***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: The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate , in a prospect i ve r and omized trial , the role of teicoplanin , a new glycopeptide antibiotic , when it was added to amikacin plus ceftazidime , as an empiric therapy of fever in these patients . Of 47 evaluable episodes , 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime . The overall response to therapy of patients treated with teicoplanin was slightly better ( 82 % improvement ) than that obtained with amikacin plus ceftazidime ( 52 % ) . The response rate of patients with gram-positive bacteremias was 80 % ( 4 of 5 ) to the regimen that included teicoplanin ; 25 % ( 1 of 4 ) of the patients treated with amikacin plus ceftazidime responded to treatment ; and for patients with gram-negative bacteremias , the response rates were , respectively , 100 % ( 4 of 4 ) and 70 % ( 7 of 10 ) . The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound ( less than 100/mm3 ) and persistent neutropenia ( 83 versus 30 % improvement ) . Furthermore , a good response rate of patients with gram-positive bacteremias ( seven of eight ; 87 % improvement ) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin . No severe side effects were documented in any patient . Teicoplanin , as a drug administered as a single daily dose , seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients In a prospect i ve r and omized study , 120 febrile , granulocytopenic patients received as initial therapy ceftazidime with or without teicoplanin . At the onset of fever , patients had no obvious infectious focus . For 103 assessable episodes , initial bacteremias were detected in 18 of 51 patients ( 35 % ) given ceftazidime and 20 of 52 patients ( 38 % ) given the combination ; 13 and 17 bacteremias caused by gram-positive bacteria occurred in these groups , respectively . There was no difference in terms of the final response ( 25 of 51 patients [ 49 % ] treated with ceftazidime alone versus 33 of 52 patients [ 63 % ] given the combination ) , and the morbidity was comparable for both treatment groups . The duration of fever and of total antibiotic therapy were similar in both groups . Initial therapy was modified in 26 patients ( 51 % ) treated with ceftazidime , with 20 surviving the infection , and in 19 patients ( 37 % ) treated with the combination , with 15 surviving . Persistent fever was the main reason for changing treatment , and no patient died of a gram-positive infection . Subsequent infective events occurred in 16 patients ( 31 % ) given ceftazidime and in 25 patients ( 48 % ) given the combination . Lung infiltrates developed in 12 and 13 patients , respectively , but more new infections occurred in the combination group . Allergic skin reactions were also more frequent in this group . Thus , while teicoplanin provides simple , reliable , and safe treatment of patients with presumed gram-positive infections , it is not useful when given empirically to this patient population , and treatment may result in more infective complications and adverse events Summary In a prospect i ve r and omized trial parenteral trimethoprim/sulphamethoxazole was added to amikacin plus piperacillin in order to compare triple-drug antibiotic combination with a st and ard regimen as empiric therapy of fever in patients with granulocytopenia . One hundred and sixty-one episodes were evaluated ; 74 episodes with amikacin plus piperacillin and 87 episodes with amikacin plus piperacillin plus trimethoprim/sulphamethoxazole . The overall response to therapy ( 63 % vs. 84 % ) as well as the response of microbiologically documented infections ( 60 % vs. 82 % ) was significantly better in patients treated with the triple-drug combination ( p < 0.05 ) . However , no statistically significant differences in response to antibiotics at different infection sites or with regard to any single pathogen was found between the two groups . Trimethoprim/sulphamethoxazole seemed to be responsible for additional toxicity ( nausea and vomiting ) when added to amikacin plus piperacillin , but these side-effects were clearly related to the rate of infusion of trimethoprim/sulphamethoxazole . The findings of this study support the use of a three-drug versus a two-drug combination as empiric antibiotic regimen in febrile granulocytopenic patients .ZusammenfassungIn einer prospektiven , r and omisierten Studie wurde die Kombination Amikacin plus Piperacillin plus Trimethoprim/Sulfamethoxazol mit der St and ard-Zweierkombination Amikacin-Piperacillin in der empirischen Beh and lung von Fieberschüben bei granulozytopenischen Patienten verglichen . 161 Fieberepisoden wurden ausgewertet , davon waren 74 mit Amikacin plus Piperacillin und 87 mit Amikacin plus Piperacillin plus Trimethoprim/Sulfamethoxazol beh and elt worden . Bei Patienten , die die Antibiotika-Dreierkombination erhalten hatten , war der Gesamt-Therapieerfolg wie auch das Ansprechen mikrobiologisch nachgewiesener Infektionen mit 84 % bzw . 82 % signifikant besser als bei Patienten , die nur Amikacin-Piperacillin erhalten hatten , mit Ansprechraten von 63 % bzw . 60 % ( p < 0,05 ) . Bei Auswertung der Ansprechraten nach Infektionslokalisation oder Erregern f and en sich hingegen keine signifikanten Unterschiede zwischen den beiden Gruppen . Die Zugabe von Trimethoprim/Sulfamethoxazol zu Amikacin-Piperacillin verstärkte offensichtlich die Toxizität der Antibiotikatherapie mit vermehrtem Auftreten von Übelkeit und Erbrechen , doch st and en diese Nebenwirkungen eindeutig in Beziehung zur Infusionsgeschwindigkeit von Trimethoprim/Sulfamethoxazol . Die Ergebnisse dieser Studie sprechen für die Verwendung einer Kombination von drei Antibiotika anstelle einer Zweierkombination in der empirischen Therapie von Fieberschüben bei granulozytopenischen Patienten UNLABELLED The objective of this analysis were an assessment of the feasibility of a more individually tailored approach of empirical antibiotic therapy in febrile neutropenia and an exploration of the reasons to modify the initial regimen . DESIGN , SETTING AND SUBJECTS The main source was a data base on febrile neutropenic cancer patients from an unblinded large trial conducted in 35 centres world-wide . This was supplemented by data from patients enrolled in a consecutive series of r and omized trials at the Department of Haematology , University Hospital Nijmegen . INTERVENTIONS Diagnostic procedures were st and ardized , types of possible infections defined and the reasons for modifying an empirical regimen were recorded . MAIN OUTCOME MEASURES Survival of the febrile neutropenic episode , development of microbiologically and clinical ly defined infection in relation to causative organisms , and results of modification . RESULTS Monotherapy was as effective as combination therapy with an overall mortality of < or = 7 % , with 21 % of neutropenic episodes accompanied by a clinical ly defined infection proving fatal compared with only 4 % of episodes without a focus . At the end of treatment the empirical regimen had been added to in 60 % of cases in the multicentre trial , in contrast to 39 % in our own institution , in many cases simply because of continuing fever . CONCLUSION The development of local guidelines for individually tailoring antibiotic therapy by complementing the empirical regimen is a feasible option for achieving an optimal anti-infective strategy for febrile neutropenic cancer patients A prospect i ve , r and omized trial was initiated to evaluate the efficacy of two antibiotic regimens , differing in the agent included with activity against gram-positive bacteria , for the empirical treatment of febrile episodes in neutropenic patients with hematologic malignancies ( group 1 , piperacillin plus amikacin ; group 2 , piperacillin plus amikacin plus teicoplanin ) . After 72 hours of therapy , patients in group 1 who were still febrile were administered teicoplanin and those in group 2 were administered amphotericin B. A total of 158 evaluable episodes were observed within 8 months . The success rate was 50.6 % in group 1 and 60 % in group 2 . The response rate among patients who did not respond to the original regimen increased to 86.7 % with the addition of teicoplanin ( group 1 ) and to 90 % with the addition of amphotericin B ( group 2 ) . There were 86 unexplained febrile episodes and 56 documented episodes of bacteremia ( 34 caused by gram-positive organisms ) . Our results indicate that teicoplanin is safe , well tolerated , and effective for the treatment of documented episodes of gram-positive bacteremia and as an empirical agent . The inclusion of teicoplanin in the initial empirical regimen appears unnecessary if a combination of antibiotics active against gram-positive organisms is used , unless infections are due to oxacillin-resistant staphylococci Glycopeptide antibiotics are used extensively in the empirical treatment of febrile patients with neutropenia . To come to a more rational and restricted application of these expensive drugs and to reduce the risk of emergence of resistance , we carried out a prospect i ve , double-blinded , placebo-controlled single-centre study to investigate whether the addition of teicoplanin improved the outcome of neutropenic patients who remained febrile after 72 - 96 h of imipenem monotherapy . Patients with known infections caused by imipenem-resistant microorganisms were excluded . From the 114 evaluable episodes ( out of a total of 125 ) in 105 patients who met the eligibility criteria , 56 episodes were r and omized to receive teicoplanin and 58 to placebo . At 72 h after the start of the assigned intervention , 52 ( 45.6 % ) of the patients were afebrile ; at the end of the aplastic phase , 10 ( 8.8 % ) had succumbed . There was no difference between the two study arms . When febrile episodes were subdivided between microbiologically documented infections , clinical ly documented infections and fevers of unknown origin , again no significant differences were observed . With the exception of methicillin-resistant bacteria , Gram-positive infections seemed to respond well to imipenem monotherapy . It is concluded that the addition of teicoplanin on empirical grounds , i.e. for persistent fever only , is not necessary and that the use of glycopeptides should be restricted to well-defined clinical situations where methicillin-resistant bacteria are involved . Furthermore , it seems that many neutropenic patients respond slowly over more than 72 - 96 h even when they are treated with antibacterial drugs such as imipenem that are effective against the causative microorganism Two hundred twenty-five patients with 358 febrile episodes were treated with tobramycin and ticarcillin ( TT ) , tobramycin and mezlocillin ( TM ) , or tobramycin , ticarcillin and cephalothin ( TTC ) . There were no satistically significant differences in the response rates for patients who were proven to have infection ( 67 % with TT , 69 % with TTC and 53 % with TM ) . Patients were more often cured of their infection if their neutrophil count rose during therapy . In this study , the addition of cephalothin to TT did not increase the frequency of azotemia ( 10 % and 12 % , respectively ) . Although mezlocillin has a broader spectrum of activity in vitro than ticarcillin , it was not more efficacious when combined with tobramycin than ticarcillin plus tobramycin for the treatment of infections in neutropenic patients Summary We evaluated teicoplanin for suspected gram-positive infections after inadequate response to initial empiric beta-lactam and aminoglycoside combination therapy . All 20 patients included in this study received either an allogeneic ( 8 patients ) or an autologous ( 12 patients ) bone marrow transplant for acute myeloid leucaemia ( AML ) , non-Hodgkin's-lymphoma ( NHL , high grade ) or other malignant diseases . All patients developing primary septicaemia of unknown origin ( 18 patients ) or catheter-related septicaemia ( 2 patients ) were treated with 400 mg teicoplanin , administered i.v . once daily in combination with a cephalosporin and an aminoglycoside ( ceftazidime 2 g i.v . , t.i.d . ; netilmicin 400 mg once daily ) . All patients responded to therapy , 19 patients were 
    Output:
    
Bacterial superinfections , mainly Gram-positive , were detected less frequently in the intervention arm .
The use of glycopeptides can be safely deferred until the documentation of a resistant Gram-positive infection