- Email: [email protected]
Aztreonam
INFECTIOUS DISEASES UPDATE
AZTREONAM John D. Davis, MD
ELSEVIER
Aztreonam is the first of a new class of p-lactam antibiotics known as monobactams. The drug is active against the majority of gram-negative bacteria and has been used successfully in combination with other antibiotics in the treatment of endometritis, cuflcellulitis, and pelvic inflammatory disease and as a single agent for the treatment of acute pyelonephritis. Common side eflects of aztreonam are pain and phlebitis at the injection site, mild gastrointestinal disturbances, and skin rash. Cross-reactivity with penicillins and nephrotoxicity are rare. Despite the drug’s eflectiveness and safety, its use is limited by high cost. Aztreonam should be used when excellent gram-negative coverage is required and aminoglycosides are contraindicated. (Prim Care Update OblGyns 1997; 4:61-64. 0 1997 Elsevier Science Inc. All rights reserved.)
Obstetrician/gynecologists diagnose and treat a variety of pelvic infections including postpartum endometritis, post-hysterectomy cellulitis, pelvic inflammatory disease (PID), pelvic abscess, mucopurulent cervicitis, cystitis, and pyelonephritis. Many of these pelvic infections are polymicrobial in nature, and frequently therapy for these infections must be initiated without identification of the responsible pathogens. As a result, initial therapy usually consists of a broad-spectrum single agent or a combination of antibiotics with specific activity against a certain class From the Department of Obstetrics ogy. University of Florida College Gainesville. Florida.
Volume
4. Number
2. 1997
0 1997
and Gynecolof Medicine.
of organisms. There are many effective single agents or combinations from which to choose, and factors such as spectrum of activity, efficacy, side effects, compliance, and cost should be taken into account when deciding on an initial antibiotic regimen. Aztreonam (Azactam; Bristol-Myers Squibb, Princeton, NJ) is a monocyclic p-lactam, or monobactam, with excellent aerobic gram-negative coverage. It has been used alone or in combination to treat a number of obstetric and gynecologic infections. The purpose of this article is to review the derivation, spectrum of activity, mechanism of action, toxicity, and clinical application of aztreonam to assist the practitioner in deciding when aztreonam should be used in the treatment of commonly encountered pelvic infections.
Derivation Aztreonam (Figure l), first marketed in 1984, is the first of a new class of p-lactam antibiotics known as monobactams. The chemical structure of monobactam antibiotics resembles that of the penicillins and cephalosporins in that all have a /3-lactam ring. However, the thiazolidine ring common to all penicillins is not present in the monobactams (Figure 2). The remaining three-amino-monobactamic-acid ring is the nucleus around which all the monobactams are structured.’ The first monobactams were naturally occurring compounds produced by certain species of
Gluconobacter, mobacterium, Agrobacterium. these
Elsevier
Science
Inc..
Acetobacter, Pseudomonas,
compounds
all rights
reserved.
Chro-
and The potency of was enhanced
1068-607X/97/$17.00
through modifications to their chemical structure. Specifically, an aminothiazole-oxime side chain was added to position three and an a-methyl group was substituted at position four, which made the monobactams highly effective against gram-negative bacteria and also stable to p-1actamases.l Aztreonam is an entirely synthetic monobactam in which the above chemical modifications have been incorporated.
Spectrum of Activity Aztreonam is active specifically against facultative or aerobic gramnegative bacteria. In general, the spectrum of activity of aztreonam is similar to that of the aminoglycosides except that aztreonam demonstrates no activity against gram-positive bacteria whereas aminoglycosides are active against Staphylococcus aureus.’ Susceptible strains include the Enterobacteriaceae, specifically Escherichia
coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, and species of Enterobacter, Serratia, and Citrobacter. Aztreonam is effective even against strains of the above bacteria that are resistant to penicillin, older cephalosporins, and aminoglycosides. In addition, aztreonam is active against Neisseria gonorrhoeae and Haemophilus influenzae, including P-lactamaseproducing strains?,’
Citrobacter freundii, Enterobatter cloacae. and Klebsiella oxytoca are slightly less susceptible to aztreonam. Aztreonam is moderately effective against most strains of P aeruginosa but demonstrates
. PII s1068-607x(96)00066-x
61
DAVIS
CH3
Figure 1. Structure of aztreonam.
poor activity against other Pseudomonas strains.’ Aztreonam has negligible activity against gram-positive bacteria and anaerobic gram-negative bacteria, including Bacteroides and Prevotella species. The drug is ineffective against some gram-negative bacteria, including Acinetobacter species, Xanthomonas maltophilia,
Achromobacter xylosoxidans, Alcaligenes species, and Legionella pneumophila.2 Chlamydia trachomatis is not susceptible to aztreonam.
Mechanism of Action Aztreonam exerts its antimicrobial effect by inhibiting bacterial cell wall formation. The drug readily crosses the cell wall and cell membrane and binds with high affinity to
0
‘SO,H Figure 2. Structure of core rings of penicillins (above) and monobactams
(below). 62
penicillin-binding protein 3 of gram-negative bacteria. By binding to this protein, which is necessary for cell division, aztreonam prevents cell replication and eventually leads to cell death.l Aztreonam possesses a high degree of resistance to most common /3-lactamases; therefore, the antibiotic is effective against bacteria that produce these substances. In addition, aztreonam maintains its antimicrobial effect even in the acidic, anaerobic conditions of an abscess cavity.l,’
Toxicity Overall, aztreonam is a safe and well-tolerated drug with a safety profile similar to or better than that of other p-lactam antibiotics. Common side effects of aztreonam are pain and phlebitis at the injection site, occurring in approximately 2% of patients; nausea and diarrhea, occurring in less than 2% of patients; and skin rash, also occurring in approximately 2% of patients.’ Because aztreonam contains a p-lactam ring similar to penicillins and cephalosporins, concerns regarding cross-reactivity with these compounds have been expressed. However, aztreonam has demonstrated little cross-reactivity with other p-lactams in experimental studies,3 and in clinical studies aztreonam has been shown to be safe even for patients allergic to penicillin. Henry and Bendush4 reported that, of 134 patients with a history of penicillin or cephalosporin allergy, only one patient had a possible IgE-mediated urticarial rash when treated with aztreonam. Jensen et al5 treated 15 patients with cystic fibrosis who previously had had severe reactions including anaphylaxis to other /3-lactam antibiotics. Each patient received three to six courses of therapy, and none developed a type I hypersensitivity reaction.
Although the spectrum of activity of aztreonam is similar to that of the aminoglycosides, the risk of nephrotoxicity associated with aztreonam is negligible when compared to that of the latter group. Henry and Bendush,4 in both preclinical and large clinical trials, demonstrated that aztreonam has little potential to cause renal damage. Other side effects also occur infrequently. Bleeding has been reported but is rare. Aztreonam can cause an elevation in hepatic transaminases, but these changes are mild and reversible. Neutropenia, thrombocytopenia, and eosinophilia all have been reported but are unusual1 Superinfections can occur with aztreonam; enterococcus and S aureus are the usual offending bacteria. Superinfections with yeast and gram-negative bacteria are rare. Likewise, the development of pseudomembranous colitis is unusual because aztreonam has minimal effect on anaerobes in the gut.’ Aztreonam, like other p-lactam antibiotics, is a Pregnancy Category B drug. Animal studies with daily doses up to fifteen times the maximum recommended human dose have demonstrated no fetal risks, but no studies have been performed on pregnant women (PDR, 1995: 706-8). Aztreonam is present in breast milk at levels less than 1% of simultaneously determined maternal levels.
Clinical Application Aztreonam has been shown to be effective in the treatment of a variety of common pelvic infections encountered by obstetriciamgynecologists. Gibbs et al6 compared clindamycin plus aztreonam with clindamycin plus gentamicin in the treatment of 119 patients with postcesarean endometritis. Patients received clindamycin 600 mg intravenously every 6 hours with either Prim
Care
Update
Ob/Gyns
aztreonam 2 g intravenously every 8 hours or gentamicin 1.5 mg/kg intravenously every 8 hours. Of the patients in the aztreonam arm, 91.4% were clinically cured, compared with 88.6% of the patients in the gentamicin arm (not significant). There were two clinical failures and three side-effect failures in the aztreonam/clindamycin treatment group. Both clinical failures had enterococcal bacteremia; two patients with side-effect failures developed diarrhea severe enough to discontinue therapy. No patient in either treatment group developed The researchers” nephrotoxicity. concluded aztreonam was as effective as gentamicin when each was used with clindamycin in the treatment of post-cesarean endometritis. Dodson et al7 treated 42 patients with a clinical diagnosis of pelvic inflammatory disease with aztreonam and clindamycin. Fifty-one percent of the patients had evidence of a pelvic abscess. Patients received aztreonam 1 g intravenously every 8 hours and clindamycin 600 mg intravenously every 6 hours. Overall, 97.5% of the patients were cured. The one patient who failed therapy had a large abscess that eventually required surgical drainage. No patients discontinued therapy because of side effects. Henry,8 from the Squibb Institute for Medical Research, reported her experience in treating a variety of pelvic infections, including endometritis, cuff cellulitis, and pelvic inflammatory disease, with aztreonam and clindamycin. A total of 73 patients were treated in comparative and noncomparative studies. The usual dose of aztreonam was 1 or 2 g intravenously every 8 hours along with clindamycin 600 mg intravenously every 8 hours. Overall, 72 of 73 patients were treated successfully. Characteristics of the patient who failed therapy were not discussed. The author’ concluded that aztreonam was effective in the Volume
4. Numhrr
2. 1997
Table 1. Inpatient Chargesof Common Regimensof Aztreonam and Gentamicin Inpatient Charge at Shands Hospital
Antibiotic Regimen Aztreonam 1 g TID for 3 d Aztreonam 2 g TID for 3 d Gentamicin 140 me loadine dose 90mgTIDfor3vd ” Total Gentamicin 350 mg QD for 3 d (single-doseregimen) TID.
three
times
a day:
$ 742.50 $1,359.00 $ 15.40 $ 134.10 $ 149.50 $ 52.50
QD, daily.
treatment of pelvic infections and could be substituted for gentamicin. Each of the above studies demonstrated aztreonam is effective, when used in combination with clindamycin, in the treatment of polymicrobial pelvic infections. In addition, aztreonam has been used successfully to treat urinary tract infections and gonococcal cervicitis. However, despite its efficacy and safety, the use of aztreonam is limited by its expense. Table 1 lists the current patient charges for 3-day courses of gentamicin and aztreonam at Shands Teaching Hospital (personal communication, Shands Drug Information Service). Depending on the regimen chosen, the patient charges for aztreonam are approximately five to 25 times greater than those for generic gentamicin. In today’s era of cost containment, the benefits of treating a patient with an expensive medication must outweigh clearly the risks of using a less costly alternative. There are a number of clinical situations in which aztreonam, rather than an aminoglycoside, may be indicated. For instance, the use of aztreonam could be justified for a patient who already has renal damage. Likewise, it would be reasonable to choose aztreonam for a patient with a malignancy who has received or will receive cisplatin or other potentially nephrotoxic agents. In addition, aztreonam might be chosen over gentamicin if it is anticipated that the patient will require repeated courses of therapy.
Appelg has argued that the expense of aztreonam is comparable to the overall cost of gentamicin use when the amount spent on aminoglycoside levels, renal function tests, and care of patients who develop nephrotoxicity is included in cost estimates. However, many obstetric and gynecologic patients are at low risk for developing nephrotoxicity, require only short courses of therapy, and do not need monitoring of antibiotic levels or renal function tests. The routine use of aztreonam seems unwarranted unless the patient has one of the above indications. When indicated, the standard dose of aztreonam is l-2 g IV every 8-12 hours for moderately severe infections and 2 g IV every 6-8 hours for severe or life-threatening infections. In patients with renal compromise, or in the elderly, the dose should be based on the patient’s creatinine clearance (C,,) using the following formula: Males: Cc1 weight (kg) x (140-age) = 72 X serum creatinine (mg/dL) Females: Cc. = same X 0.85 For patients with a creatine clearance between 10 and 30 mL/ minute/l.73 m2, an initial dose of 1 or 2 g is given, followed by one-half of the usual maintenance dose. In patients with a creatine clearance less than 10 ml/minute/l.73 m2, an initial dose of 1 or 2 g is followed by one-quarter of the initial dose every 63
DAVIS 6,8, or 12 hours (PDR, 1995:706-8).
References
Monitoring
1. Clark P. Aztreonam. Obstet Gynecol
serum levels of aztreo-
nam is not required.
Clin North Am 1992;19:519-28. 2. American Medical Association. Drug
Conclusion
3.
In conclusion, aztreonam is a relatively new antibiotic with excellent effectiveness against gram-negative aerobic bacteria. It is safe and effective in the treatment of common obstetric and gynecologic infec-
4.
tions. However, the routine use of aztreonam is limited by its expense. Aztreonam should be considered in the treatment of infections when excellent gram-negative coverage is required and aminoglycosides are contraindicated.
64
5.
6.
evaluations annual 1995.Milwaukee (WI): American Medical Association, 1995:1481-4. Saxon A, Swabb EA, Adkinson NF. Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics. Am J Med 1985;78(suppl 2A):19-26. Henry SA, Bendush CB. Aztreonam: worldwide overview of the treatment of patients with gram-negative infections. Am J Med 1985;78(suppl 2A): 57-64. Jensen T, Pedersen SS, Hoiby N, Koch C. Safety of aztreonam in patients with cystic fibrosis and allergy to beta-lactam antibiotics. Rev Infect Dis 1991;13(suppl 7):S594-7. Gibbs RS, Blanc0 JD, Lipscomb KA, St. Clair PJ. Aztreonam versus gen-
tamicin, each with clindamycin, in the treatment of endometritis. Obstet Gynecol 1985;65:825-9. Dodson MG, Faro S, Gentry LO. Treatment of acute pelvic inflammatory diseasewith aztreonam, a new monocyclic beta-lactam antibiotic, and clindamycin. Obstet Gynecol 1986;67:657-62. Henry SA. Overall clinical experiencewith aztreonam in the treatment of obstetric-gynecologic infections. Rev Infect Dis 1985;7(suppl 4): S703-8. Appel GB. Aminoglycoside nephrotoxicity. Am J Med 1990;88(suppl SC):lSS-20s.
Address correspondenceand reprint requests to John D. Davis, MD, Dept. of Obstetrics and Gynecology, University of Florida Collegeof Medicine, P.O. Box 100294, Gainesville, FL 32610-0294.
Prim
Care
Update
ObiGyns
AZTREONAM John D. Davis, MD
ELSEVIER
Aztreonam is the first of a new class of p-lactam antibiotics known as monobactams. The drug is active against the majority of gram-negative bacteria and has been used successfully in combination with other antibiotics in the treatment of endometritis, cuflcellulitis, and pelvic inflammatory disease and as a single agent for the treatment of acute pyelonephritis. Common side eflects of aztreonam are pain and phlebitis at the injection site, mild gastrointestinal disturbances, and skin rash. Cross-reactivity with penicillins and nephrotoxicity are rare. Despite the drug’s eflectiveness and safety, its use is limited by high cost. Aztreonam should be used when excellent gram-negative coverage is required and aminoglycosides are contraindicated. (Prim Care Update OblGyns 1997; 4:61-64. 0 1997 Elsevier Science Inc. All rights reserved.)
Obstetrician/gynecologists diagnose and treat a variety of pelvic infections including postpartum endometritis, post-hysterectomy cellulitis, pelvic inflammatory disease (PID), pelvic abscess, mucopurulent cervicitis, cystitis, and pyelonephritis. Many of these pelvic infections are polymicrobial in nature, and frequently therapy for these infections must be initiated without identification of the responsible pathogens. As a result, initial therapy usually consists of a broad-spectrum single agent or a combination of antibiotics with specific activity against a certain class From the Department of Obstetrics ogy. University of Florida College Gainesville. Florida.
Volume
4. Number
2. 1997
0 1997
and Gynecolof Medicine.
of organisms. There are many effective single agents or combinations from which to choose, and factors such as spectrum of activity, efficacy, side effects, compliance, and cost should be taken into account when deciding on an initial antibiotic regimen. Aztreonam (Azactam; Bristol-Myers Squibb, Princeton, NJ) is a monocyclic p-lactam, or monobactam, with excellent aerobic gram-negative coverage. It has been used alone or in combination to treat a number of obstetric and gynecologic infections. The purpose of this article is to review the derivation, spectrum of activity, mechanism of action, toxicity, and clinical application of aztreonam to assist the practitioner in deciding when aztreonam should be used in the treatment of commonly encountered pelvic infections.
Derivation Aztreonam (Figure l), first marketed in 1984, is the first of a new class of p-lactam antibiotics known as monobactams. The chemical structure of monobactam antibiotics resembles that of the penicillins and cephalosporins in that all have a /3-lactam ring. However, the thiazolidine ring common to all penicillins is not present in the monobactams (Figure 2). The remaining three-amino-monobactamic-acid ring is the nucleus around which all the monobactams are structured.’ The first monobactams were naturally occurring compounds produced by certain species of
Gluconobacter, mobacterium, Agrobacterium. these
Elsevier
Science
Inc..
Acetobacter, Pseudomonas,
compounds
all rights
reserved.
Chro-
and The potency of was enhanced
1068-607X/97/$17.00
through modifications to their chemical structure. Specifically, an aminothiazole-oxime side chain was added to position three and an a-methyl group was substituted at position four, which made the monobactams highly effective against gram-negative bacteria and also stable to p-1actamases.l Aztreonam is an entirely synthetic monobactam in which the above chemical modifications have been incorporated.
Spectrum of Activity Aztreonam is active specifically against facultative or aerobic gramnegative bacteria. In general, the spectrum of activity of aztreonam is similar to that of the aminoglycosides except that aztreonam demonstrates no activity against gram-positive bacteria whereas aminoglycosides are active against Staphylococcus aureus.’ Susceptible strains include the Enterobacteriaceae, specifically Escherichia
coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, and species of Enterobacter, Serratia, and Citrobacter. Aztreonam is effective even against strains of the above bacteria that are resistant to penicillin, older cephalosporins, and aminoglycosides. In addition, aztreonam is active against Neisseria gonorrhoeae and Haemophilus influenzae, including P-lactamaseproducing strains?,’
Citrobacter freundii, Enterobatter cloacae. and Klebsiella oxytoca are slightly less susceptible to aztreonam. Aztreonam is moderately effective against most strains of P aeruginosa but demonstrates
. PII s1068-607x(96)00066-x
61
DAVIS
CH3
Figure 1. Structure of aztreonam.
poor activity against other Pseudomonas strains.’ Aztreonam has negligible activity against gram-positive bacteria and anaerobic gram-negative bacteria, including Bacteroides and Prevotella species. The drug is ineffective against some gram-negative bacteria, including Acinetobacter species, Xanthomonas maltophilia,
Achromobacter xylosoxidans, Alcaligenes species, and Legionella pneumophila.2 Chlamydia trachomatis is not susceptible to aztreonam.
Mechanism of Action Aztreonam exerts its antimicrobial effect by inhibiting bacterial cell wall formation. The drug readily crosses the cell wall and cell membrane and binds with high affinity to
0
‘SO,H Figure 2. Structure of core rings of penicillins (above) and monobactams
(below). 62
penicillin-binding protein 3 of gram-negative bacteria. By binding to this protein, which is necessary for cell division, aztreonam prevents cell replication and eventually leads to cell death.l Aztreonam possesses a high degree of resistance to most common /3-lactamases; therefore, the antibiotic is effective against bacteria that produce these substances. In addition, aztreonam maintains its antimicrobial effect even in the acidic, anaerobic conditions of an abscess cavity.l,’
Toxicity Overall, aztreonam is a safe and well-tolerated drug with a safety profile similar to or better than that of other p-lactam antibiotics. Common side effects of aztreonam are pain and phlebitis at the injection site, occurring in approximately 2% of patients; nausea and diarrhea, occurring in less than 2% of patients; and skin rash, also occurring in approximately 2% of patients.’ Because aztreonam contains a p-lactam ring similar to penicillins and cephalosporins, concerns regarding cross-reactivity with these compounds have been expressed. However, aztreonam has demonstrated little cross-reactivity with other p-lactams in experimental studies,3 and in clinical studies aztreonam has been shown to be safe even for patients allergic to penicillin. Henry and Bendush4 reported that, of 134 patients with a history of penicillin or cephalosporin allergy, only one patient had a possible IgE-mediated urticarial rash when treated with aztreonam. Jensen et al5 treated 15 patients with cystic fibrosis who previously had had severe reactions including anaphylaxis to other /3-lactam antibiotics. Each patient received three to six courses of therapy, and none developed a type I hypersensitivity reaction.
Although the spectrum of activity of aztreonam is similar to that of the aminoglycosides, the risk of nephrotoxicity associated with aztreonam is negligible when compared to that of the latter group. Henry and Bendush,4 in both preclinical and large clinical trials, demonstrated that aztreonam has little potential to cause renal damage. Other side effects also occur infrequently. Bleeding has been reported but is rare. Aztreonam can cause an elevation in hepatic transaminases, but these changes are mild and reversible. Neutropenia, thrombocytopenia, and eosinophilia all have been reported but are unusual1 Superinfections can occur with aztreonam; enterococcus and S aureus are the usual offending bacteria. Superinfections with yeast and gram-negative bacteria are rare. Likewise, the development of pseudomembranous colitis is unusual because aztreonam has minimal effect on anaerobes in the gut.’ Aztreonam, like other p-lactam antibiotics, is a Pregnancy Category B drug. Animal studies with daily doses up to fifteen times the maximum recommended human dose have demonstrated no fetal risks, but no studies have been performed on pregnant women (PDR, 1995: 706-8). Aztreonam is present in breast milk at levels less than 1% of simultaneously determined maternal levels.
Clinical Application Aztreonam has been shown to be effective in the treatment of a variety of common pelvic infections encountered by obstetriciamgynecologists. Gibbs et al6 compared clindamycin plus aztreonam with clindamycin plus gentamicin in the treatment of 119 patients with postcesarean endometritis. Patients received clindamycin 600 mg intravenously every 6 hours with either Prim
Care
Update
Ob/Gyns
aztreonam 2 g intravenously every 8 hours or gentamicin 1.5 mg/kg intravenously every 8 hours. Of the patients in the aztreonam arm, 91.4% were clinically cured, compared with 88.6% of the patients in the gentamicin arm (not significant). There were two clinical failures and three side-effect failures in the aztreonam/clindamycin treatment group. Both clinical failures had enterococcal bacteremia; two patients with side-effect failures developed diarrhea severe enough to discontinue therapy. No patient in either treatment group developed The researchers” nephrotoxicity. concluded aztreonam was as effective as gentamicin when each was used with clindamycin in the treatment of post-cesarean endometritis. Dodson et al7 treated 42 patients with a clinical diagnosis of pelvic inflammatory disease with aztreonam and clindamycin. Fifty-one percent of the patients had evidence of a pelvic abscess. Patients received aztreonam 1 g intravenously every 8 hours and clindamycin 600 mg intravenously every 6 hours. Overall, 97.5% of the patients were cured. The one patient who failed therapy had a large abscess that eventually required surgical drainage. No patients discontinued therapy because of side effects. Henry,8 from the Squibb Institute for Medical Research, reported her experience in treating a variety of pelvic infections, including endometritis, cuff cellulitis, and pelvic inflammatory disease, with aztreonam and clindamycin. A total of 73 patients were treated in comparative and noncomparative studies. The usual dose of aztreonam was 1 or 2 g intravenously every 8 hours along with clindamycin 600 mg intravenously every 8 hours. Overall, 72 of 73 patients were treated successfully. Characteristics of the patient who failed therapy were not discussed. The author’ concluded that aztreonam was effective in the Volume
4. Numhrr
2. 1997
Table 1. Inpatient Chargesof Common Regimensof Aztreonam and Gentamicin Inpatient Charge at Shands Hospital
Antibiotic Regimen Aztreonam 1 g TID for 3 d Aztreonam 2 g TID for 3 d Gentamicin 140 me loadine dose 90mgTIDfor3vd ” Total Gentamicin 350 mg QD for 3 d (single-doseregimen) TID.
three
times
a day:
$ 742.50 $1,359.00 $ 15.40 $ 134.10 $ 149.50 $ 52.50
QD, daily.
treatment of pelvic infections and could be substituted for gentamicin. Each of the above studies demonstrated aztreonam is effective, when used in combination with clindamycin, in the treatment of polymicrobial pelvic infections. In addition, aztreonam has been used successfully to treat urinary tract infections and gonococcal cervicitis. However, despite its efficacy and safety, the use of aztreonam is limited by its expense. Table 1 lists the current patient charges for 3-day courses of gentamicin and aztreonam at Shands Teaching Hospital (personal communication, Shands Drug Information Service). Depending on the regimen chosen, the patient charges for aztreonam are approximately five to 25 times greater than those for generic gentamicin. In today’s era of cost containment, the benefits of treating a patient with an expensive medication must outweigh clearly the risks of using a less costly alternative. There are a number of clinical situations in which aztreonam, rather than an aminoglycoside, may be indicated. For instance, the use of aztreonam could be justified for a patient who already has renal damage. Likewise, it would be reasonable to choose aztreonam for a patient with a malignancy who has received or will receive cisplatin or other potentially nephrotoxic agents. In addition, aztreonam might be chosen over gentamicin if it is anticipated that the patient will require repeated courses of therapy.
Appelg has argued that the expense of aztreonam is comparable to the overall cost of gentamicin use when the amount spent on aminoglycoside levels, renal function tests, and care of patients who develop nephrotoxicity is included in cost estimates. However, many obstetric and gynecologic patients are at low risk for developing nephrotoxicity, require only short courses of therapy, and do not need monitoring of antibiotic levels or renal function tests. The routine use of aztreonam seems unwarranted unless the patient has one of the above indications. When indicated, the standard dose of aztreonam is l-2 g IV every 8-12 hours for moderately severe infections and 2 g IV every 6-8 hours for severe or life-threatening infections. In patients with renal compromise, or in the elderly, the dose should be based on the patient’s creatinine clearance (C,,) using the following formula: Males: Cc1 weight (kg) x (140-age) = 72 X serum creatinine (mg/dL) Females: Cc. = same X 0.85 For patients with a creatine clearance between 10 and 30 mL/ minute/l.73 m2, an initial dose of 1 or 2 g is given, followed by one-half of the usual maintenance dose. In patients with a creatine clearance less than 10 ml/minute/l.73 m2, an initial dose of 1 or 2 g is followed by one-quarter of the initial dose every 63
DAVIS 6,8, or 12 hours (PDR, 1995:706-8).
References
Monitoring
1. Clark P. Aztreonam. Obstet Gynecol
serum levels of aztreo-
nam is not required.
Clin North Am 1992;19:519-28. 2. American Medical Association. Drug
Conclusion
3.
In conclusion, aztreonam is a relatively new antibiotic with excellent effectiveness against gram-negative aerobic bacteria. It is safe and effective in the treatment of common obstetric and gynecologic infec-
4.
tions. However, the routine use of aztreonam is limited by its expense. Aztreonam should be considered in the treatment of infections when excellent gram-negative coverage is required and aminoglycosides are contraindicated.
64
5.
6.
evaluations annual 1995.Milwaukee (WI): American Medical Association, 1995:1481-4. Saxon A, Swabb EA, Adkinson NF. Investigation into the immunologic cross-reactivity of aztreonam with other beta-lactam antibiotics. Am J Med 1985;78(suppl 2A):19-26. Henry SA, Bendush CB. Aztreonam: worldwide overview of the treatment of patients with gram-negative infections. Am J Med 1985;78(suppl 2A): 57-64. Jensen T, Pedersen SS, Hoiby N, Koch C. Safety of aztreonam in patients with cystic fibrosis and allergy to beta-lactam antibiotics. Rev Infect Dis 1991;13(suppl 7):S594-7. Gibbs RS, Blanc0 JD, Lipscomb KA, St. Clair PJ. Aztreonam versus gen-
tamicin, each with clindamycin, in the treatment of endometritis. Obstet Gynecol 1985;65:825-9. Dodson MG, Faro S, Gentry LO. Treatment of acute pelvic inflammatory diseasewith aztreonam, a new monocyclic beta-lactam antibiotic, and clindamycin. Obstet Gynecol 1986;67:657-62. Henry SA. Overall clinical experiencewith aztreonam in the treatment of obstetric-gynecologic infections. Rev Infect Dis 1985;7(suppl 4): S703-8. Appel GB. Aminoglycoside nephrotoxicity. Am J Med 1990;88(suppl SC):lSS-20s.
Address correspondenceand reprint requests to John D. Davis, MD, Dept. of Obstetrics and Gynecology, University of Florida Collegeof Medicine, P.O. Box 100294, Gainesville, FL 32610-0294.
Prim
Care
Update
ObiGyns