***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: Isepamicin is a new aminoglycoside antibiotic which possesses greater stability to aminoglycoside-inactivating enzymes compared with other available aminoglycosides . In this prospect i ve , r and omised , open trial , the safety and efficacy of intravenous administration of isepamicin was compared with that of intravenous amikacin in seriously ill adults with nosocomial pneumonia or septicaemia . Each study aminoglycoside was administered concurrently with ceftazidime or imipenem .  Patients were r and omised to receive isepamicin 15 mg/kg once daily , isepamicin 7.5 mg/kg twice daily or amikacin 7.5 mg/kg twice daily . For patients with nosocomial pneumonia , the proportions of patients in the intent-to-treat population ( n = 130 ) who were clinical ly cured at the end of treatment were similar in each treatment group : 18/44 ( 41 % ) isepamicin once daily ; 19/45 ( 42 % ) isepamicin twice daily ; and 17/41 ( 42 % ) amikacin . Corresponding results for the efficacy population ( n = 58 ) were : 12/20 ( 60 % ) isepamicin once daily ; 14/21 ( 67 % ) isepamicin twice daily ; 9/17 ( 53 % ) amikacin . In patients with septicaemia , clinical cure was achieved in 8/10 ( 80 % ) patients treated with isepamicin once daily , compared with 8/13 ( 62 % ) patients who received isepamicin twice daily , and 7/12 ( 58 % ) patients treated with amikacin . For both diagnoses , there were no statistically significant differences between the treatment groups in clinical cure rate . The most commonly isolated target pathogen was Pseudomonas aeruginosa . For both nosocomial pneumonia and septicaemia , the proportion of patients in the intent-to-treat population whose pretreatment valid target pathogens were eliminated was similar in each treatment group . In total , 51 patients ( 30 % ) died during study , mostly due to disease progression or complications , or concurrent illness . All three treatment regimens were well tolerated . The proportion of patients experiencing at least one adverse event was 11 % , 25 % and 9 % for isepamicin once daily , isepamicin twice daily and amikacin , respectively . The incidence of ototoxicity and nephrotoxicity was relatively low in both treatment groups We evaluated the antimicrobial activity of fosfomycin against a r and omly selected sample of 30 Klebsiella pneumoniae , 30 Pseudomonas aeruginosa , and 30 Acinetobacter baumannii multidrug-resistant , clinical isolates from patients in a general tertiary care hospital in Athens , Greece . St and ard laboratory methods were used for susceptibility testing to commonly used antibiotics and the detection of extended-spectrum-β-lactamase ( ESBL ) and metallo-β-lactamase ( MBL ) production . The minimum inhibitory concentration ( MIC ) of fosfomycin for each isolate was determined by the agar dilution method . All K. pneumoniae isolates were both ESBL and MBL producers ; all P. aeruginosa isolates were ESBL producers . The K. pneumoniae strains had fosfomycin MICs distributed across a range of 8 - 64 μg/ml ; MIC50 was 16 μg/ml and MIC90 32 μg/ml . The  fosfomycin MICs of the P. aeruginosa strains had a distribution across a range of 4 to over 512 μg/ml ; MIC50 was 32 μg/ml and MIC90 128 μg/ml . The  fosfomycin MICs of the A. baumannii strains had a distribution across a range of 64 to over 512 μg/ml ; MIC50 was 256 μg/ml and MIC90 more than 512 μg/ml . Although st and ardized fosfomycin MIC interpretative breakpoints for the species studied are lacking , the findings of our study support the idea that fosfomycin may be further investigated as one among a decreasing list of therapeutic options for the treatment of infections due to multidrug-resistant strains of , primarily , K. pneumoniae and , secondly , P. aeruginosa In a prospect i ve multicentre open trial , hospitalised adult patients with acute lower respiratory tract infections , mainly pneumonia or bronchitis , were r and omised to receive either isepamicin 8 or 15 mg/kg once daily depending on the severity of the infection or amikacin 7.5 mg/kg twice daily . Patients with infections known to be caused by Pseudomonas aeruginosa were to be given concomitant treatment with ceftazidime . In the intent-to-treat population , i.e. patients who received at least one dose r and omised treatment , a clinical cure or improvement at the end of treatment was seen in 112/125 ( 90 % )  isepamicin patients and 55/60 ( 92 % ) amikacin  patients . The corresponding rates for patients with a primary diagnosis of pneumonia were 45/52 ( 87 % ) and 25/28 ( 89 % ) . Cure/improvement rates for patients with P. aeruginosa as the causative pathogen ( 34 of whom also received ceftazidime ) were 28/30 ( 93 % ) and 16/18 ( 89 % ) , respectively . In the efficacy population ( patients who had a valid pretreatment culture and who met other evaluability criteria ) , total elimination ( documented or presumed if infection had resolved ) of target pathogens occurred in 54/63 ( 86 % ) of isepamicin patients and 25/30 ( 83 % ) of amikacin patients . P. aeruginosa , Escherichia coli , Klebsiella pneumoniae and Staphylococcus aureus were commonly isolated pathogens . Treatment-related adverse were mainly mild or moderate in severity and occurred in 10 % of isepamicin patients and 13 % of amikacin patients . Four patients ( 3 isepamicin and 1 amikacin ) discontinued treatment because of severe adverse events and a further isepamicin patient withdrew because of a mild adverse event . Nephrotoxicity and ototoxicity occurred infrequently Intensive care unit (ICU)-acquired infections as a result of multidrug-resistant Gram-negative pathogens remain a serious problem in critically ill patients . Adult ICU patients who received intravenous fosfomycin  were prospect ively examined to assess its safety and effectiveness as an adjunct to the antimicrobial therapy of life-threatening infections caused by carbapenem-resistant Klebsiella pneumoniae . Fosfomycin was administered intravenously in 11 patients for treatment of hospital-acquired infections caused by carbapenem-resistant K. pneumoniae .  Fosfomycin ( 2 - 4 g every 6 h ) was administered in combination with other antibiotics . The mean + /- SD duration of treatment was 14 + /- 5.6 days . All patients had good bacteriological and clinical outcome of infection . All-cause hospital mortality was two out of 11 ( 18.2 % ) patients . No patient experienced adverse events related to the administration of fosfomycin . Intravenous fosfomycin may be a beneficial and safe adjunctive treatment in the management of life-threatening ICU-acquired infections caused by carbapenem-resistant K. pneumoniae ABSTRACT Directed evolution by r and om PCR mutagenesis of the gene for the aminoglycoside 2″-IIa phosphotransferase generated R92H/D268N and N196D/D268N mutant enzymes , result ing in elevated levels of resistance to amikacin and isepamicin but not to other aminoglycoside antibiotics . Increases in the activities of the mutant phosphotransferases for isepamicin are the result of decreases in Km values , while improved catalytic efficiency for amikacin is the result of both a decrease in Km values and an increase in turnover of the antibiotic . Enzymes with R92H , D268N , and D268N single amino acid substitutions did not result in elevated MICs for aminoglycosides Two hundred and three patients with skin and skin structure infections were treated with isepamicin once daily or amikacin twice daily in an open , r and omised , comparative multicentre trial . Patients were r and omised to treatment with isepamicin or amikacin in a 2:1 ratio . Severe infections ( 63 patients ) were treated with isepamicin 15 mg/kg once daily ( n = 15 ) or amikacin 7.5 mg/kg twice daily ( n - 18 ) , less severe infections ( 140 patients ) with isepamicin 8 mg/kg once daily ( n = 93 ) or amikacin 7.5 mg/kg twice daily ( n = 47 ) . The overall clinical response rate at the end of treatment was excellent in all treatment groups ( 94 - 96 % cured or improved ) with no significant differences between isepamicin and amikacin in patients with either server or less severe infections . The most commonly isolated target pathogens were Pseudomonas aeruginosa , Escherichia coli , Proteus mirabilis and Staphylococcus aureus . Overall , in patients who had a valid target pathogen isolated prior to treatment and who met other evaluability criteria , bacteriological eradication was achieved in over 90 % of patients ; amikacin patients with severe infections had a somewhat lower eradication rate ( 82 % ) . Over all infections , 4/110 ( 4 % ) patients in the isepamicin group and 5/54 ( 9 % ) patients in the amikacin had organisms which persisted . Adverse events were reported in 12 % of patients in the isepamicin group and 6 % in the amikacin group . The most frequently reported adverse event in the isepamicin group as headache . Two patients ( one in each treatment group ) , both of whom experienced skin rashes , were withdrawn . Potentially clinical ly significant changes in serum creatinine occurred in two patients , who received isepamicin and one who received amikacin ( who was withdrawn from the study ) . Ototoxicity was rare , occurring in one patient treated with isepamicin In this study we compared the efficacy and safety of isepamicin versus amikacin at a dose of 7.5 mg/kg i.v . q12h for 10 - 14 days in children with pyelonephritis . Sixteen children were enrolled in the study ; ten received isepamicin and six amikacin . Urine cultures grew Escherichia coli in all patients . All patients were treated successfully with either isepamicin or amikacin .  Clinical and bacteriological response rates were 100 % for both groups . No adverse events occurred . Peak serum levels ranged from 9.05 to 30.70 mg/l ( median : 16.165 ) and from 12.20 to 25.90 mg/l ( median : 19.05 ) for isepamicin and amikacin , respectively . Trough serum levels ranged from 0.11 to 3.20 mg/l ( median : 0.75 ) and from 0.1 to 2.1 mg/l ( median : 0.655 ) , respectively . Isepamicin was shown to be as effective and safe as amikacin in the treatment of children with pyelonephritis and might prove an advantageous alternative in areas with high incidence of resistance to other aminoglycosides The efficacy and safety of isepamicin 7.5 mg/kg of body weight twice daily or amikacin the same dosage regimen for the treatment of various infections in neutropenic and non-neutropenic paediatric patients were compared in a prospect i ve r and omised trial . In total , 306 patients were enrolled and received at least one dose of r and omised treatment ( 204 isepamicin  , 102 amikacin : intent-to-treat population ) ; 181 patients satisfied all criteria for evaluability ( 120 isepamicin  , 61 amikacin : efficacy population ) . Clinical cure or improvement rates in the isepamicin and amikacin groups were : intent-to-treat population , 188/204 ( 92 % ) and 94/102 ( 92 % ) , respectively ; efficacy population , 117/120 ( 98 % ) and 58/61 ( 95 % ) , respectively . The bacteriological elimination rate ( efficacy population ) in the isepamicin and amikacin treatment groups was 75/76 ( 99 % ) vs 35/38 ( 92 % ) . Nephrotoxicity , defined as an increase in serum creatinine of 0.5 mg/dL or > or = 44.2 mumol/L from baseline , occurred in 4/187 ( 2 % ) and 1/191 ( 1 % ) children treated with isep 
    Output:
    
In conclusion , isepamicin might be active in vitro against Gram-negative bacteria with resistance to amikacin and other aminoglycosides