THE JOURNAL OF INFECTIOUS DISEASES. VOL. \,1:;, SUPPLEMENT.

MARCH \977
© 1977 by the University of Chicago. All rights reserved.

Comparison of Clindamycin and Chloramphenicol in Treatment

of Serious Infections of the Female Genital Tract

William J. Ledger, Carol L. Gee, From the Departments of Obstetrics-Gynecology and

William P. Lewis, and J. Ronald Bobiu Pathology, Los Angeles County-University of
Southern California Medical Center,
Los Angeles, California

A study was performed of 102 obstetric-gynecologic patients who were thought to have
sepsis or a pelvic abscess. Fifty-three of these women received chloramphenicol and
49 received clindamycin. In addition, all patients received penicillin or a similar
antibiotic and an aminoglycoside. Similar clinical results were observed with the two
treatment regimens. In eight of the 49 patients who received clindamycin and in

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three of 52 patients who received chloramphenicol, use of the drug was discontinued
because of side effects. These combinations of antibiotics did not eliminate the nec-
essity for major operative drainage, which was required in 40 patients. Resistant
organisms were recovered from only two patients. Although sepsis and shock were
most frequently associated with gram-negative aerobic bacteremia, they occurred in
two patients in whom only anaerobes were recovered from blood cultures. Because
the clinical results with the two regimens were equivalent, a decision to use either
clindamycin or chloramphenicol should be based on the individual physician'S
assessment of the toxicity of these agents.

Recently, there has been increased interest in
the role of anaerobic bacteria in serious soft tissue
infections of the female genital tract. Several in-
vestigators have recovered anaerobic bacteria
from >50% of such infections [1-3].
A major concern for the obstetrician-gynecol-
ogist has been the recovery of Bacteroides fragilis
from serious infections, particularly those asso-
ciated with abscess formation [4, 5] because of
the relative resistance of B. fragilis to commonly
used antibiotics. In patients with serious infec-
tions in which this organism is suspected as a
pathogen, the best antibiotics, based on labora-
tory susceptibility tests, clinical experience, and
Food and Drug Administration (FDA) ap-
proval, are clindamycin and chloramphenicol.
Each has serious potential toxicity; pseudomem-
branous colitis has been associated with use of
clindamycin, and aplastic anemia has been asso-
ciated with use of chloramphenicol. These po-
tential side effects have influenced the decision-
making process of physicians in choosing between
these two drugs. The process of choosing an anti-
Please address requests for reprints to Dr. William J.
Ledger, Department of Obstetrics and Gynecology, Los An-
geles County-University of Southern California Medical
Center, Los Angeles, California 90033.
microbial agenr also should be based on efficacy
studies, but, to date, a comparative .study of these
two drugs has not been done.
This study compared the results of treatment
with clindamycin and chloramphenicol in women
with serious soft tissue infections. Because a pre-
vious study had demonstrated problems with en-
terococcal infections when antibiotic coverage
was incomplete [6], the protocol employed peni-
cillin and an aminoglycoside in addition to eith-
er clindamycin or chloramphenicol.
Materials and Methods
All patients admitted to the gynecology service
between December 1973 and November 1975
were eligible for study. Only patients with seri-
ous infections who were thought, on clinical
grounds, to have either sepsis or the possibility
of a pelvic abscess were included. The women
were informed of the nature of the study and,
if they agreed to participate, received either clin-
damycin (2.4 g iv every 24 hr in four divided
doses) or chloramphenicol (4.0 g iv every 24
hr in four divided doses). The choice of drug
was made by random selection based on a medi-
cation slip in a sealed envelope. In addition, all
patients received penicillin (2 X 104 units iv

530
Female Pelvic Infections
daily) and an aminoglycoside. Of 11 women al-
lergic to penicillin, eight received erythromycin,
and three received cephalothin. Blood cultures
from all patients were cultured aerobically and
anaerobically prior to the onset of antibiotic ther-
apy. In addition, aspirates from the cul-de-sac
or other sites of infection were cultured direct-
lyon prereduced media and incubated in a Gas-
Pak jar [7].
Results
There were 105 women enrolled in the antibiot-
ic protocol. The charts of three women were not
available for analysis; all of these women had re-
ceived clindamycin. As a result, 53 women who
received chloramphenicol and 49 who received
clindamycin were studied.
The two groups of women had similar infec-
tions (table 1). Most (89 of 102) had community-
acquired infections. The two patient populations
were also similar in age and race. The propor-
tion of blacks (39.2%) was greater than that
which exists in our total inpatient population
(--15%).
For evaluation of the pathogens, only positive
blood cultures or direct aspirates of the infected
site were used for analysis. All endocervical cul-
tures for anaerobic isolates were discarded. Blood
cultures, all obtained early in the course of in-
fection, were positive in 12 patients, nine of
whom had infected abortions (table 2). Anaer-
obes were isolated from the blood of seven pa-
tients. Seven patients, including six with bacter-
emia, had evidence of shock. In two patients with
Table 1. Diagnoses of 102 women who received
clindamycin (2.4 g iv every 24 hr in four divided
doses) or chloramphenicol (4.0 g iv every 24 hr in
four divided doses) for treatment of pelvic infections.
Clinda- Chlor-
Diagnosis mycin amphenicol
Community-acquired infection
Pelvic inflammatory disease 34 32
Infected abortion 8 15
Subtotal 42 47
Hospital-acquired infection
Postpartum infections 5 5
Posthysterectomy infections 2 1
Total 49 53
531
Table 2. Microorganisms isolated from 12 patients
with bacteremia treated with clindamycin (2.4 g iv
every 24 hr in four divided doses) or chloramphenicol
(4.0 g iv every 24 hr in four divided doses).
No. of strains
treated with
Clinda- Chlor-
Organism mycin amphenicol
Aerobes
Escherichia coli 2
Pseudomonas species 1
Enterobacter 1
Anaerobes
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Bacteroides fragilis 2
Pepto coccus 2
Bacteroides species 2
Clostridium species 1
an early onset of shock, only anaerobes were re-
covered from the bloodstream; Peptococcus was
isolated from one patient, and B. fmgilis was
found in the other.
The isolation of organisms from sites of infec-
tion was often difficult. In many patients with a
suspected tuboovarian abscess, culdocentesis was
not performed because of the fear of rupturing
an intraperitoneal abscess. Culdocentesis was per-
formed in only 15 women presenting with salpin-
gitis on admission, and anaerobes were obtained
from 11 (73%) (table 3). Fewer anaerobes
(51%) were isolated by direct aspirate cultures
of abscess contents. There was no correlation be-
tween length of time of prior antibiotic therapy
and the recovery of anaerobes from abscesses.
There were no deaths among the 102 patients.
Of special interest was the fact that 58 patients re-
quired some form of operative intervention for
cure of their infection. Forty patients underwent
major procedures such as extraperitoneal drain-
age of abscesses and laparotomy for removal of in-
fected tissue. The necessity for operation was not
related to therapy with either clindamycin or
chloramphenicol.
Therapy with clindamycin was discontinued
in one patient who developed a rash and seven
who had diarrhea. Pseudomembranous colitis
was not diagnosed in any of these women with
diarrhea. Use of chloramphenicol was discon-
tinued in only three patients because of a rash
in one and persistent low white blood cell counts
in the two others. These changes disappeared
532 Ledger et al.

Table 3. Bacteria recovered from culdocentesis in 15 tive results are obtained, is the blood culture. Al-
patients with salpingitis and in direct aspirate from 37 though blood cultures were positive in only
patients.
12% of all patients studied, these cultures were
Isolate particularly helpful in the group with infected
recovered from abortions; cultures were positive in nine (39%)
Culdo- of 23 of these women. Since the blood culture
Organism centesis Abscess was rarely positive in the other patients, the clin-
Gram-positive aerobes ician had to select other techniques for useful
Streptococcus viridans 3 microbiologic information. Direct needle aspira-
Enterococcus 2 tion of infected material in the operating room
Group B J3-hemolytic
streptococci
yields meaningful information for management
Coagulase-negative of the patient in the postoperative period. How-

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staphylococci ever, operative intervention in most of these ,P~­
Gram-positive anaerobes tients occurred after several days of antibiotic
Peptostreptococcus 5 4
therapy. Direct needle aspiration from sites ad-
Peptococcus 1 1
Clostridium species 1 jacent to the infection (i.e., culdocentesis) can
Clostridium perjringens 1 provide important information about potential
Non-spore-forming bacilli 4 pathogens. However, this diagnostic technique is
Gram-negative aerobes not always feasible since many women with seri-
Escherichia coli 3 8
Corynebacterium vaginale 2
ous pelvic infection do not have a free cul-de-
Proteus sac. Another problem is that, on occasion, little
Pseudomonas or no fluid is obtained by culdocentesis.
Citrobacter The data from our study indicated that (1)
Gram-negative anaerobes
Escherichia coli was the aerobic organism most
Bacteroides species 4 3
Bacteroides jragilis 3 4 frequently recovered by culdocentesis and from
Bacteroides melaninogenicus 1 the abscess samples; (2) enterococci were rarely
Fusobacterium 2 1 recovered; and (3) among anaerobic isolates,
Veillonella 1 gram-positive cocci and gram-negative rods, par-
ticularly B. [ragilis, were commonly recovered.
Thus, it seems important to use antibiotics that
when chloramphenicol therapy was discontin- are effective against these microorganisms. Wheth-
ued. er a third antibiotic is needed for treatment of
infection with enterococci was not established by
this study.
Discussion
No clear superiority of either the clindamycin
The 102 patients in this series represent the most or chloramphenicol regimens was determined by
seriously ill women seen in our gynecologic ser- our results. In fact, the most crucial factor asso-
vice over two years. The patients were generally ciated with cure was operative intervention. In
young (only one was postmenopausal) and had the past, it has been erroneously believed that a
many social problems. All had intact host de- patient's failure to respond to antibiotics and the
fenses, and none had an underlying fatal disease. subsequent need for operative intervention were
Thus, a good prognosis could be expected when caused by the presence of resistant organisms.
the infection was treated adequately. The response of many physicians was to change
A continuing problem in evaluation of obstet- the antibiotic regimen. (One of the reasons for
ric-gynecologic patients is obtaining an adequate use of the three antibiotics in this study was our
sample of infected material for microbiologic concern about resistance of enterococci.) How-
tests. Cultures from the endocervical canal are ever, our study showed that only two of the ab-
not useful since anaerobes isolated from this site scesses contained organisms resistant to the anti-
are similar in women with and without pelvic in- biotics being administered. Most of the women
fections [8]. Probably the best source, when posi- who required major operations probably had es-
Female Pelvic Infections
tablished abscesses at the time of initiation of
antibiotic therapy. Thus, the failure to respond
to antibiotic treatment should alert the clinician
to the possibility of abscess formation and the
need for operative intervention.
Although bacteremia and shock were most fre-
quently observed in patients with infected abor-
tions, these women recovered rapidly after cu-
rettage and initiation of antibiotic therapy.
There was a favorable prognosis, provided that
major tissue trauma associated with events at
termination of pregnancy was not present.
Recently, there has been great interest in the
animal model of infection developed by Onder-
donk et al. [9]. These investigators demon-
strated early sepsis with aerobic gram-negative
rods and the late development of abscesses due
to anaerobes. The clinical realities of our study
reflected the late development of a pelvic abscess
with recovery of anaerobes, but there were varia-
tions from the animal model: (1) the majority
of organisms isolated from the bloodstream be-
fore initiation of antibiotic therapy were anaero-
bic, not aerobic; (2) although septic shock was
associated more frequently with aerobic sepsis,
septic shock occurred in two instances in which
only anaerobes were recovered from the blood-
stream; and (3) there was a wide range of clin-
ical response in those patients with salpingitis and
suspected abscess formation; some were afebrile
within 24 hr while others had a protracted course
of infection (one patient with more than 2,000
degree-hr of fever [10].
In retrospect, the single most definitive diag-
nostic criterion that indicated a rapid clinical re-
sponse was the recovery of Neisseria gonorrhoeae
from the endocervical culture. All 10 women
with this microbiologic finding responded rapid-
ly to antibiotic therapy, and none required
operative intervention. Although Chow et al.
[11] have questioned the significance of N. gon-
orrhoeae in salpingitis, our findings suggest that
this organism may have great importance. Our
findings also support the view of Eschenbach et
al. [12] that a gonococcal form of salpingitis ex-
ists.
This study did not establish the best anti-
biotics for treatment of seriously ill women
with anaerobic pelvic infections. Since the effi-
cacy of clindamycin and chloramphenicol seemed
S33
equivalent, the choice of drug must be based
on an esimate of relative toxicity. There were
more frequent problems, particularly diarrhea,
with clindamycin. Recognition of the signifi-
cance of diarrhea associated with use of this
drug has seemed to increase since the association
of clindamycin therapy with pseudomembran-
ous colitis was demonstrated by Tedesco et al.
[13]. Despite the frequent occurrence of diarrhea,
no cases of colitis were observed in this study. In
addition, no cases of aplastic anemia were seen
with chloramphenicol therapy. Our present view
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is that clindamycin should be used in the pa-
tient who has no symptoms of gastrointestinal
disorder. If diarrhea develops, chloramphenicol
can be substituted when indicated.
References
1. Rotheram, E. B., Jr., Schick, S. F. Nonc1ostridial anaer-
obic bacteria in septic abortion. Am. J. Med. 46:80-
89,1969.
2. Thadepalli, H., Gorbach, S. L., Keith, L. Anaerobic
infections of the female genital tract: bacteriologic
and therapeutic aspects. Am. J. Obstet. Gynecol. 117:
1034-1040, 1973.
3. Swenson, R. M., Michaelson, T. C., Daly, M. J., Spauld-
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S34
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