Currently, there is insufficient clinical experience for treatment of pediatric IE with single daily dos- ing (of gentamicin) (Class III; Level of Evidence C). 3. Children with renal failure require dosage adjust- ments, and in these cases, guidance from pharma- cists, infectious disease specialists, or renal diseases consultants is recommended (Class I; Level of Evidence B). Culture-Negative Endocarditis The causes of CNE are discussed in LaboratoryAssessment. All cases of CNE are considered management conundrums for at least 2 reasons. First, empirical therapy is necessary, and thus, the antimicrobial regimen selected for administration may not provide adequate coverage for the undefined patho- gen. Second, empirical therapy could cause harm secondary to drug adverse events. A worst case scenario could develop in which the empirical regimen would result in clinical wors- ening and drug toxicity would develop because of an antimi- crobial agent that would not have been used if the pathogen had been defined. For these reasons, and with the information that antibiotic treatment is the main cause of CNE, the writing committee deemed it reasonable to obtain the proper number of cultures before antibiotic drugs are started or to stop antibi- otic drugs that were started fewer than 4 days earlier. Empirical treatment regimens are devised only after important epidemiological factors are considered, including the pivotal issue as to whether or not there has been recent antimicrobial exposure before obtaining blood cultures. 