{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T12:22:34Z","timestamp":1756902154478,"version":"3.44.0"},"reference-count":39,"publisher":"The Pediatric Pharmacy Association","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>An 11-year-old African American male with severe combined immunodeficiency variant, non-cystic fibrosis bronchiectasis, pancreatic insufficiency, chronic mycobacterium avium-intracellulare infection, chronic sinusitis, and malnutrition presented with a 1-week history of fevers. He subsequently developed respiratory decompensation and cefepime was discontinued and doripenem was initiated. Doripenem was the carbapenem used due to a national shortage of meropenem. By day 7 the patient (24.7 kg) had a positive fluid balance of 6925 mL (28% FO), and on days 7 into 8 developed acute kidney injury evidenced by an elevated serum creatinine of 0.68 mg\/dL, an increase from the baseline of 0.28 mg\/dL. On day 9, the patient was initiated on continuous renal replacement therapy (CRRT) and the doripenem dosing was changed to a continuous infusion of 2.5 mg\/kg\/hr (60 mg\/kg\/day). Approximately 12.5 hours after the start of the doripenem a serum concentration was obtained, which was 4.01 mg\/L corresponding to a clearance of 10.5 mL\/min\/kg. The pediatric dosing and pharmacokinetic data available for doripenem suggest a clearance estimate of 4.4 to 4.8 mL\/min\/kg, and the adult clearance estimate is 2.4 to 3.78 mL\/min\/kg. The calculated clearance in our patient of 10.5 mL\/min\/kg is over double the highest clearance estimate in the pediatric literature. This case demonstrates that doripenem clearance is significantly increased with CRRT in comparison with the published pediatric and adult data. An appropriate pharmacodynamic outcome (time that free drug concentration &gt; minimum inhibitory concentration) can be achieved by continuous infusion doripenem with concurrent therapeutic drug monitoring.<\/jats:p>","DOI":"10.5863\/1551-6776-22.1.69","type":"journal-article","created":{"date-parts":[[2017,3,6]],"date-time":"2017-03-06T18:52:31Z","timestamp":1488826351000},"page":"69-73","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic Drug Monitoring of Continuous Infusion Doripenem in a Pediatric Patient on Continuous Renal Replacement Therapy"],"prefix":"10.5863","volume":"22","author":[{"given":"Jeffrey J.","family":"Cies","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne S.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan B.","family":"Conley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Shea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adela","family":"Enache","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Chopra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3883","reference":[{"year":"2015","series-title":"Doripenem (Doribax) [package insert]","key":"i1551-6776-22-1-69-b1","unstructured":"Doripenem (Doribax) [package insert]. Florham Park, NJ: Shionogi Inc.; 2015."},{"issue":"9","key":"i1551-6776-22-1-69-b2","series-title":"Pol Przegl Chir","first-page":"449","article-title":"Comparison of in vitro activity of doripenem, imipenem and meropenem against clinical isolates of Enterobacteriaceae, Pseudomonas and Acinetobacter in Southern Poland","volume":"84","year":"2012","unstructured":"Drzewiecki\n              A\n            , BulandaM, TalagaK, \n          et al. Comparison of in vitro activity of doripenem, imipenem and meropenem against clinical isolates of Enterobacteriaceae, Pseudomonas and Acinetobacter in Southern Poland. Pol Przegl Chir. 2012;84(9):449\u2013453."},{"issue":"suppl 1","key":"i1551-6776-22-1-69-b3","series-title":"Clin Infect Dis","first-page":"S11","article-title":"In vitro activity of doripenem","volume":"49","year":"2009","unstructured":"Sahm\n              D.\n            \n          \n          In vitro activity of doripenem. Clin Infect Dis. 2009;49(suppl 1):S11\u2013S16."},{"issue":"1","key":"i1551-6776-22-1-69-b4","series-title":"Adv Pharm Bull","first-page":"121","article-title":"Comparison of in vitro activity of doripenem versus old carbapenems against Pseudomonas aeruginosa clinical isolates from both CF and burn patients","volume":"3","year":"2013","unstructured":"Hojabri\n              Z\n            , Ahangarzadeh RezaeeM, NahaeiMR, \n          et al. Comparison of in vitro activity of doripenem versus old carbapenems against Pseudomonas aeruginosa clinical isolates from both CF and burn patients. Adv Pharm Bull. 2013;3(1):121\u2013125."},{"issue":"11","key":"i1551-6776-22-1-69-b5","series-title":"Pediatr Infect Dis J","first-page":"1264","article-title":"Safety and tolerability of doripenem in hospitalized children with complicated intra-abdominal infection, complicated urinary tract infections and pneumonia","volume":"34","year":"2015","unstructured":"Cannavino\n              CR\n            , Castaneda-RuizB, RedmanR, \n          et al. Safety and tolerability of doripenem in hospitalized children with complicated intra-abdominal infection, complicated urinary tract infections and pneumonia. Pediatr Infect Dis J. 2015;34(11):1264\u20131267."},{"issue":"9","key":"i1551-6776-22-1-69-b6","series-title":"J Pharm Sci","first-page":"3194","article-title":"Prediction of pharmacokinetics and pharmacodynamics of doripenem in pediatric patients","volume":"104","year":"2015","unstructured":"Matsuo\n              Y\n            , IshibashiT, ShimamuraK, WajimaT.\n          Prediction of pharmacokinetics and pharmacodynamics of doripenem in pediatric patients. J Pharm Sci. 2015;104(9):3194\u20133198."},{"issue":"6","key":"i1551-6776-22-1-69-b7","series-title":"Crit Care Med","first-page":"1589","article-title":"Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock","volume":"34","year":"2006","unstructured":"Kumar\n              A\n            , RobertsD, WoodKE, \n          et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589\u20131596."},{"issue":"7","key":"i1551-6776-22-1-69-b8","series-title":"Am J Med","first-page":"529","article-title":"Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis","volume":"115","year":"2003","unstructured":"Harbarth\n              S\n            , GarbinoJ, PuginJ, \n          et al. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. 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What's behind the failure of emerging antibiotics in the critically ill? Understanding the impact of altered pharmacokinetics and augmented renal clearance. Int J Antimicrob Agents. 2012;39(6):455\u2013457."},{"issue":"5","key":"i1551-6776-22-1-69-b11","series-title":"Crit Care","first-page":"R206","article-title":"Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of beta-lactams","volume":"15","year":"2011","unstructured":"Goncalves-Pereira\n              J\n            , PovoaP.\n          Antibiotics in critically ill patients: a systematic review of the pharmacokinetics of beta-lactams. 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Pediatr Crit Care Med. 2016;17(4):e138\u2013e145."},{"issue":"4","key":"i1551-6776-22-1-69-b17","series-title":"Pharmacotherapy","first-page":"e32","article-title":"Pharmacokinetics of continuous-infusion meropenem for the treatment of Serratia marcescens ventriculitis in a pediatric patient","volume":"35","year":"2015","unstructured":"Cies\n              JJ\n            , MooreWS2nd, CalamanS, \n          et al. Pharmacokinetics of continuous-infusion meropenem for the treatment of Serratia marcescens ventriculitis in a pediatric patient. Pharmacotherapy. 2015;35(4):e32\u2013e36."},{"issue":"10","key":"i1551-6776-22-1-69-b18","series-title":"Pharmacotherapy","first-page":"e175","article-title":"Pharmacokinetics of continuous-infusion meropenem in a pediatric patient receiving extracorporeal life support","volume":"34","year":"2014","unstructured":"Cies\n              JJ\n            , MooreWS2nd, DickermanMJ, \n          et al. 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Clin Infect Dis. 2009;49(2):291\u2013298."},{"issue":"1","key":"i1551-6776-22-1-69-b26","series-title":"Yakugaku Zasshi","first-page":"87","article-title":"Doripenem pharmacokinetics in critically ill patients receiving continuous hemodiafiltration","volume":"130","year":"2010","unstructured":"Hidaka\n              S\n            , GotoK, HagiwaraS, \n          et al. Doripenem pharmacokinetics in critically ill patients receiving continuous hemodiafiltration. Yakugaku Zasshi. 2010;130(1):87\u201394."},{"issue":"3","key":"i1551-6776-22-1-69-b27","series-title":"Antimicrob Agents Chemother","first-page":"1687","article-title":"Doripenem treatment during continuous renal replacement therapy","volume":"60","year":"2015","unstructured":"Vossen\n              MG\n            , WenischJM, Maier-SalamonA, \n          et al. Doripenem treatment during continuous renal replacement therapy. Antimicrob Agents Chemother. 201528;60(3):1687\u20131694."},{"issue":"8","key":"i1551-6776-22-1-69-b28","series-title":"Crit Care Med","first-page":"2433","article-title":"Antibiotic resistance\u2014what's dosing got to do with it?","volume":"36","year":"2008","unstructured":"Roberts\n              JA\n            , KrugerP, PatersonDL, LipmanJ.\n          Antibiotic resistance\u2014what's dosing got to do with it?\n          Crit Care Med. 2008;36(8):2433\u20132440."},{"issue":"16","key":"i1551-6776-22-1-69-b29","series-title":"JAMA","first-page":"1857","article-title":"Resistance to nalidixic acid: a misconception due to underdosage","volume":"236","year":"1976","unstructured":"Stamey\n              TA\n            , BragonjeJ.\n          Resistance to nalidixic acid: a misconception due to underdosage. 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Crit Care. 2011;15(5):R206."},{"issue":"7","key":"i1551-6776-22-1-69-b35","series-title":"Am J Med","first-page":"529","article-title":"Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis","volume":"115","year":"2003","unstructured":"Harbarth\n              S\n            , GarbinoJ, PuginJ, \n          et al. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med. 2003;115(7):529\u2013535."},{"issue":"2","key":"i1551-6776-22-1-69-b36","series-title":"Chest","first-page":"462","article-title":"Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients","volume":"115","year":"1999","unstructured":"Kollef\n              MH\n            , ShermanG, WardS, FraserVJ.\n          Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest. 1999;115(2):462\u2013474."},{"issue":"6","key":"i1551-6776-22-1-69-b37","series-title":"Crit Care Med","first-page":"1589","article-title":"Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock","volume":"34","year":"2006","unstructured":"Kumar\n              A\n            , RobertsD, WoodKE, \n          et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589\u20131596."},{"issue":"2","key":"i1551-6776-22-1-69-b38","series-title":"Clin Infect Dis","first-page":"284","article-title":"Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial","volume":"38","year":"2004","unstructured":"MacArthur\n              RD\n            , MillerM, AlbertsonT, \n          et al. Adequacy of early empiric antibiotic treatment and survival in severe sepsis: experience from the MONARCS trial. Clin Infect Dis. 2004;38(2):284\u2013288."},{"issue":"4","key":"i1551-6776-22-1-69-b39","series-title":"Pediatr Infect Dis J","first-page":"295","article-title":"Timing of correct parenteral antibiotic initiation and outcomes from severe bacterial community-acquired pneumonia in children","volume":"30","year":"2011","unstructured":"Muszynski\n              JA\n            , KnatzNL, SargelCL, \n          et al. Timing of correct parenteral antibiotic initiation and outcomes from severe bacterial community-acquired pneumonia in children. 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