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Comparison of ticarcillin plus clavulanic acid with cefoxitin in the treatment of female pelvic infection
Comparison of Ticarcillin plus Clavulanic Acid with Cefoxitin in the Treatment of Female Pelvic Infection
Ninety-three female patients with post-cesarean endometrttis, posthysterectomy pelvic cellulitis, and other miscellaneous moderately severe pelvic soft-tissue infections were treated in a randomized fashion with either ticarcillin plus clavulanic acid or cefoxftln. Of the 47 patients treated with ticarcillin plus clavulanlc acid, 36 had clinical cures, four showed improvement, therapy failed in three, and two were nonevaluable, for a failure rate of 6.7 percent. Of the 46 patients treated with cefoxitin, 36 had clinical cures, five showed improvement, therapy falled in seven, and one was nonevaluable, for a failure rate of 15.6 percent. Bacteriologically, the addition of clavulanic acid to ticarcillin was found to broaden the antibacterial spectrum to include some Escherichia coli, most Klebsiella, many coagulase-negative staphylococci, and all isolates of Staphylococcus aureus. Adverse reactions were few, with only one patient having therapy with cefoxltfn discontinued because of side effects. ft is concluded that ticarcfllin plus clavulanic acid is quite suitable for antibiotic therapy of female pelvic soft-tissue infectlon, based on the (expanded) coverage of both aerobic and anaerobic bacterial species.
JOSEPH G. PASTOREK, Jr., M.D. KENNETH E. ALDRIDGE, Ph.D. GRACE L. CUNNINGHAM, R.N. New
Orleans,
Louisiana
SEBASTIAN FARO, Ph.D., M.D. SHARON GRAFFEO, R.N. Houston,
Texas
GENE S. McNEELEY, M.D. Memphis,
Tennessee
JAMES S. TAN, M.D. Akron,
Ohio
From the Sectton of Infectious Disease, Department of Obstetrics and Gynecology, and the Department of Medicine, Louisiana State University Medical Center, New Orleans, Louisiana; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; Department of Obstetrics and Gynecology, University of Tennessee Center for the Health Sciences, Memphis, Tennessee; and Infectious Disease Service, Akron City Hospital, Akron, Ohio. This study was supported by a grant from Seecham Laboratories. Requests for reprints should be addressed to Dr. Joseph G. Pastorek, Jr., Section of Infectious Disease, Department of Obstetrics and Gynecology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112-2822.
A combination of the semisynthetic penicillin antibiotic ticarcillin and the beta-lactamase inhibitor clavulanic acid (as the potassium salt) is now available. The addition of clavulanate potassium protects the ticarcillin molecule against the activity of bacterial beta-lactamases elaborated by the Enterobacteriaceae, various staphylococci, and other common bacterial species. The result is an effective broadening of the antibacterial spectrum of ticarcillin [l]. Female soft-tissue pelvic infections, such as post-cesarean endometritis and post-hysterectomy pelvic cellulitis, are considered to be polymicrobial in etiology, involving both aerobic and anaerobic bacteria [2,3]. Antibiotic therapy of these infections has classically included an antibiotic effective against aerobic gram-negative organisms (e.g., Escherichia coli) and an agent with activity against anaerobic bacteria (e.g., Bacteroides fragilis). Clindamycin plus an aminoglycoside [4] is often considered the “gold standard.” Advances in beta-lactam antibiotic technology, however, have provided new penicillin and cephalosporin drugs with a spectrum of activity sufficiently broad to include both aerobic and anaerobic bacterial species. Many such agents have been used successfully as single agents to treat
November 29,198!5
The Amewlcan Journal of Medlclne
Volume 79 (wppl
SE)
161
SYMPOSIUM
ON BETA-LACTAMASE
INHIBITION-PASTOREK
ET AL
female soft-tissue pelvic infections [5-71. A combination of ticarcillin plus clavulanic acid, by virtue of a broadened spectrum against organisms commonly involved in female pelvic infections, should be a logical choice for singleagent treatment of these infections. A study was undertaken, therefore, to compare ticarcillin plus clavulanic acid with another proven single agent (cefoxitin) in the antibiotic therapy of female pelvic soft-tissue infection. PATIENTS
AND METHODS
Patients were enrolled in this study while hospitalized in Charity Hospital of New Orleans (Louisiana State University Service), New Orleans, Louisiana, Hospital of the University of Tennessee Center for the Health Sciences, Memphis, Tennessee, and Akron City Hospital, Akron, Ohio. informed consent forms approved by the respective institutional review boards were signed by each patient prior to enrollment in the study. Patients were considered eligible for the study if the clinical diagnoses of post-cesarean endometritis, post-hysterectomy pelvic cellulitis, pelvic inflammatory disease, or other moderately severe pelvic soft-tissue infection were made. Excluded were those patients who refused to give informed consent or had allergy to penicillin and/or cephalosporin, serum creatinine levels greater than 2.5 mg/dl, creatinine clearance less than 30 ml per minute, irreversible liver disease, or previous (effective) antibiotic therapy. Pregnant or nursing women were excluded, as were patients who were not expected to be able to complete the study protocol. Patients were randomly assigned to receive either 3 g of ticarcillin plus 100 mg of clavulanate potassium intravenously every four to six hours, depending upon the examiner’s estimation of the severity of disease, or 2 g of cefoxitin intravenously every six hours, as recommended in the manufacturer’s package insert. Upon enrollment in the study, patients underwent a complete physical examination, including pelvic examination and examination of the abdominal wound (if present). Laboratory evaluation included complete blood cell count with white cell differential, platelet count, chemistry panel (including hepatic and renal functions), and complete urinalysis. Tests on which abnormal findings were obtained were repeated at intervals until normal values were achieved. Patients were monitored daily for clinical improvement and evidence of adverse effects. After the patient was afebrile and asymptomatic for 72 hours, the drug was discontinued and the patient was observed for an additional 24 hours before being discharged. Follow-up examination at one and six weeks after discharge from the hospital completed the patients’ participation in the study. At these times, any laboratory tests that had given abnormal results were repeated. Patients were considered to have clinical improvement if signs, symptoms, and laboratory evidence of infection lessened within 48 to 72 hours after initiation of antibiotic therapy. Patients were considered to have clinical cures if all signs and symptoms of infection resolved with ticarcillin plus clavulanic acid or cefoxitin therapy alone and had not returned by the final follow-up examination. Treatment was considered to have failed if signs and symptoms of infection persisted de-
162
November
26,1666
The
American
Journal
of Medlcine
spite single-agent therapy, or if additional antibiotics were added to the regimen. Several patients decided to withdraw from the study before their minimum duration of therapy (five days) was completed. In these cases, therapy was switched to an antibiotic standardly used for female pelvic infections (depending upon the institution patients were in, one of the various approved cephalosporins). These patients were considered to have improvement if signs and symptoms of infection had begun to abate with the study drug alone. Microbiology. Urine, blood, and genital specimens were obtained from each patient and sent to the laboratory for culture. In cases of post-cesarean endometritis, swabs of the uterine fundus were obtained transcervically. In patients with post-hysterectomy infection, swabs of the vaginal cuff wound were obtained at sterile speculum examination. Patients with pelvic inflammatory disease had endocervical cultures done for gonorrhea and, if obtained, culdocentesis fluid cultured for aerobic and anaerobic bacteria. Any patient thought to have an abdominal wound infection had either a swab culture done, if the wound was opened, or an aspirate of wound fluid taken for culture with a sterile needle and syringe. Blood was processed aerobically and anaerobically using a Bactek (Johnston Laboratories). A 0.1 ml aliquot of urine was plated on sheep blood and MacConkey agar and incubated at 35X, and the results were read at 24 hours. Genital swabs and wound cultures were plated on aerobic and prereduced anaerobic media and incubated at 35°C. Aerobic plates were examined at 24 hours; anaerobic plates were examined after 48 hours of incubation. Aerobic isolates were identified using conventional tube methods; anaerobic isolates were identified using the Minitek II biochemical profile in conjunction with gas-liquid chromatography. Complete organism identification was done using standard procedures [8]. Antimicrobial Susceptibility Testing. All organisms were tested for their susceptibilities to ticarcillin plus clavulanic acid and ticarcillin alone using a broth microdilution method as recommended by the National Committee for Clinical Laboratory Standards [9]. Disk sensitivity testing was also performed using antibiotic disks supplied by Beecham Laboratories. Bacteria were considered susceptible to ticarcillin plus clavulanic acid if the minimal inhibitory concentration was less than or equal to 32 pg/ml or the disk zone size was greater than or equal to 18 mm. Intermediate sensitivity was considered to be a minimal inhibitory concentration of 84 pglml or zone sizes of between 12 and 17 mm. Bacteria were considered resistant at minimal inhibitory concentrations of 128 @g/ml or more, or zone sizes of 11 mm or less. An exception was the Staphylococcus species, which were considered resistant at minimal inhibitory concentrations of 84 pglml or more, or zone sizes of 17 mm or less. RESULTS Ninety-three women were enrolled in the study; 47 were randomly assigned to receive ticarcillin plus clavulanic acid therapy and 46 were assigned to receive cefoxitin. The mean age was 26.6 years (range 14 to 48) in the ticarcillin plus clavulanic acid group and 25.3 years (range 16 to 59) in the cefoxitin group. The majority of patients
Volume
76 (suppl66)
SYMPOSIUM
ON BETA-LACTAMASE
INHIBITION-PASTOREK
ET AL
COMMENTS
were black and of low socioeconomic status, and were derived primarily from clinic populations at the respective study centers. Patients were enrolled in the study with a variety of diagnoses (some patients with more than one), including post-cesarean endometritis, post-hysterectomy pelvic cellulitis, pelvic inflammatory disease, wound infection, and urinary tract infection. Three patients, two in the group receiving ticarcillin plus clavulanic acid and one in the group receiving cefoxitin, were considered nonevaluable on the basis of being inappropriately placed in the study or having the drug discontinued too early to make an assessment. Therefore, ninety patients could be evaluated for clinical efficacy. Of the 45 patients treated with ticarcillin plus clavulanic acid who were clinically evaluable, 38 had cures, four showed improvement, and therapy failed in three (failure rate of 6.7 percent). Of the 45 evaluable patients in the cefoxitin-treated group, 33 had cures, five showed improvement, and therapy failed in seven (failure rate of 15.6 percent). Adverse reactions were equally minimal in both treatment groups. Two hundred and one bacterial isolates were recovered from these 93 patients. There were 38 anaerobic isolates, 72 gram-negative aerobic isolates, and 91 gram-positive aerobic isolates. Predominant organisms were group B streptococci, enterococci, coagulase-negative staphylococci, S. aureus, E. coli, Proteus mirabilis, Klebsiella species, and Bacteroides species. It is apparent that the addition of clavulanate potassium broadens the spectrum of ticarcillin against some E. coli, most Klebsiella, some coagulase-negative staphylococci, and all isolates of S. aureus. All anaerobic isolates (n = 18) for which sensitivity patterns were available were susceptible in vitro to both ticarcillin plus clavulanic acid and ticarcillin.
The results of this study indicate that ticarcillin plus clavulanic acid is a reasonable antibiotic for single-agent therapy of female pelvic infections caused by aerobic and anaerobic, gram-positive and gram-negative bacteria. Ticarcillin plus clavulanic acid compares quite favorably with cefoxitin, which has previously been shown to be effective in these infections [7j. Ticarcillin plus clavulanic acid also retains the benign side effects’ profile of the semisynthetic penicillins. Most adverse reactions are of a minor nature and do not preclude continuation of the drug. The addition of potassium clavulanate to ticarcillin has expanded the spectrum of the parent drug, giving greater coverage of organisms often resistant to the semisynthetic penicillins, notably some of the Enterobacteriaceae (especially Klebsiella) and staphylococci (in particular, S. aureus). At the same time, ticarcillin plus clavulanic acid retains coverage of the gram-positive cocci, including the enterococci, activity that is lacking with the broadspectrum cephalosporins (including cefoxitin) [lo]. In conclusion, ticarcillin plus clavulanic acid appears to be a safe and efficacious antibiotic for use as a single agent in the therapy of female pelvic soft-tissue infection. The added antibacterial coverage provided by the addition of clavulanic acid to ticarcillin includes beta-lactamaseproducing organisms that are commonly found in these types of infections and that may ordinarily cause physicians to add a second drug (such as an aminoglycoside or antistaphylococcal penicillin) to patients’ regimens, thus escalating cost and toxicity. ACKNOWLEDGMENT
We thank Hank G. Lemoine for his tireless and timely secretarial assistance.
REFERENCES 1.
2.
3. 4.
5.
PA, Coleman K, Fisher J, Taylor D: In vitro synergestic properties of clavulanic acid with ampicillin, amoxycillin, and ticarcillin. J Antimicrob Chemother 1980; 6: 455-470. Gilstrap LC Ill, Cunningham FG: The bacterial pathogeneses of infection following cesarean section. Obstet Gynecol 1979; 53: 545-549. Chow AW: Antimicrobial therapy of gynecological infections: an overview. J Antimicrob Chemother 1982; 9: 139-147. diZerega GS, Yonekura ML, Roy S, Nakamura RM, Ledger WJ: A comparison of clindamycin-gentamicin and penicillin-gentamicin in the treatment of post-cesarean section endomyometritis. Am J Obstet Gynecol 1979; 134: 238-242. Faro S, Sanders CV, Aldridge KE: Use of single-agent antimicrobial therapy in the treatment of polymicrobial female pelvic infections. Obstet Gynecol 1982; 60: 232-236. Hunter
November
29, 1985
6.
7.
8.
9.
10.
The
Marier RL, Faro S, Sanders CV, Williams W. Derks F, Jannev A. Aldridge K: Moxalactam in the therapy of serious. infecti& Antimicrob Agents Chemother 1982; 21: 650-654. Sweet RL, Ledger WJ: Cefoxitin: single-agent treatment of mixed aerobic-anaerobic pelvic infections. Obstet Gynecol 1979; 54: 193-198. Lennette EH, Balows A, Hausler WJ Jr, Truant JP, eds. Manual of clinical microbiology. Washington DC: American Society for Microbiology, 1990. National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1980. Fan, S, Pastorek JG: The enterococcus: myth or reality in ObGyn infections? Infections in Surgery 1963; 2: 787-794.
American
Journal
of Medicine
Volume
79 (suppl
58)
163
Ninety-three female patients with post-cesarean endometrttis, posthysterectomy pelvic cellulitis, and other miscellaneous moderately severe pelvic soft-tissue infections were treated in a randomized fashion with either ticarcillin plus clavulanic acid or cefoxftln. Of the 47 patients treated with ticarcillin plus clavulanlc acid, 36 had clinical cures, four showed improvement, therapy failed in three, and two were nonevaluable, for a failure rate of 6.7 percent. Of the 46 patients treated with cefoxitin, 36 had clinical cures, five showed improvement, therapy falled in seven, and one was nonevaluable, for a failure rate of 15.6 percent. Bacteriologically, the addition of clavulanic acid to ticarcillin was found to broaden the antibacterial spectrum to include some Escherichia coli, most Klebsiella, many coagulase-negative staphylococci, and all isolates of Staphylococcus aureus. Adverse reactions were few, with only one patient having therapy with cefoxltfn discontinued because of side effects. ft is concluded that ticarcfllin plus clavulanic acid is quite suitable for antibiotic therapy of female pelvic soft-tissue infectlon, based on the (expanded) coverage of both aerobic and anaerobic bacterial species.
JOSEPH G. PASTOREK, Jr., M.D. KENNETH E. ALDRIDGE, Ph.D. GRACE L. CUNNINGHAM, R.N. New
Orleans,
Louisiana
SEBASTIAN FARO, Ph.D., M.D. SHARON GRAFFEO, R.N. Houston,
Texas
GENE S. McNEELEY, M.D. Memphis,
Tennessee
JAMES S. TAN, M.D. Akron,
Ohio
From the Sectton of Infectious Disease, Department of Obstetrics and Gynecology, and the Department of Medicine, Louisiana State University Medical Center, New Orleans, Louisiana; Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas; Department of Obstetrics and Gynecology, University of Tennessee Center for the Health Sciences, Memphis, Tennessee; and Infectious Disease Service, Akron City Hospital, Akron, Ohio. This study was supported by a grant from Seecham Laboratories. Requests for reprints should be addressed to Dr. Joseph G. Pastorek, Jr., Section of Infectious Disease, Department of Obstetrics and Gynecology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112-2822.
A combination of the semisynthetic penicillin antibiotic ticarcillin and the beta-lactamase inhibitor clavulanic acid (as the potassium salt) is now available. The addition of clavulanate potassium protects the ticarcillin molecule against the activity of bacterial beta-lactamases elaborated by the Enterobacteriaceae, various staphylococci, and other common bacterial species. The result is an effective broadening of the antibacterial spectrum of ticarcillin [l]. Female soft-tissue pelvic infections, such as post-cesarean endometritis and post-hysterectomy pelvic cellulitis, are considered to be polymicrobial in etiology, involving both aerobic and anaerobic bacteria [2,3]. Antibiotic therapy of these infections has classically included an antibiotic effective against aerobic gram-negative organisms (e.g., Escherichia coli) and an agent with activity against anaerobic bacteria (e.g., Bacteroides fragilis). Clindamycin plus an aminoglycoside [4] is often considered the “gold standard.” Advances in beta-lactam antibiotic technology, however, have provided new penicillin and cephalosporin drugs with a spectrum of activity sufficiently broad to include both aerobic and anaerobic bacterial species. Many such agents have been used successfully as single agents to treat
November 29,198!5
The Amewlcan Journal of Medlclne
Volume 79 (wppl
SE)
161
SYMPOSIUM
ON BETA-LACTAMASE
INHIBITION-PASTOREK
ET AL
female soft-tissue pelvic infections [5-71. A combination of ticarcillin plus clavulanic acid, by virtue of a broadened spectrum against organisms commonly involved in female pelvic infections, should be a logical choice for singleagent treatment of these infections. A study was undertaken, therefore, to compare ticarcillin plus clavulanic acid with another proven single agent (cefoxitin) in the antibiotic therapy of female pelvic soft-tissue infection. PATIENTS
AND METHODS
Patients were enrolled in this study while hospitalized in Charity Hospital of New Orleans (Louisiana State University Service), New Orleans, Louisiana, Hospital of the University of Tennessee Center for the Health Sciences, Memphis, Tennessee, and Akron City Hospital, Akron, Ohio. informed consent forms approved by the respective institutional review boards were signed by each patient prior to enrollment in the study. Patients were considered eligible for the study if the clinical diagnoses of post-cesarean endometritis, post-hysterectomy pelvic cellulitis, pelvic inflammatory disease, or other moderately severe pelvic soft-tissue infection were made. Excluded were those patients who refused to give informed consent or had allergy to penicillin and/or cephalosporin, serum creatinine levels greater than 2.5 mg/dl, creatinine clearance less than 30 ml per minute, irreversible liver disease, or previous (effective) antibiotic therapy. Pregnant or nursing women were excluded, as were patients who were not expected to be able to complete the study protocol. Patients were randomly assigned to receive either 3 g of ticarcillin plus 100 mg of clavulanate potassium intravenously every four to six hours, depending upon the examiner’s estimation of the severity of disease, or 2 g of cefoxitin intravenously every six hours, as recommended in the manufacturer’s package insert. Upon enrollment in the study, patients underwent a complete physical examination, including pelvic examination and examination of the abdominal wound (if present). Laboratory evaluation included complete blood cell count with white cell differential, platelet count, chemistry panel (including hepatic and renal functions), and complete urinalysis. Tests on which abnormal findings were obtained were repeated at intervals until normal values were achieved. Patients were monitored daily for clinical improvement and evidence of adverse effects. After the patient was afebrile and asymptomatic for 72 hours, the drug was discontinued and the patient was observed for an additional 24 hours before being discharged. Follow-up examination at one and six weeks after discharge from the hospital completed the patients’ participation in the study. At these times, any laboratory tests that had given abnormal results were repeated. Patients were considered to have clinical improvement if signs, symptoms, and laboratory evidence of infection lessened within 48 to 72 hours after initiation of antibiotic therapy. Patients were considered to have clinical cures if all signs and symptoms of infection resolved with ticarcillin plus clavulanic acid or cefoxitin therapy alone and had not returned by the final follow-up examination. Treatment was considered to have failed if signs and symptoms of infection persisted de-
162
November
26,1666
The
American
Journal
of Medlcine
spite single-agent therapy, or if additional antibiotics were added to the regimen. Several patients decided to withdraw from the study before their minimum duration of therapy (five days) was completed. In these cases, therapy was switched to an antibiotic standardly used for female pelvic infections (depending upon the institution patients were in, one of the various approved cephalosporins). These patients were considered to have improvement if signs and symptoms of infection had begun to abate with the study drug alone. Microbiology. Urine, blood, and genital specimens were obtained from each patient and sent to the laboratory for culture. In cases of post-cesarean endometritis, swabs of the uterine fundus were obtained transcervically. In patients with post-hysterectomy infection, swabs of the vaginal cuff wound were obtained at sterile speculum examination. Patients with pelvic inflammatory disease had endocervical cultures done for gonorrhea and, if obtained, culdocentesis fluid cultured for aerobic and anaerobic bacteria. Any patient thought to have an abdominal wound infection had either a swab culture done, if the wound was opened, or an aspirate of wound fluid taken for culture with a sterile needle and syringe. Blood was processed aerobically and anaerobically using a Bactek (Johnston Laboratories). A 0.1 ml aliquot of urine was plated on sheep blood and MacConkey agar and incubated at 35X, and the results were read at 24 hours. Genital swabs and wound cultures were plated on aerobic and prereduced anaerobic media and incubated at 35°C. Aerobic plates were examined at 24 hours; anaerobic plates were examined after 48 hours of incubation. Aerobic isolates were identified using conventional tube methods; anaerobic isolates were identified using the Minitek II biochemical profile in conjunction with gas-liquid chromatography. Complete organism identification was done using standard procedures [8]. Antimicrobial Susceptibility Testing. All organisms were tested for their susceptibilities to ticarcillin plus clavulanic acid and ticarcillin alone using a broth microdilution method as recommended by the National Committee for Clinical Laboratory Standards [9]. Disk sensitivity testing was also performed using antibiotic disks supplied by Beecham Laboratories. Bacteria were considered susceptible to ticarcillin plus clavulanic acid if the minimal inhibitory concentration was less than or equal to 32 pg/ml or the disk zone size was greater than or equal to 18 mm. Intermediate sensitivity was considered to be a minimal inhibitory concentration of 84 pglml or zone sizes of between 12 and 17 mm. Bacteria were considered resistant at minimal inhibitory concentrations of 128 @g/ml or more, or zone sizes of 11 mm or less. An exception was the Staphylococcus species, which were considered resistant at minimal inhibitory concentrations of 84 pglml or more, or zone sizes of 17 mm or less. RESULTS Ninety-three women were enrolled in the study; 47 were randomly assigned to receive ticarcillin plus clavulanic acid therapy and 46 were assigned to receive cefoxitin. The mean age was 26.6 years (range 14 to 48) in the ticarcillin plus clavulanic acid group and 25.3 years (range 16 to 59) in the cefoxitin group. The majority of patients
Volume
76 (suppl66)
SYMPOSIUM
ON BETA-LACTAMASE
INHIBITION-PASTOREK
ET AL
COMMENTS
were black and of low socioeconomic status, and were derived primarily from clinic populations at the respective study centers. Patients were enrolled in the study with a variety of diagnoses (some patients with more than one), including post-cesarean endometritis, post-hysterectomy pelvic cellulitis, pelvic inflammatory disease, wound infection, and urinary tract infection. Three patients, two in the group receiving ticarcillin plus clavulanic acid and one in the group receiving cefoxitin, were considered nonevaluable on the basis of being inappropriately placed in the study or having the drug discontinued too early to make an assessment. Therefore, ninety patients could be evaluated for clinical efficacy. Of the 45 patients treated with ticarcillin plus clavulanic acid who were clinically evaluable, 38 had cures, four showed improvement, and therapy failed in three (failure rate of 6.7 percent). Of the 45 evaluable patients in the cefoxitin-treated group, 33 had cures, five showed improvement, and therapy failed in seven (failure rate of 15.6 percent). Adverse reactions were equally minimal in both treatment groups. Two hundred and one bacterial isolates were recovered from these 93 patients. There were 38 anaerobic isolates, 72 gram-negative aerobic isolates, and 91 gram-positive aerobic isolates. Predominant organisms were group B streptococci, enterococci, coagulase-negative staphylococci, S. aureus, E. coli, Proteus mirabilis, Klebsiella species, and Bacteroides species. It is apparent that the addition of clavulanate potassium broadens the spectrum of ticarcillin against some E. coli, most Klebsiella, some coagulase-negative staphylococci, and all isolates of S. aureus. All anaerobic isolates (n = 18) for which sensitivity patterns were available were susceptible in vitro to both ticarcillin plus clavulanic acid and ticarcillin.
The results of this study indicate that ticarcillin plus clavulanic acid is a reasonable antibiotic for single-agent therapy of female pelvic infections caused by aerobic and anaerobic, gram-positive and gram-negative bacteria. Ticarcillin plus clavulanic acid compares quite favorably with cefoxitin, which has previously been shown to be effective in these infections [7j. Ticarcillin plus clavulanic acid also retains the benign side effects’ profile of the semisynthetic penicillins. Most adverse reactions are of a minor nature and do not preclude continuation of the drug. The addition of potassium clavulanate to ticarcillin has expanded the spectrum of the parent drug, giving greater coverage of organisms often resistant to the semisynthetic penicillins, notably some of the Enterobacteriaceae (especially Klebsiella) and staphylococci (in particular, S. aureus). At the same time, ticarcillin plus clavulanic acid retains coverage of the gram-positive cocci, including the enterococci, activity that is lacking with the broadspectrum cephalosporins (including cefoxitin) [lo]. In conclusion, ticarcillin plus clavulanic acid appears to be a safe and efficacious antibiotic for use as a single agent in the therapy of female pelvic soft-tissue infection. The added antibacterial coverage provided by the addition of clavulanic acid to ticarcillin includes beta-lactamaseproducing organisms that are commonly found in these types of infections and that may ordinarily cause physicians to add a second drug (such as an aminoglycoside or antistaphylococcal penicillin) to patients’ regimens, thus escalating cost and toxicity. ACKNOWLEDGMENT
We thank Hank G. Lemoine for his tireless and timely secretarial assistance.
REFERENCES 1.
2.
3. 4.
5.
PA, Coleman K, Fisher J, Taylor D: In vitro synergestic properties of clavulanic acid with ampicillin, amoxycillin, and ticarcillin. J Antimicrob Chemother 1980; 6: 455-470. Gilstrap LC Ill, Cunningham FG: The bacterial pathogeneses of infection following cesarean section. Obstet Gynecol 1979; 53: 545-549. Chow AW: Antimicrobial therapy of gynecological infections: an overview. J Antimicrob Chemother 1982; 9: 139-147. diZerega GS, Yonekura ML, Roy S, Nakamura RM, Ledger WJ: A comparison of clindamycin-gentamicin and penicillin-gentamicin in the treatment of post-cesarean section endomyometritis. Am J Obstet Gynecol 1979; 134: 238-242. Faro S, Sanders CV, Aldridge KE: Use of single-agent antimicrobial therapy in the treatment of polymicrobial female pelvic infections. Obstet Gynecol 1982; 60: 232-236. Hunter
November
29, 1985
6.
7.
8.
9.
10.
The
Marier RL, Faro S, Sanders CV, Williams W. Derks F, Jannev A. Aldridge K: Moxalactam in the therapy of serious. infecti& Antimicrob Agents Chemother 1982; 21: 650-654. Sweet RL, Ledger WJ: Cefoxitin: single-agent treatment of mixed aerobic-anaerobic pelvic infections. Obstet Gynecol 1979; 54: 193-198. Lennette EH, Balows A, Hausler WJ Jr, Truant JP, eds. Manual of clinical microbiology. Washington DC: American Society for Microbiology, 1990. National Committee for Clinical Laboratory Standards: Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Villanova, Pennsylvania: National Committee for Clinical Laboratory Standards, 1980. Fan, S, Pastorek JG: The enterococcus: myth or reality in ObGyn infections? Infections in Surgery 1963; 2: 787-794.
American
Journal
of Medicine
Volume
79 (suppl
58)
163