Review of Antibiotics Part 1

1. Review of AntibioticsPart 1 Gary R. Skankey, MD, FACP, FIDSA University of Nevada School of Medicine

2. Penicillin - Spectrum Lancfield group streptococci Alpha streptococcus, except pneumococcus Enterococcus Oral anaerobes - peptostreptococcus, etc. Treponema pallidum and other spirochetes Actinomyces

3. Penicillin - Mechanism of  Action Penicillin is a beta-lactam antibiotic Binds to penicillin binding proteins on bacterial cell surface Inhibits cell wall synthesis

4. Penicillin and Pneumococcus About 30% resistant, 15% intermediately sensitive Altered PBPs makes penicillin and sometimes cephalosporins ineffective Plasmid mediated,possibly transferred from other species Plasmid also caries resistance genes to other antibiotics: macrolides, tetracyclines, sulfa drugs

5. Penicillin - Neisseria Increasing resistance due to beta-lactamase production in N. gonnorrhea and N. meningitidis Unless organism proven sensitive, do not use penicillin empirically for meningitis or sexually transmitted disease.

6. Penicillin - Dosing Mild infections - cellulitis, pharyngitis, etc., Penicillin V 500mg PO QID Penicillin G 1 - 2 million units IV Q4hrs Serious infections - meningitis, endocarditis Penicillin G 4 million units IV Q4hrs. Syphillis latent: 2.4 million units benzathine penicillin IM Q week x 3 weeks neurosyphillis: 4 million units IV Q4hrs x 10 days Adjust dose for renal failure

7. Penicillin - Clinical Uses Syphillis S. pyogenes pharyngitis Actinomyces infections Subacute bacterial endocarditis due to pcn-sensitive alpha-streptococci Pencillin-sensitive pneumococcal and meningococcal meningitis

8. Ampicillin - Spectrum Same gram positives as penicillin Enteric gram negatives (if sensitive): E. coli Proteus Salmonella Shigella Respiratory tract gram negatives Haemophillus influenzae, Moraxella morganii Pasteurella moltocida Listeria monocytogenes

9. Ampicillin and Enteroccocus Weak affinity for penicillin-binding proteins �bacterostatic Must add aminoglycoside (gentamicin) to create bacterocidal regimen E. faecalis usually sensitive E. faecium usually resistant

10. Ampicillin and Haemophillus About 40% of H. influenzae is resistant Produces beta-lactamase Resistance overcome by use of beta-lactamase inhibitor

11. Ampicillin and Salmonella Increasing resistance in salmonella makes it unreliable against typhoid fever. About 40% resistance

12. Ampicillin - Dosing Mild infections - cystitis, pharyngitis Amoxacillin 500 mg PO TID Moderate infections - pyelonephritis, cellulitis, osteomyelitis Ampicillin 1 - 2 gm IV Q6hrs Severe infections - meningitis, endocarditis Ampicillin 2 gm IV Q4hrs Adjust dose for renal failure

13. Ampicillin - Clinical Uses Amoxacillin for ampicillin-sensitive UTIs In combo with gentamicin for enterococcal endocarditis Listeria monocytogenes infections meningitis bacteremia Cat bite cellulitis + clindamycin Penicillin-sensitive alpha-streptococcal SBE

14. S. aureus - beta lactamase 1st described in 1945 Confers resistance to penicillin and ampicillin Coded for on plasmid Plasmids also carry resistance to other antibiotics Usually inducible

16. Beta-lactamase-Resistant Penicillins Methicillin high risk of interstitial nephritis, no longer on market Nafcillin Oxacillin Dicloxacillin (PO)

17. Nafcillin/Oxacillin - Spectrum Oxacillin-sensitive S. aureas Oxacillin-sensitive coagulase negative staph Okay against Lancfield group streptococci and viridans streptococci, but there are better drugs for these No gram negative or anaerobic coverage to speak of

18. Nafcillin/Oxacillin - Pearls Most potent anti-staph drug made Excellent CNS penetration (staph meningitis) No dose adjustment for renal failure predominantly hepatic excretion Watch out for: leukopenia thrombocytopenia interstitial nephritis

19. Nafcillin/Oxacillin - Clinical Uses All MSSA infections: Endocarditis Meningitis Osteomyelitis Pneumonia Abscesses Cellulitis

20. Anti-pseudomonal Penicillins Carbenicillin no longer on the market Ticarcillin only on market as Timentin Piperacillin hard to get as piperacillin alone, usually only available as Zosyn

21. Piperacillin - Spectrum Pseudomonas Enterobacteriacae group Beta-lactamase negative Moraxella, Neisseria, Haemophillus Same gram positive spectrum as penicillin Same anaerobic spectrum as penicillin

22. Piperacillin dosing Mild to moderate gram negative (non-pseudomonal) or streptococcal infections 3 gm IV Q6 hrs. Moderate to severe pseudomonal infections 3 gm IV Q4 hrs. Or Piperacillin/tazobactam 3.375 gm IV Q4 hrs

23. Beta-lactam/Beta-lactamase Inhibitor Combinations Unasyn ampicillin/sulbactam Timentin ticarcillin/clavulenate Zosyn piperacillin/tazobactam

24. Unasyn - Spectrum Streptococci MSSA All anaerobes Beta-lactamase-producing gram negatives Enterococcus - bacterostatic Penicillin-sensitive pneumococcus

25. Unasyn - Dosing Mild infections 1.5 gm IV Q6 hrs. Moderate to severe infections 3.0 gm IV Q6 hrs. Adjust dose for renal failure

26. Unasyn - Clinical Uses Head and neck infections Peritonsilar abscess Sinusitis Mastoiditis Mandibular osteomyelitis Actinomyocosis Infected Bite Wounds Human Dog Cat Diabetic Foot infections, including osteomyelitis Culture negative endocarditis

27. Zosyn - Spectrum Streptococci MSSA All anaerobes Beta-lactamase-producing gram negatives Enterococcus - bacterostatic Piperacillin-sensitive pseudomonas 18 gm per 24 hrs

28. Zosyn - Dosing Usual dosing 3.375 gm IV Q6 hrs. Fulminant sepsis 4.5 gm IV Q6 hrs. Pseudomonas sepsis 3.375 gm IV Q4 hrs Adjust dose for renal failure

29. Zosyn - Clinical Uses Intra-abdominal infections Nosocomial aspiration pneumonia Diabetic foot infections when Pseudomonas might be involved Pulmonary infections in patients with bronchiectasis or cystic fibrosis

30. Cephalosporins Inhibit cell wall synthesis - peptidoglycan Side effects are mild rash eosinophilia leukopenia leukocytosis biliary sludge (ceftriaxone) thromobocytosis

31. First Generation Cephalosporins Cefazolin - Ancef IV Cephalothin - Keflin IV Cephalexin - Keflex PO Cephradine - Velosef PO Cefadroxil - Duricef PO

32. Ancef - Spectrum Staphylococcus Streptococcus E. coli, Proteus, Klebsiella if sensitive

33. Ancef - Clinical Uses Any MSSA infection Cellulitis (2 gm IV Q8 hrs.) Osteomyelitis Endocarditis Pneumonia Not for meningitis Any Lancfield or viridans group streptococcal infections Endocarditis Cellulitis Sensitive enteric gram negative infections UTI

34. Second Generation Cephalosporins Cefuroxime IV - Zinacef Cefotetan IV - Cefotan Cefoxitin IV - Mefoxin Cefuroxime axitil PO - Ceftin Cefaclor PO - Ceclor Cefprozil PO - Cefzil

35. Cefuroxime/Cefotetan - Spectrum H. influenzae Anaerobes Staphylococcus Streptococcus Enterobacteriaceae

36. 1st vs 2nd Generation 1ST GENERATION H. influenzae - S. aureus ++++ Streptococcus ++++ Moraxella - Gram negatives + Anaerobes - 2ND GENERATION H. influenzae ++++ S. aureus +++ Streptococcus ++++ Moraxella ++++ Gram negatives ++ Anaerobes +++

37. Cefuroxime - Clinical Uses Upper respiratory tract infections sinusitis peritonsilar abscess otitis media etc., Lower respiratory tract infections pneumonia acute bacterial bronchitis Urinary tract infection

38. Cefotetan/Cefoxitin - Clinical Uses Intra-abdominal infections diverticulitis intra-abdominal abscess peritonitis cholycystitis etc., Osteomyelitis Diabetic foot infections

39. Third Generation Cephalosporins Cefotaxime IV - Claforan Ceftriaxone IV - Rocephin Ceftazidime IV - Fortaz Cefixime PO - Suprax Cefpodoxime PO - Vantin

40. Claforan/Rocephin - Spectrum Streptococci Viridans, Lancfield groups, pneumococcus S. aureus Enteric gram negatives H. influenzae Neisseria meningitidis and gonnorrhea some anaerobes

41. Fortaz - Spectrum All gram negatives, including Pseudomonas Weak if any gram positive coverage No anaerobic coverage

42. Claforan/Rocephin -Clinical Uses Meningitis - 2gm Q4 hrs/2gm Q12 hrs Community-acquired pneumonia UTI Upper Respiratory Tract Infections sinusitis peritonsilar abscess Intra-abdominal infections

43. Fortaz - Clinical Uses Hospital-acquired pneumonia Hospital-acquired UTI Post-op meningitis Intra-abdominal infections Pulmonary infections in patients with cystic fibrosis or bronchiectasis Nail-puncture cellulitis/osteomyelitis

44. Fourth Generation Cephalosporin Cefepime IV - Maxipime