Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!
Introduction: Broad-spectrum beta-lactams are commonly prescribed for empirical or selective treatment of bacterial infections in children with malignancies. In the immunocompromised, appropriate concentration exposure is crucial to ensure antimicrobial efficacy. Augmented renal clearance (ARC) is increasingly recognized in this population, and raises concern for unmet concentration targets. We conducted a retrospective evaluation of meropenem and piperacillin exposure in our hospital's pediatric hematology-oncology patients.Materials and Methods: We compared trough levels of meropenem and piperacillin in a cohort of unselected pediatric hematology-oncology patients stratified based on their estimated renal function as decreased, normal or with ARC, and on their neutrophil count.Results: Thirty-two children provided a total of 51 meropenem and 76 piperacillin samples. On standard intermittent intravenous regimen, 67% of all trough plasma concentrations were below targeted concentrations. In neutropenic children with bacterial infection, all meropenem and 60% of piperacillin levels were below target. Nearly two-thirds of total samples came from children with ARC. In these patients, antimicrobial exposure was insufficient in 85% of cases (compared to 36% in the decreased or normal renal function groups), despite a dosage sometimes exceeding the maximum recommended daily dose. Under continuous infusion of piperacillin, only 8% of plasma levels were insufficient.Discussion: Intermittent administration of meropenem and piperacillin often fails to ensure sufficient concentration exposure in children treated for malignancies, even at maximal recommended daily dosage. This can in part be attributed to ARC. We recommend thorough assessment of renal function, resolute dosage adjustment, continuous infusion whenever possible and systematic therapeutic drug monitoring.
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St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Pei, D.
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Wolf, J.
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Howard, S. C.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Howard, S. C.
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Hayden, R. T.
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St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Hayden, R. T.
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Go, M.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Go, M.
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Varechtchouk, O.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Varechtchouk, O.
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Hahn, T.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Hahn, T.
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Buaboonnam, J.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Buaboonnam, J.
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Metzger, M. L.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Metzger, M. L.
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Rubnitz, J. E.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Rubnitz, J. E.
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Ribeiro, R. C.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Ribeiro, R. C.
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Sandlund, J. T.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Sandlund, J. T.
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Jeha, S.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Jeha, S.
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Cheng, C.
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St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Cheng, C.
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Evans, W. E.
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St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Evans, W. E.
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Relling, M. V.
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St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Relling, M. V.
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Pui, C. -H.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Boston Childrens Hosp, Dept Radiol, Boston, MA USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Kwatra, Neha S.
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Meany, Holly J.
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Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Meany, Holly J.
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Ghelani, Sunil J.
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Boston Childrens Hosp, Dept Cardiol, Boston, MA USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Ghelani, Sunil J.
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Zahavi, David
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Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Zahavi, David
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Pandya, Nayan
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Pandya, Nayan
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Majd, Massoud
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
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St Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
Lam, Catherine G.
;
Howard, Scott C.
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Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
Guardian Res Network, Spartanburg, SC USA
Int Soc Paediat Oncol SIOP, Zug, SwitzerlandSt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
Howard, Scott C.
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Bouffet, Eric
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Pritchard-Jones, Kathy
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Int Soc Paediat Oncol SIOP, Zug, Switzerland
UCL, UCL Great Ormond St Inst Child Hlth, London, EnglandSt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
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St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Pei, D.
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Wolf, J.
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Howard, S. C.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Howard, S. C.
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Hayden, R. T.
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St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Hayden, R. T.
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Go, M.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Go, M.
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Varechtchouk, O.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Varechtchouk, O.
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Hahn, T.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Hahn, T.
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Buaboonnam, J.
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Buaboonnam, J.
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Metzger, M. L.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Metzger, M. L.
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Rubnitz, J. E.
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Rubnitz, J. E.
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Ribeiro, R. C.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Ribeiro, R. C.
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Sandlund, J. T.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Sandlund, J. T.
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Jeha, S.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Jeha, S.
;
Cheng, C.
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St Jude Childrens Res Hosp, Dept Biostat, 332 N Lauderdale St, Memphis, TN 38105 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Cheng, C.
;
Evans, W. E.
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St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Evans, W. E.
;
Relling, M. V.
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St Jude Childrens Res Hosp, Dept Pharmaceut Sci, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Clin Pharm, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Relling, M. V.
;
Pui, C. -H.
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St Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Boston Childrens Hosp, Dept Radiol, Boston, MA USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Kwatra, Neha S.
;
Meany, Holly J.
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Childrens Natl Med Ctr, Dept Hematol Oncol, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Meany, Holly J.
;
Ghelani, Sunil J.
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Boston Childrens Hosp, Dept Cardiol, Boston, MA USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Ghelani, Sunil J.
;
Zahavi, David
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Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Zahavi, David
;
Pandya, Nayan
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
Pandya, Nayan
;
Majd, Massoud
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Childrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USAChildrens Natl Med Ctr, Div Diagnost Imaging & Radiol, 111 Michigan Ave NW, Washington, DC 20010 USA
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St Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA
Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USASt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
Lam, Catherine G.
;
Howard, Scott C.
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Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA
Guardian Res Network, Spartanburg, SC USA
Int Soc Paediat Oncol SIOP, Zug, SwitzerlandSt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA
Howard, Scott C.
;
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Bouffet, Eric
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Pritchard-Jones, Kathy
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Int Soc Paediat Oncol SIOP, Zug, Switzerland
UCL, UCL Great Ormond St Inst Child Hlth, London, EnglandSt Jude Childrens Res Hosp, Dept Global Pediat Med, 332 N Lauderdale St, Memphis, TN 38105 USA