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Resistance to Non-glycopeptide Agents in Serious Staphylococcus aureus Infections

  • Antimicrobial Development and Drug Resistance (A Pakyz, Section Editor)
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Abstract

The role of vancomycin in the treatment of serious Staphylococcus aureus infections, both methicillin-susceptible and methicillin-resistant, is becoming increasingly ineffective due to increasing MIC and failure. The development of reduced vancomycin susceptibility by S. aureus to glycopeptides highlights the need for clinicians to reexamine the roles of non-glycopeptide therapy. As the use of these alternative non-glycopeptides antimicrobials increases, it will become pertinent to monitor the rates of resistance. Large surveillance programs have provided data for resistance against S. aureus for the non-glycopeptides (daptomycin, ceftaroline, tigecycline, linezolid, and tedizolid). The current published literatures suggest that worldwide resistance rates to these non-glycopeptides for serious MRSA infections are still low. Implementation of antimicrobial stewardship programs will be crucial in prevention of resistance of these antimicrobials against S. aureus.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of great importance

  1. Filice GA, Nyman JA, Lexau C, Lees CH, Bockstedt LA, Como-Sabetti K, et al. Excess costs and utilization associated with methicillin resistance for patients with Staphylococcus aureus infection. Infect Control Hosp Epidemiol. 2010;31(04):365–73.

    Article  PubMed  Google Scholar 

  2. Liu C, Bayer A, Cosgrove SE, Daum RS, Fridkin SK, Gorwitz RJ et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011.

  3. Zhang S, Sun X, Chang W, Dai Y, Ma X. Systematic review and meta-analysis of the epidemiology of vancomycin-intermediate and heterogeneous vancomycin-intermediate Staphylococcus aureus isolates. PLoS One. 2015;10(8):e0136082.

    Article  PubMed  PubMed Central  Google Scholar 

  4. van Hal SJ, Fowler VG. Is it time to replace vancomycin in the treatment of methicillin-resistant Staphylococcus aureus infections? Clin Infect Dis. 2013;56(12):1779–88.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Jacob JT, DiazGranados CA. High vancomycin minimum inhibitory concentration and clinical outcomes in adults with methicillin-resistant Staphylococcus aureus infections: a meta-analysis. Int J Infect Dis. 2013;17(2):e93–e100.

    Article  CAS  PubMed  Google Scholar 

  6. Holmes NE, Turnidge JD, Munckhof WJ, Robinson JO, Korman TM, O’Sullivan MVN, et al. Vancomycin AUC/MIC ratio and 30-day mortality in patients with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother. 2013;57(4):1654–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kalil AC, Van Schooneveld TC, Fey PD, Rupp ME. Association between vancomycin minimum inhibitory concentration and mortality among patients with Staphylococcus aureus bloodstream infections: a systematic review and meta-analysis. JAMA. 2014;312(15):1552–64.

    Article  PubMed  Google Scholar 

  8. Baxi SM, Clemenzi-Allen A, Gahbauer A, Deck D, Imp B, Vittinghoff E et al. Vancomycin minimum inhibitory concentration does not predict 90 day mortality, readmission or relapse in a prospective cohort of adults with Staphylococcus aureus bacteremia. Antimicrob Agents Chemother 2016.

  9. Yahav D, Lador A, Paul M and Leibovici L. Efficacy and safety of tigecycline: a systematic review and meta-analysis. J Antimicrob Chemother 2011;66.

  10. Moise PA, Culshaw DL, Wong-Beringer A, Bensman J, Lamp KC, Smith WJ, et al. Comparative effectiveness of vancomycin versus daptomycin for MRSA bacteremia with vancomycin MIC > 1 mg/l: a multicenter evaluation. Clin Ther. 2015;38(1):16–30.

    Article  PubMed  Google Scholar 

  11. Murray KP, Zhao JJ, Davis SL, Kullar R, Kaye KS, Lephart P, et al. Early use of daptomycin versus vancomycin for methicillin-resistant Staphylococcus aureus bacteremia with vancomycin minimum inhibitory concentration >1 mg/l: a matched cohort study. Clin Infect Dis. 2013;56(11):1562–69.

    Article  CAS  PubMed  Google Scholar 

  12. Mangili A, Bica I, Snydman DR, Hamer DH. Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2005;40(7):1058–60.

    Article  CAS  PubMed  Google Scholar 

  13. Sakoulas G, Alder J, Thauvin-Eliopoulos C, Moellering RC, Eliopoulos GM. Induction of daptomycin heterogeneous susceptibility in Staphylococcus aureus by exposure to vancomycin. Antimicrob Agents Chemother. 2006;50(4):1581–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. •• Stefani S, Campanile F, Santagati M, Mezzatesta ML, Cafiso V, Pacini G. Insights and clinical perspectives of daptomycin resistance in Staphylococcus aureus: a review of the available evidence. Int J Antimicrob Agents. 2015;46(3):278–89. An overview of daptomycin resistance: the historical development, current state of resistance, as well as current research.

    Article  CAS  PubMed  Google Scholar 

  15. van Hal SJ, Paterson DL, Gosbell IB. Emergence of daptomycin resistance following vancomycin-unresponsive Staphylococcus aureus bacteraemia in a daptomycin-naïve patient—a review of the literature. Eur J Clin Microbiol Infect Dis. 2011;30(5):603–10.

    Article  PubMed  Google Scholar 

  16. Capone A, Cafiso V, Campanile F, Parisi G, Mariani B, Petrosillo N, et al. In vivo development of daptomycin resistance in vancomycin-susceptible methicillin-resistant Staphylococcus aureus severe infections previously treated with glycopeptides. Eur J Clin Microbiol Infect Dis. 2016;35(4):625–31.

    Article  CAS  PubMed  Google Scholar 

  17. Friedman L, Alder JD, Silverman JA. Genetic changes that correlate with reduced susceptibility to daptomycin in Staphylococcus aureus. Antimicrob Agents Chemother. 2006;50(6):2137–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mishra NN, Bayer AS, Weidenmaier C, Grau T, Wanner S, Stefani S, et al. Phenotypic and genotypic characterization of daptomycin-resistant methicillin-resistant Staphylococcus aureus strains: relative roles of mprf and dlt operons. PLoS One. 2014;9(9):e107426.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Sader HS, Jones RN. The activity of daptomycin against wild-type Staphylococcus aureus and strains with reduced susceptibility to vancomycin. Clin Infect Dis. 2006;43(6):798–99.

    Article  PubMed  Google Scholar 

  20. • Sader HS, Farrell DJ, Flamm RK, Jones RN. Daptomycin activity tested against 164,457 bacterial isolates from hospitalised patients: summary of 8 years of a worldwide surveillance programme (2005–2012). Int J Antimicrob Agents. 2013;43(5):465–69. A large worldwide surveillance of 97,542 S. aureus isolates tested against daptomycin.

    Article  Google Scholar 

  21. Rand KH, Houck HJ. Synergy of daptomycin with oxacillin and other β-lactams against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2004;48(8):2871–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Leonard SN, Rolek KM. Evaluation of the combination of daptomycin and nafcillin against vancomycin-intermediate Staphylococcus aureus. J Antimicrob Chemother. 2013;68(3):644–47.

    Article  CAS  PubMed  Google Scholar 

  23. Sakoulas G, Okumura CY, Thienphrapa W, Olson J, Nonejuie P, Dam Q, et al. Nafcillin enhances innate immune-mediated killing of methicillin-resistant Staphylococcus aureus. J Mol Med. 2013;92(2):139–49.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mehta S, Singh C, Plata KB, Chanda PK, Paul A, Riosa S, et al. B-lactams increase the antibacterial activity of daptomycin against clinical methicillin-resistant Staphylococcus aureus strains and prevent selection of daptomycin-resistant derivatives. Antimicrob Agents Chemother. 2012;56(12):6192–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang S-J, Xiong YQ, Boyle-Vavra S, Daum R, Jones T, Bayer AS. Daptomycin-oxacillin combinations in treatment of experimental endocarditis caused by daptomycin-nonsusceptible strains of methicillin-resistant Staphylococcus aureus with evolving oxacillin susceptibility (the “seesaw effect”). Antimicrob Agents Chemother. 2010;54(8):3161–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Barber KE, Ireland CE, Bukavyn N, Rybak MJ. Observation of “seesaw effect” with vancomycin, teicoplanin, daptomycin and ceftaroline in 150 unique MRSA strains. Infect Dis Ther. 2014;3(1):35–43.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dhand A, Bayer AS, Pogliano J, Yang S-J, Bolaris M, Nizet V, et al. Use of antistaphylococcal β-lactams to increase daptomycin activity in eradicating persistent bacteremia due to methicillin-resistant Staphylococcus aureus: role of enhanced daptomycin binding. Clin Infect Dis. 2011;53(2):158–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Davis JS, Sud A, O’Sullivan MVN, Robinson JO, Ferguson PE, Foo H, et al. Combination of vancomycin and β-lactam therapy for methicillin-resistant Staphylococcus aureus bacteremia: a pilot multicenter randomized controlled trial. Clin Infect Dis. 2016;62(2):173–80.

    Article  PubMed  Google Scholar 

  29. Armengol-Porta M, Tenorio-Abreu A, Bandt D, Coleman DC, Gavier-Widen D, Hotzel H, et al. In vitro activity of ceftaroline against mecC-positive MRSA isolates. J Glob Antimicrob Resist. 2016;5:3–6.

    Article  PubMed  Google Scholar 

  30. Burnett YJ, Echevarria K and Traugott KA. Ceftaroline as salvage monotherapy for persistent MRSA bacteremia: a review of current literature. Ann Pharmacother 2016.

  31. Barber KE, Rybak MJ, Sakoulas G. Vancomycin plus ceftaroline shows potent in vitro synergy and was successfully utilized to clear persistent daptomycin-non-susceptible MRSA bacteraemia. J Antimicrobial Chemother. 2015;70(1):311–13.

    Article  CAS  Google Scholar 

  32. Baxi SM, Chan D, Jain V. Daptomycin non-susceptible, vancomycin-intermediate Staphylococcus aureus endocarditis treated with ceftaroline and daptomycin: case report and brief review of the literature. Infection. 2015;43(6):751–54.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Sader HS, Mendes RE, Jones RN, Flamm RK. Antimicrobial susceptibility patterns of community- and hospital-acquired methicillin-resistant Staphylococcus aureus from United States hospitals: results from the aware ceftaroline surveillance program (2012–2014). Diagn Microbiol Infect Dis 2016.

  34. Sanchez EH, Mendes RE, Sader HS, Allison GM. In vivo emergence of ceftaroline resistance during therapy for MRSA vertebral osteomyelitis. J Antimicrob Chemother. 2016;71(6):1736–38.

    Article  CAS  PubMed  Google Scholar 

  35. Marchaim D, Pogue JM, Tzuman O, Hayakawa K, Lephart PR, Salimnia H, et al. Major variation in MICs of tigecycline in gram-negative bacilli as a function of testing method. J Clin Microbiol. 2014;52(5):1617–21.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Florescu I, Beuran M, Dimov R, Razbadauskas A, Bochan M, Fichev G, et al. Efficacy and safety of tigecycline compared with vancomycin or linezolid for treatment of serious infections with methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococci: a phase 3, multicentre, double-blind, randomized study. J Antimicrob Chemother. 2008;62 suppl 1:i17–28.

    Article  CAS  PubMed  Google Scholar 

  37. De Pascale G, Montini L, Pennisi MA, Bernini V, Maviglia R, Bello G, et al. High dose tigecycline in critically ill patients with severe infections due to multidrug-resistant bacteria. Crit Care. 2014;18(3):1–9.

    Article  Google Scholar 

  38. Xu L, Wang YL, Du S, Chen L, Long LH, Wu Y. Efficacy and safety of tigecycline for patients with hospital-acquired pneumonia. Chemotherapy. 2015;61(6):323–30.

    Article  Google Scholar 

  39. • Sader HS, Castanheira M, Farrell DJ, Flamm RK, Mendes RE, Jones RN. Tigecycline antimicrobial activity tested against clinical bacteria from Latin American medical centres: results from sentry antimicrobial surveillance program (2011–2013). International Journal of Antimicrobial Agents 2014. A large surveillance of 5,118 S. aureus isolates from collected from Latin American medical centers.

  40. Tärnberg M, Nilsson LE, Dowzicky MJ. Antimicrobial activity against a global collection of skin and skin structure pathogens: results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.), 2010–2013. Int J Infect Dis. 2014;49:141–48.

    Article  Google Scholar 

  41. Chavanet P. The ZEPHyR study: a randomized comparison of linezolid and vancomycin for MRSA pneumonia. Med Mal Infect. 2013;43(11–12):451–55.

    Article  CAS  PubMed  Google Scholar 

  42. Tsiodras S, Gold HS, Sakoulas G, Eliopoulos GM, Wennersten C, Venkataraman L, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet. 2001;358(9277):207–08.

    Article  CAS  PubMed  Google Scholar 

  43. Cai JC, Hu YY, Zhou HW, Chen G-X, Zhang R. Dissemination of the same cfr-carrying plasmid among methicillin-resistant Staphylococcus aureus and coagulase-negative staphylococcal isolates in China. Antimicrob Agents Chemother. 2015;59(6):3669–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Thool V, Bhoosreddy G and Wadher B. Detection of resistance to linezolid in Staphylococcus aureus infecting orthopedic patients; 2012.

  45. Gu B, Kelesidis T, Tsiodras S, Hindler J, Humphries RM. The emerging problem of linezolid-resistant Staphylococcus. J Antimicrob Chemother. 2013;68(1):4–11.

    Article  CAS  PubMed  Google Scholar 

  46. • Flamm RK, Mendes RE, Hogan PA, Streit JM, Ross JE, Jones RN. Linezolid surveillance results for the United States (leader surveillance program 2014). Antimicrob Agents Chemother. 2016;60(4):2273–80. A large worldwide surveillance of 3,106 S. aureus isolates tested against lenizolid.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mendes RE, Hogan PA, Jones RN, Sader HS, Flamm RK. Surveillance for linezolid resistance via the Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme (2014): evolving resistance mechanisms with stable susceptibility rates. J Antimicrob Chemother. 2016;71(7):1860–65.

    Article  CAS  PubMed  Google Scholar 

  48. Sánchez García M, De la Torre M, Morales G, et al. Clinical outbreak of linezolid-resistant Staphylococcus aureus in an intensive care unit. JAMA. 2010;303(22):2260–64.

    Article  PubMed  Google Scholar 

  49. Moran GJ, Fang E, Corey GR, Das AF, De Anda C, Prokocimer P. Tedizolid for 6 days versus linezolid for 10 days for acute bacterial skin and skin-structure infections (establish-2): a randomised, double-blind, phase 3, non-inferiority trial. Lancet Infect Dis. 2014;14(8):696–705.

    Article  CAS  PubMed  Google Scholar 

  50. Prokocimer P, De Anda C, Fang E, Mehra P, Das A. Tedizolid phosphate vs linezolid for treatment of acute bacterial skin and skin structure infections: the establish-1 randomized trial. JAMA. 2013;309(6):559–69.

    Article  CAS  PubMed  Google Scholar 

  51. • Sahm DF, Deane J, Bien PA, Locke JB, Zuill DE, Shaw KJ, et al. Results of the surveillance of tedizolid activity and resistance program: in vitro susceptibility of gram-positive pathogens collected in 2011 and 2012 from the United States and Europe. Diagn Microbiol Infect Dis. 2015;81(2):112–18. A large surveillance of 4,449 S. aureus isolates tested against tedizolid from the United States and Europe.

    Article  CAS  PubMed  Google Scholar 

  52. Farrell D, Sader H, Mendes R, Jones R. The activity of tedizolid against gram-positive pathogens isolated from patients in medical centres in Europe, Turkey and Israel: 2014 surveillance. ECCMID 2016.

  53. Shaw KJ, Poppe S, Schaadt R, Brown-Driver V, Finn J, Pillar CM, et al. In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains. Antimicrob Agents Chemother. 2008;52(12):4442–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Locke JB, Zurenko GE, Shaw KJ, Bartizal K. Tedizolid for the management of human infections: in vitro characteristics. Clin Infect Dis. 2014;58 suppl 1:S35–42.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Vanthida Huang.

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Mr. Molina and Dr. Huang declare that they have no conflicts of interests.

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Molina, K.C., Huang, V. Resistance to Non-glycopeptide Agents in Serious Staphylococcus aureus Infections. Curr Infect Dis Rep 18, 47 (2016). https://doi.org/10.1007/s11908-016-0553-6

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