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Light and Shade of New Antibiotics

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Annual Update in Intensive Care and Emergency Medicine 2015

Part of the book series: Annual Update in Intensive Care and Emergency Medicine 2015 ((AUICEM,volume 2015))

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Abstract

Multidrug-resistant (MDR) bacteria or superbugs represent a challenge for clinicians and a serious and worsening threat to human health both in community and hospital settings [1]. Physicians routinely encounter patients with infections that are not responding to available treatments and when new antibacterials arrive on the market, bacteria quickly develop resistance. The microorganisms that are mainly involved in the resistance process are the so-called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and enterobacteriaceae), emphasizing their ability to ‘escape’ from commonly used antibacterial treatment [2].

Since a standardized definition of MDR, extensively drug-resistant (XDR) and pan-drug-resistant (PDR) pathogens was not available, a group of international experts joined an initiative by the European Center for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC) in the US to create a new standardized international terminology for describing acquired resistance profiles in bacteria that are often responsible for healthcare-associated infections and that are prone to multidrug resistance [3]. Multidrug resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Extensive drug resistance was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories. Pan-drug resistance was defined as non-susceptibility to all agents in all antimicrobial categories.

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References

  1. Pendleton JN, Gorman SP, Gilmore BF (2013) Clinical relevance of the ESKAPE pathogens. Expert Rev Anti Infect Ther 11:297–308

    Article  CAS  PubMed  Google Scholar 

  2. Boucher HW, Talbot GH, Bradley JS et al (2009) Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 48:1–12

    Article  PubMed  Google Scholar 

  3. Magiorakos AP, Srinivasan A, Carey RB et al (2012) Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect 18:268–281

    Article  CAS  PubMed  Google Scholar 

  4. Spellberg B, Guidos R, Gilbert D et al (2008) Infectious Diseases Society of America; The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America. Clin Infect Dis 46:155–164

    Article  PubMed  Google Scholar 

  5. Piddock LJ (2012) The crisis of no new antibiotics–what is the way forward? Lancet Infect Dis 12:249–253

    Article  PubMed  Google Scholar 

  6. Infectious Diseases Society of America (2010) The 10 × ’20 Initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin Infect Dis 50:1081–1083

    Article  Google Scholar 

  7. The Pew Charitable Trusts (2014) Tracking the Pipeline of Antibiotics in Development. http://www.pewtrusts.org/en/research-and-analysis/issue-briefs/2014/03/12/tracking-the-pipeline-of-antibiotics-in-development. Accessed September 2014

    Google Scholar 

  8. Livermore DM, Mushtaq S, Ge Y (2010) Chequerboard titration of cephalosporin CXA-101 (FR264205) and tazobactam versus beta-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother 65:1972–1974

    Article  CAS  PubMed  Google Scholar 

  9. Titelman E, Karlsson IM, Ge Y, Giske CG (2011) In vitro activity of CXA-101 plus tazobactam (CXA-201) against CTX-M-14- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae. Diagn Microbiol Infect Dis 70:137–141

    Article  CAS  PubMed  Google Scholar 

  10. Sader HS, Rhomberg PR, Farrell DJ, Jones RN (2011) Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes. Antimicrob Agents Chemother 55:2390–2394

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Umeh O, Cebrik D, Friedland I (2010) A double-blind, randomized, phase 2 study to compare the safety and efficacy of intravenous CXA-101 (CXA) and intravenous ceftazidime (CTZ) in complicated urinary tract infection (cUTI) 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, MA, September 12–15. (abst)

    Google Scholar 

  12. Wagenlehner F, Umeh O, Huntington J et al (2014) Efficacy and safety of ceftolozane/tazobactam versus levofloxacin in the treatment of complicated urinary tract infections (cUTI)/pyelonephritis in hospitalised adults: results from the phase 3 aspect-cUTI trial. 24th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), May 10–13. Barcelona (abst)

    Google Scholar 

  13. Ge Y, Whitehouse MJ, Friedland I, Talbot GH (2010) Pharmacokinetics and safety of CXA-101, a new antipseudomonal cephalosporin, in healthy adult male and female subjects receiving single- and multiple-dose intravenous infusions. Antimicrob Agents Chemother 54:3427–3431

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Miller B, Hershberger E, Benziger D, Trinh M, Friedland I (2012) Pharmacokinetics and safety of intravenous ceftolozane-tazobactam in healthy adult subjects following single and multiple ascending doses. Antimicrob Agents Chemother 56:3086–3091

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Lucasti C, Hershberger E, Miller B et al (2014) A multicenter, double-blind, randomized, phase ii trial to assess the safety and efficacy of ceftolozane/tazobactam plus metronidazole compared with meropenem in adult patients with complicated intra-abdominal infections. Antimicrob Agents Chemother 58:5350–5357

    Article  CAS  PubMed  Google Scholar 

  16. Zhanel GG, Lawson CD, Adam H et al (2013) Ceftazidime-avibactam: a novel cephalosporin/β-lactamase inhibitor combination. Drugs 73:159–177

    Article  CAS  PubMed  Google Scholar 

  17. Mushtaq S, Warner M, Livermore DM (2010) In vitro activity of ceftazidime+NXL104 against Pseudomonas aeruginosa and other non-fermenters. J Antimicrob Chemother 65:2376–2381

    Article  CAS  PubMed  Google Scholar 

  18. Citron DM, Tyrrell KL, Merriam V, Goldstein EJ (2011) In vitro activity of ceftazidime-NXL104 against 396 strains of beta-lactamase-producing anaerobes. Antimicrob Agents Chemother 55:3616–3620

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Lucasti C, Popescu I, Ramesh MK, Lipka J, Sable C (2013) Comparative study of the efficacy and safety of ceftazidime/avibactam plus metronidazole versus meropenem in the treatment of complicated intra-abdominal infections in hospitalized adults: results of a randomized, double-blind, Phase II trial. J Antimicrob Chemother 68:1183–1192

    Article  CAS  PubMed  Google Scholar 

  20. Vazquez JA, González Patzán LD, Stricklin D et al (2012) Efficacy and safety of ceftazidime-avibactam versus imipenem-cilastatin in the treatment of complicated urinary tract infections, including acute pyelonephritis, in hospitalized adults: results of a prospective, investigator-blinded, randomized study. Curr Med Res Opin 28:1921–1931

    Article  CAS  PubMed  Google Scholar 

  21. Critchley IA, Eckburg PB, Jandourek A, Biek D, Friedland HD, Thye DA (2011) Review of ceftaroline fosamil microbiology: integrated FOCUS studies. J Antimicrob Chemother 66(Suppl 3):iii45–51

    CAS  PubMed  Google Scholar 

  22. Stachyra T, Levasseur P, Péchereau MC et al (2009) In vitro activity of the β-lactamase inhibitor NXL104 against KPC-2 carbapenemase and Enterobacteriaceae expressing KPC carbapenemases. J Antimicrob Chemother 64:326–329

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Mushtaq S, Warner M, Williams G, Critchley I, Livermore DM (2010) Activity of chequerboard combinations of ceftaroline and NXL104 versus beta-lactamase-producing Enterobacteriaceae. J Antimicrob Chemother 65:1428–1432

    Article  CAS  PubMed  Google Scholar 

  24. Riccobene TA, Su SF, Rank D (2013) Single- and multiple-dose study to determine the safety, tolerability, and pharmacokinetics of ceftaroline fosamil in combination with avibactam in healthy subjects. Antimicrob Agents Chemother 57:1496–1504

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Livermore DM, Warner M, Mushtaq S (2013) Activity of MK-7655 combined with imipenem against Enterobacteriaceae and Pseudomonas aeruginosa. J Antimicrob Chemother 68:2286–2290

    CAS  PubMed  Google Scholar 

  26. Hirsch EB, Ledesma KR, Chang KT, Schwartz MS, Motyl MR, Tam VH (2012) In vitro activity of MK-7655, a novel β-lactamase inhibitor, in combination with imipenem against carbapenem-resistant Gram-negative bacteria. Antimicrob Agents Chemother 56:3753–3757

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Walkty A, Adam H, Baxter M et al (2014) In vitro activity of plazomicin against 5,015 gram-negative and gram-positive clinical isolates obtained from patients in canadian hospitals as part of the CANWARD study, 2011–2012. Antimicrob Agents Chemother 58:2554–2563

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Aggen JB, Armstrong ES, Goldblum AA et al (2010) Synthesis and spectrum of the neoglycoside ACHN-490. Antimicrob Agents Chemother 54:4636–4642

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Zhanel GG, Lawson CD, Zelenitsky S et al (2012) Comparison of the next-generation aminoglycoside plazomicin to gentamicin, tobramycin and amikacin. Expert Rev Anti Infect Ther 10:459–473

    Article  CAS  PubMed  Google Scholar 

  30. Poulikakos P, Falagas ME (2013) Aminoglycoside therapy in infectious diseases. Expert Opin Pharmacother 14:1585–1597

    Article  CAS  PubMed  Google Scholar 

  31. Cass RT, Brooks CD, Havrilla NA et al (2011) Pharmacokinetics and safety of single and multiple doses of ACHN-490 injection administered intravenously in healthy subjects. Antimicrob Agents Chemother 55:5874–5880

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Nilius AM, Shen LL, Hensey-Rudloff D et al (2003) In vitro antibacterial potency and spectrum of ABT-492, a new fluoroquinolone. Antimicrob Agents Chemother 47:3260–3269

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. O’Riordan W, Mehra P, Manos P, Kingsley J, Lawrence L, Cammarata S (2014) A randomized phase 2 study comparing two doses of delafloxacin with tigecycline in adults with complicated stain and stain-structure infections. Int J Infect Dis 30C:67–73

    Google Scholar 

  34. Melinta Therapeutics (2014) Delafloxacin. http://www.melinta.com/delafloxacin.php. Accessed September 2014

    Google Scholar 

  35. Keel RA, Tessier PR, Crandon JL, Nicolau DP (2012) Comparative efficacies of human simulated exposures of tedizolid and linezolid against Staphylococcus aureus in the murine thigh infection model. Antimicrob Agents and Chemother 56:4403–4407

    Article  CAS  Google Scholar 

  36. Choi S, Im W, Bartizal K (2012) Activity of Tedizolid Phosphate (TR-701) in murine models of infection with penicillin-resistant and penicillin-sensitive streptococcus pneumoniae. Antimicrob Agents and Chemother 56:4713–4717

    Article  CAS  Google Scholar 

  37. Flanagan S, Fang E, Muñoz KA, Minassian SL, Prokocimer PG (2014) Single- and multiple-dose pharmacokinetics and absolute bioavailability of tedizolid. Pharmacotherapy 34:891–900

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Urbina O, Ferrández O, Espona M, Salas E, Ferrández I, Grau S (2013) Potential role of tedizolid phosphate in the treatment of acute bacterial skin infections. Drug Des Devel Ther 7:243–265

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Lawrence L, Danese P, DeVito J, Franceschi F, Sutcliffe J (2008) In vitro activities of theRx-01 oxazolidinones against hospital and community pathogens. Antimicrob Agents Chemother 52:1653–1662

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Locher HH, Caspers P, Bruyère T et al (2014) Investigations of the mode of action and resistance development of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother 58:901–908

    Article  PubMed Central  PubMed  Google Scholar 

  41. Locher HH, Seiler P, Chen X et al (2014) In vitro and in vivo antibacterial evaluation of cadazolid, a new antibiotic for treatment of Clostridium difficile infections. Antimicrob Agents Chemother 58:892–900

    Article  PubMed Central  PubMed  Google Scholar 

  42. Bassetti M, Mikulska M, Righi E, Nicolini L, Viscoli C (2009) The role of telavancin in the treatment of MRSA infections in hospital. Expert Opin Investig Drugs 18:521–529

    Article  CAS  PubMed  Google Scholar 

  43. Barriere SL (2014) The ATTAIN trials: efficacy and safety of telavancin compared with vancomycin for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia. Future Microbiol 9:281–289

    Article  CAS  PubMed  Google Scholar 

  44. Corey GR, Kabler H, Mehra P et al (2014) Single-dose oritavancin in the treatment of acute bacterial skin infections. N Engl J Med 370:2180–2190

    Article  PubMed  Google Scholar 

  45. Rubino CM, Van Wart SA, Bhavnani SM, Ambrose PG, McCollam JS, Forrest A (2009) Oritavancin population pharmacokinetics in healthy subjects and patients with complicated skin and skin structure infections or bacteremia. Antimicrob Agents Chemother 53:4422–4428

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Zhanel GG, Calic D, Schweizer F et al (2010) New lipoglycopeptides: a comparative review of dalbavancin, oritavancin and telavancin. Drugs 70:859–886

    Article  CAS  PubMed  Google Scholar 

  47. Boucher HW, Wilcox M, Talbot GH, Puttagunta S, Das AF, Dunne MW (2014) Once-weekly dalbavancin versus daily conventional therapy for skin infection. N Engl J Med 370:2169–79

    Article  PubMed  Google Scholar 

  48. Noel GJ, Draper MP, Hait H, Tanaka SK, Arbeit RD (2012) A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections. Antimicrob Agents Chemother 56:5650–5654

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Sutcliffe JA, O’Brien W, Fyfe C, Grossman TH (2013) Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother 57:5548–5558

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Solomkin JS, Ramesh MK, Cesnauskas G et al (2014) Phase 2, randomized, double-blind study of the efficacy and safety of two dose regimens of eravacycline versus ertapenem for adult community-acquired complicated intra-abdominal infections. Antimicrob Agents Chemother 58:1847–1854

    Article  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Infectious Diseases Division, Santa Maria Misericordia University Hospital, 33100, Udine, Italy

    M. Bassetti, P. Della Siega & D. Pecori

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  1. M. Bassetti
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  2. P. Della Siega
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  3. D. Pecori
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Correspondence to M. Bassetti .

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  1. Université libre de Bruxelles, Dept. of Intensive Care, Erasme Hospital, Brussels, Belgium

    Jean-Louis Vincent Prof.

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Bassetti, M., Della Siega, P., Pecori, D. (2015). Light and Shade of New Antibiotics. In: Vincent, JL. (eds) Annual Update in Intensive Care and Emergency Medicine 2015. Annual Update in Intensive Care and Emergency Medicine 2015, vol 2015. Springer, Cham. https://doi.org/10.1007/978-3-319-13761-2_5

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  • DOI: https://doi.org/10.1007/978-3-319-13761-2_5

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-13760-5

  • Online ISBN: 978-3-319-13761-2

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