Article
The routine use of cefazolin in cesarean section
A.A. Rouzi
a,U, F. Khalifa
a, H. Ba’aqeel
b, H.S. Al-Hamdan
b, N. Bondagji
aaKing Abdulaziz Uni¨ersity Hospital, Jeddah, Saudi Arabia
bKing Khalid National Guard Hospital, Jeddah, Saudi Arabia
Received 28 July 1999; received in revised form 26 November 1999; accepted 2 December 1999
Abstract
Objecti¨e: To determine the effectiveness and safety of the routine use of antibiotic prophylaxis in women undergoing cesarean section. Method: Four hundred and forty-one women undergoing cesarean sections were randomly assigned either to a single dose of 1 g intravenous cefazolin or placebo after clamping of the umbilical cord.
The primary outcome was the development of post-operative febrile morbidity and the secondary outcomes were infection-related complications. Result: There were 211 emergency and 230 elective cesarean sections. In the
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emergency cesarean sections, 34 30.6% women developed post-operative febrile morbidity in the placebo group
Ž . Ž .
compared to 11 11% women in the cefazolin group. This was a statistically significant difference Ps0.001 . Similarly, there were statistically significant differences between the two groups in the development of wound
Ž . Ž . Ž .
infection P-0.001 , use of therapeutic antibiotics Ps0.001 , and post-operative days in hospital Ps0.003 . No statistically significant differences were detected in the development of other infection-related complications. In the elective cesarean sections, no statistically significant differences were found in post-operative febrile morbidity and infection-related complications. There were no serious side effects related to the use of cefazolin.Conclusion: The routine use of a single dose of cefazolin is safe and effective in emergency but not elective cesarean section.
䊚
2000 International Federation of Gynecology and Obstetrics.Keywords: Antibiotic; Prophylaxis; Cesarean; Section
UCorresponding author. Tel.:q966-2677-2027; fax:q966-2537-2502.
0020-7292r00r$20.00䊚2000 International Federation of Gynecology and Obstetrics.
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PII: S 0 0 2 0 - 7 2 9 2 9 9 0 0 2 2 5 - 8
1. Introduction
Cesarean section rate has continued to in- crease for the past 20 years. In the United States, the rate has increased from 5% in 1970 to nearly
w x
25% at the present time 1 . The risk of post-op- erative infectious morbidity after cesarean section without antibiotic prophylaxis ranges from 10%
for women undergoing elective cesarean section to 45᎐85% for women undergoing cesarean sec-
w x tion after labor or rupture of membranes 2 . A substantial body of evidence exists to verify the efficacy of prophylactic antibiotics in preventing w x infectious morbidity after cesarean section 3 . However, the routine use of antibiotic prophylaxis
w x
in cesarean section is low 4,5 . The aim of our study was to determine the effectiveness and safety of the routine use of antibiotic prophylaxis in women undergoing cesarean section.
2. Materials and methods
Pregnant women were enrolled into the study when the decision for cesarean section was made.
The inclusion criterion of the patients into the study was women undergoing cesarean section Žemergency or elective at King Abdulaziz Uni-.
Ž .
versity Hospital KAUH and King Khalid Natio-
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nal Guard Hospital KKNGH . These hospitals serve the city of Jeddah, Saudi Arabia. The so- cioeconomic class of the women is variable. The trial was approved by the institutional review board of the two hospitals and each woman gave informed consent. The exclusion criteria were: 1Ž . the use of therapeutic antibiotics andror evi- dence of existing fever an oral temperature ofŽ 38⬚C or more or other signs of infection prior to. cesarean section; Ž .2 allergy to penicillins or cephalosporins; or 3 concurrent use of otherŽ . prophylactic antibiotic regimens against infectiveŽ endocarditis ..
The experimental group received a single dose
Ž .
of 1 g of cefazolin Totacef, Bristol-Myers Squibb intravenously by the anesthetist at cesarean sec- tion after clamping of the umbilical cord. The control group received a placebo. Both the exper- imental drug and the placebo were indistinguish-
able from each other by using 50-ml minibags.
The minibag with the active drug contained 1 g of cefazolin as the sodium salt reconstituted with 5 ml of water for injection, added to 45 ml of 5%
dextrose. The minibag with the placebo contained 50 ml of 5% dextrose only. Each minibag was given a code number according to computer- generated randomization in the Department of Pharmaceutical Care at KKNGH. The code of randomization was kept strictly confidential in one safe place. Neither the care providers, nor the patients, nor those who analyzed the out- comes were aware of the actual medication re-
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ceived triple-blind . The code was broken only at the end of the statistical analysis.
The primary outcome variable was post-oper- ative febrile morbidity Žan oral temperature greater than 38⬚C in two consecutive readings at least 4 h apart, excluding the first 24 h after operation . The secondary outcomes were infec-. tion-related complications. Generally accepted
w x Ž .
criteria 6 were used to define: 1 endometritis Žfever, uterine tenderness, and abnormal lochia ;. Ž .2 wound infection fever, cellulitis or exudateŽ
. Ž .
with a positive culture ; 3 urinary tract infection Žfever, with or without dysuria, and a positive
. Ž . Ž
urine culture ; 4 pneumonia fever and abnor- . Ž . mal physical and radiologic findings ; 5 bac-
Ž . Ž .
teremia positive blood culture ; 6 pelvic abscess Ždocumented collection of pus resulting in
. Ž .
drainage of purulent material ; 7 fever of unex- plained source fever without any of the afore-Ž mentioned findings and the women are con- sidered by the attending physician to have an
. Ž .
infection ; 8 need for therapeutic antibiotics;
and 9 length of post-operative days in hospitalŽ . Žstarting the day after surgery and including the day of discharge . Data gathering was performed. by chart review after discharge of the patient.
The sample size required was 210 women in each treatment arm. Allowing a 20% dropout rate, the total number of women required was 504 Ž252 in each treatment arm . This figure was. based on a power of 80% of finding a reduction of 50% in post-operative febrile morbidity, type 1 error of 5%, type 2 error of 20%, and two-sided test. The results were analyzed according to in- tention to treat principle. No interim analysis was
performed. Statistical analysis was performed us- ing SPSS for windows version 6.1. Student t-test and 2-test were used as appropriate.
3. Results
From June 1997 to May 1998, the total number of deliveries at KAUH and KKNGH were 2030 and 2562, respectively. The cesarean section rate
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in the two hospitals was 13.2% 268 out of 2030
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and 9.8% 251 out of 2562 . The total number of cesarean deliveries was 519. Four hundred and forty-one women were included in the study. Two hundred and twenty women were randomized to placebo and 221 women to cefazolin. Seventy- eight women were excluded for the following rea- sons: use of therapeutic antibiotics andror fever
Ž .
before surgery 21 ; refusal to participate in the study andror failure of recruitment to the study Ž37 ; allergy to penicillins or cephalosporins 12 ;. Ž . and use of antibiotic prophylaxis against infective endocarditis 8 .Ž .
There were no statistically significant differ- ences between the maternal characteristics and
Ž .
the percentages of emergency unscheduled and
Ž .
elective scheduled and with intact membranes cesarean sections in the two groups of the study ŽTable 1 . In the emergency cesarean sections,. there were statistically significant differences in the rate of development of post-operative febrile morbidity, wound infection, use of therapeutic antibiotics, and number of post-operative days in hospital between women who received placebo
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and women who received cefazolin Table 2 . No statistically significant differences were detected in the development of other infection-related complications. However, in the elective cesarean sections, no statistically significant differences were found in post-operative febrile morbidity
Ž .
and infection-related complications Table 3 . There were no serious side effects related to the use of cefazolin.
With respect to fetal outcome, there were no significant differences in the birth weight, AP- GAR scores at 1 and 5 min, number of days in hospital, admission to neonatal intensive care unit,
Table 1
Maternal characteristicsa
Variable Placebo Cefazolin P-value
ŽNs220. ŽNs221. Age 30.35"0.42 30.14"0.42 NS Gravidity 4.69"0.22 4.78"0.20 NS Parity 3.83"0.21 3.85"0.19 NS Gestational age 38.45"0.15 38.26"0.17 NS
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Weight kg 73.9"1.17 74.9"1.26 NS
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Height cm 154.7"0.56 154.5"0.55 NS
Ž . Ž .
Elective cesarean 109 49.5% 121 54.8% NS section
Ž . Ž .
Emergency cesarean 111 50.5% 100 45.2% NS section
aData are presented as mean"S.E.M. or number and Ž .
percentage % .
early neonatal death, respiratory distress syn-
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drome, and neonatal sepsis Table 4 .
4. Discussion
The evidence of the efficacy of antibiotic pro- phylaxis in women undergoing cesarean section after labor or rupture of membranes is com-
w x
pelling. In 1991, Enkin et al. 3 , carried out a meta-analysis of more than 90 reports of con- trolled trials and found that prophylactic antibi- otics reduced the risk of post-operative febrile
Table 2
Maternal outcome in emergency cesarean sectiona
Variable Placebo Cefazolin P-value
ŽNs111. ŽNs100.
Ž . Ž .
Febrile morbidity 34 30.6% 11 11% 0.001
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Wound infection 12 10.8% 0 -0.001
Ž .
Endometritis 2 1.8% 0 NS
Ž . Ž .
UTI 7 6.3% 1 1.0% NS
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Pneumonia 1 0.9% 0
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Bacteremia 3 2.7% 0
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Pelvic abscess 1 0.9% 0
Ž . Ž .
Unexplained fever 8 7.2% 6 6% NS
Ž . Ž .
Therapeutic antibiotics 38 34.2% 13 13% 0.001 Post-op days in 6.59"0.23 5.73"0.15 0.003
hospital
aData are presented as mean"S.E.M. or number and Ž .
percentage % . UTI, urinary tract infection.
Table 3
Maternal outcome in elective cesarean sectiona
Variable Placebo Cefazolin P-value
ŽNs109. ŽNs121.
Ž . Ž .
Febrile morbidity 7 6.4% 4 3.3% NS
Ž . Ž .
Wound infection 4 3.7% 3 2.5% NS
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Endometritis 1 0.9% 0
Ž . Ž .
UTI 2 1.8% 2 1.7%
Pneumonia 0 0
Bacteremia 0 0
Pelvic abscess 0 0
Ž . Ž .
Unexplained fever 3 2.8% 2 1.7% NS
Ž . Ž .
Therapeutic antibiotics 15 13.8% 8 6.6% 0.06 Post-op days in 5.71"1.71 5.56"1.48 NS
hospital
aData are presented as mean"S.E.M. or number and Ž .
percentage % . UTI, urinary tract infection.
morbidity Žodds ratio, OR 0.33; 95% CI
. Ž
0.29᎐0.39 , endometritis OR 0.25; 95% CI
. Ž
0.22᎐0.29 , wound infection OR 0.35; 95% CI
. Ž
0.28᎐0.44 and serious infection septicemia, pelvic abscess, and peritonitis. ŽOR 0.24; 95% CI 0.18᎐0.32 . The majority of the trials involved. emergency cesarean section. The evidence of the efficacy of antibiotic prophylaxis for elective ce- sarean section is convincing, albeit the number of clinical trials published is not as high as in the case of the emergency cesarean section. In 1992,
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Smaill 7 , found from 17 published trials that in
Table 4
Fetal and neonatal outcomea
Variable Placebo Cefazolin P-value
ŽNs220. ŽNs221.
Birth weight gŽ . 3070.67"42.14 3058.06"46.14 NS
Ž .
APGAR 1 min 7.09"0.13 7.13"0.13 NS
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APGAR 5 min 8.88"0.02 8.74"0.02 NS Days in hospital 6.7"0.28 6.11"0.25 NS
Ž . Ž .
Admission to 6 2.7% 11 5% NS
NICU
Ž . Ž .
Early NND 1 0.5% 2 0.9%
Ž . Ž .
Respiratory 6 2.7% 8 3.6% NS
distress syndrome
Ž . Ž .
Surfactant use 4 1.8% 7 3.2% NS
Ž . Ž .
Neonatal sepsis 2 0.9% 2 0.9%
aData are presented as mean"S.E.M. or number and Ž .
percentage % .
elective cesarean section prophylactic antibiotics reduced the risk of febrile morbidity or en-
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dometritis OR 0.30; 95% CI 0.21᎐0.42 and
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wound infection OR 0.45; 95% CI 0.23᎐0.88 . In comparison with the emergency cesarean section, there was no statistically significant effect on the reduction of serious infection OR 0.09; 95% CIŽ 0.01᎐1.57 ..
With respect to the choice of antibiotic, dose, frequency and time of administration, the body of evidence suggests that a single dose of 1 g of cefazolin given after clamping of the umbilical
w x
cord is appropriate 8,9 . Longer courses of pro- phylactic antibiotics cause a shift in the mi- croflora towards resistant organisms becoming
w x dominant 10 .
The proportion of obstetricians who use antibi- otic prophylaxis routinely is small. A survey of all maternity clinics in Denmark showed that four Ž8% departments used prophylactic antibiotic in.
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elective cesarean sections and 25 52% depart- ments used prophylactic antibiotic in emergency
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cesarean sections 4 . In another report from five w x obstetric units in West Yorkshire hospitals 5 , 36% of elective and emergency cesarean sections were performed using antibiotic prophylaxis.
There was considerable variation in the rate of
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use of antibiotic prophylaxis 0᎐58.7% between the hospitals. This is due to several factors, such as the relatively reduced numbers of clinical trials of routine use of prophylactic antibiotics in ce- sarean section, the existence of studies with no
w x improvement in post-operative course 11 , and
w x questionable riskrbenefit ratio 12 .
w x Our study was an effectiveness trial 13 with minimal exclusion criteria. The routine use of a single dose of 1 g of cefazolin given after clamp- ing of the umbilical cord in emergency cesarean sections resulted in statistically significant reduc- tion in the rates of post-operative febrile morbid- ity, wound infection, use of therapeutic antibi- otics, and the maternal post-operative days in hospital. In our practice, the two most commonly used therapeutic antibiotic regimens for post- cesarean section infections are gentamicin, metronidazole, and ampicillin or cefuroxime and metronidazole. The total wholesale cost of a 5-day course of gentamicin, metronidazole, and ampi-
cillin or cefuroxime and metronidazole is approxi- mately $108 and $329, respectively. A single dose of 1 g of cefazolin costs approximately $2.6. Based upon our findings, the amount of saving with cefazolin prophylaxis in terms of reduction in the use of therapeutic antibiotics and post-operative hospital stay make the cost analysis unequivocally in favor of antibiotic prophylaxis. Therefore, the routine use of cefazolin in emergency cesarean sections is recommended.
In the elective cesarean sections, no statistically significant differences were found in post-oper- ative febrile morbidity and infection-related com- plications. This is related to the low frequency of
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post-operative febrile morbidity 6.7% , wound
Ž . Ž .
infection 4.3% , and endometritis 0.9% in women who received placebo. A sample size of 1800 women is required to show a statistically significant difference in febrile morbidity based on a power of 80%, type 1 error of 5%, type 2 error of 20%, and two-sided test.
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Jakobi et al. 6 , in 1994, reported in a ran- domized trial, significantly lower rates of febrile morbidity and post-operative therapeutic antibi- otic usage with 1 g of cefazolin in 167 low risk women elective cesarean sections, duration ofŽ rupture membranes less than 3 h, and no more than two vaginal examinations compared to 140. low risk women with no prophylaxis. However,
‘additional treatment’ was given at the discretion of the treating physician and labor and rupture of membranes are considered to be significant risk
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factors. Shah et al. 14 , in 1998, reported a ran- domized trial of 3 different prophylactic antibiotic regimens and a control group involving 198 women undergoing elective cesarean sections. The antibi- otics significantly reduced post-operative febrile morbidity. The frequency of post-operative febrile
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morbidity in the control group was high 31% . In w x
contrast, Rizk et al. 15 , in 1998, reported a randomized trial of 1.5 g of cefuroxime vs. no prophylaxis in 120 women undergoing elective cesarean sections. There were no statistically sig- nificant differences in post-operative febrile mor- bidity and infection-related complications. The frequency of post-operative febrile morbidity in the control group was 9.8%. This is low and is
somewhat similar to our rate of post-operative febrile morbidity in elective cesarean sections.
Hence, the routine use of cefazolin in elective cesarean section when febrile morbidity is low, is not recommended.
Acknowledgments
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Supported by a grant M.S.-1-77 from King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
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