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Response of lower genital tract flora to external pelvic irradiation
GYNECOLOGIC
ONCOI.OGY
35, 233-235 (1989)
Response of Lower Genital Tract Flora to External Pelvic Irradiation ALAN
N.
GORDON,
M.D.,’
MARK
MARTENS,
M.D.,
YVETTA
LAPREAD,
R.N.,
AND SEBASTIAN
FARO,
M.D.
Departtn~nt of Oh.sfrtric.\crndGywcdo,q>~,Baj4or College of' Medicirw, Ho~rsror~,T~~xcis77030 Received
October 4. 1988
Endocervical and vaginal cultures were obtained every week from patients undergoing external pelvic irradiation for gynecologic malignancy. Gram-positive aerobes accounted for 52 to 56% of isolates, gram-negative aerobes accounted for 15 to 16%, and anaerobes accounted for 29 to 32% of all isolates prior to therapy. No significant changes occurred during or after completion of radiation for the group. In individual patients, however, over 50% of organisms found on initial culture were no longer c 1989 Academic Press. Inc. present on completion of external therapy.
The endogenous bacterial flora of the lower genital tract is felt to be responsible for many infections that subsequently occur in gynecologic patients [I]. There are few studies of the microflora demonstrating their role in pelvic infections in gynecologic oncology patients. In several studies, prophylactic antibiotics were given to patients undergoing radical hysterectomy, and the organisms recovered from infected patients were similar to those from other pelvic infections in patients without malignancy [2-41. None of the patients in these studies were administered radiation therapy. In an attempt to determine if radiation therapy affected the microflora of the lower genital tract, Gilstrap examined aerobic cultures and reported that he found little or no influence in the distribution of the pathogens encountered [S]. No attempt was made to study the anaerobic bacteria in that study. The present study was undertaken to determine the effect of radiation therapy on the endogenous aerobic and anaerobic bacteria of the lower genital tract. MATERIALS
AND
METHODS
Patients were considered for inclusion in the study if they were scheduled to receive whole-pelvis or extendedfield external radiation therapy for lower genital tract cancers. All patients were seen in the Gynecologic On’ Current address: Department of Obstetrics and Gynecology. derbilt University School of Medicine, Nashville, TN 37232.
cology Clinic at Ben Taub General Hospital in Houston, Texas. They received treatment on a cobalt-60 machine at 180 to 200 rads per day for 4 or 5 days per week to a total dose of 4000 to 4589 rads. The treatment time was 32 to 54 days, with an average 40 days. The patients studied were ten patients with squamous cancer of the cervix, one patient with adenocarcinoma of the cervix, and one patient with a squamous carcinoma of unknown primary (the patient profile can be seen in Table I). All patients were seen just prior to initiation of radiation therapy and on a weekly basis while undergoing radiation therapy for examinations and cultures. No patient had received antibiotics for at least 4 weeks prior to initiation of therapy. Examinations were performed by the resident staff under the supervision of the attending staff. After a patient was placed in the dorsal lithotomy position, a speculum was introduced and a sterile cotton-tipped swab was used to obtain a specimen from the posterior fornix pool for culture. This swab was immediately placed in anaerobic transport medium (Port A Cul, BBL, Cockeysville, MD). The cervix, if present, was cleansed with a swab. A sterile cotton swab was then placed carefully into the endocervix to obtain a sample high in the canal which was placed in anaerobic transport medium (Port A Cul). All patients were cultured weekly until completion of their radiation therapy. Preparation of the samples and methods for determination of aerobic and anaerobic bacteria were performed as previously described [6]. No patient received antibiotic therapy during the course of the study. Analysis of bacterial groups was performed by x2 analysis. RESULTS
Aerobic gram-positive organisms accounted for the majority of the isolates in both endocervical and vaginal cultures (Tables 2 and 3). The cultures from the endocervix revealed 52% of isolates were gram-positive aerobes and 16% were gram-negative aerobes. Anaerobic
Van-
233 0090-8258189$ I 30 Copyright 0 1989 by Academic Press. Inc. All rights of reproduction in any form reserved.
234
GORDON ET AL.
TABLE 1 Patient Profile Carcinoma of the cervix Squamous (IB-5, IIA-I, IIB-2, IIIB-2) Adenocarcinoma (IB-I) Squamous carcinoma-unknown primary Age Field Whole pelvis Extended field Dose
TABLE 3 Vaginal Culture Results Pretherapy 10 patients 1 patient 1 patient 3l-58 years (average 42.5, median 40) 9 patients 3 patients 4000-4589 rad (average 4235) 33-54 days (average 40)
Treatment time
isolates accounted for 32% of the pretreatment cultures from the cervix. Fifty-six percent of pretreatment vaginal organisms were gram-positive aerobes, whereas gramnegative aerobes accounted for 15% of the isolates. Anaerobes accounted for 29% of the isolates in the vaginal cultures. There was no difference in the distribution of organisms recovered from either site. The post-therapy cultures revealed a distribution similar to that of the initial cultures. In the cervical cultures 55% were gram-positive and 19% were gram-negative aerobic bacteria whereas anaerobes accounted for 26%. There was no statistical difference between this distribution and the pretreatment distribution. Analysis of the vaginal isolates revealed similar findings. Gram-positive TABLE 2 Endocervical Culture Results Pretherapy
Post-therapy
Gram-positive aerobes Lactobacillus Enterococcus Staphylococcus
epidermidis
Group B streptococci Group F streptococci Total Gram-negative aerobes Escherichia coli Garducrella vaginalis Klebsiella pneumoniae Proteus mirabilis Pseudomonas
Total Anaerobes Bacteroides Bacteroides Bacteroides
melaninogenicus bivius fragilis
Total a Number. b Percentage in parentheses.
5” 4 3 0 1 13 (52)b
5 4 5 2 1 17 (55)
2 2
1 4 1
0 0 0
0 0
4 (16)
6 (19)
4 3 1
6 0 2
8 (32)
8 (26)
Post-therapy
Gram-positive aerobes Lactobacillus Enterococcus Staphylococcus
6” epidermidis
Diptheroids Group B streptococci Group F streptococci Total Gram-negative aerobes
2 2 1
Escherichia coli Garducrella vaginalis Pseudomonas Klebsiella pneumonia Proteus mirabilis
melaninogenicus bivius fragilis
Total
6 4 5 0 3 1 19 (48)
5 (15)
3 4 0 1 1 9 (23)
5 4 1 10 (29)
8 3 1 12 (30)
0 0
Total Anaerobes Bacteroides Bacteroides Bacteroides
5 4 2 1 1 19 (56)h
” Number. ’ Percentage in parentheses.
aerobes accounted for the majority of organisms, 48% of the isolates, and gram-negative aerobes accounted for 23%. Anaerobes accounted for 30% of the isolates. There was no statistical difference between pre- and post-therapy microflora. Analysis of the distribution of isolates in each week revealed results similar to those previously noted. Although the distributions of isolates before, during, and after therapy appear to be similar for the group overall, analysis of each individual patient reveals that the individual flora were not as stable throughout the course of the therapy. Examination of individual patients demonstrated that more than 50% of their original isolates were no longer present at the completion of therapy. Only Lactobacillus and Bacteroides melaninogenicus appear to be stable throughout the course of radiation therapy in each patient positive for those organisms. DISCUSSION Infections occurring in the genital tract of patients with gynecologic malignancies most likely arise from organisms populating the genital tract in a mechanism similar to that seen in other gynecologic infections [51. In an attempt to reduce the risk of infection in patients with cervical cancer, broad-spectrum antibiotic prophylaxis was administered in a manner similar to that used for benign gynecology patients [2-41. The endocervical and vaginal organisms found in the present study reflect the
BACTERIAL
235
FLORA AND RADIATION
flora found in women without genital tract malignancies. Overall, there appears to be no significant change in the pattern of bacterial isolates when the group as a whole is examined. This is similar to the results previously reported by Gilstrap et al. [5]. Blythe also reported that patients with cervical cancer had the same flora as patients without malignancy and the frequency of organisms seemed independent of the dose of radiation [7]. In Blythe’s study the anaerobes also appeared to be unchanged. Mead [8], however, reported that the frequency of Bacteroides species and Escherichia coli was increased in patients with invasive cervical cancer. Unfortunately, patients were not followed throughout radiation therapy to see if any change occurred. Gerstner et al. [9] examined patients undergoing intracavitary applications of iridium with afterloading technique. They reported that the composition of the endometrial flora was not altered significantly by the intracavitary applications. The only significant change was an increase in the frequency of aerobic spore formers. Although more organisms were recovered, the increase in the number of organisms was not significant. The authors point out, as is apparent here, that radiation is not capable of sterilizing the endocervix or endometrium. Examination of the individual patient reveals a picture somewhat different from that of the group as a whole. The overall frequency of bacterial isolates of the group does not appear to have changed as had previously been reported [5,7,9], and the isolates are similar to those reported in patients without malignancy; however, during the course of therapy, each patient had a change in more than half the organisms isolated from their pretreatment culture. Therefore, selection of antibiotic therapy, based on a preradiation therapy culture, is not valid
in an individual patient after radiation therapy has begun. If antimicrobial coverage is indicated for patients either during or following radiation therapy, broad-spectrum coverage for both gram-positive and -negative aerobes, along with anaerobes, should be included until specific culture results are available to indicate the patient’s organisms at the time of suspected infection. REFERENCES I. Schwarz, R. H. Management of postoperative infections in obstetrics and gynecology, C/in. Obster. Gynrcol. 19, 97-108 (1976).
2. Micha, J. P., Kucera, P. R., Birkett, J. P., Chambers, G., Sheets, E. E., and DiSaia, P. J. Prophylactic mezlocillin in radical hysterectomy, Obstet. Gyncwd. 69, 251-254 (1987). Marsden, D. E., Cavanagh, D., Wisniewski, B. J.. Roberts, W. S., and Lyman, G. H. Factors affecting the incidence of infectious morbidity after radical hysterectomy. Amer. J. Obstrt. Gynecol. 152, 817-821 (1985). 4. Sevin, B., Reinaldo. R.. Lichtinger, M.. Girtanner, R. E.. and Averette, H. E. Antibiotic prevention of infection complicating radical abdominal hysterectomy. Obstrt. Gynewl. 64, 539-545 (1984). s. Gilstrap. L. C., III, Gibbs, R. S., Michel, T. J., and Hauth, J. C. Genital aerobic bacterial flora of women receiving radiotherapy for gynecologic malignancy, Gynecol. Oncol. 23, 35-39 (1986). 6. Fare, S., Phillips, L. E., Baker, J. L., Goodrich, K. H., Turner, R. M.. and Riddle. G. D. Comparative efficacy and safety of mezlocillin, cefoxitin, and clindamycin plus gentamycin in post partum endometritis, Obstet. G.vnecd. 69, 760-766 (1987). Blythe, J. G. Cervical bacterial flora in patients with gynecologic malignancies, Amer. J. Obstrt. Gynecol. 131, 438-445 (1978). Mead, P. B. Cervical-vaginal flora of women with invasive cervical cancer. Obstef. GynPcol. 52, 601-604 (1978). Gerstner, G. J., Kucera. H., Weghaupt, K., and Rotter, M. Endometrial bacteriology in patients with endometrial cancer before and after irradiation using Ir-192 and an afterloading technique, Arch. G.vnecol. 231, 299-306 (1982).
ONCOI.OGY
35, 233-235 (1989)
Response of Lower Genital Tract Flora to External Pelvic Irradiation ALAN
N.
GORDON,
M.D.,’
MARK
MARTENS,
M.D.,
YVETTA
LAPREAD,
R.N.,
AND SEBASTIAN
FARO,
M.D.
Departtn~nt of Oh.sfrtric.\crndGywcdo,q>~,Baj4or College of' Medicirw, Ho~rsror~,T~~xcis77030 Received
October 4. 1988
Endocervical and vaginal cultures were obtained every week from patients undergoing external pelvic irradiation for gynecologic malignancy. Gram-positive aerobes accounted for 52 to 56% of isolates, gram-negative aerobes accounted for 15 to 16%, and anaerobes accounted for 29 to 32% of all isolates prior to therapy. No significant changes occurred during or after completion of radiation for the group. In individual patients, however, over 50% of organisms found on initial culture were no longer c 1989 Academic Press. Inc. present on completion of external therapy.
The endogenous bacterial flora of the lower genital tract is felt to be responsible for many infections that subsequently occur in gynecologic patients [I]. There are few studies of the microflora demonstrating their role in pelvic infections in gynecologic oncology patients. In several studies, prophylactic antibiotics were given to patients undergoing radical hysterectomy, and the organisms recovered from infected patients were similar to those from other pelvic infections in patients without malignancy [2-41. None of the patients in these studies were administered radiation therapy. In an attempt to determine if radiation therapy affected the microflora of the lower genital tract, Gilstrap examined aerobic cultures and reported that he found little or no influence in the distribution of the pathogens encountered [S]. No attempt was made to study the anaerobic bacteria in that study. The present study was undertaken to determine the effect of radiation therapy on the endogenous aerobic and anaerobic bacteria of the lower genital tract. MATERIALS
AND
METHODS
Patients were considered for inclusion in the study if they were scheduled to receive whole-pelvis or extendedfield external radiation therapy for lower genital tract cancers. All patients were seen in the Gynecologic On’ Current address: Department of Obstetrics and Gynecology. derbilt University School of Medicine, Nashville, TN 37232.
cology Clinic at Ben Taub General Hospital in Houston, Texas. They received treatment on a cobalt-60 machine at 180 to 200 rads per day for 4 or 5 days per week to a total dose of 4000 to 4589 rads. The treatment time was 32 to 54 days, with an average 40 days. The patients studied were ten patients with squamous cancer of the cervix, one patient with adenocarcinoma of the cervix, and one patient with a squamous carcinoma of unknown primary (the patient profile can be seen in Table I). All patients were seen just prior to initiation of radiation therapy and on a weekly basis while undergoing radiation therapy for examinations and cultures. No patient had received antibiotics for at least 4 weeks prior to initiation of therapy. Examinations were performed by the resident staff under the supervision of the attending staff. After a patient was placed in the dorsal lithotomy position, a speculum was introduced and a sterile cotton-tipped swab was used to obtain a specimen from the posterior fornix pool for culture. This swab was immediately placed in anaerobic transport medium (Port A Cul, BBL, Cockeysville, MD). The cervix, if present, was cleansed with a swab. A sterile cotton swab was then placed carefully into the endocervix to obtain a sample high in the canal which was placed in anaerobic transport medium (Port A Cul). All patients were cultured weekly until completion of their radiation therapy. Preparation of the samples and methods for determination of aerobic and anaerobic bacteria were performed as previously described [6]. No patient received antibiotic therapy during the course of the study. Analysis of bacterial groups was performed by x2 analysis. RESULTS
Aerobic gram-positive organisms accounted for the majority of the isolates in both endocervical and vaginal cultures (Tables 2 and 3). The cultures from the endocervix revealed 52% of isolates were gram-positive aerobes and 16% were gram-negative aerobes. Anaerobic
Van-
233 0090-8258189$ I 30 Copyright 0 1989 by Academic Press. Inc. All rights of reproduction in any form reserved.
234
GORDON ET AL.
TABLE 1 Patient Profile Carcinoma of the cervix Squamous (IB-5, IIA-I, IIB-2, IIIB-2) Adenocarcinoma (IB-I) Squamous carcinoma-unknown primary Age Field Whole pelvis Extended field Dose
TABLE 3 Vaginal Culture Results Pretherapy 10 patients 1 patient 1 patient 3l-58 years (average 42.5, median 40) 9 patients 3 patients 4000-4589 rad (average 4235) 33-54 days (average 40)
Treatment time
isolates accounted for 32% of the pretreatment cultures from the cervix. Fifty-six percent of pretreatment vaginal organisms were gram-positive aerobes, whereas gramnegative aerobes accounted for 15% of the isolates. Anaerobes accounted for 29% of the isolates in the vaginal cultures. There was no difference in the distribution of organisms recovered from either site. The post-therapy cultures revealed a distribution similar to that of the initial cultures. In the cervical cultures 55% were gram-positive and 19% were gram-negative aerobic bacteria whereas anaerobes accounted for 26%. There was no statistical difference between this distribution and the pretreatment distribution. Analysis of the vaginal isolates revealed similar findings. Gram-positive TABLE 2 Endocervical Culture Results Pretherapy
Post-therapy
Gram-positive aerobes Lactobacillus Enterococcus Staphylococcus
epidermidis
Group B streptococci Group F streptococci Total Gram-negative aerobes Escherichia coli Garducrella vaginalis Klebsiella pneumoniae Proteus mirabilis Pseudomonas
Total Anaerobes Bacteroides Bacteroides Bacteroides
melaninogenicus bivius fragilis
Total a Number. b Percentage in parentheses.
5” 4 3 0 1 13 (52)b
5 4 5 2 1 17 (55)
2 2
1 4 1
0 0 0
0 0
4 (16)
6 (19)
4 3 1
6 0 2
8 (32)
8 (26)
Post-therapy
Gram-positive aerobes Lactobacillus Enterococcus Staphylococcus
6” epidermidis
Diptheroids Group B streptococci Group F streptococci Total Gram-negative aerobes
2 2 1
Escherichia coli Garducrella vaginalis Pseudomonas Klebsiella pneumonia Proteus mirabilis
melaninogenicus bivius fragilis
Total
6 4 5 0 3 1 19 (48)
5 (15)
3 4 0 1 1 9 (23)
5 4 1 10 (29)
8 3 1 12 (30)
0 0
Total Anaerobes Bacteroides Bacteroides Bacteroides
5 4 2 1 1 19 (56)h
” Number. ’ Percentage in parentheses.
aerobes accounted for the majority of organisms, 48% of the isolates, and gram-negative aerobes accounted for 23%. Anaerobes accounted for 30% of the isolates. There was no statistical difference between pre- and post-therapy microflora. Analysis of the distribution of isolates in each week revealed results similar to those previously noted. Although the distributions of isolates before, during, and after therapy appear to be similar for the group overall, analysis of each individual patient reveals that the individual flora were not as stable throughout the course of the therapy. Examination of individual patients demonstrated that more than 50% of their original isolates were no longer present at the completion of therapy. Only Lactobacillus and Bacteroides melaninogenicus appear to be stable throughout the course of radiation therapy in each patient positive for those organisms. DISCUSSION Infections occurring in the genital tract of patients with gynecologic malignancies most likely arise from organisms populating the genital tract in a mechanism similar to that seen in other gynecologic infections [51. In an attempt to reduce the risk of infection in patients with cervical cancer, broad-spectrum antibiotic prophylaxis was administered in a manner similar to that used for benign gynecology patients [2-41. The endocervical and vaginal organisms found in the present study reflect the
BACTERIAL
235
FLORA AND RADIATION
flora found in women without genital tract malignancies. Overall, there appears to be no significant change in the pattern of bacterial isolates when the group as a whole is examined. This is similar to the results previously reported by Gilstrap et al. [5]. Blythe also reported that patients with cervical cancer had the same flora as patients without malignancy and the frequency of organisms seemed independent of the dose of radiation [7]. In Blythe’s study the anaerobes also appeared to be unchanged. Mead [8], however, reported that the frequency of Bacteroides species and Escherichia coli was increased in patients with invasive cervical cancer. Unfortunately, patients were not followed throughout radiation therapy to see if any change occurred. Gerstner et al. [9] examined patients undergoing intracavitary applications of iridium with afterloading technique. They reported that the composition of the endometrial flora was not altered significantly by the intracavitary applications. The only significant change was an increase in the frequency of aerobic spore formers. Although more organisms were recovered, the increase in the number of organisms was not significant. The authors point out, as is apparent here, that radiation is not capable of sterilizing the endocervix or endometrium. Examination of the individual patient reveals a picture somewhat different from that of the group as a whole. The overall frequency of bacterial isolates of the group does not appear to have changed as had previously been reported [5,7,9], and the isolates are similar to those reported in patients without malignancy; however, during the course of therapy, each patient had a change in more than half the organisms isolated from their pretreatment culture. Therefore, selection of antibiotic therapy, based on a preradiation therapy culture, is not valid
in an individual patient after radiation therapy has begun. If antimicrobial coverage is indicated for patients either during or following radiation therapy, broad-spectrum coverage for both gram-positive and -negative aerobes, along with anaerobes, should be included until specific culture results are available to indicate the patient’s organisms at the time of suspected infection. REFERENCES I. Schwarz, R. H. Management of postoperative infections in obstetrics and gynecology, C/in. Obster. Gynrcol. 19, 97-108 (1976).
2. Micha, J. P., Kucera, P. R., Birkett, J. P., Chambers, G., Sheets, E. E., and DiSaia, P. J. Prophylactic mezlocillin in radical hysterectomy, Obstet. Gyncwd. 69, 251-254 (1987). Marsden, D. E., Cavanagh, D., Wisniewski, B. J.. Roberts, W. S., and Lyman, G. H. Factors affecting the incidence of infectious morbidity after radical hysterectomy. Amer. J. Obstrt. Gynecol. 152, 817-821 (1985). 4. Sevin, B., Reinaldo. R.. Lichtinger, M.. Girtanner, R. E.. and Averette, H. E. Antibiotic prevention of infection complicating radical abdominal hysterectomy. Obstrt. Gynewl. 64, 539-545 (1984). s. Gilstrap. L. C., III, Gibbs, R. S., Michel, T. J., and Hauth, J. C. Genital aerobic bacterial flora of women receiving radiotherapy for gynecologic malignancy, Gynecol. Oncol. 23, 35-39 (1986). 6. Fare, S., Phillips, L. E., Baker, J. L., Goodrich, K. H., Turner, R. M.. and Riddle. G. D. Comparative efficacy and safety of mezlocillin, cefoxitin, and clindamycin plus gentamycin in post partum endometritis, Obstet. G.vnecd. 69, 760-766 (1987). Blythe, J. G. Cervical bacterial flora in patients with gynecologic malignancies, Amer. J. Obstrt. Gynecol. 131, 438-445 (1978). Mead, P. B. Cervical-vaginal flora of women with invasive cervical cancer. Obstef. GynPcol. 52, 601-604 (1978). Gerstner, G. J., Kucera. H., Weghaupt, K., and Rotter, M. Endometrial bacteriology in patients with endometrial cancer before and after irradiation using Ir-192 and an afterloading technique, Arch. G.vnecol. 231, 299-306 (1982).