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We queried the worldwide FDA Adverse Event Reporting System (FAERS) and performed disproportionality analysis, selecting only designated medical events (DMEs) where ceftolozane-tazobactam and ceftazidime-avibactam were reported as suspect. Serious neurological AEs were further investigated. The reporting odds ratios were calculated, deemed significant by the lower limit of the 95% confidence interval (LL95% CI) &gt;\u20091. All other drugs\/events recorded in FAERS and cephalosporins showing clinical evidence of neurological AEs were respectively selected as comparator for analysis of DMEs and neurotoxicity. Qualitative analysis including case-by-case assessment and deduplication was also performed. Overall, 654 and 506 reports mentioning respectively ceftolozane-tazobactam and ceftazidime-avibactam were found, with DMEs accounting respectively for 13.1% and 10.9% of cases. <jats:italic>Agranulocytosis<\/jats:italic> (<jats:italic>N<\/jats:italic>\u00a0=\u200912; LL95% CI\u2009=\u200912.40) and <jats:italic>pancytopenia<\/jats:italic> (14; 6.18) emerged as unexpected AEs with ceftolozane-tazobactam, while <jats:italic>acute pancreatitis<\/jats:italic> (7; 8.63) was an over-reported unexpected DME with ceftazidime-avibactam. After deduplication, four unequivocally different cases of <jats:italic>agranulocytosis<\/jats:italic> with ceftolozane-tazobactam were retained, occurring on average after 8.8\u00a0days. Causality was <jats:italic>probable<\/jats:italic> and <jats:italic>possible<\/jats:italic> respectively in three and one case. Among neurological AEs exhibiting significant disproportionality, <jats:italic>encephalopathy<\/jats:italic> with both antibiotics and <jats:italic>mental status changes<\/jats:italic> with ceftazidime-avibactam were retained in at least three cases after deduplication. Although rare, clinicians should monitor high-risk patients (i.e. individuals affected by haematological malignances, HIV infection, or treated with concomitant myelotoxic agents) for early unexpected occurrence of agranulocytosis with ceftolozane-tazobactam.<\/jats:p>","DOI":"10.1007\/s10096-020-04149-3","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T23:03:44Z","timestamp":1610060624000},"page":"1169-1176","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Serious adverse events with novel beta-lactam\/beta-lactamase inhibitor combinations: a large-scale pharmacovigilance analysis"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3018-3779","authenticated-orcid":false,"given":"Milo","family":"Gatti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0487-7996","authenticated-orcid":false,"given":"Emanuel","family":"Raschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-9595","authenticated-orcid":false,"given":"Fabrizio","family":"De Ponti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,7]]},"reference":[{"issue":"3","key":"4149_CR1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ijantimicag.2018.10.011","volume":"53","author":"D Koulenti","year":"2019","unstructured":"Koulenti D, Song A, Ellingboe A, Abdul-Aziz MH, Harris P, Gavey E, Lipman J (2019) Infections by multidrug-resistant Gram-negative Bacteria: what\u2019s new in our arsenal and what\u2019s in the pipeline? 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