5 The Canadian Journal of Hospital Pharmacy- Volume 48, No. 3, June 1995 181 11 ,t j PHARMACY PRACTICE ~ l. f e e Postpartum Endometritis: A Proposal for a Improved Patient Care and Reduced Costs Anita Kozyrskyj and Greg Ryan Guidelines for the prophylaxis and elective (low-risk) caesarean section most patients are healthy and able to treatment of postpartum endometritis patients also reduces the incidence of take medications orally, oral antibiotic have been in place in the Perinatal postpartum endometritis by at least therapy as a first line therapy was Unit at Mount Sinai Hospital since 58%. 2 entertained. Experience with oral the 1980s. During this time they have The prophylaxis of high-risk antibiotics as first line therapy for been continuously evaluated and caesarean section patients with one to postpartum endometritis was limited. revised in order to provide postpartum three doses of cefazolin lg starting at Amoxicillin, replacing intavenous patients with optimal pharmaco­ cord-clamping was the established ampicillin in the original guidelines, therapeutic care, while containing practice at Mount Sinai Hospital. was considered a possibility. treatment costs. Consistent with these During the time period July to However, the ideal oral agent would goals, the guidelines were again December 1993, patients who had not have activity against most of the revised with the additional objective received cefazolin prophylaxis at cord pathogens isolated in postpartum of introducing oral drug therapy as clamping and were subsequently endometritis, such as group B first line. In order to evaluate outcomes treated with intravenous antibiotics Streptococcus, Staphylococcus of the existing guidelines, antibiotic for postpartum endometritis repre­ epidermidis, Escherichia coli, Bac­ usage and costs were determined in sented 5% of all postpartum patients. teroides4 and especially Streptococcus postpartum patients for the time period Based on the antibiotic treatment costs f aecalis which can be selected out July to December 1993 using the drug for these patients, which include drug during cefazolin prophylaxis.5 utilization report capabilities of the acquisition, preparation, admini­ Oral amoxicillin-clavulanic acid Digimedics computer system. stration and laboratory monitoring represents such an agent. In a study Presented here are the questions asked costs, the annual treatment costs were by Fernandez et al, 73 postpartum during the revision process, the projected to be $27,500. Therefore, patients with mild endometritis, resultant changes to the guidelines cefazolin prophylaxis was extended defined as a temperature less than and the rationale for change. to all caesarean section patients with 38.5°C, were treated with either the aim of decreasing postpartum mor­ amoxicillin-clavulanic acid 500 mg Should prophylaxis be extended bidity and associated treatment costs. orally q8h or amoxicillin 500 mg/ to all caesarean section patients? metronidazole 500 mg orally q8h. For the most part, antibiotic Could oral antibiotic therapy be There was no difference between the prophylaxis of caesarean section has used as first line therapy in the groups in the number of days to been limited to high-risk caesarean treatment of mild to moderate defervescence or the infection rate. 6 section patients, for example those infections? Our guidelines were subsequently with prolonged premature rupture of Traditionally intravenous antibiotics changed to oral amoxicillin-clavulanic membranes. Prophylaxis of these had been used to treat postpartum acid for mild to moderate endometritis. patients reduces the incidence of endometritis, with ampicillin as the Oral amoxicillin was included as an postpartum endometritis by 50% .1 drug of choice, 3 followed by cefotetan alternative to amoxicillin-clavulanic However, a recently published meta­ or clindamycin and gentamicin if no acid. Oral clindamycin was reserved analysis showed that prophylaxis of response was seen in 24-48 hours. As for penicillin-allergic patients. Anita Kozyrskyj, B.Sc. Phm., was Supervisor, Perinatal Pharmacy Services, Mount Sinai Hospital, Toronto, Ontario. Ms. Kozyrskyj is now a Master's candidate, Dept. of Community Health, University of Manitoba. Greg Ryan, M.B., is Staff Obstetrician, Perinatal Unit, Mount Sinai Hospital, Toronto, Ontario. Address correspondence to: Anita Kozyrskyj, B.Sc.Phm., 505-44 The Promenade, Winnipeg, Manitoba, R3B 3H9. 182 The Canadian Journal of Hospital Pharmacy- Volume 48, No. 3, June 1995 T Should cefotetan be recommended Is it necessary to switch to oral Susceptibility of female pelvic pathogens F as a first line agent for severe therapy once the patient was afebrile to oral antibiotic agents in patients who develop postpartum endometritis. Am J endometritis and at what dose? or could therapy be stopped? Obstet Gynecol 1991; 164(5): 1383-6. From the Digimedics drug utilization In the past, all postpartum patients on 5. Stiver HG, Forward KR, Tyrrell DL, et reports it was revealed that the intravenous therapy who were afebrile al. Comparative cervical microflora majority of patients were treated with for 24-48 hours were switched to oral shifts after cefoxitin or cefazolin intravenous clindamycin and genta­ therapy. There was some evidence to prophylaxis against infection following caesarean section. Am J Obs Gyn micin. There was poor compliance indicate that switching to oral therapy 1984; 149(7):718-21. with the exisiting guidelines recom­ was not necessary in this population. 6. Fernandez H, Claquin C, Guibert M, et mending the use of ampicillin initially In two randomized studies, one of al. Suspected postpartum endometritis:a or the use of cefotetan as an alternative which was placebo controlled, the controlled clinical trial of single-agent to clindamycin and gentamicin. As efficacy rate was similar in groups antibiotic therapy with Amox-CA (Augumentin) vs ampicillin­ cefotetan has documented efficacy in switched to oral antibiotics and those metronidazole+-aminoglycoside. Eur J 7 8 postpartum endometritis , it was receiving no oral antibiotics after Obstet Gynecol Reprod Biology recommended as the treatment of patients were afebrile for 48-72 hours l 990;36:69-74. choice for severe infections because on intravenous therapy. 14,15 Only a 7. MacGregor R, Graziani A, Samuels P. of its convenient q 12h dosing. 50% compliance rate was documented Randomized, double-blind study of cefotetan and cefoxitin in post-caesarian Although mainly administered as a in mothers discharged on oral section endometritis. Am J Obstet 7 8 15 2 g dose in clinical trials, • as a beta­ antibiotics. Moreover, it has been Gynecol 1992; 167(1 ): 139-43. lactam, cefotetan exhibits time­ shown that breast-feeding mothers 8. Hemsell D, Wendel G, Gall S, et al. dependent, not concentration­ discharged on oral antibiotics Multicenter comparison of cefotetan and dependent bacterial killing. Higher discontinued the antibiotic or stopped cefoxitin in the treatment of acute obstetric and gynecologic infections. Am serum concentrations achieved with breast-feeding despite reassuring J Obstet Gynecol 1988;158:722-7. the 2 g dose do not result in greater advice that they could breastfeed while 9. Vogelman B, Gudmundsson S, LeggettJ, efficacy, provided that trough levels taking these antibiotics. 16 Therefore, et al. Correlation of antimicrobial exceed the MIC of the infecting discontinuation of therapy once the pharrnacokinetic parameters with organisms. 9 A serum trough concen­ patient was afebrile on intravenous therapeutic efficacy in an animal model. J Infect Dis 1988;1 58(4):831-47 tration of 7.4 mg/L is achieved 12 antibiotics was included as an option. 10. Martin C, Thomachot L, Albanes J. hours after a 1 g dose, greater than the Clinical Pharrnacokinetics of cefotetan. MIC of Bacteroides and other What were the outcomes of the Clin pharmacokinet 1994:26(4):249-58. susceptible bacteria. 10,11 Moreover, proposed changes? 11. Ward A, Richards D. Cefotetan, a review uterine and parametrial tissue levels The new guidelines were approved of its antibacterial activity, pharrnacokinetic properties and far exceed the MIC following a 1 g by the Antibiotic Subcommittee of therapeutic use. Drugs 1985;30:382-426. 12 dose. Therefore, it was also pro­ the Pharmacy and Therapeutics 12. Orr J, Sisson P, Barrett J, et al. posed that the cefotetan dose be Committee and updated in the annual Pharrnacokinetics and tissue kinetics of 1 modified from 2 g to 1 g q 12h. edition of the Hospital Drug gm cefotetan prophylaxis in adbominal Formulary in July 1994 (see Figure or vaginal hysterectomy. Am J Obstet Gynecol 1988; 158(3):742-3. What place in therapy do 1). Ongoing review of antibiotic 13. Bourget P, Fernandez H, Delouis C, et clindamycin and gentamicin have? utilization in postpartum patients and al. Pharrnacokinetics of tobramycin in Consistent with the previous guide­ monitoring of health outcomes, such pregnant women, safety and efficacy of a lines, clindamycin and gentamicin as the incidence of endometritis, was once-daily dose regimen. J Clin Pharm were reserved for patients with recommended to evaluate the new Therap 1991;16:167-76 W, M, M. guidelines. - 14. Hager Pascuzzi Vernon penicillin allergies or those not Efficacy of oral antibiotics following responding to cefotetan after 48-72 REFERENCES parenteral antibiotics for serious hours of therapy. Once daily genta­ 1. Monga M, Oshiro B. Puerperal infections in obstetrics and gynecology. micin dosing was proposed for these infections. Semin Perinatol Obstet Gynecol l 989;73:326-9 patients, following dosing recom­ 1993; 17(6):426-31. 15. Dinsmoor M, Newton E, Gibbs. A randomized, double-blind, placebo­ mendations used at Mount Sinai 2. Smail! F. Antibiotic prophylaxis and caesarian section. Br J Obs Gyn controlled trial of oral antibiotic therapy Hospital. As there was little experi­ 1992;99:789-90. following intravenous antibiotic therapy ence with the once daily regimen in 3. Pond DG, Bernstein PE, Love KR, et al. for postpartum endometritis. Obstet the postpartum population, 13 a pilot Comparison of ampicillin with Gynecol 1991;77:60-2 study of peak and 12-hour serum clindamycin plus gentamicin in the 16. Ito S, Koren G, Einarson T.