{"id":1451,"date":"2015-05-14T14:50:23","date_gmt":"2015-05-14T18:50:23","guid":{"rendered":"http:\/\/allphasepharma.com\/dir\/?p=1451"},"modified":"2015-05-16T03:02:52","modified_gmt":"2015-05-16T07:02:52","slug":"no-easy-day-dose-calculations-for-aminoglycosides-and-vancomycin","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2015\/05\/14\/1451\/no-easy-day-dose-calculations-for-aminoglycosides-and-vancomycin\/","title":{"rendered":"No Easy Day: Dose Calculations for Aminoglycosides and Vancomycin"},"content":{"rendered":"
\"Dosing<\/a>
Fig 1: Dosing Nomogram for AG – once daily<\/figcaption><\/figure>\n

Searching data on antibiotic use in surgery prophylaxis, I came across an article from the Mayo Clinic\u00a0[1]<\/a>.\u00a0 The authors mention that approx. 75% of patients that developed surgical site\u00a0infections did not get proper antibiotic prophylaxis.\u00a0 Errors were made in (1) selection of the antibiotic, (2) timing of administration, (3) antibiotic dosing, or (4) lack of repeat dosing when a short half-life\u00a0drug would have required a second\u00a0dose during surgery.<\/p>\n

This was a retrospective review and these performance criteria were applied quite strictly.\u00a0 For instance, an error related to re-dosing could be 3-fold: not done when required; done but with a wrong dose, or done but not at the right time.<\/p>\n

This all makes sense but I am not sure I would have gotten all these details\u00a0right myself, even come close.\u00a0 Actually, I would have done very poorly because I did not know that aminoglycosides are supposed to be dosed according to ideal body weight (IBW).<\/p>\n

So, what is ideal BW?\u00a0 Thankfully, Columbia University\u00a0[2]<\/a> provides the answer:
\nIBW (males) = 50 kg + (2.3 x height in inches > 60 inches)\u00a0[3]<\/a>.<\/p>\n

Can a formula be correct which mixes kg and inches, metric and imperial units?\u00a0 Well, you may have to convert your patient\u2019s weight from pounds to kg first but that\u2019s straightforward if not easy to remember: 50 kg is equivalent to 110.231 lbs.<\/p>\n

Now we are making progress: let\u2019s assume our patient weighs 68 kg (149.914 lbs) and is 170 cm tall (66.9291\u201d).\u00a0 With 7 inches over\u00a060 inches, we get an IBW of 66.1 kg.\u00a0 Assuming our anesthesiologist does not have to make adjustments for: severe illness, obesity, female gender, renal compromise, or loading dose, we can now order gentamicin or tobramycin confidently at 2 mg\/kg IBW q8h IV, or 132 mg per dose, rounded off\u00a0to 130 mg\/dose. \u00a0If you prefer a\u00a01.5 mg\/kg IBW q8h regimen, you end up\u00a0with\u00a0a dose of 100 mg.<\/p>\n

Note: Dosing for high-dose once-daily kidney-sparing extended-interval regimens has its own formula and PK profile (see Fig. 1).\u00a0 Dosing for Gram-positive synergy, for mycobacterial infections, and pediatric infections is different as well, of course.\u00a0 And for patients weighing less than IBW, one should\u00a0use actual BW (ABW), \u00a0for those with BW >20% above IBW (or is it: > 30%?), you should use DBW (which stands for \u201cDosing Body Weight\u201d).<\/p>\n

Obviously, these dosing guidelines require several megabytes of storage on your computer, and\u00a0the equivalent of approx. 50% of my\u00a0cerebral memory banks.\u00a0 However, it is important to heed these dosing recommendations\u00a0in order to avoid aminoglycoside-associated nephro-, neuro-, and ototoxicity, and a later court summons.\u00a0\u00a0 Hence, we should also look into proper infusion times and when to measure peak and trough levels.<\/p>\n

The package insert specifies a 30-60 min infusion time for our 130 mg dose; peak measurements after 4 half-lives should be done 30 min post-infusion. \u00a0The goal is to have a peak-to-MIC ratio of approx. 10 for efficacy. \u00a0Okay, now let\u2019s move on to vancomycin, the other major drug used in surgical prophylaxis.<\/p>\n

For starters, vancomycin is dosed according to actual body weight (ABW).\u00a0 No need to calculate the IBW but conversion of BW into kg is still needed (for estimating creatinine clearance with the Cockcroft Gault method). In hospitals using the metric system, conversion of S-creatinine (1 mg\/dL = 88.4 \u00b5mol\/L or 1 \u00b5mol\/L = 0.0113 mg\/dL) to the old units is also required.<\/p>\n

At the recommended dose of 12-15 mg\/kg, our 68 kg patient should receive a maintenance dose between 816 \u2013 1020 mg IV q12h, with a loading dose possibly as high as 1500 mg.\u00a0 These doses would be infused over 60 min.\u00a0 We no longer\u00a0check peak concentrations as they do not correlate with either efficacy or safety, but if you do measure peak vancomycin levels, the Tmax is approx. 1-2 hours post infusion.\u00a0 Peak levels of > 35 mg\/L should prompt dose adjustment.<\/p>\n

\"Vanco<\/a>
Fig. 2: Vancomycin at Steady State after 3rd dose; PK profile: no LD, 900 mg IV q8h, 68 kg, normal Cl\/cr<\/figcaption><\/figure>\n

However, dose adjustments are based on trough values which should be obtained after the 3rd<\/sup> dose and not exceed 15 mg\/L [4]<\/a>.<\/p>\n

\"abacus\"<\/a>
Fig. 3: Collaboration with a competent hospital pharmacist is essential<\/figcaption><\/figure>\n

After all this math, the surgical procedure is already well underway and it is time to call in your second antibiotic dose from the pharmacy (where a helpful colleague will have done all the necessary calculations for you).\u00a0 Next time you see your hospital pharmacist, thank him for doing the math for you.\u00a0 Obviously, he has all the modern\u00a0dosing tools at his fingertips (Fig. 3).<\/p>\n

Indeed, there are many excellent detailed dosing tools\u00a0[5]<\/a> and PK calculators available on the web.\u00a0 No need to go back to the package insert and wreck your brain.<\/p>\n

The reader interested in the history of aminoglycoside dosing will find the recent article by Pai et al. informative\u00a0[6]<\/a>.<\/p>\n

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

[1]<\/a> W Goede Hosp Pharm. 2013; 48: 560
\n[2]<\/a> http:\/\/www.cumc.columbia.edu\/dept\/id\/documents\/Clinical%20References\/Aminoglycoside_Conventional_Dosing_and_Monitoring_in_Adults_ONEPAGE.pdf
\n<\/a>[3]<\/a> http:\/\/www.cumc.columbia.edu\/dept\/id\/documents\/Clinical%20References\/Aminoglycoside_Conventional_Dosing_and_Monitoring_in_Adults_ONEPAGE.pdf
\n<\/a>[4]<\/a> http:\/\/www.cumc.columbia.edu\/dept\/id\/downloads\/Vancomycin_5-26-05.pdf
\n<\/a>[5]<\/a> http:\/\/www.hopkinsmedicine.org\/amp\/guidelines\/Antibiotic_guidelines.pdf
\n[6]<\/a> M Pai\u00a0 Diagnostic Microbiol Infectious Dis 78 (2014): 178<\/p>\n","protected":false},"excerpt":{"rendered":"

Searching data on antibiotic use in surgery prophylaxis, I came across an article from the Mayo Clinic\u00a0[1].\u00a0 The authors mention that approx. 75% of patients that developed surgical site\u00a0infections did not get proper antibiotic prophylaxis.\u00a0 Errors were made in (1) selection of the antibiotic, (2) timing of administration, (3) antibiotic Continue reading No Easy Day: Dose Calculations for Aminoglycosides and Vancomycin<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":1452,"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":[140,227],"tags":[983,176,403,832,976,982,766,981,738,977,978,975,985,984,979,980,887,48],"class_list":["post-1451","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-interesting_facts","category-recent_literature","tag-actual-body-weight","tag-aminoglycoside","tag-antibiotic-blog","tag-dose-adjustment","tag-dosing-algorithm","tag-dosing-body-weight","tag-gentamicin","tag-ideal-body-weight","tag-infusion-time","tag-loading-dose","tag-maintenance-dose","tag-nomogram","tag-prophylactic-antibiotic-dosing","tag-surgical-skin-infections","tag-tdm","tag-therapeutic-drug-monitoring","tag-tobramycin","tag-vancomycin"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2015\/05\/Vanco-g-Dosing-banner-copy.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-np","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":249,"url":"https:\/\/allphasepharma.com\/dir\/2014\/06\/05\/249\/here-they-are-dalbavancin-oritavancin-the-new-long-acting-lipoglycopeptides\/","url_meta":{"origin":1451,"position":0},"title":"Here They Are: Dalbavancin and Oritavancin \u2013 The New Long-Acting Lipoglycopeptides","author":"Harald","date":"June 5, 2014","format":false,"excerpt":"The development history of glycopeptide drugs is anything but normal.\u00a0 Daptomycin (Cubicin\u00ae) was abandoned by Lilly but resurrected by Francis Tally at Cubist by adjusting the dosing schedule to once daily and careful uptitration.\u00a0 The drug did superbly in a landmark endocarditis trial and everything looked rosy.\u00a0 Then we learned\u2026","rel":"","context":"In "The News"","block_context":{"text":"The News","link":"https:\/\/allphasepharma.com\/dir\/category\/the_news\/"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":1216,"url":"https:\/\/allphasepharma.com\/dir\/2015\/01\/06\/1216\/meropenem-dosing-for-vap-high-prolonged-beats-conventional-dosing\/","url_meta":{"origin":1451,"position":1},"title":"Meropenem Dosing for VAP: High + Prolonged Beats Conventional Dosing","author":"Harald","date":"January 6, 2015","format":false,"excerpt":"Sometimes an article pops up addressing a question we have been mulling over for quite some time.\u00a0 It so happened with a recent publication which shed new light on penem dosing for ICU patients[1]. 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