{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:41:48Z","timestamp":1772232108443,"version":"3.50.1"},"reference-count":31,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Empirical combination antibiotic regimens consisting of a \u03b2-lactam and an aminoglycoside are frequently employed in the pediatric population. Data to demonstrate the comparative benefit of empirical \u03b2-lactam combination therapy relative to monotherapy for culture-proven Gram-negative bacteremia are lacking in the pediatric population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study of children treated for Gram-negative bacteremia at The Johns Hopkins Hospital from 2004 through 2012. We compared the estimated odds of 10-day mortality and the relative duration of bacteremia for children receiving empirical combination therapy versus empirical monotherapy using 1:1 nearest-neighbor propensity-score matching without replacement, before performing regression analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified 226 matched pairs of patients well balanced on baseline covariates. Ten-day mortality was similar between the groups (odds ratio, 0.84; 95% confidence interval [CI], 0.28 to 1.71). Use of empirical combination therapy was not associated with a decrease in the duration of bacteremia (\u22120.51 days; 95% CI, \u22122.22 to 1.48 days). There was no survival benefit when evaluating 10-day mortality for the severely ill (pediatric risk of mortality III score \u226515) or profoundly neutropenic patients (absolute neutrophil count \u2264100 cells\/mL) receiving combination therapy. However, a survival benefit was observed when empirical combination therapy was prescribed for children growing multidrug-resistant Gram-negative organisms from the bloodstream (odds ratio, 0.70; 95% CI, 0.51 to 0.84).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Although there appears to be no advantage to the routine addition of an aminoglycoside to a \u03b2-lactam as empirical therapy for children who have Gram-negative bacteremia, children who have risk factors for MDRGN organisms appear to benefit from this practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1542\/peds.2013-3363","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T23:24:44Z","timestamp":1396913084000},"page":"e1148-e1155","source":"Crossref","is-referenced-by-count":29,"title":["Empiric Combination Therapy for Gram-Negative Bacteremia"],"prefix":"10.1542","volume":"133","author":[{"given":"Anna C.","family":"Sick","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Tschudin-Sutter","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison E.","family":"Turnbull","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott J.","family":"Weissman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, Seattle, Washington; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranita D.","family":"Tamma","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"417","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"issue":"2","key":"2021120903364781200_B1","first-page":"105","article-title":"Monotherapy with meropenem versus combination therapy with piperacillin plus amikacin as empiric therapy for neutropenic fever in children with lymphoma and solid tumors.","volume":"43","author":"D\u00fczova","year":"2001","journal-title":"Turk J Pediatr"},{"issue":"9","key":"2021120903364781200_B2","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1093\/cid\/cir145","article-title":"Central line-associated bloodstream infection in hospitalized children with peripherally inserted central venous catheters: extending risk analyses outside the intensive care unit.","volume":"52","author":"Advani","year":"2011","journal-title":"Clin Infect Dis"},{"issue":"10","key":"2021120903364781200_B3","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1001\/jamapediatrics.2013.196","article-title":"Less is more: combination antibiotic therapy for the treatment of gram-negative bacteremia in pediatric patients.","volume":"167","author":"Tamma","year":"2013","journal-title":"JAMA Pediatr"},{"issue":"2","key":"2021120903364781200_B4","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.idc.2009.01.004","article-title":"Combination antimicrobial treatment versus monotherapy: the contribution of meta-analyses.","volume":"23","author":"Paul","year":"2009","journal-title":"Infect Dis Clin North Am"},{"issue":"1","key":"2021120903364781200_B5","first-page":"CD003344","article-title":"Beta lactam antibiotic monotherapy versus beta lactam-aminoglycoside antibiotic combination therapy for sepsis.","author":"Paul","year":"2006","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"2021120903364781200_B6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination therapy for treatment of infections with gram-negative bacteria.","volume":"25","author":"Tamma","year":"2012","journal-title":"Clin Microbiol Rev"},{"issue":"9","key":"2021120903364781200_B7","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1097\/CCM.0b013e3181eb3ccd","article-title":"Early combination antibiotic therapy yields improved survival compared with monotherapy in septic shock: a propensity-matched analysis.","volume":"38","author":"Kumar","year":"2010","journal-title":"Crit Care Med"},{"key":"2021120903364781200_B8"},{"issue":"4","key":"2021120903364781200_B9","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1080\/08880010802016847","article-title":"Piperacillin\/tazobactam plus amikacin versus carbapenem monotherapy as empirical treatment of febrile neutropenia in childhood hematological malignancies.","volume":"25","author":"Yildirim","year":"2008","journal-title":"Pediatr Hematol Oncol"},{"issue":"4","key":"2021120903364781200_B10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.3109\/08880018.2011.557144","article-title":"Piperacillin\/tazobactam monotherapy versus piperacillin\/tazobactam plus amikacin as initial empirical therapy for febrile neutropenia in children with acute leukemia.","volume":"28","author":"Zengin","year":"2011","journal-title":"Pediatr Hematol Oncol"},{"issue":"2","key":"2021120903364781200_B11","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/08880010490277321","article-title":"Meropenem plus amikacin versus piperacillin-tazobactam plus netilmicin as empiric therapy for high-risk febrile neutropenia in children.","volume":"21","author":"Aksoylar","year":"2004","journal-title":"Pediatr Hematol Oncol"},{"issue":"4","key":"2021120903364781200_B12","first-page":"254","article-title":"Monotherapy with meropenem versus combination therapy with ceftazidime plus amikacin as empirical therapy for neutropenic fever in children with malignancy.","volume":"36","author":"Hung","year":"2003","journal-title":"J Microbiol Immunol Infect"},{"key":"2021120903364781200_B13"},{"key":"2021120903364781200_B14"},{"key":"2021120903364781200_B15"},{"issue":"7","key":"2021120903364781200_B16","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1742-1241.1988.tb08583.x","article-title":"Ticarcillin plus clavulanic acid (Timentin) compared with standard antibiotic regimes in the treatment of early and late neonatal infections.","volume":"42","author":"Miall-Allen","year":"1988","journal-title":"Br J Clin Pract"},{"key":"2021120903364781200_B17"},{"key":"2021120903364781200_B18","unstructured":"Johns Hopkins Medicine. Available at: www.insidehopkinsmedicine.org\/amp\/pediatrics\/downloads\/Aminoglycoside_Guidelines.pdf. Accessed February 19, 2014"},{"key":"2021120903364781200_B19","unstructured":"Johns Hopkins Medicine. Available at: www.insidehopkinsmedicine.org\/amp\/pediatrics\/downloads\/CA-BSI_Guidelines.pdf. Accessed February 19, 2014"},{"issue":"Oct","key":"2021120903364781200_B20","first-page":"24","article-title":"Short versus prolonged courses of antibiotic therapy for children with uncomplicated Gram-negative bacteraemia.","author":"Park","year":"2013","journal-title":"J Antimicrob Chemother"},{"issue":"6","key":"2021120903364781200_B21","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1093\/cid\/cit395","article-title":"The use of cefepime for treating AmpC \u03b2-lactamase-producing Enterobacteriaceae.","volume":"57","author":"Tamma","year":"2013","journal-title":"Clin Infect Dis"},{"issue":"11","key":"2021120903364781200_B22","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1093\/cid\/cir203","article-title":"Ventilator-associated tracheitis in children: does antibiotic duration matter?","volume":"52","author":"Tamma","year":"2011","journal-title":"Clin Infect Dis"},{"key":"2021120903364781200_B23","unstructured":"Centers for Disease Control and Prevention. Available at: www.cdc.gov\/hai\/settings\/lab\/lab_esbl.html. Accessed February 19, 2014"},{"key":"2021120903364781200_B24","unstructured":"The Centers for Disease Control and Prevention. Available at: www.ndhealth.gov\/microlab\/Uploads\/HodgeTest.pdf. Accessed February 19, 2014"},{"key":"2021120903364781200_B25","unstructured":"R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2013. Available at: www.R-project.org\/"},{"issue":"12","key":"2021120903364781200_B26","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1086\/673974","article-title":"Pediatric antimicrobial susceptibility trends across the United States.","volume":"34","author":"Tamma","year":"2013","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"5","key":"2021120903364781200_B27","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.ijantimicag.2007.05.022","article-title":"Pseudomonas aeruginosa infections in the Intensive Care Unit: can the adequacy of empirical beta-lactam antibiotic therapy be improved?","volume":"30","author":"Bhat","year":"2007","journal-title":"Int J Antimicrob Agents"},{"issue":"5","key":"2021120903364781200_B28","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jamda.2010.06.012","article-title":"Assessment of risk factors for multi-drug resistant organisms to guide empiric antibiotic selection in long term care: a dilemma.","volume":"12","author":"Drinka","year":"2011","journal-title":"J Am Med Dir Assoc"},{"issue":"3","key":"2021120903364781200_B29","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1128\/AAC.02235-12","article-title":"Outcomes of appropriate empiric combination versus monotherapy for Pseudomonas aeruginosa bacteremia.","volume":"57","author":"Bowers","year":"2013","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"2021120903364781200_B30","doi-asserted-by":"crossref","first-page":"3590","DOI":"10.1128\/AAC.00115-10","article-title":"Influence of empiric therapy with a beta-lactam alone or combined with an aminoglycoside on prognosis of bacteremia due to gram-negative microorganisms.","volume":"54","author":"Mart\u00ednez","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"4","key":"2021120903364781200_B31","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1097\/INF.0b013e31820f0f3a","article-title":"Extended-interval aminoglycoside dosing in pediatrics.","volume":"30","author":"Jenh","year":"2011","journal-title":"Pediatr Infect Dis J"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/133\/5\/e1148\/1059714\/peds_2013-3363.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/133\/5\/e1148\/1059714\/peds_2013-3363.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,11]],"date-time":"2023-07-11T19:01:01Z","timestamp":1689102061000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/133\/5\/e1148\/32785\/Empiric-Combination-Therapy-for-Gram-Negative"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":31,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,1]]},"published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2013-3363","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718342961.793494704","asserted-by":"object"}]},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,1]]}}}