Understanding Resistant Gram-Negative Infections Through Emerging Research

In this interview with Pharmacy Times, Ashlan Kunz Coyne, PharmD, MPH, discussed 3 pieces of research conducted by her and her team, of which one evaluated antimicrobial strategies for complex polymicrobial infections involving Pseudomonas and Stenotrophomonas, organisms that are frequently isolated together in clinical practice and can complicate treatment decisions. Her team investigated whether single-drug regimens effective against each pathogen individually could maintain activity when both organisms are present simultaneously, evaluating agents including ceftazidime/avibactam plus aztreonam, cefiderocol, and levofloxacin. Kunz Coyne explained that the goal was to identify regimens capable of targeting both organisms without immediately resorting to broader combination therapy, while also generating mechanistic insights that may eventually inform drug development and improve treatment approaches for polymicrobial infections.

She also detailed findings from retrospective analyses examining outcomes in hospitalized infections and the ongoing challenge of antimicrobial stewardship. Kunz Coyne noted that patients whose cultures were obtained more than 48 hours after admission experienced substantially higher mortality, though several factors may contribute to this difference, including higher baseline comorbidity burden and potentially more virulent or resistant isolates acquired during hospitalization. She emphasized the persistent uncertainty clinicians face when deciding whether to initiate newer broad-spectrum antimicrobials for resistant Gram-negative infections versus standard therapies, noting that although earlier active treatment is associated with improved outcomes, pharmacists and clinicians still lack reliable patient-level predictors to guide these decisions. According to Kunz Coyne, identifying which patients warrant earlier targeted therapy remains an important area of ongoing research.

Finally, Kunz Coyne highlighted emerging findings on the complex relationship between severe infections and neuropsychiatric outcomes in people living with HIV. One unexpected observation was that psychiatric comorbidity appeared to be associated with a longer interval before serious hospitalized bacterial or fungal infection, a finding that may reflect increased health care engagement, earlier intervention, or greater access to supportive services among some patients. However, she cautioned that important questions remain regarding causality and directionality, including whether severe infections accelerate neurocognitive decline or whether underlying vulnerabilities predispose patients to worse outcomes.

Looking ahead, Kunz Coyne expressed strong interest in antimicrobial stewardship discussions at the joint MAD-ID/SIDP meeting, particularly surrounding the long-term performance and resilience of newer antimicrobials for resistant Gram-negative infections as clinicians continue refining their role in practice.