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Aztreonam plus clindamycin as therapy for pelvic infections in women
Aztreonam Pius Clindamycin as Therapy for Pelvic Infections in Women
JOSEPH G. PASTOREK 11,M.D. CANDACE COLE, R.N. KENNETH E. ALDRIDGE, Ph.D. JOSEPH C. CRAPANZANO, M.D. New
Orleans,
Louisiana
Aztreonam, a new monobactam antibiotic with specific gram-negative aerobic activity, was used in combination with clindamycin in the treatment of 40 women with pelvic infection, including post-parturn endometritis, pelvic inflammatory disease, and post-hysterectomy pelvic cellulitis. Clinical cure was achieved in 87 percent of patients. Failure was related to the limited gram-positive aerobic spectrum of clindamycin. All aerobic gram-negative enteric organisms were sensitive in vitro to less than 0.125 pg/ml of aztreonam. The bacterial pathogenesis of pelvic infections in females has been extensively studied during recent years. Pelvic inflammatory disease [l], puerperal endometritis [2], and similar infectious gynecologic processes are thought to be mixed infections due to anaerobic and aerobic bacteria. Therapy for such diseases is usually directed against the aerobic and anaerobic components of the infection, classically by combination of an aminoglycoside with an anti-anaerobic drug [3,4]. Aztreonam, a new monobactam antibiotic, possesses a potent antimicrobial spectrum against a broad range of gram-negative aerobic organisms. The usual minimal inhibitory concentrations are below 0.5 pgiml [5,6]. Therefore, the combination of aztreonam with a specifically antianaerobic antibiotic (clindamycin) is reasonable for the treatment of mixed aerobic-anaerobic female pelvic infections. Forty female patients with pelvic infection, including pelvic inflammatory disease, puerperal endometritis, and post-hysterectomy pelvic cellulitis, were treated with aztreonam plus clindamycin at the Louisiana State University Obstetrics and Gynecologic Services at Charity Hospital in New Orleans, Louisiana.
PATIENTS AND METHODS
From the Department of Obstectrics and Gynecology, Louisiana State University Medical Center, New Orleans, Louisiana. Requests for reprints should be addressed to Dr. Joseph G. Pastorek II, Sections of Infectious Disease and Gynecology, Department of Obstetrics and Gynecology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112-2822. This work was supported by a grant from E.R. Squibb and Sons.
Forty hospitalized women over 16 years of age were entered into this open, noncomparative study after giving their informed, written consent for a study protocol approved by the Institutional Review Board of the Louisiana State University Medical Center in New Orleans. Women with pelvic inflammatory disease, puerperal endometritis, or post-hysterectomy pelvic cellulitis were considered for study. Excluded were patients with penicillin or cephalosporin allergy, severely compromised hepatic or renal function, or a high probability of death from other causes during hospitalization. Women who had received prior antibiotic therapy were also excluded. After appropriate pretherapy baseline laboratory testing, including complete blood and platelet counts, hepatic and renal function studies, clotting times, and cultures of blood, urine, and sites of possible pathogen recovery (endocervix, cul-de-sac, endometrium, vaginal cuff), patients were treated with clindamycin, 600 mg intravenously every six hours, and aztreonam, 1 or 2 g every 12 hours.
February
8, 1985
The
American
Journal
of Medicine
Volume
78 (suppl
2A)
47
AZTREONAM
TABLE
SYMPOSIUM-PASTOREK
I
ET AL
Comparison’ of Patients According to Status of Aerobic Gram-Negative isolates Absent
Present
Age Gravity Diagnosis Pelvic inflammatory disease Endometritis Cuff cellulitis Maximal tem’perature Maximal white blood cell count Initial hematocrit Cure rate
RESULTS
31 2 7 years 3?2
29 i. 7 years 3?2
3 8 11
6 6 6
38.6 1 0.4%
38.9 2 0.5%
13,886 2 4,053/mm3
15,556 ? 6,084/mm3
33.5 * 3.4 percent 19/22 (86 percent)
33.2 ? 6.5 percent 16/l 8 (89 percent)
Patients receiving antibiotic therapy were followed by the Infectious Disease Service of the Obstetrics and Gynecologic Department for clinical response to the regimen. Any patients in whom therapy failed were.reexamined, recultured, and treated as judged appropriate by the Obstetrics and Gynecologic Infectious Disease staff. Laboratory testing was repeated at intervals and at discontinuation of the drugs to monitor toxicity. Patients were treated until they were afebrile and asymptomatic for 72 hours. They were then discharged and followed at one and six weeks by study personnel. Specimens for aerobic and anaerobic culture were obtained by: (1) sterile, cotton-tipped swab of the endocervix, and culdocentesis, if possible, via sterile syringe and needle in cases of suspected pelvic inflammatory disease; (2) sterile cotton-tipped swab of the high endometrial cavity (transcervitally) in cases pf suspected puerperal endometritis; and (3) sterile, cotton-tipped swab of the apex of the vaginal cuff in cases of suspected post-hysterectomy cellulitis. Specimens thus obtained were placed immediately in fresh Port-a-Cul vials (Baltimore Biological Laboratory, Cockeysville, Maryland) for transportation to the Louisiana State University Department of Medicine Microbiology Research Laboratory. Aerobic bacteria were isolated and identified using standard techniques [7]. Anaerobic species were identified in standard fashion [8,9]. Antibiotic sensitivities for aerobic species were performed by the Kirby-Bauer disk method [IO] and also the agar dilution technique. Anaerobic isolates were not expected to be sensitive to aztreonam and were therefore not tested. Response to antibiotic therapy was considered successful if: (1) the patient became and remained afebrile; (2) signs and symptoms of infection resolved: (3) the white blood cell count returned to within the normal range. Therapy was considered to have failed if: (1) the temperature remained elevated or rose after 48 to 72 hours of therapy; (2) the patient did not show clear improvement in physical findings after 48 to 72 hours of therapy; (3) antibiotics were changed because of toxicity; (4) the infection recurred after discontinuation of the study drug; or (5) the patient failed to complete a course of therapy for any other reason.
48
February
8, 1985
The American
Joukal
of Medicine
Volume
Forty patients enrolled in the study fit the demographic characteristics. Mean age was 30 years (+7), gravity 3 (+2), temperature 38.7% (?O#C), white blood cell count 14,683/mm3 (*$I 36/mm3), and hematocrit level 33.4 percent (25.1 percent). There were nine women with pelvic inflammatory disease, 14 with puerperal endometritis, and 17 with post-hysterectomy pelvic cellulitis. Gram-negative aerobic organisms from these patients included Escherichia coli (17), Klebsiella pneumoniae (six), Proteus mirabilis (three), Citrobacter freundii (two), Acinetobacter calcoaceticus (one), and Enterobacter cloacae (one). All gram-negative aerobes were sensitive in vitro to less than 0.125 @g/ml of aztreonam. Eighteen patients had no aerobic gram-negative bacteria isolated. It is useful to compare these patients with the 22 patients harboring gram-negative aerobes (Table I). There were no appreciable differences between those patients with and those without gram-riegative aerobic isolates. The cure rate among pa?ients for the aztreonam-clindamycin regimen was 87.5 percent (35 of 40) overall. Five failures included two patients with puerperal endometritis and three patients with post-hysterectomy pelvic cellulitis (Table II). One patient actually left the hospital against medical advice before satisfactory therapy could be completed and, therefore, treatment could not be considered a success. All gram-negative aerobic isolates from these patients were sensitive in vitro to aztreonam. However, most organisms isolated from these five patients were either anaerobes or gram-positive aerobes. There wa,s no untoward toxicity directly associated with aztreonam administration observed in any patient. Clostridium difficile pseudomembranous enterocolitis developed in one patient, presumably due to clindamycin therapy. COMMENTS Traditionally, antibiotic treatment of female pelvic infection has been combination therapy with a drug effective against anaerobic organisms and one combating gramnegative organisms (aminoglycoside) [3,4]. The rationale for this choice of antibiotics may be based on the polymicrobial etiology of these infections [I ,2] and on data demonstrating efficacy of this type of antimicrobial combination in experimental intra-abdominal sepsis in rodents [l I]. Use of aminoglycosides is difficult because of Zhe narrow therapeutic range and potential for toxicity [12,13]. In particular, the obstetric and gynecologic patient is often underdosed if usual “package-insert” dosing of aminoglycosides is employed [14-161. Aztreonam, a new monobactam antibiotic, has been shown to be effective against many gram-negative aerobic species of bacteria, even some that are resistant to
78
(suppl 2A)
AZTREONAM
TABLE
II
Aztreonam-Clindamycin
cellulitis
Pelvic
cellulitis
Endometritis Pelvic
cellulitis
Endometritis
*Isolates
sensitive
0.125
pgiml
of aztreonam
Additional Therapy
Subsequent Diagnosis
Escherichia coli* Citrobacter freundi? Group B streptococci Enterococci Group D streptococci (not enterococci) Fusobacterium necleatum Bacteroides asaccharolyticus Gaffkya anaerobia Group D streptococci (not enterococci) Group A streptococci Coagulase-negative staphylococci Group D streptococci (not enterococci) Nonhemolytic streptococci (not group B or D) Enterococci Escherichia coli* Enterococci Coagulase-negative staphylococci Bacteroides fragilis Peptococcus asaccharolyticus Clostridium difficile (stool) to less than
ET AL
Failures
Organism Isolated
Initial Diagnosis Pelvic
Treatment
SYMPOSIUM-PASTOREK
Persistent
cellulitis
Ampicillin
Ampicillin, heparin
Persistent cellulitis, retroperitoneal hematoma
Left hospital Persistent
against
medical
advice
cellulitis
Wound dehiscence, pseudomembranous
Ampicillin
enterocolitis
Vancomycin, cholestyramine
in vitro.
other more commonly used drugs. Toxicity is low, comparable to most other beta-lactam antibiotics [17]. Therefore, aztreonam would make a good replacement for the aminoglycosides in a combination regimen, along with an antianaerobic drug such as clindamycin, for treatment of polymicrobial pelvic infections in women. The present study demonstrated that aztreonam-clindamycin is an effective regimen for mixed pelvic infections. The 87.5 percent cure rate compares with studies of clindamycin-aminoglycoside therapy reported in the obstetric and gynecologic literature [3]. The obvious benefits of substitution with aztreonam for the aminoglycosides are: (1) lowered potential or real toxicity: (2) ease in ad-
ministration (i.e., no serum level monitoring); and (3) reservation of the aminoglycosides for other use. Disadvantages are few. Patients allergic to beta-lactam drugs were purposefully excluded from this study. However, there are data to indicate that aztreonam has no allergic cross-reactivity with penicillin in penicillin-allergic individuals [I 81. This may, therefore, be an unnecessary precaution. What remains to be answered for the gynecologist, perhaps through animal models developed previously [l 11, is whether aztreonam penetrates well and is active in abscesses and other areas of hypoxic and acidotic tissue for appropriate gram-negative (facultative) coverage-a clear deficiency of the aminoglycosides.
REFERENCES 1.
2.
3.
4.
Chow, AW, Patten V, Marshall JR: Bacteriology of acute pelvic inflammatory disease. Am J Obstet Gynecol 1979; 133: 362365. Gilstrap LC, Cunningham FG: The bacterial pathogenesis of infection following cesarean section. Obstet Gynecol 1979; 53: 545-549. diZerega G, Yonekura L, 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. Gall SA, Kohan AP, Ayers DM, Huges CE, Addison WA, Hill GD: Intravenous metronidazole or clindamycin tobramycin for therapy of pelvic infections. Obstet Gynecol 1981; 57: 51-58.
February 8, 1985
5.
6.
7.
8.
Sykes RB, Bonner DP, Bush K, Georgopapadakou NH: Azthreonam (SQ 26,776) a synthetic monobactam specifitally active against aerobic gram-negative bacteria. Antimicrob Agents Chemother 1982; 21: 85-92. Jacobus NV, Ferreira MC, Barza M: In vitro activity of azthreonam, a monobactam antibiotic. Antimicrob Agents Chemother 1982; 22: 832-838. Lennete EH, Spaulding EH, Traunt JP, eds: Manual of clinical microbiology. Washington: American Society for Microbiology, 1974. Holdeman LV, Moor WEC: Anaerobe laboratory manual. Blacksburg, Virginia: Virginia Polytechnic Institute Anaerobe Laboratory, 1975.
The American Journal of Medicine
Volume 78 (suppl 2A)
49
AZTHEONAM
9.
10.
11.
12.
13.
14.
50
SYMPOSIUM-PASTOREK
ET AL
Starge MD, Thompson FS, Phillips SE, et al: Modification of the Minitek miniaturized differentiation system for characterization of anaerobic bacteria. J Clin Microbial 1976; 3: 291-299. Bauer AW, Kirby WMM, Sherris JC, et al: Antibiotic susceptibility testing by a standardized single disc method. Am J Clin Pathol 1966; 45: 493-501. Weinstein WM, Onderdonk AB, Bartlett JG, Gorbach SL: Antimicrobial therapy of experimental intraabdominal sepsis. J Infect Dis 1975; 132: 282-286. Smith CR, Lipsky JJ, Laskin OL, et al: Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med 1980; 302: 7 106-l 109. Keys TF, Kurtz SB, Jones JD, Muller SM: Renal toxicity during theraov with aentamicin or tobramvcin. Mavo Clin Proc 1981; 56: 5%-559: Zaske DE, Cipoile RJ, Strate RG, Malo JW, Koszalka MF: Rapid
February
8, 1985
The American
Journal
of Medicine
15.
16.
17.
18.
Volume
gentamicin elimination in obstetrics patients. Obstet Gynecol 1980; 56: 559-564. Lesar RS, Rotschafer JC, Strand LM, Solem LD, Zaske DE: Gentamicin dosing errors with four commonly used nomograms. JAMA 1982; 248: 1190-I 193. Duff P, Jorgensen JH, Gibbs RS, Blanc0 D, Alexander G, Castaneda YS: Serum gentamicin levels in patients with post-cesarean endomyometritis. Obstet Gynecol 1983; 61: 723-727. Giamarellon H, Galanakis, N, Douzinas E, et al: Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up. Antimicrob Agents Chemotiier 1984; 26: 245-249. Saxon A, Hassner A, Swabb EA, Wheeler B, Adkinson NF: Lack of cross-reactivity between aztreonam, a monobactam antibiotic, and penicillin in ,penicillin-allergic subjects, J Infect Dis 1984; 149: 16-22.
78 (suppl
2A)
JOSEPH G. PASTOREK 11,M.D. CANDACE COLE, R.N. KENNETH E. ALDRIDGE, Ph.D. JOSEPH C. CRAPANZANO, M.D. New
Orleans,
Louisiana
Aztreonam, a new monobactam antibiotic with specific gram-negative aerobic activity, was used in combination with clindamycin in the treatment of 40 women with pelvic infection, including post-parturn endometritis, pelvic inflammatory disease, and post-hysterectomy pelvic cellulitis. Clinical cure was achieved in 87 percent of patients. Failure was related to the limited gram-positive aerobic spectrum of clindamycin. All aerobic gram-negative enteric organisms were sensitive in vitro to less than 0.125 pg/ml of aztreonam. The bacterial pathogenesis of pelvic infections in females has been extensively studied during recent years. Pelvic inflammatory disease [l], puerperal endometritis [2], and similar infectious gynecologic processes are thought to be mixed infections due to anaerobic and aerobic bacteria. Therapy for such diseases is usually directed against the aerobic and anaerobic components of the infection, classically by combination of an aminoglycoside with an anti-anaerobic drug [3,4]. Aztreonam, a new monobactam antibiotic, possesses a potent antimicrobial spectrum against a broad range of gram-negative aerobic organisms. The usual minimal inhibitory concentrations are below 0.5 pgiml [5,6]. Therefore, the combination of aztreonam with a specifically antianaerobic antibiotic (clindamycin) is reasonable for the treatment of mixed aerobic-anaerobic female pelvic infections. Forty female patients with pelvic infection, including pelvic inflammatory disease, puerperal endometritis, and post-hysterectomy pelvic cellulitis, were treated with aztreonam plus clindamycin at the Louisiana State University Obstetrics and Gynecologic Services at Charity Hospital in New Orleans, Louisiana.
PATIENTS AND METHODS
From the Department of Obstectrics and Gynecology, Louisiana State University Medical Center, New Orleans, Louisiana. Requests for reprints should be addressed to Dr. Joseph G. Pastorek II, Sections of Infectious Disease and Gynecology, Department of Obstetrics and Gynecology, Louisiana State University Medical Center, 1542 Tulane Avenue, New Orleans, Louisiana 70112-2822. This work was supported by a grant from E.R. Squibb and Sons.
Forty hospitalized women over 16 years of age were entered into this open, noncomparative study after giving their informed, written consent for a study protocol approved by the Institutional Review Board of the Louisiana State University Medical Center in New Orleans. Women with pelvic inflammatory disease, puerperal endometritis, or post-hysterectomy pelvic cellulitis were considered for study. Excluded were patients with penicillin or cephalosporin allergy, severely compromised hepatic or renal function, or a high probability of death from other causes during hospitalization. Women who had received prior antibiotic therapy were also excluded. After appropriate pretherapy baseline laboratory testing, including complete blood and platelet counts, hepatic and renal function studies, clotting times, and cultures of blood, urine, and sites of possible pathogen recovery (endocervix, cul-de-sac, endometrium, vaginal cuff), patients were treated with clindamycin, 600 mg intravenously every six hours, and aztreonam, 1 or 2 g every 12 hours.
February
8, 1985
The
American
Journal
of Medicine
Volume
78 (suppl
2A)
47
AZTREONAM
TABLE
SYMPOSIUM-PASTOREK
I
ET AL
Comparison’ of Patients According to Status of Aerobic Gram-Negative isolates Absent
Present
Age Gravity Diagnosis Pelvic inflammatory disease Endometritis Cuff cellulitis Maximal tem’perature Maximal white blood cell count Initial hematocrit Cure rate
RESULTS
31 2 7 years 3?2
29 i. 7 years 3?2
3 8 11
6 6 6
38.6 1 0.4%
38.9 2 0.5%
13,886 2 4,053/mm3
15,556 ? 6,084/mm3
33.5 * 3.4 percent 19/22 (86 percent)
33.2 ? 6.5 percent 16/l 8 (89 percent)
Patients receiving antibiotic therapy were followed by the Infectious Disease Service of the Obstetrics and Gynecologic Department for clinical response to the regimen. Any patients in whom therapy failed were.reexamined, recultured, and treated as judged appropriate by the Obstetrics and Gynecologic Infectious Disease staff. Laboratory testing was repeated at intervals and at discontinuation of the drugs to monitor toxicity. Patients were treated until they were afebrile and asymptomatic for 72 hours. They were then discharged and followed at one and six weeks by study personnel. Specimens for aerobic and anaerobic culture were obtained by: (1) sterile, cotton-tipped swab of the endocervix, and culdocentesis, if possible, via sterile syringe and needle in cases of suspected pelvic inflammatory disease; (2) sterile cotton-tipped swab of the high endometrial cavity (transcervitally) in cases pf suspected puerperal endometritis; and (3) sterile, cotton-tipped swab of the apex of the vaginal cuff in cases of suspected post-hysterectomy cellulitis. Specimens thus obtained were placed immediately in fresh Port-a-Cul vials (Baltimore Biological Laboratory, Cockeysville, Maryland) for transportation to the Louisiana State University Department of Medicine Microbiology Research Laboratory. Aerobic bacteria were isolated and identified using standard techniques [7]. Anaerobic species were identified in standard fashion [8,9]. Antibiotic sensitivities for aerobic species were performed by the Kirby-Bauer disk method [IO] and also the agar dilution technique. Anaerobic isolates were not expected to be sensitive to aztreonam and were therefore not tested. Response to antibiotic therapy was considered successful if: (1) the patient became and remained afebrile; (2) signs and symptoms of infection resolved: (3) the white blood cell count returned to within the normal range. Therapy was considered to have failed if: (1) the temperature remained elevated or rose after 48 to 72 hours of therapy; (2) the patient did not show clear improvement in physical findings after 48 to 72 hours of therapy; (3) antibiotics were changed because of toxicity; (4) the infection recurred after discontinuation of the study drug; or (5) the patient failed to complete a course of therapy for any other reason.
48
February
8, 1985
The American
Joukal
of Medicine
Volume
Forty patients enrolled in the study fit the demographic characteristics. Mean age was 30 years (+7), gravity 3 (+2), temperature 38.7% (?O#C), white blood cell count 14,683/mm3 (*$I 36/mm3), and hematocrit level 33.4 percent (25.1 percent). There were nine women with pelvic inflammatory disease, 14 with puerperal endometritis, and 17 with post-hysterectomy pelvic cellulitis. Gram-negative aerobic organisms from these patients included Escherichia coli (17), Klebsiella pneumoniae (six), Proteus mirabilis (three), Citrobacter freundii (two), Acinetobacter calcoaceticus (one), and Enterobacter cloacae (one). All gram-negative aerobes were sensitive in vitro to less than 0.125 @g/ml of aztreonam. Eighteen patients had no aerobic gram-negative bacteria isolated. It is useful to compare these patients with the 22 patients harboring gram-negative aerobes (Table I). There were no appreciable differences between those patients with and those without gram-riegative aerobic isolates. The cure rate among pa?ients for the aztreonam-clindamycin regimen was 87.5 percent (35 of 40) overall. Five failures included two patients with puerperal endometritis and three patients with post-hysterectomy pelvic cellulitis (Table II). One patient actually left the hospital against medical advice before satisfactory therapy could be completed and, therefore, treatment could not be considered a success. All gram-negative aerobic isolates from these patients were sensitive in vitro to aztreonam. However, most organisms isolated from these five patients were either anaerobes or gram-positive aerobes. There wa,s no untoward toxicity directly associated with aztreonam administration observed in any patient. Clostridium difficile pseudomembranous enterocolitis developed in one patient, presumably due to clindamycin therapy. COMMENTS Traditionally, antibiotic treatment of female pelvic infection has been combination therapy with a drug effective against anaerobic organisms and one combating gramnegative organisms (aminoglycoside) [3,4]. The rationale for this choice of antibiotics may be based on the polymicrobial etiology of these infections [I ,2] and on data demonstrating efficacy of this type of antimicrobial combination in experimental intra-abdominal sepsis in rodents [l I]. Use of aminoglycosides is difficult because of Zhe narrow therapeutic range and potential for toxicity [12,13]. In particular, the obstetric and gynecologic patient is often underdosed if usual “package-insert” dosing of aminoglycosides is employed [14-161. Aztreonam, a new monobactam antibiotic, has been shown to be effective against many gram-negative aerobic species of bacteria, even some that are resistant to
78
(suppl 2A)
AZTREONAM
TABLE
II
Aztreonam-Clindamycin
cellulitis
Pelvic
cellulitis
Endometritis Pelvic
cellulitis
Endometritis
*Isolates
sensitive
0.125
pgiml
of aztreonam
Additional Therapy
Subsequent Diagnosis
Escherichia coli* Citrobacter freundi? Group B streptococci Enterococci Group D streptococci (not enterococci) Fusobacterium necleatum Bacteroides asaccharolyticus Gaffkya anaerobia Group D streptococci (not enterococci) Group A streptococci Coagulase-negative staphylococci Group D streptococci (not enterococci) Nonhemolytic streptococci (not group B or D) Enterococci Escherichia coli* Enterococci Coagulase-negative staphylococci Bacteroides fragilis Peptococcus asaccharolyticus Clostridium difficile (stool) to less than
ET AL
Failures
Organism Isolated
Initial Diagnosis Pelvic
Treatment
SYMPOSIUM-PASTOREK
Persistent
cellulitis
Ampicillin
Ampicillin, heparin
Persistent cellulitis, retroperitoneal hematoma
Left hospital Persistent
against
medical
advice
cellulitis
Wound dehiscence, pseudomembranous
Ampicillin
enterocolitis
Vancomycin, cholestyramine
in vitro.
other more commonly used drugs. Toxicity is low, comparable to most other beta-lactam antibiotics [17]. Therefore, aztreonam would make a good replacement for the aminoglycosides in a combination regimen, along with an antianaerobic drug such as clindamycin, for treatment of polymicrobial pelvic infections in women. The present study demonstrated that aztreonam-clindamycin is an effective regimen for mixed pelvic infections. The 87.5 percent cure rate compares with studies of clindamycin-aminoglycoside therapy reported in the obstetric and gynecologic literature [3]. The obvious benefits of substitution with aztreonam for the aminoglycosides are: (1) lowered potential or real toxicity: (2) ease in ad-
ministration (i.e., no serum level monitoring); and (3) reservation of the aminoglycosides for other use. Disadvantages are few. Patients allergic to beta-lactam drugs were purposefully excluded from this study. However, there are data to indicate that aztreonam has no allergic cross-reactivity with penicillin in penicillin-allergic individuals [I 81. This may, therefore, be an unnecessary precaution. What remains to be answered for the gynecologist, perhaps through animal models developed previously [l 11, is whether aztreonam penetrates well and is active in abscesses and other areas of hypoxic and acidotic tissue for appropriate gram-negative (facultative) coverage-a clear deficiency of the aminoglycosides.
REFERENCES 1.
2.
3.
4.
Chow, AW, Patten V, Marshall JR: Bacteriology of acute pelvic inflammatory disease. Am J Obstet Gynecol 1979; 133: 362365. Gilstrap LC, Cunningham FG: The bacterial pathogenesis of infection following cesarean section. Obstet Gynecol 1979; 53: 545-549. diZerega G, Yonekura L, 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. Gall SA, Kohan AP, Ayers DM, Huges CE, Addison WA, Hill GD: Intravenous metronidazole or clindamycin tobramycin for therapy of pelvic infections. Obstet Gynecol 1981; 57: 51-58.
February 8, 1985
5.
6.
7.
8.
Sykes RB, Bonner DP, Bush K, Georgopapadakou NH: Azthreonam (SQ 26,776) a synthetic monobactam specifitally active against aerobic gram-negative bacteria. Antimicrob Agents Chemother 1982; 21: 85-92. Jacobus NV, Ferreira MC, Barza M: In vitro activity of azthreonam, a monobactam antibiotic. Antimicrob Agents Chemother 1982; 22: 832-838. Lennete EH, Spaulding EH, Traunt JP, eds: Manual of clinical microbiology. Washington: American Society for Microbiology, 1974. Holdeman LV, Moor WEC: Anaerobe laboratory manual. Blacksburg, Virginia: Virginia Polytechnic Institute Anaerobe Laboratory, 1975.
The American Journal of Medicine
Volume 78 (suppl 2A)
49
AZTHEONAM
9.
10.
11.
12.
13.
14.
50
SYMPOSIUM-PASTOREK
ET AL
Starge MD, Thompson FS, Phillips SE, et al: Modification of the Minitek miniaturized differentiation system for characterization of anaerobic bacteria. J Clin Microbial 1976; 3: 291-299. Bauer AW, Kirby WMM, Sherris JC, et al: Antibiotic susceptibility testing by a standardized single disc method. Am J Clin Pathol 1966; 45: 493-501. Weinstein WM, Onderdonk AB, Bartlett JG, Gorbach SL: Antimicrobial therapy of experimental intraabdominal sepsis. J Infect Dis 1975; 132: 282-286. Smith CR, Lipsky JJ, Laskin OL, et al: Double-blind comparison of the nephrotoxicity and auditory toxicity of gentamicin and tobramycin. N Engl J Med 1980; 302: 7 106-l 109. Keys TF, Kurtz SB, Jones JD, Muller SM: Renal toxicity during theraov with aentamicin or tobramvcin. Mavo Clin Proc 1981; 56: 5%-559: Zaske DE, Cipoile RJ, Strate RG, Malo JW, Koszalka MF: Rapid
February
8, 1985
The American
Journal
of Medicine
15.
16.
17.
18.
Volume
gentamicin elimination in obstetrics patients. Obstet Gynecol 1980; 56: 559-564. Lesar RS, Rotschafer JC, Strand LM, Solem LD, Zaske DE: Gentamicin dosing errors with four commonly used nomograms. JAMA 1982; 248: 1190-I 193. Duff P, Jorgensen JH, Gibbs RS, Blanc0 D, Alexander G, Castaneda YS: Serum gentamicin levels in patients with post-cesarean endomyometritis. Obstet Gynecol 1983; 61: 723-727. Giamarellon H, Galanakis, N, Douzinas E, et al: Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up. Antimicrob Agents Chemotiier 1984; 26: 245-249. Saxon A, Hassner A, Swabb EA, Wheeler B, Adkinson NF: Lack of cross-reactivity between aztreonam, a monobactam antibiotic, and penicillin in ,penicillin-allergic subjects, J Infect Dis 1984; 149: 16-22.
78 (suppl
2A)