Skip to main content
SpringerLink
Log in

Pharmacodynamics of Macrolides, Azalides, and Ketolides

  • Protocol
  • First Online:
Antibiotic Pharmacodynamics

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Macrolides and azalides have been widely utilized in clinical practice. With the increased use of these agents over the past two decades an accompanied increase in bacterial resistance as defined by laboratory based criteria has been observed. As a result, new derivatives have been introduced or are under development to overcome this emerging resistance. As the chemical structure of the macrolides progressed to the azalides and then ketolides, convenient once-daily oral dosing regimens and enhanced antibacterial activity over the earlier generation macrolides contributed to their widespread use for the treatment of community-acquired respiratory tract infections. As a result of the high penetration into respiratory tract tissues/fluids, the post antibiotic effect, uptake into white blood cells, and their immunomodulatory properties as well as their pharmacodynamic profile, the newer generation macrolides and azalides continue to be used in clinical practice with a high level of treatment success. Despite escalating macrolide resistance in target pathogens, the commercial withdrawal of telithromycin due to drug-related toxicities has tempered the development of new ketolides. The aims of this chapter are to provide principles to understand pharmacokinetic and pharmacodynamic properties of these agents and to provide insights supporting the application of this knowledge in clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Mutak S (2007) Azalides from azithromycin to new azalide derivatives. J Antibiot 60(2):85–122

    Article  CAS  PubMed  Google Scholar 

  2. Zuckerman JM, Qamar F, Bono BR (2011) Review of macrolides (Azithromycin, Clarithromycin), ketolids (telithromycin) and glycylcyclines (tigecycline). Med Clin N Am 95:761–791

    Article  CAS  PubMed  Google Scholar 

  3. Zeitlinger M, Wagner CC, Heinisch B (2009) Ketolides – the modern relatives of macrolides: the pharmacokinetic perspective. Clin Pharmacokinet 48(1):23–38

    Article  CAS  PubMed  Google Scholar 

  4. Agouidas C, Denis A, Auger JM et al (1998) Synthesis and antibacterial activity of ketolides (6-O-methyl-3-oxoerythromycin derivatives): a new class of antibacterials highly potent against macrolide-resistant and -susceptible respiratory pathogens. J Med Chem 41(21):4080–4100

    Article  Google Scholar 

  5. Van Bambeke F, Harms JM, Van Laethem Y et al (2008) Ketolides: pharmacological profile and rational positioning in the treatment of respiratory tract infections. Expert Opin Pharmacother 9(2):267–283

    Article  PubMed  Google Scholar 

  6. Douthwaite S, Champney WS (2001) Structures of ketolides and macrolides determine their mode of interaction with the ribosomal target site. J Antimicrob Chemother 48(Suppl T1):1–8

    Article  CAS  PubMed  Google Scholar 

  7. Sanofi-Aventis (2007) Ketek® (telithromycin) dear healthcare professional letter. http://www.fda.gov/downloads/safety/medwatch/safetyinformation/safetyalertsforhumanmedicalproducts/ucm154544.pdfSanofi. Accessed 10 Dec 2013

  8. Clay KD, Hanson JS, Pope SD et al (2006) Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review. Ann Intern Med 144:415–420

    Article  PubMed  Google Scholar 

  9. Sanofi-Aventis-US (2010) Prescribing information. http://products.sanofi.us/ketek/ketek.html. Accessed 10 Dec 2013

  10. Georgopapadakou NH (2014) The wobbly status of ketolides: where do we stand? Expert Opin Investig Drugs 23(10):1313–1319

    Article  CAS  PubMed  Google Scholar 

  11. Clinicaltrials.gov

    Google Scholar 

  12. Mansour H, Chahine EB, Karaoui LR et al (2013) Cethromycin: a new ketolide antibiotic. Ann Pharmacother 47:368–379

    Article  PubMed  Google Scholar 

  13. Sato T, Kawai Y, Matsuda H et al (2011) In vitro and in vivo antibacterial activity of modithromycin against streptococci and Haemophilus influenzae. J Antimicrob Chemother 66(7):1547–1554

    Article  CAS  PubMed  Google Scholar 

  14. Llano-Sotelo B, Dunkle J, Klepacki D et al (2010) Binding and action of CEM-101, a new fluoroketolide antibiotic that inhibits protein synthesis. Antimicrob Agents Chemother 54:4961–4970

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Ban N, Nissen P, Hansen J et al (2000) The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. Science 289(5481):905–920

    Article  CAS  PubMed  Google Scholar 

  16. Rodgers W, Frazier AD, Champney WS (2013) Solithromycin inhibition of protein synthesis and ribosome biogenesis in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. Antimicrob Agents Chemother 57:1632–1637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hansen LH, Mauvais P, Douthwaite S (1999) The macrolide-ketolide antibiotic binding site is formed by structures in domains II and V of 23S ribosomal RNA. Mol Microbiol 31(2):623–631

    Article  CAS  PubMed  Google Scholar 

  18. Jain S, Bishai W, Nightingale CH (2007) Macrolide, azalide, and ketolide. In: Nightingale CH, Ambrose PG, Drusano GL et al (eds) Antimicrobial pharmacodynamics in theory and clinical practice, 2nd edn. pp. 217–230, New York, NY

    Google Scholar 

  19. Xiong L, Shah S, Mauvais P et al (1999) A ketolide resistance mutation in domain II of 23S rRNA reveals the proximity of hairpin 35 to the peptidyl transferase centre. Mol Microbiol 31:633–639

    Article  CAS  PubMed  Google Scholar 

  20. Farrell DJ, Castanheira M, Sader HS et al (2010) The in vitro evaluation of solithromycin (CEM-101) against pathogens isolated in the United States and Europe (2009). J Infect 61:476–483

    Article  PubMed  Google Scholar 

  21. Sato T, Tateda K, Kimura S et al (2011) In vitro antibacterial activity of modithromycin, a novel 6,11-bridged bicyclolide, against respiratory pathogens, including macrolide-resistant gram-positive cocci. Antimicrob Agents Chemother 55:1588–1593

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Credito KL, Lin G, Pankuch GA et al (2001) Susceptibilities of Haemophilus influenza and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents. Antimicrob Agents Chemother 45:67–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Waites KB, Crabb DM, Duffy LB (2003) In vitro activities of ABT-773 and other antimicrobials against human mycoplasmas. Antimicrob Agents Chemother 47:39–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Roblin PM, Hammerschlag MR (1998) In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae. Antimicrob Agents Chemother 42:1515–1516

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Bozzolasco M, Debbia EA, Roveta S et al (2004) In vitro activity of ABT773, a new ketolide derivative exhibiting innovative microbiological properties against well-characterised antibiotic resistant pathogens in Italy. Int J Antimicrob Agent 23:11–16

    Article  CAS  Google Scholar 

  26. Jenkins SG, Brown SD, Farrell DJ et al (2008) Trends in antibacterial resistance among Streptococcus pneumoniae isolated in the USA: update from Protekt US years 1-4. Ann Clin Microbiol Antimicrob 7:1–11

    Article  PubMed  PubMed Central  Google Scholar 

  27. Jorgensen JH, Crawford SA, McElmeel ML et al (2004) Activities of cethromycin and telithromycin against recent North American isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 48:605–607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mallegol J, Fernandes P, Melano RG et al (2014) Antimicrobial activity of solithromycin against clinical isolates of Legionella pneumophila serogroup 1. Antimicrob Agents Chemother 58(2):909–915

    Article  PubMed  PubMed Central  Google Scholar 

  29. Waites KB, Crabb DM, Duffy LB (2009) Comparative in vitro susceptibilities of human mycoplasmas and ureaplasmas to a new investigational ketolide, CEM-101. Antimicrob Agents Chemother 53(5):2139–2141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Morrissey I, Fernandes P, Lemos B et al (2014) Activity of solithromycin and comparators against Streptococci isolated from respiratory samples collected in 2012-2013 (Abstract No. eP1584). The 24th European Congress of clinical microbiology and infectious diseases, Barcelona, Spain, May 2014.

    Google Scholar 

  31. Roblin PM, Kohlhoff SA, Parker C et al (2010) In vitro activity of CEM-101, a new fluoroketolide antibiotic, against Chlamydia trachomatis and Chlamydia (Chlamydophila) pneumoniae. Antimicrob Agents Chemother 54(3):1358–1359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bonnefoy A, Girard AM, Aqouridas C et al (1997) Ketolides lack inducibility properties of MLS(B) resistance phenotype. J Antimicrob Chemother 40(1):85–90

    Article  CAS  PubMed  Google Scholar 

  33. Cao Z, Zhong P, Ruan X et al (2004) Ribosome affinity and the prolonged molecular postantibiotic effect of cethromycin (ABT-773) in Haemophilus influenzae. Int J Antimicrob Agents 24:362–368

    Article  CAS  PubMed  Google Scholar 

  34. Richter SS, Heilmann KP, Dohrn CL et al (2008) Increasing telithromycin resistance among Streptococcus pyogenes in Europe. J Antimicrob Chemother 61:603–611

    Article  CAS  PubMed  Google Scholar 

  35. Douthwaite S, Jalava J, Jakobsen L (2005) Ketolide resistance in Streptococcus pyogenes correlates with the degree of rRNA dimethylation by ERM. Mol Microbiol 58:613–622

    Article  CAS  PubMed  Google Scholar 

  36. Mazzariol A, Koncan R, Vitali LA et al (2007) Activities of 16-membered ring macrolides and telithromycin against different genotypes of erythromycin-susceptible and erythromycin-resistant Streptococcus pyogenes and Streptococcus pneumoniae. J Antimicrob Chemother 59:1171–1176

    Article  CAS  PubMed  Google Scholar 

  37. Putnam SD, Sader HS, Farrell DJ et al (2011) Antimicrobial characterization of solithromycin (CEM-101), a novel fluoroketolide: activity against staphylococci and enterococci. Int J Antimicrob Agents 37:39–45

    Article  CAS  PubMed  Google Scholar 

  38. Zhanel GG, Dueck M, Hoban DJ et al (2001) Review of macrolides and ketolides focus on respiratory tract infections. Drugs 61(4):443–498

    Article  CAS  PubMed  Google Scholar 

  39. Still JG, Schranz J, Degenhardt TP et al (2011) Pharmacokinetics of Solithromycin (CEM-101) after single or multiple oral doses and effects of food on single-dose bioavailability in healthy adult subjects. Antimicrob Agents Chemother 55(5):1997–2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Jiang LJ, Or YS (2009) Pharmacokinetics of EDP-420 after multiple oral doses in healthy adult volunteers and in a bioequivalence study. Antimicrob Agents Chemother 53(8):3218–3225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Conte JE Jr, Golden JA, Kipps J et al (2004) Steady-state plasma and intrapulmonary pharmacokinetics and pharmacodynamics of cethromycin. Antimicrob Agents Chemother 48(9):3508–3515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Tessier PR, Mattoes HM, Dandekar PK et al (2005) Pharmacodynamic profile of telithromycin against macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae in a neutropenic mouse thigh model. Antimicrob Agents Chemother 49(1):188–194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Gattringer R, Urbauer E, Traunmuller F et al (2004) Pharmacokinetics of telithromycin in plasma and soft tissues after single-dose administration to healthy volunteers. Antimicrob Agents Chemother 48(12):4650–4653

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Maglio D, Nicolau DP, Nightingale CH (2003) Impact of pharmacodynamics on dosing of macrolides, azalides, and ketolides. Infect Dis Clin N Am 17:563–577

    Article  Google Scholar 

  45. Johnson JD, Hand WL, Franis B et al (1980) Antibiotic uptake by alveolar macrophages. J Lab Clin Med 95:429–439

    CAS  PubMed  Google Scholar 

  46. Nightingale CH, Mattoes HM (2002) Macrolide, azalide, and ketolide pharmacodynamics. In: Nightingale CH, Murakawa T, Ambrose PG (eds) Antimicrobial pharmacodynamics in theory and clinical practice, 1st edn. pp. 205–220, New York, NY

    Google Scholar 

  47. Conte JE Jr, Golden JA, Duncan S et al (1995) Intrapulmonary pharmacokinetics of clarithromycin and of erythromycin. Antimicrob Agents Chemother 39(2):334–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Rodvold KA, Gotfried MH, Danziger LH et al (1997) Intrapulmonary steady-state concentrations of clarithromycin and azithromycin in healthy adult volunteers. Antimicrob Agents Chemother 41(6):1399–1402

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Muller-Serieys C, Soler P, Cantalloube C et al (2001) Bronchopulmonary disposition of the ketolide telithromycin (HMR 3647). Antimicrob Agents Chemother 45(11):3104–3108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Rodvold KA, Gotfried MH, Still JG et al (2012) Comparison of plasma, epithelial lining fluid, and alveolar macrophage concentrations of solithromycin (CEM-101) in healthy adult subjects. Antimicrob Agents Chemother 56(10):5076–5081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Furuie H, Saisho Y, Yoshikawa T et al (2010) Intrapulmonary pharmacokinetics of S-013420, a novel bicyclolide antibacterial, in healthy Japanese subjects. Antimicrob Agents Chemother 54(2):866–870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Capitano B, Mattoes H, Shore E et al (2004) Steady-state intrapulmonary concentrations of moxifloxacin, levofloxacin, and azithromycin in older adults. Chest 125:965–973

    Article  CAS  PubMed  Google Scholar 

  53. Ong CT, Dandekar PK, Sutherland C et al (2005) Intrapulmonary concentrations of telithromycin: clinical implications for respiratory tract infections due to Streptococcus pneumoniae. Chemotherapy 51:339–346

    Article  CAS  PubMed  Google Scholar 

  54. Togami K, Chono S, Morimoto K (2011) Distribution characteristics of clarithromycin and azithromycin, macrolide antimicrobial agents used for treatment of respiratory infections, in lung epithelial lung fluid and alveolar macrophages. Biopharm Drug Metabol 32:389–397

    Article  CAS  Google Scholar 

  55. Drusano GL (2005) Infection site concentrations: their therapeutic importance and the macrolide and macrolide-like class of antibiotics. Pharmacotherapy 25:150S–158S

    Article  CAS  PubMed  Google Scholar 

  56. Levison ME (2004) Pharmacodynamics of antimicrobial drugs. Infect Dis Clin North Am 18(3):451–465

    Article  PubMed  Google Scholar 

  57. Mandell GL, Coleman E (2001) Uptake, transport, and delivery of antimicrobial agents by human polymorphonuclear neutrophils. Antimicrob Agents Chemother 45(6):1794–1798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Frank MO, Sullivan GW, Carper HT et al (1992) In vitro demonstration of transport and delivery of antibiotics by polymorphonuclear leukocytes. Antimicrob Agents Chemother 36(12):2584–2588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Abdelghaffar H, Vazifeh D, Labro MT (2001) Cellular uptake of two fluoroketolides, HMR 3562 and HMR 3787, by human polymorphonuclear neutrophils in vitro. Antimicrob Agents Chemother 45(10):2798–2806

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gladue RP, Bright GM, Isaacson RE et al (1989) In vitro and in vivo uptake of azithromycin by phagocytic cells: possible mechanism of delivery and release at sites of infection. Antimicrob Agents Chemother 33(3):277–282

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Odenholt-Tornqvist I, Lowdin E, Cars O (1995) Postantibiotic effects and postantibiotic sub-MIC effects of roxithromycin, clarithromycin, and azithromycin on respiratory tract pathogens. Antimicrob Agents Chemother 39(1):221–226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Dornbusch K, Olofsson C, Holm S (1999) Postantibiotic effect and postantibiotic sub-mic effect of dirithromycin and erythromycin against respiratory tract pathogenic bacteria. APMIS 107(5):505–513

    Article  CAS  PubMed  Google Scholar 

  63. Carbon C (1998) Pharmacodynamics of macrolides, azalides, and streptogramins: effect on extracellular pathogens. Clin Infect Dis 27:28–32

    Article  CAS  PubMed  Google Scholar 

  64. Neuhauser MM, Prause JL, Danziger LH et al (2001) Postantibiotic effects of ABT-773 and amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae. Antimicrob Agents Chemother 45(12):3613–3615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Woosley LN, Castanheira M, Jones RN (2010) CEM-101 activity against Gram-positive organisms. Antimicrob Agents Chemother 54(5):2182–2187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jacobs MR, Bajaksouzian S, Appelbaum PC (2003) Telithromycin post-antibiotic and post-antibiotic sub-MIC effects for 10 Gram-positive cocci. J Antimicrob Chemother 52:809–812

    Article  CAS  PubMed  Google Scholar 

  67. Kobayashi Y, Wada H, Rossios C et al (2013) A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition. J Pharmacol Exp Ther 345(1):76–84

    Article  CAS  PubMed  Google Scholar 

  68. Sakito O, Kadota J, Kohno S et al (1996) Interleukin 1 beta, tumor necrosis factor alpha, and interleukin 8 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis: a potential mechanism of macrolide therapy. Respiration 63:42–48

    Article  CAS  PubMed  Google Scholar 

  69. Oda H, Kadota J, Kohno S et al (1995) Leukotriene B4 in bronchoalveolar lavage fluid of patients with diffuse panbronchiolitis. Chest 108:116–122

    Article  CAS  PubMed  Google Scholar 

  70. Kaneko Y, Yanagihara K, Seki M et al (2003) Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis. Respir Med 97:844–850

    Article  Google Scholar 

  71. Li M, Zhong X, He Z et al (2012) Effect of erythromycin on cigarette-induced histone deacetylase protein expression and nuclear factor-κB activity in human macrophages in vitro. Int Immunopharmacol 12:643–650

    Article  CAS  PubMed  Google Scholar 

  72. Leiva M, Ruiz-Bravo A, Moreno E et al (2008) Telithromycin inhibits the production of proinflammatory mediators and the activation of NF-kappaB in in vitro-simulated murine cells. FEMS Immunol Med Microbiol 53(3):343–350

    Article  CAS  PubMed  Google Scholar 

  73. Novelli A, Fallani S, Cassetta MI et al (2002) In vivo pharmacodynamic evaluation of clarithromycin in comparison to erythromycin. J Chemother 14(6):584–590

    Article  CAS  PubMed  Google Scholar 

  74. Drusano GL, Craig WA (1997) Relevance of pharmacokinetics and pharmacodynamics in the selection of antibiotics for respiratory tract infections. J Chemother 9(Suppl 3):38–44

    CAS  PubMed  Google Scholar 

  75. Periti P, Mazzei T (1999) Clarithromycin: pharmacokinetic and pharmacodynamic interrelationships and dosage regimen. J Chemother 11:11–27

    Article  CAS  PubMed  Google Scholar 

  76. Tessier PR, Kim MK, Zhou W et al (2002) Pharmacodynamic assessment of clarithromycin in a murine model of pneumococcal pneumonia. Antimicrob Agents Chemother 46:1425–1434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Noreddin AM, El-Khatib WF, Aolie J et al (2009) Pharmacodynamic target attainment potential of azithromycin, clarithromycin, and telithromycin in serum and epithelial lining fluid of community-acquired pneumonia patients with penicillin-susceptible, intermediate, and resistant Streptococcus pneumonia. Int J Infect Dis 13(4):483–487

    Article  CAS  PubMed  Google Scholar 

  78. Boswell FJ, Andrews JM, Wise R (1998) Pharmacodynamic properties of HMR 3647, a novel ketolide, on respiratory pathogens, enterococci and Bacteroides fragilis demonstrated by studies of time-kill kinetics and postantibiotics effect. J Antimicrob Chemother 41:149–153

    Article  CAS  PubMed  Google Scholar 

  79. Kim MK, Zhou W, Tessier PR et al (2002) Bactericidal effect and pharmacodynamics of cethromycin (ABT-773) in a murine pneumococcal pneumonia model. Antimicrob Agents Chemother 46(10):3185–3192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Capitano B, Maglio D, Banevicius MA et al (2003) Bactericidal effect of cethromycin (ABT-773) in an immunocompetent murine pneumococcal pneumonia model. Int J Antimicrob Agents 22:588–593

    Article  CAS  PubMed  Google Scholar 

  81. Maglio D, Sun HK, Patel T et al (2014) Pharmacodynamic profiling of modithromycin: assessment in a pneumococcal murine pneumonia model. Int J Antimicrob Agents 43:540–546

    Article  CAS  PubMed  Google Scholar 

  82. Bishai W (2002) The in vivo-in vitro paradox in pneumococcal respiratory tract infections. J Antimicrob Chemother 49:433–436

    Article  CAS  PubMed  Google Scholar 

  83. Austrian R, Gold J (1964) Pneumococcal bacteremia with especial reference to bacteremic pneumococcal pneumonia. Ann Intern Med 60:759–776

    Article  CAS  PubMed  Google Scholar 

  84. Feikin DR, Schuchat A, Kolczak M et al (2000) Mortality from invasive pneumococcal pneumonia in the era of antibiotic resistance, 1995-1997. Am J Public Health 90(2):223–229

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Yu VL, Chiou CCC, Feldman C et al (2003) An international prospective study of pneumococcal bacteremia: correlation with in vitro resistance, antibiotics administered and clinical outcome. Clin Infect Dis 37:230–237

    Article  CAS  PubMed  Google Scholar 

  86. Nuermberger EL, Bishai WR (2003) Significance of macrolide resistance in Streptococcus pneumoniae. J Antimicrob Chemother 52(3):524–525

    Article  CAS  PubMed  Google Scholar 

  87. Rodvold KA, George JM, Yoo L (2011) Penetration of anti-infective agents into pulmonary epithelial lining fluid: focus on antibacterial agents. Clin Pharmacokinet 50(10):637–664

    Article  CAS  PubMed  Google Scholar 

  88. Zhanel GG, DeCorby M, Noreddin A et al (2003) Pharmacodynamic activity of azithromycin against macrolide-susceptible and -resistant Streptococcus pneumoniae simulating clinically achievable free serum, epithelial lining fluid and middle ear fluid concentration. J Antimicrob Chemother 52:83–88

    Article  CAS  PubMed  Google Scholar 

  89. Zhanel GG, Wolter KD, Calciu C et al (2014) Clinical cure rates in subjects treated with azithromycin for community-acquired respiratory tract infections caused by azithromycin-susceptible or azithromycin-resistant Streptococcus pneumoniae: analysis of phase 3 clinical trial data. J Antimicrob Chemother 69:2835–2840

    Article  CAS  PubMed  Google Scholar 

  90. Lodise TP, Preston S, Bhargava V et al (2005) Pharmacodynamics of an 800-mg dose of telithromycin in patients with community-acquired pneumonia caused by extracellular pathogens. Diagn Microbiol Infect Dis 52:45–52

    Article  CAS  PubMed  Google Scholar 

  91. Doern GV (2006) Macrolide and ketolide resistance with Streptococcus pneumoniae. Med Clin North Am 90(6):1109–1124

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA

    Wonhee So Pharm.D., B.C.P.S. & David P. Nicolau Pharm.D., F.C.C.P., F.I.D.S.A.

  2. Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA

    David P. Nicolau Pharm.D., F.C.C.P., F.I.D.S.A.

Authors
  1. Wonhee So Pharm.D., B.C.P.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David P. Nicolau Pharm.D., F.C.C.P., F.I.D.S.A.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David P. Nicolau Pharm.D., F.C.C.P., F.I.D.S.A. .

Editor information

Editors and Affiliations

  1. College of Pharmacolgy,Univ of Minnesota, Dept of Experimental and Clinical Pharma, Minneapolis, Minnesota, USA

    John C. Rotschafer

  2. Division of Infectious Diseases, University of Wisconsin, Madison, Wisconsin, USA

    David R. Andes

  3. College of Pharmacy and Medicine, University of Illinois, Chicago, Illinois, USA

    Keith A. Rodvold

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

So, W., Nicolau, D.P. (2016). Pharmacodynamics of Macrolides, Azalides, and Ketolides. In: Rotschafer, J., Andes, D., Rodvold, K. (eds) Antibiotic Pharmacodynamics. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3323-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3323-5_14

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3321-1

  • Online ISBN: 978-1-4939-3323-5

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation