{"id":972,"date":"2014-09-29T22:04:06","date_gmt":"2014-09-30T02:04:06","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=972"},"modified":"2014-09-29T22:04:06","modified_gmt":"2014-09-30T02:04:06","slug":"perusing-the-literature","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2014\/09\/29\/972\/perusing-the-literature\/","title":{"rendered":"Perusing the Literature"},"content":{"rendered":"

Inhibitor\u00a0of the\u00a0NDM\u00a0Enzyme<\/h3>\n

Aspergillomarasmine (AMA) was identified as an inhibitor of the New Delhi \"Bangla_Sahib_New_Delhi\"<\/a>
\nmetallo-betalactamase (NDM) enzyme. This substance, when combined with meropenem, restored antibiotic activity against an NDM lab strain.\u00a0 \u00a0AMA is a substance which was already tested in the past in humans.\u00a0 Concerns about interference with human metalloenzymes proved unfounded; it seems to have negligible toxicity.\u00a0 Currently, only colistin is active against NDM bacteria.\u00a0 None of the newer B-lactamase inhibitors (avibactam, MK-7655) inactivates NDMs.
\nOf note, tigecycline has poor activity against NDM-producers. [1]<\/a><\/p>\n

Altered Antibiotic\u00a0PK in Critically Ill Patients Requires Dosing Adjustments<\/h3>\n

Cefuroxime dosing, like that of other B-lactams, needs to be adjusted upwards in critically ill ICU patients. Especially when CLcr is in the normal range, standard doses are unlikely to achieve levels of T > MIC of 65% or greater.\u00a0 Hence, pathogens with MICs close to break point or patients with high CLcr may not be adequately covered with intermittent dosing.\u00a0 Based on PK\/PD data, a continuous infusion of high doses may be able to still provide bacterial killing.\u00a0 As the authors point out, clinical studies to confirm this approach\u00a0have\u00a0yet to be\u00a0performed.[2]<\/a><\/p>\n

First Case of Ciprofloxacin-Resistant Legionella pneumophila<\/h3>\n
\"Bellevue<\/a>
Bellevue Stratford – Philadelphia<\/figcaption><\/figure>\n

I guess it had to happen eventually: Bruin et al. report a patient infected with
\nL. pneumophila serogroup 1 who presented with severe respiratory insufficiency and interstial pneumonia.\u00a0 The organism MIC \u2013 tested at a reference lab – was 2 mg\/L.\u00a0 Sequencing of the gyrA gene revealed a point mutation in the QRDR (quinolone resistance determining region).\u00a0 It was not clear whether the organism was resistant already prior to ciprofloxacin therapy.[3]<\/a><\/p>\n

References<\/strong><\/p>\n

[1]<\/a> A King\u00a0 Nature 2014, 510: 503
\n[2]<\/a> M Carlier\u00a0 J Antimicrob Chemother 2014; 69: 2797
\n[3]<\/a> J Bruin,\u00a0 J Antimicrob Chemother 69: 2869, 2014<\/p>\n","protected":false},"excerpt":{"rendered":"

Inhibitor\u00a0of the\u00a0NDM\u00a0Enzyme Aspergillomarasmine (AMA) was identified as an inhibitor of the New Delhi metallo-betalactamase (NDM) enzyme. This substance, when combined with meropenem, restored antibiotic activity against an NDM lab strain.\u00a0 \u00a0AMA is a substance which was already tested in the past in humans.\u00a0 Concerns about interference with human metalloenzymes proved Continue reading Perusing the Literature<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":988,"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":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[227,3],"tags":[570,572,566,353,575,177,573,571,577,574,346,568,569,567,576,43],"class_list":["post-972","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-recent_literature","category-the_news","tag-antibiotic-pk","tag-antibiotic-pkpd","tag-aspergillomarasmine","tag-avibactam","tag-ciprofloxacin-resistance","tag-colistin","tag-continuous-infusion","tag-dosing-in-critically-ill-patients","tag-gyra","tag-legionella-pneumophila","tag-meropenem","tag-metallo-betalactamase","tag-mk-7655","tag-ndm","tag-qrdr","tag-tigecycline"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2014\/09\/NewLit-slider-copy.jpg?fit=640%2C200&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-fG","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":2186,"url":"https:\/\/allphasepharma.com\/dir\/2015\/12\/19\/2186\/aztreonam-plus-avibactam-a-new-bright-star-in-the-night-sky\/","url_meta":{"origin":972,"position":0},"title":"Aztreonam PLUS Avibactam \u2013 A New Bright Star in the Night Sky","author":"Harald","date":"December 19, 2015","format":false,"excerpt":"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\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"Avibactam - 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That may seem like an impressive record but it is also\u2026","rel":"","context":"In "QIDP Antibiotics"","block_context":{"text":"QIDP Antibiotics","link":"https:\/\/allphasepharma.com\/dir\/category\/qidp_antibiotic\/"},"img":{"alt_text":"qidp-part2-slider","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=350%2C200","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=350%2C200 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2016\/10\/QIDP-Part2-slider.jpg?resize=525%2C300 1.5x"},"classes":[]},{"id":3100,"url":"https:\/\/allphasepharma.com\/dir\/2017\/01\/24\/3100\/kill-mocking-bug-cre-crab-variety\/","url_meta":{"origin":972,"position":4},"title":"To Kill A Mocking Bug – of the CRKP or CRAB Variety","author":"Harald","date":"January 24, 2017","format":false,"excerpt":"Meropenem stands out as an antibiotic to be used first in ESBL and MDR infections, given its efficacy profile and safety record (see earlier blog). 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