Antibiotics 101
Puja Van Epps
1/20/14
Beta-lactams
Core PCN
structure
Core Cephalosporin
structure
Beta-lactams
 Beta-lactamases are enzymes produced
by some bacteria that provide resistance
against beta lactams through hydrolysis of
the β-lactam ring
Natural Penicillins
 Bicillin L-A (Penicillin G benzathine) – IM
only
 Penicillin G (IV)
 Penicillin V = PO
Natural Penicillins- Spectra
Groups
Gram Positive
Gram Negative
Anaerobes
Other
Important Organisms
Group A/B/C/G strep
S. pneumoniae*
viridans streptococci gr.*, Strep milleri*
Enterococcus (feacalis>faecium)
Neisseria meningitidis*
Pasteuralla multocida
Haemophilus ducreyi
Actinomyces
Clostridial sp.
Peptostreptococcus
Fusobacterium
Treponema pallidum
Natural Penicillins
Bicillin: Primary, secondary, latent and
late latent syphillis
PCN G: Neurosyphillis; systemic
infection due to susceptible bacteria
(Streptococci)
PCN V: Group A strep pharyngitis
Anti-staphylococcal Penicillins
 Nafcillin, oxacillin, methicillin, dicloxacillin (PO)
 Penicillinase is a specific type of β-lactamase,
showing specificity for Penicillins
 First β-lactamase to be identified; PCN R in S.
aureus
 Major Uses:
Methicillin-susceptible S. aureus or Coagulase
Negative Staph; PCN-susceptible strains of
Streptococci
 No gram negative activity
Aminopenicillins
 Ampicillin/amoxicillin; Augmentin (AmoxClav); Unasyn (Amp-Sulbactam)
 Amp/amox – Great for susceptible streps
and enterococcus; very limited GN activity;
cover anaerobes
 Addition of Clavulanate or Sulbactam
enhances Gram negative activity
 No activity against MSSA without the betalactamase inhibitor.
Aminopenicillins
 Important holes in coverage
 Pseudomonas sp.
 Atypical gram negatives – mycoplasma
pneumoniae, chlamydia pneumoniae,
legionella sp.
 Enterobacter sp.
 If susceptible Ampicillin is the DOC
for Enterococcus and Listeria
Anti-Pseudomonal Penicillins
 Ticarcillin, Ticar-Clav, Piperacillin, Pip-Tazo
 Generally good gram positive, gram negative and
anaerobic coverage
 Ticarcillin and Piperacillin without their beta-lactamase
inhibitor DO NOT cover MSSA
 Important holes in coverage: MRSA (ESBL+, KPC+, or
other resistant GN)
 Stenotrophomonas maltophilia – Ticar-Clav is second
line, Pip/Tazo does not cover.
Cephalosporins
 5 generations, increasing gram negative
coverage with each generation
First Generation Cephalosporins
 Cefadroxil, Cephalexin (PO)
 Cefazolin (IV)
Gram Positive
Group A, B, C, G Strep
Strep pneumo
Viridans strep
MSSA
Gram Negative
E. coli, Klebsiella sp.,
Proteus mirabilis
Anaerobes
No activity
First Generation Cephalosporins
 Important holes in coverage –
 MRSA, Enterococcus, Pseudomonas,
anerobes
Second Generation Cephalosporins
 Cefuroxime (IV, PO), Cefotetan (IV),
Cefoxitin (IV)
 In addition to the coverage of 1st
generation
- H. influenzae, M. catarrhalis, Neisseria
sp., and anearobic coverage (variable)
 Important holes in coverage:
- MRSA, Enterococcus, Pseudomonas
Third Generation Cephalosporins
 Ceftriaxone, Cefotaxime, Ceftazadime (IV)
 Cefixime, Cefdinir (PO)
 In general less active against gram-positive
aerobes than previous generations, but
have greater activity against gramnegatives
 Cefotaxime and Ceftriaxone have the best
gram + coverage in the group
 Only Ceftazadime covers Pseudomonas
Third Generation Cephalosporins
 Major holes in coverage –
- Enterococcus, MRSA, Pseudomonas
(except Ceftazidime), +/- Acinetobacter,
Listeria
 Ceftazidime crosses BBB, Ceftriaxone in
inflamed meninges
Fourth Generation Cephalosporins
 Cefepime (IV)
 gram-positives:
similar to first
generation
 gram-negatives: broad, including
Pseudomonas
 Major holes: MRSA, poor anaerobic
coverage, listeria
 Crosses BBB
Fifth Generation Cephalosporin
 Ceftaroline (IV)
 Major advantage:
- MRSA
Major holes in coverage:
- Pseudomonas, enterococcus and
anaerobes
 CAP, SSTI
Cephalosporin Review
 Antipseudomonal –
Ceftazadime and Cefepime
 Anti-MRSA –
Ceftaroline
 Anti-Enterococcal –
None (Ceftaroline has in-vitro activity against
E. faecalis)
 Enterobacter sp. can develop resistance to
cephalosporins during treatment, therefore
not the treatment of choice
Carbapenems
 Ertapenem, Doripenem, Imipenem, Meropenem
 Broadest spectrum of activity
 Have activity against gram-positive and gramnegative aerobes and anaerobes
 Bacteria not covered by carbapenems include
MRSA, VRE, MR coagulase-negative staph
 Additional ertapenem exceptions:
 Pseudomonas, Acinetobacter, Enterococcus
Carbapenems
 Major holes in coverage:
- Atypicals (Legionella, Mycoplasma) ,
MRSA, VRE, Stenotrophomonas
maltophilia, KPC+
 Ertapenem does not cover:
- Pseudomonas, Acinetobacter,
Enterococcus
Monobactam
 Aztreonam: binds preferentially to PBP 3
of gram-negative aerobes
 No gram positive or anaerobic activity
 Major uses – Hospital acquired infections
in patients with anaphylaxis to any beta
lactams (does not have cross reactivity)
 Important gram neg holes: Acinetobacter,
ESBL+, KPC+
Fluoroquinolones
 Ciprofloxacin, Levofloxacin, Moxifloxacin
 Broad spectrum of activity, excellent
bioavailability, tissue penetration
 Cipro has poor gram + coverage
 Disadvantages: resistance, expense, C
diff
 Advantages: Atypical coverage,
Antipseudomonal (Cipro, Levo)
Aminoglycosides
 Gentamicin, Tobramycin, Amikacin
 inhibit protein synthesis by irreversibly
binding to 30S ribosome, bactericidal
 For gram + use in combination with cell
wall agents
 Broad spectrum gram neg coverage
including Pseudomonas and
Acinetobacter
 Also have mycobacterial coverage
Aminoglycosides – adverse
effects
 Nephrotoxicity
– Nonoligouric renal failure from damage to the proximal
tubules
– Underlying CKD, Age, other nephrotixins, duration,
high troughs
 Ototoxicity
– 8th cranial nerve damage - vestibular and auditory
toxicity; irreversible
– Related to duration of therapy (>2wks)
Macrolides
 Clarithromycin, Erythromycin,
Azithromycin
 Inhibit protein synthesis by reversibly
binding to the 50s ribosomal unit
Macrolides
 Gram-Positive Aerobes –
Clarithro>Erythro>Azithro
 Gram-Negative Aerobes –
Azithro>Clarithro>Erythro
No activity against any Enterobacteriaceae or
Pseudomonas
 Anaerobes – activity against upper airway anaerobes
 Atypical Bacteria – Excellent
 Also cover – Mycobacterium avium complex,
Campylobacter, Borrelia, Bordetella, Brucella.
Anti-MRSA drugs
Vancomycin
 Inhibits synthesis and assembly of the
second stage of peptidoglycan polymers
 Gram-positive bacteria: excellent coverage
 Major uses:
MRSA, MSSA (in PCN all), PCN R
streptococci
 No activity against gram-negatives or
anaerobes
 If MIC to Vancomycin in MRSA is ≥ 2, Do not
use
Vancomycin
Red-Man Syndrome
– flushing, pruritus, rash
– related to rate of infusion
– resolves spontaneously
– may lengthen infusion
NOT AN ALLERGY
Daptomycin
 Lipopeptide; binds to components of the cell
membrane and causes rapid depolarization,
inhibiting intracellular synthesis of DNA, RNA,
and protein
 Major uses
- SAB, Right-sided IE caused by S. aureus, VRE
 Indicated for SSTI, R sided IE
Do not use for lung infections including MRSA PNA
– pulmonary surfactant inhibits Daptomycin
Linezolid
 Binds to the 50S ribosomal subunit near the
surface interface of 30S subunit – causes
inhibition of 70S initiation complex which inhibits
protein synthesis
 Active against wide range of Gram + bacteria,
limited to no Gram negative or anearobic activity
 Major uses –
MRSA, VRE.
 Major problem
thrombocytopenia with prolonged use (>2wks),
bacteriostatic (cidal against Enterococcus)
Tigecyline
 Binds to the 30S ribosomal subunit of susceptible bacteria,
inhibiting protein synthesis.
 Broad spectrum of activity including –
- MRSA, VRE, gram negatives (including resistant GN)
 Major holesThe 3 P’s – Pseudomonas, Proteus and doesn’t get in the
urine
 Indicated for complicated SSTI, intra-abdominal infections,
CAP
 Major problems: GI issues, and shown to have increased
mortality in serious infections – monotherapy only as a last
resort.
Clindamycin
Inhibits protein synthesis by binding
exclusively to the 50S ribosomal subunit
Major uses
- MRSA (some isolates), anaerobic
coverage
Clindamycin
A positive D test indicates the presence of macrolide-inducible
resistance to clindamycin produced by an inducible methylase
that alters the common ribosomal binding site for macrolides,
clindamycin
Tetracylines
 Doxycyline, Minocyline
 Good gram pos, neg and anaerobic
coverage
 Major uses
MRSA, anti-malarial prophylaxis,
rickettsial infections, Borrelia burgdorferi
Trimethoprim, TMX-Sulfa
 Inhibit various steps within the folic acid
biosynthetic pathway
 Good gram pos and gram neg coverage
(CA-MRSA)
 Important uses: Pneumocystis,
Stenotrophomonas maltophilia, Nocardia
 Major holes
 Pseudomonas, anaerobes