Antimicrobials Flashcards
goals/general rules of antimicrobials
- inhibit microorganisms at concentrations that are tolerated by the host
- seriously ill/immunocompromised select bactericidal
- narrow spectrum before broad spectrum (or a combination therapy to preserve normal flora)
roles of antimicrobials in anesthesia practice
- prophylaxis before surgery (at least 1 hour before incision)
- potential for adverse reactions (hypersensitivity, direct organ toxicity, super-infections, ID patients at risk for complications)
- cross-reactions with other meds we give
SSI
surgical site infections; infection related to an operative procedure that occurs at or near the surgical incision within 30 days of the procedure
SSI facts
- second most common healthcare associated infection
- develop in 2-5% of 30 million surgical patients
- represent 14-16% of all hospital acquired infections annually in the US
- cost 1 billion dollars/year
- account for 3% of surgical mortality
SSIs lead to
- increased re-admissions
- increased LOS in hospital (7-10 days)
- increased hospital costs (additional $3000-29,000 per SSI diagnosis
Signs indicative of SSI
- purulent drainage from surgical site
- positive culture obtained from surgical site that was closed initially
- surgeon diagnoses infection
- surgical site that requires reopening due to at least one of the following s/s –> tenderness, swelling, redness or heat
surgical risk for SSI
- procedure type
- skill of surgeon (longer it takes, the greater the chance for infection)
- use of foreign material or implantable device
- degree of tissue trauma
patient risks for SSI
- diabetes
- smoking
- obesity
- malnutrition (not enough protein to support healing)
- systemic steroid use
- immunosuppressive therapy
- intra op hypothermia (slows BMR, constricts blood vessels, and makes blood more viscous –> shift of oxy hgb curve to left)
- trauma
- prosthetic heart valves
SSI prevention
- timely and appropriate use of antibiotics
- maintenance of normothermia
- proper syringe/med administration practices
SCIP
Surgical Care Improvement Project
Antibiotic timing
- abx prophylaxis 1 hour before incision had the lowest rate of SSI
- 30-60 min before incision is ideal window for drug admin
normothermia
hypothermia associated with adverse outcomes like…
- increased blood loss
- increased transfusion requirements
- prolonged PACU stay
- post-op pain
- impaired immune function
- compromised neutrophil function –> vasoconstriction –> tissue hypoxia + increased incidence of SSI
bactericidal
if they kill the susceptible bacteria
- more common
- what we use in the OR
bacteriostatic
if they reversibly inhibit the growth of bacteria; for this type of abx, the duration of therapy must be sufficient to allow cellular and humoral defense mechanisms to eradicate the bacteria
list of bactericidal abx
- penicillins
- cephalosporins
- isoniazid
- metronidazole
- polymyxins
- rifampin
- vancomycin
- aminoglycosides
- bacitracin
- quinolones
list of bacteriostatic abx
- chloramphenicol
- clindamycin
- macrolides
- sulfonamides
- tetracyclines
- trimethoprim
Penicillin Structure
dicyclic nucleus that consists of a thiazolidine ring connected to a b-lactam ring
penicillin MOA
bactericidal; interferes with the synthesis of peptidoglycan which is an essential component to cell walls of susceptible bacteria
peptidoglycan
glycolic membrane of bacterial cell wall
penicillin effective against
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
penicillin excretion
- renal excretion
- rapid plasma concentration decreases 50% in 1st hour
- 10% glomerular filtration
- 90% renal tubular secretion
- anuria increases elimination half time by 10 fold
penicillin DOA
-administration of probenecid (med used for gout) will reduce renal excretion and prolong action
penicillin adverse reactions
- hypersensitivity (most allergenic of antimicrobials; up to 10% of population allergic)
- rash and/or fever
- hemolytic anemia
- maculopapular rash (delayed)
- immediate sensitivity - anaphylaxis
- cross-sensitivity common with all penicillin drugs and cephalosporins (3%) due to common beta-lactam ring
penicillin uses
- otitis media
- peritonitis
- meningitis
- sore throat
- pneumonia & respiratory infections
- septicemia
- gonorrhea UTIs
penicillin routes
- oral
- IV
penicillin known issues
- resistance (beta-lactamase, and other mechanisms)
- allergic rxns
- cross-hypersensitivity (1-3% with cephalosporins)
second generation penicillin
- amoxicillin
- ampicillin
- have a wider range of activity than first generation penicillins
- gram negative bacilli –> haemophilus influenza
- e coli
type of cephalosporin
cefazolin
cephalosporin facts
- MOA - bactericidal antimicrobial that inhibits bacterial cell wall synthesis and have low toxicity
- broad spectrum
- SE - low incidence of allergic rxns
- cross reactivity with other cephalosporins
- penicillin and cephalosporin allergy 3-5%
- renal excretion
1st generation cephalosporin
cephazolin coverage: -gram negative + -strep pneumoniae +++ -gram positives +++
2nd generation cephalosporin
cefuroxime coverage: -gram negative ++ -strep pneumoniae ++ -gram positives ++
3rd generation cephalosporin
cefetaxime coverage: -gram negative +++ -strep pneumoniae +++ -gram positives +
4th generation cephalosporin
cefepime coverage: -gram negative +++ -strep pneumoniae +++ -gram positives ++
which cephalosporins achieve therapeutic levels in CSF
- 3rd generation
- makes it a good option for meningitis
- lower toxicity than earlier generations
macrolides structure
compounds characterized by a macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached
type of macrolide
- erythromycin
- azithromycin
macrolides effective against
- gram positive bacilli
- pneumococci
- streptococci
- staphylococci
- mycoplasma
- chlamydia
macrolide routes
- oral
- IV
macrolide uses
- Upper respiratory tract (pharyngitis, tonsillitis, sore throat)
- otitis media
- lower respiratory tract infections (pneumonia, MAC, Legionnaire’s, anthrax)
- ulcers (h. pylori)
- uncomplicated skin infections (staph)
- STDs (chancroid disease in men, chlamydia, gonorrhea)
macrolide MOA
- bacteriostatic
- binds to 50S and blocks translocation step in protein synthesis
macrolide pharmacokinetics
- azithro half life = 3 days
- a 1 gram dose provides 7 day coverage
- common therapy consists of 500 mg loading dose and 250 mg/day for 4 more days
macrolide adverse effects
- N/V, diarrhea
- abdominal pain
- liver toxicity (estolate related)
- erythromycin inhibits P-450 (drug interactions) & increases QTc
erythromycin MOA
- bacteriostatic or bactericidal depending on organism and dose
- inhibits bacterial protein synthesis
erythromycin PK/PD
- metabolized by CYP-450 system and thus increases serum concentration of theophylline, warfarin, cyclosporine, methylprednisone, and digoxin
- excreted mostly in bile
- no need to alter dose in renal disease
erythromycin side effects
- GI intolerance (most common SE)
- severe N/V with IV infusion
- increased gastric emptying time
- cholestasic hepatitis
- QT effects (prolongs cardiac repolarization and reports of torsades)
- thrombophlebitis - common with prolonged IV use
clindamycin class
-linomycin
clindamycin MOA
- bacteriostatic
- similar to erythromycin in antimicrobial activity
- binds to 50S and inhibits peptidyl transferase and translocation
clindamycin effective against
-more active with anaerobes
clindamycin dosing
- 10% of administered dose excreted unchanged in urine, rest is inactive
- decrease dose with severe liver disease
clindamycin use
- most commonly used in female GU surgery
- severe complications (GI) limit its use to infections that are difficult to treat
- oral infections
- lung abscess
- aspiration pneumonia
- necrotizing fasciitis
- MRSA
clindamycin side effects
- skin rash
- prolonged pre and post junction effects at NMJ in the absences of NDMR (prolonged NMB/muscle weakness)
- not antagonized with anticholinesterases or calcium - concurrent admin with NDMR can produce long lasting, profound NMB
- N/V, diarrhea
- fever, rash
- C. Diff enterocolitis (~6%)
- pseudomembranous colitis –> severe diarrhea should indicate discontinuation of therapy
clindamycin PK/PD
- half life = 2.5 hours
- penetrates most tissues including abscesses
- does not penetrate into CNS or intracellular
- hepatic metabolism, no dosage adjustment with renal failure
vancomycin MOA
- bacteriocidal
- impairs cell wall synthesis
vancomycin effective against
- gram positive bacteria
- streptococcal, enterococcal endocarditis
- DOC for MRSA
- penicillin/cephalosporin allergy
- administered with aminoglycoside for endocarditis
vancomycin PK/PD
- renal excretion 90% unchanged in urine
- renal excretion by glomerular filtration
- elimination 1/2 time is 6 hours and can be prolonged (up to 9 days) with renal failure
- very poor absorption on oral administration
- slow CSF penetration unless meningeal inflammation
vancomycin dose
- 10-15 mg/kg over 60 min (to prevent histamine release)
- 1 gram mixed in 250 mL
vancomycin adverse effects
- rapid infusion associated with profound hypotension due to histamine release
- red man syndrome - intense facial and truncal erythema from histamine release; usually occurs if given in less than 30 min
- maculopapular skin rash
- ototoxicity (when concentration >30 mcg/mL)
- nephrotoxicity (RARE unless concomitant tx with other nephrotoxic drugs)
- return of neuromuscular blockade
- phlebosclerotic (irritating to tissues)
vancomycin indications
- cardiac/ortho procedures using prosthetic devices
- CSF and shunt related infections
- MRSA
- endocarditis due to strep viridans or enterococci
- patients allergic to beta lactams
- use typically reserved for bacterial infections resistant to other abx or patients with severe hypersensitivity to other abx
vancomycin red mans treatment
-administration of 1 mg/kg diphenhydramine and 4 mg/kg cimetidine 1 hour before administration limits histamine release
aminoglycosides
- streptomycin and kanamycin
- gentamicin
- amikacin
- neomycin
streptomycin and kanamycin
- limited uses
- frequent occurrence of vestibular damage
gentamicin
- broader spectrum
- toxic level = >9mcg/mL
- used frequently in GU surgery
amikacin
- a BIG GUN
- derivative of kanamycin
- treatment for infections caused by gentamicin or tobramycin resistant gram negative bacilli
neomycin
- treatment for skin, eye, mucous membrane infections
- adjunct therapy to hepatic coma
- administered to decrease bacteria in intestine before GI surgery
- MOST nephrotoxic of aminoglycosides
- can be used for irrigation
aminoglycosides MOA
- bactericidal
- effective for aerobic gram negative and positive bacteria
- mycobacterium tuberculosis
- irreversible inhibition of protein synthesis (30S)
aminoglycosides PK/PD
- extensive renal excretion through glomerular filtration
- 2-3 hour elimination half time that is increased 20-40 fold with renal failure
aminoglycosides adverse effects
- limited by toxicity
- ototoxicity
- nephrotoxicity
- skeletal muscle weakness
- potentiation of NDMR blockade
- muscle weakness - inhibit pre-junctional release of ACh and decrease postsynaptic sensitivity to neurotransmitter (impact on pt with neuromuscular pathology like myasthenia gravis)
treatment of aminoglycoside potentiation of NDMR blockade
- can potentiate non-depolarizing neuromuscular blocking drugs
- paralysis usually reversible with calcium gluconate or neostigmine
- effect may not be sustained
fluroquinolones
- ciprofloxacin
- moxifloxacin
ciprofloxacin
-treatment for respiratory infections, TB, anthrax
moxifloxacin
- suitable for long acting treatment of acute sinusitis, bronchitis, complicated abdominal infections
- QT prolongation
- peripheral neuropathy
- psychosis
- stevens-johnson syndrome
- achillies tendon rupture
fluroquinolones MOA
- bactericidal
- inhibits DNA gyrase and topoisomerase IV
fluroquinolones uses
- effective for enteric gram negative bacilli and mycobacterium
- treatment of complicated GI and GU infections
- cipro - variety of systemic infections like bone, soft tissue, and respiratory tract
fluroquinolones PK/PD
- GI absorption rapid and penetration to body fluids and tissues is excellent
- renal excretion through glomerular filtration and renal tubular secretion
- decrease dose in renal dysfunction
- elimination 1/2 time is 3-8 hours
- can inhibit CYP 450 enzymes
fluroquinolones adverse effects
- mild GI disturbances
- N/V
- CNS dizziness, insomnia
- tendon or achilles rupture
- muscle weakness in patients with myasthenia gravis
sulfonamides
- sulfamethoxazole
- trimethoprim
sulfonamides MOA
- bacteriostatic
- antimicrobial activity due to the ability of these drugs to prevent the normal use of PABA by bacteria and to synthesize folic acid (only work against those bacteria that use folic acid)
- inhibit microbial synthesis of folate production
sulfonamides PK/PD
- portion of drug acetylated in liver and other is renal excretion
- renal disease reduce dose
sulfonamides clinical uses
- portion of drug acetylated in liver and other is renal excretion
- renal disease reduce dose
sulfonamides adverse effects
-skin rash to anaphylaxis
-photosensitivity
-allergic nephritis
-drug fever
-hepatotoxicity
-acute hemolytic anemia
-thrombocyotopenia
increase effect of PO anticoagulant
Metronidazole (flagyl) MOA
- bactericidal
- anaerobic gram negative bacilli clostridium
Metronidazole (flagyl) clinical uses
- CNS infections
- abdominal/pelvic sepsis
- pseudomembranous colitis (C. diff) –> in combo with vanc is treatment
- endocarditis
- recommended for pre-op prophylaxis for colorectal surgery
Metronidazole (flagyl) PK/PD
-well absorbed orally and widely distributed in tissue including CNS
Metronidazole (flagyl) side effects
- dry mouth
- metallic taste
- nausea
- avoid alcohol
antimycobacterial agents 1st line
- TB drugs that include…
- rifampin
- ethambutol
- pyrazinamide
- isoniazid
- these are used in combination therapy (3-4 agents) for 2 months followed by a minimum of 4 months of therapy with 2 agents
rifampin
- bacteriocidal
- hepatic enzyme induction
- hepato-renal toxicity, thrombocytopenia, anemia
ethambutol
- bacteriostatic
- optic neuritis
pyrazinamide
- bacteriostatic
- liver toxicity
isoniazid
- bacteriostatic
- can be bacteriocidal if the bacteria are actively dividing
- hepato-renal toxicity
antimycobacterial agents 1st line MOA
-distributed through tissues, CSF
antifungals
-example is amphotericin B
antifungal use
- yeast infection
- fungal infection
antifungal PK/PD
- poor PO absorption, given IV
- slow renal excretion
- renal toxic –> renal function is impaired in 80% of patients treated with this drug; most recover after drug stopped, but there can be some permanent decrease in glomerular filtration
- monitor plasma Cr levels
antifungals adverse effects
- fever, chills, dyspnea
- hypotension can occur during infusion
- impaired hepatic function
- hypokalemia
- allergic reactions
- seizure
- anemia
- thrombocytopenia
antiviral drugs
- virus = obligate intracellular parasite
- difficult to kill virus and not the host cell
- some cell surface receptors are unique for viruses and this gives a location for potential drug therapy
acyclovir
- treat herpes
- may cause renal damage if infused rapidly
- thrombophlebitis
- patient may c/o HA during IV infusion
interferons
- term used to designate glycoproteins produced in response to viral infections
- bind to receptors on host cell membranes and induce the production of enzymes that inhibit viral replication, degrade viral mRNA
- enhance tumoricidal activities of macrophages
interferons use
- treatment for chronic hepatitis B and C
- nasal sprays
interferons SE
- flu like symptoms
- hematologic toxicity
- depression, irritability
- decreased mental concentration
- development of autoimmune conditions
- rashes, alopecia
- changes in CV, thyroid, hepatic function
- VERY difficult treatment
antiretroviral drugs
-drugs that have led diseases like HIV to become a chronic condition
classes of antiretroviral drugs
- nucleoside/non nucleotide reverse transcriptase inhibitors (NRTIs and NNRTIs like Delavirdine)
- protease inhibitors (PI’s like Ritonavir)
- fusion inhibitors (enfuvirtide)
- CCR5 receptor antagonists
- integrase inhibitors (Lamivudine)
treatment regimen for HIV
usually includes triple therapy, so 3 different antiretroviral drugs
antiretroviral anesthetic implications
- existence of adverse effects (liver toxicity, peripheral neuropathy, nephrotoxicity, neuromuscular weakness)
- interactions with other medications (PPIs, cimetidine, NDMR, opioids, benzos)
