title: Duration of preventive antibiotic administration for open extremity fractures. Comparison the Efficacy of Cefazolin plus Gentamicin with Cefazolin plus Ciprofloxacin in Management of Type –IIIA Open Fractures GRADE guidelines: 4. Rating the quality of evidence--study limitations (risk of bias). Prospective, randomized, double-blind study comparing single-agent antibiotic therapy, ciprofloxacin, to combination antibiotic therapy in open fracture wounds. GRADE guidelines: 5. Rating the quality of evidence--publication bias. Antibiotics in trauma and orthopedic surgery -- a primer of evidence-based recommendations. Epidemiology of Bacterial Infection During Management of Open Leg Fractures Prophylactic Antibiotics in Open Fractures: A Pilot Randomized Clinical Safety Study GRADE guidelines: 3. Rating the quality of evidence. Comparison of Antibiotic Beads and Intravenous Antibiotics in Open Fractures Fluid lavage of open wounds (FLOW): a multicenter, blinded, factorial pilot trial comparing alternative irrigating solutions and pressures in patients with open fractures. Antibiotic prophylaxis in open and closed fractures: a controlled clinical trial. Clindamycin versus cloxacillin in the treatment of 240 open fractures. A randomized prospective study. Severe Open Tibial Fractures: A Study Protocol Once daily, high dose versus divided, low dose gentamicin for open fractures. Risk of infection after open fracture of the arm or leg. Cephradine and flucloxacillin in the prophylaxis of infection in patients with open fractures. Treatment of open fractures: a prospective study. A Double‐Blind Clinical Trial of Prophylactic Cloxacillin in Open Fractures
abstract: The necessary duration of antibiotic administration after open fracture has not been established . In a double-blind prospect i ve trial we r and omized 248 patients with open fractures to receive one or five days of cefonicid sodium therapy or five days of cefam and ole nafate therapy as part of the initial treatment . Rates of fracture-associated infections in the three groups were ten ( 13 % ) of 79 , ten ( 12 % ) of 85 , and 11 ( 13 % ) of 84 , respectively . The 95 % confidence limit for the difference in infection rates between the one-day group and the combined five-day groups was 0 % to 8.3 % . The actual difference was 0.2 % . A brief course of antibiotic administration is not inferior to a prolonged course of antibiotics for prevention of postoperative fracture-site infections Background The optimal antibiotic regimen is still controversial in open fractures . The purpose of this study was to evaluate the efficacy of two different antibiotic regimens in management of type III-A open fractures . Methods From January 2001 to January 2008 , patients with type IIIA open fractures admitted in Shahid Beheshti Hospital Affiliated to Babol University of Medical Sciences were enrolled . Patients r and omly received cefazolin plus gentamicin ( group I ) or cefazolin plus ciprofloxacin ( group II ) . Both regimens were administered for 3 days . All patients were followed for 3 months . The efficacy of both regimens was compared . Results One hundred-forty eight and 153 patients were treated in group I and II , respectively . The mean age of the patients treated in group I was 36.96±14.4 and in group II was 36.93±13.51 years .  The rate of deep infection in group I was 5.4 % and in group II was 6.5 % . The efficacy of regimen I was 94.6 % and regimen II was 93.5 % . Conclusion Cefazolin plus gentamicin , or cefazolin plus ciprofloxacin both can be successfully used for prevention of infection in type IIIA open fractures In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if most of the relevant evidence comes from studies that suffer from a high risk of bias . Well-established limitations of r and omized trials include failure to conceal allocation , failure to blind , loss to follow-up , and failure to appropriately consider the intention-to-treat principle . More recently recognized limitations include stopping early for apparent benefit and selective reporting of outcomes according to the results . Key limitations of observational studies include use of inappropriate controls and failure to adequately adjust for prognostic imbalance . Risk of bias may vary across outcomes ( e.g. , loss to follow-up may be far less for all-cause mortality than for quality of life ) , a consideration that many systematic review s ignore . In deciding whether to rate down for risk of bias -- whether for r and omized trials or observational studies -- authors should not take an approach that averages across studies . Rather , for any individual outcome , when there are some studies with a high risk , and some with a low risk of bias , they should consider including only the studies with a lower risk of bias OBJECTIVE The purpose of this study was to compare the efficacy of a single agent , ciprofloxacin , with that of combination antibiotic therapy consisting of cefam and ole and gentamicin in all types of open fracture wounds . STUDY DESIGN A prospect i ve double-blind r and omized clinical trial . SETTING A Level 1 trauma center . PATIENTS One hundred ninety-five consecutive patients with 203 open fractures were enrolled over a twenty-month period . Twenty-nine fractures from low-velocity gunshot wounds were excluded , and three other patients were excluded because of protocol violations . Our final number of patients were 163 , with 171 open fractures . MAIN OUTCOME MEASUREMENT The infection rates for Type I and Type II open fractures for both antibiotic groups were calculated . The infection rate of Type III open fractures for both antibiotic groups was also calculated . Chi-square analysis with Yates correction was used to assess statistical significance of two treatment groups . RESULTS The infection rate for Types I and II open fractures in the ciprofloxacin group was 5.8 percent and 6 percent for the cefam and ole/gentamicin group ( p = 1.000 ) . The infection rate for Type III open fractures for the ciprofloxacin group was 31 percent ( 8 of 26 ) versus 7.7 percent ( 2 of 26 ) for the cefam and ole/gentamicin group ( p = 0.079 ) . There were no statistically significant differences in infection rate between the group treated with ciprofloxacin and that treated with cefam and ole/gentamicin for Types I and II open fracture wounds . However , there appeared to be a high failure rate for the ciprofloxacin Type III open fracture group , with patients being 5.33 times more likely to become infected than those in the combination therapy group . Although this difference was not statistically significant , possibly because of the small sample size , there was a definite trend toward statistical significance . CONCLUSION Single-agent antibiotic therapy with ciprofloxacin is effective in treatment of Type I and Type II open fracture wounds . However , on the basis of our results , we can not recommend ciprofloxacin alone for Type III wounds . Possibly one can use fluoroquinolones in combination therapy , specifically as an alternate to an aminoglycoside In the GRADE approach , r and omized trials start as high- quality evidence and observational studies as low- quality evidence , but both can be rated down if a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted Systematic review s and meta-analyses published in recent years have allowed drafting of evidence -based guidelines for antibiotic prophylaxis in orthopedic and trauma surgery . It is important to recognize the limitations of the recommendations derived from the available body of evidence . Since some of the most relevant r and omized controlled clinical trials were performed more than 20 years ago , it is sometimes difficult to apply the data to today 's clinical practice . In establishing consensus guidelines , it could prove difficult to identify areas for improvement through further research and better compliance . Although recommendations for optimized treatment of orthopedic implant infections are not currently based on first-class evidence , there are very promising new concepts emerging in this field , and we are awaiting more data and decisive conclusions from larger clinical trials Abstract In a r and omised double-blind trial conducted between 1990 and 1994 , 616 patients from 43 centres , pefloxacin ( group P , 316 patients ) and a cefazolin-oxacillin combination ( group C , 300 patients ) were compared in the prophylaxis of bone infection after grade 1 and 2 open leg fractures . Sample s were obtained at emergency , before and during surgery , and from drain aspirates . Antimicrobial susceptibility , slime production and adherence properties of the bacteria were tested . Cultures at emergency and before surgery showed similar distributions of gram-positive and gram-negative bacteria in both groups , while wound closure and infecting isolates showed prevailing gram-positive bacteria in group P and gram-negative bacteria in group C. Positive cultures at each stage were correlated with the occurrence of infection but were not predictive of the infecting species , which were nosocomial bacteria in most cases . Positive cultures at wound closure warn of a higher infection risk . Twenty-one of 316 ( 6.6 % ) patients in group P and 24 of 300 ( 8 % ) in group C were considered infected within 3 months . The difference is not significant ( chi-square test = 0.42;P=0.51 ) . Infecting strains were isolated from 38 patients ( group P , 18 ; group C , 20 ) . Infecting species , although not predictable , appear to be those escaping the spectrum of the prescribed antimicrobial prophylaxis Objective : To develop preliminary data on Staphylococcus aureus colonization and surgical site infections ( SSIs ) in patients with open fractures who received st and ard antibiotic prophylaxis  compared with a regimen including targeted methicillin-resistant Staphylococcus aureus ( MRSA ) coverage . Design : R and omized prospect i ve clinical trial . Patients : Adult patients who presented to the emergency department with an open fracture between April 2009 and July 2011 . Interventions : One hundred thirty patients were r and omized to receive prophylaxis with either cefazolin alone ( control arm ) or vancomycin and cefazolin ( experimental arm ) from presentation to the emergency department until 24 hours after the surgical intervention . Screening for S. aureus carriage was performed with nares swabs and predebridement and postdebridement open fracture wound swabs . Patients underwent prospect i ve assessment for the development of SSI for no less than 30 days and up to 12 months . Results : Nasal colonization of methicillin-sensitive S. aureus and MRSA among the sample was 20 % and 3 % , respectively . No significant difference in the rates of SSI was observed between the study arms ( 15 % vs 19 % , respectively , P = 0.62 ) . Staphylococcus aureus caused 55 % of the deep incisional/organ space SSI , with 18 % attributed to MRSA . A significantly higher rate of MRSA SSIs was observed among MRSA carriers compared with noncarriers ( 33 % vs 1 % , respectively , P = 0.003 ) . Conclusions : Staphylococcus aureus nasal colonization in trauma patients with open fractures is similar to that of the general community . In this pilot study , the addition of vancomycin to st and ard antibiotic prophylaxis was found safe , but its efficacy should be evaluated in a larger multiinstitutional trial . Level of Evidence : Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence This study compared the efficacy of antibiotic impregnated beads with conventional intravenous antibiotics in the treatment of open fractures . A r and omized prospect i ve study was design ed and conducted during a 29-month period . Sixty-seven patients with 75 open fractures were treated similarly , with the exception of the method of antibiotic administration , and were followed up for at least 1 year after injury . Infection occurred in two of 24 ( 8.3 % ) fractures treated with antibiotic beads alone and in two of 38 ( 5.3 % ) fractures treated with conventional intravenous antibiotics . In an unanticipated nonr and omized third cohort group , patients received antibiotic beads and intravenous antibiotics administered for nonorthopaedic reasons or limb threatening injury , or both . Two of 13 ( 15.4 % ) fractures in this high risk group became infected . Infection ultimately resolved in all fractures treated with antibiotic beads alone or antibiotic beads in conjunction with conventional intravenous antibiotics . This study was unable to achieve statistical significance ; however , the data suggest antibiotic beads may be useful in preventing infection in open fractures . Thus , a larger multicenter r and omized prospect i ve study of isolated open fractures , eliminating other variables , is justified BACKGROUND Open fractures are an important source of morbidity and are associated with delayed union , nonunion , and infection . Preventing infection through meticulous irrigation and debridement is an important goal in management , and different lavage fluids and irrigation techniques ( e.g. , high- or low-pressure lavage ) have been described for this purpose . However , there are a limited number of r and omized trials comparing irrigating solutions or irrigating technique . We compared the use of castile soap versus normal saline and high- versus low-pressure pulsatile lavage on the rates of reoperations and complications in patients with open fracture wounds . METHODS We conducted a multicenter , blinded , r and omized 2 × 2 factorial pilot trial of 111 patients in whom an open fracture wound was treated with either castile soap solution or normal saline and either high- or low-pressure pulsatile lavage . The primary composite outcome of reoperation , measured at 12 months after initial operative procedure , included infection , wound healing problems , and nonunion . Planned reoperations were not included . Secondary outcomes included all infection , all wound healing problems , and nonunion as well as functional outcomes scores ( EuroQol-5 dimensions and short form-12 ) . RESULTS Eighty-nine patients completed the 1-year follow-up . Among all patients , 13 ( 23 % ) in the castile soap group and 13 ( 24 % ) in the saline group had a primary outcome event ( hazard ratio , 0.91 , 95 % confidence interval : 0.42 - 2.00 , p = 0.52 ) . Sixteen patients ( 28 % ) in the high-pressure group and 10 patients ( 19 % ) in the low-pressure group had a primary outcome event ( hazard ratio 0.55 , 95 % confidence interval : 0.24 - 1.27 , p = 0.17 ) . Functional outcome scores showed no significant differences at any time point between groups . CONCLUSION The fluid lavage of open wounds pilot r and omized controlled trial demonstrated the possibility that the use of low pressure may decrease the reoperation rate for infection , wound healing problems , or nonunion . We have demonstrated the desirability and feasibility of a definitive trial examining the effects of alternative irrigation approaches The value of prophylactic antibiotics in fracture surgery was studied in a series of 90 patients with open fractures of various bones and 180 patients with closed malleolar fractures treated by open surgery .  Dicloxacillin and benzyl penicillin were compared to saline ( placebo ) . The soft tissue lesions of the open fractures were divided into Grade I wounds and Grade II & III wounds . Of the patients with Grade I wounds , 17 received dicloxacillin , 21 benzyl penicillin and 17 saline . No major infections occurred . Twelve patients with Grade II & III wounds were treated with dicloxacillin , 10 with benzyl penicillin and 13 with saline . In the saline group , 2 patients developed a deep infection .  Fifty-eight patients with closed malleolar fractures received dicloxacillin , 59 benzyl penicillin and 63 saline . Two infections developed in the placebo group . A statistically significant difference was found between the number of infections in the antibiotic groups and the number in the placebo group . Superficial thromboplebitis following the antibiotic infusion occurred in 16 per cent of the dicloxacillin treated patients and in 1 per cent of those treated with benzyl penicillin or placebo BACKGROUND AND AIMS Systemic administration of antibiotics is recommended and has proved to lower infection rates in open fractures . However , no antibiotic has proved to be superior to any other . MATERIAL AND METHODS In a prospect i ve study 227 patients with 240 open fractures were r and omized to receive either clindamycin or cloxacillin for infection prevention . RESULTS The overall infection rate was 15 % . Infection occurred in 9.3 % of the clindamycin treated and in 20 % of the cloxacillin treated fractures ( p < 0.05 ) . In the Gustillo Type I and II open fractures all the pathogens causing infection were gram-positive , while in the Type III open fractures 21 pathogens ( 57 % ) were gram-positive and 16 ( 43 % ) gram-negative . In the clindamycin treated fractures the infection rates in Type I and II open fractures were 3.3 and 1.8 % , respectively , while in the cloxacillin group they were 20 and 3.8 % , respectively . Both clindamycin and cloxacillin showed low effectiveness in the treatment of Type III open fractures , the highest infection rates being 75 and 67 % , respectively ( Type III B ) . CONCLUSIONS Clindamycin provides good antimicrobic coverage against the most common pathogens causing Type I and II open fracture infections . In the treatment of Type III open fractures additional administration of an antibiotic with good gram-negative coverage is recommended A prospect i ve r and omized study of severe open tibial fractures ( Type II and III ) was performed . Individual fractures were r and omized to treatment groups according to initial antibiotic therapy : One consisted of a first-generation cephalosporin , and the other consisted of a third-generation cephalosporin . Initial antibiotic therapy was given in all patients for 48 h and then specific antibiotic treatment was used as indicated by culture . The purpose of this study was to determine whether or not additional gram-negative coverage had an effect on the overall infection rate or the type of infection in severe open tibial fractures . Additional factors , such as the timing of bone grafts and soft tissue coverage , were evaluated in this study as well . Although there was no statistical difference in the rate of infection with the use of a first-versus a third-generation cephalosporin , there was a trend toward a decreased infection rate as well as toward less morbid infections with the use of a third-generation cephalosporin . The study also confirms that early bone graft should not be performed prior to 6 weeks post injury or after successful soft tissue coverage has been achieved . On the other h and , soft tissue coverage procedures should be performed at the earliest possible date to decrease the overall infection rate A prospect i ve , r and omized study was performed on 75 Gustilo Grade s II and III open fractures to determine the efficacy of once daily , high dose aminoglycoside therapy , compared with more conventional dosing , in reducing the infection rate when used in conjunction with an aggressive operative treatment protocol . All patients enrolled in the study were treated with immediate irrigation , debridement , operative stabilization of the fracture , and 1 g of cefazolin every 8 hours . At the time of admission patients were r and omized to two groups . Patients in Group I received gentamicin 5 mg/kg divided into twice daily doses , and patients in Group II received gentamicin 6 mg/kg given once daily . All patients were monitored for renal toxicity and observed for radiographic and clinical signs of infection until fracture union . The results of the study revealed no statistically significant difference between once daily , high dose versus divided , low dose gentamicin in infection rates . Thus , daily dosing of gentamicin was found to be safe , effective , and cost efficient in the treatment of open fractures when combined with a cephalosporin and aggressive operative debridement and stabilization Two hundred forty consecutive patients admitted for operative treatment of an open fracture of the arm or leg were followed up prospect ively for the development of fracture infection . The independent risk of fracture infection was increased in patients with grade IIIB or IIIC fractures , internal or external fixation , lower-leg fracture , any blood transfusion , or injuries result ing from motorcycle accidents or motor vehicle-pedestrian accidents . By stepwise multivariate logistic regression , the most significant risk factors were the grade of the fracture , internal or external fixation , and fractures of the lower leg . These risk factors all represent local wound characteristics , and we conclude that the most important actions by the surgeon to prevent infection involve local wound care . There was no relation between the timing of antibiotic administration or duration of antibiotic therapy and infection risk A comparison of prophylactic antibiotic cover of cephradine or flucloxacillin in sixty patients with open fractures is reported . There were more infections in the flucloxacillin than in the cephradine group and gastrointestinal side-effects were more common . The overall incidence of infection in the whole group , two out of 60 or 3.3 % , was acceptably low A double-blind prospect i ve study was done to assess the benefit of delaying closure of the wounds associated with open fractures . An additional double-blind study compared the effectiveness of clindamycin versus cefazolin for prophylactic antibiotic coverage . Quantitative cultures of the wounds were accomplished at the time of debridement and again at the time of closure if the wound was not closed initially . Almost half of the wounds were contaminated ( 46 % ) at the time of debridement , although the incidence of wound infection was low ( 6.5 % ) . Gram-negative organisms resistant to the prophylactic antibiotic were recovered initially only eight times , but four of these ( 50 % ) became infected . The contaminating organisms in each case were present in high concentration ( greater than 10(5 ) CFU/gm of tissue ) at initial culture . The time of wound closure , cefazolin versus clindamycin , and internal fixation of the fracture were not followed by significant differences in the development of clinical infection in this series In 100 patients with first- , second- , and third-degree open fractures , a r and omized , double-blind study was carried out to compare prophylactic cloxacillin and placebo . Prophylaxis was started preoperatively and continued for 10 days . The st and ard fracture treatment consisted of operative stabilization , mostly by means of plates or external fixators . In the cloxacillin group two infections were observed as compared to 12 in the control group . This difference was significant
target: Results of r and omized controlled trials performed to date provide evidence that antibiotic prophylaxis reduces subsequent infection and that courses as short as one day are as effective as courses of three to five days , although the evidence warrants only low to moderate confidence .
background: BACKGROUND The purpose of the present study was to perform a systematic review and meta- analysis of the use of alternative antibiotic regimens-including ( A ) antibiotic prophylaxis versus no prophylaxis , ( B ) longer versus shorter duration of antibiotic prophylaxis , and ( C ) alternative drugs-for  patients with open fracture of the extremities .