***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND The combination of ceftazidime plus aminoglycoside is widely used for the treatment of febrile neutropenic patients but requires multiple daily administration . Because the frequency of Pseudomonas aeruginosa is low in many centers , there is a rationale to test other antibiotic regimens that provide appropriate antibacterial coverage with the advantage of reduced dosing frequency , such as once daily ceftriaxone plus amikacin . METHODS Febrile neutropenic children with leukemia , lymphoma or solid tumors after chemotherapy were included in an open , prospect i ve , r and omized , multinational study comparing once daily ceftriaxone plus amikacin vs. 8-hourly ceftazidime and amikacin . The response to antimicrobial therapy was defined as complete response , improvement or failure . Assessment of adverse events was supplemented by specific definitions of nephrotoxicity , ototoxicity , hepatotoxicity and hypokalemia . Costs were estimated from published values of acquisition costs , delivery costs and hospitalization costs . RESULTS Efficacy was evaluable in 364 of 468 episodes in 265 children .  Response rates in ceftriaxone and amikacin vs. ceftazidime and amikacin-treated episodes were 119 of 181 ( 66 % ) vs. 121 of 183 ( 66 % ) , 7 of 181 ( 4 % ) vs. 9 of 183 ( 5 % ) and 55 of 181 ( 30 % ) vs. 53 of 181 ( 29 % ) for complete response , improvement and failure , respectively . Safety profiles were similar with both treatment regimens . The acquisition and administration costs were lower for the ceftriaxone and amikacin regimen . CONCLUSIONS A once daily regimen of ceftriaxone and amikacin is as safe and clinical ly effective as that of three times daily ceftazidime and amikacin for the treatment of febrile neutropenic children with cancer and is more cost-effective . The once daily regimen of ceftriaxone and amikacin is suitable for outpatient treatment In a prospect i ve , r and omized trial , netilmicin given once daily ( OD ) was compared in terms of efficacy and safety with the conventional 8-hourly dosing regimen ( TD ) , both in combination with a broad spectrum beta-lactam , as initial empirical therapy for febrile neutropenic patients ; the total daily dosage of netilmicin in each group was 6 mg/kg body weight . Twenty-nine of the 116 ( 25 % ) evaluable patients had microbiologically documented septicaemia , most of which were caused by Gram-positive bacteria , 41 ( 35 % ) had microbiologically documented infection without bacteraemia and 46 ( 40 % ) had possible infection .  Highest peak serum concentrations of netilmicin in the OD group were significantly higher and trough serum concentrations significantly lower than in the TD group . A multivariate analysis revealed that neither the dosage regimen nor the peak serum concentration of netilmicin were determinants of a favourable outcome . The response rates of both groups to the initial treatment regimens were comparable and increased similarly following modification of the initial therapy . Response rates were particularly poor in patients with lower respiratory tract infection and in those who remained neutropenic throughout the course of treatment . The incidence of nephrotoxicity was low and did not differ significantly between groups . Once-daily dosing of netilmicin appears to be as effective and as safe as thrice-daily dosing , but is unlikely to further improve the response of febrile neutropenic patients to empirical therapy OBJECTIVE Empirical antibiotic treatment for febrile neutropenic patients has been the mainstay of treatment for many years . Beta-lactam antibiotics and aminoglycosides have been the most frequently used drug combination . The purpose of this study was to evaluate the efficacy , safety , tolerance and costs of single-daily ceftriaxone plus amikacin versus thrice-daily dose of ceftazidime plus amikacin . METHODOLOGY One hundred and ninety-one episodes of fever and neutropenia in 128 patients from October 1997 to December 1998 were included in a prospect i ve , open-label , single-centre study . Patients were r and omly assigned to either treatment group and evaluated as successes or failures according to defined criteria . Daily assessment s were made on all patients and all adverse events recorded . Univariate and multivariate analysis of outcomes and a cost analysis were carried out . RESULTS There were 176 evaluable patient-episodes with 51.1 % in the single-daily ceftriaxone-amikacin group and 48.9 % in the ceftazidime-amikacin group . There were 50 positive blood cultures : 12 Gram-positive bacteria , 33 Gram-negative bacteria and five fungi . Pseudomonas aeruginosa ( P. aeruginosa ) accounted for 14 % of total isolates . The overall success rate was 55.5 % in the ceftriaxone group compared to 51.2 % in the ceftazidime group ( P = 0.56 ) . Mean time to defervescence was 4.2 days in the single-daily group and 4.3 days in the thrice-daily group . There were nine infection-related deaths ; five in the single-daily ceftriaxone group . The daily cost of the once-daily regime was 42 Malaysian Ringgit less than the thrice-daily regime . There was a low incidence of adverse effects in both groups , although ototoxicity was not evaluable . CONCLUSIONS The once-daily regime of ceftriaxone plus amikacin was as effective as the ' st and ard ' combination of thrice-daily ceftazidime and amikacin with no significant adverse effects in either group . The convenience and substantial cost benefit of the once-daily regime will be particularly useful in developing countries with limited health re sources and in centres with a low prevalence of P. aeruginosa In an examination of the relationships among plasma aminoglycoside concentrations , the minimal inhibitory concentration ( MIC ) for the infecting organism , and therapeutic outcome , data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin , tobramycin , and amikacin .  Clinical response to therapy occurred in 188 ( 80 % ) patients . Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response ( P less than .00001 and P less than .0001 , respectively ) . A grade d dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response . By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response . These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy Recently , much interest has focused on the use of once-daily aminoglycosides ( ODA ) in the medical literature . In late 1992 , we implemented a hospital-wide ODA program  for adult patients at our 850-bed community-teaching hospital . In the first phase of implementation , therapeutic drug monitoring ( TDM ) was accomplished with the use of a r and om serum concentration and a nomogram that had been developed at our institution . In the second phase , serum drug concentrations were eliminated on patients with normal renal function . The fully implemented program result ed in a 40 % decrease in the request for gentamicin and tobramycin serum concentrations as compared with historic ordering patterns for conventional aminoglycoside dosing regimens . In addition , the incidence of nephrotoxicity was also reduced from 3 to 5 % with conventional aminoglycoside dosing , to 1.2 and 1.3 % for phases 1 and 2 , respectively . Furthermore , the elimination of TDM requests totaling 300 for gentamicin and 50 for tobramycin per month is expected to result in an annual institutional savings of > $ 100,000 BACKGROUND The benefits of aminoglycoside antibiotics , such as tobramycin , administered as a once-daily dose to manage febrile neutropenia , have been demonstrated in many patient population s. However , toxicity and safety data are lacking for pediatric stem cell transplant recipients , who are at especially high risk for aminoglycoside-related toxicity and infectious morbidity . In particular , the relative nephrotoxicity and efficacy of tobramycin administered as a single daily dose or as three daily doses among this patient population is not known . METHODS We conducted a r and omized , double-blind controlled study of tobramycin dosing among children 18 years or younger who had fever and neutropenia while undergoing stem cell transplantation . From October 2000 through November 2002 , 60 children were r and omly assigned to receive intravenous tobramycin , as either a single daily dose ( n = 29 ) or every 8 hours ( n = 31 ) , in combination with either piperacillin or ceftazidime ( intravenous ) . Tobramycin doses were adjusted to achieve pharmacokinetic targets . The primary outcome was nephrotoxicity , as represented by the maximal percent increase in serum creatinine concentration throughout the episode of febrile neutropenia relative to the baseline serum creatinine concentration . Efficacy was a secondary outcome and was defined as survival of the episode without modification of the antibacterial regimen . All statistical tests were two-sided . RESULTS In a modified intent-to-treat analysis , the mean maximal percent increase in serum creatinine concentration was 32 % ( N = 26 ) in the once daily dose group and 51 % ( N = 28 ) in the every 8 hours dose group ( difference = 19 % , 95 % confidence interval [ CI ] = 0 % to 38 % ; P = .054 ) . Among patients evaluable for efficacy , 12 ( 46 % ) of 26 patients in the once daily dose group and five ( 19 % ) of 27 patients in the every 8 hours dose group survived the episode of febrile neutropenia without requiring antibacterial treatment modification ( difference = 27 % , 95 % CI = 4 % to 52 % ; P = .03 ) . There was one death in each group . CONCLUSIONS In febrile neutropenic children undergoing stem cell transplantation , tobramycin may be less nephrotoxic and more efficacious when administered as a once daily dose than when administered every 8 hours Amikacin is an aminoglycoside commonly used to provide empirical double gram-negative treatment for febrile neutropenia and other suspected infections . Strategies of extended-interval and conventional dosing have been utilized extensively in the general medical population ; however , data are lacking to support a dosing strategy in the hematology/oncology population . To evaluate amikacin-associated nephrotoxicity in an adult hematology/oncology population , a prospect i ve , r and omized , open-label trial was conducted at a university-affiliated medical center . Forty patients with a diagnosis consistent with a hematologic/oncologic disorder that required treatment with an aminoglycoside were r and omized to either conventional or extended-interval amikacin . The occurrence of nephrotoxicity by means of an increase in serum creatinine and evaluation of efficacy via amikacin serum concentrations with respective pathogens were assessed . The occurrence of nephrotoxicity was similar between the conventional and extended-interval groups , at 10 % and 5 % , respectively ( P = 1.00 ) . Six patients in the conventional group had a positive culture , compared with none in the extended-interval group ( P = 0.002 ) . The occurrence of nephrotoxicity was similar between the two dosing regimens , but the distribution of risk factors was variable between the two groups . Efficacy could not be assessed Once-daily aminoglycoside ( ODA ) regimens have been instituted to maximize bacterial killing by optimizing the peak concentration/MIC ratio and to reduce the potential for toxicity . We initiated an ODA program at our institution that utilizes a fixed 7-mg/kg intravenous dose with a drug administration interval based on estimated creatinine clearance : > or = 60 ml/min every 24 h ( q24h ) , 59 to 40 ml/min q36h , and 39 to 20 ml/min q48h . Subsequent interval adjustments are made by using a single concentration in serum and a nomogram design ed for monitoring of ODA therapy . Since initiation of the program , 2,184 patients have received this ODA regimen .  The median dose was 450 ( range , 200 to 925 ) mg , while the median length of therapy was 3 ( range , 1 to 26 ) days . The median age of the population was 46 ( range , 13 to 97 ) years . Gentamicin accounted for 94 % of the aminoglycoside use , and the majority ( 77 % ) of patients received the drug q24h . The 36- , 48- , and > 48-h intervals were used for 15 , 6 , and 2 % of this population , respectively . Three patients exhibited clinical ly apparent ototoxicity . Twenty-seven patients ( 1.2 % ) developed nephrotoxicity ( the Hartford Hospital historical rate is approximately 3 to 5 % ) after a median of 7 ( range , 3 to 19 ) days of therapy . On the basis of a prospect i ve evaluation 
    Output:
    
Although the generalization of our findings may be restricted by the relatively small sample size and other method ological limitations of the included RCTs , ODD appears to be at least as effective and as safe as MDD  in patients with febrile neutropenia .