Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by Preterm Premature Rupture of Membranes

Abstract

Objective To quantify the potential cost savings if azithromycin is substituted for erythromycin in women with preterm premature rupture of membranes (PPROM).

Study Design Secondary analysis of a multicentered study investigating magnesium sulfate for the prevention of cerebral palsy in premature infants. All patients with PPROM who received antibiotics for prophylaxis were included in the analysis. The number of expected doses each patient would have received was calculated for erythromycin, multidose azithromycin, and single-dose azithromycin regimens accounting for latency from PPROM to delivery. The wholesale acquisition cost was used to calculate the expected cost of each regimen.

Results There were 981 PPROM patients who received a penicillin class antibiotic and erythromycin. Patients would have received 7,528 intravenous doses and 10,194 oral doses of erythromycin at a combined cost of $357,169. In comparison, patients would have received 6,422 and 3,942 doses at a cost of $15,669 and $9,574 for the multidose and single-dose azithromycin regimens respectively, which represents a more than 95% cost reduction for either regimen compared with erythromycin.

Conclusion The use of azithromycin substituted for erythromycin in the standard antibiotic regimen of women with PPROM represents a potential for substantial cost reduction.

Keywords

azithromycin - preterm premature rupture of membranes - antibiotics - erythromycin - latency - cost

Note

This research was previously presented as a poster presentation at The Society for Maternal–Fetal Medicine (abstract no. 382) on January 26, 2017, in Las Vegas, NV.

• References

• 1 Alexander GR. Prematurity at Birth: Determinants, Consequences, and Geographic Variation. Washington, DC: National Academies Press; 2007
• 2 Hamilton BE, Martin JA, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2014. Natl Vital Stat Rep 2015; 64 (12) 1-64
• 3 Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol 2011; 54 (02) 307-312
• 4 Mercer BM, Miodovnik M, Thurnau GR. , et al; National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. JAMA 1997; 278 (12) 989-995
• 5 Kenyon SL, Taylor DJ, Tarnow-Mordi W. ; ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. Lancet 2001; 357 (9261): 979-988
• 6 Kenyon S, Taylor DJ. , Tarnow-Mordi W; ORACLE Collaborative Group. ORACLE--antibiotics for preterm prelabour rupture of the membranes: short-term and long-term outcomes. Acta Paediatr 2002; 91 (437) 12-15
• 7 Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev 2010; (08) CD001058
• 8 American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. Practice Bulletin No. 172: premature rupture of membranes. Obstet Gynecol 2016; 128 (04) e165-e177
• 9 Finneran MM, Appiagyei A, Templin M, Mertz H. Comparison of azithromycin versus erythromycin for prolongation of latency in pregnancies complicated by preterm premature rupture of membranes. Am J Perinatol 2017; 34 (11) 1102-1107
• 10 Pierson RC, Gordon SS, Haas DM. A retrospective comparison of antibiotic regimens for preterm premature rupture of membranes. Obstet Gynecol 2014; 124 (03) 515-519
• 11 Amsden GW. Erythromycin, clarithromycin, and azithromycin: are the differences real?. Clin Ther 1996; 18 (01) 56-72
• 12 Rapp RP. Pharmacokinetics and pharmacodynamics of intravenous and oral azithromycin: enhanced tissue activity and minimal drug interactions. Ann Pharmacother 1998; 32 (7-8): 785-793
• 13 Hopkins S. Clinical toleration and safety of azithromycin. Am J Med 1991; 91 (3A): 40S-45S
• 14 Edwards MS, Newman RB, Carter SG, Leboeuf FW, Menard MK, Rainwater KP. Randomized clinical trial of azithromycin vs. erythromycin for the treatment of chlamydia cervicitis in pregnancy. Infect Dis Obstet Gynecol 1996; 4 (06) 333-337
• 15 Azithromycin: pharmacokinetics. In Micromedex [Electronic version]. Greenwood Village, CO: Truven Health Analytics. Available at: http://www.micromedexsolutions.com . Accessed April 15, 2017
• 16 Rouse DJ, Hirtz DG, Thom E. , et al; Eunice Kennedy Shriver NICHD Maternal-Fetal Medicine Units Network. A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy. N Engl J Med 2008; 359 (09) 895-905
• 17 Reichert S, Simon T, Halm EA. Physicians' attitudes about prescribing and knowledge of the costs of common medications. Arch Intern Med 2000; 160 (18) 2799-2803
• 18 Allan GM, Lexchin J. Physician awareness of diagnostic and nondrug therapeutic costs: a systematic review. Int J Technol Assess Health Care 2008; 24 (02) 158-165
• 19 Allan GM, Lexchin J, Wiebe N. Physician awareness of drug cost: a systematic review. PLoS Med 2007; 4 (09) 1486-1496
• 20 Newman KL, Varkey J, Rykowski J, Mohan AV. Yelp for prescribers: a quasi-experimental study of providing antibiotic cost data and prescription of high-cost antibiotics in an academic and tertiary care hospital. J Gen Intern Med 2015; 30 (08) 1140-1146
• 21 Feldman LS, Shihab HM, Thiemann D. , et al. Impact of providing fee data on laboratory test ordering: a controlled clinical trial. JAMA Intern Med 2013; 173 (10) 903-908
• 22 Ramsey PS, Vaules MB, Vasdev GM, Andrews WW, Ramin KD. Maternal and transplacental pharmacokinetics of azithromycin. Am J Obstet Gynecol 2003; 188 (03) 714-718
• 23 Miura Y, Payne MS, Keelan JA. , et al. Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection. Antimicrob Agents Chemother 2014; 58 (09) 5413-5420
• 24 Heikkinen T, Laine K, Neuvonen PJ, Ekblad U. The transplacental transfer of the macrolide antibiotics erythromycin, roxithromycin and azithromycin. BJOG 2000; 107 (06) 770-775
• 25 Acosta EP, Grigsby PL, Larson KB. , et al. Transplacental transfer of azithromycin and its use for eradicating intra-amniotic ureaplasma infection in a primate model. J Infect Dis 2014; 209 (06) 898-904
• 26 Zhanel GG, Dueck M, Hoban DJ. , et al. Review of macrolides and ketolides: focus on respiratory tract infections. Drugs 2001; 61 (04) 443-498
• 27 Bohte R, van't Wout JW, Lobatto S. , et al. Efficacy and safety of azithromycin versus benzylpenicillin or erythromycin in community-acquired pneumonia. Eur J Clin Microbiol Infect Dis 1995; 14 (03) 182-187
• 28 Wubbel L, Muniz L, Ahmed A. , et al. Etiology and treatment of community-acquired pneumonia in ambulatory children. Pediatr Infect Dis J 1999; 18 (02) 98-104
• 29 Roord JJ, Wolf BH, Gossens MM, Kimpen JL. Prospective open randomized study comparing efficacies and safeties of a 3-day course of azithromycin and a 10-day course of erythromycin in children with community-acquired acute lower respiratory tract infections. Antimicrob Agents Chemother 1996; 40 (12) 2765-2768