***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: BACKGROUND Early identification of pathogens from blood cultures using matrix-assisted laser desorption ionization time-of-flight ( MALDI-TOF ) mass spectrometry may optimize the choice of empirical antibiotic therapy in the setting of bloodstream infections . We aim ed to assess the impact of this new technology on the use of antibiotic treatment in patients with gram-negative bacteremia . METHODS We conducted a prospect i ve observational study from January to December 2010 to evaluate the sequential and separate impacts of Gram stain reporting and MALDI-TOF bacterial identification performed on blood culture pellets in patients with gram-negative bacteremia . The primary outcome was the impact of MALDI-TOF on empirical antibiotic choice . RESULTS Among 202 episodes of gram-negative bacteremia , Gram stain reporting had an impact in 42 cases ( 20.8 % ) . MALDI-TOF identification led to a modification of empirical therapy in 71 of all 202 cases ( 35.1 % ) , and in 16 of 27 cases ( 59.3 % ) of monomicrobial bacteremia caused by AmpC-producing Enterobacteriaceae . The most frequently observed impact was an early appropriate broadening of the antibiotic spectrum in 31 of 71 cases ( 43.7 % ) . In total , 143 of 165 episodes ( 86.7 % ) of monomicrobial bacteremia were correctly identified at genus level by MALDI-TOF . CONCLUSIONS In a low prevalence area for extended spectrum betalactamases ( ESBL ) and multiresistant gram-negative bacteria , MALDI-TOF performed on blood culture pellets had an impact on the clinical management of 35.1 % of all gram-negative bacteremia cases , demonstrating a greater impact than Gram stain reporting . Thus , MALDI-TOF could become a vital second step beside Gram stain in guiding the empirical treatment of patients with bloodstream infection Two hundred twenty-six patients with bacteremia were prospect ively enrolled in a r and omized trial that was performed to determine the clinical impact of the receipt of in vitro microbiological data by the physician soon after organism detection as opposed to having the physicians wait until similar data were available by routine methods . Identification and antibiotic susceptibility patterns of 110 isolates were determined by direct inoculation of the Vitek AutoMicrobic system ( Vitek Systems , Inc. , Hazelwood , Mo. ) with a sample from a positive blood culture vial . One hundred sixteen isolates were processed by routine methods . Microbiological results were available within an average of 8.8 h by the direct method versus an average of 48 h by the routine method . In both groups an infectious disease fellow used the information to make therapeutic recommendations to the responsible physician . When compared with that provided by the routine method , the information provided by the direct method was significantly more likely to result in an initiation of antibiotic therapy , a change to more effective therapy , or a change to less expensive therapy . Recommendations were significantly more likely to be followed in patients whose isolates were processed by the direct method versus the routine method . A projected savings of $ 158 per patient was estimated for the patients who were changed to less expensive therapy or in whom antibiotics were discontinued because results were available sooner . These cost savings , coupled with changes in therapy made for reasons of efficacy , support the usefulness of the earlier reporting of the identity and antibiotic susceptibility patterns of bacterial blood culture isolates Fluorescence in situ hybridization using peptide nucleic acid probes ( PNA-FISH ) differentiates Staphylococcus aureus from other Gram-positive-cocci in clusters ( GPCC ) . 101/202 patients with GPCC+ blood cultures were r and omly assigned to clinician-notification of PNA FISH results . Notification was associated with reduced mortality ( 8 % vs.17 % , p = 0.05 ) , further antibiotic use ( median −2.5 days , p = 0.01 ) , and trended toward reduced hospital stay and charges OBJECTIVES The aim of this work was to establish the clinical impact of rapid oxacillin susceptibility testing in nosocomial Staphylococcus aureus bacteraemia . METHODS This study was performed in 145 critically ill patients infected by S. aureus . Patients were r and omly assigned to one of two groups : patients for whom susceptibility testing was performed using a rapid same day multiplex PCR assay for detection of the staphylococcal mecA ( mean delay of response : 6 h ) and those for whom testing was accomplished using traditional overnight techniques ( 21 h ) . RESULTS The results of this study showed no significant difference between the two groups in terms of age , Simplified Acute Physiologic Score , severity of infection , severity of underlying disease and clinical outcome ( control vs. PCR ) : unfavourable outcome of infection , 12.32 vs. 12.5 % ; 95 % CI for the difference = -11.49 to 11.09 ( P = 0.975 ) ; unfavourable general outcome , 16.43 vs. 20.83 % ; 95 % CI for the difference = -17.35 to 8.50 ( P = 0.497 ) . For the oxacillin-susceptible S. aureus bactaeraemia , results were : unfavourable outcome of infection = 13.04 vs. 11.11 % ; 95 % CI for the difference = -11.38 to 16.18 ( P = 0.767 ) ; unfavourable general outcome = 13.04 vs. 20.37 % ; 95 % CI for the difference = -22.12 to 8.07 ( P = 0.331 ) . CONCLUSION This study seemed to demonstrate that rapid oxacillin susceptibility testing using a PCR assay did not have a major impact on the care and outcome of patients with S. aureus bactaeremia Effective empirical treatment is of paramount importance to improve the outcome of patients with Staphylococcus aureus bacteraemia . We aim ed to evaluate a PCR-based rapid diagnosis of methicillin resistance ( GeneXpert MRSA ) after early detection of S. aureus bacteraemia using matrix-assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF MS ) . Patients with a first episode of S. aureus bacteraemia identified using MALDI-TOF MS were r and omized in a prospect i ve interventional open study between October 2010 and August 2012 . In the control group , antibiotic susceptibility testing was performed after MALDI-TOF MS identification on blood culture pellets . In the intervention group , a GeneXpert MRSA was performed after S. aureus identification . The primary outcome was the performance of GeneXpert MRSA directly on blood cultures . We then assessed the impact of early diagnosis of methicillin resistance on the empirical treatment . In all , 197 episodes of S. aureus bacteraemia were included in the study , of which 106 were included in the intervention group .  Median time from MALDI-TOF MS identification to GeneXpert MRSA result was 97 min ( range 25 - 250 ) . Detection of methicillin resistance using GeneXpert MRSA had a sensitivity of 99 % and a specificity of 100 % . There was less unnecessary coverage of MRSA in the intervention group ( 17.1 % versus 29.2 % , p 0.09 ) . GeneXpert MRSA was highly reliable in diagnosing methicillin resistance when performed directly on positive blood cultures . This could help to avoid unnecessary prescriptions of anti-MRSA agents and promote the introduction of earlier adequate coverage in unsuspected cases During the past decade , a variety of instrument-assisted bacterial identification and antimicrobial susceptibility test systems have been developed which permit provision of test results in a matter of hours rather than days , as has been the case with traditional overnight procedures . These newer rapid techniques are much more expensive than older methods . It has been presumed but not proven that the clinical benefits of rapid testing to patients with infection offset the added cost . The intent of this study was to objective ly define the clinical impact of rapid bacterial identification and antimicrobial susceptibility testing . A 1-year study was performed in which infected , hospitalized patients in a tertiary-care , teaching , medical center were r and omly assigned to one of two groups : patients for whom identification and susceptibility testing was performed by using a semi-automated , rapid , same-day procedure and those for whom testing was accomplished by using traditional overnight techniques . The two groups were compared with respect to numerous demographic descriptors , and then patients were monitored prospect ively through the end of their hospitalization with the aim of determining whether there existed objective ly defineable differences in management and outcome between the two groups . The mean lengths of time to provision of susceptibility and identification test results in the rapid test group were 11.3 and 9.6 h , respectively . In the overnight test group , these values were 19.6 and 25.9 h , respectively ( P < 0.0005 ) . There were 273 evaluable patients in the first group and 300 in the second group . Other than the length of time required to provide susceptibility and identification test results , no significant differences were noted between the two groups with respect to > 100 demographic descriptors . With regard to measures of outcome , the mean lengths of hospitalization were also the same in both groups . Mortality rates were however , lower in the rapid test group ( i.e. , 8.8 % versus 15.3 % ) . Similarly , statistically significantly fewer laboratory studies , imaging procedures , days of intubation , and days in an intensive or intermediate-care area were observed with patients in the rapid test group . Rapid testing was also associated with significantly shortened lengths of elapsed time prior to alterations in antimicrobial therapy . Lastly , patient costs for hospitalization were significantly lower in the rapid test group . The results of this study indicate the rapid same-day bacterial identification and susceptibility testing in the microbiology laboratory can have a major impact on the care and outcome of hospitalized patients with infection We analyzed data from a prospect i ve observational cohort study that included 108 adult intensive care units ( ICUs ) in 41 United States hospitals . Use of  vancomycin  ( defined daily doses per 1,000 patient-days ) , nosocomial infection rates , and proportion of all Staphylococcus aureus isolates resistant to methicillin ( MRSA rate ) were recorded from January 1996 through November 1997 . The median rate of vancomycin use was lowest in coronary care ICUs and highest in general surgical ICUs . Prior approval before use of vancomycin was required in only 26 ( 24 % ) of the 108 ICUs . In a multivariate linear regression model , rates of MRSA , central line-associated bloodstream infection , and the type of ICU were independent predictors of vancomycin use . None of the vancomycin control practice s was associated with lower rates of vancomycin use ; however , it is important to recognize that this data base was not design ed to measure rates of inappropriate use .  Vancomycin use is heavily determined by rates of endemic MRSA and central line-associated bloodstream infection . Efforts to reduce these rates through infection control activities should be included in hospitals ' efforts to reduce vancomycin use Matrix assisted laser desorption ionization time-of-flight mass spectrometry ( MALDI-TOF MS ) allows the identification of microorganisms directly from positive blood culture broths . Use of the MALDI-TOF MS for rapid identification of microorganisms from blood culture broths can reduce the turnaround time to identification and may lead to earlier appropriate treatment of bacteremia . During February and April 2010 , direct MALDI-TOF MS was routinely performed on all positive blood cultures . During December 2009 and March 2010 no direct MALDI-TOF MS was used . Information on antibiotic therapy was collected from the hospital and intensive care units ' information systems from all positive blood cultures during the study period . In total , 253 episodes of bacteremia were included of which 89 during the intervention period and 164 during the control period . Direct performance of MALDI-TOF MS on positive blood culture broths reduced the time till species identification by 28.8-h and was associated with an 11.3 % increase in the proportion of patients receiving appropriate antibiotic treatment 24 hours after blood culture positivity ( 64.0 % in the control period versus 75.3 % in the intervention period ( p0.01 ) ) . Routine implementation of this technique increased the proportion of patients on adequate antimicrobial treatment within 24 hours CONTEXT Controversy and uncertainty ensue when the results of clinical research on the effectiveness of interventions are subsequently contradicted . Controversies are most prominent when high-impact research is involved . OBJECTIVES To underst and how frequently highly cited studies are contradicted or find effects that are stronger than in other similar studies and to discern whether specific characteristics are associated with such refutation over time . DESIGN All original clinical research studies published in 3 major general clinical journals or high-impact-factor specialty journals in 1990 - 2003 and cited more than 1000 times in the literature were examined . MAIN OUTCOME MEASURE The results of highly cited articles were compared against subsequent studies of comparable or larger sample size and similar or better controlled design s. The same analysis was also performed comparatively for matched studies that were not so highly cited . RESULTS Of 49 highly cited original clinical research studies , 45 cl aim ed that the intervention was effective .  Of these , 7 ( 16 % ) were contradicted by subsequent studies , 7 others ( 16 % ) had found effects that were stronger than those of subsequent studies , 20 ( 44 % ) were replicated , and 11 ( 24 % ) 
    Output:
    
MAIN RESULTS Rapid molecular testing with direct communication significantly improves timeliness compared to st and ard testing .
Rapid phenotypic techniques with direct communication likely improve the timeliness of targeted therapy .
Studies show a significant and homogeneous reduction in mortality associated with rapid molecular testing combined with direct communication .
The overall strength of evidence is suggestive ; the data suggest that each of these three practice s has the potential to improve the time required to initiate targeted therapy and possibly improve other patient outcomes , such as mortality .
The meta- analysis results suggest that the implementation of any of the three practice s may be more effective at increasing timeliness to targeted therapy than routine microbiology techniques for identification of the microorganisms causing BSIs .
Based on the included studies , results for all three practice s appear applicable across multiple microorganisms , including methicillin-resistant Staphylococcus aureus ( MRSA ) , methicillin-sensitive S. aureus ( MSSA ) , C and ida species , and Enterococcus species