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Beta Lactam Antibiotics
Cell wall disruption –attach to receptor called penicillin binding protein ltranspeptidase lautolysinbactericidal

4 similar groups of drugs
–penicillin
–cephalosporin
–carbapenem
–monobactam
Extremely safe drugs
Extensive experience
Expensive drugs
Penicillins - Families
Natural –penicillin G –penicillin V Anti-staphylococcal –nafcillin –oxacillin –dicloxacillin
Broad spectrum (aminopenicillins) –ampicillin amoxicillin
Extended spectrum –mezlocillin –piperacillin
Combination products with enzyme inhibitor –amoxicillin/clavulanic acid –ampicillin/sulbactam –ticarcillin/clavulanic acid –piperacillin/tazobactam
Penicillins
Penicillin still effective:
–endocarditis & meningitis caused by susceptible organisms  (20-24 mu/day)
     -Strept viridans group
–susceptible pneumococcal infections
Penicillin still drug of choice for: early & latent stages of syphilis
streptococcal cellulitis or pharyngitis
Penicillins - Penicillinase Resistant
Niche in therapy:  Penicillinase-producing Staph aureus –Micro reporting usu. Methicillin (MSSA) –If Staph aureus is methicillin susceptible (MSSA) use a penicillinase-resistant pcn over vancomycin more rapid killing, reduced cost, less monitoring
Penicillins - Aminopenicillins
Ampicillin, amoxicillin (oral)
Niche
in therapy: susceptible Enterococcus and Listeria monocytogenes  Oral amoxicillin:  acute otitis media; prophylaxis for endocarditis
Penicillins - b-lactamase Inhibitors
Ticarcillin-clavulanic acid, ampicillin-sulbactam, piperacillin-tazobactam, amoxicillin-clavulanic acid (oral)
Used in treatment of pneumonia, UTI’s, osteomyelitis, soft tissue and intra-abdominal infections, bacteremias
Cephalosporins
1st GENERATION cephalothin (Keflin) 
cefazolin (Ancef, Kefzol) 
cephalexin (Keflex) 
cefadroxil (Duricef)
2nd GENERATION cefuroxime (Zinacef, Ceftin)
cefaclor (Ceclor)
cefprozil (Cefzil)
loracarbef (Lorabid)
cefotetan (Cefotan)
cefoxitin (Mefoxin)
3rd GENERATION cefotaxime (Claforan)
ceftazidime (Fortaz)
ceftizoxime (Cefizox)
ceftriaxone (Rocephin)
cefdinir (Omnicef)
cefixime (Suprax)
cefpodoxime (Vantin)  oxime (Vantin)  
Cephalosporins...
-Grouped into “generations” –Initially a marketing tool –Based loosely on their spectrum of activity
-Wide variety of clinical uses –Must consider desired spectrum and site of infection
Doses –Broad range –Depend on severity/site of infection
–Require adjustment in renal insufficiency ® except ceftriaxone
Well tolerated –Rash/hypersensitivity lFew drug interactions
Cefazolin
IV only
Clinical Use
–Routine peri-operative prophylaxis –Alternative to nafcillin/oxacillin for serious MSSA infection
–Bone & joint infections, endocarditis, respiratory tract infections, skin/skin structure infections (SSSI), urinary tract infections (UTI)
Cephalexin
PO only
Clinical Use
–Alternative to dicloxacillin for uncomplicated MSSA/streptococcal infection ® usually SSSI
–Uncomplicated UTI
–Respiratory tract infection/otitis media
-Requires four times daily dosing in normal renal function
Ceftriaxone
IV only –Once daily dosing
–No adjustment in renal insufficiency
Clinical use (many)
–Bone & joint infection
–Community-acquired pneumonia (CAP)
–Endocarditis
–Gonorrhea/pelvic inflammatory disease
–Meningitis/CNS infection ® must use 2g Q12H
–SSSI
–UTI/pyelonephritis
Carbapenems & Monobactams
lImipenem, meropenem, ertapenem, aztreonam
Carbapenems
MOA:  Bind bacterial peptidases - impairs cell wall construction
-Very broad spectrum
“miss”  MRSA, resistant Enterococcus faecium, resistant strains of P. aeruginosa, MRSE, Stenotrophomonas maltophilia, Burkholderia cepacia & atypicals
Uses:  –Proven efficacious for variety of infxns (empiric trmt of bacteremia and sepsis, CAP & HAP, skin & soft tissue infxns, complicated UTIs, intra-abdominal infxns, Ob-Gyn infxns, osteomyelitis, neutropenic fever)
–Reserve for:  mixed, polymicrobial infxns, empiric trmt for neutropenic fever, gram (-) bacilli resistant to other b-lactam abs
Monobactams
Aztreonam
MOA:  binds transpeptidases, inhibits bacterial cell wall synthesis –Synthetic compound
–Coverage is strictly gram (-) aerobes
–ok in pcn allergic pts
Uses:  alternative for gram (-) coverage in pcn allergic pts   
Vancomycin
Glycopeptide antibiotic 
MOA:  inhibits biosynthesis of major structural polymer of the bacterial cell wall - peptidoglycan Activity against almost all gram (+) bacteria
Vancomycin
Uses:
–MSSA lNafcillin/oxacillin vs. vancomycin
–Beta-lactam-resistant gram positive organisms
-MRSA
Vancomycin Indication
Empiric Therapy
–Patients with evidence of a line infection (until cultures return).
–Patients with suspected gram-positive infection AND severe β-lactam allergy (immediate-type reaction)
Patients with suspected MRSA infection
Prophylaxis
–Surgical procedures involving implantation of prosthetic devices
–Surgical prophylaxis in patients with severe β-lactam allergy (immediate-type reaction)Prevention of endocarditis (AHA)
Oral vancomycin
Treatment of antibiotic-associated colitis which has failed 2 courses of metronidazole therapy or is severe and life-threatening
Poor oral bioavailability – oral drug used only for C. difficile diarrhea
Red Man Syndrome
Infusion related reactions
–Red man syndrome
non-specific release of histamine lcauses flushing upper extremity or entire body
Signs and symptoms
–Pruritis
–Erythema of the face, neck, and upper torso
–Hypotension

–Serious cases:
Angioedema
Cardiovascular collapse
Generally appears 4-10 mins after infusion
Drugs That Inhibit the Synthesis
of Bacterial Proteins
(Tetracyclines, Macrolides, Clindamycin, Aminoglycosides)
Tetracyclines
Tetracycline, doxycycline, minocycline
Spectrum: –Community-acquired respiratory pathogens: Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma, Legionella, & Chlamydia spp., penicillin-susceptible Streptococcus pneumoniae
Other bacteria . . . –CA-MRSA –H. pylori (w/ bismuth subsalicylate & metronidazole or clarithromycin)
–Propionibacterium acnes (P. acnes)
-Malaria
-Anthrax
Toxicities - Tetracycline
Binds to calcium in bone / teeth –bone growth delayed / teeth become discolored
–avoid in children up to 8 yrs and last half of pregnancy Photosensitivity –Red rash
GI –Epigastric distress and nausea (take w/ food)
Esophageal ulcerations –Fluids
Prescriber Concerns - Tetracyclines
Decreased oral bioavailability with food / antacids
–binds to calcium, magnesium, zinc
Avoid in pregnant women, children

Intravenous administered in sodium chloride to decrease phlebitis

Sunscreen for patients exposed to sunlight
Tigecycline
–Derivative of minocycline
–Inhibits protein synthesis lStable to efflux & ribosomal mechanisms
-Spectrum includes gram (+), gram (-) and anaerobes; covers MRSA and VRE
FDA indications –Complicated intra-abdominal and skin/soft tissue Adverse effects:
–Nausea and vomiting
Macrolides
Erythromycin, Azithromycin, Clarithromycin
MOA:  inhibit RNA-dependent protein synthesis by binding to 50S ribosomal subunit
–Prevents transpeptidation & translocation reactions
Generally bacteriostatic
Ok for pcn-allergic 
New macrolides (azithromycin, clarithromycin)
–Semisynthetic derivatives
–Better tissue penetration
–Greater spectrum of activity
–Better tolerability
–Qd or bid dosing
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