Penicillins Group

1. Penicillins Group Aminopenicillin Antipseudomonas Extended-Spectrum Ampicillin Carbenicillin Piperacillin Ticarcillin Azlocillin Penicillin Semi-Synthetic Penicillin + Beta-lactamase inhibitor Nafcillin Ampicillin + Sulbactam Cloxacillin Amoxicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam

2. Cephalosporins Aminopenicillin Antipseudomonas Extended-Spectrum Gram -ve rod Pseudomonas Pseudomonas B.fragilis K.pneumoniae Penicillin Semi-Synthetic Staphylococci First generation (except H. influ)

3. First generation cephalosporins IV: Cefazolin PO: Cephalexin (Keflex) Cefadroxil

4. Cephalosporins Aminopenicillin Antipseudomonas Extended-Spectrum Gram -ve rod Pseudomonas Pseudomonas B.fragilis K.pneumoniae Penicillin Semi-Synthetic Staphylococci Second generation (include H. influ)

5. Second generation cephalosporins IV: Cefuroxime (Zinnat) PO: Cefuroxime (Zinnat), Cefaclor (Distraclor)

6. Cephalosporins Aminopenicillin Antipseudomonas Extended-Spectrum Gram -ve rod Pseudomonas Pseudomonas B.fragilis K.pneumoniae Penicillin Semi-Synthetic Third generation Staphylococci

7. Third generation cephalosporins • IV: Cefotaxime (Claforan), Ceftriaxone (Rocephin), Ceftazidime (Fortum), Cefoperazone (Cefobid) • PO: Cefixime (Cefspan), Cefdinir (Omnicef), Ceftibuten (Cedax), Cefodoxime proxetil (Banan)

8. Second generation (include H. influ) Cephalosporins Aminopenicillin Antipseudomonas Extended-Spectrum Gram -ve rod Pseudomonas Pseudomonas B.fragilis K.pneumoniae Penicillin Semi-Synthetic Third generation Staphylococci First generation (except H. influ)

9. Penicillin + Beta-Lactamase Inhibitors Active against Beta-lactamases producing organisms. Extension of the antimicrobial activity of the parent antibiotic. Except that neither ticarcillin nor piperacillin has been rended more active against Beta-Lactamases producing strains of Pseudomonas aeruginosa.

10. Drug interaction with AG Amphotericin BAdditive nephrotoxicity Cephalosporin/Enhanced nephrotoxicity &cephaloridineototoxicity CisplastinAdditive nephrotoxicity IndomethacinReduced renal clearance Loop diureticsEnhanced ototoxicity NeuromuscularEnhanced neuromuscular blocking agentsblockage

11. Vancomycin use MRSA CNS shunt infections Hemodialysis shunt infections Clostridium difficile ( Diarrhea, Colitis ) Meningitis caused by Gram-positive cocci, Diphtheroids Endocarditis ( Streptococcus viridans, MRSE ) Group D streptococci (enterococci) Group D non enterococci ( Streptococcus bovis )

12. NOT use Vancomycin Prophylaxis :Infections in ICU Surgical procedures General, Intra-abdominal Neurosurgical, Shunt, Graft Intravenous lines Antistaphylococcal coverage in febrile neutropenia Long-term ambulatory peritoneal dialysis

13. NOT use Vancomycin Therapy :MRSA colonization Enterococcal infections (esp. UTI) Gram +ve infections treatable by other antibiotics.

14. Imipenem Generally resistant MRSA Xanthomonas maltophilia Enterococcus faecium Pseudomonas cepacia Corynebacterium jeikeium Flavobacterium Clostridium difficile

15. NOT use Imipenem Alone in Rx serious Pseudomonasinfections (pneumonia) Community-acquired infection. Surgical prophylaxis. MRSA infection. Alone in Rx serious Enterococcalinfection (S. fecalis) Non-aeruginosa pseudomonal infections.

16. Lymphadenitis • S. aureus (MSSA or MRSA), group A strep • Empiric IV therapy • Oxacillin or • Cefazolin • For possible CA-MRSA • Clindamycin • Vancomycin

17. Bone and Joint Infections, Osteomyelitis, Infants and Children, Acute Infection • S. aureus, group A strep, rarely Kingella • For communities with over 5-10% MRSA • Start empirical therapy with clindamycin or vancomycin • Otherwise start oxacillin or cefazolin • Transition to oral therapy may be considered with cephalexin or dicloxacillin for MSSA once clinical improvement is documented and compliance ensured. • Total therapy (IV plus PO) for 4-6 wk

18. Arthritis – BacterialChildren • S. aureus, group A strep • MSSA • Oxacillin or cefazolin • Total therapy (IV plus PO) for 3 wk • MRSA • Clindamycin or vancomycin • As for osteomyelitis, transition to oral therapy may be considered once clinically improved

19. Pneumonia: Lobar or Segmental Consolidation – Community-Acquired • Pneumococcus (even if immunized), group A strep and S. aureus more likely in younger infants; Mycoplasma pneumonia pneumoniae and other atypical agents may cause lobar pneumonia in school-age children and adolescents • For hospitalized children: cefuroxime or ceftriaxone or cefotaxime; 10-14 d • For suspect mycoplasma and other atypical pneumonia pathogens: Add a macrolide • Oral outpatient therapy for less severe: Amoxicillin • For atypical pneumonia: Add agents as above

20. Pneumonia: Lobar or Segmental Consolidation – With Empyema • Group A strep • Penicillin G x 10 d • Pneumococcal • See above, Pneumonia: Lobar or segmental consolidation • S. aureus (consider CA-MRSA) • Vancomycin • For susceptible strains of MSSA: Oxacillin or cefazolin • MRSA: Clindamycin x > 21 d

21. Peritonitis - Primary • Pneumococcus • Ceftriaxone • Cefotaxime • If penicillin-susceptible • Penicillin G x 7-10 d

22. Peritonitis – Secondary to Bowel Perforation or Appendicitis • Enteric gram-negative bacilli, Bacteroides, Enterococcus • Meropenem • Imipenem • Clindamycin and ampicillin and gentamicin > 10 d

23. Abscess - Brain • Respiratory tract flora, skin flora, or bowel flora, depending on the pathogenesis of infection in a particular child • Until etiology established • Meropenem • Nafcillin and cefotaxime • Ceftriaxone and metronidazole • x 7-10 d after successful drainage • Longer therapy if no surgery • 3-6 wk

24. Empirical Therapy for Bacterial Meningitis • Cefotaxime • Ceftriaxone • Add vancomycin if gram-stain suggests pneumococcus

25. E. coli, Klebsiella • Extended-spectrum Β-lactamases • Resistance to cefotaxime, ceftriaxone, and ceftazidime

26. Gram negative: Drug resistance Enterobacter Serratia Klebsiella Acinetobacter Providentia/ Pseudomonas E.coli

27. Mechanism of Antifungal Agents

28. CANDIDIASISEcology • Other clinically relevant species of Candida: • C. tropicalis – a cause of disseminated infection in compromised hosts • C. parapsilosis – second to C. albicans as a cause of endocarditis • C. glabrata – rare cause of endocarditis and disseminated infection in compromised hosts and catheter associated fungemia. Resistant to azoles • C. lusitaniae – can be a cause of fungemia and deep infection. Resistance to amphotericin B reported

29. Overview of Activity

30. COMMON CANDIDA SPECIES AND ANTIFUNGAL SUSCEPTIBILITY PATTERNS Continue on the next slide… (Treatment and Prevention of Fungal Infections: Focus on Candidemia, 2007.)

31. COMMON CANDIDAS SPECIES AND ANTIFUNGAL SUSCEPTIBILITY PATTERNS CONTINUE… (AMB=amphotericin B; FLU=fluconazole; ICU=intensive care unit; MIC=minimum inhibitory concentration)

32. Candida Species Flucon-azole Itracon-azole Voricon-azole Flucyto-sine AmBd Can-dins C. albicans S S S S S S C. tropicalis S S S S S S C.parapsilosis S S S S S S (to I?)‏ C. glabrata S-DD to R S-DD to R S to I S S to I S C. krusei R S-DD to R S to I I to R S to I S C. lusitaniae S S S S S to R S General Patterns of Susceptibility of Candida Species S = Susceptible; I = Intermediate; S=DD = Susceptible dose-dependent; R = Resistant

33. NEW ANTIFUNGAL ACTIONS