Inappropriate combinations of antimicrobial agents<br />Munzur Morshed, Pharm D. candidate 2011<br />Arnold & Marie Schwar...
Bacterial Targets for Antimicrobials<br />
Resistant Nosocomial Pathogens.<br /><ul><li>Staphylococcus Aureus
Streptococcus Pneumonia.
Enterococcus Species
Pseudomonas aeruginosa
Enterobacter Species
Acinobacter Species
Klebsiella Pneumonia</li></ul>- Extended Spectrum Beta-Lactamase producing.<br />-  Carbapenem resistant (KPC) <br />John ...
New Antimicrobials in the pipeline<br />??????<br />John Papadopoulos- Pharmacodynamic Principles of Antimicrobial Pharmac...
Risk factor of developing bacterial resistance <br /><ul><li>Inappropriate prescribing-overprescribing, under prescribing ...
Prior use of the same antimicrobial
Prolonged administrations of antimicrobial
Hospital Stay-Length of stay and prior hospitalization
Use of invasive devices
Lack of patient compliance
Sub-Optimal antibiotic concentration in the critically-ill patients
Inadequate infection control practice</li></li></ul><li>Inappropriate Antimicrobial Combinations<br />
Spectrum of Activity<br />
Spectrum of Activity cont…<br />
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Inappropriate Prescribing Of Antimicrobials

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Inappropriate Prescribing Of Antimicrobials

  1. 1. Inappropriate combinations of antimicrobial agents<br />Munzur Morshed, Pharm D. candidate 2011<br />Arnold & Marie Schwartz College of Pharmacy and Health Sciences<br />North Shore- Long Island Jewish Health System<br />Infectious Diseases-Advanced Pharmacy Practice<br />
  2. 2. Bacterial Targets for Antimicrobials<br />
  3. 3. Resistant Nosocomial Pathogens.<br /><ul><li>Staphylococcus Aureus
  4. 4. Streptococcus Pneumonia.
  5. 5. Enterococcus Species
  6. 6. Pseudomonas aeruginosa
  7. 7. Enterobacter Species
  8. 8. Acinobacter Species
  9. 9. Klebsiella Pneumonia</li></ul>- Extended Spectrum Beta-Lactamase producing.<br />- Carbapenem resistant (KPC) <br />John Papadopoulos- Pharmacodynamic Principles of Antimicrobial Pharmacotherapy.<br />
  10. 10. New Antimicrobials in the pipeline<br />??????<br />John Papadopoulos- Pharmacodynamic Principles of Antimicrobial Pharmacotherapy.<br />
  11. 11. Risk factor of developing bacterial resistance <br /><ul><li>Inappropriate prescribing-overprescribing, under prescribing and wrong dose
  12. 12. Prior use of the same antimicrobial
  13. 13. Prolonged administrations of antimicrobial
  14. 14. Hospital Stay-Length of stay and prior hospitalization
  15. 15. Use of invasive devices
  16. 16. Lack of patient compliance
  17. 17. Sub-Optimal antibiotic concentration in the critically-ill patients
  18. 18. Inadequate infection control practice</li></li></ul><li>Inappropriate Antimicrobial Combinations<br />
  19. 19. Spectrum of Activity<br />
  20. 20. Spectrum of Activity cont…<br />
  21. 21. Beta-Lactams plus Beta-Lactams<br /><ul><li>Subclasses of Beta-Lactam Antibiotics
  22. 22. Penicillins- Ampicillin, Piperacillin, Nafcillin
  23. 23. Cephalosporins- Ceftazidime, Cefazolin, Cefoxitin
  24. 24. Carbapenems- Imipenem/Cilastatin (Primaxin), Meropenem
  25. 25. β-lactamase inhibitors- Tazobactam, Sulbactam/ Unasyn, Zosyn
  26. 26. MOA- Inhibits or disrupts the synthesis of the peptidoglycan layer hence inhibition of cell-wall growth</li></li></ul><li>Beta-Lactams plus Beta-Lactamscont…<br /><ul><li> Zosyn plus Unasyn
  27. 27. Avoid use b/c of therapeutic Duplication
  28. 28. Same MOA and same class and same spectrum of activity
  29. 29. Clinical Trials-Zosyn more efficacious than Unasyn if empiric treatment is desired- Pseudomonal Coverage
  30. 30. Zosyn plus Primaxin/Meropenem or Unasyn plus Primaxin/ Meropenem
  31. 31. Combination of a Beta-Lactam and Carbapenem
  32. 32. Same class but different Sub-Class
  33. 33. Avoid use
  34. 34. Major Drug Interactions- Antagonistic Effect
  35. 35. Carbapenems inhibits the destruction of Beta-Lactamases
  36. 36. Carbapenems induces the production of Beta-Lactamases
  37. 37. Zosyn/Unasyn induces the destruction of the Beta-Lactamase producing organism
  38. 38. Clinical Trial- Zosyn is as effective as Primaxin and it constitutes a good choice as an initial empiric monotherapy.</li></li></ul><li>Beta-Lactams plus Beta-Lactamscont…<br /><ul><li>Ceftazidime plus Zosyn or Cefoxitin plus Zosyn
  39. 39. Combination of a cephalosporin and a Beta-Lactam
  40. 40. Same class but different Sub-Class
  41. 41. Ceftazadime- Third Generation; Cefoxitin- Second Generation
  42. 42. Ceftazadime SOA- serious gram (+) infections, DRSP, pseudomonas, nosocomial pneumonia.
  43. 43. Cefoxitin SOA- Anaerobes-Bacteroides Fragilis; gram (-) such as Proteus, Klebsiella, E-Coli
  44. 44. Avoid use
  45. 45. Both combo represents therapy duplication; similar spectrum of activity
  46. 46. Clinical Trial
  47. 47. Each antimicrobial in both combo’s are equally efficacious
  48. 48. Same spectrum of activity
  49. 49. Eradication rate of each antimicrobial in both combo for the corresponding pathogens are similar</li></ul>.<br />
  50. 50. Beta-Lactams plus Beta-Lactamscont…<br /><ul><li>Ceftazadime plus Primaxin/Meropenem or Cefoxitin plus Primaxin/Meropenem
  51. 51. Combination of a cephalosporin and a carbapenem
  52. 52. Same class but different Sub-Class
  53. 53. Avoid use
  54. 54. Major Drug Interactions- Antagonistic effect
  55. 55. Carbapenems inhibits the destruction of Beta-Lactamases
  56. 56. Carbapenems induces the production of Beta-Lactamases
  57. 57. Ceftazadime/ Cefoxitin induces the destruction of the Beta-Lactamase producing organisms
  58. 58. Clinical Trials
  59. 59. Primaxin- enhanced efficacy in tx. of both gram (+) and gram (-) infections
  60. 60. Ceftazadime has greater pseudomonal coverage- advantage</li></li></ul><li>Beta-Lactams plus Beta-Lactamscont…<br /><ul><li>Naficillin plus Cefazolin
  61. 61. Same class, but different sub-class
  62. 62. Naficillin- a penicillinase resistant penicillin
  63. 63. SOA- mostly gram (+)- staph, strep
  64. 64. Common therapy for skin and soft tissue infection, Endocarditis, Bacteremia
  65. 65. Cefazolin- 1 st generation cephalosporin.
  66. 66. Mainly gram (+) coverage- Staph, strep, NO enterococci
  67. 67. Partial Gram (-) coverage- E.Coli, Proteus, Klebsiella
  68. 68. Commonly used as surgical prophylaxis
  69. 69. Avoid use
  70. 70. Represents Therapy Duplication
  71. 71. Same MOA at the bacterial site</li></li></ul><li>Fluoroquinolone plus Macrolides<br />Fluoroquinolones<br />Avelox-Moxifloxacin<br />MOA- Inhibts DNA gyrase , which maintains the superhelical structure of DNA and necessary for DNA replication, transcription, and DNA repair; hence inhibition of the synthesis of DNA<br />BBW- Tendon Rupture<br />Macrolides<br />Erythromycin-Erythrocin<br />Azithromycin-Zithromax, Zmax<br />MOA- Inhibits the ribosomal protein synthesis by inhibiting the 50s ribosomal subunits, resulting in blockage of transpeptidation<br />QT prolongation<br />
  72. 72. Fluoroquinolone plus Macrolides cont…<br />Avelox plus Erythromycin or Avelox plus Azithromycin<br />Combination of a fluoroquinolone and a macrolide<br />Avelox SOA- Pseudomonas, Strep. , Staph. Enterobacter<br />Erythro./Azithro. SOA- Strep. , Moraxella Catarrahalis, Chlamydia pneumonia. <br />Avoid use <br />Major Drug Interactions- additive effect<br />Causes QT interval prolongation-Life threatening ventricular arrhythmias<br />
  73. 73. Lincosamide plus Beta-Lactam<br /><ul><li>Clindamycin plus Unasyn, or Clindamycin PO plus Augmentin or Clindamycin plus Zosyn, or Clindamycin plus Primaxin/Meropenem
  74. 74. Combination of 1st and 2nd line agents
  75. 75. Clindamycin- has excellent bone penetration ability-osteomyelitis, dental surgery
  76. 76. MOA- binds to 50S ribosomal subunit of the bacteria and therefore interfering with protein synthesis
  77. 77. SOA- mostly gram (+)-Excellent MSSA, strep, bacteroides
  78. 78. BBW- colitis and excessive GI upset and diarrhea (C. Difficile associated)
  79. 79. Augmentin- beta –lactam/ beta-lactamse inhibitor combinations
  80. 80. Mainly gram (+) coverage- MSSA, Bacteroides, strep.
  81. 81. No pseudomonas coverage
  82. 82. Avoid use
  83. 83. The Beta-lactam’s are cross-sensitive with penicillin
  84. 84. Clindamycin is a substitute for patients who is unable to take the Beta-lactam’s
  85. 85. Usage of both can lead to developing significant resistance</li></li></ul><li>Lincosamide plus Nitroimidazole<br /><ul><li>Clindamycin plus Metronidazole
  86. 86. Metronidazole- Drug of choice for Mixed infections, Trichomonas, and alternative for C-Difficile
  87. 87. SOA- Bacteroides, streptococci, C-Difficile, Gardnerella Vaginalis
  88. 88. Avoid alcohol- Good for alcoholics( Disulfiram reaction- nausea, vomiting, tachycardia)
  89. 89. Clindamycin- has excellent bone penetration ability-osteomyelitis, dental surgery
  90. 90. MOA- binds to 50S ribosomal subunit of the bacteria and therefore interfering with protein synthesis
  91. 91. SOA- mostly gram (+)-Excellent MSSA, strep, bacteroides
  92. 92. BBW- colitis and excessive GI upset and diarrhea (C. Difficile associated)
  93. 93. Avoid use
  94. 94. Therapeutic Duplication
  95. 95. Metronidazole- alternative for clindamycin induced C-Diffcile associated diarrhea
  96. 96. Usage of both can lead to developing significant resistance</li></li></ul><li>Glycopeptides plus Oxazolidinone<br />Vancomycin plus Linezolid<br />Vancomycin-Bactericidal agent; works by inhibiting the cell wall synthesis, resulting in cell death<br />SOA- Gram (+), Penicillin resistant Pneumococci, Gram positive anaerobes,no gram (-) coverage<br />DOC for MRSA, PCN allergy gram (+) infection, C-Difficile Colitis alternative to Metronidazole<br />Linezolid- inhibits protein synthesis by binding to the 23s ribosomal subunit; Preventing them from multiplying<br />1:1 IV to Po conversion (advantage)<br />SOA- VRE, Gram (+) aerobes, anaerobes, MRSA, Penicillin resistant pneumococci<br />Avoid use<br />Therapy duplication; Equally efficacious<br />Clinical Trials- Linezolid effective alternative to vancomycin for the tx. of cSSTI caused by MRSA .<br />Vancomycin DOC of hospital acquired C-Dif<br />
  97. 97. Thank You!<br />
  98. 98. References<br /><ul><li>Papadopoulos, J. Pharmacodynamic principles of antimicrobial pharmacotherapy. Kinetics Lecture.2010
  99. 99. Arnold SR, Straus SE. "Interventions to improve antibiotic prescribing practices in ambulatory care". Cochrane Database Syst Rev,2005 (4)-Accessed on may 25,2010.
  100. 100. Tausk F, Evans ME, Patterson LS, et al. Imipenem-induced resistance to antipseudomonal beta-lactams in Pseudomonas aeruginosa. Antimicrob Agents Chemother1985; 28(1):41—45. Accessed on May 25, 2010. Accessed on may 25,2010
  101. 101. Boghossian J, Caputo W,, Dana A, Gray S, Harkless L, Pollak R,, Wu D. An open-label, randomized study comparing efficacy and safety of intravenous piperacillin/tazobactam and ampicillin/sulbactam for infected diabetic foot ulcers. Surgical Infections. 2005: 6(1): 27-40. Accessed on may 25,2010
  102. 102. Arranz R, de La Cámara R, Figuera A,, Font P, Leyra F, Pajuelo F,  Rivero N. Comparative study of piperacillin/tazobactam versus imipenem/cilastatin in febrile neutropenia (1994-1996). Med Clin (Barc). 2001 May 5;116(16):610-1. Accessed on may 25,2010
  103. 103. Alvarez-Lerma F, Barcenilla F., Insausti-Ordeñana J, Jordá-Marcos R,, Maraví-Poma E, Martínez-Pellús A, Nava J,, Palomar M, Barcenilla F, Torres-Martí A,. Efficacy and tolerability of piperacillin/tazobactam versus ceftazidime in association with amikacin for treating nosocomial pneumonia in intensive care patients: a prospective randomized multicenter trial. Intensive Care Med. 2001 Mar;27(3):493-502. Accessed on may 25,2010
  104. 104. Brun-Buisson C,Brière S, Petit C. Sollet JP, Schweich H Treatment of ventilator-associated pneumonia with piperacillin-tazobactam/amikacin versus ceftazidime/amikacin: a multicenter, randomized controlled trial. VAP Study Group. Clin Infect Dis. 1998 Feb;26(2):346-54. Accessed on may 25,2010
  105. 105. Andrien F,  Anniko M,  Baudrihaye M, Bow E, Burman LA,  Louie T, Norrby SR, Vandercam B. Imipenem/cilastatin versus amikacin plus piperacillin in the treatment of infections in neutropenic patients: a prospective, randomized multi-clinic study. Perit Dial Int. 2004 Sep-Oct;24(5):440-6. Accessed on may 25,2010
  106. 106. ,Chow KM., Leung CB, , Lui SF, Li PK. , Szeto CC, Wang AY, Cefazolin plus ceftazidime versus imipenem/cilastatin monotherapy for treatment of CAPD peritonitis--a randomized controlled trial. Perit Dial Int. 2004 Sep-Oct;24(5):440-6. Accessed on may 25,2010
  107. 107. Lexi-Comp Online [database online]. Hudson, Oh: Lexi-Comp; 2010. Updated February 2010.
  108. 108. MICROMEDEX® Healthcare Series: Micromedex, Greenwood Village, Colorado
  109. 109. Clinical Pharmacology-Gold Standard ( database online)2010.
  110. 110. Facts and Comparisons(database online) Indianapolis, IN : Facts and Comparison 2010.</li>
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