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A follow-up study on prophylactic antibiotics in cesarean section
A follow-up study on prophylactic antibiotics in cesarean section RONALD JOHN RICHARD Philadelphia,
S. E.
GIBBS,
HUNT, H.
M.D. M.D.
SCHWARZ,
M.D.
Pennsylvania
A follow-up, double-blind study was performed to re-evaluate the eflect of an 8 hour perioperative course of prophylactic antibiotics in 68 service patients undergoing cesarean section. The correlation between the initial and follow-up studies was good. In the combined investigations, 129 patients were evaluated. The over-all morbidity rate was 63 per cent in the placebo group and 25 per cent in the antibiotic group (p < 0.2 per cent). A highly significant decrease in wound infections and endometritis was found in the patients receiving antibiotics. Also, average hospital stay was less in the antibiotic group.
tion, routine studies, postoperative care, or morbidity determinations. The only change was that methicillin was dropped from the regimen in view of culture and sensitivity data from the first study. In this regimen, then, each patient received 3 pairs of intramuscular injections. The first was given just prior to the operation, and the second and third were given 2 and 8 hours postoperatively. Each pair consisted of 1 Gm. of ampicillin and r/z Gm. of kanamycin. The materials were prepared by the pharmacy service in coded, identical vials, containing identically appearing solutions.
I N A R E c E N T report’ from this department, the >?ffect of an 8 hour perioperative course of prophylactic antibiotics in selective cesarean sections was evaluated. In doubleblind fashion, 61 service patients were given ampicillin, kanamycin, and methicillin or their respective placebos before as well as 2 and 8 hours after operation. An over-all 27 per cent morbidity rate was found in the antibiotic group as compared to a 61 per cent morbidity rate in the placebo group (p < 5 per cent). Nevertheless, some important questions were left unanswered because of the size of patient subgroupings. Therefore, the present follow-up study was undertaken.
Results A total of 93 service patients underwent cesarean section during the study period of August 7, 1972, to February 4, 1973. Twentyfive patients were eliminated because of penicillin allergy, fever in labor, errors in giving the medication, etc. None was used as a control. Therefore, 68 patients were included in the second study. As shown in Table I, randomization of patients is acceptable. In Table II, the results of the second study
Methods No changes were made in the protocol from the first study concerning patient selecFrom the Jerrold R. Golding Division of Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine. Reprint requests: Dr. Ronald S. Gibbs, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104. 419
420
Gibbs,
Hunt,
and
Table I. Characteristics
Schwarz
of patient
groups
by drug Part
NO. Age No. with rupture of membranes Average duration of rupture of membranes No. with rupture of membranes > 12 hr. No. with rupture of membranes > 3 hr. rupture No. without of membranes No. with primary cesarean section No. with repeat cesarean section No. with anemia (hemoglobin < 10.0 Gm. Hospital stay (postoperative days)
Table II. Morbidity
by type, operation,
II
Parts
I and II
Antibiotic
Placebo
Antibiotic
Placebo
34 ‘22.0 16 6.1 7 13 19 17 17 10 6.3
34 22.5 19 4.3 1 15 15 24 10 10 8.5
67 22.3 31 7.4 9 25 36 39 28 21 6.4
62 22.6 36 5.6 2 24 26 39 23 15 7.8
(hr.)
% )
and drug
(Part
II) -
Antibiotic
Urinary tract infection Endometritis Wound infection (total) Grade 1 Grade 2 Grade 3 Atelectasis Pneumonia Pelvic abscess Total No. with morbidities Total morbid patients Total patients Patients morbid
(% )
Total
Primary
2 6 0
0 4 0
Placebo 1 Repeat
Total
Primary
4 20 6
2 17 3
2 2 0 1 4 1
1 2 0
Repeat 2 3 3 0 2 1
0 0 0 8 8
0 0 0 4 4
0 0 0 4 4
1 0 1 32 22
1 0 0 23 18
0 0 1 9 4
34 24
It 24
It 24
34 65
e 75
10 40
are presented. The x2 value for the over-all results in this part is 6.53, and p = 0.8 to 1.4 per cent. The organisms cultured during this study were quite similar to those found in the first study. Ampicillin remained the drug of choice in treating postpartum fever and was used in 23 patients. Five patients also received kanamycin; 2 received cephalothin or cephaloridine ; and one each, tetracycline, oxacillin, and clindamycin. Chi square values were then calculated to determine whether the data of the first study correlated with those of the second. In all cases, correlation was acceptable. Therefore, the results of the first and second studies were combined and are presented in Table III. These results are highly significant for the total groups (X 2 = 10.47, p < 0.2 per
cent). Since the subgroupings of primary and repeat sections are of appropriate size, X2 values were calculated here also. For the primary sections only, x2 = 4.90, p = 2.5 to 4.6 per cent; and for the repeat sections, x2 = 5.78, p = 1.4 to 2.5 per cent. Both of the values are statistically significant. Further, among 67 patients receiving antibiotics, there were no wound infections while, among 62 patients receiving placebos, there were 10 wound infections (x2 = 11.9, p < 0.1 per cent). Also, in comparing the incidence of endometritis, 13 of 67 (19 per cent) in the antibiotic group were classified as having this type of morbidity compared with 28 of 62 (45 per cent) in the placebo group. With a x2 value of 6.72 (p = 0.8 to 1.4 per cent), the difference is also statistically significant. It does not appear that this antibiotic regi-
Volume Number
Prophylactic
117 3
Table III.
Morbidity
by type, operation,
and drug
antibiotics
1 Primary
5 13 0
3 11 0
men reduces the incidence urinary morbidities.
(
Repeat
Total
Primary
8 28 10
3 23 5
2 2 0 5 4 1
(% )
of pulmonary
421
Placebo
Antibiotic
Total No. of patients Patients with morbidities
section
(Parts I and II)
Total Urinary tract infection Endometritis Wound infection (total) Grade 1 Grade 2 Grade 3 Pneumonia Atelectasis Drug reaction Total No. of morbidities Total morbid patients
in cesarean
3 2 0
/ Repeat 5 5 5 2 2 1
1 1 0 20 17
1 1 0 16 13
0 0 0 4 4
1 3 0 50 39
1 2 0 34 27
0 1 0 16 12
z 25
39 33
ii 14
s:! 63
39 69
23 52
or
Comment Upon completion of the first study, the investigators reported that an 8 hour course of prophylactic ampicillin, kanamycin, and methicillin resulted in a decrease in over-all morbidity from 61 per cent in patients receiving placebos to 27 per cent in patients receiving antibiotics (p < 5 per cent). However, because the subpopulations became too small, the results in important subgroups fell short of statistical significance. Consequently, the follow-up study was undertaken to answer the following questions: (1) Would the results be reproduced? (2) Would the regimen be effective in the presence of ruptured membranes? (3) Specifically, would endometritis and wound infections be decreased? (4) Was methicillin necessary? (5) Would hospitalization be decreased? For the first question, the answer is that the results have been reproduced with good correlation. Second, when the patients were grouped by morbidity (from endometritis or wound infection only) according to drug and presence or absence of ruptured membranes, the antibiotics showed effectiveness whether or not membranes were ruptured. In those patients with ruptured membranes, one third of the antibiotic group compared with two
thirds of the placebo group became morbid. In those patients with unruptured membranes, one tenth of the antibiotic group compared with one third of the placebo group became morbid. Third, the effect in decreasing endometritis and wound infections was highly significant with p < 1.4 and 0~1 per cent, respectively. Fourth, it is concluded that methicillin added no benefit in view of the similarity of results between the 2 studies and in view of the sensitivity data. Fifth, a decreased hospitalization length was achieved in the antibiotic group primarily as a result of decreasing prolonged hospitalization associated with wound infections. These results are of particular note in view of a recent study by Ledger and associates’ on the use of perioperative cephaloridine in premenopausal women undergoing vaginal hysterectomy. In a double-blind study, he reported that patients receiving the antibiotic had significantly less morbidity (p < 0.025). In decreasing pelvic infections, the regimen was especially effective (p < 0.001). It would now appear that a perioperative, prophylactic course of antibiotics achieves an effect as marked as those in which the “prophylactic” course is 3 to 5 days. Finally, it must be emphasized that the major stimulation for these studies was the known high morbidity rate of service patients
422
Gibbs,
Hunt,
and
Schwarz
undergoing cesarean section. Here, prophylactic antibiotics are effective and appropriate. In other situations in which the risk of infection is not marked, the use of prophylactic antibiotics is not supported.
The authors express their gratitude to Dr. Rob Roy MacGregor, Infectious Disease Section, Department of Medicine, and Dr. Joseph Link?with, Pharmacy Service, for their assistance in these studies.
REFERENCES
1. Gibbs, R. S., DeCherney, R. S.: AM. J. OBSTET. 1972.
A. H., and Schwan, 114: 1048,
GYNECOL.
2. Ledger, W. J., Sweet, R. L., and Headington, J. T.: AM. J. OBSTET. GYNECOL. 115: 766, 1973.
S. E.
GIBBS,
HUNT, H.
M.D. M.D.
SCHWARZ,
M.D.
Pennsylvania
A follow-up, double-blind study was performed to re-evaluate the eflect of an 8 hour perioperative course of prophylactic antibiotics in 68 service patients undergoing cesarean section. The correlation between the initial and follow-up studies was good. In the combined investigations, 129 patients were evaluated. The over-all morbidity rate was 63 per cent in the placebo group and 25 per cent in the antibiotic group (p < 0.2 per cent). A highly significant decrease in wound infections and endometritis was found in the patients receiving antibiotics. Also, average hospital stay was less in the antibiotic group.
tion, routine studies, postoperative care, or morbidity determinations. The only change was that methicillin was dropped from the regimen in view of culture and sensitivity data from the first study. In this regimen, then, each patient received 3 pairs of intramuscular injections. The first was given just prior to the operation, and the second and third were given 2 and 8 hours postoperatively. Each pair consisted of 1 Gm. of ampicillin and r/z Gm. of kanamycin. The materials were prepared by the pharmacy service in coded, identical vials, containing identically appearing solutions.
I N A R E c E N T report’ from this department, the >?ffect of an 8 hour perioperative course of prophylactic antibiotics in selective cesarean sections was evaluated. In doubleblind fashion, 61 service patients were given ampicillin, kanamycin, and methicillin or their respective placebos before as well as 2 and 8 hours after operation. An over-all 27 per cent morbidity rate was found in the antibiotic group as compared to a 61 per cent morbidity rate in the placebo group (p < 5 per cent). Nevertheless, some important questions were left unanswered because of the size of patient subgroupings. Therefore, the present follow-up study was undertaken.
Results A total of 93 service patients underwent cesarean section during the study period of August 7, 1972, to February 4, 1973. Twentyfive patients were eliminated because of penicillin allergy, fever in labor, errors in giving the medication, etc. None was used as a control. Therefore, 68 patients were included in the second study. As shown in Table I, randomization of patients is acceptable. In Table II, the results of the second study
Methods No changes were made in the protocol from the first study concerning patient selecFrom the Jerrold R. Golding Division of Fetal Medicine, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine. Reprint requests: Dr. Ronald S. Gibbs, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104. 419
420
Gibbs,
Hunt,
and
Table I. Characteristics
Schwarz
of patient
groups
by drug Part
NO. Age No. with rupture of membranes Average duration of rupture of membranes No. with rupture of membranes > 12 hr. No. with rupture of membranes > 3 hr. rupture No. without of membranes No. with primary cesarean section No. with repeat cesarean section No. with anemia (hemoglobin < 10.0 Gm. Hospital stay (postoperative days)
Table II. Morbidity
by type, operation,
II
Parts
I and II
Antibiotic
Placebo
Antibiotic
Placebo
34 ‘22.0 16 6.1 7 13 19 17 17 10 6.3
34 22.5 19 4.3 1 15 15 24 10 10 8.5
67 22.3 31 7.4 9 25 36 39 28 21 6.4
62 22.6 36 5.6 2 24 26 39 23 15 7.8
(hr.)
% )
and drug
(Part
II) -
Antibiotic
Urinary tract infection Endometritis Wound infection (total) Grade 1 Grade 2 Grade 3 Atelectasis Pneumonia Pelvic abscess Total No. with morbidities Total morbid patients Total patients Patients morbid
(% )
Total
Primary
2 6 0
0 4 0
Placebo 1 Repeat
Total
Primary
4 20 6
2 17 3
2 2 0 1 4 1
1 2 0
Repeat 2 3 3 0 2 1
0 0 0 8 8
0 0 0 4 4
0 0 0 4 4
1 0 1 32 22
1 0 0 23 18
0 0 1 9 4
34 24
It 24
It 24
34 65
e 75
10 40
are presented. The x2 value for the over-all results in this part is 6.53, and p = 0.8 to 1.4 per cent. The organisms cultured during this study were quite similar to those found in the first study. Ampicillin remained the drug of choice in treating postpartum fever and was used in 23 patients. Five patients also received kanamycin; 2 received cephalothin or cephaloridine ; and one each, tetracycline, oxacillin, and clindamycin. Chi square values were then calculated to determine whether the data of the first study correlated with those of the second. In all cases, correlation was acceptable. Therefore, the results of the first and second studies were combined and are presented in Table III. These results are highly significant for the total groups (X 2 = 10.47, p < 0.2 per
cent). Since the subgroupings of primary and repeat sections are of appropriate size, X2 values were calculated here also. For the primary sections only, x2 = 4.90, p = 2.5 to 4.6 per cent; and for the repeat sections, x2 = 5.78, p = 1.4 to 2.5 per cent. Both of the values are statistically significant. Further, among 67 patients receiving antibiotics, there were no wound infections while, among 62 patients receiving placebos, there were 10 wound infections (x2 = 11.9, p < 0.1 per cent). Also, in comparing the incidence of endometritis, 13 of 67 (19 per cent) in the antibiotic group were classified as having this type of morbidity compared with 28 of 62 (45 per cent) in the placebo group. With a x2 value of 6.72 (p = 0.8 to 1.4 per cent), the difference is also statistically significant. It does not appear that this antibiotic regi-
Volume Number
Prophylactic
117 3
Table III.
Morbidity
by type, operation,
and drug
antibiotics
1 Primary
5 13 0
3 11 0
men reduces the incidence urinary morbidities.
(
Repeat
Total
Primary
8 28 10
3 23 5
2 2 0 5 4 1
(% )
of pulmonary
421
Placebo
Antibiotic
Total No. of patients Patients with morbidities
section
(Parts I and II)
Total Urinary tract infection Endometritis Wound infection (total) Grade 1 Grade 2 Grade 3 Pneumonia Atelectasis Drug reaction Total No. of morbidities Total morbid patients
in cesarean
3 2 0
/ Repeat 5 5 5 2 2 1
1 1 0 20 17
1 1 0 16 13
0 0 0 4 4
1 3 0 50 39
1 2 0 34 27
0 1 0 16 12
z 25
39 33
ii 14
s:! 63
39 69
23 52
or
Comment Upon completion of the first study, the investigators reported that an 8 hour course of prophylactic ampicillin, kanamycin, and methicillin resulted in a decrease in over-all morbidity from 61 per cent in patients receiving placebos to 27 per cent in patients receiving antibiotics (p < 5 per cent). However, because the subpopulations became too small, the results in important subgroups fell short of statistical significance. Consequently, the follow-up study was undertaken to answer the following questions: (1) Would the results be reproduced? (2) Would the regimen be effective in the presence of ruptured membranes? (3) Specifically, would endometritis and wound infections be decreased? (4) Was methicillin necessary? (5) Would hospitalization be decreased? For the first question, the answer is that the results have been reproduced with good correlation. Second, when the patients were grouped by morbidity (from endometritis or wound infection only) according to drug and presence or absence of ruptured membranes, the antibiotics showed effectiveness whether or not membranes were ruptured. In those patients with ruptured membranes, one third of the antibiotic group compared with two
thirds of the placebo group became morbid. In those patients with unruptured membranes, one tenth of the antibiotic group compared with one third of the placebo group became morbid. Third, the effect in decreasing endometritis and wound infections was highly significant with p < 1.4 and 0~1 per cent, respectively. Fourth, it is concluded that methicillin added no benefit in view of the similarity of results between the 2 studies and in view of the sensitivity data. Fifth, a decreased hospitalization length was achieved in the antibiotic group primarily as a result of decreasing prolonged hospitalization associated with wound infections. These results are of particular note in view of a recent study by Ledger and associates’ on the use of perioperative cephaloridine in premenopausal women undergoing vaginal hysterectomy. In a double-blind study, he reported that patients receiving the antibiotic had significantly less morbidity (p < 0.025). In decreasing pelvic infections, the regimen was especially effective (p < 0.001). It would now appear that a perioperative, prophylactic course of antibiotics achieves an effect as marked as those in which the “prophylactic” course is 3 to 5 days. Finally, it must be emphasized that the major stimulation for these studies was the known high morbidity rate of service patients
422
Gibbs,
Hunt,
and
Schwarz
undergoing cesarean section. Here, prophylactic antibiotics are effective and appropriate. In other situations in which the risk of infection is not marked, the use of prophylactic antibiotics is not supported.
The authors express their gratitude to Dr. Rob Roy MacGregor, Infectious Disease Section, Department of Medicine, and Dr. Joseph Link?with, Pharmacy Service, for their assistance in these studies.
REFERENCES
1. Gibbs, R. S., DeCherney, R. S.: AM. J. OBSTET. 1972.
A. H., and Schwan, 114: 1048,
GYNECOL.
2. Ledger, W. J., Sweet, R. L., and Headington, J. T.: AM. J. OBSTET. GYNECOL. 115: 766, 1973.