Abstract
This study reports the integrated analysis of two phase III studies of novel β-lactam/β-lactamase combination versus meropenem for treating nosocomial pneumonia (NP) including ventilator-associated pneumonia (VAP). The ASPECT-NP trial compared the efficacy and safety of ceftolozane–tazobactam versus meropenem for treating NP/VAP. The REPROVE trial compared ceftazidime–avibactam and meropenem in the treatment of NP/VAP. A total of 1528 patients (361 in the ceftolozane–tazobactam group; 405 in the ceftazidime–avibactam group; 762 in the meropenem group) were analyzed. The clinical cure rates at test-of-cure among the novel β-lactam/β-lactamase combinations group were non-inferior to those of the meropenem (70.7% vs. 72.1%, risk difference (RD) −0.01, 95% confidence interval (CI) 0.06–0.05) in the clinical evaluable populations. Overall 28-day mortality did not differ between novel β-lactam/β-lactamase combinations and the meropenem group (RD, −0.02, 95% CI, −0.09 to 0.05). Regarding the microbiological eradication rate, novel β-lactam/β-lactamase combinations were non-inferior to meropenem for Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Haemophilus influenzae, Staphylococcus marcescens, and Enterobacter cloacae. Finally, novel β-lactam/β-lactamase combinations had a similar risk of (i) treatment-emergent adverse events (RD, 0.02, 95% CI, −0.02 to 0.06), (ii) events leading to the discontinuation of the study drug (RD, 0.00, 95% CI, −0.02 to 0.03), (iii) severe adverse events (RD, 0.03, 95% CI, −0.01 to 0.07), and (iv) death (RD, 0.02, 95% CI, −0.02 to 0.05) when compared with meropenem group. In conclusion, our findings suggest that novel β-lactam/β-lactamase combinations of ceftolozane−tazobactam and ceftazidime–avibactam can be recommended as one of the therapeutic options in the treatment of NP/VAP.
Highlights
Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is the most common type of health care-associated infections [1]
Overall 28-day mortality did not differ between novel β-lactam/β-lactamase combinations and the meropenem group (RD, −0.02, 95% confidence interval (CI), −0.09 to 0.05)
The clinical cure rates at test-of-cure among the novel β-lactam/β-lactamase combinations group were non-inferior to those of the meropenem (70.7% vs. 72.1%, risk difference (RD), −0.01, 95% CI, 0.06−0.05) in the clinical evaluable populations (Figure 1)
Summary
Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is the most common type of health care-associated infections [1]. The emergence of antimicrobial resistance has largely limited the therapeutic option in this clinical condition. Novel β-lactam/β-lactamase combinations including ceftazidime–avibactam and ceftolozane–tazobactam have demonstrated potent in vitro activity against many multidrug-resistant organisms, and both of them have demonstrated clinical efficacy in the treatment of complicated intra-abdominal infection (cIAI) and complicated urinary tract infection (cUTI) [2,3,4,5,6]. Their role in the entity of NP/VAP remains unclear. Two large randomized trials, ASPECT-NP [7] and REPROVE [8], Antibiotics 2019, 8, 219; doi:10.3390/antibiotics8040219 www.mdpi.com/journal/antibiotics
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