PRACTICAL USAGE OF ANTIBACTERIAL AGENTS

1. PRACTICAL USAGE OF ANTIBACTERIAL AGENTS Rema Merhi, D.O. PGY-3 Infectious Disease University of Nevada School of Medicine Pisespong Patamasucon, M.D. Professor of Pediatrics Director Pediatric Infectious Diseases University of Nevada School of Medicine

2. Penicillins

3. Carbenicillin Ticarcillin Piperacillin Ampicillin Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Nafcillin Oxacillin Methicillin

4. Penicillin • Gram-Positive Cocci • Streptococci • Except Enterococcus • Gram-Positive Rods • C. diphtheria • Gram-Negative Cocci • Neisseria • Spirochete • Treponema pallidum • Anerobic • Except Bacteroides fragilis No Gram Negative Rod Coverage Amino-penicillin

5. Gram Negative Carbenicillin Ticarcillin Piperacillin (low Na load) Ampicillin E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella Pseudomonas, B. fragilis GPC, GPR, GNC, SpirocheteAnaerobes Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Nafcillin Oxacillin Methicillin Staphylococci (MSSA) *increased anaerobic coverage Staphylococci (MSSA)

6. Cephalosporins

7. Cephalosporin • Same mechanism as penicillin • If allergic to PCN can react to this too! • Bacteriostatic • Does not cover: • L- listeria • A- anaerobes* • M- MRSA • E- enterococcus **Cefoxitin, Cefotetan cover anaerobes

8. 1st Generation Cephalosporin (except H. influ) Gram Negative Carbenicillin Ticarcillin Piperacillin Ampicillin E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella Pseudomonas, B.fragilis GPC, GPR, GNC, SpirocheteAnaerobes Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Nafcillin Oxacillin Methicillin Staphylococci (MSSA) Staphylococci (MSSA)

9. Cephalosporin • 1st Generation: • Gram Positive • S. aureus, S. epidermidis, Streptococcus species • NO MRSA • Gram Negative • E. coli, K. pneumoniae, P. mirabilis • NO Enterococci • Anaerobes • NO B. fragilis

10. Cephalosporin • 1st Generation: • Cefazolin (Ancef) • IV • Given q 8º • Surgery prophylaxis • Cephalexin (Keflex) • PO • Skin 50mg/kg/day • Bone 2-3x skin dose • Cefadroxil (Duricef) • PO • Given q 12º • UTI • Especially for ampicillin and TMP/SMZ resistant

11. 2nd Generation Cephalosporin

12. 2nd Generation Cephalosporin (including H. influ) Gram Negative Carbenicillin Ticarcillin Piperacillin Ampicillin E.coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella Pseudomonas, B. fragilis GPC, GPR, GNC, SpirocheteAnaerobes Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Nafcillin Oxacillin Methicillin Staphylococci (MSSA) Staphylococci (MSSA)

13. Cephalosporin • 2nd Generation: • Less GM+ coverage, More GNB coverage • Beta-Lactamase +/ Beta-Lactamase – • Add H.influ (with BL+ and -), Enterobacter, Neisseria • CNS penetration < than 3rd generation • Cefuroxime • CNS penetration • Cefoxitin • Anaerobic coverage! • Surgeons/ OB-GYNs • Cefotetan • Anaerobic coverage! • GN coverage (PID)

14. 3rd Generation Cephalosporin

15. 3rd Generation Cephalosporin Gram Negative Carbenicillin Ticarcillin Piperacillin Ampicillin E.Coli, Shigella, Proteus, Salmonella, Listeria, H.influ, Klebsiella Pseudomonas, B.fragilis GPC, GPR, GNC, SpirocheteAnaerobes Nafcillin Oxacillin Methicillin Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Staphylococci (MSSA) Staphylococci (MSSA)

16. Cephalosporin • 3rd Generation: • Great GN coverage; No staph coverage • CNS coverage • Ceftriaxone • IV q 24º • CNS penetration • High activity against beta-lactamase producing H.influ, N.gonorrhoeae • Cefotaxime • IV q 6º • CNS penetration • High activity against beta-lactamase producing H.influ, N.gonorrhoeae • Ceftazidime • Antipseudomonal

17. 3rd Generation Cephalosporins Gram Negative 1st Generation Cephalosporins (except H. influ) Carbenicillin Ticarcillin Piperacillin Ampicillin E.Coli, Shigella, Proteus, Salmonella, Listeria, H.influ Pseudomonas, B.fragilis 2nd Generation Cephalosporins (including H. influ) GPC, GPR, GNC, SpirocheteAnerobes Ampicillin + Sulbactam Ampicillin + Clavulanate Ticarcillin + Clavulanate Piperacillin + Tazobactam Nafcillin Oxacillin Methicillin Staphylococci (MSSA) Staphylococci (MSSA)

18. Cephalosporin • 4th Generation: • Cefepime- pseudomonas • Covers GN • Nosocomial GNB acinobacter • S. pneumo • Does NOT cover Extended Spectrum Beta-Lactamase • ESBL’s

19. ESBL’s • Extended Spectrum Beta-Lactamases • Enterococcus faecium • Serratia • Klebsiella pneumoniae • Acinetobacter baumanii • Providencia/pseudomonas • Enterobacter spp. • Salmonella, E. coli • Treatment: • Meropenem • Pipercillin+Tazobactam • Zosyn

20. Side Effects • Penicillin: • Black or hairy tongue • Exaggerated reflexes • Mild diarrhea • Nausea or vomiting • Pain, swelling, or redness at the injection site • Twitching • Anaphylaxis

21. Side Effects • Cephalosporins: • Generally few side effects • Hypersensitivity if allergic to PCN • Mild stomach cramps • Nausea/vomiting/diarrhea • Yeast overgrowth

22. Aminoglycosides • Amikacin • Gentamicin • Tobramycin • Paromomycin • Coverage: • Gram negative bacilli • Enterobacteriaceae, Pseudomonas spp., Haemophilus influenzae • Paromomycin covers protozoa • Bactericidal • Inhibits bacterial translocation • Concentration-dependent killing • Concentration of drug (relative to bacteria MIC) induces more rapid, and complete, killing of the pathogen

23. Aminoglycosides • Disadvantages • Target concentration • Peak and Trough levels • Frequent dose changes • Side Effects: • Ototoxicity • 2º to vestibular or cochlear damage • Nephrotoxic • 10-20% • Neuromuscular blockade • Blocks neuromuscular transmission at neuromuscular junction • Presynaptic (block acetylcholine synthesis/release) or Postsynaptic (at motor nerve end plate) action • Postsynaptic

24. Vancomycin • Glycopeptide antibiotic • Bacteriostatic • Inhibits cell wall synthesis in GPB • Use to cover resistant Strep pneumo • Synergistic with PCN or Ampicillin • Coverage: • Gram positive bacteria • MRSA • Coag Neg Staph • C.diff • Enterococcus • Except VRE

25. Vancomycin • Renal excretion • Side Effects: • Red-man syndrome • Hypotension • Steven Johnson Syndrome (SJS) • Toxic epidermal necrolysis (TENs) • Interstitial nephritis • Poor bone and brain penetration • 7-13% bone • <10% brain • 60/mg/kg • Usually 20-40 mg/kg

26. Vancomycin • VRE- Vancomycin Resistant Enterococcus • Treatment: • Linezolid (Zyvox) • Daptomycin • Can not use to treat PNA surfactant in lung breaks down drug • Synercid • Quinupristin and dalfopristin • Enterococcus faecium (not faecalis)

27. Clindamycin • Coverage: (PO=IV) • Gram positive cocci • Staph/Strep • Anaerobes • Above diaphragm • Bacteriostatic • But considered bactericidal against • Some staph, strep, and B.fragilis • Great BONE penetration 60% • Linezolid 50% • Side Effects: • Diarrhea • Allergic reactions

28. Macrolides • Azithromycin • Clarithromycin • Erythromycin • Coverage: • GPC, Haemophilus spp, Moraxella catarrhalis • Atypical: Legionella, Chlamydia and Mycoplasma pneumoniae • Rickettsia, helicobacter, toxoplasma • Good tissue and intracellular penetration • Long half lives • Azithromycin ½ life is 68 hrs

29. Macrolides • Side Effects: • Erythromycin: • Hypertrophic pyloric stenosis • Long QT syndrome • Interstitial nephritis • Azithromycin • Hepatotoxicity- increased LFT’s, cholestatic jaundice • All three (clarithromycin, erythromycin, azithromycin) • N/V/DIARRHEA • Anaphylaxis • SJS • Pseudomembranous colitis

30. Miscellaneous Antibiotics • Tetracycline: (PO=IV) • Bacteriostatic • GP, GN, rickettsia, mycoplasma, chlamydia, spirochete (Borrelia), malaria, tularemia, leptospirosis, RMSF • Side effects: • Tooth discoloration • Do not take with milk • Use in patients > 8 yo • Fluoroquinolones: • Bactericidal • Use if >18 yo • Arthropathy, erosion of cartilage in weight bearing joints • GNB, GP except MRSA, some pseudomonas, chlamydia, mycobacteria • Metronidazole (Flagyl): • Anaerobes and CNS coverage • Below diaphragm

31. CNS INFECTION

32. Bacterial Meningitis: Treatment

33. Duration of Treatment • Neonate • 10-14 days: • GBS, L.monocytogenes • 3 weeks: • gram-neg enteric meningitis • Infant/Child • 10-14 days: • N. meningitides 7 days • H. influenza • S. pneumoniae

34. Pneumonia

35. Etiology of Pneumonia in Infants and Children { Viral Agents Para 1,2,3 Influenza A, B. Etc. Winter Summer S. Pneumoniae Mycoplasma RSV C. Trachomatis CMV 1 Staph 2 Staph Chlamydia Pneumoniae Strep.Gr.B E. Coli H. Inf. b 1 mo 3 mo 6 mo 1 yr 3 yrs 5 yrs 10 yrs

36. Antimicrobial Agents for Community Acquired Pneumonia in Various Pediatric Age Groups

37. Children with Pneumonia Warranting Consideration of Inpatient Management • Toxic appearance • Respiratory distress • Pleural effusion • Immunocompromised host • Progression during outpatient therapy • Age factors • Less than 3 mos • Less than 3 yrs with lobar • Less than 5 years with more than 1 lobe • Those with chronic disease • Pulmonary • Cardiac • Renal • Diabetes • Metabolic disorders • Anemia • malignancies

38. HEMATOGENOUS OSTEOMYELITIS

39. Neonates

40. Infants/ Children

41. Initial Treatment of Osteomyelitis

42. S. aureus Coverage • Semi-synthetic PCN • Nafcillin or Oxacillin • 1st generation cephalosporin • 2nd generation cephalosporin • Clindamycin/Vancomycin

43. Important Information • Treatment less than 3 weeks associated with increase risk for recurrence • Treatment with IV less than 7 days associated with morbidity • Total duration of treatment 4-6 weeks • Time to stop – resolution of symptoms with normalized WBC, CRP, or ESR • CRP < 1 • ESR < 15

44. The # 1 “Scary Bug” MRSA

45. Comparison of HA-MRSA and CA-MRSA

46. MRSA • In 2005 60% of soft skin tissue infections (SSTI) were MRSA • Clindamycin resistance at UMC and sunrise 46% • 6% 26% 46% (in 2009) • Alternative treatment: • Vancomycin- slow so add gentamicin for synergy • Since it can still be MSSA….add Nafcillin or Oxacillin

47. MRSA Treatment • Outpatient: • Tetracycline • Bactrim • Clindamycin • Inpatient: • Clindamycin • Vancomycin • Linezolid • Daptomycin • Synercid • Quinupristin and dalfopristin

48. CA-MRSAAntibiotic Susceptibility • Vancomycin • Gentamicin/rifampin (synergy 3-5 days) • Trimethoprim-sulfamethoxazole • Clindamycin • Doxycycline/minocycline • Linezolid (Zyvox) • Daptomycin (Cubicin) • Quinupristin/dalfopristin (Synercid)

49. Infectious Disease Clinics. Infect Dis Clin N Am 19 (2005) 747-757

50. Board Review • You admit an 18yo boy to the hospital with RLL PNA. While gathering your history, you discover that 4 years ago he developed a rash and respiratory difficulty when he received IM ceftriaxone. Of the following, the BEST antimicrobial agent for this patient is: • Ceftriaxone • Levofloxacin • Meropenem • Penicillin