What are the guidelines for antibiotic use according to the Lancet study?

WHO AWaRe Framework for Antibiotic Stewardship

The WHO Essential Medicines List establishes a three-tier classification system—Access, Watch, and Reserved—to optimize antibiotic use and combat antimicrobial resistance, with recommendations prioritizing infection-based treatment approaches over individual drug selection. 1

Core Framework Principles

The WHO guidelines fundamentally restructured antibiotic recommendations by shifting from medicine-based to infection-based approaches, identifying priority infections based on incidence, clinical relevance, treatment impact, and contribution to global antibiotic use. 1 This methodology privileges community-acquired infections over hospital-acquired infections and addresses empiric treatment (presumptive diagnosis) rather than targeted laboratory-confirmed treatment. 1

The AWaRe Classification System

The three-category system has clear implications for stewardship, monitoring, and assessment:

• Access antibiotics: First-line agents for common infections with narrow spectrum activity 1
• Watch antibiotics: Broader-spectrum agents requiring stewardship oversight due to higher resistance potential 1
• Reserved antibiotics: Last-resort agents for multidrug-resistant organisms, requiring strict restriction 1

Critical Context: The Resistance Crisis

Inappropriate antibiotic use affects 30-50% of all prescriptions, representing a well-established driver of antimicrobial resistance. 1 The COVID-19 pandemic exacerbated this problem, with most hospitalized patients receiving antibiotics (predominantly azithromycin and ceftriaxone) despite SARS-CoV-2 being viral and rarely complicated by bacterial superinfections. 1

Low- and middle-income countries bear the greatest AMR burden, yet reliable surveillance data remains concentrated in high-income countries. 1

Specific Antibiotic Selection Guidance

For Common Infections

The guidelines emphasize that antibiotic selection must consider local bacterial distribution and resistance patterns, not just broad efficacy data. 1 A critical limitation of many existing guidelines is their failure to match recommendations to local epidemiology or discuss ecological consequences of selecting broad-spectrum agents in low-resistance settings. 1

High-Risk vs. Low-Risk Patients

High-risk patients (prolonged neutropenia >7 days, ANC <100 cells/mm³, hypotension, pneumonia, abdominal pain, neurologic changes) require:

• Hospitalization with IV empirical therapy 1
• Monotherapy with anti-pseudomonal β-lactam agents: cefepime, meropenem, imipenem-cilastatin, or piperacillin-tazobactam 1
• Vancomycin is NOT recommended as standard initial therapy but reserved for specific indications: suspected catheter-related infection, skin/soft-tissue infection, pneumonia, or hemodynamic instability 1

Low-risk patients (anticipated brief neutropenia <7 days, minimal comorbidities):

• Candidates for oral empirical therapy 1
• Ciprofloxacin plus amoxicillin-clavulanate recommended for oral empirical treatment 1

Dosing and Duration Principles

Standard Treatment Duration

Treatment should continue for 48-72 hours beyond symptom resolution or bacterial eradication evidence. 2 For Streptococcus pyogenes infections, minimum 10 days treatment is mandatory to prevent acute rheumatic fever. 2

Renal Impairment Adjustments

For GFR <30 mL/min: Do NOT use 875 mg amoxicillin doses. 2

• GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours 2
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours 2
• Hemodialysis: Additional dose during and after dialysis 2

Critical Pitfalls to Avoid

Inappropriate Broad-Spectrum Use

Approximately 50% of ICU patients receiving antibiotics lack confirmed infections, while de-escalation and shortened treatment duration remain infrequently performed. 3 This represents a major stewardship failure.

Ignoring Local Resistance Patterns

Only 6.4% of guideline recommendations discuss antibiotic selection in relation to specific resistance and microbiological data. 4 An additional 27.5% reference resistance inconsistently. 4 This disconnect between recommendations and local epidemiology can lead to treatment failure or unnecessary broad-spectrum use.

Delayed Modification of Therapy

Antibiotic therapy should be streamlined at the earliest opportunity using laboratory results. 1 Sepsis parameters (temperature, respiratory rate, pulse, blood pressure, WBC, CRP) should be documented for audit purposes and chart review to enable rationalization. 1

Acute Respiratory Tract Infections

For acute uncomplicated bronchitis, pharyngitis, rhinosinusitis, and common cold in adults:

An estimated 50% of outpatient antibiotic prescriptions are unnecessary or inappropriate, equating to >$3 billion in excess costs annually in the United States. 1 The American College of Physicians and CDC emphasize that most acute respiratory infections do not require antibiotics, as they are predominantly viral. 1

Specific Syndrome Recommendations

The guidelines address empiric treatment for:

• Bloodstream infection 5
• Pneumonia 5
• Cellulitis/skin abscess 5
• Meningitis (ceftriaxone 50 mg/kg twice daily for 7-10 days as first-line) 1
• Urinary tract infections 1

Insufficient data exists for national-level recommendations for six other investigated syndromes, highlighting gaps in current surveillance systems. 5

Implementation Requirements

Healthcare System Level

• Antibiotic policy and formulary created after widespread consultation 1
• Regular measurement of antibiotic consumption with benchmarking 1
• Restricted lists of key agents 1
• Single-dose surgical prophylaxis should be standard practice 1
• Multidisciplinary drugs and therapeutics committee with transparent proceedings and declared conflicts of interest 1

Prescriber Level

All healthcare professionals involved in prescribing/dispensing (physicians, nurses, pharmacists), infection prevention specialists, AMR surveillance professionals, and policy-makers are the intended audience. 1

Blood cultures (minimum 2 sets) should be obtained before antibiotic initiation, with specimens from other suspected infection sites as clinically indicated. 1 Chest radiograph is indicated for respiratory signs or symptoms. 1