Access without Excess: Stewardship-Linked Access to Reserve Antibiotics

Abstract

This seminar presents antimicrobial resistance (AMR) is a major global health threat, associated with roughly 5 million deaths annually, 4.3 million of which occur in low- and middle-income countries (LMICs). As frontline antibiotics fail, care depends on reserve antibiotics, yet access to these last-line drugs remains severely limited in LMICs: the parties that supply them face weak incentives to enter markets where overuse erodes effectiveness. Stewardship-linked access (SLA) conditions reserveantibiotic availability on demonstrated stewardship and has been proposed to address this access problem. We develop a game-theoretic model of the reserve-antibiotic supply chain to analyze what SLA costs and delivers for the hospital that prescribes and for the parties that supply thedrug. The supply side comprises an originator, which licenses the drug and bears the cross-market cost of the resistance it generates, and a manufacturer, which pays the entry cost and sells at a wholesale price. The hospital chooses frontline intensity and two stewardship actions for the reserve drug: rational access, prescribing it only when frontline treatment fails, and excess use, prescribing it when frontline drugs would suffice. Demand is endogenized through resistance dynamics. Rational access complements frontline treatment, while excess use substitutes for it, and both accelerate resistance. Wholesale pricing alone cannot ensure stewardship, which motivates an SLA cap on excess use. We calibrate the model to cefiderocol for urinary tract infections in India, charging the social cost of infection on the untreated population. Availability dominates the welfare comparison: at the documented cost-plus margin, introduction under SLA raises welfare by about USD 155 billion at India scale, while the differences among regimes, margins and caps amount 1 to a few billion. Under SLA, hospital compliance is self-enforcing, so no stewardship payment to hospitals is needed. Supply-side profit is negative at the calibrated resistance externality under every regime and margin, so entry requires external support that is an order of magnitude smaller than the value of availability. The welfare-maximizing cap on excess use is interior: a maximal cap leaves treatable patients untreated.