Research Proposal for Antimicrobial Stewardship Programs in Filipino Patients
A cluster-randomized controlled trial evaluating a multidisciplinary antimicrobial stewardship program in Philippine hospitals should prioritize mortality, length of stay, and antimicrobial resistance patterns as co-primary outcomes, with mandatory inclusion of clinical safety endpoints alongside process measures of antibiotic consumption.
Recommended Study Design
Primary Study Framework
Conduct a cluster-randomized controlled trial (cRCT) across multiple Philippine hospitals to establish both effectiveness and implementation outcomes simultaneously using a hybrid design 1. This approach addresses the critical gap in high-quality stewardship research, which currently consists predominantly of single-center observational studies with inadequate external validity 1.
Essential Outcome Domains
The study must prospectively define outcomes across three mandatory domains 1:
Clinical Outcomes (Safety Assessment):
- All-cause mortality at 30 days (primary safety endpoint) 1
- Length of hospital stay 1
- Clinical cure rates and time to clinical response 1
- Hospital readmission rates within 30 days 1
- Need for escalation of care to intensive care units 1
Microbiological Outcomes (Resistance Impact):
- Colonization rates with multidrug-resistant organisms (MDRO), specifically carbapenem-resistant Enterobacteriaceae and ESBL-producing organisms 1
- Healthcare-associated Clostridioides difficile infection incidence 2, 3
- Antimicrobial resistance patterns stratified by department, particularly ICUs 1
- Surveillance cultures for carbapenem-resistant organisms in high-risk units 1
Process Outcomes (Quality Measures):
- Antibiotic consumption measured in defined daily doses (DDD) per 1000 patient-days 4, 2
- Guideline adherence rates for empiric antibiotic selection 1
- Appropriateness of antibiotic prescribing (indication, spectrum, duration) 1
- Documentation quality of antibiotic indication and planned duration 1
Intervention Components
Core Stewardship Team Structure
Establish a multidisciplinary team coordinated by an infectious disease specialist (or specialist with documented infectious disease expertise if ID specialists are limited) 1. The team must include:
- Infectious disease physician or trained internist (coordinator) 1
- Clinical pharmacist with infectious disease training 1
- Infection control specialist/hospital epidemiologist 1
- Microbiologist for surveillance data and rapid reporting 1
- Surgeon with expertise in surgical infections 1
- Emergency department physician (critical for ED-based interventions) 1
- Hospital administrator for sustainability support 1
Specific Intervention Strategies
Implement systematic infectious disease consultation for all patients receiving broad-spectrum intravenous antibiotics, modeled after successful rehabilitation hospital programs that reduced antibiotic consumption from 42 to 22 DDD per 100 patient-days 3. This approach demonstrated:
- 71% reduction in carbapenem use 3
- 67% reduction in C. difficile infections 3
- Significant decreases in extensively drug-resistant organisms 3
Target specific high-impact antibiotics for restriction and audit:
- Carbapenems (imipenem, meropenem) 4, 2
- Piperacillin-tazobactam 2
- Fluoroquinolones (ciprofloxacin, moxifloxacin) 4, 2
- Colistin and tigecycline 2
- Glycopeptides (vancomycin, teicoplanin) 2
Establish immediate concurrent feedback (ICF) model with two-stage review: initial audit by trained infection control nurses, followed by physician-level feedback for non-compliant prescriptions 4. This sustainable model achieved 79.4% guideline conformance and 83.8% ICF compliance 4.
Critical Design Considerations
Sample Size and Non-Inferiority Margins
Power the study to demonstrate non-inferiority for mortality (ensuring patient safety) while showing superiority for antibiotic consumption reduction 1. The non-inferiority margin for 30-day mortality should be pre-specified at no more than 2% absolute difference, justified by baseline mortality rates in Philippine hospitals 1.
Include at least 8-12 hospital clusters (4-6 intervention, 4-6 control) to account for clustering effects and ensure adequate power 1. Single-center studies lack external validity and fail to address implementation barriers across diverse settings 1.
Addressing Context-Specific Barriers
Conduct baseline needs assessment addressing Philippine-specific challenges:
- Limited infectious disease specialist availability in rural/provincial hospitals 1
- Baseline antibiotic resistance patterns specific to local epidemiology 1
- Cultural factors affecting antibiotic prescribing and patient expectations 1
- Resource constraints for microbiology laboratory capacity 1
Incorporate qualitative evaluation through interviews with healthcare workers, administrators, and patients to identify implementation barriers and cultural factors affecting antibiotic use 1. This process evaluation is essential for distinguishing interventions that successfully change behavior from those that fail 1.
Surveillance Infrastructure Requirements
Mandate three baseline requirements before intervention implementation 1:
- Functional multidisciplinary antimicrobial stewardship team 1
- Annual microbiological resistance reports stratified by department (minimum: ICU data) 1
- Baseline antibiotic consumption data in standardized metrics (DDD per 1000 patient-days) 1
Establish active surveillance protocols for carbapenem-resistant Enterobacteriaceae using rectal surveillance cultures in high-risk units, proven highly effective when part of comprehensive infection control programs 1.
Implementation and Sustainability
Phased Rollout Strategy
Use stepped-wedge design where hospitals sequentially cross over from control to intervention at randomized time points 1. This design:
- Allows all hospitals to eventually receive the intervention (ethical advantage) 1
- Provides multiple baseline and post-intervention measurements 1
- Accounts for temporal trends in resistance patterns 1
Assess sustainability at 12,24, and 36 months post-implementation, particularly evaluating organizational impact, resource diversion, and cost-effectiveness 1. Programs showing initial success often fail without sustained administrative support 1.
Cost-Effectiveness Analysis
Include direct antibiotic cost savings as secondary outcome, with previous programs demonstrating 28-45% reductions in antimicrobial expenditures 2. One multi-hospital program achieved cumulative savings of 6.3 million Saudi Riyals with minimal program costs 2.
Calculate cost per MDRO infection prevented and cost per C. difficile case avoided, as these represent substantial downstream healthcare costs 2, 3.
Common Pitfalls to Avoid
Do not rely solely on process measures (antibiotic consumption) without clinical safety outcomes 5. Studies measuring only DDD reduction without mortality or clinical cure data cannot confirm patient safety 1.
Avoid uncontrolled before-after designs that dominate current stewardship literature but fail to account for temporal trends, regression to the mean, and selection bias 1. These designs provide low-quality evidence unsuitable for practice-changing recommendations 1.
Do not implement multifaceted interventions without process evaluation to identify which specific components drive observed effects 1, 6. Without fidelity assessment, it remains unclear whether interventions that fail did so because they were ineffective or poorly implemented 1.
Ensure adequate follow-up duration for resistance outcomes, as changes in colonization and infection patterns may require 12-24 months to manifest 1, 3. Short-term studies miss critical long-term safety and resistance signals 1.