The Rising Price of Resistance – Confronting the Cost of Care in Gram-negative Bacterial Infections

Antimicrobial resistance (AMR) is a critical global health issue, driven by the misuse and overuse of antibiotics across human, animal, and environmental sectors. Among the most pressing concerns is the rise of AMR in Gram-negative bacteria (GNB)–notably Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa. These pathogens are often multidrug-resistant (MDR) or extensively drug-resistant, leaving clinicians with limited therapeutic options and patients with poor prognoses. Resistant Gram-negative bacterial infections are consistently associated with prolonged hospital stays, increased intensive care unit admissions, higher mortality rates, and substantial financial burdens for both healthcare systems and patients. MDR GNB infections, in particular, can extend hospitalization by up to 2 weeks and increase costs by USD 4000–9000 per patient, depending on the infection site and resistance profile.1,2 In India and other low- and middle-income countries (LMICs), where out-of-pocket healthcare expenditure is high, such infections often lead to catastrophic health spending. Direct costs include extended hospitalizations, the use of expensive last-line antibiotics like ceftazidime-avibactam or colistin, and intensive supportive care for complications such as sepsis or organ failure. Indirect costs–ranging from lost productivity to long-term disability and postdischarge rehabilitation–are less quantifiable but significantly contribute to the economic impact.3 Carbapenem-resistant Enterobacterales and A. baumannii are particularly concerning, with mortality rates ranging from 30% to over 50%, especially in cases of bloodstream infections or ventilator-associated pneumonia.4,5 Diagnostic delay, presence of severe comorbid conditions, limited antimicrobial availability, and inappropriate empiric therapy often lead to worse outcomes and inflated treatment costs.6 Despite the magnitude of the problem, investments in antimicrobial stewardship, infection prevention, and rapid diagnostics remain insufficient. A study from Southeast Asia demonstrated that targeted antimicrobial stewardship interventions reduced antibiotic usage and costs by nearly 20% without compromising clinical outcomes.7 Unfortunately, access to new and effective antibiotics remains inequitable. Advanced agents like cefiderocol and meropenem–vaborbactam are often unavailable in LMICs due to high costs and regulatory delays. Consequently, clinicians may resort to less effective or more toxic therapies, compounding both clinical failures and financial strain. A WAY FORWARD Addressing the rising cost of resistant Gram-negative bacterial infections requires a comprehensive, multisectoral approach. Health systems must integrate AMR cost tracking, expand investments in stewardship, diagnostics, and surveillance, and improve access to last-line antibiotics through subsidies or pooled procurement. Insurance reforms are essential to protect patients in low-resource settings from catastrophic expenses. Simultaneously, accelerating diagnostic innovation, enforcing strict antimicrobial stewardship, investing in next-generation therapies such as phage or antibody-based treatments, and strengthening infection control measures are critical. Global collaboration is vital to harmonize data sharing and coordinate international efforts to combat AMR effectively. The World Bank has projected that by 2050, drug-resistant infections could cause a 3.8% drop in global GDP and push up to 28 million people into extreme poverty annually.8 This economic dimension of AMR must no longer be an afterthought. Every resistant infection averted is a life saved and a cost avoided. The global health community must urgently align clinical practice, policy, and economic strategy to mitigate the growing toll of GNB