Combination therapy is an attractive option for the treatment of multidrug-resistant (MDR) infections; however, limited data are available on combinations with ceftolozane-tazobactam (C-T). The pharmacodynamic chemostat model was employed to compare human-simulated exposures of C-T at 3 g every 8 h alone or in combination with amikacin at 25 mg/kg of body weight daily or colistin at 360 mg daily against four MDR isolates. C-T alone resulted in 24-h changes in the number of CFU of -0.02 ± 0.21, -1.81 ± 0.55, -1.44 ± 0.40, and +0.62 ± 0.05 log CFU/ml against isolates with C-T MICs of 4, 4, 8, and 16 μg/ml, respectively. Amikacin and colistin monotherapy displayed various results. The addition of amikacin to C-T resulted in -2.00 ± 0.23 ( < 0.001, additive)-, -1.50 ± 0.83 ( = 0.687, indifferent)-, -2.84 ± 0.08 ( = 0.079, indifferent)-, and -2.67 ± 0.54 ( < 0.001, synergy)-log CFU/ml reductions, respectively. The addition of colistin to C-T resulted in -3.02 ± 0.22 ( < 0.001, additive)-, -3.21 ± 0.24 ( > 0.05, indifferent)-, -4.6 ± 0.11 ( = 0.002, synergy)-, and -3.01 ± 0.28 ( < 0.001, synergy)-log CFU/ml reductions, respectively, against the MDR isolates with these MICs. Greater overall reductions in bacterial burden, including additive or synergistic interactions at 24 h, with C-T plus amikacin or colistin were observed against 3 out of 4 MDR strains tested, particularly those strains that were intermediate or resistant to C-T. Further studies assessing combination regimens containing C-T against MDR are warranted.

Background In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world, therefore, clinical strategies to avoid ICU admission are needed. Objective We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. Methods A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. Results 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P= 0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0∙1, P=0.0001) of ICU admission or death. Conclusions Tocilizumab in the early stages of the inflammatory flare, could avoid an important number of ICU admissions and mechanical ventilation use. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports.