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Penicillin - Spectrum. Lancfield group streptococciAlpha streptococcus, except pneumococcusEnterococcusOral anaerobes - peptostreptococcus, etc.Treponema pallidum and other spirochetesActinomyces. Penicillin - Mechanism of Action. Penicillin is a beta-lactam antibioticBinds to penicillin b
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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