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81 Cards in this Set
- Front
- Back
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Vancomycin MOA
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Inhibits cell wall synthesis by binding to D-Ala-D-Ala end of peptidoglycan pentapeptide; prevents elongation of peptidoglycan
Bactericidal Acts step earlier than PCNs; no cross-resistance |
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Vancomycin Resistance
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VRE - vancomycin resistant enterococcus -- terminal D-Ala replaced by D-lactate
Staph aureus: VISA and VRSA VISA may be d/t thicker cell wall, VRSA similar gene to enterococci |
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Vancomycin route of admin
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IV only! except for treatment of C. difficile colitis
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Vancomycin Clinical Use
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MRSA - drug of choice!
Meningitis caused by PCN-resistant penumococci (+ ceftriaxone) Surgical prophylaxis in PCN-allergic (can't take cefazolin) gram + multi-drug resistant organisms |
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Vancomycin Toxicity
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Well tolerated in general
Nephrotoxicity Ototoxicity Phlebitis "Red Man" syndrome - infusion related - prevent by giving it slower rash - rare |
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Vancomycin elimination
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90% glomerular filtration
accumulates in renal insuffiency |
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Vancomycin therapeutic monitoring
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Time dependent killing- above MBC
want trough level to exceed the MIC (usually ~4ug/ml), so 5-15ug/ml and up to 20ug/ml for meningitis and ICU pneumonia |
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Drug of choice for MRSA
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Vancomycin
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Drug to use for PCN-allergic patient requiring broad-spectrum gram-negative coverage for nosocomial infection (sepsis, pneumonia, febrile neutropenia, etc)
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Aztreonam (Monobactam)
IV ONLY! |
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1st line therapy for extended spectrum beta-lactamase producing E coli and Klebsiella
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Carbapenems:
Ertapenem for community acquired, known E coli, Klebsiella ESBL Nosocomial infection: Imipenem, Meropenem, Doripenem Risk for seizures - no imipenem! |
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2nd most common cause of meningitis in adults
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Neisseria meningitidis
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gram negative diplococci
Thayer-Martin media Oxidase positive Ferments glucose, NOT maltose |
Neisseria gonorrhoeae
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gram negative diplococci
oxidase positive ferments glucose and maltose |
Neisseria meningitidis
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Disseminated Gonococcal Infection (DGI)
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pustular rash
arthritis tenosynovitis (tendon - usually in foot) |
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neisseria gonorrhoeae virulence factors
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Pili - attachment to mucosal surfaces and antiphagocytic
IgA protease outer membrane proteins endotoxin LOS (lipooligosaccharide) |
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Neisseria gonorrhoeae Clinical Disease
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Urethritis
Cervicitis Proctitis Pharyngitis Pelvic Inflammatory Disease Ophthalmia neonatorum (purulent conjunctivitis) |
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Treatment of gonorrhea
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Cephalosporins:
IM Ceftriaxone (single dose) or Oral Cefixime -penicillinase so can't use PCNs -NOT quinolones - new recommendation d/t resistance |
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Patients w/o a spleen - worry about these three bacteria: (and why?)
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Neisseria meningiditis
H. influenza strep pneumo -- encapsulated bacteria |
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Macrolides MOA
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Bind 50S and blocks translocation from acceptor site to peptidyl site (donor site)
Bacteriostatic |
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Tetracyclines MOA
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Bind to 30S and prevent attachment of aminoacyl-tRNA
Bacteriostatic limited CNS penetration |
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Chloramphenicol MOA
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Inhibits 50S peptidyltransferase activity
Bacteriostatic |
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Clindamycin MOA
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Blocks peptide bond formation at 50S subunit
Bacteriostatic |
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Aminoglycosides MOA
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Bactericidal
Inhibit formation of intiation complex and cause misreading of mRNA |
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Pneumocystis pneumonia (PCP)
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TMP-SMX
Sulfamethoxazole-Trimethoprim |
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Are antifolates active against pseudomonas?
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NO
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Indications for TMP-SMX (Trimethoprim/Sulfamethoxazole)
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PCP (Pneumocystis pneumonia) - prophylaxis & treatment
UTIs (active against E coli) Nocardia, Chlamydia (atypicals) community acquired MRSA infectious diarrhea (salmonella, shigella) - comm. acquired Gm - |
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Trimethoprim & Pyrimethamine MOA
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Antifolate (2nd step of folic acid synthesis)
inhibits dihydrofolate reductase trimethoprim - bacterial pyrimethamine - protozoa |
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Sulfamethoxazole MOA
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Anti-folate
structural analog of PABA competitive inhibitor of dihydropteroate synthase |
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Pyrimethamine indications
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Toxoplasmosis
Malaria |
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Sulfadiazine
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antifolate
burn wounds (silver ointment, topical) toxoplasmosis (w pyramethamine) |
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Sulfadoxine
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antifolate
2nd line malarial agent |
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Sulfasalazine
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antifolate - oral, nonabsorbable
for local effect in GI tract ulcerative colitis, inflammatory bowel disease (have antiinflammatory effects) |
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Sulfonamides spectrum of activity
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Broad: Gm +, Gm-, protozoa, atypicals (nocardia, chlamydia)
NOT active against pseudomonas |
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Sulfamethoxazole Adverse Effects
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Hemolytic effects "dropping their counts": anemia, granulocytopenia, thrombocytopenia
** higher risk in G6PD deficiency also: GI effects, hypoglycemia, renal tubular acidosis Hypersensitivity reactions (rash is most common, IgE mediated Idiosyncratic: hepatitis, Stevens-Johnson 60% of HIV patients experience adverse effects!! |
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Sulfamethoxazole - Resistance
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Overproduction of PABA!!
loss of permeability mutation in dihyropteroate synthetase |
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Trimethoprim Adverse Effects
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Megaloblastic anemia, leukopenia, granulocytopenia
-folinic acid for prophylaxis |
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Fluoroquinolones (names)
MOA, quick facts |
"floxacin"s: Oral + IV
Cipro, Levo, Moxi Gemi - oral only MOA: inhibit DNA gyrase and topoisomerase IV good bioavailability and distribution -- including BONE!! multiple dosage forms resistance develops quickly Concentration Dependent Killing |
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Fluoroquinolones - Resistance
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Efflux pumps!
changes in permeability mutation in target enzyme |
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Fluoroquinolones - Adverse Effects
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Damage to growing cartilage -- not recommended for kids!!
Tendonitis Cipro - seizures (esp w theophylline) Moxi - QTc prolongation |
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Ciprofloxacin
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Gm -
including pseudomonas |
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Levofloxacin
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Gm - (including pseudomonas at high concentrations)
some Gm +, including strep pneumoniae |
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Moxifloxacin
Gemfloxacin |
improved Gm + activity esp. Strep pneumonaie
no pseudomonas, less Gm - moxi - staph & some anaerobic gem - oral only |
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what impairs bioavailability of fluoroquinolones?
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divalent cations (ie Antacids!) separate by 2hrs
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Elimination of fluoroquinones
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Renal
except moxi!! Can't use for UTIs!! |
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Community acquired pneumonia (strep) - possible fluroquinones
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Levo
Moxi Gem (oral only) |
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UTIs involving pseudomonas
(fluoroquinones) |
Cipro
Levo |
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Intra-abdominal infections
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Moxiflox - has anaerobic activity
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Multi-drug resistant TB
(fluoroquinolone) |
Cipro
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Nosocomial pneumonia
(fluoroquinolone) |
Cipro
Levo |
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Gastroenteritis
(shigella, salmonella, E coli, campylobacter) |
Cipro
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Penicillins
MOA |
structural analogs of substrate of PBPs
Inhibits transpeptidases (PBP) that cross-link peptidoglycans CIDAL - on dividing bacteria Time dependent killing |
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Penicillins
MO Resistance |
Beta-lactamases cleave beta-lactam ring, inactivating!! (most common, >100 different types, plasmid mediated)
Change in PBP Gm negatives: efflux pump, down regulation of porins (impaired penetration) |
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Beta lactam ring
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essential for biological activity of penicillin
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Administration of penicillins
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few acid stable, suitable for oral use
most should be separated from a meal by 1-2 hrs except amoxicillin - should be given with food IV preferred over IM oral: PCN VK, dicloxacillin/cloxacillin, ampicillin/amoxicillin |
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Tissue distribution of PCNs
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most tissues
EXCEPT: eye, prostate, CNS (unless inflammation of meninges) |
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Elimination of PCNs
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Renal
* need to adjust dose w kidney problems Exception! Nafcillin (biliary) Short half lives - short dosing intervals ie q4hrs |
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Time dependent killing
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depends on presence of sustained concentrations of active drug above the MIC of the organism
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Classification of PCNs:
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natural PCNs
penicillinase-resistant PCNs Extended spectrum: aminopenicillins, carboxypenicillins, ureidopenicillans penicillin/beta lactamase inhibitor combinations |
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PCN to use with renal impairment
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Nafcillin
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Natural Penicillins - Clinical
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Strep, Enterococci, Strep pneumoniae, anaerobes, meningococci, syphillis
susceptible to hydrolysis by beta-lactamases Penicillin G - IV Penicillin V - oral not used empirically -- narrow to endocarditis, meningitis - once know susceptibility- PCN G respiratory tract infections, soft tissue infections, syphillis - PCN V |
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Penicillinase-Resistant PCNs
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Methicillin (no longer used)
Nafcillin, oxacillin Cloxacillin, Dicloxacillin -- oral side chain sterically inhibits action of penicillinase |
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Penicillinase-Resistant PCNs
mechanism of resistance |
change in PBPs (production of a new PBP)
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Drug of choice for staph infections (MSSA)
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Nafcillin or oxacillin
"Use naf for staph" |
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Penicililinase-Resistant PCNs
Spectrum of activity |
staph and strep
resistant to staph beta-lactamases (not inactivated by them) |
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Penicililinase-Resistant PCNs
Indications |
drugs of choice for MSSA (naf and oxa)
skin and soft tissue infections remember diclox and clox are oral |
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Aminopenicillins
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Ampicillin - IV
Amoxicillin - oral inactivated by beta-lactamases able to pass through porins in Gm - cell walls |
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Aminopenicillins
Spectrum of Activity |
improved Gm - : E coli, H flu (community acquired)
enterococci, listeria anaerobes not active against: Klebsiella, pseudomonas |
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Aminopenicillins
Indications |
Drug of choice for enterococci
IV: for serious infections caused by susceptible bacteria PO: sinusitis, otitis, lower respiratory tract infections, dental prophylaxis |
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Ampicillin and Amoxicillin - which is oral, which is IV?
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Amp - IV (plug your IV into the amp)
amoxi - oral |
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Drug of choice for enterococci
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Ampicillin
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Ticarcillin
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A Carboxypenicillin
spectrum includes pseudomonas and enterobacter, no klebsiella significant adverse reactions: prolonged bleeding time d/t platelet dysfunction & hypokalemia not commonly used (holes in spectrum) Piperacillin is better! |
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Piperacillin
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Ureidopenicillin
susceptible to beta-lactamases - therefore, used in combination w/ tazobactam Spectrum: most Gm - including: Pseudomonas, Klebsiella, Enterobacteriaceae |
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Piperacillin - drug-specific reaction
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neutropenia
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Piperacillin
indications |
Serious Gm - infections:
nosocomial pneumonia, bacteremia, UTIs, osteomyelitis, soft tissue infections Used in combination with aminoglycoside for pseudomonas infection |
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Beta-lactamase inhibitors
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Clavulanic Acid
Sulbactam Tazobactam |
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Beta-lactamase inhibitors
MOA |
binds to and inactivates beta-lactamases
Binds to PBP, increasing affinity for PCN does not overcome change in PBP in MRSA |
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Beta-lactamase inhibitors extend spectrum to include:
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beta-lactamase producing staph aureus, Gm -s and bacteriodes
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PCN/ Beta-lactamase Combinations
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amoxicillin + clavulanic acid
ampicillin + sulbactam piperacillin + tazobactam |
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Amoxicillina/ Clavulanic Acid
Ampicillin/ Sulbactam |
amox is oral, amp is IV
increased activity to: MSSA, H flu, E coli, Klebsiella, bacteriodes, anaerobes |
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PCNs
Allergy |
Hypersensitivity - 3-10% of pop
anaphylactic shock, serum sickness, skin rashes d/t degradation product: penicilloic acid proportional to dose and duration cross allergenicity can desensitize with increasing doses |
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PCNs
Adverse Reactions |
Seizures - assoc w high doses in renal failure
C. difficile enterocolitis Drug specific: piperacillin - neutropenia carboxypenicilins: hypokalemica, platelet dysfunction |
