***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: To determine whether combination antibiotic therapy including a short course of an aminoglycoside was as effective and less toxic than a conventional long course of the combination for the empirical therapy of gram-negative bacteremia in patients with cancer and granulocytopenia , we conducted a r and omized multicenter trial comparing ceftazidime plus a short course ( three days ) of amikacin , ceftazidime plus a long course ( nine days ) of amikacin , and azlocillin plus a long course ( nine days ) of amikacin .  Single-organism gram-negative bacteremia occurred in 129 of 872 evaluable patients . Without a change in antibiotics , the response rates were 81 percent with ceftazidime and long-course amikacin , 48 percent with ceftazidime and short-course amikacin ( P = 0.002 ) , and 40 percent with azlocillin and long-course amikacin ( P less than 0.001 ) . Among patients with fewer than 100 granulocytes per cubic millimeter throughout therapy , the response rates were 6 percent with ceftazidime and short-course amikacin and 50 percent with ceftazidime and long-course amikacin ( P = 0.03 ) . Linear logistic-regression analysis showed that therapy with ceftazidime and long-course amikacin was the most favorable prognostic factor of the response to infection , whereas the presence of leukemia or shock was the least favorable . We conclude that ceftazidime should be given in combination with a conventional full course of an aminoglycoside ( amikacin ) when used for the empirical treatment of gram-negative bacteremia in cancer patients with granulocytopenia OBJECTIVES To study the effect of previously administered antibiotics on the antibiotic susceptibility profile of Enterobacter , the factors affecting mortality , and the emergence of antibiotic resistance during therapy for Enterobacter bacteremia . DESIGN Prospect i ve , observational study of consecutive patients with Enterobacter bacteremia . SETTING Three university tertiary care centers , one major university-affiliated hospital , and two university-affiliated Veterans Affairs medical centers . PATIENTS A total of 129 adult patients were studied . MEASUREMENTS The two main end points were emergence of resistance during antibiotic therapy and death . MAIN RESULTS Previous administration of third-generation cephalosporins was more likely to be associated with multiresistant Enterobacter isolates in an initial , positive blood culture ( 22 of 32 , 69 % ) than was administration of antibiotics that did not include a third-generation cephalosporin ( 14 of 71 , 20 % ; P less than 0.001 ) . Isolation of multiresistant Enterobacter sp. in the initial blood culture was associated with a higher mortality rate ( 12 of 37 , 32 % ) than was isolation of a more sensitive Enterobacter sp. ( 14 of 92 , 15 % ; P = 0.03 ) . Emergence of resistance to third-generation cephalosporin therapy  ( 6 of 31 , 19 % ) occurred more often than did emergence of resistance to aminoglycoside ( 1 of 89 , 0.01 % ; P = 0.001 ) or other beta-lactam ( 0 of 50 ; P = 0.002 ) therapy . CONCLUSIONS More judicious use of third-generation cephalosporins may decrease the incidence of nosocomial multiresistant Enterobacter spp . , which in turn may result in a lower mortality for Enterobacter bacteremia . When Enterobacter organisms are isolated from blood , it may be prudent to avoid third-generation cephalosporin therapy regardless of in-vitro susceptibility PURPOSE To assess the feasibility of early discharge to home therapy with st and ard intravenous antibiotics in 30 patients with fever and neutropenia at low risk by a vali date d clinical decision rule . PATIENTS AND METHODS Newly admitted out patients with fever and neutropenia were evaluated for home therapy during 2 days of inpatient observation . To evaluate enrolled patients ' acceptance of home care , we assessed patient attitudes and quality of life before and after home therapy . To assess economic effects , we compared the medical charges of patients treated at home with those of medically eligible patients who remained in the hospital . RESULTS Of the first 84 patients , 50 ( 60 % ) were medically ineligible , and neutropenia was resolved in another eight ( 10 % ) during the observation period . Only nine patients of the remaining 26 who were medically eligible ( 35 % ) were enrolled in the home-therapy trial . Thereafter , 21 of 31 medically eligible patients ( 68 % ) were enrolled . The 30 patients treated at home were neutropenic for a median of 6 days ( mean , 8.2 ) . Four had medical complications , and five others were readmitted for observation . Patients ' quality of life improved during home therapy , and favorable attitudes toward home care persisted after treatment . Medically eligible patients not enrolled had briefer neutropenia than patients treated at home , but had 44 % higher daily medical charges and equivalent overall charges despite treatment half as long . CONCLUSION We conclude that early discharge of low-risk patients to home intravenous antibiotic therapy is feasible , is well received by patients , and may prove to be cost-saving . However , these conclusions must be vali date d in a large r and omized trial Five combinations of antibiotics ( ampicillin/gentamicin , cephalothin/gentamicin , carbenicillin/gentamicin , polymyxin/carbenicillin , and carbenicillin/cephalothin ) were investigated in vitro and in 148 severe infectious episodes caused by gram-negative bacilli in patients with disseminated cancer . The use of combinations that were synergistic in vitro against the offending microorganism ( synergy was defined as occurring when the minimal inhibitory concentration of each of the drugs in the combination was one-quarter or less of the minimal inhibitory concentration of each drug alone ) was associated with a significantly better response to antibacterial therapy ( P < 0.01 ) than the use of combinations that were not synergistic against the causative agent 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 The rapid , empiric institution of broad-spectrum antibacterial therapy for the febrile , neutropenic patient has had a profound effect in reducing the mortality from gram-negative infection to approximately 10 % [ 1 , 2 ] . All the evidence accumulated during the 1970s indicated that adequate therapy could only be achieved by administering antibiotics in combinations , leading to the widespread practice of using either a -lactam with an aminoglycoside [ 3 , 4 ] or two -lactams [ 5 , 6 ] . Concerns about the toxicity associated with combination therapy encouraged several investigators to assess the feasibility of using certain broad-spectrum -lactams as single agents for empiric therapy in febrile neutropenic patients [ 7 - 9 ] . Among the drugs investigated , ceftazidime has emerged as a c and i date for effective monotherapy [ 9 - 11 ] . However , previous studies have had several shortcomings , including inadequate statistical power [ 12 - 16 ] , the inclusion of a large number of patients at relatively low risk for major infection [ 17 ] , and the limited number of patients with gram-negative sepsis [ 18 , 19 ] . Therefore , the issue of monotherapy remained controversial and a definitive study with sufficient patients was warranted . When evaluating empiric therapy in this setting , the criteria for assessment have a major effect on the outcome [ 20 ] . Regardless of the method of assessment , the principal goal of empiric antibacterial therapy is to ensure that the patient survives both the infection and the neutropenic episode . Consequently , we used the criteria proposed by Pizzo and colleagues [ 17 ] , in which the outcome of treatment is only scored as a failure if the patient dies of infection . Importantly , this method of assessment takes account of the initial infective event as well as any event that might subsequently develop during the same neutropenic episode . We also wished to reflect the common clinical practice of adjusting therapy whenever it is proved or perceived to be inadequate . Therefore , the protocol allowed modification of the empiric regimen by addition or substitution , but the reasons for altering therapy had to be reported in the case report form . By so doing , we were then able to subdivide the category of success with modification as defined by Pizzo and colleagues [ 17 ] and discriminate between true failures , such as persistence of the initial pathogen , and changes in therapy made simply because the clinician lacked confidence in the regimen without any objective sign of clinical deterioration caused by a bacterial infection . Several alternatives were available for the comparative arm , but the combination of piperacillin and tobramycin was established as the st and ard empiric therapy for the febrile , neutropenic adult patient in most centers . We therefore selected this combination to compare its efficacy and toxicity with that of ceftazidime alone as empiric therapy for fever in the neutropenic patient , particularly focusing on infections caused by gram-negative bacteria . Methods The study was design ed as a multicenter , nonblinded , r and omized , parallel-group comparison of ceftazidime and a combination of piperacillin and tobramycin for the empiric management of fever defined as a single axillary temperature of 38.5 C or at least two readings of more than 38 C taken 2 hours apart ( Figure 1 ) . Patients with cancer who were older than 12 years were included provided that intensive chemotherapy induced neutropenia with granulocyte counts of less than 500 cells/mm3 within 3 days of starting antibiotic treatment . Those who received only palliative therapy for their malignant disease were not eligible . Patients were excluded if they were allergic to any of the trial antibiotics , if their serum creatinine exceeded 265 mol/L ( 3 mg/dL ) , or if they had received previous parenteral antibiotic therapy during the same neutropenic episode . Any prophylactic antibacterial agents were to be withdrawn at the onset of fever with the exception of tuberculostatics and sulfamethoxazole-trimethoprim when administered twice weekly for the prevention of Pneumocystis carinii infection [ 21 ] . As is common practice in such trials [ 22 ] , patients could re-enter the protocol for multiple , separate episodes of neutropenia provided that each episode was followed by an interval of at least one week with granulocyte counts in excess of 1000/mm3 and the patient also satisfied all inclusion criteria . The protocol was approved by the ethical committees of the participating institutions . Figure 1 . Flow diagram of the study . R and omization Procedure After giving informed consent , patients were assigned to one of six strata . They were first stratified according to underlying disease , namely leukemia and bone marrow transplants or solid tumor and lymphoma , following which , they were stratified according to the infection at presentation , skin or soft-tissue infection likely to be caused by gram-positive bacteria ( for example exit-site infections related to venous access devices ) , anaerobic infection associated with the alimentary tract , or other infectious complications . The last group comprised the principal group of patients who were to be treated with either ceftazidime alone or a combination of piperacillin and tobramycin , whereas patients with skin and soft-tissue infections and those with anaerobic infections were to receive vancomycin and metronidazole , respectively , in addition to these core regimens . We do not report results obtained for episodes treated with these additional antibiotics because the data were not germane to the primary objective of the study and only a limited number of patients were involved . Treatment Allocation After having been placed in one of the three strata , patients were sequentially and r and omly assigned to receive one of the regimens by means of opening sealed envelopes that contained the treatment allocation that had been generated central ly for each participating institution in blocks of eight to ensure balance . All drugs were given intravenously : ceftazidime as a 20- to 30-minute infusion of 2 g every 8 h ; piperacillin by slow injection of 16 to  
    Output:
    
Although our study was limited by the small number of trials available for review , the results suggest that SDD of aminoglycosides may be efficacious for febrile , immunocompromised patients .