Antibiotic Therapy of Obstetric and Gynecologic Infections

Symposium on Surgical Infections and Antibiotics

Antibiotic Therapy of Obstetric and Gynecologic Infections

Sherwood L. Gorbach, M.D. *

Successful treatment of suppurative disease of the female pelvis involves a combined approach of adequate surgical drainage and appropriate selection of antimicrobial agents. Recent bacteriologic studies of such infections· have provided a firm foundation for rational antibiotic choices.6 The pathogens causing upper tract pelvic infections are usually related to the indigenous microflora of the vagina. In addition to the well known components of lactobacilli and streptococci, modern bacteriologic techniques have shown anaerobes to be present in the vagina in approximately 70 per cent of healthy women. 7 Bacteroides is the most common anaerobe isolated; the various species include B. fragilis, B. melaninogenicus and B. oralis. Peptostreptococci and clostridia are also part of this complex flora. These microorganisms are all potential pathogens and are undoubtedly related to upper tract infections. In the past, anaerobic infections of the female pelvis have been synonymous with two bacteria, anaerobic streptococci and Clostridium perfringens. Recent studies14 • 16 have revealed a far more complicated picture. Multiple microorganisms, both facultative and anaerobic, are involved, but the current weight of evidence favors obligate anaerobes as the predominant pathogens in most serious infections of the female pelvic tract.

Pelvic Abscess Septic conditions in the female pelvis tend to localize with the formation of single or multiple abscesses. Pelvic abscess is a life threatening disease that can present acutely or have a delayed and undulating course. The anatomic setting has a number of variations: (1) unilateral or bilateral parametrium abscess which points either to the vagina or the inguinal area; (2) cuI de sac collection that points to the posterior fornix of the vagina; (3) tubo-ovarian abscess that becomes fixed high in *Infectious Diseases Section, Veterans Administration Hospital, Sepulveda, California

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the pelvic lateral wall; (4) tubo-ovarian or ovarian abscess that presents as an abdominal mass; and (5) catastrophic rupture of an abscess leading to pelvic peritonitis. Bacteriologic study of pelvic abscess reveals that two thirds of cases are associated with a mixed anaerobic-aerobic culture; the remaining one third will have an entirely aerobic or anaerobic infectionP' 14, 16 The aerobic and facultative microflora consists of E. coli, Klebsiella and streptococci. Rarely, Pseudomonas, S. aureus and Candida are isolated. The anaerobic microorganisms involved, in decreasing order of frequency, include B. fragilis, anaerobic streptococci, B. melaninogenicus and several species of clostridia. There is a high incidence of positive blood cultures in patients with suppurative pelvic disease.2 ,10 The most common bloodstream invaders are Bacteroides, anaerobic streptococci, E. coli, Klebsiella and clostridia. More than one species of bacteria are often isolated from a single blood culture, provided both anaerobic and aerobic bacteriologic media are utilized. Several antibiotic regimens have been suggested for the treatment of pelvic abscess. 4 ,9,15-17 A strong case can be made for using two drugs, one active against the aerobes and the other designed to suppress the anaerobes. Some of the recommended regimens are as follows: 1. Clindamycin 600 mg. intravenously every 6 hours Gentamicin 1.0 to 1.5 mg./kg. every 8 hours 2. Chloramphenicol 750 to 1000 mg. intravenously every 6 hours Gentamicin 1.0 to 1.5 mg./kg. every 8 hours 3. "Penicillin 5 million units intravenously every 6 hours Chloramphenicol 750 to 1000 mg. intravenously every 6 hours *Recommended by some authorities, but we would not endorse this combination.

Ovarian Abscess The ovaries may be involved in a localized suppurative process in which the tubes remain free of infection. IS This condition is often associated with peritonitis which is usually limited but may later become more widespread. The infecting flora consists of aerobic and anaerobic microorganisms. Bacteroides, anaerobic streptococci, clostridia, E. coli, and Klebsiella are the major pathogens, often in association with one another.I. 6 Hence, antibiotic treatment of ovarian abscess is identical to the regimen suggested for pelvic abscess. The predisposing causes of ovarian abscess are: (1) pelvic surgery, especially vaginal hysterectomy; (2) postpartum infection, abortion and cesarean section; (3) endometritis following a dilatation and curettage; and (4) inflammatory bowel disease or diverticulitis. This infection must be approached surgically following initial supportive measures and antimicrobial therapy. The major risk of ovarian abscess is that the diagnosis is missed, and there may be subsequent rupture of the abscess with catastrophic results. Pyometra Pyometra is caused by obstruction of the cervix which leads to accumulation of pus and enlargement of the uterus. 3 Surprisingly, this

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process may be an insidious infection with relatively few systemic manifestations. The clinical settings include: (1) carcinoma of the cervix or endometrium, seen in approximately 70 per cent of the patients; (2) radiation therapy to the pelvis; (3) previous cauterization; (4) spontaneous cervical stenosis in postmenopausal women; (5) polyps or leiomyomas that obstruct the cervix; and (6) tuberculosis, as a rare cause, leading to cervical stenosis. The infecting bacteria involved in pyometra are derived from the normal vaginal flora, and resemble those described above for pelvic and ovarian abscess. 14 Treatment is initially with antibiotics along with conservative management. Following stabilization, surgical intervention is usually indicated.

Septic Pelvic Thrombophlebitis Thrombosis of the pelvic veins associated with an inflammatory process represents a serious threat to the patient. In addition to the local suppuration, there is the risk of embolism to the lungs or kidneys. Virtually all forms of pelvic surgery and obstetrical complications can lead to thrombophlebitis. The most common situations are: (1) vaginal delivery, particularly associated with prolonged rupture of membranes or puerperal sepsis; (2) abortions, either criminal or therapeutic; (3) pelvic operations such as hysterectomy; (4) cesarean section; and (5) pelvic inflammatory disease and pelvic abscess. Multiple veins are often involved with the thrombotic process. The most frequent veins affected are, in the order of occurrence, the ovarian, uterine, common iliac, hypogastric, vaginal, and inferior vena cava. Pathologic findings include edema, induration of the vessel wall that often progresses to suppuration, and destruction of the wall by the infecting process. The major pathogens associated with septic thrombophlebitis of the pelvis are anaerobic streptococcus and Bacteroides species, particularly B. fragilis and B. melaninogenicus. Rare cases are caused by Streptococcus pyogenes or Staphylococcus aureus. Septic thrombophlebitis is suspected in a patient with suppurative disease of the pelvis who is not responding to conventional antibiotic therapy. Signs of pulmonary embolism lend support to this diagnosis. Antibiotics should be appropriate for the major pathogens, the anaerobic streptococcus and Bacteroides fragilis. This means that either chloramphenicol or clindamycin should be included in the regimen. Coliforms may also be involved in the primary suppurative process so that either gentamicin or kanamycin should be combined with the drug against anaerobes. An important component of treatment is the use of heparin. 16 Several regimens have been recommended, but it is generally agreed that the clotting time should be maintained at two to three times normal. In the event that appropriate antibiotics and adequate anticoagulation prove ineffective, an exploratory operation is recommended to deal with the primary suppurative process and to remove infected clots from the veins in the pelvis.

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Streptococcal Infections One of the classic causes of childbed fever is infection with the group A, beta-hemolytic Streptococcus pyogenes. This organism may also be associated with pelvic surgery and has been related to an IUD (Lippes loop or Dalkon shield). Puerperal sepsis and postoperative infections due to this organism are usually spread by a physician or nurse due to contamination from the mouth or nose, or on rare occasions, from a streptococcal lesion on the fingers. There is added risk associated with prolonged labor and excessive blood loss, although streptococcal infections can occur in apparently uncomplicated situations. The most striking feature is the high, spiking fever that occurs very early in the course. Many patients have symptoms within 12 hours of delivery or surgery; two thirds of cases have occurred within the first day, and the additional one third has presented by the second day. There is often pelvic pain, and a diffuse, spreading redness that travels by the lymphatics. A thin, watery discharge may occur. Wound dehiscence is an early complication. Streptococcal peritonitis is a diffuse erythema with few adhesions and rare loculation of pus. Approximately 40 per cent of patients have a bacteremia that may be associated with disseminated intravascular coagulation (DIC) and hemolytic anemia. Treatment is high doses of penicillin G (5 million units intravenously every 4 to 6 hours). Besides antibiotics, support measures are critical to a good outcome. The patients often develop septic shock with a decreased intravascular volume. Fluid and electrolyte replacement is always indicated. Colloid may be required, and many patients require transfusions due to DIC and hemolysis. There is usually no indication for surgery, except in circumstances where necrotic tissue is present, and then only simple debridement is required. If appropriate treatment is instituted early, the outlook is favorable for patients with streptococcal infections. However, delay in recognition can lead to a rapidly fatal course. Group B streptococci are a common cause of infection in newborns, and may cause a mild illness in the mother. Because of its importance in the newborn, the following guidelines are provided "for comparing Group A and Group B streptococci: Group A streptococci Group B streptococci Vaginal carrier Occurrence of infection in newborns Mode of acquisition Maternal disease Prognosis in mother Prognosis in neonate

Rare Rare

5 to 14 per cent Common

Doctors, nurses and attendants Severe Guarded Good

Vaginal flora acquired during birth Mild Good Poor (50 per cent mortality)

Group B streptococci are sensitive to penicillin. The neonate should be treated with large doses of ampicillin (200 mg./kg./day divided in six doses for infants under 7 days of age).

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Staphylococcal Infections Staphylococci may be acquired from the patients' nasopharyngeal flora, or from the physicians and nursing staff in attendance. Hospital workers have a high incidence (approximately 40 per cent) of carriage of staphylococci in the anterior nares, the throat and the anus. Staphylococcal infections may occur in the skin, producing discrete abscess or carbuncle formation or a diffuse cellulitis. These organisms may occasionally cause endometritis or wound infections. Staphylococcal pneumonia is occasionally seen as a result of aspiration during induction of anesthesia. Treatment consists of a semisynthetic penicillin or cephalosporin since these organisms are frequently resistant to penicillin G. Among the drugs that are recommended are cefazolin (l gm. every 6 to 8 hours intravenously or intramuscularly,) nafcillin (1.5 gm. every 6 hours intravenously or intramuscularly) or oxacillin (2 gm. every 6 hours intravenously or intramuscularly). Milder cases can be treated with oral antibiotics.

Prophylactic Antibiotics The use of prophylactic antibiotics in gynecologic surgery remains a highly controversial subject. There are proponents who recommend antibiotics for uncomplicated deliveries, D&C's, and other procedures with a low incidence of infection. However, antibiotics should not be used to assuage the microbial paranoia of the surgeon, particularly in situations of low risk. Not withstanding this unbridled enthusiasm, there are recent investigations which show a definite place for preoperative antimicrobial prophylaxis in certain conditions. Vaginal hysterectomies have a high incidence of postoperative infection, varying between 25 and 40 per cent in several clinics. There is now convincing evidence that preoperative antibiotics significantly reduce the risk of vaginal cuff infections. Several prophylactic regimens have been used successfully including cephalothin, cephaloridine, clindamycin and metronidazole. A most convincing approach has been recommended by Ledger et alP Cephaloridine was administered 1 gm. intramuscularly on three occasions:' on call to the operating room, on return from the recovery room and at bedtime the evening after operation. This regimen was associated with a significant reduction in the incidence of postoperative pelvic infections. An alternative antibiotic that avoids the possibility of renal damage is cefazolin in the same doses listed for cephaloridine. Another situation that may be deserving of prophylactic antibiotics is cesarean section. This procedure is associated with a 30 to 40 per cent risk of postoperative infections. Recent studies have shown that this incidence can be reduced by approximately two thirds with the intraoperative use of a cephalosporin, in a similar regimen as suggested above.12 The "short-course" use of antibiotics in this situation carries a low risk of toxicity. It would appear that the substantial decline in postoperative sepsis justifies this prophylactic regimen.

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A balanced assessment of prophylactic antibiotics must consider the potential danger of widespread usage of these agents. These dangers are in terms of harm to the individual patient receiving the drug and harm to the hospital environment where patients are exposed to nosocomial pathogens. For these reasons, a brief, intraoperative regimen is an appealing concept, especially in situations where controlled studies have demonstrated significant reductions in septic morbidity.

REFERENCES 1. Altemeier, W. A.: The anaerobic streptococci in tubo-ovarian abscess. Amer. J. Obstet. Gynecol., 39:1038,1940. 2. Barnes, A. B., and Ulfelder, H.: Septic abortion. J.A.M.A.,189:919, 1964. 3. Carter, B., Jones, C. P., Ross, R. A., et al.: A bacteriologic and clinical study of pyometra. Amer. J. Obstet. Gynecol., 62:793, 1951. 4. Chow, A. W., Marshall, J. R., and Guze, L. B.: Anaerobic infections of the female genital tract. Prospects and perspectives. Surg. Gynecol. Obstet., in press. 5. Chow, A. W., and Guze, L. B.: Bacteroidaceae bacteremia: Clinical experience with 112 patients. Medicine, 53:93,1974. 6. Gorbach, S. L., and Bartlett, J. G.: Medical progress: Anaerobic infections. New Engl. J. Med., 290:1177,1237,1289,1974. 7. Gorbach, S. L., Menda, K. B., Thadepalli, H., et al.: Anaerobic microflora of the cervix in healthy women. Amer. J. Obstet. Gynecol., 117:1053,1973. 8. Josey, W. E., and Staggers, S. R., Jr.: Heparin therapy in septic pelvic thrombophlebitis: A study of 46 cases. Amer. J. Obstet. Gynecol., 120:228,1974. 9. Ledger, W. J.: Infections in obstetrics and gynecology. New developments in treatment. SURG. CLIN. N. AMER., 52:1447,1972. 10. Ledger, W. J., Norma, M., Gee, C., and Lewis, W.: Bacteremia on an obstetric-gynecologic service. Amer. J. Obstet. Gynecol., 121 :205,1975. 11. Ledger, W. J., Sweet, R. L., and Headington, J. T.: Prophylactic cephaloridine in the prevention of postoperative pelvic infections in premenopausal women undergoing vaginal hysterectomy. Amer. J. Obstet. Gynecol., 115:766,1973. 12. Moro, M., and Andrews, M.: Prophylactic antibiotics in Cesarean section. Obstet. Gynecol., 44:688,1974. 13. Parker, R. T., Jones, C. P.: Anaerobic pelvic infections and developments in hyperbaric oxygen therapy. Amer. J. Obstet. Gynecol., 96:645,1966. 14. Swenson, R. M., Michaelson, T. C., Daly, M. J., et al.: Anaerobic bacterial infections of the female genital tract. Obstet. Gynecol., 42:538,1973. 15. Swenson, R. M., Michaelson, T. C., Daly, M. C., and Spalding, E. H.: Clindamycin in infections of the female genital tract. Obstet. Gynecol., 44:699,1974. 16. Thadepalli, H., Gorbach, S. L., Keith, L.: Anaerobic infections of the female genital tract: bacteriologic and therapeutic aspects. Amer. J. Obstet. Gynecol., 117:1034, 1973. 17. Wilkowske, C. J., and Hermans, P. E.: Antimicrobial agents in the treatment of obstetric and gynecologic infections. Med. Clin. N. Amer., 58:711,1974. 18. Willson, J. R., and Black, J. R., III: Ovarian abscess. Amer. J. Obstet. Gynecol., 90:34, 1964. Infectious Disease Section Tufts-New England Medical Center 171 Harrison Avenue Boston, Massachusetts 02111