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

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

SKIN AND SOFT TISSUE INFECTIONS SSTI SKIN AND SOFT TISSUE INFECTIONS Rajia Ghoneim pharm.D. candidate

SSTI 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 Rajia Ghoneim pharm.D. candidate

MRSA SSTI inpatient Drug Regimen (IV) HMC 2006 Vancomycin 1g q12hr 100% TMP/SMX 10-20mg/kg/day divided q6-8hr 95% Doxycycline 100mg q12hr 93% Clindamycin 600-900mg q8hr 65% Linezolid (ZYVOX) 600mg q12hr Daptomycin (CUBICIN) 4mg/kg q24hr Tigecycline (TYGACIL) 100mg then 50mg q12hr Dalfopristin/quinupristin (SYNERCID) 7.5mg/kg q12hr Rajia Ghoneim pharm.D. candidate

MRSA SSTI outpatient Drug Regimen PO HMC 2006 TMP/SMX 1-2 DS tablets q12hr 95% Doxycycline 100mg q12hr 93% Clindamycin 300-450mg q6hr 65% Linezolid 600mg q12hr 100% Duration : 7-14 days Rajia Ghoneim pharm.D. candidate

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.

pNEUMONIA Rajia Ghoneim pharm.D. candidate

Pneumonia Rajia Ghoneim pharm.D. candidate pneumonia HAP CAP outpatients hospitalized non ICU hospitalized ICU Rajia Ghoneim pharm.D. candidate

CAP (hospitalized non ICU) ATA/IDSA 2007 Type of therapy Drug class Level of evidance Combination : Beta lactam + Macrolide Strong Beta lactam + doxycycline (IV) Weak Monotherapy: resp.flouroquinolones Type of therapy Drug Regimen 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

HAP VAP MDR Rajia Ghoneim pharm.D. candidate

+ + HAP cont’d… ATS/IDSA2004: suspected MDR Type of therapy Class Drug regimen Combination of 3 - Antipseudomonal cephalosporin Or Antipseudomonal carbapenem -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 - Aminoglycoside Ciprofloxacin Levofloxacin Gentamicin Amikacin Tobramycin 750 mg every d (5d) 7 mg/kg per d 20 mg/kg per d Anti MRSA Vancomycin 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

HAP cont’d… 2 combinations or 3? anti pseudomonal βlactam + (vancomycin or linezolid) (FQ or Aminoglycosides) HMC 2006 Ps.aeruginosa Amikacin 94% Pip/tazo 90% Ceftazidime Genta Imipenem 85% Cipro 64% Rajia Ghoneim pharm.D. candidate

ATS/IDSA2004: Rajia Ghoneim pharm.D. candidate

URINARY tract infections Rajia Ghoneim pharm.D. candidate

UTI UTI Cystitis female male Pyelonephritis Acute uncomplicated Obstruction Reflux Azotemia Transplant Foley Catheter Rajia Ghoneim pharm.D. candidate

Cont’d UTI IDSA 1999 Uncomplicated Cystitis in females: Route Drug Dose Frequency duration LEVEL OF EVIDENCE PO TMP/SMX DS q12hr 3D A,I Ofloxacin Ciprofloxacin Levofloxacin Norfloxacin 250mg Q12hr 7D TMP 100mg Nitrofurantoin (macrobid) B,I Fosfomycin

Cont’d UTI Uncomplicated cystitis in females: Special conditions: Days HMC 2006 (E.coli) PO TMP/SMX DS q12hr 3d 69% Ciprofloxacin Levofloxacin 250mg q24hr 81% Nitrofurantoin (macrobid) 100mg 5d 96% Cefpodoxime 7d* Ampicillin/sulbactam 1.5g q6hr 7d 75% Cephalexin 500mg 90% Special conditions: Pregnant: beta lactam (7days) Diabetic, >65y, symptomatic for 7 days7days Recurrent (re-infection) 7days Recurrent (relapse)14days Rajia Ghoneim pharm.D. candidate

Cont’d UTI Uncomplicated Cystitis in male: PO Ciprofloxacin Levofloxacin 500mg 250-500mg Q12hr Q24hr 7D TMP/SMX DS q12hr Rajia Ghoneim pharm.D. candidate

Cont’d UTI IDSA 1999 Acute uncomplicated Pyelonephritis in females: Level of evidence PO ciprofloxacin 500mg q12hr 7D A,II Levofloxacin 250mg q24hr TMP/SMX DS Q12hr 14D B,II Severe Pyelonephritis in females: IV flourquinolones 10-14D Gentamycin +/- Ampicillin Extended spectrum ceph +/- Gentamycin HMC Rajia Ghoneim pharm.D. candidate

Cont’d UTI Acute Uncomplicated Pyelonephritis HMC 2006 (E.coli) HMC 2006 (Enterococcus sp.) PO Ciprofloxacin Levofloxacin 500mg 750mg Q12hr Q24hr 10D 5D 81% 58% TMP/SMX DS q12hr 7D 69% unreliable Cefpodoxime 200mg 14D 96% Cephalexin Q6hr 90% Ampicillin/sulbactam 1.5g 75% 85% IV Ceftriaxone 1g Aztreonam Q8-12hr 400mg 5d 10d Rajia Ghoneim pharm.D. candidate

Cont’d UTI Complicated /catheter UTI: 10-14days Drug Dose HMC 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 q6hr 74% Imipenem (IV)500 mg q6hr 85% Meropenem (IV)1g q8hr 86% Ceftazidime 1g q8hr Ciprofloxacin (IV)400mg q12hr 64% Levofloxacin (IV/PO)750mgq24hr (5d)

Intra abdominal Infections Primary Secondary (community, hospital acquired) Rajia Ghoneim pharm.D. candidate

Intra abdominal infections Primary peritonitis (SBP) Drug Dose Route Duration Cefotaxime 2g q12hr 2g q8hr IV 5 days Ceftrioxone 2g q24hr Ertapenem 1g q24hr Ampicillin/sulbactam 1.5-3gq6hr 6-12 days Ofloxacin 400mg q12hr Oral 8 days Rajia Ghoneim pharm.D. candidate

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

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

Bacterial Meningitis Rajia Ghoneim pharm.D. candidate

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

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

Cont’d meningitis… Age group >50years 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 Alternative Meropenem + Vancomycin + Dexamethazone 2g q8hr 500-750mg q6hr Rajia Ghoneim pharm.D. candidate

Update on Febrile Neutropenia Rajia Ghoneim pharm.D. candidate

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 Rajia Ghoneim pharm.D. candidate

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

SSTI 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 Rajia Ghoneim pharm.D. candidate

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 Rajia Ghoneim pharm.D. candidate

UTI Cooper D.H.,Krainik A.J.,The Washington Manual of Medical Therapeutics. 32nd ed.2007.ch13,384- 388 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. 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.   Thomas M. Walter .E.Acute cystitis and asymptomatic bacteriuria in men. Uptodate.com. Last literature review JAN 2008 Krieger JN; Ross SO; Simonsen JM. Urinary tract infections in healthy university men.J Urol 1993 May;149(5):1046-8.   Thomas M. Walter .EAcute pyelonephritis: Symptoms; diagnosis; and treatment. Uptodate.com. Last literature review JAN 2008 Clinical Approach To Initial Choice Of Antimicrobial Therapy.Acute Uncomplicated Pyelonephritis, Hospitalzed. Sanford Guide For Antimicrobial Therapy 2007 Clinical Approach To Initial Choice Of Antimicrobial.Complicated Urinary Tract Infections/Catheters. Sanford Guide For Antimicrobial Therapy 2007 Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women. Clinical Infectious Diseases 1999;29:745–58. 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. 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 Lindsay E. Nicolle Catheter-Related Urinary Tract Infection. Drugs Aging 2005; 22 (8): 627-639

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) Rajia Ghoneim pharm.D. candidate

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. Rajia Ghoneim pharm.D. candidate

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 Rajia Ghoneim pharm.D. candidate