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Antimicrobial resistance poses a substantial threat to global public health. The pursuit of new antibiotics has decreased and very few options have been investigated for the treatment of complicated multidrug-resistant Gram-negative (MDR-GN) infections in adult population and even less in pediatric patients. Ceftazidime-avibactam (CAZ-AVI) is novel cephalosporin/β-lactamase inhibitor (BL-BLI) combination with broad antibacterial spectrum. The aim of this review is to describe the current and future role CAZ-AVI in the pediatric population with suspected or confirmed MDR-GN infections.

Introduction: Antimicrobial resistance poses a substantial threat to global public health since it decreases the probability of effectively treating an infection and increases the risk of morbidity and mortality.Areas covered: In this review, the authors discuss the advantages and disadvantages of classical and novel trial designs for evaluating novel antibiotics for infections due to multidrug-resistant organisms (MDRO). An inductive literature search was performed using different keywords pertinent to the reviewed topics.Expert opinion: The need for active, effective compounds has strengthened regulatory, academic, and industry cooperation, leading to the recent approval of some novel anti-MDRO agents, with other promising compounds being also in the late phase of clinical development. Nonetheless, some important issues regarding the design of clinical trials have gained importance that are peculiar for novel anti-MDRO agents and should be addressed for continuing to guarantee the availability of effective treatments in the future. Very importantly, concerted cooperation with regulatory agencies will always be needed for continuously discussing and refining the acceptable level of evidence to be pursued through non-conventional and/or innovative trial designs or development strategies. Failure to do so would seriously pose the risk of perpetuating the unmet need for effective anti-MDRO agents.

Introduction Tedizolid phosphate is an oxazolidinone approved for the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) and active against methicillin-resistant Staphylococcus aureus. Aims The objective of this article was to review the evidence for the efficacy and safety of tedizolid phosphate for the treatment of ABSSSI. Evidence review Approval of tedizolid phosphate for the treatment of ABSSSI was based on the results of two phase III randomized controlled trials, ESTABLISH-1 (NCT01170221) and ESTABLISH-2 (NCT01421511), comparing 6-day once-daily tedizolid vs 10-day twice-daily linezolid. In ESTABLISH-1, noninferiority was met with early clinical response rates of 79.5% and 79.4% in tedizolid and linezolid groups, respectively (difference 0.1%, 95% CI -6.1% to 6.2%, with a 10% noninferiority margin). In ESTABLISH-2, noninferiority was met with 85% and 83% rates of early clinical response in tedizolid and linezolid groups, respectively (difference 2.6%, 95% CI -3.0% to 8.2%). Pooled data from ESTABLISH-1 and ESTABLISH-2 indicated a lower frequency of thrombocytopenia in tedizolid-treated than in linezolid-treated patients. Conclusion Tedizolid offers the option of an intravenous to oral switch, allows once-daily administration, and presents lower risk of myelotoxicity when a 6-day course is used for the treatment of ABSSSI. Greater economic cost associated with this antibiotic could be offset by its shorter treatment duration and possibility of oral administration in routine clinical practice, although either sponsored or nonsponsored postmarketing observational experience remains essential for ultimately confirming the effectiveness and tolerability of tedizolid outside clinical trials.