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Infections complicating low-risk cesarean sections in community hospitals: Efficacy of antimicrobial prophylaxis
Infections complicating low-risk cesarean sections in community hospitals: Efficacy of antimicrobial prophylaxis N. Joel Ehrenkranz, MD, William C. Blackwelder, PhD, Sandra J. Pfaff, BSN, Dolores Poppe, RRA, Diane E. Yerg, MA, MSPH, and Richard A. Kaslow, MD South Miami, Florida, and Bethesda, Maryland A prospective study of women with low-risk cesarean sections was conducted in four community hospitals to determine the frequency of postoperative infections and identify factors predisposing to endometritis and wound infection. Low-risk cesarean section was defined as a scheduled procedure without an urgent indication, with any duration of ruptured membranes being'" 12 hours. In a cohort of 1863 patients, 26 (1.4%) developed endometritis and 21 (1 .1%) had wound infections. Primary cesarean section was associated with endometritis in the cohort (p < 0.01) and in a retrospective study with the same cases as in the cohort (p = 0.01). Absence of antibiotic prophylaxis was associated with endometritis (p '" 0.013) or endometritis with wound infection (p < 0.01) in both studies. Without prophylaxis 37 such infections occurred in 957 (3.7%) women; with prophylaxis eight infections occurred in 906 (0.9%) women. Routine timely antibiotic prophylaxis in low-risk cesarean sections could lead to an annual national savings of approximately $9 million. (AM J OBSTET GVNECOL 1990;162:337-43.)
Key words: Prevention of infection after low-risk cesarean sections; cesarean sections and antibiotic prophylaxis; endometritis and wound infections after cesarean sections; risk factors for infection after cesarean sections; cesarean sections in community hospitals
Cesarean section is the most common operation performed among inpatients in United States hospitals; a total of 851,000 live births was estimated to have taken place by cesarean delivery in 1985 .' In the United States the rate of cesarean section has increased fivefold between 1965 and 1985; worldwide, there is also a trend to increased cesarean delivery." Major postoperative infectious complications such as endometritis and wound infection are important causes of maternal morbidity. Various factors have been identified as predisposing to such serious postoperative infections in women at high risk in municipal and referral hospitals;'"' and routine antibiotic prophylaxis has been generally advised for this population. 3 • 6 However, little is known of the factors associated with infection among women at low risk of infection who are delivered in community hospitals, where the vast majority of cesarean sections are performed . In contrast to recommendations for women at high risk of infection, antibiotic prophylaxis is not suggested for those considel'ed to be at low risk' 5 in view From the Florida ConsortIum for Infection Control and the NatIOnal Institute of Allergy and InfectIOUS DISeases. The study was supported In part by the Wreath of Honm' Program. Presented in part at the Twent.v-seventh Interscience Conference on Antl11!1crobzal Agents and Chemothemp.v. October 4-7. 1987. New York, New York. Received for publicatIOn june 7. 1989; revISed August 8. 1989; accepted September 12, 1989. Reprint requests: N. J. Ehrenkranz, MD , 5901 S. W. 74th SI .. Suite 300, South Mzami. FL 33143 .
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of the absence of demonstrated benefits of such antibiotic usage and the hazards of side effects, notably severe diarrhea. 7 " The present study was carried out during 1980 to 1982 in women undergoing cesarean section who were regarded to be at low risk for infection and who were delivered at four member hospitals of the Florida Consortium for Infection Control, an organization of community hospitals devoted to improving quality of medical care by control of nosocomial infections! Each participating hospital had been a consortium member since 1975 and had attained a stable low level of postoperative infections with no outbreaks detected by methodical surveillance. '0 There were three study objectives: (1) to measure the frequency of infections complicating low-risk cesarean sections in women in community hospitals, (2) to determine the host and operative risk factors predisposing to endometritis and wound infection in this population, and (3) to explore the efficacy of antibiotic prophylaxis as used by attending obstetricians. Certain factors were studied prospectively in all patients. A case-control study was then done to provide an analysis of additional host, therapeutic, and operative factors.
Methods Participating hospitals had 350 to 600 licensed beds. No hospital served as a referral center for management of high-risk patients or as an obstetric training program. All physicians who performed cesarean sections
337
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Ehrenkranz et al.
were certified by the America n Board of Obstetrics and Gynecology or were eligible to be certified. Infection surveillance was done by experienced infection control practitioners who were registered nurses. Surveillance was conducted as previously described.g · IO Patients in the cohort were selected by regular review of the operating schedule by the infection control practitioners and were entered into surveillance before identification of postoperative infection by infection control practitioners. Women with cesarean sections were prospectively surveyed starting in the early postoperative period, except at irregularly occurring times when unrelated infection control duties, vacations, or other similar events precluded routine surveillance. In three hospitals with two infection control practitioners, cesarean section surveillance was done virtually without interruption. The infection control practitioners used a data collection form to record observations. One of us (S. J. P.) conducted educational programs at 3- to 4-month intervals to ensure accurate surveillance and record keeping and also reviewed all forms on completion. Site inspections of individual hospital obstetric facilities were generally carried out twice yearly by consortium consulting physicians and nurses, and during these times surveillance techniques of the infection control practitioners were reviewed to ensure consistency. Patients with low-risk cesarean section were selected as follows: (I) Infection control practitioners identified the operation on the operating schedule as a routine procedure and not as an "add-on" or emergency procedure; (2) rupture of maternal membranes, if present, had not occurred more than 12 hours before incision. Patients were excluded from the low-risk category if the cesarean section was done because of an urgent indication such as fetal distress, eclampsia, preeclampsia with maternal distress, prolapsed umbilical cord, or abruptio placentae with heavy or continuous vaginal bleeding. Women who had mild vaginal bleeding or were in early labor were not excluded. When application of criteria was not clear to the infection control practitioners, one of us (S. J. P.) made the final decision by telephone consultation. When there was a conflict in the medical record about the time of membrane rupture between the patient's initial history and the information recorded in the cesarean section operative form and the conflict could not be resolved by discussion with the patient or physician, the information recorded in the initial history was accepted as being correct. Information recorded by the infection control practitioners included patient's age, date of hospital admission, date of operation, cesarean section being done as a primary or repeat procedure, presence of infection
February 1990 Am J Obstet Gynecol
at a nonoperative site (remote infection), perioperative antibiotic usage, diabetes mellitus requiring insulin treatment, and body weight exceeding the ideal for height and weight, according to 1959 Metropolitan Life Insurance tables. ll Antibiotics administered up to 24 hours before operation, during operation, or after operation during recovery from anesthesia were regarded as having been given for the purpose of antimicrobial prophylaxis. Generally accepted criteria for postoperative infections were used l2 : bacteremia-one blood culture yielding bacteria, drawn at a time of new unexplained fever (temperature > 100.6° F [38.1° C] orally or > 101 F [38.3° C] rectally) or two blood cultures from separate venipunctures yielding the same bacteria; endometritis-either fever and purulent discharge from the uterus or fever and physician-documented uterine tenderness; wound infection-purulent discharge or extensive cellulitis in the surgical wound ; lower respiratory infection-fever and purulent sputum or fever and new chest x-ray findings compatible with respiratory infection; severe diarrhea or gastroenteritis-five or more bowel movements per day for >3 days or attending physician's diagnosis; new urinary tract infection-new manifestation of pyuria (> 10 white blood cells per high-power urine field) or bacteriuria (;a: 10' colony-forming units of bacteria per milliliter). New urinary tract infections were further classified as either asymptomatic or symptomatic (associated with fever and/or symptoms of urinary tract inflammation). Infections first evident after the patient's discharge and requiring readmission to the same hospital were recorded. Information about infections in study patients that resulted in admission to other Dade County hospitals was provided by the nosocomial infection reporting network of the Dade County chapter of the Association for Practitioners in Infection Control. A case-control study was carried out by retrieving medical records of all except two women with prospectively identified endometritis and/ or wound infection; for each case, medical records of three control patients lacking these infections were retrieved. Cases and controls were matched by hospital and time of operation. Controls were the three patients in whom low-risk cesarean sections were done immediately before, immediately after, and next closest in time (either before or after) to the case. Since patient identification was removed after verification of data for the cohort analysis, it is possible that a small proportion of control cesarean sections were not in the original cohort. The information sought included: height and weight on admission, the number of out-patient prenatal visits, the number of vaginal examinations after admission, use 0
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339
Table I. Potential risk factors: endometritis and wound infection complicating low-risk cesarean sections performed in four community hospitals: cohort study, 1980 to 1982 Endometnt1S*
Age (yr)
:s19 20-35 > 35
Days from admission
0 1
to
operation
~2
Primary cesarean section Repeat cesarean section Diabetes mellitus Absent Present Any obesity Absent Present Remote infection Absent Present Antibiotic prophylaxis Absent Present
Wound mfectlOn
p Value
No. of ca.\el
<0.001
0 20
No of ;ubJects
No. of
85 1647 129
5 18 3
5.9
998 787 78 1082 781
18 8 0 23 3
1.8 1.0
1848 15
26 0
1.4
21 0
l.l
1558 305
23 3
1.5 1.0
18 3
1.2 1.0
1673 190
22 4
1.3 2.1
20 1
1.2 0.5
957 906
20 6
2.1 0.7
19 2
2.0 0.2
eme.1
I
'if
I
l.l
:sO.05
2.3
2.1 0.4
I
12 8 0.002
0.009
I
13 8
I
%
I
p Value :s0.05
1.2 0.8 1.2 1.0 1.3 1.2 1.0
<0.001
*Two persons had both endometritis and wound infection.
and duration of intrauterine monitor, prior amniocentesis, preoperative and postoperative packed red blood cell volume (hematocrit) and hemoglobin levels, general or spinal anesthesia, presence and duration of labor, occurrence and duration of rupture of membranes, infant birth weight, and exact time of perioperative antibiotic usage in relation to the surgical incision. Body mass index was calculated as weight in pounds divided by the square of height in inches . Timely antibiotic prophylaxis, as modified from Burke,1 3 was defined as administration of antibiotics at any time fwm 2 hours before skin incision through 4 hours after incision. For the cohort data, association of possible risk factors with endometritis or wound infection was determined by the usual contingency table X2 statistic for heterogeneity or Fisher's exact test, as appropriate. H Logistic regression was used to assess effects of several characteristics simultaneously. " For each case-control comparison an odds ratio was estimated and its significance evaluated by methods appropriate for matched data. 15 Conditional logistic regression for matched data " was used to calculate approximate confidence intervals for odds ratios of individual variables and also to assess the association of several characteristics simultaneously with endometritis and/or wound infection. Mean lengths of stay were compared by a normal test (difference in means divided by standard deviation
of difference) without regard to matching. In describing results, we have taken p < 0.05 as an indication of statistical significance, without regard to the multiplicity of analyses done. Results
There were 23,105 deliveries performed during 1980 to 1982, of which 7311 (31.6%) were by cesarean section. Among women with cesarean sections, 1863 (25 .5%) were identified as low risk and were prospectively surveyed. Antibiotic prophylaxis was administered to 906 (49%) of the women in the cohort. Severe diarrhea-gastroenteritis did not occur after operation in any women who received prophylactic antibiotics but did occur in one who did not receive antibiotics. Twenty-six (1.4%) patients had endometritis and 21 (1.1%) had wound infection; two women had both infections. Eleven women (0.6%) had new symptomatic urinary tract infection, 36 (1.9%) had new asymptomatic urinary tract infection, and two (0.1 %) had lower respiratory tract infection. Bacteremia was identified in four women (0.2%); iIi one of them Escherichia coli bacteremia was a primary event with no evident source, in one Peptostreptococcus bacteremia was associated with endometritis, and in two bacteremia complicated symptomatic urinary tract infection (one caused by Staphylococcus aureus and the other by an unidentified gramnegative bacillus). A total of 94 women (5.0%) had at
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Table II. Potential risk factors for endometritis and wound infection complicating low-risk cesarean sections performed in four community hospitals: case-control study, 1980 to 1982 E ndornetritlS
RISk factor
Age $, 19 yr >35 yr Primary cesarean section Not married Not white Self-pay $, 7 Prenatal visits Body mass index >0.045 Preoperative hematocrit $,35% Postoperative hematocrit $,35% Any labor Labor >5 hr Artificial rupture of membranes ~3 Vaginal examinations No intrauterine monitor General anesthesia Operation length >90 min No timely antibiotic prophylaxis No timely antibiotic prophylaxis, primary cases and their primary controls
Odds ratio
95 % Confidence interval
3.4 7.2 4.5
0.89-12 .7 0.73-72.0 1.2-16.1
5.2 2.1 2.5 0.37t 1.8
0.92-28.8 0.60-7.6 0.52-12.3 0. 10-1.4 0.51-6.1
1.2
Endometrztv. and/or wound mfection
Wound infection
p
Value $,0.05
Odds ratIO
95 % Confidence interval
0.014
0 3.0 0.61
p
Value $,0.05
P
Odds ratio
95 % Confidence Interval
Value $,0.05
-* 0.19-48.0 0.20-1.9
2.3 5.2
I.7
0 6. 8-7.5 0 9. 2-28 .8 0.77-3.6
0 0. 39
3.0 1.7 2.4 l.lt 3.9
0.19-48.0 0.23-13.2 0.46-12.5 0.31-3.6 0.91-17.0
4.5 2.0 2.1 0.64t 2.5
1.0-18.9 0.68-5.9 0.66-6.8 0.26-1.5 0.97-6.3
0.48-3.3
1.8
0.60-5.2
1.3
0.63-2.8
3.0
0.82-10.9
1.9
0.58-6.5
2. 1
0.87-5. 1
7.7t 2.5t 0.61
0.89-65.9 0.60-10.6 0.25-1.5
0.034
1.7t 1.3t 0.55
0.37-7.9 0.32-5.1 0.19-1.6
3.2t 1.8t 0.58
0.98-10.5 0.67-4.8 0.29-1.2
3.1
1.0-9.7
0.038
1.5
0.34-6.8
2.2
0.89-5.7
1.2
0.38-3.7
1.6
0.33-7.4
1.4
0.54-3.6
1.4 1.0
0.49-4.2 0.41-2.5
1.2 2.2
0.39-3.4 0.65-7.5
1.2
0.54-2.5 0.55-2.4
3.2
0.66-15.4
0.039
4.5
1.3-16.2
0.013
5.2
l,4-18.7
0.006
0.050
1.1
0.13
3.7
NO
1.4-10.0
0.028
0.046
0.007
NO
ND, Not done. *Not calculated because of small numbers. tOata missing for at least 25% of individuals. tBody mass index = Weight (lbs) / Height' (in); body mass index > 0.045 indicates top quartile.
least one infection after operation. The factors that significantly correlated with endometritis were age ~ 19 years, primary cesarean section, and antibiotic prophylaxis (Table I). Only antibiotic prophylaxis was significantly related to wound infection. In the absence of antibiotic prophylaxis the frequency of endometritis and/or wound infection was 3.9% (37 occurrences in 957 patients), whereas in association with antibiotic prophylaxis the frequency was 0.9% (eight occurrences in 906 patients). In a multiple logistic regression analysis , age ~ 19 years, primary cesarean section, and antibiotic prophylaxis remained significantly associated with increased risk of endometritis. Host and therapeutic risk factors associated with endometritis and wound infection were further evaluated
in a case-control study comparing 43 infected cases (26 occurrences of endometritis and 19 of wound infection, including two women with both infections) and 129 matched controls (Table II). Because of small numbers of women with prior amniocentesis or babies with birth weight <2500 or >4500 gm, these factors are not included in the analysis. Significant correlations were found between increased risk of endometritis and being in labor (odds ratio = 7.7), being unmarried (odds ratio = 5.2), lack of timely prophylaxis (odds ratio = 4.5), primary cesarean section (odds ratio = 4.5), and having three or more vaginal examinations (odds ratio = 3.1). Lack of timely antibiotic prophylaxis was also significant in an analysis restricted to cases of primary cesarean section and their primary controls (odds
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Volume 162 l'\umber 2
ratio = 5.2). There were only five women age ",; 19 years with endometritis in the case-control study and the association with this factor was not significant (odds ratio = 3.4). The single significant risk factor for wound infection was body mass index >0.045 (corresponding to the upper quartile for cases and controls combined). For both infections combined, the significant risk factors were age >35 years (odds ratio = 5.2), being unmarried (odds ratio = 4.5), lack of timely antibiotic prophylaxis (odds ratio = 3.7), and being in labor (odds ratio = 3.2); information on labor, however, was not available for 30% of the women in the case-control evaluation. The mean duration of hospitalization for endometritis and / or wound infection cases was 8.8 days, compared with 5.0 for controls (P < 0.05). There was no significant difference in the mean length of stay between endometritis (8.4 days) and wound infection (9.9 days) cases. In a conditional logistic regression analysis of multiple possible risk factors, timely antibiotic prophylaxis remained significantly associated with all endometritis, endometritis complicating primary cesarean section, and all endometritis and wound infection taken together as a group, but it was not significantly correlated with wound infection alone. Primary cesarean section remained a significant risk factor for endometritis. For endometritis and wound infection combined, age > 35 and being unmarried were significant factors. Although 49% of the cohort did receive some perioperative antibiotic prophylaxis,. timely antibiotic usage appears to have been less frequent. In the case-control study the proportion of women with endometritis and/or wound infection receiving timely prophylaxis was 11.6% (5 of 43), and the proportion of controls was 33.9% (43 of 127). To estimate the potential savings resulting from routine timely antibiotic prophylaxis of low-risk cesarean sections in the United States at a time when 1 million cesarean sections will be performed annually, calculations were made on the basis of these assumptions: (1) There will be 25% (as in our experience) or 250,000 women having low-risk cesarean sections, 66% (as in our experience) of whom or 165,000 women do not receive timely antibiotic prophylaxis; (2) three 1 gm doses of cefazolin are effective in preventing endometritis or wound infection in low-risk cesarean sections, as is the case for nonelective cesarean sections," at a total cost including administration of $18; (3) the side effects of the cefazolin treatment are negligible in cost; (4) the excess length of hospitalization for endometritis or wound infection is 3.8 days (8.8 to 5.0 days); (5) the odds ratio for endometritis-wound infection without timely prophylaxis is 3.7 (Table II); (6) the combined endometritis-wound infection rate without antibiotic prophylaxis is 3.9%; (7) the daily cost of man-
341
agement of postoperative endometritis or wound infection is $540 per day (derived from 1981 daily hospitalization costs for urban hospitals 1fi adjusted to 1986 17 plus $25 daily physician charges). From the odds ratio of 3.7 and risk of endometritis or wound infection without antibiotic prophylaxis of 3.9%, we estimate the risk of these infections with timely antibiotic prophylaxis to be 1.1 %. The excess hospitalization for patients without timely antibiotic prophylaxis is then estimated to be (0.039 - 0.011) x 3.8 days = 0.106 days. Multiplying 0.106 days by $522 ($540 - $18) for daily costs by 165,000 women results in an estimate of national annual health-care savings of some $9,100,000. This may well be a conservative estimate, since it does not include consideration of additional costs for infant care necessitated by maternal hospitalization consequent to infection or the costs of malpractice litigation. Even if we use a minimal estimate of 1.4 for odds ratio (lower confidence limit from Table II), we estimate annual savings to be approximately $3,600,000. If there is no benefit from such antibiotic usage, the additional healthcare costs would be $18 x 165,000 women = $2,970,000. If cefazolin were equally effective in a single preoperative dose, the projected annual savings would be $9,400,000, the low estimate would be $3,700,000, and the additional costs in the event of no benefit would be $990,000. Comment
We believe our data closely reflect the actual experience of women who had a cesarean section in these four Florida community hospitals in 1980 to 1982. The infection control practitioners selected patients lacking an urgent indication for cesarean section from the routine operating schedule and excluded only those women with rupture of membranes> 12 hours before incision. Prospective surveillance was interrupted infrequently and randomly, because of events such as investigation of unrelated outbreaks or vacations. In three hospitals the presence of two infection control practitioners permitted almost continuous surveillance. Of 23,105 infants born at these hospitals during the observation period, 31.6% were delivered by cesarean section. This figure is considerably higher than the 1985 United States rate of cesarean delivery of 22.7%1; however, it is consistent with a higher cesarean section frequency reported in the southern United States!S and in one study conducted in a private setting. 14 It is noteworthy that serious postoperative infections in our sample of 1863 women were uncommon. The finding of an overall infection rate of 5.0% in these Florida community hospital patients is in keeping with the low rate of 4.1 % reported in 659 nonindigent Swedish women with low-risk elective cesarean sections. 1 Our study is
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Ehrenkranz et al.
by far the largest of this type yet reported and permits a meaningful description of infection rates complicating an operation associated with a low risk of infection. In both the cohort and case-control studies, primary cesarean section was a significant risk factor for endometritis. This association was noted previously'" 5 Age ~ 19 years was significantly associated with endometritis in the cohort study but not in the case-control evaluation. The odds ratio of 3.4 for the association of age ~ 19 and endometritis in the case-control study, although not statistically significant, is consistent with the finding in the cohort study. Factors not examined in the cohort study that were significantly related to endometritis in the case-control study included being unmarried and having three or more vaginal examinations. Being in labor also was a significant factor for endometritis in the case-control study; however, the lack of any information on labor in 30% of reviewed medical records raises some doubt about the validity of this relationship. No host factor was significantly associated with wound infection in either cohort or casecontrol study. The standard method of evaluating efficacy of antibiotic prophylaxis is a placebo-controlled double-blind study. However, the large population required for a meaningful study of low-risk cesarean sections discourages such an undertaking without some preliminary indication of potential value. The case-control method has been used previously to estimate the clinical efficacy of vaccines!O Lack of antibiotic prophylaxis in the cohort study and lack of timely antibiotic prophylaxis in the case-control study were significantly associated with an increased frequency of endometritis, and in the cohort study lack of antibiotic prophylaxis was associated with wound infection. Both the cohort and case-control findings indicate that prophylactic antibiotic usage might be associated with a 70% to 75% reduction of risk of either endometritis or wound infection (Tables I and II). The trend in the case-control study toward efficacy of timely antibiotic prophylaxis in preventing wound infection (odds ratio = 3.2), even though not statistically significant, is consistent with the finding in the cohort study and the finding for endometritis. As in any non randomized study some sort of bias may have influenced our results. However, it seems highly improbable that obstetricians would have deliberately withheld prophylaxis in anticipation of serious infection. Thus the possibility of that sort of selection bias seems remote. We believe consistency of findings in the cohort and case-control studies provides substantial evidence that antibiotic prophylaxis is, in fact, effective in preventing endometritis or wound infection after low-risk cesarean sections. This is in keeping with the observations of efficacy of antibiotic prophylaxis in preventing these infections in high-risk patients. 3 . 6
February 1990 Am J Obstet Gynecol
Despite the large number of women treated with prophylactic antibiotics, none was recorded as having severe diarrhea. Indeed, the only person who had diarrhea-gastroenteritis did not receive an antibiotic. If our findings and assumptions are correct, as the number of cesarean sections in the United States reaches 1 million annually, the benefits from routine administration of no more than three 1 gm doses of cefazolin to prevent serious postoperative infectious morbidity in women with low-risk cesarean sections will be in the range of $9 million. This figure does not include considerations of additional costs for infant care and medicolegal actions. In summary, we found that community hospital obstetricians administered antimicrobial prophylaxis to approximately half of their patients with low-risk cesarean sections, yet in many instances prophylaxis was not properly timed. Timely antimicrobial prophylaxis appears to prevent certain important postoperative infections and to be cost-effective. Further, it is unlikely that experimental studies of antimicrobial prophylaxis in low-risk cesarean sections will be forthcoming soon, if ever. On the basis of these observations and the current unavailability of experimental data, we advocate use of brief timely antimicrobial prophylaxis for all cesarean sections as a routine. We acknowledge the help of Elizabeth Mazzei, RN, Pamela Phillips, RN, Barbara Terry, RN, Barbara Russell, RN, and Martha Unger, RN, in conducting the study. We are grateful to William Ledger, MD, for advice. REFERENCES 1. Taffel SM, Placek P], Liss T. Trends in the United States cesarean section rate and reasons for the 1980-85 rise. Am] Public Health 1985;77:955-9. 2. Notzon FC, Placek P], Taffel SM. Comparisons of national cesarean-section rates. N Engl] Med 1987;316:386-9. 3. Harger ]H, English DH. Selection of patients for antibiotic prophylaxis in cesarean sections. AM] OBSTET GvNECOL 1981;141:752-8. 4. Nielsen TF, Hokegard K-H. Postoperative cesarean section morbidity: a prospective study. AM] OBSTET GVNECOL 1983;146:911-6. 5. Hawrylyshyn PA, Bernstein P, Papsin FR. Risk factors associated with infection following cesarean section. AM] OBSTET GVNECOL 1981 ;39:294-8. 6. Stiver HG, Forward KR, Livingstone RA, et al. Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section. AM] OBSTET GVNECOL 1983; 145: 158-63. 7. Ansura EL, Fazio RA, Wickremesinghe PC. Pseudomembranous colitis following prophylactic antibiotic use in primary cesarean section. AM] OBSTET GVNECOL 1985; 151:87-9. 8. Block BS, Mercer L], Ismail MA, Moawad AH. Clostridium difficile-associated diarrhea follows perioperative prophylaxis with cefoxitin. AM] OBSTET GVNECOL 1985; 153:835-8. 9. Ehrenkranz N]. South Florida Hospital Consortium for Infection Control: structure and function. Am ] Infect Control 1987;15:36-41.
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10. Ehrenkranz NJ. The efficacy of a Florida hospital consortium for infection control. Infect Control 1986;7: 321-6. 11. Bierman EL. Obesity. In: Beeson PB, McDermott W. Wyngaarden ]B, eds. Cecil textbook of medicine. 15th ed. Philadelphia: WB Saunders, 1979: 1678-80. 12. Bennett lV, Brachman PS. Hospital infections. 1st ed. Boston: Little, Brown. 1979. 13. Burke ]F. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1961 ;50: 161-8. 14. Armitage P. Statistical methods in medical research. New York: Wiley, 1971. 15. Breslow NE, Day NE. Statistical methods in cancer research. The analysis of case-control studies. Lyon: International Agency for Research on Cancer, 1980, vol 1.
16. Freeman MP, Cromwell J. Reimbursement of sole community hospitals under Medicare's prospective payment system. Health Care Financ Rev 1987;9:39-54. 17. Cymer WE. Health care financing trends: update on provider input price indexes. Health Care Finane Rev 1988;9:89-94. 18. Placek Pl. Taffel SM, Moien M. Cesarean rate increases in 1985 [Letter]. Am] Pub Health 1987;77:241-2. 19. de Reget RH, Minkoff HL, Feldman], Schwarz RH. Relation of private or clinic care to the cesarean birth rate. N Engl] Med 1986;315:619-24. 20. Shapiro ED. Murphy TV, Wald ER, Brady CA. The protective efficacy of Hemophzlus b polysaccharide vaccine. ]AMA 1988;260:1419-22.
Clindamycin therapy for Chlamydia trachomatis in women William F. Campbell, PhD, and Melvin G. Dodson, MD, PhD Johnson City, Tennessee The population for this study consisted of 4013 sexually active women seen for family planning. Culture for Chlamydia trachomatis yielded an isolation rate of 6.1%. Women aged 16 to 25 accounted for 81.7% of the C. trachoma tis infections, while those younger than 16 or older than 35 accounted for only 2.4% of the infections. Of the 246 patients whose cultures were positive for C. trachomatis, 159 (65%) were asymptomatic. The incidence of C. trachomatis was 11.2% among those with symptoms but only 6.4% among the asymptomatic group. Among 63 patients with Neisseria gonorrhoeae (who were excluded from the study), 26 (41.3%) also were infected by C. trachomatis. There were no microbiologic drug failures with erythromycin or clindamycin. Of 56 patients who enrolled in the clindamycin arm of the protocol, 48 (85.7%) completed therapy and experienced microbiologic and clinical cures. In contrast, erythromycin therapy was completed by only 25 of 57 women (43.9%) enrolled. The number of side effect failures for erythromycin was 22 of 57 (38.6%). This was more than five times the number of side effect failures for clindamycin (4 of 56, or 7.1%). (AM J OSSTET GVNECOL1990;162:343-7.)
Key words: Clindamycin, erythromycin, Chlamydza trachomatis, endocervicitis
Chlamydia tmchomatis currently is the most common sexually transmitted disease in the United States I.2 and is two to five times more prevalent than Neisseria gonorrhoeae. [.ol There are an estimated 3 to 5 million new cases of C. trachomatis infection each year in the United States alone. [ The incidence of C. trachomatis in sexually active women at risk is 6% to 23%. [ I Coinfec-
From the Departments of MicrobIOlogy and Obstetncs and Gynecology, College of Medicine, ElLlt Tennessee State UnlVemty. ThIS work was supported b.V a grant from The Upjohn Company, Kalamazoo, Mlch Received for publzcatlOn May 10, 1989; reVISed July 24, 1989; accepted September 12, 1989. Repnnt reque,t.l: William F. Campbell, PhD, Department of MicrobIOlogy. College of Medicine, East Tennessee State Umversi/'V, Johnson City, TN 37614. 611116685
tion by C, trachomatis and N. gonorrhoeae is quite common; one quarter to one half of the patients with N. gonorrhoeae also are infected by C. trachomatis." The treatment of choice for C. trachomatis infection is tetracycline or its derivatives. Erythromycin is recommended as the drug of choice in patients who are intolerant or allergic to tetracycline and in pregnant patients. Considering the number of cases of C. trachomatis and the incidence of drug intolerance, contraindications, and individual allergies, the availability of alternative therapeutic modalities would be of value. Clindamycin previously has been demonstrated to have in vitro activity against C. trachomatis similar to erythromycin.' However, clinical trials have been very limited. Bowie et al. 6 reported that a 7-day clindamycin regimen of 600 mg t.i.d. was only partially effective for the treatment of chlamydial urethritis in men. Wasser-
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Key words: Prevention of infection after low-risk cesarean sections; cesarean sections and antibiotic prophylaxis; endometritis and wound infections after cesarean sections; risk factors for infection after cesarean sections; cesarean sections in community hospitals
Cesarean section is the most common operation performed among inpatients in United States hospitals; a total of 851,000 live births was estimated to have taken place by cesarean delivery in 1985 .' In the United States the rate of cesarean section has increased fivefold between 1965 and 1985; worldwide, there is also a trend to increased cesarean delivery." Major postoperative infectious complications such as endometritis and wound infection are important causes of maternal morbidity. Various factors have been identified as predisposing to such serious postoperative infections in women at high risk in municipal and referral hospitals;'"' and routine antibiotic prophylaxis has been generally advised for this population. 3 • 6 However, little is known of the factors associated with infection among women at low risk of infection who are delivered in community hospitals, where the vast majority of cesarean sections are performed . In contrast to recommendations for women at high risk of infection, antibiotic prophylaxis is not suggested for those considel'ed to be at low risk' 5 in view From the Florida ConsortIum for Infection Control and the NatIOnal Institute of Allergy and InfectIOUS DISeases. The study was supported In part by the Wreath of Honm' Program. Presented in part at the Twent.v-seventh Interscience Conference on Antl11!1crobzal Agents and Chemothemp.v. October 4-7. 1987. New York, New York. Received for publicatIOn june 7. 1989; revISed August 8. 1989; accepted September 12, 1989. Reprint requests: N. J. Ehrenkranz, MD , 5901 S. W. 74th SI .. Suite 300, South Mzami. FL 33143 .
611116686
of the absence of demonstrated benefits of such antibiotic usage and the hazards of side effects, notably severe diarrhea. 7 " The present study was carried out during 1980 to 1982 in women undergoing cesarean section who were regarded to be at low risk for infection and who were delivered at four member hospitals of the Florida Consortium for Infection Control, an organization of community hospitals devoted to improving quality of medical care by control of nosocomial infections! Each participating hospital had been a consortium member since 1975 and had attained a stable low level of postoperative infections with no outbreaks detected by methodical surveillance. '0 There were three study objectives: (1) to measure the frequency of infections complicating low-risk cesarean sections in women in community hospitals, (2) to determine the host and operative risk factors predisposing to endometritis and wound infection in this population, and (3) to explore the efficacy of antibiotic prophylaxis as used by attending obstetricians. Certain factors were studied prospectively in all patients. A case-control study was then done to provide an analysis of additional host, therapeutic, and operative factors.
Methods Participating hospitals had 350 to 600 licensed beds. No hospital served as a referral center for management of high-risk patients or as an obstetric training program. All physicians who performed cesarean sections
337
338
Ehrenkranz et al.
were certified by the America n Board of Obstetrics and Gynecology or were eligible to be certified. Infection surveillance was done by experienced infection control practitioners who were registered nurses. Surveillance was conducted as previously described.g · IO Patients in the cohort were selected by regular review of the operating schedule by the infection control practitioners and were entered into surveillance before identification of postoperative infection by infection control practitioners. Women with cesarean sections were prospectively surveyed starting in the early postoperative period, except at irregularly occurring times when unrelated infection control duties, vacations, or other similar events precluded routine surveillance. In three hospitals with two infection control practitioners, cesarean section surveillance was done virtually without interruption. The infection control practitioners used a data collection form to record observations. One of us (S. J. P.) conducted educational programs at 3- to 4-month intervals to ensure accurate surveillance and record keeping and also reviewed all forms on completion. Site inspections of individual hospital obstetric facilities were generally carried out twice yearly by consortium consulting physicians and nurses, and during these times surveillance techniques of the infection control practitioners were reviewed to ensure consistency. Patients with low-risk cesarean section were selected as follows: (I) Infection control practitioners identified the operation on the operating schedule as a routine procedure and not as an "add-on" or emergency procedure; (2) rupture of maternal membranes, if present, had not occurred more than 12 hours before incision. Patients were excluded from the low-risk category if the cesarean section was done because of an urgent indication such as fetal distress, eclampsia, preeclampsia with maternal distress, prolapsed umbilical cord, or abruptio placentae with heavy or continuous vaginal bleeding. Women who had mild vaginal bleeding or were in early labor were not excluded. When application of criteria was not clear to the infection control practitioners, one of us (S. J. P.) made the final decision by telephone consultation. When there was a conflict in the medical record about the time of membrane rupture between the patient's initial history and the information recorded in the cesarean section operative form and the conflict could not be resolved by discussion with the patient or physician, the information recorded in the initial history was accepted as being correct. Information recorded by the infection control practitioners included patient's age, date of hospital admission, date of operation, cesarean section being done as a primary or repeat procedure, presence of infection
February 1990 Am J Obstet Gynecol
at a nonoperative site (remote infection), perioperative antibiotic usage, diabetes mellitus requiring insulin treatment, and body weight exceeding the ideal for height and weight, according to 1959 Metropolitan Life Insurance tables. ll Antibiotics administered up to 24 hours before operation, during operation, or after operation during recovery from anesthesia were regarded as having been given for the purpose of antimicrobial prophylaxis. Generally accepted criteria for postoperative infections were used l2 : bacteremia-one blood culture yielding bacteria, drawn at a time of new unexplained fever (temperature > 100.6° F [38.1° C] orally or > 101 F [38.3° C] rectally) or two blood cultures from separate venipunctures yielding the same bacteria; endometritis-either fever and purulent discharge from the uterus or fever and physician-documented uterine tenderness; wound infection-purulent discharge or extensive cellulitis in the surgical wound ; lower respiratory infection-fever and purulent sputum or fever and new chest x-ray findings compatible with respiratory infection; severe diarrhea or gastroenteritis-five or more bowel movements per day for >3 days or attending physician's diagnosis; new urinary tract infection-new manifestation of pyuria (> 10 white blood cells per high-power urine field) or bacteriuria (;a: 10' colony-forming units of bacteria per milliliter). New urinary tract infections were further classified as either asymptomatic or symptomatic (associated with fever and/or symptoms of urinary tract inflammation). Infections first evident after the patient's discharge and requiring readmission to the same hospital were recorded. Information about infections in study patients that resulted in admission to other Dade County hospitals was provided by the nosocomial infection reporting network of the Dade County chapter of the Association for Practitioners in Infection Control. A case-control study was carried out by retrieving medical records of all except two women with prospectively identified endometritis and/ or wound infection; for each case, medical records of three control patients lacking these infections were retrieved. Cases and controls were matched by hospital and time of operation. Controls were the three patients in whom low-risk cesarean sections were done immediately before, immediately after, and next closest in time (either before or after) to the case. Since patient identification was removed after verification of data for the cohort analysis, it is possible that a small proportion of control cesarean sections were not in the original cohort. The information sought included: height and weight on admission, the number of out-patient prenatal visits, the number of vaginal examinations after admission, use 0
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Table I. Potential risk factors: endometritis and wound infection complicating low-risk cesarean sections performed in four community hospitals: cohort study, 1980 to 1982 Endometnt1S*
Age (yr)
:s19 20-35 > 35
Days from admission
0 1
to
operation
~2
Primary cesarean section Repeat cesarean section Diabetes mellitus Absent Present Any obesity Absent Present Remote infection Absent Present Antibiotic prophylaxis Absent Present
Wound mfectlOn
p Value
No. of ca.\el
<0.001
0 20
No of ;ubJects
No. of
85 1647 129
5 18 3
5.9
998 787 78 1082 781
18 8 0 23 3
1.8 1.0
1848 15
26 0
1.4
21 0
l.l
1558 305
23 3
1.5 1.0
18 3
1.2 1.0
1673 190
22 4
1.3 2.1
20 1
1.2 0.5
957 906
20 6
2.1 0.7
19 2
2.0 0.2
eme.1
I
'if
I
l.l
:sO.05
2.3
2.1 0.4
I
12 8 0.002
0.009
I
13 8
I
%
I
p Value :s0.05
1.2 0.8 1.2 1.0 1.3 1.2 1.0
<0.001
*Two persons had both endometritis and wound infection.
and duration of intrauterine monitor, prior amniocentesis, preoperative and postoperative packed red blood cell volume (hematocrit) and hemoglobin levels, general or spinal anesthesia, presence and duration of labor, occurrence and duration of rupture of membranes, infant birth weight, and exact time of perioperative antibiotic usage in relation to the surgical incision. Body mass index was calculated as weight in pounds divided by the square of height in inches . Timely antibiotic prophylaxis, as modified from Burke,1 3 was defined as administration of antibiotics at any time fwm 2 hours before skin incision through 4 hours after incision. For the cohort data, association of possible risk factors with endometritis or wound infection was determined by the usual contingency table X2 statistic for heterogeneity or Fisher's exact test, as appropriate. H Logistic regression was used to assess effects of several characteristics simultaneously. " For each case-control comparison an odds ratio was estimated and its significance evaluated by methods appropriate for matched data. 15 Conditional logistic regression for matched data " was used to calculate approximate confidence intervals for odds ratios of individual variables and also to assess the association of several characteristics simultaneously with endometritis and/or wound infection. Mean lengths of stay were compared by a normal test (difference in means divided by standard deviation
of difference) without regard to matching. In describing results, we have taken p < 0.05 as an indication of statistical significance, without regard to the multiplicity of analyses done. Results
There were 23,105 deliveries performed during 1980 to 1982, of which 7311 (31.6%) were by cesarean section. Among women with cesarean sections, 1863 (25 .5%) were identified as low risk and were prospectively surveyed. Antibiotic prophylaxis was administered to 906 (49%) of the women in the cohort. Severe diarrhea-gastroenteritis did not occur after operation in any women who received prophylactic antibiotics but did occur in one who did not receive antibiotics. Twenty-six (1.4%) patients had endometritis and 21 (1.1%) had wound infection; two women had both infections. Eleven women (0.6%) had new symptomatic urinary tract infection, 36 (1.9%) had new asymptomatic urinary tract infection, and two (0.1 %) had lower respiratory tract infection. Bacteremia was identified in four women (0.2%); iIi one of them Escherichia coli bacteremia was a primary event with no evident source, in one Peptostreptococcus bacteremia was associated with endometritis, and in two bacteremia complicated symptomatic urinary tract infection (one caused by Staphylococcus aureus and the other by an unidentified gramnegative bacillus). A total of 94 women (5.0%) had at
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February 1990 Am J Obslet Gynecol
Table II. Potential risk factors for endometritis and wound infection complicating low-risk cesarean sections performed in four community hospitals: case-control study, 1980 to 1982 E ndornetritlS
RISk factor
Age $, 19 yr >35 yr Primary cesarean section Not married Not white Self-pay $, 7 Prenatal visits Body mass index >0.045 Preoperative hematocrit $,35% Postoperative hematocrit $,35% Any labor Labor >5 hr Artificial rupture of membranes ~3 Vaginal examinations No intrauterine monitor General anesthesia Operation length >90 min No timely antibiotic prophylaxis No timely antibiotic prophylaxis, primary cases and their primary controls
Odds ratio
95 % Confidence interval
3.4 7.2 4.5
0.89-12 .7 0.73-72.0 1.2-16.1
5.2 2.1 2.5 0.37t 1.8
0.92-28.8 0.60-7.6 0.52-12.3 0. 10-1.4 0.51-6.1
1.2
Endometrztv. and/or wound mfection
Wound infection
p
Value $,0.05
Odds ratIO
95 % Confidence interval
0.014
0 3.0 0.61
p
Value $,0.05
P
Odds ratio
95 % Confidence Interval
Value $,0.05
-* 0.19-48.0 0.20-1.9
2.3 5.2
I.7
0 6. 8-7.5 0 9. 2-28 .8 0.77-3.6
0 0. 39
3.0 1.7 2.4 l.lt 3.9
0.19-48.0 0.23-13.2 0.46-12.5 0.31-3.6 0.91-17.0
4.5 2.0 2.1 0.64t 2.5
1.0-18.9 0.68-5.9 0.66-6.8 0.26-1.5 0.97-6.3
0.48-3.3
1.8
0.60-5.2
1.3
0.63-2.8
3.0
0.82-10.9
1.9
0.58-6.5
2. 1
0.87-5. 1
7.7t 2.5t 0.61
0.89-65.9 0.60-10.6 0.25-1.5
0.034
1.7t 1.3t 0.55
0.37-7.9 0.32-5.1 0.19-1.6
3.2t 1.8t 0.58
0.98-10.5 0.67-4.8 0.29-1.2
3.1
1.0-9.7
0.038
1.5
0.34-6.8
2.2
0.89-5.7
1.2
0.38-3.7
1.6
0.33-7.4
1.4
0.54-3.6
1.4 1.0
0.49-4.2 0.41-2.5
1.2 2.2
0.39-3.4 0.65-7.5
1.2
0.54-2.5 0.55-2.4
3.2
0.66-15.4
0.039
4.5
1.3-16.2
0.013
5.2
l,4-18.7
0.006
0.050
1.1
0.13
3.7
NO
1.4-10.0
0.028
0.046
0.007
NO
ND, Not done. *Not calculated because of small numbers. tOata missing for at least 25% of individuals. tBody mass index = Weight (lbs) / Height' (in); body mass index > 0.045 indicates top quartile.
least one infection after operation. The factors that significantly correlated with endometritis were age ~ 19 years, primary cesarean section, and antibiotic prophylaxis (Table I). Only antibiotic prophylaxis was significantly related to wound infection. In the absence of antibiotic prophylaxis the frequency of endometritis and/or wound infection was 3.9% (37 occurrences in 957 patients), whereas in association with antibiotic prophylaxis the frequency was 0.9% (eight occurrences in 906 patients). In a multiple logistic regression analysis , age ~ 19 years, primary cesarean section, and antibiotic prophylaxis remained significantly associated with increased risk of endometritis. Host and therapeutic risk factors associated with endometritis and wound infection were further evaluated
in a case-control study comparing 43 infected cases (26 occurrences of endometritis and 19 of wound infection, including two women with both infections) and 129 matched controls (Table II). Because of small numbers of women with prior amniocentesis or babies with birth weight <2500 or >4500 gm, these factors are not included in the analysis. Significant correlations were found between increased risk of endometritis and being in labor (odds ratio = 7.7), being unmarried (odds ratio = 5.2), lack of timely prophylaxis (odds ratio = 4.5), primary cesarean section (odds ratio = 4.5), and having three or more vaginal examinations (odds ratio = 3.1). Lack of timely antibiotic prophylaxis was also significant in an analysis restricted to cases of primary cesarean section and their primary controls (odds
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Volume 162 l'\umber 2
ratio = 5.2). There were only five women age ",; 19 years with endometritis in the case-control study and the association with this factor was not significant (odds ratio = 3.4). The single significant risk factor for wound infection was body mass index >0.045 (corresponding to the upper quartile for cases and controls combined). For both infections combined, the significant risk factors were age >35 years (odds ratio = 5.2), being unmarried (odds ratio = 4.5), lack of timely antibiotic prophylaxis (odds ratio = 3.7), and being in labor (odds ratio = 3.2); information on labor, however, was not available for 30% of the women in the case-control evaluation. The mean duration of hospitalization for endometritis and / or wound infection cases was 8.8 days, compared with 5.0 for controls (P < 0.05). There was no significant difference in the mean length of stay between endometritis (8.4 days) and wound infection (9.9 days) cases. In a conditional logistic regression analysis of multiple possible risk factors, timely antibiotic prophylaxis remained significantly associated with all endometritis, endometritis complicating primary cesarean section, and all endometritis and wound infection taken together as a group, but it was not significantly correlated with wound infection alone. Primary cesarean section remained a significant risk factor for endometritis. For endometritis and wound infection combined, age > 35 and being unmarried were significant factors. Although 49% of the cohort did receive some perioperative antibiotic prophylaxis,. timely antibiotic usage appears to have been less frequent. In the case-control study the proportion of women with endometritis and/or wound infection receiving timely prophylaxis was 11.6% (5 of 43), and the proportion of controls was 33.9% (43 of 127). To estimate the potential savings resulting from routine timely antibiotic prophylaxis of low-risk cesarean sections in the United States at a time when 1 million cesarean sections will be performed annually, calculations were made on the basis of these assumptions: (1) There will be 25% (as in our experience) or 250,000 women having low-risk cesarean sections, 66% (as in our experience) of whom or 165,000 women do not receive timely antibiotic prophylaxis; (2) three 1 gm doses of cefazolin are effective in preventing endometritis or wound infection in low-risk cesarean sections, as is the case for nonelective cesarean sections," at a total cost including administration of $18; (3) the side effects of the cefazolin treatment are negligible in cost; (4) the excess length of hospitalization for endometritis or wound infection is 3.8 days (8.8 to 5.0 days); (5) the odds ratio for endometritis-wound infection without timely prophylaxis is 3.7 (Table II); (6) the combined endometritis-wound infection rate without antibiotic prophylaxis is 3.9%; (7) the daily cost of man-
341
agement of postoperative endometritis or wound infection is $540 per day (derived from 1981 daily hospitalization costs for urban hospitals 1fi adjusted to 1986 17 plus $25 daily physician charges). From the odds ratio of 3.7 and risk of endometritis or wound infection without antibiotic prophylaxis of 3.9%, we estimate the risk of these infections with timely antibiotic prophylaxis to be 1.1 %. The excess hospitalization for patients without timely antibiotic prophylaxis is then estimated to be (0.039 - 0.011) x 3.8 days = 0.106 days. Multiplying 0.106 days by $522 ($540 - $18) for daily costs by 165,000 women results in an estimate of national annual health-care savings of some $9,100,000. This may well be a conservative estimate, since it does not include consideration of additional costs for infant care necessitated by maternal hospitalization consequent to infection or the costs of malpractice litigation. Even if we use a minimal estimate of 1.4 for odds ratio (lower confidence limit from Table II), we estimate annual savings to be approximately $3,600,000. If there is no benefit from such antibiotic usage, the additional healthcare costs would be $18 x 165,000 women = $2,970,000. If cefazolin were equally effective in a single preoperative dose, the projected annual savings would be $9,400,000, the low estimate would be $3,700,000, and the additional costs in the event of no benefit would be $990,000. Comment
We believe our data closely reflect the actual experience of women who had a cesarean section in these four Florida community hospitals in 1980 to 1982. The infection control practitioners selected patients lacking an urgent indication for cesarean section from the routine operating schedule and excluded only those women with rupture of membranes> 12 hours before incision. Prospective surveillance was interrupted infrequently and randomly, because of events such as investigation of unrelated outbreaks or vacations. In three hospitals the presence of two infection control practitioners permitted almost continuous surveillance. Of 23,105 infants born at these hospitals during the observation period, 31.6% were delivered by cesarean section. This figure is considerably higher than the 1985 United States rate of cesarean delivery of 22.7%1; however, it is consistent with a higher cesarean section frequency reported in the southern United States!S and in one study conducted in a private setting. 14 It is noteworthy that serious postoperative infections in our sample of 1863 women were uncommon. The finding of an overall infection rate of 5.0% in these Florida community hospital patients is in keeping with the low rate of 4.1 % reported in 659 nonindigent Swedish women with low-risk elective cesarean sections. 1 Our study is
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Ehrenkranz et al.
by far the largest of this type yet reported and permits a meaningful description of infection rates complicating an operation associated with a low risk of infection. In both the cohort and case-control studies, primary cesarean section was a significant risk factor for endometritis. This association was noted previously'" 5 Age ~ 19 years was significantly associated with endometritis in the cohort study but not in the case-control evaluation. The odds ratio of 3.4 for the association of age ~ 19 and endometritis in the case-control study, although not statistically significant, is consistent with the finding in the cohort study. Factors not examined in the cohort study that were significantly related to endometritis in the case-control study included being unmarried and having three or more vaginal examinations. Being in labor also was a significant factor for endometritis in the case-control study; however, the lack of any information on labor in 30% of reviewed medical records raises some doubt about the validity of this relationship. No host factor was significantly associated with wound infection in either cohort or casecontrol study. The standard method of evaluating efficacy of antibiotic prophylaxis is a placebo-controlled double-blind study. However, the large population required for a meaningful study of low-risk cesarean sections discourages such an undertaking without some preliminary indication of potential value. The case-control method has been used previously to estimate the clinical efficacy of vaccines!O Lack of antibiotic prophylaxis in the cohort study and lack of timely antibiotic prophylaxis in the case-control study were significantly associated with an increased frequency of endometritis, and in the cohort study lack of antibiotic prophylaxis was associated with wound infection. Both the cohort and case-control findings indicate that prophylactic antibiotic usage might be associated with a 70% to 75% reduction of risk of either endometritis or wound infection (Tables I and II). The trend in the case-control study toward efficacy of timely antibiotic prophylaxis in preventing wound infection (odds ratio = 3.2), even though not statistically significant, is consistent with the finding in the cohort study and the finding for endometritis. As in any non randomized study some sort of bias may have influenced our results. However, it seems highly improbable that obstetricians would have deliberately withheld prophylaxis in anticipation of serious infection. Thus the possibility of that sort of selection bias seems remote. We believe consistency of findings in the cohort and case-control studies provides substantial evidence that antibiotic prophylaxis is, in fact, effective in preventing endometritis or wound infection after low-risk cesarean sections. This is in keeping with the observations of efficacy of antibiotic prophylaxis in preventing these infections in high-risk patients. 3 . 6
February 1990 Am J Obstet Gynecol
Despite the large number of women treated with prophylactic antibiotics, none was recorded as having severe diarrhea. Indeed, the only person who had diarrhea-gastroenteritis did not receive an antibiotic. If our findings and assumptions are correct, as the number of cesarean sections in the United States reaches 1 million annually, the benefits from routine administration of no more than three 1 gm doses of cefazolin to prevent serious postoperative infectious morbidity in women with low-risk cesarean sections will be in the range of $9 million. This figure does not include considerations of additional costs for infant care and medicolegal actions. In summary, we found that community hospital obstetricians administered antimicrobial prophylaxis to approximately half of their patients with low-risk cesarean sections, yet in many instances prophylaxis was not properly timed. Timely antimicrobial prophylaxis appears to prevent certain important postoperative infections and to be cost-effective. Further, it is unlikely that experimental studies of antimicrobial prophylaxis in low-risk cesarean sections will be forthcoming soon, if ever. On the basis of these observations and the current unavailability of experimental data, we advocate use of brief timely antimicrobial prophylaxis for all cesarean sections as a routine. We acknowledge the help of Elizabeth Mazzei, RN, Pamela Phillips, RN, Barbara Terry, RN, Barbara Russell, RN, and Martha Unger, RN, in conducting the study. We are grateful to William Ledger, MD, for advice. REFERENCES 1. Taffel SM, Placek P], Liss T. Trends in the United States cesarean section rate and reasons for the 1980-85 rise. Am] Public Health 1985;77:955-9. 2. Notzon FC, Placek P], Taffel SM. Comparisons of national cesarean-section rates. N Engl] Med 1987;316:386-9. 3. Harger ]H, English DH. Selection of patients for antibiotic prophylaxis in cesarean sections. AM] OBSTET GvNECOL 1981;141:752-8. 4. Nielsen TF, Hokegard K-H. Postoperative cesarean section morbidity: a prospective study. AM] OBSTET GVNECOL 1983;146:911-6. 5. Hawrylyshyn PA, Bernstein P, Papsin FR. Risk factors associated with infection following cesarean section. AM] OBSTET GVNECOL 1981 ;39:294-8. 6. Stiver HG, Forward KR, Livingstone RA, et al. Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section. AM] OBSTET GVNECOL 1983; 145: 158-63. 7. Ansura EL, Fazio RA, Wickremesinghe PC. Pseudomembranous colitis following prophylactic antibiotic use in primary cesarean section. AM] OBSTET GVNECOL 1985; 151:87-9. 8. Block BS, Mercer L], Ismail MA, Moawad AH. Clostridium difficile-associated diarrhea follows perioperative prophylaxis with cefoxitin. AM] OBSTET GVNECOL 1985; 153:835-8. 9. Ehrenkranz N]. South Florida Hospital Consortium for Infection Control: structure and function. Am ] Infect Control 1987;15:36-41.
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10. Ehrenkranz NJ. The efficacy of a Florida hospital consortium for infection control. Infect Control 1986;7: 321-6. 11. Bierman EL. Obesity. In: Beeson PB, McDermott W. Wyngaarden ]B, eds. Cecil textbook of medicine. 15th ed. Philadelphia: WB Saunders, 1979: 1678-80. 12. Bennett lV, Brachman PS. Hospital infections. 1st ed. Boston: Little, Brown. 1979. 13. Burke ]F. The effective period of preventive antibiotic action in experimental incisions and dermal lesions. Surgery 1961 ;50: 161-8. 14. Armitage P. Statistical methods in medical research. New York: Wiley, 1971. 15. Breslow NE, Day NE. Statistical methods in cancer research. The analysis of case-control studies. Lyon: International Agency for Research on Cancer, 1980, vol 1.
16. Freeman MP, Cromwell J. Reimbursement of sole community hospitals under Medicare's prospective payment system. Health Care Financ Rev 1987;9:39-54. 17. Cymer WE. Health care financing trends: update on provider input price indexes. Health Care Finane Rev 1988;9:89-94. 18. Placek Pl. Taffel SM, Moien M. Cesarean rate increases in 1985 [Letter]. Am] Pub Health 1987;77:241-2. 19. de Reget RH, Minkoff HL, Feldman], Schwarz RH. Relation of private or clinic care to the cesarean birth rate. N Engl] Med 1986;315:619-24. 20. Shapiro ED. Murphy TV, Wald ER, Brady CA. The protective efficacy of Hemophzlus b polysaccharide vaccine. ]AMA 1988;260:1419-22.
Clindamycin therapy for Chlamydia trachomatis in women William F. Campbell, PhD, and Melvin G. Dodson, MD, PhD Johnson City, Tennessee The population for this study consisted of 4013 sexually active women seen for family planning. Culture for Chlamydia trachomatis yielded an isolation rate of 6.1%. Women aged 16 to 25 accounted for 81.7% of the C. trachoma tis infections, while those younger than 16 or older than 35 accounted for only 2.4% of the infections. Of the 246 patients whose cultures were positive for C. trachomatis, 159 (65%) were asymptomatic. The incidence of C. trachomatis was 11.2% among those with symptoms but only 6.4% among the asymptomatic group. Among 63 patients with Neisseria gonorrhoeae (who were excluded from the study), 26 (41.3%) also were infected by C. trachomatis. There were no microbiologic drug failures with erythromycin or clindamycin. Of 56 patients who enrolled in the clindamycin arm of the protocol, 48 (85.7%) completed therapy and experienced microbiologic and clinical cures. In contrast, erythromycin therapy was completed by only 25 of 57 women (43.9%) enrolled. The number of side effect failures for erythromycin was 22 of 57 (38.6%). This was more than five times the number of side effect failures for clindamycin (4 of 56, or 7.1%). (AM J OSSTET GVNECOL1990;162:343-7.)
Key words: Clindamycin, erythromycin, Chlamydza trachomatis, endocervicitis
Chlamydia tmchomatis currently is the most common sexually transmitted disease in the United States I.2 and is two to five times more prevalent than Neisseria gonorrhoeae. [.ol There are an estimated 3 to 5 million new cases of C. trachomatis infection each year in the United States alone. [ The incidence of C. trachomatis in sexually active women at risk is 6% to 23%. [ I Coinfec-
From the Departments of MicrobIOlogy and Obstetncs and Gynecology, College of Medicine, ElLlt Tennessee State UnlVemty. ThIS work was supported b.V a grant from The Upjohn Company, Kalamazoo, Mlch Received for publzcatlOn May 10, 1989; reVISed July 24, 1989; accepted September 12, 1989. Repnnt reque,t.l: William F. Campbell, PhD, Department of MicrobIOlogy. College of Medicine, East Tennessee State Umversi/'V, Johnson City, TN 37614. 611116685
tion by C, trachomatis and N. gonorrhoeae is quite common; one quarter to one half of the patients with N. gonorrhoeae also are infected by C. trachomatis." The treatment of choice for C. trachomatis infection is tetracycline or its derivatives. Erythromycin is recommended as the drug of choice in patients who are intolerant or allergic to tetracycline and in pregnant patients. Considering the number of cases of C. trachomatis and the incidence of drug intolerance, contraindications, and individual allergies, the availability of alternative therapeutic modalities would be of value. Clindamycin previously has been demonstrated to have in vitro activity against C. trachomatis similar to erythromycin.' However, clinical trials have been very limited. Bowie et al. 6 reported that a 7-day clindamycin regimen of 600 mg t.i.d. was only partially effective for the treatment of chlamydial urethritis in men. Wasser-
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