Antibiotic activity against small-colony variants of staphylococcus aureus: Review of in vitro, animal and clinical data

Journal of Antimicrobial Chemotherapy

Volumn 68, Issue 7, 2013, Pages 1455-1464

  Garcia, Laetitia G ^a   Lemaire, Sandrine ^a   Kahl, Barbara C ^b   Becker, Karsten ^b   Proctor, Richard A ^c   Denis, Olivier ^d   Tulkens, Paul M ^a   Van Bambeke, Françoise ^a  

^a UNIVERSITÉ CATHOLIQUE DE LOUVAIN   (Belgium)

^b UNIVERSITY HOSPITAL MÜNSTER   (Germany)

^c UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^d ERASME HOSPITAL   (Belgium)

Author keywords

Biofilms; Haemin; intracellular infections; Menadione; Persistence; Thymidine

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE; CEFAPIRIN; CEFOTAXIME; CEPHALOSPORIN; CIPROFLOXACIN; CLINDAMYCIN; DAPTOMYCIN; DICLOXACILLIN; FOLIC ACID ANTAGONIST; FUSIDIC ACID; GENTAMICIN; HEMIN; HYDROXYAPATITE; KANAMYCIN; LINEZOLID; MENADIONE; MOXIFLOXACIN; ORITAVANCIN; OXACILLIN; RIFAMPICIN; THYMIDINE; TOBRAMYCIN; TRIMETHOPRIM; VANCOMYCIN;

ANTIBIOTIC SENSITIVITY; ANTIMICROBIAL ACTIVITY; ARTICLE; AUXOTROPHY; BACTERIAL GROWTH; BACTERICIDAL ACTIVITY; BIOFILM; CELL ACTIVATION; CONFORMATIONAL TRANSITION; CYSTIC FIBROSIS; ELECTRON TRANSPORT; HOST RESISTANCE; HUMAN; IN VITRO STUDY; INTRACELLULAR KILLING; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PHAGOLYSOSOME; PHENOTYPE; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS INFECTION;

EID: 84879473819     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dkt072     Document Type: Article

References (67)

1. Proctor RA, von Eiff C, Kahl BC et al. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Nat Rev Microbiol 2006; 4: 295-305.
2. Kahl B, Herrmann M, Everding AS, et al. Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis. J Infect Dis 1998; 177: 1023-9.
3. von Eiff C, Becker K, Metze D, et al. Intracellular persistence of Staphylococcus aureus small-colony variants within keratinocytes: a cause for antibiotic treatment failure in a patient with Darier's disease. Clin Infect Dis 2001; 32: 1643-7.
4. von Eiff C, Heilmann C, Proctor RA, et al. A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly. J Bacteriol 1997; 179: 4706-12.
5. von Eiff C. Staphylococcus aureus small colony variants: a challenge to microbiologists and clinicians. Int J Antimicrob Agents 2008; 31: 507-10.
6. McNamara PJ, Proctor RA. Staphylococcus aureus small colony variants, electron transport and persistent infections. Int J Antimicrob Agents 2000; 14: 117-22.
7. Kriegeskorte A, Konig S, Sander G, et al. Small colony variants of Staphylococcus aureus reveal distinct protein profiles. Proteomics 2011; 11: 2476-90.
8. Lannergard J, von Eiff C, Sander G, et al. Identification of the genetic basis for clinical menadione-auxotrophic small-colony variant isolates of Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52: 4017-22.
9. Acar JF, Goldstein FW, Lagrange P. Human infections caused by thiamine- or menadione-requiring Staphylococcus aureus. J Clin Microbiol 1978; 8: 142-7.
10. Sadowska B, Bonar A, von Eiff C, et al. Characteristics of Staphylococcus aureus, isolated from airways of cystic fibrosis patients, and their small colony variants. FEMS Immunol Med Microbiol 2002; 32: 191-7.
11. Bates DM, von Eiff C, McNamara PJ, et al. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J Infect Dis 2003; 187: 1654-1.
12. Baumert N, von Eiff C, Schaaff F, et al. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb Drug Resist 2002; 8: 253-60.
13. von Eiff C, Bettin D, Proctor RA, et al. Recovery of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis. Clin Infect Dis 1997; 25: 1250-1.
14. Lannergard J, Cao S, Norstrom T, et al. Genetic complexity of fusidic acid-resistant small colony variants (SCV) in Staphylococcus aureus. PLoS One 2011; 6: e28366.
15. Chatterjee I, Kriegeskorte A, Fischer A, et al. In vivo mutations of thymidylate synthase (encoded by thyA) are responsible for thymidine dependency in clinical small-colony variants of Staphylococcus aureus. J Bacteriol 2008; 190: 834-42.
16. Bayston R, Ashraf W, Smith T. Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics. J Antimicrob Chemother 2007; 59: 848-53.
17. Edwards AM. Phenotype switching is a natural consequence of Staphylococcus aureus replication. J Bacteriol 2012; 194: 5404-12.
18. Chuard C, Vaudaux PE, Proctor RA, et al. Decreased susceptibility to antibiotic killing of a stable small colony variant of Staphylococcus aureus in fluid phase and on fibronectin-coated surfaces. J Antimicrob Chemother 1997; 39: 603-8.
19. Gao W, Chua K, Davies JK, et al. Two novel point mutations in clinical Staphylococcus aureus reduce linezolid susceptibility and switch on the stringent response to promote persistent infection. PLoS Pathog 2010; 6: e1000944.
20. Yagci S, Hascelik G, Dogru D, et al. Prevalence and genetic diversity of Staphylococcus aureus small-colony variants in cystic fibrosis patients. Clin Microbiol Infect 2013; 19: 77-84.
21. Begic D, von Eiff C, Tsuji BT. Daptomycin pharmacodynamics against Staphylococcus aureus hemB mutants displaying the small colony variant phenotype. J Antimicrob Chemother 2009; 63: 977-81.
22. Garcia LG, Lemaire S, Kahl BC, et al. Pharmacodynamic evaluation of the activity of antibiotics against hemin- and menadione-dependent small-colony variants of Staphylococcus aureus in models of extracellular (broth) and intracellular (THP-1 monocytes) infections. Antimicrob Agents Chemother 2012; 56: 3700-11.
23. Nguyen HA, Denis O, Vergison A, et al. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: pharmacodynamic evaluation and comparison with isogenic normal-phenotype and revertant strains. Antimicrob Agents Chemother 2009; 53: 1434-2.
24. Idelevich EA, Kriegeskorte A, Stubbings W, et al. Comparative in vitro activity of finafloxacin against staphylococci displaying normal and small colony variant phenotypes. J Antimicrob Chemother 2011; 66: 2809-13.
25. Vaudaux P, Huggler E, Rhys-Williams W, et al. Extracellular and intracellular bactericidal activities of XF-70 against small-colony variant hemB mutants of meticillin-susceptible and meticillin-resistant Staphylococcus aureus. Int J Antimicrob Agents 2011; 37: 576-9.
26. Mitchell G, Gattuso M, Grondin G, et al. Tomatidine inhibits replication of Staphylococcus aureus small-colony variants in cystic fibrosis airway epithelial cells. Antimicrob Agents Chemother 2011; 55: 1937-45.
27. Mitchell G, Lafrance M, Boulanger S, et al. Tomatidine acts in synergy with aminoglycoside antibiotics against multiresistant Staphylococcus aureus and prevents virulence gene expression. J Antimicrob Chemother 2012; 67: 559-68.
28. Samuelsen O, Haukland HH, Kahl BC, et al. Staphylococcus aureus small colony variants are resistant to the antimicrobial peptide lactoferricin B. J Antimicrob Chemother 2005; 56: 1126-9.
29. Koo SP, Bayer AS, Sahl HG, et al. Staphylocidal action of thrombin-induced platelet microbicidal protein is not solely dependent on transmembrane potential. Infect Immun 1996; 64: 1070-4.
30. Tuchscherr L, Medina E, Hussain M, et al. Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol Med 2011; 3: 129-41.
31. Proctor RA, Peters G. Small colony variants in staphylococcal infections: diagnostic and therapeutic implications. Clin Infect Dis 1998; 27: 419-22.
32. Vesga O, Groeschel MC, Otten MF, et al. Staphylococcus aureus small colony variants are induced by the endothelial cell intracellular milieu. J Infect Dis 1996; 173: 739-42.
33. Nguyen HA, Denis O, Vergison A, et al. Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: study of antibiotic combinations. Antimicrob Agents Chemother 2009; 53: 1443-9.
34. Baltch AL, Ritz WJ, Bopp LH, et al. Activities of daptomycin and comparative antimicrobials, singly and in combination, against extracellular and intracellular Staphylococcus aureus and its stable small-colony variant in human monocyte-derived macrophages and in broth. Antimicrob Agents Chemother 2008; 52: 1829-33.
35. Garcia LG, Lemaire S, Kahl BC, et al. Intracellular forms of menadione-dependent small-colony variants of methicillin-resistant Staphylococcus aureus are hypersusceptible to b-lactams in a THP-1 cell model due to cooperation between vacuolar acidic pH and oxidant species. J Antimicrob Chemother 2012; 67: 2873-1.
36. Garcia LG, Lemaire S, Kahl BC, et al. Influence of the protein kinase C activator phorbol myristate acetate on the intracellular activity of antibiotics against hemin- and menadione-auxotrophic small-colony variant mutants of Staphylococcus aureus and their wild-type parental strain in human THP-1 cells. Antimicrob Agents Chemother 2012; 56: 6166-74.
37. Lemaire S, Fuda C, Van Bambeke F, et al. Restoration of susceptibility of methicillin-resistant Staphylococcus aureus to b-lactam antibiotics by acidic pH: role of penicillin-binding protein PBP 2a. J Biol Chem 2008; 283: 12769-76.
38. Maduka-Ezeh A, Seville MT, Kusne S, et al. Thymidine auxotrophic Staphylococcus aureus small-colony variant endocarditis and left ventricular assist device infection. J Clin Microbiol 2012; 50: 1102-5.
39. Singh R, Ray P, Das A, et al. Enhanced production of exopolysaccharide matrix and biofilm by a menadione-auxotrophic Staphylococcus aureus small-colony variant. J Med Microbiol 2010; 59: 521-7.
40. Mitchell G, Seguin DL, Asselin AE, et al. Staphylococcus aureus sigma B-dependent emergence of small-colony variants and biofilm production following exposure to Pseudomonas aeruginosa 4-hydroxy-2- heptylquinoline-N-oxide. BMC Microbiol 2010; 10: 33.
41. Mitchell G, Brouillette E, Seguin DL, et al. A role for sigma factor B in the emergence of Staphylococcus aureus small-colony variants and elevated biofilm production resulting from an exposure to aminoglycosides. Microb Pathog 2010; 48: 18-27.
42. Latimer J, Forbes S, McBain AJ. Attenuated virulence and biofilm formation in Staphylococcus aureus following sublethal exposure to triclosan. Antimicrob Agents Chemother 2012; 56: 3092-100.
43. Singh .R Ray P, DasAet al. Role of persisters and small-colony variants in antibiotic resistance of planktonic and biofilm-associated Staphylococcus aureus: an in vitro study. J Med Microbiol 2009; 58: 1067-73.
44. Miller MH, Wexler MA, Steigbigel NH. Single and combination antibiotic therapy of Staphylococcus aureus experimental endocarditis: emergence of gentamicin-resistant mutants. Antimicrob Agents Chemother 1978; 14: 336-43.
45. Brouillette E, Martinez A, Boyll BJ, et al. Persistence of a Staphylococcus aureus small-colony variant under antibiotic pressure in vivo. FEMS Immunol Med Microbiol 2004; 41: 35-41.
46. Joosten U, Joist A, Gosheger G, et al. Effectiveness of hydroxyapatitevancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Biomaterials 2005; 26: 5251-8.
47. Sandberg A, Lemaire S, Van Bambeke F, et al. Intra- and extracellular activities of dicloxacillin and linezolid against a clinical Staphylococcus aureus strain with a small-colony-variant phenotype in an in vitro model of THP-1 macrophages and an in vivo mouse peritonitis model. Antimicrob Agents Chemother 2011; 55: 1443-52.
48. Besier S, Zander J, Kahl BC, et al. The thymidine-dependent small-colony-variant phenotype is associated with hypermutability and antibiotic resistance in clinical Staphylococcus aureus isolates. Antimicrob Agents Chemother 2008; 52: 2183-9.
49. Green N, Burns JL, Mayer-Hamblett N, et al. Lack of association of small-colony-variant Staphylococcus aureus strains with long-term use of azithromycin in patients with cystic fibrosis. J Clin Microbiol 2011; 49: 2772-3.
50. Spearman P, Lakey D, Jotte S, et al. Sternoclavicular joint septic arthritis with small-colony variant Staphylococcus aureus. Diagn Microbiol Infect Dis 1996; 26: 13-5.
51. Agarwal H, Verrall R, Singh SP, et al. Small colony variant Staphylococcus aureus multiorgan infection. Pediatr Infect Dis J 2007; 26: 269-71.
52. Prunier AL, Malbruny B, Laurans M, et al. High rate of macrolide resistance in Staphylococcus aureus strains from patients with cystic fibrosis reveals high proportions of hypermutable strains. J Infect Dis 2003; 187: 1709-16.
53. Jolivet-Gougeon A, Kovacs B, Gall-David S, et al. Bacterial hypermutation: clinical implications. J Med Microbiol 2011; 60: 563-73.
54. Yuan J, Wei B, Lipton MS, et al. Impact of ArcA loss in Shewanella oneidensis revealed by comparative proteomics under aerobic and anaerobic conditions. Proteomics 2012; 12: 1957-69.
55. Kohanski MA, Dwyer DJ, Hayete B, et al. A common mechanism of cellular death induced by bactericidal antibiotics. Cell 2007; 130: 797-810.
56. Gaupp R, Schlag S, Liebeke M, et al. Advantage of upregulation of succinate dehydrogenase in Staphylococcus aureus biofilms. J Bacteriol 2010; 192: 2385-94.
57. Moisan H, Brouillette E, Jacob CL, et al. Transcription of virulence factors in Staphylococcus aureus small-colony variants isolated fromcystic fibrosis patients is influenced by SigB. J Bacteriol 2006; 188: 64-76.
58. Besier S, Ludwig A, Ohlsen K, et al. Molecular analysis of the thymidine-auxotrophic small colony variant phenotype of Staphylococcus aureus. Int J Med Microbiol 2007; 297: 217-25.
59. Rolauffs B, Bernhardt TM, von Eiff C, et al. Osteopetrosis, femoral fracture, and chronic osteomyelitis caused by Staphylococcus aureussmall colony variants (SCV) treated by girdlestone resection-6-year follow-up. Arch Orthop Trauma Surg 2002; 122: 547-50.
60. Sendi P, Rohrbach M, Graber P, et al. Staphylococcus aureus small colony variants in prosthetic joint infection. Clin Infect Dis 2006; 43: 961-7.
61. Seifert H, von Eiff C, Fatkenheuer G. Fatal case due tomethicillin-resistant Staphylococcus aureus small colony variants inanAIDS patient.Emerg Infect Dis 1999; 5: 450-3.
62. Goring H, Waldner H, Emmerling P, et al. [Chronic fistulating wound infection after Lichtenstein repair of inguinal hernia, caused by a small colony variant of Staphylococcus aureus]. Chirurg 2001; 72: 441-3.
63. Coman G, Mardare N, Copacianu B, et al. [Persistent and recurrent skin infection with small-colony variant methicillin-resistant Staphylococcus aureus]. Rev Med Chir Soc Med Nat Iasi 2008; 112: 104-7.
64. Seifert H, Wisplinghoff H, Schnabel P, et al. Small colony variants of Staphylococcus aureus and pacemaker-related infection. Emerg Infect Dis 2003; 9: 1316-8.
65. Nielsen XC, Nielsen FT, Kurtzhals JA, et al. Management of recurrent pacemaker-related bacteraemia with small colony variant Staphylococcus aureus in a haemodialysis patient. BMJ Case Rep 2009; doi:10.1136/ bcr.05.2009.1910.
66. Kipp F, Ziebuhr W, Becker K, et al. Detection of Staphylococcus aureus by 16S rRNA directed in situ hybridisation in a patient with a brain abscess caused by small colony variants. J Neurol Neurosurg Psychiatry 2003; 74: 1000-2.
67. Spanu T, Romano L, D'Inzeo T, et al. Recurrent ventriculoperitoneal shunt infection caused by small-colony variants of Staphylococcus aureus. Clin Infect Dis 2005; 41: e48-52.