Collective assessment of antimicrobial susceptibility among the most common Gram-negative respiratory pathogens driving therapy in the ICU.

Objectives: To describe the pathogen predominance and to evaluate the probability of covering the most common Gram-negative pathogens collectively in both empirical and early adjustment prescribing scenarios in ICU patients with respiratory infections.

Methods: Data were collected from an international cohort of hospitals as part of the SMART Surveillance Program (2018). Susceptibility testing (mg/L) was performed by broth microdilution methods.

Results: 7171 Gram-negative respiratory isolates from adult ICU patients across 209 hospitals from 56 different countries were studied. Overall, the most common ICU respiratory pathogens isolated were (25%), (18%), (14%), and (11%), with inter-regional differences among these pathogens. Among Enterobacterales, 36% were ESBL positive. When the collective susceptibility profile of this set of pathogens ( plus Enterobacterales; comprising 78% of all organisms isolated) was performed, ceftolozane/tazobactam (84%), followed by meropenem (81%), provided the most reliable activity in the empirical prescribing scenario compared with other β-lactam antibiotics. co-resistance was common among first-line β-lactam antibiotics. If was non-susceptible to piperacillin/tazobactam, less than one-third were susceptible to meropenem or ceftazidime. In contrast, ceftolozane/tazobactam offered coverage in over two-thirds of these resistant pathogens.

Conclusions: Ceftolozane/tazobactam demonstrated high cumulative susceptibility levels and activity in both empirical and adjustment antibiotic prescribing scenarios. High frequency of co-resistance undermines reliable coverage for Gram-negative pathogens already resistant to first-line agents. Ceftolozane/tazobactam would offer additional coverage in this setting.