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Antimicrobial activity of tigecycline alone or in combination with rifampin against Staphylococcus epidermidis in biofilm

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Staphylococcus epidermidis is a commensal inhabitant of the healthy human skin, but in the recent years, it has been recognized as a nosocomial pathogen especially in immunocompromised patients. The pathogenesis of S. epidermidis is thought to be based on its capacity to form biofilms on the surface of medical devices, where bacterial cells may persist, protected from host defence and antimicrobial agents. Rifampin has been shown to be one of the most active antimicrobial agents in the eradication of the staphylococcal biofilm. However, this antibiotic should not be used in monotherapy. Therefore, one of the objectives of our research was to study the efficacy of the tigecycline/rifampin combination against methicillin-resistant S. epidermidis embedded in biofilms. Of the 80 clinically significant S. epidermidis isolates, 75 strains possess the ability to form a biofilm. These bacteria formed the biofilm via ica-dependent mechanisms. However, other biofilm-associated genes, including aap (encoding accumulation-associated protein) and bhp (coding cell wall-associated protein), were present in 85 and 29 % of isolates, respectively. The biofilm structures of S. epidermidis strains were also analyzed in confocal laser scanning microscopy (CLSM) and the obtained image demonstrated differences in their architecture. In vitro studies showed that the MIC value for tigecycline against S. epidermidis growing in the biofilm ranged from 0.125 to 2 μg/mL. Tigecycline in combination with rifampin demonstrated higher activity against bacteria embedded in biofilms than tigecycline alone.

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Fig. 1

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Confocal laser scanning microscopy


Coagulase negative staphylococci


Congo red agar


icaADBC gene


Bacteriology collection of the Department of Microbiology, A. Mickiewicz University, Poznań


Phosphate-buffered saline


Polymerase chain reaction


Propidium iodide


Polysaccharide intercellular adhesion


  • Arciola CR, Baldassarri L, Montanaro L (2001) Presence of icaA and icaD genes and slime production in a collection of staphylococcal strains from catheter-associated infections. J Clin Microbiol 39:2151–2156

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Aybar Y, Ozaras R, Besirli K, Engin E, Karabulut E, Salihoglu T, Mete B, Tabak F, Mert A, Tahan G, Yilmaz MH, Ozturk R (2012) Efficacy of tigecycline and vancomycin in experimental catheter-related Staphylococcus epidermidis infection: microbiological and electron microscopic analysis of biofilm. Int J Antimicrob Agents 39:338–342

    Article  CAS  PubMed  Google Scholar 

  • Bradford R, Manan RA, Garland SM, Daley AJ, Deighton MA (2011) Coagulase-negative staphylococci in low birth weight infants: environmental factors affecting biofilm production in Staphylococcus epidermidis. Curr Microbiol 62:850–854

    Article  CAS  PubMed  Google Scholar 

  • Christensen GD, Simpson A, Younger JJ, Baddour LM, Barrett FF, Melton DM, Beachey EH (1985) Adherence of coagulase-negative staphylococci to plastic tissue culture plates: a quantitative model for the adherence of staphylococci to medical devices. J Clin Microbiol 22:996–1006

    CAS  PubMed Central  PubMed  Google Scholar 

  • Costa AR, Henriques M, Oliveira R, Azeredo J (2009) The role of polysaccharide intercellular adhesin (PIA) in Staphylococcus epidermidis adhesion to host tissues and subsequent antibiotic tolerance. Eur J Clin Infect Dis 28:623–629

    Article  CAS  Google Scholar 

  • Fredheim EGA, Klingenberg C, Rodhe H, Frankenberger S, Gaustad P, Fllaegstad T, Sollid JE (2009) Biofilm formation by Staphylococcus haemolyticus. J Clin Microbiol 47:1172–1180

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Geha DJ, Uhl JR, Gustaferro CA, Persing DH (1994) Multiplex PCR for identification of methicillin-resistant staphylococci in the clinical laboratory. J Clin Microbiol 32:1768–1772

    CAS  PubMed Central  PubMed  Google Scholar 

  • Giacometti A, Cirioni O, Ghiselli R, Orlando F, Mocchegiani F, Silvestri C, Licci A, De Fusco M, Provinciali M, Saba V, Scalise G (2005) Comparative efficacies of quinupristin-dalfopristin, linezolid, vancomycin, and ciprofloxacin in treatment, using the antibiotic-lock technique, of experimental catheter-related infection due to Staphylococcus aureus. Antimicrob Agents Chemother 49:4042–4045

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Henning S, Wai SN, Ziebuhr W (2007) Spontaneous switch to PIA-independent biofilm formation in a ica-positive Staphylococcus epidermidis isolate. Int J Med Microbiol 297:117–122

    Article  Google Scholar 

  • Iorio NLP, Lopes APCN, Schuenck RP, Barcellos AG, Olendzki AN, Lopez GL, dos Santos KRN (2011) A combination of methods to evaluate biofilm production may help to determine the clinical relevance of Staphylococcus in blood cultures. Microbiol Immunol 55:28–33

    Article  CAS  PubMed  Google Scholar 

  • Izano EA, Amarante MA, Kher WB, Kaplan JB (2008) Differential roles of poly-N-acetylglucosamine surface polysaccharide and extracellular DNA in Staphylococcus aureus and Staphylococcus epidermidis biofilms. Appl Environ Microbiol 74:470–476

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim J-H, Kim C-H, Hacker J, Ziebuhr W, Lee BK, Cho S-H (2008) Molecular characterization of regulatory genes associated with biofilm variation in Staphylococcus aureus strains. J Microbiol Biotechnol 18:28–34

    CAS  PubMed  Google Scholar 

  • Koskela A, Nilsdotter-Augustinsson Å, Personn L, Söderquist B (2009) Prevalence of ica operon and insertion sequence IS256 among Staphylococcus epidermidis prosthetic joint infections isolates. Eur J Clin Infect Dis 28:655–660

    Article  CAS  Google Scholar 

  • Kozitskaya S, Cho S-H, Dietrich K, Marre R, Naber K, Ziebuhr W (2004) The bacterial insertion sequence element IS256 occurs preferentially in nosocomial Staphylococcus epidermidis isolates: association with biofilm formation and resistance to aminoglycosides. Infect Immun 72:1210–1215

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lim Y, Jana M, Luong TT, Lee CY (2004) Control of glucose- and NaCl-induced biofilm formation by rbf in Staphylococcus aureus. J Bacteriol 186:722–729

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mack D, Rohde H, Harris LG, Davies AP, Horstkotte MA, Knobloch JK-M (2006) Biofilm formation in medical device-related infection. Int J Artif Organs 29:343–359

    CAS  PubMed  Google Scholar 

  • Mack D, Davies AP, Harris LG, Rodhe H, Horstkotte MA, Knobloch JK-M (2007) Microbial interaction in Staphylococcus epidermidis biofilms. Anal Bioanal Chem 387:399–408

    Article  CAS  PubMed  Google Scholar 

  • Mercier RC, Kennedy C, Meadows C (2002) Antimicrobial activity of tigecycline (GAR-936) against Enterococcus faecium and Staphylococcus aureus used alone and in combination. Pharmacotherapy 22:1517–23

    Article  CAS  PubMed  Google Scholar 

  • Nilsdotter-Augustinsson Å, Koskela A, Ӧhman L, Söderquist B (2007) Characterization of coagulase-negative staphylococci isolated from patients with infected hip prostheses: use of phenotypic and genotypic analyses, including test for the presence of the ica operon. Eur J Clin Infect Dis 26:255–265

    Article  CAS  Google Scholar 

  • Petersen PJ, Labthavikul P, Jones CH, Bradford PA (2006) In vitro antibacterial activities of tigecycline in combination with other antimicrobial agents determined by chequerboard and time-kill kinetic analysis. J Antimicrob Chemother 57:573–576

    Article  CAS  PubMed  Google Scholar 

  • Qin Z, Yang X, Yang L, Jiang J, Qu Y, Molin S, Qu D (2007) Formation and properties of in vitro biofilms of ica-negative Staphylococcus epidermidis clinical isolates. J Med Microbiol 56:83–93

    Article  CAS  PubMed  Google Scholar 

  • Raad I, Hanna H, Jiang Y, Dvorak T, Reitzel R, Chaiban G, Sherertz R, Hachem R (2007) Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrobial Agents Chemother 51:1656–1660

    Article  CAS  Google Scholar 

  • Rodhe H, Kalitzky M, Kröger N, Scherpe S, Horstkotte MA, Knobloch JK-M, Zander AR, Mack D (2004) Detection of virulence-associated genes not useful for discrimination between invasive and commensal Staphylococcus epidermidis strains from a bone marrow transplant unit. J Clin Microbiol 42:5614–5619

    Article  Google Scholar 

  • Rodhe H, Mack D, Christner M, Burdelski C, Franke G, Knobloch JK-M (2006) Pathogenesis of staphylococcal device-related infections: from basic science to new diagnostic, therapeutic and prophylactic approaches. Rev Med Microbiol 17:45–54

    Article  Google Scholar 

  • Rodhe H, Burandt EC, Siemssen N, Frommelt L, Burdelski C, Wurster S, Scherpe S, Davies AP, Harris LG, Horstkotte MA, Knobloch JK-M, Ragunath C, Kaplan JB, Mack D (2007) Polysaccharide intercellular adhesion or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and joint infections. Biomaterials 28:1711–1720

    Article  Google Scholar 

  • Rodhe H, Frankenberger S, Zähringer U, Mack D (2010) Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biofilm-associated infections. Eur J Cell Biol 89:102–111

    Google Scholar 

  • Rohde H, Burdelski C, Bartscht K, Hussain M, Buck F, Horstkotte MA, Knobloch JK, Heilmann C, Herrmann M, Mack D (2005) Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases. Mol Microbiol 55:1883–95

    Article  CAS  PubMed  Google Scholar 

  • Stevens NT, Greene CM, O’Gara JP, Humphreys H (2009) Biofilm characteristics of Staphylococcus epidermidis isolates associated with device-related meningitis. J Med Microbiol 58:855–862

    Article  CAS  PubMed  Google Scholar 

  • Vandecasteele SJ, Peetermans WE, Merckx RR, Rijnders BJA, Van Eldere J (2003) Reliability of the ica, aap and atlE genes in the discrimination between invasive, colonizing and contaminant Staphylococcus epidermidis isolates in the diagnosis of catheter-related infections. Clin Microbiol Infect 9:114–119

    Article  CAS  PubMed  Google Scholar 

  • Voung C, Otto M (2002) Staphylococcus epidermidis infections. Microb Infect 4:481–489

    Article  Google Scholar 

  • Yin L-Y, Lazzarini L, Li F, Stevens CM, Calhoun JH (2005) Comparative evaluation of tigecycline and vancomycin, with and without rifampicin, in the treatment of methicillin-resistant Staphylococcus aureus experimental osteomyelitis in a rabbit model. J Antimicrob Chemother 55:995–1002

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Ewa Szczuka.

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Szczuka, E., Kaznowski, A. Antimicrobial activity of tigecycline alone or in combination with rifampin against Staphylococcus epidermidis in biofilm. Folia Microbiol 59, 283–288 (2014).

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