Quantifying Gram-negative Resistance to Empiric Therapy in the Intensive Care Unit

Gram-Negative Bacterial Infections

Antimicrobial resistance is a global health emergency estimated to be responsible for 700,000 deaths per year worldwide, and it is well known that previous antibiotic exposure is the single most contributing factor. For example, the use of non-antipseudomonal agents can increase risk for any P. aeruginosa strain; however, the use of an agent with antipseudomonal activity would select for resistance to that particular antimicrobial agent or class. Demonstrated that each additional day of exposure to any antipseudomonal beta-lactam is associated with an increased risk of new resistance development. The study seeks to determine whether the choice of empiric therapy (i.e., the same agent versus a different agent from prior antibiotic exposure) has any effect on the likelihood of in vitro activity against GN pathogens (GNPs) in a subsequent infection.

Antimicrobials are the most commonly prescribed drugs in medicine, resulting in inappropriate use in approximately 50% of cases Misuse can have devastating effects through resistance development which further complicates selection of appropriate empiric antibiotics. In cases of severe illness, it is easy for clinicians to rely on broad spectrum antibiotics to cover the majority of likely pathogens when dealing with a presumed bacterial infection. However, this practice perpetuates the cycle of resistance. Inappropriate empiric therapy is associated with worse outcomes in resistant Gram-negative (GN) bacteremia and pneumonia, so clinicians should strive for targeted coverage that is specific to the pathogen of interest when possible. Johnson et al. showed that patients with recent antibiotic exposure had greater inappropriate initial antimicrobial therapy (45.4% vs. 21.2%; p \< 0.001) and higher in-hospital mortality (51.3% vs. 34.0%; p \< 0.001) compared with patients without recent antibiotic exposure. The 2020 Infectious Diseases Society of America (IDSA) Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections reports an increased risk of resistance with antibiotic exposure in the past 30 days. Additionally, expert opinion prompts consideration of empiric coverage with a GN agent from a different class that offers comparable spectrum of activity from previous exposure. The 2019 Community-acquired Pneumonia (CAP) Guidelines from the American Thoracic Society and IDSA lists prior antibiotic use in the last 90 days as a risk factor for P. aeruginosa.The 2016 Hospital-acquired and Ventilator-associated Pneumonia (HAP, VAP) Guidelines from IDSA, list antibiotic use in the past 90 days as a risk factor for P. aeruginosa and other GN organisms in HAP. Additionally, antibiotic use in the past 90 days is listed as having an association with increased risk of multi-drug resistant VAP. The CAP, HAP, and VAP Guidelines do not mention using the same versus different agent as empiric choice if previous antibiotic exposure is to an anti-pseudomonal agent.

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