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

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

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

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

5. 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
mg 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

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

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.

8. pNEUMONIA
Rajia Ghoneim pharm.D. candidate

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

10. 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

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

12. + + 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

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

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

15. URINARY tract infections
Rajia Ghoneim pharm.D. candidate

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

17. 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

18. 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

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

20. 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

21. 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

22. 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)

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

24. 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

25. 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)

26. 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

27. Bacterial
Meningitis
Rajia Ghoneim pharm.D. candidate

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

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

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

31. Update on
Febrile Neutropenia
Rajia Ghoneim pharm.D. candidate

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
Rajia Ghoneim pharm.D. candidate

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

34. SSTI
Guidelines for Skin and Soft-Tissue Infections,Clinical Infectious Diseases 2005; 41:1373– 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

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– 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

36. UTI
Cooper D.H.,Krainik A.J.,The Washington Manual of Medical Therapeutics. 32nd ed.2007.ch13,
Gupta K; Hooton TM; Roberts PL; Stamm WE . Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women. Arch Intern Med Nov 12;167(20):
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 Mar;47(3):  
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 May;149(5):  
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):
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):

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)
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.
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 Guidelines for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer
Rajia Ghoneim pharm.D. candidate