Top

BMC Infectious Diseases

Published in:

Open Access 01-12-2014 | Research article

Prevention of Clostridium difficilespore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam

Authors: Julian R Garneau, Louis Valiquette, Louis-Charles Fortier

Published in: BMC Infectious Diseases | Issue 1/2014

Abstract

Background

Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro.

Methods

The reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic.

Results

All strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates.

Conclusions

The capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.

Available only for authorised users

Loo V, Poirier L, Miller M, Oughton M, Libman M, Michaud S, Bourgault A, Nguyen T, Frenette C, Kelly M, Vibien A, Brassard P, Fenn S, Dewar K, Hudson T, Horn R, Rene P, Monczak Y, Dascal A: A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N Engl J Med. 2005, 353: 2442-2449. 10.1056/NEJMoa051639.CrossRefPubMed

Kuijper E, Coignard B, Tull P: Emergence of Clostridium difficile-associated disease in North America and Europe. Clin Microbiol Infect. 2006, 12 (Suppl 6): 2-18.CrossRefPubMed

McFarland LV, Elmer GW, Surawicz CM: Breaking the cycle: treatment strategies for 163 cases of recurrent Clostridium difficile disease. Am J Gastroenterol. 2002, 97: 1769-1775. 10.1111/j.1572-0241.2002.05839.x.CrossRefPubMed

Aslam S, Hamill R, Musher D: Treatment of Clostridium difficile-associated disease: old therapies and new strategies. Lancet Infect Dis. 2005, 5: 549-557. 10.1016/S1473-3099(05)70215-2.CrossRefPubMed

Pepin J, Routhier S, Gagnon S, Brazeau I: Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis. 2006, 42: 758-764. 10.1086/501126.CrossRefPubMed

Johnson S: Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J Infect. 2009, 58: 403-410. 10.1016/j.jinf.2009.03.010.CrossRefPubMed

Surawicz CM, Alexander J: Treatment of refractory and recurrent Clostridium difficile infection. Nat Rev Gastroenterol Hepatol. 2011, 8: 330-339. 10.1038/nrgastro.2011.59.CrossRefPubMed

Wilson KH: The microecology of Clostridium difficile. Clin Infect Dis. 1993, 16 (Suppl 4): S214-S218.CrossRefPubMed

Chang JY, Antonopoulos DA, Kalra A, Tonelli A, Khalife WT, Schmidt TM, Young VB: Decreased diversity of the fecal Microbiome in recurrent Clostridium difficile-associated diarrhea. J Infect Dis. 2008, 197: 435-438. 10.1086/525047.CrossRefPubMed

10.

Pepin J, Saheb N, Coulombe M, Alary M, Corriveau M, Authier S, Leblanc M, Rivard G, Bettez M, Primeau V, Nguyen M, Jacob C, Lanthier L: Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis. 2005, 41: 1254-1260. 10.1086/496986.CrossRefPubMed

11.

Kamboj M, Khosa P, Kaltsas A, Babady NE, Son C, Sepkowitz KA: Relapse versus Reinfection: surveillance of clostridium difficile infection. Clin Infect Dis. 2011, 53: 1003-1006. 10.1093/cid/cir643.CrossRefPubMedPubMedCentral

12.

Wilcox MH, Fawley WN: Hospital disinfectants and spore formation by Clostridium difficile. Lancet. 2000, 356: 1324-10.1016/S0140-6736(00)02819-1.CrossRefPubMed

13.

Fawley WN, Underwood S, Freeman J, Baines SD, Saxton K, Stephenson K, Owens RC, Wilcox MH: Efficacy of hospital cleaning agents and germicides against epidemic Clostridium difficile strains. Infect Control Hosp Epidemiol. 2007, 28: 920-925. 10.1086/519201.CrossRefPubMed

14.

Baines SD, O’Connor R, Saxton K, Freeman J, Wilcox MH: Activity of vancomycin against epidemic Clostridium difficile strains in a human gut model. J Antimicrob Chemother. 2009, 63: 520-525. 10.1093/jac/dkn502.CrossRefPubMed

15.

Burns DA, Heeg D, Cartman ST, Minton NP: Reconsidering the Sporulation Characteristics of Hypervirulent Clostridium difficile BI/NAP1/027. PLoS ONE. 2011, 6: e24894-10.1371/journal.pone.0024894.CrossRefPubMedPubMedCentral

16.

Sirard S, Valiquette L, Fortier L-C: Lack of association between clinical outcome of Clostridium difficile infections, strain type, and virulence-associated phenotypes. J Clin Microbiol. 2011, 49: 4040-4046. 10.1128/JCM.05053-11.CrossRefPubMedPubMedCentral

17.

Janoir C, Denève C, Bouttier S, Barbut F, Hoys S, Caleechum L, Chapetón Montes D, Pereira F, Henriques A, Collignon A, Monot M, Dupuy B: Adaptive strategies and pathogenesis of Clostridium difficile from in vivo transcriptomics. Infect Immun. 2013, 81: 3757-3769. 10.1128/IAI.00515-13.CrossRefPubMedPubMedCentral

18.

Ochsner UA, Bell SJ, O’Leary AL, Hoang T, Stone KC, Young CL, Critchley IA, Janjic N: Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model. J Antimicrob Chemother. 2009, 63: 964-971. 10.1093/jac/dkp042.CrossRefPubMed

19.

Mathur T, Kumar M, Barman TK, Kumar GR, Kalia V, Singhal S, Raj VS, Upadhyay DJ, Das B, Bhatnagar PK: Activity of RBx 11760, a novel biaryl oxazolidinone, against Clostridium difficile. J Antimicrob Chemother. 2011, 66: 1087-1095. 10.1093/jac/dkr033.CrossRefPubMed

20.

Babakhani F, Bouillaut L, Gomez A, Sears P, Nguyen L, Sonenshein AL: Fidaxomicin Inhibits Spore Production in Clostridium difficile. Clin Infect Dis. 2012, 55 (Suppl 2): S162-S169. 10.1093/cid/cis453.CrossRefPubMedPubMedCentral

21.

Babakhani F, Bouillaut L, Sears P, Sims C, Gomez A, Sonenshein AL: Fidaxomicin inhibits toxin production in Clostridium difficile. J Antimicrob Chemother. 2013, 68: 515-522. 10.1093/jac/dks450.CrossRefPubMed

22.

Dhalluin A, Lemee L, Pestel-Caron M, Mory F, Leluan G, Lemeland J, Pons J: Genotypic differentiation of twelve Clostridium species by polymorphism analysis of the triosephosphate isomerase (tpi) gene. Syst Appl Microbiol. 2003, 26: 90-96. 10.1078/072320203322337362.CrossRefPubMed

23.

NCCLS/CLSI: M11-A7, M11–S1 supplement. Methods for antimicrobial susceptibility testing of anaerobic bacteria; approved standard. 2007, Wayne, PA: Clinical and Laboratory Standards Institute, 2

24.

Zaiss NH, Rupnik M, Kuijper EJ, et al: Typing Clostridium difficile strains based on tandem repeat sequences. BMC Microbiol. 2009, 9: 6-10.1186/1471-2180-9-6.CrossRefPubMedPubMedCentral

25.

Warren CA, Opstal EJV, Riggins MS, Li Y, Moore JH, Kolling GL, Guerrant RL, Hoffman PS: Vancomycin Treatment’s association with delayed intestinal tissue injury, clostridial overgrowth and recurrence of Clostridium difficile infection in mice. Antimicrob Agents Chemother. 2013, 57: 689-696. 10.1128/AAC.00877-12.CrossRefPubMedPubMedCentral

26.

Sun X, Wang H, Zhang Y, Chen K, Davis B, Feng H: Mouse relapse model of Clostridium difficile infection. Infect Immun. 2011, 79: 2856-2864. 10.1128/IAI.01336-10.CrossRefPubMedPubMedCentral

27.

Gerber M, Walch C, Loffler B, Tischendorf K, Reischl U, Ackermann G: Effect of sub-MIC concentrations of metronidazole, vancomycin, clindamycin and linezolid on toxin gene transcription and production in Clostridium difficile. J Med Microbiol. 2008, 57: 776-783. 10.1099/jmm.0.47739-0.CrossRefPubMed

28.

Aldape MJ, Packham AE, Nute DW, Bryant AE, Stevens DL: Effects of ciprofloxacin on the expression and production of exotoxins by Clostridium difficile. J Med Microbiol. 2013, 62: 741-747. 10.1099/jmm.0.056218-0.CrossRefPubMedPubMedCentral

29.

Denève C, Bouttier S, Dupuy B, Barbut F, Collignon A, Janoir C: Effects of subinhibitory concentrations of antibiotics on colonization factor expression by moxifloxacin-susceptible and moxifloxacin-resistant Clostridium difficile strains. Antimicrob Agents Chemother. 2009, 53: 5155-5162. 10.1128/AAC.00532-09.CrossRefPubMedPubMedCentral

30.

Emerson JE, Stabler RA, Wren BW, Fairweather NF: Microarray analysis of the transcriptional responses of Clostridium difficile to environmental and antibiotic stress. J Med Microbiol. 2008, 57: 757-764. 10.1099/jmm.0.47657-0.CrossRefPubMed

31.

Nord CE, Sillerström E, Wahlund E: Effect of tigecycline on normal oropharyngeal and intestinal microflora. Antimicrob Agents Chemother. 2006, 50: 3375-3380. 10.1128/AAC.00373-06.CrossRefPubMedPubMedCentral

32.

Dawson LF, Valiente E, Faulds-Pain A, Donahue EH, Wren BW: Characterisation of Clostridium difficile Biofilm Formation, a Role for Spo0A. PLoS One. 2012, 7: e50527-10.1371/journal.pone.0050527.CrossRefPubMedPubMedCentral

33.

Lawley TD, Clare S, Walker AW, Goulding D, Stabler RA, Croucher N, Mastroeni P, Scott P, Raisen C, Mottram L, Fairweather NF, Wren BW, Parkhill J, Dougan G: Antibiotic treatment of Clostridium difficile carrier mice triggers a supershedder state, spore-mediated transmission, and severe disease in immunocompromised hosts. Infect Immun. 2009, 77: 3661-3669. 10.1128/IAI.00558-09.CrossRefPubMedPubMedCentral

34.

Ethapa T, Leuzzi R, Ng YK, Baban ST, Adamo R, Kuehne SA, Scarselli M, Minton NP, Serruto D, Unnikrishnan M: Multiple factors modulate biofilm formation by the anaerobic pathogen Clostridium difficile. J Bacteriol. 2013, 195: 545-555. 10.1128/JB.01980-12.CrossRefPubMedPubMedCentral

35.

Cheong EYL, Gottlieb T: Intravenous tigecycline in the treatment of severe recurrent Clostridium difficile colitis. Med J Aust. 2011, 194: 374-375.PubMed

36.

Herpers BL, Vlaminckx B, Burkhardt O, Blom H, Biemond-Moeniralam HS, Hornef M, Welte T, Kuijper EJ: Intravenous tigecycline as adjunctive or alternative therapy for severe refractory Clostridium difficile infection. Clin Infect Dis. 2009, 48: 1732-1735. 10.1086/599224.CrossRefPubMed

37.

Larson KC, Belliveau PP, Spooner LM: Tigecycline for the treatment of severe Clostridium difficile infection. Ann Pharmacother. 2011, 45: 1005-1010. 10.1345/aph.1Q080.CrossRefPubMed

38.

Lu C-L, Liu C-Y, Liao C-H, Huang Y-T, Wang H-P, Hsueh P-R: Severe and refractory Clostridium difficile infection successfully treated with tigecycline and metronidazole. Int J Antimicrob Agents. 2010, 35: 311-312. 10.1016/j.ijantimicag.2009.11.008.CrossRefPubMed

39.

Bossé D, Lemire C, Ruel J, Cantin AM, Ménard F, Valiquette L: Severe anaphylaxis caused by orally administered vancomycin to a patient with Clostridium difficile infection. Infection. 2013, 41: 579-582. 10.1007/s15010-012-0328-4.CrossRefPubMed

The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/14/29/prepub

Title: Prevention of Clostridium difficilespore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam
Authors: Julian R Garneau
Louis Valiquette
Louis-Charles Fortier
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2014
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/1471-2334-14-29

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Prevention of Clostridium difficilespore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2014

Bloodstream infections and sepsis in Greece: over-time change of epidemiology and impact of de-escalation on final outcome

Clinical features and management of a severe paradoxical reaction associated with combined treatment of Buruli ulcer and HIV co-infection

Effects of ezetimibe on cholesterol metabolism in HIV-infected patients with protease inhibitor-associated dyslipidemia: a single-arm intervention trial

Outcomes of second-line combination antiretroviral therapy for HIV-infected patients: a cohort study from Rio de Janeiro, Brazil

Treatment of bloodstream infections in ICUs

Rationale and design of REACT: a randomised controlled trial assessing the effectiveness of home-collection to increase chlamydia retesting and detect repeat positive tests

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page