1,059
Views
45
CrossRef citations to date
0
Altmetric
Review

Mechanisms of antimicrobial resistance among hospital-associated pathogens

ORCID Icon, &
Pages 269-287 | Received 09 Jan 2018, Accepted 21 Mar 2018, Published online: 16 Apr 2018

References

  • D’Costa VM, King CE, Kalan L, et al. Antibiotic resistance is ancient. Nature. 2011;477(7365):457–461.
  • Organization WH Antimicrobial Resistance: global report on surveillance 2014. 2014. Accessed on December 12, 2017, Available from: http://www.who.int/drugresistance/documents/surveillancereport/en/.
  • Magill SS, Edwards JR, Bamberg W, et al. Multistate point-prevalence survey of health care-associated infections. N Engl J Med. 2014;370(13):1198–1208.
  • Cosgrove SE. The relationship between antimicrobial resistance and patient outcomes: mortality, length of hospital stay, and health care costs. Clin Infect Dis. 2006;42(Suppl 2):S82–S89.
  • DiazGranados CA, Zimmer SM, Klein M, et al. Comparison of mortality associated with vancomycin-resistant and vancomycin-susceptible enterococcal bloodstream infections: a meta-analysis. Clin Infect Dis. 2005;41(3):327–333.
  • Sydnor ER, Perl TM. Hospital epidemiology and infection control in acute-care settings. Clin Microbiol Rev. 2011;24(1):141–173.
  • Goldstein BP. Resistance to rifampicin: a review. J Antibiot (Tokyo). 2014;67(9):625–630.
  • Thomas CM, Nielsen KM. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nat Rev Microbiol. 2005;3(9):711–721.
  • Canton R, Gonzalez-Alba JM, Galan JC. CTX-M Enzymes: origin and Diffusion. Front Microbiol. 2012;3:110.
  • Hakenbeck R. Transformation in Streptococcus pneumoniae: mosaic genes and the regulation of competence. Res Microbiol. 2000;151(6):453–456.
  • Billard-Pomares T, Fouteau S, Jacquet ME, et al. Characterization of a P1-like bacteriophage carrying an SHV-2 extended-spectrum beta-lactamase from an Escherichia coli strain. Antimicrob Agents Chemother. 2014;58(11):6550–6557.
  • Mazaheri Nezhad Fard R, Barton MD, Heuzenroeder MW. Bacteriophage-mediated transduction of antibiotic resistance in enterococci. Lett Appl Microbiol. 2011;52(6):559–564.
  • Wilson DN. Ribosome-targeting antibiotics and mechanisms of bacterial resistance. Nat Rev Microbiol. 2014;12(1):35–48.
  • Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat. 2010;13(6):151–171.
  • Costa Y, Galimand M, Leclercq R, et al. Characterization of the chromosomal aac(6ʹ)-Ii gene specific for Enterococcus faecium. Antimicrob Agents Chemother. 1993;37(9):1896–1903.
  • Krogstad DJ, Korfhagen TR, Moellering RC, et al. Aminoglycoside-inactivating enzymes in clinical isolates of Streptococcus faecalis. An explanation for resistance to antibiotic synergism. J Clin Invest. 1978;62(2):480–486.
  • Eliopoulos GM, Farber BF, Murray BE, et al. Ribosomal resistance of clinical enterococcal to streptomycin isolates. Antimicrob Agents Chemother. 1984;25(3):398–399.
  • Courvalin P, Carlier C, Collatz E. Plasmid-mediated resistance to aminocyclitol antibiotics in group D streptococci. J Bacteriol. 1980;143(2):541–551.
  • Tipper DJ, Strominger JL. Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine. Proc Natl Acad Sci U S A. 1965;54(4):1133–1141.
  • Bush K. The ABCD’s of beta-lactamase nomenclature. J Infect Chemother. 2013;19(4):549–559.
  • Bush K, Jacoby GA. Updated functional classification of beta-lactamases. Antimicrob Agents Chemother. 2010;54(3):969–976.
  • Vincent J-L, Rello J, Marshall J, et al. International study of the prevalence and outcomes of infection in intensive care units. Jama. 2009;302(21):2323–2329.
  • Sievert DM, Ricks P, Edwards JR, et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2009-2010. Infect Control Hosp Epidemiol. 2013;34(1):1–14.
  • Bonnet R. Growing group of extended-spectrum beta-lactamases: the CTX-M enzymes. Antimicrob Agents Chemother. 2004;48(1):1–14.
  • Jacob, J. T., Klein, G. E., Laxminarayan, R., et al. (2013). Vital signs: carbapenem-resistant Enterobacteriaceae. MMWR Morb Mortal Wkly Rep. 2013;62(9):165–169.
  • Queenan AM, Bush K. Carbapenemases: the versatile beta-lactamases. Clin Microbiol Rev. 2007;20(3):440–458. table of contents.
  • Cornaglia G, Giamarellou H, Rossolini GM. Metallo-beta-lactamases: a last frontier for beta-lactams? Lancet Infect Dis. 2011;11(5):381–393.
  • Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10(9):597–602.
  • Jeon JH, Lee JH, Lee JJ, et al. Structural basis for carbapenem-hydrolyzing mechanisms of carbapenemases conferring antibiotic resistance. Int J Mol Sci. 2015;16(5):9654–9692.
  • van Duin D, Bonomo RA. Ceftazidime/avibactam and ceftolozane/tazobactam: second-generation beta-lactam/beta-lactamase inhibitor combinations. Clin Infect Dis. 2016;63(2):234–241.
  • Potron A, Poirel L, Rondinaud E, et al. Intercontinental spread of OXA-48 beta-lactamase-producing Enterobacteriaceae over a 11-year period, 2001 to 2011. Euro Surveill. 2013;18(31):20549.
  • Potron A, Poirel L, Nordmann P. Derepressed transfer properties leading to the efficient spread of the plasmid encoding carbapenemase OXA-48. Antimicrob Agents Chemother. 2014;58(1):467–471.
  • Johnson JW, Fisher JF, Mobashery S. Bacterial cell-wall recycling. Ann N Y Acad Sci. 2013;1277:54–75.
  • Schmidtke AJ, Hanson ND. Model system to evaluate the effect of ampD mutations on AmpC-mediated beta-lactam resistance. Antimicrob Agents Chemother. 2006;50(6):2030–2037.
  • Weber DA, Sanders CC. Diverse potential of beta-lactamase inhibitors to induce class I enzymes. Antimicrob Agents Chemother. 1990;34(1):156–158.
  • Walther-Rasmussen J, Hoiby N. OXA-type carbapenemases. J Antimicrob Chemother. 2006;57(3):373–383.
  • Livermore DM. Antibiotic resistance in staphylococci. Int J Antimicrob Agents. 2000;16(Suppl 1):S3–S10.
  • Kirby WM. Extraction of a highly potent penicillin inactivator from penicillin resistant staphylococci. Science. 1944;99(2579):452–453.
  • Barber M, Rozwadowska-Dowzenko M. Infection by penicillin-resistant staphylococci. Lancet. 1948;2(6530):641–644.
  • Lowy FD. Staphylococcus aureus infections. N Engl J Med. 1998;339(8):520–532.
  • Fisher JF, Mobashery S. beta-Lactam resistance mechanisms: gram-positive bacteria and mycobacterium tuberculosis. Cold Spring Harb Perspect Med. 2016;6(5):a025221.
  • Zhang HZ, Hackbarth CJ, Chansky KM, et al. A proteolytic transmembrane signaling pathway and resistance to beta-lactams in staphylococci. Science. 2001;291(5510):1962–1965.
  • Zygmunt DJ, Stratton CW, Kernodle DS. Characterization of four beta-lactamases produced by Staphylococcus aureus. Antimicrob Agents Chemother. 1992;36(2):440–445.
  • Nannini EC, Stryjewski ME, Singh KV, et al. Inoculum effect with cefazolin among clinical isolates of methicillin-susceptible Staphylococcus aureus: frequency and possible cause of cefazolin treatment failure. Antimicrob Agents Chemother. 2009;53(8):3437–3441.
  • Nannini EC, Stryjewski ME, Singh KV, et al. Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus. Antimicrob Agents Chemother. 2010;54(5):2206–2208.
  • Saeki, M., et al. Inoculum effect of high concentrations of methicillin-susceptible Staphylococcus aureus on the efficacy of cefazolin and other beta-lactams. J Infect Chemother. 2017;24(3). 212-215.
  • Rincón S, Reyes J, Carvajal LP, et al. Cefazolin high-inoculum effect in methicillin-susceptible Staphylococcus aureus from South American hospitals. J Antimicrob Chemother. 2013;68(12):2773–2778.
  • Pagès J-M, James CE, Winterhalter M. The porin and the permeating antibiotic: a selective diffusion barrier in Gram-negative bacteria. Nat Rev Microbiol. 2008;6(12):893–903.
  • Hancock RE, Brinkman FS. Function of pseudomonas porins in uptake and efflux. Annu Rev Microbiol. 2002;56:17–38.
  • Quale J, Bratu S, Gupta J, et al. Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates. Antimicrob Agents Chemother. 2006;50(5):1633–1641.
  • Gribun A, Nitzan Y, Pechatnikov I, et al. Molecular and structural characterization of the HMP-AB gene encoding a pore-forming protein from a clinical isolate of Acinetobacter baumannii. Curr Microbiol. 2003;47(5):434–443.
  • Livermore DM. Interplay of impermeability and chromosomal beta-lactamase activity in imipenem-resistant Pseudomonas aeruginosa. Antimicrob Agents Chemother. 1992;36(9):2046–2048.
  • Poole K. Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria. Curr Pharm Biotechnol. 2002;3(2):77–98.
  • Singh KV, Weinstock GM, Murray BE. An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin. Antimicrob Agents Chemother. 2002;46(6):1845–1850.
  • Yoshida Y, Matsuo M, Oogai Y, et al. Bacitracin sensing and resistance in Staphylococcus aureus. FEMS Microbiol Lett. 2011;320(1):33–39.
  • Poole K. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother. 2005;56(1):20–51.
  • Fournier P-E, Vallenet D, Barbe V, et al. Comparative genomics of multidrug resistance in Acinetobacter baumannii. PLoS Genet. 2006;2(1):e7.
  • Martí S, Fernández-Cuenca F, Pascual A, et al. [Prevalence of the tetA and tetB genes as mechanisms of resistance to tetracycline and minocycline in Acinetobacter baumannii clinical isolates]. Enferm Infecc Microbiol Clin. 2006;24(2):77–80.
  • Coyne S, Courvalin P, Perichon B. Efflux-mediated antibiotic resistance in Acinetobacter spp. Antimicrob Agents Chemother. 2011;55(3):947–953.
  • Livermore DM. Multiple mechanisms of antimicrobial resistance in Pseudomonas aeruginosa: our worst nightmare? Clin Infect Dis. 2002;34(5):634–640.
  • Takeda S, Nakai T, Wakai Y, et al. In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa. Antimicrob Agents Chemother. 2007;51(3):826–830.
  • Moya B, Zamorano L, Juan C, et al. Activity of a new cephalosporin, CXA-101 (FR264205), against beta-lactam-resistant Pseudomonas aeruginosa mutants selected in vitro and after antipseudomonal treatment of intensive care unit patients. Antimicrob Agents Chemother. 2010;54(3):1213–1217.
  • Cabot G, Bruchmann S, Mulet X, et al. Pseudomonas aeruginosa ceftolozane-tazobactam resistance development requires multiple mutations leading to overexpression and structural modification of AmpC. Antimicrob Agents Chemother. 2014;58(6):3091–3099.
  • Achkar JM, Fries BC. Candida infections of the genitourinary tract. Clin Microbiol Rev. 2010;23(2):253–273.
  • Hof H. A new, broad-spectrum azole antifungal: posaconazole–mechanisms of action and resistance, spectrum of activity. Mycoses. 2006;49(Suppl 1):2–6.
  • Skiest DJ, Vazquez JA, Anstead GM, et al. Posaconazole for the treatment of azole-refractory oropharyngeal and esophageal candidiasis in subjects with HIV infection. Clin Infect Dis. 2007;44(4):607–614.
  • Redding SW, Kirkpatrick WR, Saville S, et al. Multiple patterns of resistance to fluconazole in Candida glabrata isolates from a patient with oropharyngeal candidiasis receiving head and neck radiation. J Clin Microbiol. 2003;41(2):619–622.
  • Cannon RD, Lamping E, Holmes AR, et al. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev. 2009;22(2):291–321. Table of Contents.
  • Martinez-Martinez L, Pascual A, Jacoby GA. Quinolone resistance from a transferable plasmid. Lancet. 1998;351(9105):797–799.
  • Tran JH, Jacoby GA, Hooper DC. Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV. Antimicrob Agents Chemother. 2005;49(7):3050–3052.
  • Jacoby GA, Walsh KE, Mills DM, et al. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob Agents Chemother. 2006;50(4):1178–1182.
  • Cavaco LM, Hasman H, Xia S, et al. qnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovar Kentucky and Bovismorbificans strains of human origin. Antimicrob Agents Chemother. 2009;53(2):603–608.
  • Hata M, Suzuki M, Matsumoto M, et al. Cloning of a novel gene for quinolone resistance from a transferable plasmid in Shigella flexneri 2b. Antimicrob Agents Chemother. 2005;49(2):801–803.
  • Wang Y, Lv Y, Cai J, et al. A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in Enterococcus faecalis and Enterococcus faecium of human and animal origin. J Antimicrob Chemother. 2015;70(8):2182–2190.
  • Sharkey LKR, Edwards TA, O’Neill AJ. ABC-F proteins mediate antibiotic resistance through ribosomal protection. MBio. 2016;7(2):e01975.
  • Kerr ID. Sequence analysis of twin ATP binding cassette proteins involved in translational control, antibiotic resistance, and ribonuclease L inhibition. Biochem Biophys Res Commun. 2004;315(1):166–173.
  • Nguyen F, Starosta AL, Arenz S, et al. Tetracycline antibiotics and resistance mechanisms. Biol Chem. 2014;395(5):559–575.
  • Marchese A, Schito GC. The oxazolidinones as a new family of antimicrobial agent. Clin Microbiol Infect. 2001;7(Suppl 4):66–74.
  • Burkhardt O, Pletz MW, Mertgen C-P, et al. Linezolid - the first oxazolidinone in the treatment of nosocomial MRSA pneumonia. Recent Pat Antiinfect Drug Discov. 2007;2(2):123–130.
  • Gales AC, Sader HS, Andrade SS, et al. Emergence of linezolid-resistant Staphylococcus aureus during treatment of pulmonary infection in a patient with cystic fibrosis. Int J Antimicrob Agents. 2006;27(4):300–302.
  • Meka VG, Pillai SK, Sakoulas G, et al. Linezolid resistance in sequential Staphylococcus aureus isolates associated with a T2500A mutation in the 23S rRNA gene and loss of a single copy of rRNA. J Infect Dis. 2004;190(2):311–317.
  • Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet. 2001;358(9277):207–208.
  • Mendes RE, Deshpande LM, Jones RN. Linezolid update: stable in vitro activity following more than a decade of clinical use and summary of associated resistance mechanisms. Drug Resist Updat. 2014;17(1–2):1–12.
  • Marshall SH, Donskey CJ, Hutton-Thomas R, et al. Gene dosage and linezolid resistance in Enterococcus faecium and Enterococcus faecalis. Antimicrob Agents Chemother. 2002;46(10):3334–3336.
  • Chen H, Wu W, Ni M, et al. Linezolid-resistant clinical isolates of enterococci and Staphylococcus cohnii from a multicentre study in China: molecular epidemiology and resistance mechanisms. Int J Antimicrob Agents. 2013;42(4):317–321.
  • Yoshida H, Bogaki M, Nakamura M, et al. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother. 1990;34(6):1271–1272.
  • Wohlkonig A, Chan PF, Fosberry AP, et al. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol. 2010;17(9):1152–1153.
  • Laponogov I, Veselkov DA, Crevel IM-T, et al. Structure of an ‘open’ clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport. Nucleic Acids Res. 2013;41(21):9911–9923.
  • Noel T. The cellular and molecular defense mechanisms of the Candida yeasts against azole antifungal drugs. J Mycol Med. 2012;22(2):173–178.
  • White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clin Microbiol Rev. 1998;11(2):382–402.
  • Pfaller MA. Antifungal drug resistance: mechanisms, epidemiology, and consequences for treatment. Am J Med. 2012;125(1 Suppl):S3–S13.
  • Perlin DS. Resistance to echinocandin-class antifungal drugs. Drug Resist Updat. 2007;10(3):121–130.
  • Park S, Kelly R, Kahn JN, et al. Specific substitutions in the echinocandin target Fks1p account for reduced susceptibility of rare laboratory and clinical Candida sp. isolates. Antimicrob Agents Chemother. 2005;49(8):3264–3273.
  • Sanglard D, Odds FC. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect Dis. 2002;2(2):73–85.
  • Leclercq R. Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications. Clin Infect Dis. 2002;34(4):482–492.
  • Roberts MC. Update on macrolide-lincosamide-streptogramin, ketolide, and oxazolidinone resistance genes. FEMS Microbiol Lett. 2008;282(2):147–159.
  • Katz L, Ashley GW. Translation and protein synthesis: macrolides. Chem Rev. 2005;105(2):499–528.
  • Kehrenberg C, Ojo KK, Schwarz S. Nucleotide sequence and organization of the multiresistance plasmid pSCFS1 from Staphylococcus sciuri. J Antimicrob Chemother. 2004;54(5):936–939.
  • Toh S-M, Xiong L, Arias CA, et al. Acquisition of a natural resistance gene renders a clinical strain of methicillin-resistant Staphylococcus aureus resistant to the synthetic antibiotic linezolid. Mol Microbiol. 2007;64(6):1506–1514.
  • Morales G, Picazo JJ, Baos E, et al. Resistance to linezolid is mediated by the cfr gene in the first report of an outbreak of linezolid-resistant Staphylococcus aureus. Clin Infect Dis. 2010;50(6):821–825.
  • LaMarre JM, Locke JB, Shaw KJ, et al. Low fitness cost of the multidrug resistance gene cfr. Antimicrob Agents Chemother. 2011;55(8):3714–3719.
  • Locke JB, Zurenko GE, Shaw KJ, et al. Tedizolid for the management of human infections: in vitro characteristics. Clin Infect Dis. 2014;58 Suppl 1(Suppl 1):S35–S42.
  • Locke JB, Hilgers M, Shaw KJ. Novel ribosomal mutations in staphylococcus aureus strains identified through selection with the oxazolidinones linezolid and torezolid (TR-700). Antimicrob Agents Chemother. 2009;53(12):5265–5274.
  • Diaz L, Kiratisin P, Mendes RE, et al. Transferable plasmid-mediated resistance to linezolid due to cfr in a human clinical isolate of Enterococcus faecalis. Antimicrob Agents Chemother. 2012;56(7):3917–3922.
  • Tong SYC, Davis JS, Eichenberger E, et al. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev. 2015;28(3):603–661.
  • Lee AS, Huttner B, Harbarth S. Prevention and control of methicillin-resistant Staphylococcus aureus in acute care settings. Infect Dis Clin North Am. 2016;30(4):931–952.
  • DeLeo FR, Chambers HF. Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era. J Clin Invest. 2009;119(9):2464–2474.
  • Jevons MP, Parker MT. The evolution of new hospital strains of Staphylococcus aureus. J Clin Pathol. 1964;17:243–250.
  • Jessen O, Rosendal K, Bülow P, et al. Changing staphylococci and staphylococcal infections. A ten-year study of bacteria and cases of bacteremia. N Engl J Med. 1969;281(12):627–635.
  • Panlilio AL, Culver DH, Gaynes RP, et al. Methicillin-resistant Staphylococcus aureus in U.S. hospitals, 1975-1991. Infect Control Hosp Epidemiol. 1992;13(10):582–586.
  • McDougal LK, Steward CD, Killgore GE, et al. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus isolates from the United States: establishing a national database. J Clin Microbiol. 2003;41(11):5113–5120.
  • Stapleton PD, Taylor PW. Methicillin resistance in Staphylococcus aureus: mechanisms and modulation. Sci Prog. 2002;85(Pt 1):57–72.
  • Hiramatsu K, Hanaki H, Ino T, et al. Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility. J Antimicrob Chemother. 1997;40(1):135–136.
  • Garcia-Castellanos R, Mallorquí-Fernández G, Marrero A, et al. On the transcriptional regulation of methicillin resistance: mecI repressor in complex with its operator. J Biol Chem. 2004;279(17):17888–17896.
  • Pucci MJ, Dougherty TJ. Direct quantitation of the numbers of individual penicillin-binding proteins per cell in Staphylococcus aureus. J Bacteriol. 2002;184(2):588–591.
  • Okuma K, Iwakawa K, Turnidge JD, et al. Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol. 2002;40(11):4289–4294.
  • de Lencastre H, Oliveira D, Tomasz A. Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power. Curr Opin Microbiol. 2007;10(5):428–435.
  • Archer GL, Niemeyer DM. Origin and evolution of DNA associated with resistance to methicillin in staphylococci. Trends Microbiol. 1994;2(10):343–347.
  • Couto I, De Lencastre H, Severina E, et al. Ubiquitous presence of a mecA homologue in natural isolates of Staphylococcus sciuri. Microb Drug Resist. 1996;2(4):377–391.
  • Pinho MG, Errington J. Recruitment of penicillin-binding protein PBP2 to the division site of Staphylococcus aureus is dependent on its transpeptidation substrates. Mol Microbiol. 2005;55(3):799–807.
  • Ender M, McCallum N, Adhikari R, et al. Fitness cost of SCCmec and methicillin resistance levels in Staphylococcus aureus. Antimicrob Agents Chemother. 2004;48(6):2295–2297.
  • Saravolatz LD, Stein GE, Johnson LB. Ceftaroline: a novel cephalosporin with activity against methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2011;52(9):1156–1163.
  • Alm RA, McLaughlin RE, Kos VN, et al. Analysis of Staphylococcus aureus clinical isolates with reduced susceptibility to ceftaroline: an epidemiological and structural perspective. J Antimicrob Chemother. 2014;69(8):2065–2075.
  • Long SW, Olsen RJ, Mehta SC, et al. PBP2a mutations causing high-level Ceftaroline resistance in clinical methicillin-resistant Staphylococcus aureus isolates. Antimicrob Agents Chemother. 2014;58(11):6668–6674.
  • Nigo M, Diaz L, Carvajal LP, et al. Ceftaroline-resistant, daptomycin-tolerant, and heterogeneous vancomycin-intermediate methicillin-resistant staphylococcus aureus causing infective endocarditis. Antimicrob Agents Chemother. 2017;61(3):e01235-e01216.
  • Rice LB, Carias LL, Rudin S, et al. Role of class A penicillin-binding proteins in the expression of beta-lactam resistance in Enterococcus faecium. J Bacteriol. 2009;191(11):3649–3656.
  • Courvalin P. Vancomycin resistance in gram-positive cocci. Clin Infect Dis. 2006;42(Suppl 1):S25–S34.
  • Kahne D, Leimkuhler C, Lu W, et al. Glycopeptide and lipoglycopeptide antibiotics. Chem Rev. 2005;105(2):425–448.
  • Arias CA, Courvalin P, Reynolds PE. vanC cluster of vancomycin-resistant Enterococcus gallinarum BM4174. Antimicrob Agents Chemother. 2000;44(6):1660–1666.
  • Boyd DA, Willey BM, Fawcett D, et al. Molecular characterization of Enterococcus faecalis N06-0364 with low-level vancomycin resistance harboring a novel D-Ala-D-Ser gene cluster, vanL. Antimicrob Agents Chemother. 2008;52(7):2667–2672.
  • Lebreton F, Depardieu F, Bourdon N, et al. D-Ala-d-Ser VanN-type transferable vancomycin resistance in Enterococcus faecium. Antimicrob Agents Chemother. 2011;55(10):4606–4612.
  • Xu X, Lin D, Yan G, et al. vanM, a new glycopeptide resistance gene cluster found in Enterococcus faecium. Antimicrob Agents Chemother. 2010;54(11):4643–4647.
  • Sievert DM, Rudrik JT, Patel JB, et al. Vancomycin-resistant Staphylococcus aureus in the United States, 2002-2006. Clin Infect Dis. 2008;46(5):668–674.
  • Chang S, Sievert DM, Hageman JC, et al. Infection with vancomycin-resistant Staphylococcus aureus containing the vanA resistance gene. N Engl J Med. 2003;348(14):1342–1347.
  • Gardete S, Tomasz A. Mechanisms of vancomycin resistance in Staphylococcus aureus. J Clin Invest. 2014;124(7):2836–2840.
  • Rossi F, Diaz L, Wollam A, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med. 2014;370(16):1524–1531.
  • Showsh SA, De Boever EH, Clewell DB. Vancomycin resistance plasmid in Enterococcus faecalis that encodes sensitivity to a sex pheromone also produced by Staphylococcus aureus. Antimicrob Agents Chemother. 2001;45(7):2177–2178.
  • Weigel LM, Clewell DB, Gill SR, et al. Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science. 2003;302(5650):1569–1571.
  • Panesso D, Planet PJ, Diaz L, et al. Methicillin-susceptible, vancomycin-resistant staphylococcus aureus, Brazil. Emerg Infect Dis. 2015;21(10):1844–1848.
  • O’Driscoll T, Crank CW. Vancomycin-resistant enterococcal infections: epidemiology, clinical manifestations, and optimal management. Infect Drug Resist. 2015;8:217–230.
  • Brade KD, Rybak JM, Rybak MJ. Oritavancin: a new lipoglycopeptide antibiotic in the treatment of gram-positive infections. Infect Dis Ther. 2016;5(1):1–15.
  • Karlowsky JA, Nichol K, Zhanel GG. Telavancin: mechanisms of action, in vitro activity, and mechanisms of resistance. Clin Infect Dis. 2015;61(Suppl 2):S58–S68.
  • Johnson JA, Feeney ER, Kubiak DW, et al. Prolonged use of oritavancin for vancomycin-resistant enterococcus faecium prosthetic valve endocarditis. Open Forum Infect Dis. 2015;2(4):ofv156.
  • Julian K, Kosowska-Shick K, Whitener C, et al. Characterization of a daptomycin-nonsusceptible vancomycin-intermediate staphylococcus aureus strain in a patient with endocarditis. Antimicrob Agents Chemother. 2007;51(9):3445–3448.
  • Jones T, Yeaman MR, Sakoulas G, et al. Failures in clinical treatment of staphylococcus aureus infection with daptomycin are associated with alterations in surface charge, membrane phospholipid asymmetry, and drug binding. Antimicrob Agents Chemother. 2008;52(1):269–278.
  • Murthy MH, Olson ME, Wickert RW, et al. Daptomycin non-susceptible meticillin-resistant staphylococcus aureus USA 300 isolate. J Med Microbiol. 2008;57(Pt 8):1036–1038.
  • Fowler VG, Boucher HW, Corey GR, et al. Daptomycin versus standard therapy for bacteremia and endocarditis caused by staphylococcus aureus. N Engl J Med. 2006;355(7):653–665.
  • Cunha BA, Pherez FM. Daptomycin resistance and treatment failure following vancomycin for methicillin-resistant staphylococcus aureus (MRSA) mitral valve acute bacterial endocarditis (ABE). Eur J Clin Microbiol Infect Dis. 2009;28(7):831–833.
  • Jung D, Rozek A, Okon M, et al. Structural transitions as determinants of the action of the calcium-dependent antibiotic daptomycin. Chem Biol. 2004;11(7):949–957.
  • Silverman JA, Perlmutter NG, Shapiro HM. Correlation of daptomycin bactericidal activity and membrane depolarization in staphylococcus aureus. Antimicrob Agents Chemother. 2003;47(8):2538–2544.
  • Cotroneo N, Harris R, Perlmutter N, et al. Daptomycin exerts bactericidal activity without lysis of staphylococcus aureus. Antimicrob Agents Chemother. 2008;52(6):2223–2225.
  • Mascio CT, Alder JD, Silverman JA. Bactericidal action of daptomycin against stationary-phase and nondividing staphylococcus aureus cells. Antimicrob Agents Chemother. 2007;51(12):4255–4260.
  • Müller A, Wenzel M, Strahl H, et al. Daptomycin inhibits cell envelope synthesis by interfering with fluid membrane microdomains. Proc Natl Acad Sci U S A. 2016;113:E7077-E7086.
  • Mishra NN, Yang S-J, Sawa A, et al. Analysis of cell membrane characteristics of in vitro-selected daptomycin-resistant strains of methicillin-resistant staphylococcus aureus. Antimicrob Agents Chemother. 2009;53(6):2312–2318.
  • Ernst CM, Grigoriu S, Kim Y, et al. The bacterial defensin resistance protein MprF consists of separable domains for lipid lysinylation and antimicrobial peptide repulsion. PLoS Pathog. 2009;5(11):e1000660.
  • Bayer AS, Mishra NN, Chen L, et al. Frequency and distribution of single-nucleotide polymorphisms within mprF in methicillin-resistant staphylococcus aureus clinical isolates and their role in cross-resistance to daptomycin and host defense antimicrobial peptides. Antimicrob Agents Chemother. 2015;59(8):4930–4937.
  • Yang S-J, Mishra NN, Rubio A, et al. Causal role of single nucleotide polymorphisms within the mprF gene of staphylococcus aureus in daptomycin resistance. Antimicrob Agents Chemother. 2013;57(11):5658–5664.
  • Cafiso V, Bertuccio T, Purrello S, et al. dltA overexpression: a strain-independent keystone of daptomycin resistance in methicillin-resistant staphylococcus aureus. Int J Antimicrob Agents. 2014;43(1):26–31.
  • Peleg AY, Miyakis S, Ward DV, et al. Whole genome characterization of the mechanisms of daptomycin resistance in clinical and laboratory derived isolates of Staphylococcus aureus. PLoS One. 2012;7(1):e28316.
  • Dubrac S, Bisicchia P, Devine KM, et al. A matter of life and death: cell wall homeostasis and the WalKR (YycGF) essential signal transduction pathway. Mol Microbiol. 2008;70(6):1307–1322.
  • Dubrac S, Msadek T. Identification of genes controlled by the essential YycG/YycF two-component system of staphylococcus aureus. J Bacteriol. 2004;186(4):1175–1181.
  • Türck M, Bierbaum G, Otto M. Purification and activity testing of the full-length YycFGHI proteins of staphylococcus aureus. PLoS One. 2012;7(1):e30403.
  • Jordan S, Junker A, Helmann JD, et al. Regulation of LiaRS-dependent gene expression in bacillus subtilis: identification of inhibitor proteins, regulator binding sites, and target genes of a conserved cell envelope stress-sensing two-component system. J Bacteriol. 2006;188(14):5153–5166.
  • Kuroda M, Kuroda H, Oshima T, et al. Two-component system VraSR positively modulates the regulation of cell-wall biosynthesis pathway in staphylococcus aureus. Mol Microbiol. 2003;49(3):807–821.
  • Mehta S, Cuirolo AX, Plata KB, et al. VraSR two-component regulatory system contributes to mprF-mediated decreased susceptibility to daptomycin in in vivo-selected clinical strains of methicillin-resistant staphylococcus aureus. Antimicrob Agents Chemother. 2012;56(1):92–102.
  • Arias CA, Panesso D, McGrath DM, et al. Genetic basis for in vivo daptomycin resistance in enterococci. N Engl J Med. 2011;365(10):892–900.
  • Palmer KL, Daniel A, Hardy C, et al. Genetic basis for daptomycin resistance in enterococci. Antimicrob Agents Chemother. 2011;55(7):3345–3356.
  • Mishra NN, Das S, Panicker L, et al. Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content. PLoS One. 2012;7(8):e43958.
  • Tran TT, Panesso D, Mishra NN, et al. Daptomycin-resistant enterococcus faecalis diverts the antibiotic molecule from the division septum and remodels cell membrane phospholipids. MBio. 2013;4(4):e00281-13-e00281-13.
  • Munita JM, Tran TT, Diaz L, et al. A liaF codon deletion abolishes daptomycin bactericidal activity against vancomycin-resistant enterococcus faecalis. Antimicrob Agents Chemother. 2013;57(6):2831–2833.
  • Diaz L, Tran TT, Munita JM, et al. Whole-genome analyses of enterococcus faecium isolates with diverse daptomycin MICs. Antimicrob Agents Chemother. 2014;58(8):4527–4534.
  • Panesso D, Reyes J, Gaston EP, et al. Deletion of liaR reverses daptomycin resistance in enterococcus faecium independent of the genetic background. Antimicrob Agents Chemother. 2015;59(12):7327–7334.
  • Munita JM, Panesso D, Diaz L, et al. Correlation between mutations in liaFSR of enterococcus faecium and MIC of daptomycin: revisiting daptomycin breakpoints. Antimicrob Agents Chemother. 2012;56(8):4354–4359.
  • Shukla BS, Shelburne S, Reyes K, et al. Influence of minimum inhibitory concentration in clinical outcomes of enterococcus faecium bacteremia treated with daptomycin: is it time to change the breakpoint? Clin Infect Dis. 2016;62(12):1514–1520.
  • Howden BP, Davies JK, Johnson PDR, et al. Reduced vancomycin susceptibility in staphylococcus aureus, including vancomycin-intermediate and heterogeneous vancomycin-intermediate strains: resistance mechanisms, laboratory detection, and clinical implications. Clin Microbiol Rev. 2010;23(1):99–139.
  • Mwangi MM, Wu SW, Zhou Y, et al. Tracking the in vivo evolution of multidrug resistance in staphylococcus aureus by whole-genome sequencing. Proc Natl Acad Sci U S A. 2007;104(22):9451–9456.
  • Hafer C, Lin Y, Kornblum J, et al. Contribution of selected gene mutations to resistance in clinical isolates of vancomycin-intermediate staphylococcus aureus. Antimicrob Agents Chemother. 2012;56(11):5845–5851.
  • Boyle-Vavra S, Labischinski H, Ebert CC, et al. A spectrum of changes occurs in peptidoglycan composition of glycopeptide-intermediate clinical staphylococcus aureus isolates. Antimicrob Agents Chemother. 2001;45(1):280–287.
  • Cui L, Murakami H, Kuwahara-Arai K, et al. Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by staphylococcus aureus Mu50. Antimicrob Agents Chemother. 2000;44(9):2276–2285.
  • Murakami K, Tomasz A. Involvement of multiple genetic determinants in high-level methicillin resistance in staphylococcus aureus. J Bacteriol. 1989;171(2):874–879.
  • Van Boeckel TP, Gandra S, Ashok A, et al. Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data. Lancet Infect Dis. 2014;14(8):742–750.
  • Biswas S, Brunel J-M, Dubus J-C, et al. Colistin: an update on the antibiotic of the 21st century. Expert Rev Anti Infect Ther. 2012;10(8):917–934.
  • Falagas ME, Michalopoulos A. Polymyxins: old antibiotics are back. Lancet. 2006;367(9511):633–634.
  • Raetz CRH, Reynolds CM, Trent MS, et al. Lipid A modification systems in gram-negative bacteria. Annu Rev Biochem. 2007;76:295–329.
  • Barrow K, Kwon DH. Alterations in two-component regulatory systems of phoPQ and pmrAB are associated with polymyxin B resistance in clinical isolates of pseudomonas aeruginosa. Antimicrob Agents Chemother. 2009;53(12):5150–5154.
  • McPhee JB, Lewenza S, Hancock REW. Cationic antimicrobial peptides activate a two-component regulatory system, PmrA-PmrB, that regulates resistance to polymyxin B and cationic antimicrobial peptides in pseudomonas aeruginosa. Mol Microbiol. 2003;50(1):205–217.
  • Fernández L, Gooderham WJ, Bains M, et al. Adaptive resistance to the “last hope” antibiotics polymyxin B and colistin in pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS. Antimicrob Agents Chemother. 2010;54(8):3372–3382.
  • Gutu AD, Sgambati N, Strasbourger P, et al. Polymyxin resistance of Pseudomonas aeruginosa phoQ mutants is dependent on additional two-component regulatory systems. Antimicrob Agents Chemother. 2013;57(5):2204–2215.
  • Kim SY, Choi HJ, Ko KS. Differential expression of two-component systems, pmrAB and phoPQ, with different growth phases of klebsiella pneumoniae in the presence or absence of colistin. Curr Microbiol. 2014;69(1):37–41.
  • Cannatelli A, Di Pilato V, Giani T, et al. In vivo evolution to colistin resistance by PmrB sensor kinase mutation in KPC-producing klebsiella pneumoniae is associated with low-dosage colistin treatment. Antimicrob Agents Chemother. 2014;58(8):4399–4403.
  • Poirel L, Jayol A, Bontron S, et al. The mgrB gene as a key target for acquired resistance to colistin in klebsiella pneumoniae. J Antimicrob Chemother. 2015;70(1):75–80.
  • Llobet E, Tomas JM, Bengoechea JA. Capsule polysaccharide is a bacterial decoy for antimicrobial peptides. Microbiology. 2008;154(Pt 12):3877–3886.
  • Campos MA, Vargas MA, Regueiro V, et al. Capsule polysaccharide mediates bacterial resistance to antimicrobial peptides. Infect Immun. 2004;72(12):7107–7114.
  • Liu -Y-Y, Wang Y, Walsh TR, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16(2):161–168.
  • Ye H, Li Y, Li Z, et al. Diversified mcr-1-harbouring plasmid reservoirs confer resistance to colistin in human gut microbiota. MBio. 2016;7(2):e00177.
  • Hu, Y., Liu, F., Lin, I.Y., et al. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect Dis. 2016;16(2):146–147.
  • Du H, Chen L, Tang Y-W, et al. Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant enterobacteriaceae. Lancet Infect Dis. 2016;16(3):287–288.
  • Yao X, Doi Y, Zeng L, et al. Carbapenem-resistant and colistin-resistant escherichia coli co-producing NDM-9 and MCR-1. Lancet Infect Dis. 2016;16(3):288–289.
  • Falgenhauer L, Waezsada S-E, Yao Y, et al. Colistin resistance gene mcr-1 in extended-spectrum beta-lactamase-producing and carbapenemase-producing Gram-negative bacteria in Germany. Lancet Infect Dis. 2016;16(3):282–283.
  • Adams MD, Nickel GC, Bajaksouzian S, et al. Resistance to colistin in acinetobacter baumannii associated with mutations in the PmrAB two-component system. Antimicrob Agents Chemother. 2009;53(9):3628–3634.
  • Moffatt JH, Harper M, Harrison P, et al. Colistin resistance in acinetobacter baumannii is mediated by complete loss of lipopolysaccharide production. Antimicrob Agents Chemother. 2010;54(12):4971–4977.
  • Hraiech S, Roch A, Lepidi H, et al. Impaired virulence and fitness of a colistin-resistant clinical isolate of acinetobacter baumannii in a rat model of pneumonia. Antimicrob Agents Chemother. 2013;57(10):5120–5121.
  • Marshall S, Hujer AM, Rojas LJ, et al. Can ceftazidime-avibactam and aztreonam overcome beta-lactam resistance conferred by metallo-beta-lactamases in enterobacteriaceae? Antimicrob Agents Chemother. 2017;61(4).
  • Davido B, Fellous L, Lawrence C, et al. Ceftazidime-avibactam and aztreonam, an interesting strategy to overcome beta-lactam resistance conferred by metallo-beta-lactamases in enterobacteriaceae and pseudomonas aeruginosa. Antimicrob Agents Chemother. 2017;61(9):e01008-e01017.
  • Falcone M, Paterson D. Spotlight on ceftazidime/avibactam: a new option for MDR Gram-negative infections. J Antimicrob Chemother. 2016;71(10):2713–2722.
  • Rawat D, Nair D. Extended-spectrum beta-lactamases in gram negative bacteria. J Glob Infect Dis. 2010;2(3):263–274.
  • Alm RA, Johnstone MR, Lahiri SD. Characterization of escherichia coli NDM isolates with decreased susceptibility to aztreonam/avibactam: role of a novel insertion in PBP3. J Antimicrob Chemother. 2015;70(5):1420–1428.
  • Asli A, Brouillette E, Krause KM, et al. Distinctive binding of avibactam to penicillin-binding proteins of gram-negative and gram-positive bacteria. Antimicrob Agents Chemother. 2016;60(2):752–756.
  • King AM, King DT, French S, et al. Structural and kinetic characterization of diazabicyclooctanes as dual inhibitors of both serine-beta-lactamases and penicillin-binding proteins. ACS Chem Biol. 2016;11(4):864–868.
  • Dhand A, Bayer AS, Pogliano J, et al. Use of antistaphylococcal beta-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):158–163.
  • Sierra-Hoffman M, Zhao L, Mondick J, et al. Combination therapy with ampicillin and daptomycin for treatment of enterococcus faecalis endocarditis. Antimicrob Agents Chemother. 2012;56(11):6064.
  • Sakoulas G, Moise-Broder PA, Schentag J, et al. Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant staphylococcus aureus bacteremia. J Clin Microbiol. 2004;42(6):2398–2402.
  • Renzoni A, Kelley WL, Rosato RR, et al. Molecular bases determining daptomycin resistance-mediated resensitization to beta-lactams (seesaw effect) in methicillin-resistant staphylococcus aureus. Antimicrob Agents Chemother. 2017;61(1):e01634-e01616.
  • Tran TT, Miller WR, Shamoo Y, et al. Targeting cell membrane adaptation as a novel antimicrobial strategy. Curr Opin Microbiol. 2016;33:91–96.
  • Shelburne SA, Kim J, Munita JM, et al. Whole-genome sequencing accurately identifies resistance to extended-spectrum beta-lactams for major gram-negative bacterial pathogens. Clin Infect Dis. 2017;65(5):738–745.
  • Pamer EG. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens. Science. 2016;352(6285):535–538.
  • Sassone-Corsi M, Raffatellu M. No vacancy: how beneficial microbes cooperate with immunity to provide colonization resistance to pathogens. J Immunol. 2015;194(9):4081–4087.
  • Brandl K, Plitas G, Mihu CN, et al. Vancomycin-resistant enterococci exploit antibiotic-induced innate immune deficits. Nature. 2008;455(7214):804–807.
  • Ubeda C, Bucci V, Caballero S, et al. Intestinal microbiota containing barnesiella species cures vancomycin-resistant enterococcus faecium colonization. Infect Immun. 2013;81(3):965–973.
  • Olsan EE, Byndloss MX, Faber F, et al. Colonization resistance: the deconvolution of a complex trait. J Biol Chem. 2017;292(21):8577–8581.
  • Earle KA, Billings G, Sigal M, et al. Quantitative imaging of gut microbiota spatial organization. Cell Host Microbe. 2015;18(4):478–488.
  • Gilmore MS, Rauch M, Ramsey MM, et al. Pheromone killing of multidrug-resistant enterococcus faecalis V583 by native commensal strains. Proc Natl Acad Sci U S A. 2015;112(23):7273–7278.
  • Drekonja D, Reich J, Gezahegn S, et al. Fecal microbiota transplantation for clostridium difficile infection: a systematic review. Ann Intern Med. 2015;162(9):630–638.
  • Jang M-O, An JH, Jung S-I, et al. Refractory clostridium difficile infection cured with fecal microbiota transplantation in vancomycin-resistant enterococcus colonized patient. Intest Res. 2015;13(1):80–84.
  • Singh R, Van Nood E, Nieuwdorp M, et al. Donor feces infusion for eradication of extended spectrum beta-lactamase producing escherichia coli in a patient with end stage renal disease. Clin Microbiol Infect. 2014;20(11):O977–O978.
  • Lagier JC, Million M, Fournier PE, et al. Faecal microbiota transplantation for stool decolonization of OXA-48 carbapenemase-producing klebsiella pneumoniae. J Hosp Infect. 2015;90(2):173–174.
  • Davido B, Batista R, Michelon H, et al. Is faecal microbiota transplantation an option to eradicate highly drug-resistant enteric bacteria carriage? J Hosp Infect. 2017;95(4):433–437.
  • Bilinski J, Grzesiowski P, Sorensen N, et al. Fecal microbiota transplantation in patients with blood disorders inhibits gut colonization with antibiotic-resistant bacteria: results of a prospective, single-center study. Clin Infect Dis. 2017;65(3):364–370.
  • Millan B, Park H, Hotte N, et al. Fecal microbial transplants reduce antibiotic-resistant genes in patients with recurrent clostridium difficile infection. Clin Infect Dis. 2016;62(12):1479–1486.
  • Jouhten H, Mattila E, Arkkila P, et al. Reduction of antibiotic resistance genes in intestinal microbiota of patients with recurrent clostridium difficile infection after fecal microbiota transplantation. Clin Infect Dis. 2016;63(5):710–711.
  • Caballero S, Kim S, Carter RA, et al. Cooperating commensals restore colonization resistance to vancomycin-resistant enterococcus faecium. Cell Host Microbe. 2017;21(5):592–602.e4.
  • Watanabe R, Matsumoto T, Sano G, et al. Efficacy of bacteriophage therapy against gut-derived sepsis caused by pseudomonas aeruginosa in mice. Antimicrob Agents Chemother. 2007;51(2):446–452.
  • Nale JY, Spencer J, Hargreaves KR, et al. Bacteriophage combinations significantly reduce clostridium difficile growth in vitro and proliferation in vivo. Antimicrob Agents Chemother. 2016;60(2):968–981.
  • Biswas B, Adhya S, Washart P, et al. Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant enterococcus faecium. Infect Immun. 2002;70(1):204–210.
  • Wang J, Hu B, Xu M, et al. Therapeutic effectiveness of bacteriophages in the rescue of mice with extended spectrum beta-lactamase-producing escherichia coli bacteremia. Int J Mol Med. 2006;17(2):347–355.
  • Pouillot F, Chomton M, Blois H, et al. Efficacy of bacteriophage therapy in experimental sepsis and meningitis caused by a clone O25b: H4-ST131Escherichia coli strain producing CTX-M-15. Antimicrob Agents Chemother. 2012;56(7):3568–3575.
  • Chan BK, Sistrom M, Wertz JE, et al. Phage selection restores antibiotic sensitivity in MDR pseudomonas aeruginosa. Sci Rep. 2016;6:26717.
  • Lood R, Winer BY, Pelzek AJ, et al. Novel phage lysin capable of killing the multidrug-resistant gram-negative bacterium acinetobacter baumannii in a mouse bacteremia model. Antimicrob Agents Chemother. 2015;59(4):1983–1991.
  • Schmelcher M, Shen Y, Nelson DC, et al. Evolutionarily distinct bacteriophage endolysins featuring conserved peptidoglycan cleavage sites protect mice from MRSA infection. J Antimicrob Chemother. 2015;70(5):1453–1465.
  • Gilmer DB, Schmitz JE, Euler CW, et al. Novel bacteriophage lysin with broad lytic activity protects against mixed infection by Streptococcus pyogenes and methicillin-resistant staphylococcus aureus. Antimicrob Agents Chemother. 2013;57(6):2743–2750.
  • Keary R, Sanz-Gaitero M, Van Raaij MJ, et al. Characterization of a bacteriophage-derived murein peptidase for elimination of antibiotic-resistant staphylococcus aureus. Curr Protein Pept Sci. 2016;17(2):183–190.
  • Schuch R, Lee HM, Schneider BC, et al. Combination therapy with lysin CF-301 and antibiotic is superior to antibiotic alone for treating methicillin-resistant staphylococcus aureus-induced murine bacteremia. J Infect Dis. 2014;209(9):1469–1478.
  • Wang Q, Euler CW, Delaune A, et al. Using a novel lysin to help control clostridium difficile infections. Antimicrob Agents Chemother. 2015;59(12):7447–7457.
  • Wittekind M, Schuch R. Cell wall hydrolases and antibiotics: exploiting synergy to create efficacious new antimicrobial treatments. Curr Opin Microbiol. 2016;33:18–24.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.