***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: ABSTRACT Tigecycline , a novel glycylcycline antibiotic , exhibits strong activity against gram-positive , gram-negative , aerobic , anaerobic , and atypical bacterial species , including many resistant pathogens , i.e. , vancomycin-resistant enterococci , methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae . The safety and tolerability of tigecycline administered as single or multiple doses or at various infusion rates were explored in three phase 1 , r and omized , double-blind , placebo-controlled studies in healthy subjects . Full pharmacokinetic profiles of tigecycline were determined in two of these studies . Subjects in the single-dose study received 12.5 to 300 mg of tigecycline , which differed with respect to the duration of infusion , subjects ' feeding status , and ondansetron pretreatment . Subjects in the ascending multiple-dose study received 25 to 100-mg doses of tigecycline as a 1-h infusion every 12 h. The variable volume and infusion rate study consisted of administration of 100-mg loading dose of tigecycline , followed by 50 mg every 12 h for 5 days . Serum sample s were analyzed for tigecycline by vali date d high-pressure liquid chromatography or liquid chromatography/t and em mass spectrometry methods . Systemic clearance ranged from 0.2 to 0.3 liters/h/kg , and the tigecycline half-life ranged from 37 to 67 h. Tigecycline had a large volume of distribution ( 7 to 10 liters/kg ) , indicating extensive distribution into the tissues . Food increased the maximum tolerated single-dose from 100 to 200 mg , but the duration of infusion did not affect tolerability . Side effects , mainly nausea and vomiting , which are common to the tetracycline class of antimicrobial agents , were seen in these studies . Tigecycline exhibits linear pharmacokinetics and is safe and well tolerated in the dose ranges examined To compare efficacy and safety of a tigecycline regimen with an imipenem/cilastatin regimen in hospital-acquired pneumonia patients , a phase 3 , multicenter , r and omized , double-blind , study evaluated 945 patients . Co primary end points were clinical response in clinical ly evaluable ( CE ) and clinical modified intent-to-treat ( c-mITT ) population s at test-of-cure . Cure rates were 67.9 % for tigecycline and 78.2 % for imipenem ( CE patients ) and 62.7 % and 67.6 % ( c-mITT patients ) , respectively . A statistical interaction occurred between ventilator-associated pneumonia ( VAP ) and non-VAP subgroups , with significantly lower cure rates in tigecycline VAP patients compared to imipenem ; in non-VAP patients , tigecycline was noninferior to imipenem . Overall mortality did not differ between the tigecycline ( 14.1 % ) and imipenem regimens ( 12.2 % ) , although more deaths occurred in VAP patients treated with tigecycline than imipenem . Overall , the tigecycline regimen was noninferior to the imipenem/cilastatin regimen for the c-mITT but not the CE population ; this difference appears to have been driven by results in VAP patients Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction Tigecycline is an established treatment option for infections with multiresistant bacteria ( MRB ) . It retains activity against many strains with limited susceptibility to other antibiotics . Efficacy and safety of tigecycline as monotherapy or in combination regimens were investigated in a prospect i ve noninterventional study involving 1,025 severely ill patients in clinical routine at 137 German hospitals . Material s and methods Data on the full population have been published ; our present analysis focuses on infections caused by MRB . The study population included patients with complicated infections , high disease severity ( APACHE II > 15 : 65 % ) and high MRB prevalence . Most patients had comorbidities , including cardiovascular disease , renal insufficiency , and /or diabetes mellitus . Treatment success was defined as cure/improvement without requirement of further antibiotic therapy . Results Pathogens isolated from 215 evaluable patients with documented MRB infections included 132 methicillin-resistant Staphylococcus aureus ( MRSA ) , 42 vancomycin-resistant Enterococci ( VRE ) and 67 Gram-negative extended beta-lactamase ( ESBL ) producers . Of the MRB sub population , 140 patients received tigecycline  monotherapy , 75 were treated with combination regimens . High overall clinical success rates were recorded for MRB infections treated with tigecycline alone ( 94 % ) or in combinations ( 88 % ) ; in detail intraabdominal infections ( monotherapy : 90 % ; combinations : 93 % ) , skin/soft tissue infections ( 93 ; 100 % ) , community-acquired pneumonia ( 100 ; 100 % ) , hospital-acquired pneumonia ( 94,7 ; 72,7 % ) , diabetic foot infections ( 89 ; 33 % ) , blood stream infections ( 100 ; 100 % ) and multiple-site infections ( 92 ; 71 % ) . Conclusions Tigecycline achieved high clinical success rates in patients with documented infections involving MRB strains despite high disease severity . These results add to the evidence indicating that tigecycline is a valuable therapeutic option for complicated infections in severely ill patients with a high likelihood of multidrug-resistant pathogen involvement Introduction The high incidence of multidrug-resistant ( MDR ) bacteria among patients admitted to ICUs has determined an increase of tigecycline ( TGC ) use for the treatment of severe infections . Many concerns have been raised about the efficacy of this molecule and increased dosages have been proposed . Our purpose is to investigate TGC  safety and efficacy at higher than st and ard doses . Methods We conducted a retrospective study of prospect ively collected data in the ICU of a teaching hospital in Rome . Data from all patients treated with TGC for a microbiologically confirmed infection were analyzed . The safety profile and efficacy of high dosing regimen use were investigated . Results Over the study period , 54 patients ( pts ) received  TGC  at a st and ard dose ( SD group : 50 mg every 12 hours ) and 46 at a high dose ( HD group : 100 mg every 12 hours ) . Carbapenem-resistant Acinetobacter.baumannii ( blaOXA-58 and blaOXA-23 genes ) and Klebsiella pneumoniae ( blaKPC-3 gene ) were the main isolated pathogens ( n = 79 ) . There were no patients requiring TGC discontinuation or dose reduction because of adverse events . In the ventilation-associated pneumonia population ( VAP ) subgroup ( 63 patients : 30 received SD and 33 HD ) , the only independent predictor of clinical cure was the use of high tigecycline dose ( odds ratio ( OR ) 6.25 ; 95 % confidence interval ( CI ) 1.59 to 24.57 ; P = 0.009 ) whilst initial inadequate antimicrobial treatment ( IIAT ) ( OR 0.18 ; 95 % CI 0.05 to 0.68 ; P = 0.01 ) and higher Sequential Organ Failure Assessment ( SOFA ) score ( OR 0.66 ; 95 % CI 0.51 to 0.87 ; P = 0.003 ) were independently associated with clinical failure . Conclusions TGC was well tolerated at a higher than st and ard dose in a cohort of critically ill patients with severe infections . In the VAP subgroup the high-dose regimen was associated with better outcomes than conventional administration due to Gram-negative MDR bacteria BACKGROUND Tigecycline is effective in the treatment of complicated skin/skin-structure infection ( cSSSI ) , complicated intraabdominal infection ( cIAI ) , and community-acquired bacterial pneumonia ( CAP ) , but its efficacy in subjects with secondary bacteremia is unknown . METHODS Pooled data from subjects enrolled for treatment of cSSSI , cIAI , or CAP presenting with bacteremia from 7 double-blind and 1 open-label trial of tigecycline  compared with vancomycin-aztreonam , imipenem-cilastatin , levofloxacin , vancomycin , or linezolid were analyzed . The primary efficacy end point was the clinical cure rate at the test-of-cure assessment . RESULTS A total of 170 subjects were identified ( 91 tigecycline recipients and 79 recipients of the comparator agent ) . Clinical cure rates were 81.3 % and 78.5 % for tigecycline and the comparator , respectively ( P = .702 ) . Analysis by sex , age , creatinine clearance , infection site , Acute Physiology and Chronic Health Evaluation score , and Fine score demonstrated no significant between-group differences . Clinical cure rates for the most commonly represented pathogens ( Staphylococcus aureus , Streptococcus pneumoniae , and gram-negative species ) were also not significantly different between treatment groups . No decrease in the rate of cure was found in organisms with increasing tigecycline minimum inhibitory concentrations . Nine subjects treated with tigecycline and 1 subject treated with comparator were found to have persistent bacteremia . No clinical ly significant differences in safety parameters were identified . CONCLUSIONS Tigecycline was generally safe and well tolerated in the treatment of secondary bacteremia associated with cSSSI , cIAI , and CAP ; cure rates were similar to comparative st and ard therapies ABSTRACT In a previous phase 3 study , the cure rates that occurred in patients with hospital-acquired pneumonia treated with tigecycline  at the approved dose were lower than those seen with patients treated with imipenem and cilastatin ( imipenem/cilastatin ) . We hypothesized that a higher dose of tigecycline is necessary in patients with hospital-acquired pneumonia . This phase 2 study compared the safety and efficacy of two higher doses of tigecycline with imipenem/cilastatin in subjects with hospital-acquired pneumonia . Subjects with hospital-acquired pneumonia were r and omized to receive one of two doses of tigecycline ( 150 mg followed by 75 mg every 12 h or 200 mg followed by 100 mg every 12 h ) or 1 g of imipenem/cilastatin every 8 h. Empirical adjunctive therapy was administered for initial coverage of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa infection , depending on the r and omization regimen . Clinical response , defined as cure , failure of treatment , or indeterminate outcome , was assessed 10 to 21 days after the last day of therapy . In the clinical ly evaluable population , clinical cure with tigecycline 100 mg ( 17/20 , 85.0 % ) was numerically higher than with tigecycline 75 mg ( 16/23 , 69.6 % ) and imipenem/cilastatin ( 18/24 , 75.0 % ) . No new safety signals with the high-dose tigecycline were identified . A numerically higher clinical response was observed with the 100-mg dose of tigecycline . This supports our hypothesis that a higher area under the concentration-time curve over 24 h in the steady state divided by the MIC ( AUC/MIC ratio ) may be necessary to achieve clinical cure in patients with hospital-acquired pneumonia . Further studies are necessary . ( The Clinical Trials.gov identifier for this clinical trial is NCT00707239 . This large prospect i ve non-interventional study investigated the effects of tigecycline either as single agent or in combination with other antimicrobial agents in 1,025 patients treated in clinical routine at German hospitals . Sixty-five percent of the patients had APACHE II scores > 15 , indicating high overall disease severity . Complicated intra-abdominal infections ( cIAI ) or complicated skin and skin tissue infections ( cSSTI ) were the most common indications , with Staphylococcus aureus , Enterococcus faecium and Escherichia coli being the most frequently isolated pathogens . Clinical success was reported at the end of tigecycline therapy in 74.2 % of the total population , in 75.4 % of the cIAI and in 82.2 % of the cSSTI patients . The sub population ( 28.0 % of the patients ) infected with multidrug-resistant pathogens ( methicillin-resistant S. aureus , extended-spectrum β- 
    Output:
    
The st and ard-dose tigecycline and comparator groups did not differ significantly in their rates of clinical cure .
However , high-dose tigecycline was more effective than st and ard-dose tigecycline or the comparators for the treatment of HAP .
There was no significant difference in mortality between the st and ard-dose or high-dose regimen and the comparators .
Although the safety profile of st and ard-dose tigecycline was similar to the comparators , the high-dose regimen exhibited more AEs compared with the other groups .
Conclusion : High-dose tigecycline is efficient for the treatment of HAP but is associated with more AEs