are not needed) improves parental satisfaction without prescribing antibiotics.

5.2. Actionable Strategies

1. Guidelines for Acute Respiratory Infections (ARIs): Since ARIs (otitis media, pharyngitis, sinusitis) drive most pediatric prescribing, strict adherence to diagnostic criteria is vital. For example, ensuring a diagnosis of Group A Streptococcus via rapid test/culture before treating pharyngitis.
2. Delayed Prescribing ("Wait-and-See"): For conditions like acute otitis media or sinusitis in eligible children, providers give a prescription but instruct parents to fill it only if symptoms worsen or do not improve after 48–72 hours. This empowers parents while reducing use.
3. Diagnostic Precision: avoiding empiric treatment for conditions where viral etiology is high (e.g., bronchiolitis) unless bacterial coinfection is proven.

6. Principles of Rational Antimicrobial Therapy

To support stewardship, every pediatric prescription should follow the principles of rational therapy:

1. Right Diagnosis: Use antibiotics only when a bacterial infection is suspected or proven. Do not treat viral infections or colonization (e.g., asymptomatic bacteriuria).
2. Right Drug: Choose the narrowest spectrum agent effective against the likely pathogen. For example, using amoxicillin for community-acquired pneumonia rather than broad-spectrum cephalosporins unless local resistance dictates otherwise.
3. Right Dose: Ensure adequate tissue concentrations to kill the bacteria while minimizing toxicity. Sub-therapeutic dosing contributes to resistance.
4. Right Duration: Treat for the shortest effective duration. Evidence now supports shorter courses for many pediatric infections (e.g., community-acquired pneumonia).
5. De-escalation: Streamline therapy from broad to narrow spectrum once culture and susceptibility results are available (usually at 48–72 hours).

7. Metrics and Measuring Success

An ASP must track its performance to demonstrate value and identify areas for improvement.

• Process Measures:
  • Days of Therapy (DOT): The preferred inpatient metric, defined as the number of days a patient receives an antimicrobial (normalized per 1,000 patient days).
  • Outpatient Metrics: Proportion of visits for ARIs resulting in an antibiotic prescription, or the percentage of broad-spectrum vs. narrow-spectrum agents used.
• Outcome Measures:
  • Reductions in C. difficile infection rates.
  • Reductions in antimicrobial resistance rates (though this takes time to manifest).
  • Cost savings (drug acquisition and administration costs).
  • Clinical outcomes (readmissions, length of stay, mortality) to ensure stewardship is safe.