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 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.