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Rajia H. Ghoneim pharm.D. candidate Supervised by: Kenneth Jarman pharm.D. Empiric Antimicrobials for hospitalized patients 1.

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Presentation on theme: "Rajia H. Ghoneim pharm.D. candidate Supervised by: Kenneth Jarman pharm.D. Empiric Antimicrobials for hospitalized patients 1."— Presentation transcript:

1 Rajia H. Ghoneim pharm.D. candidate Supervised by: Kenneth Jarman pharm.D. Empiric Antimicrobials for hospitalized patients 1

2 Outline:  SSTI  Pneumonia  UTI  Intra abdominal infections  Meningitis  Neutropenic fever Rajia Ghoneim pharm.D. candidate 2

3 SSTI Rajia Ghoneim pharm.D. candidate 3

4 James I.Merlino.Mark A.Malagoni, Complicated skin and soft-tissue infections: Diagnostic approach and empiric treatment options Cleve Clin J Med. 2007 Aug ;74 Suppl 4 SSTI 4 Rajia Ghoneim pharm.D. candidate

5 DrugRegimen (IV)HMC 2006 Vancomycin1g q12hr100% TMP/SMX10-20mg/kg/day divided q6-8hr95% Doxycycline100mg q12hr93% Clindamycin600-900mg q8hr65% Linezolid (ZYVOX)600mg q12hr100% Daptomycin (CUBICIN)4mg/kg q24hr100% Tigecycline (TYGACIL)100mg then 50mg q12hr Dalfopristin/quinuprist in (SYNERCID) 7.5mg/kg q12hr MRSA SSTI inpatient Rajia Ghoneim pharm.D. candidate 5

6 MRSA SSTI outpatient Rajia Ghoneim pharm.D. candidate 6 DrugRegimen POHMC 2006 TMP/SMX1-2 DS tablets q12hr95% Doxycycline100mg q12hr93% Clindamycin300-450mg q6hr65% Linezolid600mg q12hr100% Duration : 7-14 days

7 Adapted, with permission, from Stevens et al, Clinical Infectious Diseases (2005; 41:1373–1406),2 published by University of Chicago Press. ©2005 by the Infectious Diseases Society of America. All rights reserved. 7

8 Rajia Ghoneim pharm.D. candidate 8

9 Pneumonia pneumonia HAPCAP outpatients hospitalized non ICU hospitalized ICU 9 Rajia Ghoneim pharm.D. candidate

10 CAP (hospitalized non ICU) Type of therapyDrug classLevel of evidance Combination :Beta lactam + MacrolideStrong Beta lactam + doxycycline (IV)Weak Monotherapy:resp.flouroquinolonesStrong ATA/IDSA 2007 Type of therapyDrugRegimen Beta lactam (IV) + Macrolide (IV) (Ceftriaxone or Cefotaxime or Ampicillin or ertapenem ) + Azithromycin 1-2g q24hr 1g q8hr 1gq6hr 500mg q24hr Beta lactam (IV) + doxycycline (IV)100mg q12hr flouroquinolones (IV/PO)Levofloxacin Moxifloxacin Gemifloxacin 750 mg q24hr (5d) 400 mg q24hr 10

11 HAP  VAP  MDR 11 Rajia Ghoneim pharm.D. candidate

12 HAP cont’d… ATS/IDSA2004: suspected MDR Type of therapyClassDrugregimen Combination of 3 - Antipseudomonal cephalosporin Or -Antipseudomonal carbapenem Or -β lactam/ β lactamase inhibitor Ceftazidime Cefepime * Imipenem Meropenem Piperacillin/tazobactam 2 g every 8 h 1–2 g every 8–12 h 0.5g every 6 h or 1 g every 8 h or 1 g every 8 h 4.5 g every 6 h - Antipseudomonal fluoroquinolone Or - Aminoglycoside Ciprofloxacin Levofloxacin Gentamicin Amikacin Tobramycin 4.5 g every 6 h 750 mg every d (5d) 7 mg/kg per d 20 mg/kg per d 7 mg/kg per d Anti MRSAVancomycin Linezolid 15 mg/kg every 12 h 600 mg every 12 h + + *(All cause mortality was higher with cefepime),Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis 2007; 7:338–48 12

13 HAP cont’d…  2 combinations or 3? anti pseudomonal βlactam + (vancomycin or linezolid) anti pseudomonal βlactam + (FQ or Aminoglycosides) + (vancomycin or linezolid) HMC 2006 Ps.aeruginosa Amikacin94% Pip/tazo90% Ceftazidime90% Genta90% Imipenem85% Cipro64% 13 Rajia Ghoneim pharm.D. candidate

14 ATS/IDSA2004: 14 Rajia Ghoneim pharm.D. candidate

15 15

16 UTI Cystitis female male Pyelonephritis Acute uncomplicated Complicated 16 Rajia Ghoneim pharm.D. candidate

17 Cont’d UTI RouteDrugDoseFrequencyduration LEVEL OF EVIDENCE POTMP/SMXDSq12hr3DA,I POOfloxacin Ciprofloxacin Levofloxacin Norfloxacin 250mg Q12hr 3D 7D A,I POTMP100mgQ12hr7DA,I PONitrofurantoin (macrobid) 100mgq12hr7DB,I POFosfomycinB,I IDSA 1999 Uncomplicated Cystitis in females: 17

18 DaysHMC 2006 (E.coli) POTMP/SMXDSq12hr3d69% POCiprofloxacin Levofloxacin 250mg q12hr q24hr 3d 81% PONitrofurantoin (macrobid) 100mgq12hr5d96% POCefpodoxime100mgq12hr7d*96% POAmpicillin/sulbactam1.5gq6hr7d75% POCephalexin500mgq6hr7d90% Cont’d UTI Special conditions: Pregnant: beta lactam (7days) Diabetic, >65y, symptomatic for 7 days  7days Recurrent (re-infection)  7days Recurrent (relapse)  14days 18 Rajia Ghoneim pharm.D. candidate Uncomplicated cystitis in females:

19 POCiprofloxacin Levofloxacin 500mg 250-500mg Q12hr Q24hr 7D POTMP/SMXDSq12hr7D Uncomplicated Cystitis in male: Cont’d UTI 19 Rajia Ghoneim pharm.D. candidate

20 Level of evidence POciprofloxacin500mgq12hr7DA,II POLevofloxacin250mgq24hr7DA,II POTMP/SMXDSQ12hr14DB,II Acute uncomplicated Pyelonephritis in females: IDSA 1999 Cont’d UTI 20 Rajia Ghoneim pharm.D. candidate HMC IVflourquinolones10-14D IVGentamycin +/- Ampicillin 10-14D IVExtended spectrum ceph +/- Gentamycin 10-14D Severe Pyelonephritis in females:

21 HMC 2006 (E.coli) HMC 2006 (Enterococc us sp.) POCiprofloxacin Levofloxacin 500mg 750mg Q12hr Q24hr 10D 5D 81%58% POTMP/SMXDSq12hr7D69%unreliable POCefpodoxime200mgq12hr14D96%0 POCephalexin500mgQ6hr14D90%0 POAmpicillin/sulbactam1.5gQ6hr14D75%85% IVCeftriaxone1gQ24hr14D96%0 IVAztreonam1gQ8-12hr14D0 IVLevofloxacin Ciprofloxacin 750mg 400mg Q24hr Q12hr 5d 10d 81%58% Cont’d UTI 21 Rajia Ghoneim pharm.D. candidate Acute Uncomplicated Pyelonephritis

22 Complicated /catheter UTI: 10-14days DrugDoseHMC 2006 (Ps. aeruginosa) Gentamycin + Ampicillin (IV)1mg/kg q8hr 1-2g q4-6hr Piperacillin-tazobactam(IV)3.375 g q6hr 90% Ticarcillin-clavulanate (IV)3.1 g q6hr74% Imipenem(IV)500 mg q6hr 85% Meropenem(IV)1g q8hr 86% Ceftazidime1g q8hr 90% Ciprofloxacin(IV)400mg q12hr 64% Levofloxacin(IV/PO)750mgq24hr (5d) Cont’d UTI 22

23 Primary Secondary (community, hospital acquired) Rajia Ghoneim pharm.D. candidate 23

24 Intra abdominal infections DrugDoseRouteDuration Cefotaxime2g q12hr 2g q8hr IV5 days Ceftrioxone2g q24hrIV5 days Ertapenem1g q24hrIV Ampicillin/sulbactam1.5-3gq6hrIV6-12 days Ofloxacin400mg q12hrOral8 days Primary peritonitis (SBP) 24 Rajia Ghoneim pharm.D. candidate

25 IAl cont’d… Secondary peritonitis: community acquired IDSA, the Surgical Infection Society, the American Society for Microbiology, and the Society of Infectious Disease Pharmacists (last updated in 2003) IDSA ……..2003 25

26  Moxifloxacin PO/IV 400mg q24hr for complicated intra abdominal infections (alone)  Abscess? β lactams  poor aminoglycosides  poor  Hospital acquired intra abdominal infections. 26 Rajia Ghoneim pharm.D. candidate IAl cont’d…

27 Bacterial Rajia Ghoneim pharm.D. candidate 27

28 Meningitis  Bactericidal..  CSF penetration/IV.. 28 Rajia Ghoneim pharm.D. candidate

29 Drug (IV)regimen First lineCeftrioxone or cefotaxmine + Vancomycin + dexamethazone 2g q12hr, 2g q4-6hr 500-750mg q6hr 10 mg q6hr for 2- 4days alternativeMeropenem +vancomycin +dexamethazone 2g q8hr 500-750mg q6hr 10mg q6hr for 2- 4days Meningitis cont’d…. Age group 1month-50years 29 Rajia Ghoneim pharm.D. candidate

30 Drug (IV)regimen First line(Ceftriaxone or cefotaxime) + Vancomycin + Ampicillin + Dexamethazone (2g q12hr 2g q6hr) 500-750mg q6hr (2g/d) 2g q4hr 10mg q6hr for 2-4days AlternativeMeropenem + Vancomycin + Dexamethazone 2g q8hr 500-750mg q6hr 10mg q6hr for 2-4days Cont’d meningitis… Age group >50years 30 Rajia Ghoneim pharm.D. candidate

31 Update on Rajia Ghoneim pharm.D. candidate 31

32 Febrile Neutropenia (update)  Cefepime no longer first line? The difference in all-cause mortality was significant for febrile Neutropenia (1·42 [1·09– 1·84]; p=0·009). Dafna Y., Mical P.,et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet 32 Rajia Ghoneim pharm.D. candidate

33 NF cont’d… IDSA 2002 2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer 33 Rajia Ghoneim pharm.D. candidate

34 Guidelines for Skin and Soft-Tissue Infections,Clinical Infectious Diseases 2005; 41:1373–406 2005 by the Infectious Diseases Society of America Sabol KE, Echevarria KL, Lewis JS II. Community-associated methicillin-resistant Staphylococcus aureus: new bug, old drugs. Ann Pharmacother 2006; 40:1125–1133. Wargo KA, Eiland EH III. Appropriate antimicrobial therapy for community-acquired methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis 2005; 40:1376–1378. Maltezou HC, Giamarellou H. Community-acquired methicillinresistant Staphylococcus aureus infections. Int J Antimicrob Agents 2006; 27:87–96. Noskin GA. Tigecycline: a new glycylcycline for treatment of serious infections. Clin Infect Dis 2005; 41(Suppl 5):S303–S314. McAleese F, Murphy E, Babinchak T, et al. Use of ribotyping to retrospectively identify methicillin-resistant Staphylococcus aureus isolates from phase 3 clinical trials for tigecycline that are genotypically related to community- associated isolates. Antimicrob Agents Chemother 2005; 49:4521–4529. Zinner SH. Overview of antibiotic use and resistance: setting the stage for tigecycline. Clin Infect Dis 2005; 41(Suppl 5):S289–S292. Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E. The efficacy and safety of tigecycline in the treatment of skin and skinstructure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis 2005; 41(Suppl 5):S341–S353. For daptomycin: Scheinfeld N. A comparison of available and investigational antibiotics for complicated skin infections and treatment-resistant Staphylococcus aureus and enterococcus. J Drugs Dermatol 2007; 6:97–103. Linden PK. Treatment options for vancomycin-resistant enterococcal infections. Drugs 2002; 62:425–441 Jo¨rg J. Ruhe* and Anupama Menon Tetracyclines as an Oral Treatment Option for Patients with Community Onset Skin and Soft Tissue Infections Caused by Methicillin-Resistant Staphylococcus aureus SSTI Rajia Ghoneim pharm.D. candidate 34

35 pneumonia  Mitka, M. JCAHO tweaks emergency departments' pneumonia treatment standards. JAMA 2007; 297:1758.  IDSA/ATS Guidelines for CAP in Adults.Clinical Infectious Diseases 2007; 44:S27–72 2007 by the Infectious Diseases Society of America.  Beardsley JR, Williamson JC, Johnson JW, et al. Using local microbiologic data to develop institutional-specific guidelines for the treatment of hospital-acquired pneumonia. Chest 2006  Guidelines for the Management of Adults with Hospital-acquired, Ventilator-associated, and Healthcare-associated Pneumonia This official statement of the American Thoracic Society and the Infectious Diseases. Am J Respir Crit Care Med Vol 171. pp 388–416, 2005  Iregui M, Ward S, Sherman G, et al. Clinical importance of delays in the initiation of appropriate antibiotic therapy.Chest 2002; 122:262–268  Hilf M, Yu VL, Sharp J, et al. Antibiotic therapy for Pseudomonas aeruginosa bacteremia: outcome correlations in a prospective study of 200 patients. Am J Med 1989; 87:540–546  Bliziotis IA, Samonis G, Vardakas KZ, et al. Effect of aminoglycoside and -lactam combination therapy versus -lactam monotherapy on the emergence of antimicrobial resistance: a meta-analysis of randomized, controlled trials.Clin Infect Dis 2005; 41:149–158  Kollef MH, Rello J, Cammarata S, et al. Clinical cure and survival in Gram-positive ventilator- associated pneumonia: retrospective analysis of two double-blind studies comparing linezolid with vancomycin. Intensive Care Med 2004; 30: 388–394 35 Rajia Ghoneim pharm.D. candidate

36 UTI 1. Cooper D.H.,Krainik A.J.,The Washington Manual of Medical Therapeutics. 32 nd ed.2007.ch13,384- 388 2. Gupta K; Hooton TM; Roberts PL; Stamm WE. Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med. 2007 Nov 12;167(20):2207-12. 3. Kavatha D; Giamarellou H; Alexiou Z; Vlachogiannis N; Pentea S; Gozadinos T; Poulakou G; Hatzipapas A; Koratzanis G.Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short- term therapy of uncomplicated acute cystitis in women. Antimicrob Agents Chemother 2003 Mar;47(3):897-900. 4. Thomas M. Walter.E.Acute cystitis and asymptomatic bacteriuria in men. Uptodate.com. Last literature review JAN 2008 5. Krieger JN; Ross SO; Simonsen JM. Urinary tract infections in healthy university men.J Urol 1993 May;149(5):1046-8. 6. Thomas M. Walter.EAcute pyelonephritis: Symptoms; diagnosis; and treatment. Uptodate.com. Last literature review JAN 2008 7. Clinical Approach To Initial Choice Of Antimicrobial Therapy.Acute Uncomplicated Pyelonephritis, Hospitalzed. Sanford Guide For Antimicrobial Therapy 2007 8. Clinical Approach To Initial Choice Of Antimicrobial.Complicated Urinary Tract Infections/Catheters. Sanford Guide For Antimicrobial Therapy 2007 9. Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women. Clinical Infectious Diseases 1999;29:745–58. 10. Wing DA; Hendershott CM; Debuque L; Millar LK, A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy. Obstet Gynecol 1998 Aug;92(2):249-53. 11. Double-Blind, Randomized Comparison of Levofloxacin 750 mg Once-Daily for Five Days With Ciprofloxacin 400/500 mg Twice-Daily for 10 Days for the Treatment of Complicated Urinary Tract Infections and Acute Pyelonephritis 12. Lindsay E. Nicolle Catheter-Related Urinary Tract Infection. Drugs Aging 2005; 22 (8): 627-639 36

37 Intra abdominal infections  Guidelines for the Selection of Anti-infective Agents for Complicated Intra-abdominal Infections. Clinical Infectious Diseases 2003, 37:997–1005  Parsi,MA, Atreja, A, Zein,NN. Spontaneous bacterial peritonitis, Cleveland clinic journal of medicine, 2004, 71(7) 37 Rajia Ghoneim pharm.D. candidate

38 Meningitis  Thomas F.& Vincent Q. Treatment and prevention of bacterial meningitis in adults, Last literature review : January 2008, UpToDate.com  Practice Guidelines for the Management of Bacterial Meningitis. Clinical Infectious Diseases 2004; 39:1267–84  de Gans, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549–56. 38 Rajia Ghoneim pharm.D. candidate

39 Neutropenic fever  Dafna Y., Mical P.,et al. Efficacy and safety of cefepime: a systematic review and meta-analysis. Lancet Infect Dis 2007; 7:338–48.  Walter T., Donald A, et al. 2002 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer 39 Rajia Ghoneim pharm.D. candidate


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