title: Intraoperative serum and tissue activity of cefazolin and cefoxitin. Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind comparison of two-day and six-day regimens. Risk of surgical site infection and efficacy of antibiotic prophylaxis: a cohort study of appendectomy patients in Thailand Risk factors for surgical-wound infection in general surgery: a prospective study. Multistate point-prevalence survey of health care-associated infections. Evaluating the optimal timing of surgical antimicrobial prophylaxis: study protocol for a randomized controlled trial Re-emphasis of priorities in surgical antibiotic prophylaxis. Timing of vancomycin prophylaxis for cardiac surgery patients and the risk of surgical site infections. Antibiotic prophylaxis and the risk of surgical site infections following total hip arthroplasty: timely administration is the most important factor. Antibiotic regimen and the timing of prophylaxis are important for reducing surgical site infection after elective abdominal colorectal surgery. Timing of Antimicrobial Prophylaxis and the Risk of Surgical Site Infections: Results From the Trial to Reduce Antimicrobial Prophylaxis Errors Antibiotic Pharmacodynamics in Surgical Prophylaxis: an Association between Intraoperative Antibiotic Concentrations and Efficacy The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection.
abstract: We determined the intraoperative serum and wound-muscle concentrations of cefazolin and cefoxitin in 40 patients who were undergoing cholecystectomies . The study employed an open-label design in which all of the patients r and omly received cefazolin sodium ( 20 mg/kg ) or cefoxitin sodium ( 30 mg/kg ) intravenously while the patient was in the ward ( " on call " ) or with the induction of anesthesia . Multiple blood and wound-muscle sample s were collected intraoperatively and assayed for their cephalosporin concentrations . Considerable differences in intraoperative serum and tissue concentrations between antibiotics were apparent ; there were usually higher levels of cefazolin . In all of the patients who received cefazolin sodium , the antimicrobial was detectable in wound tissue at wound closure , while it was detectable in 86 % and 38 % of patients who received cefoxitin sodium with anesthesia and on call , respectively . Because cefoxitin has a much shorter elimination half-life than cefazolin it seems prudent to administer the agent as close to the start of the operation as possible , and readminister the agent every two to three hours until the wound is closed . For cefazolin , on-call administration appears to be acceptable , with readministration not required for at least four hours A prospect i ve , double-blind study comparing a 6 day with a 2 day regimen of cephalothin prophylaxis was conducted among 200 patients undergoing prosthetic valve replacement . No cases of endocarditis occurred during the 2 month follow-up . Sternal wound infection developed in 2.8 per cent of the 6 day group and 2.1 per cent of the 2 day group . Pneumonia developed in 8.5 per cent of the 6 day and 5.3 per cent of the 2 day group ; most of the bacteria isolated were susceptible to cephalothin .  Urinary tract infection developed more frequently in the 2 day group ( 17.0 versus 8.5 per cent ) , particularly during the first 6 postoperative days . Three of 11 patients with no detectable cephalothin in their sera at the close of operation developed staphylococcal wound infections , compared with 2 of 175 patients whose sera contained cephalothin at the close of surgery ( p = 0.002 , Fisher 's exact test ) . A short course of prophylactic antibiotics is prudent , but there is no justification for prolonging their administration Background No data currently exist about use of antibiotics to prevent surgical site infections ( SSI )  among patients undergoing appendectomy in Thail and . We therefore examined risk factors , use , and efficacy of prophylactic antibiotics for surgical site infection SSI among patients with uncomplicated open appendectomy . Methods From July 1 , 2003 to June 30 , 2004 we conducted a prospect i ve cohort study in eight hospitals in Thail and . We used the National Nosocomial Infection Surveillance ( NNIS ) system criteria to identify SSI associated with appendectomy . We used logistic regression analysis to obtain relative risk estimates for predictors of SSI . Results Among 2139 appendectomy patients , we identified 26 SSIs , yielding a SSI rate of 1.2 infections/100 operations . Ninety-two percent of all patients ( 95 % CI , 91.0–93.3 ) received antibiotic prophylaxis . Metronidazole and gentamicin were the two most common antibiotic agents , with a combined single dose administered in 39 % of cases . In 54 % of cases , antibiotic prophylaxis was administered for one day . We found that a prolonged duration of operation was significantly associated with an increased SSI risk . Antibiotic prophylaxis was significantly associated with a decreased risk of SSI regardless of whether the antibiotic was administered preoperatively or intraoperatively . Compared with no antibiotic prophylaxis , SSI relative risks for combined single-dose of metronidazole and gentamicin , one-day prophylaxis , and multiple-day antibiotic prophylaxis were 0.28 ( 0.09–0.90 ) , 0.30 ( 0.11–0.88 ) and 0.32 ( 0.10–0.98 ) , respectively . ConclusionS ingle-dose combination of metronidazole and gentamicin seems sufficient to reduce SSIs in uncomplicated appendicitis patients despite whether the antibiotic was administered preoperatively or intraoperatively OBJECTIVE To quantify surgical-infection rate , to assess adherence with the antibiotic prophylaxis protocol , and to identify independent factors associated with surgical-wound infection ( SWI ) . METHODS We carried out a prospect i ve study of a cohort of 2,237 general surgery patients with postsurgery stays of more than 48 hours .  Odds ratios ( OR ) were estimated using unconditional multiple logistic regression . SETTING A 1,300-bed , university-affiliated , tertiary-care hospital in Madrid , Spain . RESULTS 254 patients developed SWI .  The rate of adherence to the antibiotic prophylaxis protocol  was 63.5 % . Eight factors were independently associated with risk of SWI : age ( OR = 1.2 for every 10 years of age ) ; wound classification ( clean-contaminated , OR = 6.4 ; contaminated , OR = 3.7 ; dirty or infected , OR = 9.3 ) ; antimicrobial prophylaxis ( OR = 0.5 ) ; stay prior to surgery ( OR = 1.1 for every 3 days ) ; duration of operation ( OR = 1.5 for every 60 minutes ) ; malignant neoplasm ( OR = 1.7 ) ; emergency procedure ( OR = 1.99 ) ; intensive-care unit stay prior to surgery ( OR = 2.6 ) ; and antimicrobial prophylaxis administered 2 or more hours before operation ( OR = 5.3 ) . CONCLUSION In general , antimicrobial prophylaxis protects against SWI ( OR = 0.5 ) ; however , administration 2 hours or more before the operation increases the risk of SWI by a factor of 5.3 . Therefore , measures should be taken to ensure the correct timing of antimicrobial prophylaxis BACKGROUND Currently , no single U.S. surveillance system can provide estimates of the burden of all types of health care-associated infections across acute care patient population s. We conducted a prevalence survey in 10 geographically diverse states to determine the prevalence of health care-associated infections in acute care hospitals and generate up date d estimates of the national burden of such infections . METHODS We defined health care-associated infections with the use of National Healthcare Safety Network criteria .  One-day surveys of r and omly selected in patients were performed in participating hospitals . Hospital personnel collected demographic and limited clinical data . Trained data collectors review ed medical records retrospectively to identify health care-associated infections active at the time of the survey . Survey data and 2010 Nationwide Inpatient Sample data , stratified according to patient age and length of hospital stay , were used to estimate the total numbers of health care-associated infections and of in patients with such infections in U.S. acute care hospitals in 2011 . RESULTS Surveys were conducted in 183 hospitals . Of 11,282 patients , 452 had 1 or more health care-associated infections  ( 4.0 % ; 95 % confidence interval , 3.7 to 4.4 ) . Of 504 such infections , the most common types were pneumonia ( 21.8 % ) , surgical-site infections ( 21.8 % ) , and gastrointestinal infections ( 17.1 % ) . Clostridium difficile was the most commonly reported pathogen ( causing 12.1 % of health care-associated infections ) . Device-associated infections ( i.e. , central -catheter-associated bloodstream infection , catheter-associated urinary tract infection , and ventilator-associated pneumonia ) , which have traditionally been the focus of programs to prevent health care-associated infections , accounted for 25.6 % of such infections . We estimated that there were 648,000 patients with 721,800 health care-associated infections in U.S. acute care hospitals in 2011 . CONCLUSIONS Results of this multistate prevalence survey of health care-associated infections indicate that public health surveillance and prevention activities should continue to address C. difficile infections . As device- and procedure-associated infections decrease , consideration should be given to exp and ing surveillance and prevention activities to include other health care-associated infections Background Surgical site infections are the most common hospital-acquired infections among surgical patients . The administration of surgical antimicrobial prophylaxis reduces the risk of surgical site infections . The optimal timing of this procedure is still a matter of debate . While most studies suggest that it should be given as close to the incision time as possible , others conclude that this may be too late for optimal prevention of surgical site infections . A large observational study suggests that surgical antimicrobial prophylaxis should be administered 74 to 30 minutes before surgery . The aim of this article is to report the design and protocol of a r and omized controlled trial investigating the optimal timing of surgical antimicrobial prophylaxis . Methods / Design In this bi-center r and omized controlled trial conducted at two tertiary referral centers in Switzerl and , we plan to include 5,000 patients undergoing general , oncologic , vascular and orthopedic trauma procedures . Patients are r and omized in a 1:1 ratio into two groups : one receiving surgical antimicrobial prophylaxis in the anesthesia room ( 75 to 30 minutes before incision ) and the other receiving surgical antimicrobial prophylaxis in the operating room ( less than 30 minutes before incision ) . We expect a significantly lower rate of surgical site infections with surgical antimicrobial prophylaxis administered more than 30 minutes before the scheduled incision . The primary outcome is the occurrence of surgical site infections during a 30-day follow-up period ( one year with an implant in place ) . When assuming a 5 % surgical site infection risk with administration of surgical antimicrobial prophylaxis in the operating room , the planned sample size has an 80 % power to detect a relative risk reduction for surgical site infections of 33 % when administering surgical antimicrobial prophylaxis in the anesthesia room ( with a two-sided type I error of 5 % ) . We expect the study to be completed within three years . Discussion The results of this r and omized controlled trial will have an important impact on current international guidelines for infection control strategies in the hospital . Moreover , the results of this r and omized controlled trial are of significant interest for patient safety and healthcare economics . Trial registration This trial is registered on Clinical Trials.gov under the identifier NCT01790529 The results of two prospect i ve , r and omized trials , comparing single dose piperacillin with multidose cefoxitin prophylaxis in elective surgical procedures of the gastrointestinal tract were combined to examine some basic aspects of clinical ly , applied antibiotic prophylaxis . As there was no difference in the efficacy of prophylaxis between the groups , data from both centers and both drug groups were combined for analysis . Patients whose ages were greater than 40 years , the presence of cancer and the administration of an antibiotic for longer than 60 minutes preoperatively were associated with a higher rate of infectious complications . Duration of operation was also related to subsequent infection , ranging from 6 per cent in procedures lasting less than two hours to 27 per cent in operations lasting more than four hours . There was a greater failure of prophylaxis in patients undergoing rectal procedures , with a 29 per cent rate of infectious complications compared with 14 per cent in patients undergoing operations upon the colon . This difference was present even when duration of operation was taken into account BACKGROUND Increased incidence of methicillin-resistant Staphylococcus species has required some hospitals to choose vancomycin for surgical prophylaxis . Guidelines for appropriate timing of vancomycin prophylaxis state that the infusion should begin within 120 min before the first surgical incision . However , no studies have investigated the proper timing of vancomycin prophylaxis in relationship to surgical site infections ( SSI ) . The objective of the present study was to assess the effect of vancomycin prophylaxis timing in relation to the first surgical incision on the incidence of SSI . METHODS We prospect ively monitored vancomycin prophylaxis timing and incidence of SSI in 2048 patients undergoing coronary bypass graft or valve replacement surgery . The timing of vancomycin was categorized into five groups based on the relation between the start of the infusion and the surgical cut time . Study hypotheses were tested using logistic analysis and further vali date d using a Heckman two-stage model . RESULTS The incidence of SSI were lowest in the 176 patients given vancomycin between 16 and 60 min before the surgical incision ( 3.4 % ) compared with 15 patients given vancomycin between 0 and 15 min [ 26.7 % ; relative risk ( RR ) : 7.8 ; 95 % CI : 2.5 - 24.7 ] , 888 patients given vancomycin between 61 and 120 min ( 7.7 % ; RR : 2.2 ; 95 % CI : 0.99 - 5.09 ) , 700 patients given vancomycin between 121 and 180 min ( 6.9 % ; RR : 2.0 ; 95 % CI : 0.87 - 4.62 ) or 269 patients given vancomycin > 180 min ( 7.8 % ; RR : 2.3 ; 95 % CI : 0.94 - 5.56 ) ( P = 0.0119 by chi(2 ) analysis ) . Stepwise logistic regression analysis and a Heckman two-stage model confirmed that vancomycin administration between 16 and 60 min before the first surgical incision was associated with the lowest incidence of SSI . CONCLUSIONS Vancomycin administration within 16 - 60 min before the first surgical incision reduced the risk of SSI in cardiac surgery patients BACKGROUND Surgical site infections ( SSIs ) following total hip arthroplasty can lead to prolonged hospitalization , increased morbidity and mortality , and high costs . This article analyzes the effect of various parameters of surgical antibiotic prophylaxis on the risk of SSI following total hip arthroplasty . METHODS Data about SSI and potential prophylaxis- , patient- , and procedure-related risk factors were prospect ively collected for 1922 patients who underwent elective total hip arthroplasty in 11 hospitals that participated in the Dutch intervention project , Surgical Prophylaxis and Surveillance .  Multivariate logistic regression analysis was performed to correct for r and om variation among hospitals . RESULTS SSIs ( superficial and deep ) occurred in 50 patients ( 2.6 % ) . The highest odds ratios for SSI were found in patients who received prophylaxis after incision ( 2.8 , 95 % confidence interval [ CI ] , 0.9 - 8.6 ; P=.07 ) , had an American Society of Anesthesiology score that was > 2 ( 2.8 , 95 % CI , 0.8 - 9.2 ; P=.09 ) , and experienced a duration of surgery that was > 75th percentile ( 2.5 ; 95 % CI , 1.1 - 5.8 ; P=.04 ) . Prolonged prophylaxis after the end of surgery and the use of antibiotic-impregnated cement did not contribute to fewer SSIs in this study . CONCLUSIONS This study suggests that intervention programs in search of amendable factors to prevent SSI should focus on timely administration of antibiotic prophylaxis BACKGROUND Surgical site infections ( SSIs ) cause morbidity after elective colorectal surgery , and antibiotic prophylaxis can decrease SSIs . The aim of this study was to determine compliance with an antibiotic administration protocol , including regimen , initial dose timing , and re-dosing , and determine the risk of SSI associated with each . We hypothesized that appropriate antibiotic administration reduces the risk of SSI . METHODS Retrospective review from a prospect i ve data base of a r and om sample of patients undergoing elective abdominal colorectal procedures with anastomosis .  Antibiotic regimens , initial dose timing ( IDT ) , and re-dosing were evaluated . Appropriate regimens covered gram-positive cocci , gram-negative bacilli , and anaerobes . The IDT was considered proper if completed within 30 min prior to incision ; re-dosing parameters were determined pharmacokinetically for each agent . The main outcome was SSI . Sequential logistic models were generated : Model 1 assessed antibiotic administration factors , whereas Model 2 controlled for patient and clinical factors , including disease process , patient characteristics , intra-operative factors , and post-operative factors . RESULTS Six hundred five patients ( mean age 59.7 [ st and ard deviation 17.8 ] years , 42.8 % male ) were included . The most common diagnoses were cancer ( 38.8 % ) and inflammatory bowel disease ( 22.0 % ) . Seventy-six patients ( 12.6 % ) had superficial or deep incisional SSI , and 54 ( 8.9 % ) had organ/space SSI . Regimens included cefazolin + metronidazole for 219 patients ( 36.2 % ) , cefoxitin for 214 ( 35.4 % ) , and levofloxacin + metronidazole for 48 ( 7.9 % ) . One hundred fourteen patients ( 18.8 % ) received other/nonst and ard regimens , and ten had no documented antibiotic prophylaxis . Fifty-five patients ( 9.1 % ) received insufficient coverage , whereas 361 patients ( 59.7 % ) had proper IDT , and 401 regimens ( 66.3 % ) were re-dosed properly . In Model 1 , the use of other/nonst and ard regimens ( odds ratio [ OR ] 2.069 ; 95 % confidence interval [ CI ] 1.078 - 1.868 ) and early administration of the initial prophylaxis dose ( OR 1.725 ; 95 % CI 1.147 - 2.596 ) were associated with greater odds of SSI . After adding clinical factors in Model 2 , both of these factors remained significant ( OR 2.505 ; 95 % CI 1.066 - 5.886 and OR 1.733 ; 95 % CI 1.017 - 2.954 , respectively ) . CONCLUSIONS Appropriate antibiotic selection and timing of administration for prophylaxis are crucial to reduce the likelihood of SSI after elective colorectal surgery with intestinal anastomosis Objective : The objective of this study is to determine the optimal timing for surgical antimicrobial prophylaxis ( AMP ) . Summary Background Data : National AMP guidelines should be supported by evidence from large contemporary data sets . Methods : Twenty-nine hospitals prospect ively obtained information on AMP from 4472 r and omly selected cardiac , hip/knee arthroplasty , and hysterectomy cases .  Surgical site infections ( SSIs ) were ascertained through routine surveillance , using National Nosocomial Infections Surveillance system methodology . The association between the prophylaxis timing and the occurrence of SSI was assessed using conditional logistic regression ( conditioning on hospital ) . Results : One-hundred thirteen SSI were detected in 109 patients .  SSI risk increased incrementally as the interval of time between antibiotic infusion and the incision increased ( overall association between timing and infection risk P = 0.04 ) . When antibiotics requiring long infusion times ( vancomycin and fluoroquinolones ) were excluded , the infection risk following administration of antibiotic within 30 minutes prior to incision was 1.6 % compared with 2.4 % associated with administration of antibiotic between 31 to 60 minutes prior to surgery ( OR : 1.74 ; 95 % confidence interval , 0.98–3.04 ) . The infection risk increased as the time interval between preoperative antibiotic and incision increased or if the antibiotic was first infused after incision . Intraoperative redosing ( performed in only 21 % of long operations ) appeared to reduce SSI risk in operations lasting more than 4 hours ( OR of 3.08 with no redosing ; 95 % confidence interval 0.74–12.90 ) , but only when the preoperative dose was given correctly . Conclusions : These data from a large multicenter collaborative study confirm and extend previous observations and show a consistent relationship between the timing of AMP and SSI risk with a trend toward lower risk occurring when AMP with cephalosporins and other antibiotics with short infusion times were given within 30 minutes prior to incision ABSTRACT The objective of this study was to characterize the relationship between gentamicin concentrations during surgery and the development of wound infection following colorectal operations . Despite decades of research in surgical prophylaxis , the relationship between intraoperative antibiotic concentrations and postoperative infection and the concentrations required for effective prophylaxis have not been established . A pharmacodynamic analysis was conducted using data from a previous prospect i ve , r and omized , double-blind clinical study which compared two dosage regimens of gentamicin plus metronidazole for prophylaxis in connection with elective colorectal surgery . Univariate and multivariate analyses of risk factors for postoperative wound infection were conducted , and the relationship between intraoperative gentamicin concentrations and surgical outcome was characterized . The gentamicin concentration at the time of surgical closure was one of the strongest independent risk factors for infection ( P = 0.02 ) , along with the presence of diabetes mellitus ( P = 0.02 ) , stoma ( P = 0.04 ) , and advanced age ( P = 0.05 ) . Gentamicin concentrations at closure of less than 0.5 mg/liter were associated with an infection rate of 80 % ( representing 8 of 10 patients with concentrations below that level ) ( P = 0.003 ) . Receiver operating characteristic curve analysis identified a critical closure concentration of 1.6 mg/liter for effective surgical prophylaxis ( P = 0.002 ; sensitivity , 70.8 % ; specificity , 65.9 % ) . This study provides new and important information on antibiotic pharmacodynamics in surgical prophylaxis . It demonstrates the critical effect of the antibiotic concentration at closure on wound infection and suggests a significant association between the concentration and other well-established risk factors , like the timing of preoperative antibiotic administration and surgery duration BACKGROUND R and omized , controlled trials have shown that prophylactic antibiotics are effective in preventing surgical-wound infections . However , it is uncertain how the timing of antibiotic administration affects the risk of surgical-wound infection in actual clinical practice . METHODS We prospect ively monitored the timing of antibiotic prophylaxis and studied the occurrence of surgical-wound infections in 2847 patients undergoing elective clean or " clean-contaminated " surgical procedures at a large community hospital . The administration of antibiotics 2 to 24 hours before the surgical incision was defined as early ; that during the 2 hours before the incision , as preoperative ; that during the 3 hours after the incision , as perioperative ; and that more than 3 but less than 24 hours after the incision , as postoperative . RESULTS Of the 1708 patients who received the prophylactic antibiotics preoperatively , 10 ( 0.6 percent ) subsequently had surgical-wound infections . Of the 282 patients who received the antibiotics perioperatively , 4 ( 1.4 percent ) had such infections ( P = 0.12 ; relative risk as compared with the preoperatively treated group , 2.4 ; 95 percent confidence interval , 0.9 to 7.9 ) . Of 488 patients who received the antibiotics postoperatively , 16 ( 3.3 percent ) had wound infections ( P less than 0.0001 ; relative risk , 5.8 ; 95 percent confidence interval , 2.6 to 12.3 ) . Finally , of 369 patients who had antibiotics administered early , 14 ( 3.8 percent ) had wound infections ( P less than 0.0001 ; relative risk , 6.7 ; 95 percent confidence interval , 2.9 to 14.7 ) . Stepwise logistic-regression analysis confirmed that the administration of antibiotics in the preoperative period was associated with the lowest risk of surgical-wound infection . CONCLUSIONS We conclude that in surgical practice there is considerable variation in the timing of prophylactic administration of antibiotics and that administration in the two hours before surgery reduces the risk of wound infection
target: Administration of antibiotic prophylaxis more than 120 minutes before incision or after incision is associated a higher risk of surgical site infections than administration less than 120 minutes before incision .
background: Abstract The aim of the study was to assess the effect of timing of preoperative surgical antibiotic prophylaxis ( SAP ) on  surgical site infection ( SSI )  and compare the different timing intervals .
  The benefit of routine use of SAP prior to surgery has long been recognized .
  However , the optimal timing has not been defined .