Surotomycin (A Novel Cyclic Lipopeptide) vs. Vancomycin for the Treatment of Clostridioides difficile Infection: A Systematic Review and Meta-analysis

Page: [166 - 174] Pages: 9

  • * (Excluding Mailing and Handling)

Abstract

Background: Current guidelines recommend the use of vancomycin for the initial treatment of moderate to severe Clostridioides difficile Infection (CDI). Surotomycin, a novel antibiotic, has been utilized for the management of CDI with variable results.

Methods: A systematic literature search was performed using the following electronic databases [Medline, Embase, google scholar and Cochrane] for eligible studies. Randomized controlled trials comparing Surotomycin with Vancomycin for the CDI treatment were included. Demographic variables and outcomes (CDI resolution, CDI recurrence, B1/NAP1/027-specific strain treatment, B1/NAP1/027-strain recurrence, death not related to treatment) were analyzed. The primary outcome was clinical cure rate defined as the resolution of CDI at the end of the 10-day drug course.

Results: Three RCTs met the inclusion criteria with a total of 1280 patients with CDI who received either surotomycin 250 mg twice daily (642 patients) or vancomycin 125 mg four times daily (638 patients). Clinical cure rates after 10 days of treatment with either surotomycin or vancomycin were not significantly different (pooled OR: 0.89, 95% CI 0.66-1.18, p=0.41). Sustained clinical response at clinical follow-up and the overall recurrence of CDI were also not significantly different between the two groups – pooled OR 1.15 (95% CI 0.89-1.50, p=0.29) and pooled OR 0.74 (95%CI 0.52- 1.04, p=0.08), respectively. With regards to the NAP1/BI/027 strain, patients in the surotomycin group had significantly lower rates of recurrence compared to vancomycin (pooled OR 0.35, 95% CI 0.19-0.63, p<0.01).

Conclusion: Surotomycin is non-inferior to vancomycin and offers a promising alternative for the treatment and prevention of C. diff infection.

Keywords: Surotomycin, Vancomycin, Clostridium difficile, NAP1/BI/027, diarrhea, treatment, recurrence.

Graphical Abstract

[1]
Aziz M, Fatima R, Douglass LN, Abughanimeh O, Raza S. Current updates in management of Clostridium difficile infection in cancer patients. Curr Med Res Opin 2019; 35(3): 473-8.
[http://dx.doi.org/10.1080/03007995.2018.1487389] [PMID: 29888965]
[2]
Reveles KR, Lee GC, Boyd NK, Frei CR. The rise in Clostridium difficile infection incidence among hospitalized adults in the United States: 2001-2010. Am J Infect Control 2014; 42(10): 1028-32.
[http://dx.doi.org/10.1016/j.ajic.2014.06.011] [PMID: 25278388]
[3]
O’Connor JR, Johnson S, Gerding DN. Clostridium difficile infection caused by the epidemic BI/NAP1/027 strain. Gastroenterology 2009; 136(6): 1913-24.
[http://dx.doi.org/10.1053/j.gastro.2009.02.073] [PMID: 19457419]
[4]
Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev 2017. 3CD004610
[PMID: 28257555]
[5]
Johnson S, Louie TJ, Gerding DN, et al. Polymer alternative for CDI Treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: Results from two multinational, randomized, controlled trials. Clin Infect Dis 2014; 59(3): 345-54.
[http://dx.doi.org/10.1093/cid/ciu313] [PMID: 24799326]
[6]
Crook DW, Walker AS, Kean Y, et al. Study 003/004 Teams. Fidaxomicin versus vancomycin for Clostridium difficile infection: Meta-analysis of pivotal randomized controlled trials. Clin Infect Dis 2012; 55(Suppl. 2): S93-S103.
[http://dx.doi.org/10.1093/cid/cis499] [PMID: 22752871]
[7]
Petrella LA, Sambol SP, Cheknis A, et al. Decreased cure and increased recurrence rates for Clostridium difficile infection caused by the epidemic C. difficile BI strain. Clin Infect Dis 2012; 55(3): 351-7.
[http://dx.doi.org/10.1093/cid/cis430] [PMID: 22523271]
[8]
Alam MZ, Wu X, Mascio C, Chesnel L, Hurdle JG. Mode of action and bactericidal properties of surotomycin against growing and nongrowing Clostridium difficile. Antimicrob Agents Chemother 2015; 59(9): 5165-70.
[http://dx.doi.org/10.1128/AAC.01087-15] [PMID: 26055381]
[9]
Mascio CT, Chesnel L, Thorne G, Silverman JA. Surotomycin demonstrates low in vitro frequency of resistance and rapid bactericidal activity in Clostridium difficile, Enterococcus faecalis, and Enterococcus faecium. Antimicrob Agents Chemother 2014; 58(7): 3976-82.
[http://dx.doi.org/10.1128/AAC.00124-14] [PMID: 24798273]
[10]
Chilton CH, Crowther GS, Todhunter SL, et al. Efficacy of surotomycin in an in vitro gut model of Clostridium difficile infection. J Antimicrob Chemother 2014; 69(9): 2426-33.
[http://dx.doi.org/10.1093/jac/dku141] [PMID: 24816211]
[11]
Lee CH, Patino H, Stevens C, et al. Surotomycin versus vancomycin for Clostridium difficile infection: Phase 2, randomized, controlled, double-blind, non-inferiority, multicentre trial. J Antimicrob Chemother 2016; 71(10): 2964-71.
[http://dx.doi.org/10.1093/jac/dkw246] [PMID: 27432604]
[12]
Boix V, Fedorak RN, Mullane KM, et al. Primary outcomes from a phase 3, randomized, double-blind, active-controlled trial of surotomycin in subjects with Clostridium difficile infection. Open Forum Infect Dis 2017; 4(1) ofw275
[http://dx.doi.org/10.1093/ofid/ofw275] [PMID: 28480267]
[13]
Daley P, Louie T, Lutz JE, et al. Surotomycin versus vancomycin in adults with Clostridium difficile infection: Primary clinical outcomes from the second pivotal, randomized, double-blind, Phase 3 trial. J Antimicrob Chemother 2017; 72(12): 3462-70.
[http://dx.doi.org/10.1093/jac/dkx299] [PMID: 28961905]
[14]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[15]
Shuster J. Review: Cochrane handbook for systematic reviews for interventions Version 510, published 3/2011. Julian P.T. Higgins and Sally Green, Editors. Res Synth Methods 2011; 2: pp. 126-30.
[16]
Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomized trials. BMJ 2011; 343: d5928-8.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[17]
Lee C, Louie TJ, Weiss K, et al. Fidaxomicin versus Vancomycin in the treatment of Clostridium difficile Infection: Canadian outcomes. Can J Infect Dis Med Microbiol 2016; 20168048757
[http://dx.doi.org/10.1155/2016/8048757] [PMID: 27366179]
[18]
Louie TJ, Miller MA, Mullane KM, et al. OPT-80-003 Clinical study group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011; 364(5): 422-31.
[http://dx.doi.org/10.1056/NEJMoa0910812] [PMID: 21288078]
[19]
McDonald LC, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clin Infect Dis 2018; 66(7): e1-e48.
[http://dx.doi.org/10.1093/cid/cix1085] [PMID: 29462280]
[20]
Ooijevaar RE, van Beurden YH, Terveer EM, et al. Update of treatment algorithms for Clostridium difficile infection. Clin Microbiol Infect 2018; 24(5): 452-62.
[http://dx.doi.org/10.1016/j.cmi.2017.12.022] [PMID: 29309934]
[21]
Fatima R, Aziz M. The hypervirulent strain of Clostridium Difficile: NAP1/B1/027 - A brief overview. Cureus 2019; 11(1)e3977
[http://dx.doi.org/10.7759/cureus.3977] [PMID: 30967977]
[22]
Cheknis AK, Citron DM, Nagaro KJ, et al. Epidemic BI/NAP1 is the dominant strain of Clostridium difficile found in patients in the OPT-80 vs. vancomycin clinical trial in North America and the European Union.Program and abstracts of the 48th Annual ICAAC/46th Annual IDSA Annual Meeting. 2008 Oct 25-28; Washington, DC, USA. Abstract K-508. .
[23]
Cheknis AK, Davidson D, Nagaro KJ, et al. Prevalence of epidemic REA types of Clostridium difficile from a recentEuropean clinical treatment trial program and abstracts of the 9th Biennial Congress of the Anaerobe Society of the Americas. 2008 Jul 24-27; Long Beach, California, USA . Abstract PII-6.