Antimicrobial Therapy Flashcards
Antimicrobial rules 4
- inhibit microorganisms at [ ]s that are tolerable by host–lowest possible dose
- Immunocompromised–BacterialCidal
- Narrow spectrum first or combination therapy to preserve normal flora
- Prophylactic given no more than 1 hr before incision
Prophylactic abs given in OR…how often?
single dose or up to 48hrs
-no proof that this results in emergence of resistant organisms
Abx selection
- *identify organism–essential
- efficacy depends on drug delivery to site (ex does it cross bbb)
- usually tx with single drug (but! is pt already on abx?)
- Route, Duration, Cost
- hardware
- Co-morbities (DM, immunosuppressed)
Hypersensitivity
independent of dose
Direct drug toxicity
dose related
Parturient
pregers
- most abs cross placenta and enter maternal milk
- Teratogenecity–concern with any drug
Elderly
renal impairment
decreased: plasma protein, gastric motility and acidity, liver function/mass
increase: body fat
Penicillin and (gm what and their names)
Bactericidal gram + pneumo, meningo, streptococcal Renal excretion *most common for hypersensitivity--anaphylactic, rash/fever -Ampicillin, Amoxicillin
Ampicillin
wider range of activity
Gm neg bacilli–H Flu and E coli
highest incidence of skin rash
Amoxicillin
more efficiently absorbed from the GI tract than ampicillin
PO–ear infection
Cephalosporin
Batericidal Broad spectrum Renal excretion Adverse reaction: allergic--rash --anaphylactic reaction 0.02% cross sensitivity btwn cephalosporins and PCN but only 8%
Cephalosporin classification
increased activity against bacteria as generation increase
1st: cefazolin
2nd: cefoxitin
3rd: cefotaxime
Aminoglycosides
Bactericidal gram neg Extensive renal excretion --2-3hr elimnation half time Increased 20-40 fold in RENAL FAILURE adverse reactions: -ototoxicity -nephrotoxicity -skeletal muscle weakness -prolongs neuromuscular blockade
Aminoglycosides Ototoxicity
Vestibular/auditory dysfunction
- destruction of cochlear sensory hairs
- does dependent– usually occurs with chronic therapy
Aminoglycosides Nephrotoxicity
accumulate in renal cortex-tubular necrosis
- inability to concentrate urine, proteinuria and RBC casts
- Reversible–when drug stopped
- Most nephrotoxic: NEOMYCIN– monitor BUN and creatin
Aminoglycosides Skeletal muscle weakness
- can inhibit PRE junctional release of ACH
- decreased POST synaptic sensitivity to neurotransmitter
- Myasthenia graves–uniquely sensitive to weakness
- *single dose in healthy pt not a problem
- can give Ca to help
Aminoglycosides Potentiation of neuromuscular (NM) blockade
- high plasma [ ] when given IV
- systemic absorption from lg volumes of irrigation
- Reappearance of NM blockage in PACU
- NM blocking properties of lidocaine are enhanced
- *neostigmine or Ca induced antagonism may be imcomplete or transient— monitor and use nerve stimulator
Aminoglycosides types 4
- Streptomycin & Kanamycin
- Limited uses
- Frequent occurrence of vestibular damage
- Gentamicin
- Broader spectrum
- Toxic level – (> 9mcg/ml)
- Amikacin
- Derivative of kanamycin
- Neomycin
- Adjunct therapy to hepatic coma
Tetracycline
bacteriostatic Tx-acne Excreted in urine and bile Side effects: -permanent discoloration of the teeth--not given to parturients or children -phototoxicity
Tetracycline types
tetracycline-PO only
Doxycyline- IV or PO, long acting preparation
Macrolides
Erythromycin bacteriostatic or -cidal -Narrow spectrum-- mostly gram + metabolized by C-450-excreted mostly in bile -no altered dose in renal disease
Erythromycin adverse reactions
GI intolerance, sever N/V with IV infusion*most common
-Gastric emptying
QT effects-prolongs cardiac repolarization and report of torsades
-Thrombophlebitis– with prolonged IV use
Clindamycin
class: lincosamides
bacteriostatic
-similar to erythromycin, more active on anaerobes
Tx-serious infection in GI tract and female genital tract
-decrease with sever liver disease
Clindamycin side effects
- Pseudomembranous colitis– severe diarrhea
- Pre and post junctional effects at the neuromuscular junction
- -Not antagonized with anticholinesterases or calcium
- -Large doses can produce long lasting, profound neuromuscular blockade
Vancomycin
Glycopeptide derivative -bactericidal for Gram pos: -severe staph infection -streptococcal, enterococcal endocarditis -methicillin resistant staph aureus -PCN/Cephalosporin allergy Renal excretion: elimination 1/2 life is 6hrs **can be up to 9 days with renal failure puts **monitor renal--Renal dosing
Vanco tx
Cardiac procedures
Ortho with prosthetic devices
CSF and shunt related infections
Vanco dosing and adverse effects
10-15mg/kg over 60 min---1gm in 250ml Adverse effects: -rapid infusion--profound HypOtension -red man--facial and truncal erythema form histamine release -Ototoxicity/Nephrotoxicity -return of neuromuscular blockade?
Sulfonamides
bacteriostatic *inhibit microbial synthesis of folic acid Tx- UTIs hepatic metabolism with renal excretion Adverse effects: -skin rash to anaphylaxis **increase effect of PO anticoagulants
Polymycxin B and Colistimethate
bactericidal
gram neg
Tx- UTI, infections of skin, mucous membranes, eyes and ears
Eliminated by kidneys–accumulate in renal failure
Polymycxin B and Colistimethate Side Effects
*most potent of all antimicrobials in their action at NM junction
*predominantly PRE junctional
-can produce skeletal muscle weakness resembling nondepolarizing NM blockade
-Marked potentiation of nondepolarizing neuromuscular blocking drugs
-Neostigmine or calcium do not reliably antagonize this drug induced effect at the NM junction
HIGHLY nephrotoxic
Metronidazole
Bactericidal
- Anaerobic Gm (-) bacilli
- Tx:
- CNS infections
- Abdominal and pelvic sepsis
- Pseudomembranous colitis
Fluoroquinolone
BacteriCidal broad spectrum Enteric gm neg -elimination 1.2 time 3-8hrs -can inhibit P450 enzymes -mostly renal excretion --decrease dose in renal dysfunction Tx-complicated GI and GU **Ciprofloxacin-tx of systemic infection-bone, soft tissue and resp tract
Fluoroquinolone side effects
minimal
mild GI disturbances
Rifampin
for TB bactericidal for mycovateria inhibits most Gm+ and many gm- -fat soluble--penetration of tissue including CNS -oral or IV -excreted in blie and urine
Rifampin side effects
usually infrequent
- High doses- thrombocytopenia, anemia, hepatitis, fatigue, numbness, skeletal muscle weakness
- potent inducer of C P450 system- accelerate metabolism of opioids, NM blocking agents, warfarin
Amphotericin B
antifungal
tx-yeast and fungi
Slow renal excretion
–renal function is impaired in 80% of pt treated with this drug
–most recover, some result in permanent decrease in glomerular filtration rate
–monitor plama creatinine levels
Amphotericin B side effects
- fever, chills, dyspnes, hypotension-can occur during infusion
- impaired hepatic function
- allergic reaction
- seizure
- anemia
- thrombocytopenia
Viruses
-intracellur parasites, can’t reproduce outside of host cell
-composed of a nucleic acid core surrounded by a protein containing outer coat
-genome either DNA or RNA, never both-classified on this basis-use many biochemical mechanisms of host cell
*development of antiviral is difficult
Vaccines are the alternative
-hep A and B
-HPV
-herpes zoster
Antivirals (6)
- *Acyclovir and Valacyclovir
- limited to Tx of herpes viruses
- excreted by kidney
- *Vidarabine
- cytomegalic inclusion disease
- herpes simplex encephalitis
- mutagenic and carcinogenic
- Famciclovir
- acute herpes zoster
- Ganciclovir
- Cytomegalovirus disease
- hematologic toxicity
- Amantadine
- influenza A virus/ parkinsons
- renal excretion
interferons
- glycoproteins produced in response to viral infections
- bind to receptors on host cell membranes and induce the production of enzymes that inhibit viral replication
- -degradation of viral mRNA
- enhances tumoricidal activities of macrophages
- Chronic hep B
- hepatitis C
- Nasal sprays
interferons side effects
flu like symptoms hematologic toxicity depression, irritability decreased mental concentration development of autoummune conitions rashes, slopecia changes in CV, thyroid, hepatic functions
Antivirals for AIDS
NUcleoside reverse transcriptase inhibitors (NRTI)
–imposter
Nonnucleoside revers transcriptase inhibitors (NNRTI)
–inhibit function of enzyme used by virus
Protease inhibitors
–Bind to HIV protease
*combination therapy
Antivirals for AIDS side effects
Many and varied:
- Pancreatitis, hepatotoxicity , lactic acidosis, fat redistribution, increases in serum cholesterol and triglycerides, hypersensitivity
- *Proteaseinhibitor
- Most all inhibit CP450 system
- Ritonavir most potent inhibitor
- Large plasma increases of many drugs including analgesics, lidocaine, antimicrobials, anticonvulsants, anticoagulants, antiemetics, calcium channel
