{"id":2186,"date":"2015-12-19T11:48:29","date_gmt":"2015-12-19T16:48:29","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=2186"},"modified":"2016-03-23T04:39:09","modified_gmt":"2016-03-23T08:39:09","slug":"aztreonam-plus-avibactam-a-new-bright-star-in-the-night-sky","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/12\/19\/2186\/aztreonam-plus-avibactam-a-new-bright-star-in-the-night-sky\/","title":{"rendered":"Aztreonam PLUS Avibactam \u2013 A New Bright Star in the Night Sky"},"content":{"rendered":"

\"Avibactam<\/a><\/p>\n

Looking at the molecular structure of ceftazidime (CTAZ) and aztreonam (ATM), the differences are clear, and so are the similarities: ATM does not have the cephem ring structure of CTAZ, only the 4-member beta-lactam ring.\u00a0 However, the side chains are identical in both CTAZ and ATM which explains the overlapping gram-negative spectrum of both drugs.\"CTAZ<\/a><\/p>\n

With so little difference between the 2 molecules one would assume an augmented but otherwise identical Gram-negative activity spectrum when either drug is combined with avibactam (AVI).\u00a0 Avibactam, formerly known as NVX-104, is a novel non-beta-lactam beta-lactamase inhibitor (BLI). The combination with CTAZ was recently approved for cUTI and cIAI; it is on the market as Avycaz.\u00a0 A registration study for HAP\/VAP is ongoing, a logical next indication.\u00a0 So what could possibly be the rationale for developing an Aztreonam \/ Avibactam combination?\u00a0 What does it have over Avycaz?<\/p>\n

A recent publication by Vasoo et al. provides some helpful side-by-side comparison data.[1]<\/a>\u00a0 In this study of 177 carbapenemase-producing Gram-negatives, the combination of CTAZ\/AVI and ATM\/AVI had similar activity against isolates expressing Class A, C and D beta-lactamases, however only ATM\/AVI had reliable activity against the NDM pathogens which are Class B metallo-beta-lactamase producers.<\/p>\n

Table: \u00a0Comparison of Aztreonam and Ceftazidime with and without Avibactam\u00a0[1]<\/a>,\u00a0[2]<\/strong><\/a>, [3]<\/strong><\/a>,\u00a0[4]
\n<\/strong><\/a><\/strong><\/p>\n

\"Table<\/a>
Note<\/strong>: Corrections \/ comments \/ differentiating data are appreciated – will update based on your feed-back. Thank you!<\/figcaption><\/figure>\n

That is no minor differentiating factor\u00a0as only colistin, tigecycline and fosfomycin provide fairly reliable\u00a0coverage against these dreaded pathogens. As we know, reports of colistin resistance have recently sprung up more frequently. Colistin is a favorite drug in\u00a0pig farms in Southern China; it will soon lose the aura\u00a0of impregnable activity against MDR pathogens. Unfortunately, the tetracycline class of drugs does not seem to be quite as potent as other antibiotics even for pathogens in the susceptible MIC range, and resistance is also on the increase. For fosfomycin, there is just not enough data to determine whether it will hold up against CPEs. In addition, fosfomycin has a track record of\u00a0resistance developing rather quickly. [5]<\/p>\n

Both Avycaz and the combination ATM\/AVI were active against ESBLs, KPC and OXA-48 group isolates, demonstrating the superior potency of both drugs over carbapenem antibiotics.<\/p>\n

From a marketing perspective, it will be interesting to see how CTAZ\/AVI and ATM\/AVI will be positioned in the market.\u00a0 As it turns out, AstraZeneca has both combos in its portfolio.\u00a0 Well, with such outstanding potency ATM\/AVI should be an easy pitch:<\/p>\n

May The A+A<\/span> Force Be With You!<\/span><\/strong><\/h1>\n

Btw, the combination of ceftaroline plus avibactam seems to have been abandoned by Actavis\/Allergan.<\/p>\n

Abbreviations:
\n<\/strong>ATM\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 aztreonam
\nAVI\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 avibactam
\nBLI\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 beta-lactamase inhibitor
\ncIAI\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 complicated intra-abdominal infection
\nCPE \u00a0 \u00a0 \u00a0 carbapenemase-producing enterobacteriaceae
\nCTAZ \u00a0 \u00a0 ceftazidime
\ncUTI\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 complicated urinary tract infection
\nESBL \u00a0 \u00a0 extended-spectrum beta-lactamase
\nHAP \u00a0 \u00a0 \u00a0 hospital-acquired pneumonia
\nNDM\u00a0\u00a0\u00a0\u00a0\u00a0 New Delhi Metallo-beta-lactamase
\nVAP \u00a0 \u00a0 \u00a0 ventilator-associated pneumonia<\/p>\n

References:
\n<\/strong>[1]<\/a> Vasoo, S.\u00a0 In Vitro Activities of Ceftazidime-Avibactam, Aztreonam-Avibactam, and a Panel of Older and Contemporary Antimicrobial Agents against Carbapenemase-Producing Gram-Negative Bacilli.\u00a0 AAC 2015; 59: 7842
\n[2]<\/a> Bush, K. Other B-lactam antibiotics. Finch, R.: Antibiotic and Chemotherapy, Chapter 15; 9th ed, Elsevier, 2010
\n[3]<\/a> Craig, W. Chapter 21: Cephalosporins. In: Mandell: PPID 2015
\n[4]<\/a> Doi, Y.\u00a0 Chapter 22: Other Betalactam Antibiotics.\u00a0 In: Mandell: PPID 2015
\n[5]<\/a>\u00a0Morrill, \u00a0Treatment Options for Carbapenem-Resistant\u00a0Enterobacteriaceae<\/em> Infections. Open Forum Infect Dis<\/abbr> (Spring 2015) <\/span>2 <\/span>(2):<\/span>doi: 10.1093\/ofid\/ofv050<\/span><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

Looking at the molecular structure of ceftazidime (CTAZ) and aztreonam (ATM), the differences are clear, and so are the similarities: ATM does not have the cephem ring structure of CTAZ, only the 4-member beta-lactam ring.\u00a0 However, the side chains are identical in both CTAZ and ATM which explains the overlapping Continue reading Aztreonam PLUS Avibactam \u2013 A New Bright Star in the Night Sky<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":2191,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3],"tags":[292,1469,1271,403,585,353,974,1468,1471,1359,828,1467,288,177,358,898,78,1583,181,1466,43,79,1470],"class_list":["post-2186","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","tag-actavis","tag-allergan","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-astrazeneca","tag-avibactam","tag-avycaz","tag-aztreonamavibactam","tag-beta-lactamase-inhibitor","tag-bli","tag-ceftaroline","tag-ceftarolineavibactam","tag-ceftazidimeavibactam","tag-colistin","tag-cpe","tag-fosfomycin","tag-hap","tag-harald-reinhart","tag-mdr","tag-nxl-104","tag-tigecycline","tag-vap","tag-zinforo"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/12\/Avibactam-slider.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-zg","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":5040,"url":"https:\/\/allphasepharma.com\/dir\/2025\/08\/21\/5040\/an-intro-to-emblaveo-aztreonam-avibactam\/","url_meta":{"origin":2186,"position":0},"title":"An Intro to Emblaveo (aztreonam + avibactam)","author":"Harald","date":"August 21, 2025","format":false,"excerpt":"The FDA web site usually provides label and review documents for approved drugs.[1]\u00a0 Emblaveo, the combination of aztreonam and avibactam, was approved in February 2025, almost \u00bd year ago, but clinical review documents are still not posted at the site.[2]\u00a0 Hence, we do not know how Regulators felt about the\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=525%2C300&ssl=1 1.5x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=700%2C400&ssl=1 2x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=1050%2C600&ssl=1 3x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/08\/avibactam-Stick-Model.jpg?resize=1400%2C800&ssl=1 4x"},"classes":[]},{"id":2289,"url":"https:\/\/allphasepharma.com\/dir\/2016\/02\/10\/2289\/the-10-x-20-goal-are-we-on-track\/","url_meta":{"origin":2186,"position":1},"title":"The 10 x \u201920 Goal \u2013 Are We On Track?","author":"Harald","date":"February 10, 2016","format":false,"excerpt":"In the last decade (2000-2010), we saw the number of new antibiotic approvals drop successively each year; FDA changed the rules of the approval process without providing public guidance; many antibiotic companies fled the therapeutic area; investments were redirected to oncology projects which had a much better ROI. 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