***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: One hundred and two patients with neutropenia ( less than 1 x 10(9)/L ) secondary to primary hematological disorders or chemotherapy for hematological malignancies were prospect ively r and omised , upon the development of fever or other signs of infection , to receive empirical antibiotic treatment with either ceftazidime ( + /- flucloxacillin ) ( n = 52 ) or azlocillin plus amikacin ( + /- flucloxacillin ) ( A&A , n = 50 ) . The two groups were equivalent with respect to clinical and laboratory parameters prior to antibiotic therapy and flucloxacillin was added to approximately 25 % of the patients in each group on the clinical suspicion of Gram positive infection . When assessed at 96 hours , the complete response rates were 59.6 % for the ceftazidime treated patients and 44 % for A&A treated patients . Partial response rates were 17 % and 20 % respectively . This difference was not statistically significant . Eight patients died whilst on the trial , three of those initially r and omised to ceftazidime and five initially r and omised to A&A. Moderate to severe hypokalemia was encountered significantly less often in the ceftazidime treated group ( p less than 0.01 ) , whilst other parameters of toxicity were equivalent . No primary or acquired resistance to ceftazidime was encountered . Separate analysis of those patients who did not receive flucloxacillin yielded identical results . We conclude that ceftazidime ( + /- flucloxacillin ) is as efficacious as azlocillin plus amikacin ( + /- flucloxacillin ) in the empirical antibiotic management of such patients and is associated with a lower incidence of moderate to severe hypokalemia ABSTRACT The nephrotoxicity and ototoxicity associated with once-daily versus twice-daily administration of aminoglycosides was assessed in patients with suspected or proven gram-negative bacterial infections in a r and omized , double-blind clinical trial . Patients who received therapy for ≥72 h were evaluated for toxicity . Patients also received concomitant antibiotics as deemed necessary for treatment of their infection . Plasma aminoglycoside concentrations , prospect i ve aminoglycoside dosage adjustment , and serial audiologic and renal status evaluations were performed . The probability of occurrence of a nephrotoxic event and its relationship to doses and daily aminoglycoside exposure served as the main outcome measurement . One hundred twenty-three patients were enrolled in the study , with 83 patients receiving therapy for at least 72 h. For 74 patients plasma aminoglycoside concentrations were available for analysis , and the patients formed the group evaluable for toxicity . The primary infectious diagnosis for the patients who were enrolled in the study were bacteremia or sepsis , respiratory infections , skin and soft tissue infections , or urosepsis or pyelonephritis . Of the 74 patients evaluable for toxicity , 39 received doses twice daily and 35 received doses once daily and a placebo 12 h later . Nephrotoxicity occurred in 6 of 39 ( 15.4 % ) patients who received aminoglycosides twice daily and 0 of 35 patients who received aminoglycosides once daily . The schedule of aminoglycoside administration , concomitant use of vancomycin , and daily area under the plasma concentration-time curve ( AUC ) for the aminoglycosides were found to be significant predictors of nephrotoxicity by multivariate logistic regression analysis ( P ≤ 0.001 ) . The time to a nephrotoxic event was significantly influenced by vancomycin use and the schedule of administration , as assessed by Cox proportional hazards modeling ( P ≤ 0.002 ) . The results of the multivariate logistic regression analysis and the Cox proportional hazards modeling demonstrate that both the probability of occurrence and the time to occurrence of aminoglycoside nephrotoxicity are influenced by the schedule on which the aminoglycoside is administered as well as by the concomitant use of vancomycin . Furthermore , this risk of occurrence is modulated by the daily AUC for aminoglycoside exposure . These data suggest that once-daily administration of aminoglycosides has a predictably lower probability of causing nephrotoxicity than twice-daily administration This study aim ed to evaluate the efficacy of amikacine and ceftazidime as an empirical antibiotic therapy for neutropenic patients affected by haematological neoplasms and to investigate the presence of prognostic features suggesting a poor outcome with this antibiotic combination at the onset of infection . This could allow the identification of subgroups of patients with a low rate of response to amikacin/ceftazidime therapy  ; in these patients different initial empirical therapy may be indicated . The study population comprised 166 severely neutropenic ( absolute neutrophil count below 500/μl ) oncohaematological patients with fever or clinical signs of infection . Multivariate analysis confirmed four negative prognostic factors : 3 or more days of hospitalization at the onset of an infectious episode , a diagnosis of acute myeloid leukaemia , a haematological disease status different from complete remission , the presence of pneumonia . Depending on how many factors are present , cases can be stratified into three groups , of significantly different prognosis : favourable ( 0 or 1 factor ) 76 % success ; intermediate ( 2 factors ) 52 % success ; unfavourable ( 3 or 4 factors ) 19 % success . At the onset of an infectious episode a subgroup of patients with a very low response rate to empirical  amikacin/ceftazidime antibiotic therapy is identifiable , for whom a different therapy is indicated . Because of the high rate of proven or probable fungal infections in this group , the immediate administration of a systemic antifungal therapy , in addition to antibacterial agents , could be considered in these high-risk patients . Studies should be specifically addressed to evaluating a stratification of empirical antibiotic therapy according to risk factors present at the onset of infection A prospect i ve , r and omized clinical trial was conducted to compare the efficacy of piperacillin/tazobactam and amikacin combination with carbapenem monotherapy for the empirical treatment of febrile neutropenic episodes of children with acute lymphoblastic leukemia or acute myeloblastic leukemia . Patients aged 2–16 years with hematological malignancies who had febrile neutropenia were r and omly assigned to receive piperacillin/tazobactam ( 80 mg/kg piperacillin/10 mg/kg tazobactam , q6h ) combined with amikacin ( PTA ) ( 7.5 mg/kg , q12h ) or meropenem or imipenem ( 20 mg/kg , q8h ) ( C ) . Response to antimicrobial therapy , evaluated for etiological agents , was measured . Duration of fever , neutropenia , and hospitalization , mortality , and the need for additional antibiotics or antifungal drugs were compared for the treatment success between the two groups . Out of 87 febrile neutropenic episodes that were evaluable for comparison , 46 patients received PTA and 41 patients were treated with carbapenems ( imipenem or meropenem ) . Overall , the microbiologically documented infection rate was 21.9 % , with Staphylococcus epidermidis as the most common cause of bacteremia . The rate of treatment modification was 56.5 % in the PTA group and 53.6 % in the carbapenem group with no statistical difference ( p > . 05 ) . There was no infection-related mortality during the study period . There was no difference between the two regimens for duration s of fever , neutropenia , and hospitalization ( p > . 05 for all categories ) . PTA was as effective as carbapenem monotherapy as an initial empirical regimen in febrile neutropenic episodes of pediatric hematological malignancies 143 aplastic episodes with fever in 91 haematological patients with granulocytopenia were treated empirically in a r and omized prospect i ve study using either imipenem ( Imi ) or a combination of tobramycin and cefuroxime ( T/C ) .  Response after 72 h was significantly better in patients receiving Imi ( 44/75 vs 27/68 , p < 0.05 ) . This was seen especially in patients with bacteriologically proven infections where the isolated staphylococci and streptococci were more susceptible to Imi . In both groups , patients who failed to respond to the initial antibiotic therapy were given vancomycin and aztreonam ( V/A ) . The response rate after another 72 h , measured using the same criteria as after the first 72 h , did not differ statistically between the groups . One patient in each study group died from the bacterial infection , both from Gram-positive bacteraemia . Duration of fever was significantly shorter in the Imi group ( 4 days vs 7 days , p < 0.04 ) . Serum peak and trough concentrations of the antibiotics were comparable . Both regimens were well tolerated . Our results show that monotherapy with imipenem is superior to the combination of tobramycin and cefuroxime during the first 72 h of therapy and can be safely administered to neutropenic patients with predominantly Gram-positive infections . A combination of vancomycin and aztreonam , given when initial imipenem treatment has failed , was effective in only a few patients . Adjuvant glycopeptide therapy from the outset in the treatment of febrile granulocytopenic patients did not seem worthwhile 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 Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin . In the ceftriaxone-treated group , 60 out of 143 febrile 
    Output:
    
Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure .
No correlation was noted between mortality and failure rates and these trials .
Beta-lactam monotherapy is advantageous compared with beta-lactam-aminoglycoside combination therapy with regard to survival , adverse events and fungal super-infections .