title: Timing of prophylactic antibiotic administration in the uninfected laboring gravida: a randomized clinical trial. Prophylactic Cesarean Section Antibiotics: Maternal and Neonatal Morbidity Before or After Cord Clamping Microbiology and Treatment of Late Postpartum Endometritis Antibiotic for cesarean section: the case for 'true' prophylaxis. Decreasing Incidence of Postcesarean Endometritis With Extended-Spectrum Antibiotic Prophylaxis Randomized Clinical Trial of Extended Spectrum Antibiotic Prophylaxis With Coverage for Ureaplasma urealyticum to Reduce Post–Cesarean Delivery Endometritis Polymicrobial early postpartum endometritis with facultative and anaerobic bacteria, genital mycoplasmas, and Chlamydia trachomatis: treatment with piperacillin or cefoxitin. Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping. Maternal and transplacental pharmacokinetics of azithromycin. Uterine flora at cesarean and its relationship to postpartum endometritis. Administration of cefazolin prior to skin incision is superior to cefazolin at cord clamping in preventing postcesarean infectious morbidity: a randomized, controlled trial. The Microbiology of Post‐Cesarean Wound Morbidity Cefazolin versus Cefazolin plus Metronidazole for Antibiotic Prophylaxis at Cesarean Section Adjunctive Intravaginal Metronidazole for the Prevention of Postcesarean Endometritis: A Randomized Controlled Trial The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. Post‐cesarean surgical site infections according to CDC standards: rates and risk factors. A prospective cohort study Ampicillin vs. ampicillin-gentamicin prophylaxis in high-risk primary cesarean section.
abstract: OBJECTIVE The purpose of this prospect i ve study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal/neonatal infectious morbidity . STUDY DESIGN In this double-blind placebo-controlled trial , cefazolin was given at skin incision ( group A ) or at cord clamping ( group B ) . Patients were eligible for the trial if they had labored and required a cesarean delivery . RESULTS Over a 30-month period 303 patients with singleton pregnancies entered the trial ; 153-group A , 149-group B. Demographics , indication for cesarean delivery ( P = .54 ) , and operative time ( P = .999 ) , as well as rates of endometritis ( RR 0.67 , 95 % CI 0.42 - 1.07 ) , wound infection ( RR 0.84 , 95 % CI 0.45 - 1.55 ) , neonatal sepis ( RR 1.28 , 95 % CI 0.91 - 1.79 ) , and NICU admissions ( RR 1.28 , 95 % CI 0.91 - 1.79 ) were similar between the 2 groups . CONCLUSION There was no difference in maternal infectious morbidity whether antibiotics were given before skin incision or at cord clamping In an ongoing prospect i ve study at 2 hospitals , 114 cesarean section patients were studied to determine whether giving ampicillin after umbilical cord clamping is as effective as perioperative ampicillin in reducing maternal postoperative morbidity . The same patients have also been studied to determine the effect of prophylactic cesarean section ampicillin on the newborn . Results have shown that prophylactic ampicillin initiated after cord clamping is as effective in reducing maternal morbidity as ampicillin initiated prior to the surgery . There is also no evidence from our study that the transplacental passage of prophylactic ampicillin increases immediate or delayed neonatal infections Eighteen vaginally delivered women who developed late postpartum endometritis seven to 42 days after delivery were prospect ively studied . Multiple microorganisms were recovered from the endometrium , including Chl aim ydia trachomatis , genital mycoplasmas , and a wide variety of bacteria . Erythromycin therapy was successful in ten of the 13 women who were followed OBJECTIVES To assess prospect ively the efficiency and safety of two extended spectrum cephalosporins used as pre-operative prophylaxis in nonelective cesarean sections , and compare the results to those of a third group of patients that received cefamezine post cord clamping . METHODS Two hundred and forty one patients undergoing a nonscheduled cesarean section were assigned to receive either cefonicid or ceftriaxone prior to skin incision . These patients were followed prospect ively for infectious and fetal complications . The outcome of these patients was also compared with another group of 194 patients that received cefamezine prophylaxis post cord clamping  , and whose data were collected retrospectively . Chi-square analysis of variance were performed with P < 0.05 considered significant . RESULTS There were no significant differences in the febrile complications among the two groups of patients that received pre-operative prophylaxis . However , these patients had significantly less wound infections ( P = 0.008 ) and a significantly shorter hospital stay ( P < 0.001 ) than the patients who received their prophylactic antibiotics post cord clamping . CONCLUSIONS Extended-spectrum cephalosporins , when given pre-operatively , are both effective and safe , and may have an advantage over intra-operative first generation cephalosporins in the reduction of post cesarean section infectious morbidity OBJECTIVE : To describe the effect of an extended-spectrum prophylactic antibiotic regimen on  postcesarean endometritis .  METHODS : This is a cohort study of trends in  postcesarean endometritis  using data both from prospect i ve surveillance by the infection control unit and from query of our obstetric computerized data base to compare three periods of antibiotic prophylaxis : st and ard narrow-spectrum with intravenous first- or second-generation cephalosporin ( 1992–1996 ) , clinical trial of extended-spectrum with addition of intravenous doxycycline and oral azithromycin ( 1997–1999 ) , and routine use of extended-spectrum with addition of intravenous azithromycin ( 2001–2006 ) to st and ard cephalosporin prophylaxis . RESULTS : A total of 48,913 deliveries at 24 weeks or more of gestation occurred from 1992 to 2006 , of which 10,966 ( 22.4 % ) were cesarean deliveries . Annual cesarean rates increased from 16 % to 27.5 % . Trends in the incidence of postcesarean endometritis revealed a biphasic decrease consistent with the phased introduction of extended-spectrum prophylaxis . Incidence ( 95 % confidence interval [ CI ] ) of endometritis by prospect i ve surveillance dropped from 19.9 % ( 95 % CI 18.6–21.3 % ) to 15.4 % ( 95 % CI 13.2–17.9 % ) during the clinical trial period : relative risk ( RR ) 0.77 ( 95 % CI 0.66–0.91 ) , P=.002 ; and then to 6.3 % ( 95 % CI 5.0–7.9 % ) during routine use of extended-spectrum prophylaxis : RR 0.41 ( 95 % CI 0.31–0.54 ) , P<.001 . Corresponding incidence by data base query dropped from 23 % ( 95 % CI 21.5–24.4 % ) to 16 % ( 95 % CI 14.4–17.9 % ) : RR 0.69 ( 95 % CI 0.61–0.79 ) , P<.001 ; and then to 2.1 % ( 95 % CI 1.8–2.6 % ) : RR 0.13 ( 95 % CI 0.11–0.16 ) , P<.001 . These findings were unchanged after adjusting for potential confounders . CONCLUSION : Extended-spectrum antibiotic prophylaxis involving the addition of azithromycin to st and ard narrow-spectrum prophylaxis was associated with a significant reduction in postcesarean endometritis . LEVEL OF EVIDENCE : OBJECTIVE To determine if extended spectrum prophylactic antibiotic treatment ( with efficacy against Ureaplasma urealyticum ) reduces post – cesarean delivery clinical endometritis . METHODS After cord clamping at cesarean delivery , subjects received prophylaxis with cefotetan . Subjects were then simultaneously r and omized ( double blind ) to receive doxycyline plus azithromycin versus placebo .  Post – cesarean delivery endometritis was defined clinical ly as fever of 100.4F or higher with one or more supporting clinical signs or a physician diagnosis of endometritis plus the absence of a nonpelvic source of fever . RESULTS A total of 597 women were enrolled , 301 in the doxycycline/azithromycin group and 296 in the placebo group . The study population was 56 % black , 25.5 ± 6.2 years of age , and 43 % nulliparous . The groups were similar ( P > .05 ) for black race , parity , maternal age , and most risk factors for post – cesarean delivery endometritis . The frequency of post – cesarean delivery endometritis ( 16.9 % versus 24.7 % , P = .020 ) , wound infections ( 0.8 % versus 3.6 % , P = .030 ) , and a combination of these two outcomes ( 19.0 % versus 27.8 % , P = .019 ) were significantly lower in the doxycycline/azithromycin group compared with the placebo-treated group . The doxycycline/azithromycin versus placebo groups were dissimilar for maternal leukocytosis ( 24.9 % versus 12.5 % , P = .042 ) and frequency of classic uterine incision ( 7.6 % versus 12.5 % , P = .048 ) . Adjusting for these factors did not alter the risk ratio for post – cesarean delivery endometritis in the active versus placebo-treated group ( relative risk 0.65 , 95 % confidence interval 0.43 , 0.98 ) . Length of stay was longer in the placebo group overall ( 104 ± 56 versus 95 ± 32 hours , P = .016 ) and among women with endometritis ( 146 ± 52 versus 127 ± 46 hours , P = .047 ) . CONCLUSION Extended spectrum prophylactic antibiotic treatment ( with presumed efficacy against U urealyticum ) given to women undergoing cesarean delivery at term shortens hospital stay and reduces the frequency of post – cesarean delivery endometritis and wound infections A protected , triple-lumen transcervical culture method was used to recover organisms from the endometrium . At least one facultative or one anaerobic species of bacteria was recovered from 82 % of the patients , and genital mycoplasmas were recovered from 76 % of the women with endometritis .  Bacteria together with genital mycoplasmas were present in 61 % of the women , bacteria alone were present in 20 % , genital mycoplasmas alone were present in 16 % , and Chlamydia trachomatis was isolated from 2 % of the patients . The most common organisms included Gardnerella vaginalis , Peptococcus spp . , Bacteroides spp . , Staphylococcus epidermidis , group B Streptococcus , and Ureaplasma urealyticum . A r and omized , double-blind regimen of either piperacillin or cefoxitin was equally successful in treating the postpartum endometritis The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity .  Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were r and omized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded , placebo-controlled study . The 2 groups were compared for differences in maternal and neonatal demographics , and intrapartum and operative characteristics associated with postcesarean infection . Primary maternal outcome variables were endometritis or wound infection . Secondary outcomes included intra-abdominal abscess formation , septic pelvic thrombophlebitis , pneumonia , or urinary tract infection . Neonatal outcomes included sepsis screens , sepsis , pneumonia , and meningitis . Subjects were followed 6 weeks postoperatively for late complications . Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics , and intrapartum and operative characteristics . One patient in the former group experienced both endometritis and wound infection . In the latter group , 2 wound infections and 1 case of endometritis occurred ( P = 0.35 ) . There were no secondary maternal infections . Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively . Overall , 8 neonates were evaluated for suspected sepsis and all had negative studies . Six of these infants ' mothers received cefazolin preoperatively ( P = 0.28 ) . In conclusion , 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity , but is associated with a trend toward increased suspected sepsis in the newborn . However , this trend may be related to differences between the study groups ' risk factors for infection OBJECTIVE The purpose of this study was to characterize the pharmacokinetics of orally administered azithromycin in the term gravid woman . STUDY DESIGN Twenty women who were scheduled for elective cesarean delivery were enrolled prospect ively and received 1 g of oral azithromycin at either 6 , 12 , 24 , 72 , or 168 hours before the operation . All women received spinal anesthesia , at which time a sample of cerebrospinal fluid was obtained for analysis . Maternal serum and urine were obtained immediately before the operation . Intraoperatively , sample s of myometrium , maternal adipose tissue , placenta , amniotic fluid , and umbilical arterial and venous cord blood were obtained . Azithromycin levels were determined quantitatively with high-pressure liquid chromatography with electrochemical detection . RESULTS All participants tolerated the preoperative azithromycin without significant adverse reactions . Peak maternal serum azithromycin levels occurred within 6 hours of drug administration . Although high serum levels of azithromycin  were reached early , a rapid decline in drug concentration was noted over the initial 24 hours after the drug administration ( 6-hour : 311 ng/mL ; 24-hour : 63 ng/mL ) . In contrast ,  azithromycin levels in myometrial , adipose , and placental tissue were higher ( > 500 ng/mL ) and sustained for up to 72 hours after administration . High urine levels of azithromycin  ( > 5000 ng/mL ) were noted similarly during the initial 72 hours after drug administration . Umbilical arterial and venous serum azithromycin levels were low ( 19 - 38 ng/mL ) during the first 72 hours . Amniotic fluid levels were highest at 6 hours ( 151 ng/mL ) and declined rapidly . Maternal cerebrospinal azithromycin concentrations were undetectable for all time points . CONCLUSION Azithromycin has a rapid serum half-life in the term gravid woman with a prolonged half-life and high-sustained antibiotic levels noted within myometrium , adipose , and placental tissue . Given the broad antimicrobial spectrum and placental penetration , azithromycin may have potential use for the treatment of perinatal infections OBJECTIVE To evaluate the relationship between the presence of microorganisms at the time of cesarean at different sites of the genital tract and the development of postpartum endometritus . METHODS One-hundred thirty-three healthy women who delivered by cesarean were enrolled in this prospect i ve study . Cultures were obtained during the surgery and on days 3 - 5 postoperatively . Gram staining of uterine cavity fluid was done on days 3 - 5 . Gram stains were examined under a high-power microscope for the presence of polymorphonuclear leukocytes . RESULTS Twenty patients ( 15.0 % ) met the criteria for postpartum endometritis .  Forty-five patients ( 33.8 % ) had one or more positive cultures ( n = 133 ) at the time of surgery , result ing in 93 positive cultures and 123 bacterial isolates . Forty-four patients had positive postoperative uterine cavity cultures at days 3 - 5 postpartum , result ing in 65 isolates . Of 44 patients with a positive postoperative culture , 26 ( 59.1 % ) also had Gram stain positive for polymorphonuclear leukocytes in the uterine cavity fluid , whereas only six of 89 patients ( 6.7 % ) with negative postoperative culture had a positive Gram stain ( P < .05 ) . The relative risk of having a positive culture on postoperative day 3 - 5 if the culture at surgery was positive at any site was 15.6 ( 95 % confidence interval [ CI ] 5.9 , 42.2 ) , and it was 19.5 ( 95 % CI 6.8 , 57.8 ) if the culture was positive at the lower uterine segment . CONCLUSION The presence of bacteria in the lower uterine segment at the time of the surgery predicts their presence in the uterine cavity during puerperium . The Gram stain of uterine cavity fluid on postcesarean days 3 - 5 is another quick tool that can expedite the diagnosis of postpartum endometritis OBJECTIVE The objective of the study was to determine whether the administration of cefazolin prior to skin incision was superior to administration at the time of umbilical cord clamping for the prevention of postcesarean infectious morbidity . STUDY DESIGN This was a prospect i ve , r and omized , double-blind , placebo-controlled trial . Study subjects received cefazolin 15 - 60 minutes prior to incision and controls received cefazolin at the time of cord clamping . The occurrence of endomyometritis , wound infection , total infectious morbidity , and neonatal complications were compared . RESULTS There were 357 subjects enrolled . No demographic differences were observed between groups . There were decreased total infectious morbidity in the study group ( relative risk [ RR ] = 0.4 , 95 % confidence interval [ CI ] 0.18 to 0.87 ) , decreased endometritis ( RR = 0.2 , 95 % CI 0.15 to 0.94 ) . No increase in neonatal sepsis ( P = .99 ) , sepsis workups ( P = .96 ) , or length of stay ( P = .17 ) was observed . CONCLUSION Administration of prophylactic cefazolin prior to skin incision result ed in a decrease in both endomyometritis and total postcesarean infectious morbidity , compared with administration at the time of cord clamping . This dosing did not result in increased neonatal septic workups or complications Objective : To determine the microbiology of wound morbidity following cesarean deliveries . Methods : Nine hundred thirty‐nine wounds in post‐cesarean patients were followed prospect ively . Aspirates from the abdominal incision were collected if the wounds developed erythema , in duration , or pain and had demonstrable fluid collection noted on ultrasound . Cultures were also obtained of wound exu date s when there was spontaneous separation of the skin . Gram stains were performed concomitantly with culture . Results : The cumulative incidence of  post‐cesarean wound morbidity between September 1990 and June 1991 was 6.9 % ( 65 of 939 ) , and the rate of culture‐positive wounds was 72 % ( 47 of 65 ) . Ureaplasma urealyticum was the most frequent isolate at a rate of 62 % ( 29 of 47 ) , followed by coagulase‐negative staphylococci at 32 % ( 15 of 47 ) and Enterococcus faecalis at 28 % ( 13 of 47 ) . Gram stains of the exu date s obtained were used to predict microbiologic results . Organisms present on Gram stain yielded a sensitivity of 0.55 , specificity of 1.0 , positive predictive value of 1.0 , and negative predictive value of 0.71 when used to predict positive culture results for bacterial wound infection other than with genital mycoplasmas . White blood cell counts greater than ten per 400 × high‐power fields yielded a sensitivity of 0.83 , specificity of 0.72 , positive predictive value of 0.89 , and negative predictive value of 0.62 when used to predict wound infection including genital mycoplasmas . Conclusions : Genital mycoplasmas are the most prevalent bacterium in post‐cesarean wound infections in this population . If genital mycoplasmas are pathogenic in this setting , then the Gram stain may be useful in predicting wound microbiology . More research is needed on the pathogenic role of genital mycoplasmas in wound infections Background Although prophylactic antibiotic medications have been shown to reduce the incidence of postoperative infectious morbidity after cesarean delivery , the most effective regimens have not been established . The purpose of this investigation was to compare the efficacy and costs of prophylaxis with cefazolin alone with cefazolin plus metronidazole . Methods Women undergoing cesarean delivery were r and omized to prophylaxis with 2 g cefazolin ( n = 81 ) or 1 g cefazolin plus 500 mg metronidazole  ( n = 79 ) . Postoperative infectious morbidity and the duration of hospitalization in the two groups were compared . Results Thirty-seven ( 23 % ) of 160 patients developed endomyometritis . There was a significant reduction in the number of postoperative infections ( 14 versus 32 % ) and hospital days ( 3.12 versus 4.46 ) with cefazolin and metronidazole prophylaxis ( P = 0.0064 versus P = 0.014 ) compared with cefazolin alone . The estimated antibiotic prophylaxis cost per person was less with cefazolin and metronidazole than with cefazolin alone ( $ 9.12 versus $ 26.73 ) . Conclusion Antibiotic prophylaxis with metronidazole and cefazolin results in fewer postoperative infections , decreased duration of hospitalization , and lower medication cost than cefazolin alone OBJECTIVE To estimate the efficacy of preoperative administration of intravaginal metronidazole for the prevention of postcesarean endometritis . METHODS This double‐masked , placebo‐controlled  r and omized trial included patients of at least 24 weeks ' gestation undergoing cesarean deliveries for various indications . Patients were r and omized to receive either 5 g of metronidazole gel intravaginally or matching placebo before the initiation of the cesarean . All patients underwent surgical cleansing of the abdomen , and most received prophylactic antibiotics after cord clamping . Patients with chorioamnionitis and /or suspected allergy to metronidazole were excluded . For a two‐sided α of 0.05 and β of 0.20 ( 80 % power ) , 120 subjects were required in each group . The main outcome variable was the incidence of postcesarean endometritis . Secondary outcome variables included presence of febrile morbidity , wound infection , days on antibiotics , and length of postpartum hospitalization . Neonatal outcomes included birth weight , Apgar scores less than 7 at 5 minutes , umbilical arterial pH less than 7.16 , admission and length of stay in the neonatal intensive care unit , and length of hospital stay . RESULTS Of 112 patients receiving metronidazole  , eight ( 7 % ) developed postcesarean endometritis , compared with 19 of 112 ( 17 % ) of those receiving placebo gel ( relative risk 0.42 , 95 % confidence interval 0.19 , 0.92 ) . No significant differences were noted between treatment groups with respect to the other outcome variables . CONCLUSION The preoperative administration of 5 g of intravaginal metronidazole gel appears to reduce the incidence of postcesarean endometritis 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 Objectives . The aim of this study was to document the true incidence of post‐cesarean surgical site infections ( SSI ) , according to the definition of the US Centers for Disease Control and Prevention ( CDC ) , and to identify independent risk factors for infection . Design . Prospect i ve  population ‐based cohort study in Norway . Setting . Sykehuset Asker og Bærum HF , a secondary community hospital , associated with the University of Oslo ( UiO ) , Norway , accounting for 2,000 deliveries per year . Participants . All cesarean deliveries during a 12‐month period from September 2003 . Main outcome measures . Rate and risk factors for SSI . Results . The total rate of SSI was 8.9 % , with an observation period of 30 days post‐operatively , compared to 1.8 % registered at hospital discharge . The total response rate was 100 % . There was no significant difference in SSI rate in elective or emergency cesarean section ( CS ) , respectively . All SSI were superficial . We found 2 significant independent risk factors : operating time ≥38 min and body mass index ( BMI ) > 30 . Conclusion . The rate of SSI is underestimated if the observation time is limited to the hospital stay . Operating time exceeding 38 min substantially increases the risk of SSI . The finding of no significant difference in SSI rate between elective and emergency CS should lead to a different approach concerning the use of antibiotics : subgroup at risk ( operating time ≥38 min and BMI > 30 ) may benefit from antibiotics in relation to the operation , whether the CS is an emergency or elective operation A r and omized , prospect i ve comparison of ampicillin and ampicillin-gentamicin therapy was conducted in a group of 123 women undergoing primary cesarean section after the onset of labor . All pretreatment patient profiles indicated similar high-risk factors for infection . Febrile morbidity , complication rate and hospital stay were all more favorable in women receiving ampicillin-gentamicin
target: Although current guidelines for antibiotic prophylaxis recommend the administration of narrow-spectrum antibiotics ( cefazolin ) after clamping of the umbilical cord , the data suggest that antibiotic administration before surgical incision or the use of extended-spectrum regimens ( involving azithromycin or metronidazole ) after cord clamp may reduce postcesarean maternal infection by up to 50 % .
  : The use of either cefazolin alone before surgical incision or an extended-spectrum regimen after cord clamp seems to be associated with a reduction in  postcesarean maternal infection .
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