{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T16:16:07Z","timestamp":1770740167724,"version":"3.49.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T00:00:00Z","timestamp":1656892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>After the MERINO trial with piperacillin\/tazobactam, the efficacy of \u03b2-lactam\/tazobactam combinations in serious infections involving extended-spectrum \u03b2-lactamase (ESBL)-producing pathogens merits special evaluation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To further confirm the efficacy of ceftolozane\/tazobactam in treating hospital-acquired\/ventilator-associated bacterial pneumonia (HABP\/VABP) involving ESBL-positive and\/or AmpC-producing Enterobacterales.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective subgroup analysis of the ASPECT-NP trial comparing ceftolozane\/tazobactam with meropenem for treating HABP\/VABP in mechanically ventilated adults (ClinicalTrials.gov NCT02070757). ESBLs were identified using whole genome sequencing. Chromosomal AmpC production was quantified employing a high-sensitivity mRNA transcription assay.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Overall, 61\/726 (8.4%) participants had all baseline lower respiratory tract (LRT) isolates susceptible to both study treatments and \u22651 baseline ESBL-positive\/AmpC-overproducing Enterobacterales isolate. In this subgroup (ceftolozane\/tazobactam n\u200a=\u200a30, meropenem n\u200a=\u200a31), baseline characteristics were generally comparable between treatment arms. The most frequent ESBL-positive and\/or AmpC-overproducing Enterobacterales isolates (ceftolozane\/tazobactam n\u200a=\u200a31, meropenem n\u200a=\u200a35) overall were Klebsiella pneumoniae (50.0%), Escherichia coli (22.7%), and Proteus mirabilis (7.6%). The most prevalent ESBLs were CTX-M-15 (75.8%), other CTX-M (19.7%), and SHV (4.5%); 10.6% of isolates overproduced chromosomal AmpC. Overall, 28\u2005day all-cause mortality was 6.7% (2\/30) with ceftolozane\/tazobactam and 32.3% (10\/31) with meropenem (25.6% difference, 95% CI: 5.54 to 43.84). Clinical cure rate at test-of-cure, 7\u201314\u2005days after end of therapy, was 73.3% (22\/30) with ceftolozane\/tazobactam and 61.3% (19\/31) with meropenem (12.0% difference, 95% CI: \u221211.21 to +33.51). Per-isolate microbiological response at test-of-cure was 64.5% (20\/31) with ceftolozane\/tazobactam and 74.3% (26\/35) with meropenem (\u22129.8% difference, 95% CI: \u221230.80 to +12.00).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data confirm ceftolozane\/tazobactam as an effective treatment option for HABP\/VABP involving ceftolozane\/tazobactam-susceptible ESBL-positive and\/or AmpC-producing Enterobacterales.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac184","type":"journal-article","created":{"date-parts":[[2022,7,4]],"date-time":"2022-07-04T13:06:59Z","timestamp":1656940019000},"page":"2522-2531","source":"Crossref","is-referenced-by-count":20,"title":["Ceftolozane\/tazobactam for hospital-acquired\/ventilator-associated bacterial pneumonia due to ESBL-producing Enterobacterales: a subgroup analysis of the ASPECT-NP clinical 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G","family":"Johnson","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0126-1782","authenticated-orcid":false,"given":"Mariana","family":"Castanheira","sequence":"additional","affiliation":[{"name":"JMI Laboratories , North Liberty, IA , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erin H","family":"Jensen","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer A","family":"Huntington","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Yu","sequence":"additional","affiliation":[{"name":"Merck & Co., Inc. , Rahway, NJ , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominik 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