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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  Pseudomonas aeruginosa  (25%),  Klebsiella pneumoniae  (18%),  Acinetobacter baumannii  (14%), and  Escherichia coli  (11%), with inter-regional differences among these pathogens. Among Enterobacterales, 36% were ESBL positive. When the collective susceptibility profile of this set of pathogens ( P. aeruginosa  plus Enterobacterales; comprising 78% of all organisms isolated) was performed, ceftolozane/tazobactam (84%), followed by meropenem (81%), provided the most reliable  in vitro  activity in the empirical prescribing scenario compared with other β-lactam antibiotics.  P. aeruginosa  co-resistance was common among first-line β-lactam antibiotics. If  P. aeruginosa  was non-susceptible to piperacillin/tazobactam, less than one-third were susceptible to meropenem or ceftazidime. In contrast, ceftolozane/tazobactam offered  in vitro  coverage in over two-thirds of these resistant pathogens.    Conclusions  Ceftolozane/tazobactam demonstrated high cumulative susceptibility levels and  in vitro  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.

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