For emergency C/S and vaginal hyserectomy, the benefits of prophylactic antibiotics are clear-cut. In contrast, studies evaluating prophylaxis for elective C/S and abdominal hysterectomy are harder to interpret. The authors review the evidence.
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For emergency C/S and vaginal hysterectomy, the benefits of prophylactic antibiotics are clear-cut. In contrast, studies evaluating prophylaxis for elective C/S and abdominal hysterectomy are harder to interpret. The authors review the evidence.
Postop infections remain a stubborn problem for many women who have undergone obstetric and gynecologic procedures. In fact, they continue to be the most common complication after surgery. And the two most frequently encountered infections are operative site infections such as endometritis following cesarean delivery and pelvic cellulitis after hysterectomy.1,2
During these surgical procedures, micro-organisms that normally inhabit the genital tract enter the pelvic cavityand sometimes the bloodstream. The most prevalent of these micro-organisms are Escherichia coli and other aerobic gram-negative rods; group B streptococci (GBS); enterococcus; Staphylococcus aureus and coagulase-negative staphylococci; anaerobes, including Peptostreptococcus species, Prevotella species, and Bacteroides species; Gardnerella vaginalis; and genital mycoplasmas.2 Other postsurgical infections to be concerned about include urinary tract infection, wound infection, and rarebut serioussecondary infections such as pelvic abscess, bacteremia, septic shock, septic pelvic thrombophlebitis, and necrotizing fasciitis.1 Patients who develop an infection postoperatively suffer increased morbidity, require a longer hospital stay in some cases, and generate higher hospital costs.
One way to cut back on these infections is to administer prophylactic antibiotics to patients about to undergo a procedure. To justify their use, however, the following criteria should be met:
Assuming a patient meets these criteria, the goals of giving prophylactic antibiotics are fourfold: 1
These drugs will help physicians achieve these four goals by reducing the size of the bacterial inoculum introduced into the pelvic cavity, altering the culture medium at the surgical site to prevent the growth of pathogenic bacteria, penetrating the epithelium of the genital tract to render it less susceptible to invasion by bacteria, and enhancing phagocytosis by concentrating the antimicrobial in macrophages and polymorphonuclear leukocytes.2
Numerous studies over the past two decades have tried to determine whether postoperative infection rate could be reduced by giving prophylactic antibiotics. In some cases, the benefits of antimicrobial prophylaxis have been obvious. For instance, study after study has demonstrated that for nonelective C/S delivery and vaginal hysterectomy, the incidence of infection is significantly reduced when patients are given prophylactic antibiotics. In contrast, studies that have specifically evaluated prophylaxis for elective C/S delivery and abdominal hysterectomy are more difficult to interpret. We will review the data on the subject and make recommendations regarding the use of prophylactic antibiotics for these procedures.
A wide variety of studies have evaluated the effect of prophylactic antibiotics on patients undergoing elective C/S delivery prior to labor or rupture of membranes. Several of these investigations are outlined in Table 1.3-9 In addition, a recent meta-analysis of seven prospective, randomized, placebo-controlled trials concluded that antibiotic prophylaxis clearly benefited nonlaboring women with intact membranes who had C/S deliveries.10 Similarly, fever and endometritis were significantly reduced, and there was a trend toward fewer wound infections. Moreover, the results were statistically significant regardless of the patient population or the antibiotic regimen chosen. On the basis of their meta-analysis, the authors suggested that prophylactic antibiotics should be considered for all elective C/S deliveries and prophylaxis should definitely be given to patient populations in whom the combined incidence of endometritis and wound infection equals or exceeds 5%.
|Study||Patients (No.)||Outcome||Level of evidence|
|Allen et al.||12||Decreased frequency of pooled infection in the antibiotic group (43% vs 0%) (||A|
|Duff and Park||25||Decreased rate of endometritis in the antibiotic group (42% vs. 0%) (||A|
|Dillon et al.||38||Decreased pooled infection rate (20% vs. 0%) (NS) and fever rate (30% vs. 6%) (NS) in the antibiotic group||A|
|Duff et al.||82||Decreased incidence of fever (33% vs. 10%) (||A|
|Apuzzio et al.||15||Decreased rate of endometritis in the antibiotic group (43% vs. 0%)*||A|
|Roex et al.||42||Increased frequency of fever in the antibiotic group (6% vs. 4%)*||A|
|Mahomed et al.||232||Decreased frequency of pooled infection (37% vs. 19%) fever (20% vs. 6%), endometritis (5% vs. 0%), and wound infection (10% vs. 6%) in the antibiotic group*||A|
The Cochrane database, which was most recently updated on this subject in May 2001, reported recommendations similar to the meta-analysis.11 The results of all the trials included in the Cochrane review were consistent both in direction of effect and in effect size with regard to reducing infection with prophylactic antibiotics. The risk of endometritis in patients having elective C/S was reduced by 75% in women who received prophylactic antibiotics, compared to those who did not (RR=0.25, 95% CI, 0.110.55). The incidence of postpartum febrile morbidity and urinary tract infection also fell.
The Cochrane summary did report a 1.5% incidence of maternal side effects, however, which included rash and phlebitis at the infusion site; but no serious drug-related adverse events occurred. The researchers recommended that all maternity units establish a policy for administering prophylactic antibiotics to women undergoing C/S and also suggested withholding antibiotics only in units with a confirmed low rate of infection. Finally, they found no substantive support for the contention that appropriate use of short-course antimicrobial prophylaxis causes clinically significant bacterial resistance and that the potential adverse consequences of antimicrobial prophylaxis are theoretical and shouldn't detract from the solid evidence supporting the role of antibiotic prophylaxis for C/S delivery.
Table 2 summarizes some of the most important prospective studies that looked at the effects of prophylactic antibiotics for abdominal hysterectomy.12-19 A meta-analysis published in 1993 evaluated 25 prospective, randomized, controlled trials on postoperative infection.20 Infection was defined as one or more of the following: abdominal wound infection, pelvic cellulitis, pelvic abscess, vaginal cuff abscess, postoperative pelvic inflammatory disease, or postoperative septicemia. As a group, the control patients had a 21% incidence of serious postoperative infection, compared to 9% (P=0.00001) among patients who received antibiotic prophylaxis. They found that antibiotics were highly protective against serious infection-related morbidity associated with abdominal hysterectomy and can prevent more than half of the serious infections experienced by women having this procedure. In fact, the evidence was so compelling that they concluded that further randomized controlled trials of antibiotic prophylaxis in abdominal hysterectomy using controls are no longer justified.
|Study||Patients (No.)||Outcome||Level of evidence|
|Allen et al.||168||Reduction in incidence of standard febrile morbidity, UTI, wound infection and hospitalization in antibiotic group. Increased incidence of pelvic cellulitis in the antibiotic group.||B|
|Ohm and Galask||93||Reduction in incidence of standard febrile morbidity, UTI. Statistically insignificant reduction in incidence of pelvic cellulitis and wound infection.||A|
|Applebaum et al.||104||Significant reduction in incidence of wound infection.||A|
|Holman et al.||80||Significant reduction in incidence of UTI, pelvic cellulitis, wound infection.||A|
|Jennings||102||Significant reduction in wound infection, UTI.||A|
|Roberts and Homesley||47||Significant reduction in incidence of UTI. No significant difference in incidence of pelvic cellulitis or wound infection.||B|
|Polk et al.||429||Significant reduction in wound infection, pelvic infection, UTI and febrile morbidity.||A|
|Duff||91||No significant decrease in incidence of pelvic cellulitis, UTI, or wound infection.||A|
|Hemsell et al.||112||Reduction in incidence of major infection and length of hospital stay.||A|
A second meta-analysis published in 1994 reviewed 17 prospective trials (some of which were the same studies analyzed in the previously mentioned analysis) that included 2,752 patients who received cephalosporin prophylaxis for no more than 24 hours in the perioperative period.21 All generations of cephalosporins were found to be useful in preventing postoperative infection (P<0.001), while febrile morbidity was most effectively prevented by first-generation cephalosporins. The authors concluded that a single, preoperative dose of a first- or second-generation cephalosporin yielded the most cost-effective clinical results.
Investigators have evaluated many different prophylactic regimens, as well as various dosing schedules and routes of administration, for C/S delivery and abdominal hysterectomy. None of the individual trials, nor all considered collectively, has been able to show that any of the more expensive, extended-spectrum drugs are more effective in decreasing postoperative infection than more narrow-spectrum, less expensive drugs. Almost any antibiotic seems to be effective in decreasing infection after clean-contaminated cases; therefore, a clinician should base his or her decision on factors such as potential adverse effects and cost.
There's at least theoretical concern about potential adverse effects when prophylactic antibiotics are administered to large groups of women. Although there have been isolated case reports of anaphylactic reactions in patients receiving antibiotics during other surgical procedures, such reactions have not been documented in obstetric or gynecologic patients. Even so, be careful to elicit a history of drug allergy from any patient who will be receiving prophylaxis.
Ob/gyns should also be at least theoretically concerned about altering the vaginal flora of women given prophylactic antibiotics. Some investigators have shown changes in the vaginal flora of these women. But there's no evidence that women who become infected despite prophylaxis develop more serious complications. Nevertheless, those who have received cephalosporins preoperatively are also more likely to become infected with enterococci, and many antibiotics used for the treatment of post-cesarean infection do not cover enterococci. Therefore, maintain careful surveillance to detect unusual changes in antimicrobial susceptibilities in each patient population.23,24
Ideally, prophylactic antibiotics should have the following characteristics: They should be relatively inexpensive and easy to administer; have fairly broad coverage against most, but not necessarily all, of the bacteria likely to be encountered at the operative site; and should be drugs that are not ordinarily used to treat an established infection.1 The recommended prophylactic regimens for women having C/S delivery or abdominal hysterectomy are outlined in Table 3.25,26 In general, a single dose is just as effective as multiple doses. In the case of C/S delivery, the antibiotic should be given immediately after the infant's umbilical cord is clamped. Delaying the antibiotic until after cord clamp does not reduce the drug's preventive effects and will prevent exposure of the newborn to antibiotics, which could complicate the workup for suspected sepsis.27
|Cesarean delivery||Cefazolin||1 g IV||At the time of cord clamping|
|B-lactam allergy||Clindamycin plus gentamicin||900 mg IV 1.5 mg/kg IV||At the time of cord clamping|
|Abdominal hysterectomy||Cefazolin||1 g IV||Immediately prior to procedure|
|B-lactam allergy||Doxycycline||100 mg IV||Immediately prior to procedure|
Our evidence-based review of the scientific evidence yields the following recommendations on prophylactic antibiotics. Based on the method outlined by the US Preventive Services Task Force, these "level A" ratings designate "good and consistent scientific evidence."
1. Antibiotic prophylaxis is indicated for elective C/S delivery.
2. Antibiotic prophylaxis is indicated for abdominal hysterectomy.
3. A single dose of a limited-spectrum antibiotic, such as cefazolin, is the drug of choice for prophylaxis for clean-contaminated procedures including C/S delivery and abdominal hysterectomy.
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2. Duff P. Prophylactic antibiotics for hysterectomy. Contemporary OB/GYN. 1997;42:21-26.
3. Allen JL, Rampone JF, Wheeless CR. Use of prophylactic antibiotic in elective major gynecologic operations. Obstet Gynecol. 1972;39:218-224.
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14. Holman JF, McGowan JE, Thompson JD. Perioperative antibiotics in major elective gynecologic surgery. South Med J. 1978:71:417-420.
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17. Polk BF, Tager IB, Shapiro M, et al. Randomised clinical trial of perioperative cefazolin in preventing infection after hysterectomy. Lancet. 1980;1:437-440.
18. Duff P. Antibiotic prophylaxis for abdominal hysterectomy. Obstet Gynecol. 1982;60:25-29.
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24. Gibbs RS, St Clair PJ, Castillo MS, et al. Bacteriologic effects of antibiotic prophylaxis in high-risk cesarean section. Obstet Gynecol. 1981;57:277-282.
25. Duff P. Antibiotic selection in obstetric patients. Infect Dis Clin North Am. 1997;11:1-12.
26. Duff P. Antibiotic selection in obstetrics: making cost-effective choices. Clin Obstet Gynecol. 2002;45:59-72.
27. Sweet RC, Gibbs RS. Antimicrobial agents. In: Sweet RL, Gibbs RS, eds: Infectious Diseases of the Female Genital Tract. 3rd ed. Baltimore, Md: Williams & Wilkins; 1995.
Patrick Duff, Whitney Jamie, Whitney Jamie. Preventing infections during elective C/S and abdominal hysterectomy.