Antimicrobials Flashcards
What are the goals of administering antimicrobials?
- to inhibit growth of microorganisms but not hurting the host
- give as narrow a spectrum as possible so that the normal flora can be maintained.
- consider if the pt is seriously ill or immunocompromised
- these patients will need bacteriocidal antibiotics
what are some types of adverse reactions that can be had with antimicrobials?
- hypersensitivity reaction (dose dependent)
- direct organ toxicity (dose related)
- potential for superinfections
- cross-reactions with other medications we give
What is an SSI? How is it defined?
- An infection related to an operative procedure that occurs at or near the surgical incision within 30 days of the procedure
- purulent exudate from surgical site
- a positive culture obtained from a surgical site that was closed initially
- A surgeon’s diagnosis
- A surgical site that requires reopening due to at least one of the following:
- tenderness, swelling, redness, or heat
What specific aspects of a surgery can increase the risk of infection?
What surgeries have the highest incidence of infection?
- procedure type
- skill of surgeon
- use of foreign meterial or implantable device
- degree of tissue trauma
- highest incidence: Carotid endarterectomy, urologic, colon
What patient traits increase the risk of surgical site infection?
- DM
- smoking
- obesity
- malnutrition
- systemic steroid use
- immunosuppressive therapy
- intraoperative hypothermia
- trauma
- prosthetic heart valves
What adverse outcomes are associated with hypothermia?
- increased blood loss
- increased transfusion requirements
- prolonged PACU stay
- post-op pain
- impaired immune function
- compromised neutrophil function causing vasoconstriction and tissue hypoxia; increasing incidence of SSI
What are the appropriate antibiotics for Cardiothoracic and vascular surgery?
What if the pt has a b-lactam allergy?
- Cefazolin, cefuroxime, or vancomycin
- b-lactam allergy: vancomycin or clindamycin
What is the difference between bacteriocidal and bacteriostatic?
- Bacteriocidal: kills the susceptible bacteria
- Bacteriostatic: reversibly inhibits the growth of bacteria
- for bacteriostatic, the duration of the therapy must be long enough to allow the person’s defense mechanisms to eradicate the bacteria
What are some bacteriocidal antibiotics?
- PCNs and cephalosporins
- Isoniazid
- metronidazole
- polymyxins
- rifampin
- bacitracin
- aminoglycosides
- vancomycin
- quinolones
- PIMP-R-BAVQ (this mneumonic has been censored due to adult content)
What are some bacteriostatic antibiotics?
- Chloramphenicol
- clindamycin
- macrolides
- sulfonamides
- tetracyclines
- trimethoprim
- Cora carries more sulfur than Tim
from the list of ABX she elaborated on during lecture, “the list is SLiM”: (by default the rest she talked about are bacteriocidal)
- Sulfa
- cLindamycin
- Macrolides
What is the structure of Penicillin?
-
- dicyclic nucleus that has a thiazolidine ring connected to a B-lactam ring
Is Penicillin bacteriocidal or bacteriostatic?
MOA?
What kind of organisms can affect?
- interferes with the synthesis of peptidoglycan which is an essential component to cell walls of susceptible bacteria
- Organisms:
- pneumococcal
- meningococcal
- streptococcal
- actinomycosis
How is Penicillin excreted?
What can increase the E 1/2t?
- Rapid renal excretion; plasma concentration decreases 50% in 1st hour
- 10% is excreted through glomerular filtration
- 90% secreted by renal tube
- anuria increases elimination half time by 10x
Penicillin adverse reactions
- Most allergenic antimicrobial (up to 10%)
- rash, with or without fever
- hemolytic anemia
- maculopapular rash (delayed)
- immediate sensitivity: anaphylaxis
- cross-sensitivity common with all PCN drugs AND cephalosporins
Why is there cross sensitivity between PCN and cephalosporins?
How common is it?
Because both classes have a b-lactam ring
anywhwere from 2-8% of people with PCN allergy are also allergic to cephalosporins
What is the difference between 1st and 2nd generation PCNs?
Examples?
- The later generations are also efective on some gram- bacilli
- haemophilus influenza
- E coli
- Examples: Amoxicillan, ampicillin
If your patient is allergic to 1st generation PCN, can you give them a 2nd?
No! You should substitue it with clindamycin or vancomycin
Are cephalosporins (Cefazolin) -cidal or -static?
MOA?
- Bactericidal- inhibits bacterial cell wall synthesis and have low toxicity
Facts about Cefazolin:
spectrum of activity?
allergy incidence?
excretion?
- Broad spectrum activity
- allergy incidence is 1-10%
- anaphylaxis is 0.02%,
- PCN and cephalosporin allergy 1-3%
- Renal excretion
Which generation of cephalosporin is best for Menningitis?
- 3rd generation
- achieves therapeutic levels in the CSF and they also have lower toxicity than earlier generations
What is the structure of Macrolides?
two examples?
Which is the prototype?
- macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached
- Erythromycin, Azithromycin
- Prototype: erythromycin
Is Erythromycin -cidal or -static?
MOA?
What kinds of bacteria is it effective against?
- It can be either, depending on the type of organism they are treating
- MOA: inhibits bacterial protein synthesis
- Effective against:
- Gram + bacilli
- pneumococci
- streptococci
- staphylococci
- mycoplasma
- chlamydia
How is Erythromycin metabolized?
How might this effect other meds?
- metabolized by the CYP450 and excreted in bile
- ay increase serum concentration of theophylline, warfarin, cyclosporine, methylprednisone, and digoxin
- no need to alter dose in renal patients
What are the side effects of Erythromycin?
- GI intolerance
- promotes gastric emptying- causes cramping
- N/V
- Cholestasic hepatitis
- decreased bile secretion from hepatocytes or decreased flow of bile through ducts
- QT effects
- prolongs cardiac repolarization
- torsades de pointes
- thrombophlebitis
- common with prolonged IV use
Clindamycin
class?
-cidal or -static?
Effective against what kinds of bacteria?
- Class: Linomycins
- Bacteriostatic
- Effective against: (similar to Erythromycin)
- gram + bacilli
- pneumococci
- streptococci
- staphylococci
- mycoplasma
- chlamydia
- **more effective against anaerobes
Why is Clindamycin’s use limited to infections that are difficult to treat?
What surgeries is it most commonly used for?
- Severe GI complications
- pseudomembranous colitis (stop abx if pt has diarrhea)
- most commonly used in female GU surgeries
What are the side effects of Clindamycin?
- Severe GI complications
- skin rash
- Prolonged NMB
- prolonged pre and post junctional effects at NMJ
- these effects cannot be antagonized with anticholinesterases of calcium
Vancomycin:
structure
-cidal or -static?
MOA
- Glycopeptide derivative
- Bacteriocidal
- impairs cell wall synthesis
What kinds of infections is Vancomycin effective against?
When else would we give vanco?
- Gram + bacteria
- severe staph infections
- streptococcal, enterococcal endocarditis
- PCN/Cephalosporin allergy
- administered with aminoglycoside for endocarditis
- drug of choice for MRSA
- procedures with prosthetic devices
- CSF and shunt related infections
How is vanco eliminated?
E1/2t?
- Renal excretion 90% unchanged in the urine
- E1/2t = 6 hours
- can be prolonged (up to 9 days) in renal failure patients
What is the dose of Vanco?
- 10-15 mg/kg over 60 minutes
- 1 gram mixed in 250 ml
What are side effects of vanco?
- profound hypotension- if administered rapidly
- Red man syndrome
- ototoxicity- when concentrations >30mcg/ml; worsened with aminoglycosides
- nephrotoxicity-rare unless given with aminoglycosides
- return of Neuromuscular blockade
- phlebitis
When is the combination of vancomycin and aminoglycosides indicated?
- endocarditis caused by strep. viridans or enterococci
(combo increases risk of otoxicity and nephrotoxcity**)
Vancomycin:
excretion
Does it penetrate the CSF?
- Renal excretion by glomerular filtration (80-90% is 24 hours
- Slow CSF penetration unless there is meningeal inflammation
What are 5 Aminoglycosides?
- Streptomycin & Kanamycin
- older, not often used
- Gentamicin
- broad spectrum, used for GU procedures
- toxic > 9mcg/ml
- Amikacin (derivative of kanamycin)
- heavy hitter; used for gentamicin or tobramycin resistang gram - bacilli
- Neomycin
- for skin, eye, or mucous membrane infections
- only topical b/c most nephrotoxic
What antibiotic can be used to treat hepatic coma? How?
Neomycin- used to bring down ammonia levels
Aminoglycosides
-cidal or -static?
what kind of bacteria?
excretion
E1/2t?
- Bactericidal
- effective for aerobic gram - and + bacteria
- Extensive renal excretion through glomerular filtration
- E1/2t 2-3 hours
- increased 20-40x with renal failure
Which antibiotics potentiate NDMRs?
- Aminoglycosides
- can be reversed with neostigmine or calcium gluconate
- Clindamycin
- cannot be reversed with reversal agents or calcium
What are two fluroquinolones and what are they used to treat?
- Ciprofloxacin
- respiratory infections
- TB
- anthrax
- bone and soft tissue infections
- Moxifloxacin
- acute sinusitis
- bronchitis
- complicated abdominal infections
What are side effects of Fluoroquinolones?
- QT prolongation
- peripheral neuropathy
- psychosis
- Stevens-Johnson Syndrome
- Mild GI disturbance- N/V
- dizziness, insomnia
- tendon or achilles rupture
- muscle weakness in patients with myasthenia gravis
Fluoroquinolones:
-cidal or -static?
effective against what kind of bacteria?
- Bactericidal- broad spectrum
- effective for enteric gram - bacilli and mycobacterium
- GI/GU infections
Fluoroquinolones
Excretion
E1/2t?
- Renal excretion, through glomerular filtration and renal tubular secretion
- decrease dose in renal dysfunction
- E1/2t: 3-8 hours
- can inhibit CYP450
Sulfonamides:
-cidal or -static?
MOA?
- Bacteriostatic
- prevent normal use of PABA by bacteria to synthesize folic acid
Sulfonamides:
clinical use
elimination
- Clinical uses:
- UTI
- inflammatory bowel disease
- burns
- Elimination: portion of drug is acetylated in the liver and other is renally excreted
- reduce dose in renal dysfunction
Sulfonamides Side effects
- skin rash
- anaphylaxis
- photosensitivity
- allergic nephritis
- drug fever
- hepatotoxicity
- acute hemolytic anemia
- thrombocytopenia
- increased effect of PO anticoagulant
Metronidazole
-cidal or -static?
types of bacteria
Clinical use
- Bactericidal
- Anaerobic gram - bacilli clostridium
- Useful in many infections
- CNS infections
- abdominal and pelvic sepsis
- C-diff (with vanco)
- endocarditis
- pre-op prophylaxis for colorectoal surgery
Metronidazole
administration
side effects
- PO or IV
- well absorbed orally and widely distributed in tissue including CNS
- Side effects
- dry mouth
- metallic taste
- nausea
- avoid alcohol
What are the 1st line antimycobacterial agents?
- Isoniazid- bacteriostatic, -cidal if bacteria are dividing
- hepato-renal toxicity
- Rifampin- bacteriocidal
- Induces CYP450
- hepato-renal toxicity, thrombocytopenia, anemia
- Ethambutol- bacteriostatic
- optic neuritis
- Pyrazinamide- bacteriostatic
- liver toxicity
Amphotericin B
Use
elimination
- Given for yeasts and fungi
- slow renal excretion
- renal function is impaired in 80% of pts
- most recover, some have permanent decrease in GFR
Amphotericin B
Side effects
- fever, chills, dyspnea, hypotension during infusion
- impaired hepatic function
- hypokalemia
- allergic reactions
- seizure
- anemia
- thrombocytopenia
Acyclovir
uses
side effects
- used to treat herpes
- may cause renal damage if infused rapidly
- thrombophlebitis
- HA during infusion
What are interferons?
What are they used for?
- glycoproteins produced in response to viral infections
- bind to receptors on host cell membranes and induce the production of enzymes that inhibit viral replication
- enhance tumoricidal activities of macrophages
- used to treat Hep B & C
Interferon side effects
- flu like symptoms
- hematologic toxicity
- depression/irritability
- decreased mental concentration
- development of autoimmune conditions
- rashes
- alopecia
- changes in CV, thyroid, hepatic function
What anesthesia interactions can you expect with Nucleoside reverse transcriptase inhibitors?
Other Side effects?
- Can change drug clearance and effect of methadone
- Nausea, diarrhea, myalgia, increase LFTs, peripheral neuopathy, marrow suppression, inhibition of CYP450
What anesthesia interactions can you expect with Non-nucleoside reverse transcriptase inhibitors?
Other side effects?
- extends the half life and effects of:
- midazolam, diazepam, triazolam
- fentanyl, meperidine, methadone
- Nevirapine- induces CYP450
- Delavirdine- inhibition of CYP450- decreased fentanyl clearance by about 67%
What anesthesia interactions can you expect with Rotanavir (protease inhibitors)?
Other side effects?
- Prolongs the half life and effects of:
- amiodarone, digoxin
- diazepam, midazolam, triazolam
- fentanyl, meperidine, methandone
- inhibits CYP450
- hyperlipidemia, glucose intolerance, abnormal fat distribution
What anesthesia interactions can you expect with integrase strand transfer inhibitors?
none
What kind of anesthesia interactions can you expect with early inhibitors?
- changes clearance and effect of midazolam
Which antimicrobials are safe in pregnancy?
- PCNs
- cephalosporins
- erythromycin
Why must dosing for elderly be carefully considered?
- renal impairment- decreased GFR
- decreased plasma protein (mostly albumin)
- reduced gastric motility and acidity
- increased total body fat
- decreased hepatil blood flow
Which antimicrobials must you use with caution during pregnancy?
contraindicated?
- Caution:
- aminoglycosides (ototoxicity in mom and baby)
- clindamycin (colitis in mom)
- contraindicated:
- tetracyclines (tooth discoloration in baby)
Which antimicrobials are safe in the elderly if creatinine level is normal?
Which should you use caution with?
- safe:
- PCNs
- cephalosporins
- caution:
- aminoglycosides and vancomycin
Clindamycin pharmacokinetics
- E1/2t = 2.5 hours
- penetrates most tissues and abcesses
- does NOT penetrate into CNS or intracellular
- hepatic metabolism, no dose adjustment for renal failure
Aminoglycoside pharmacokinetics
- VD = 25% of body weight
- adjust maintenance dosing based upon creatinine
- plasma monitoring necessary
Which antimicrobials are CYP450 inhibitors?
Sulfonamides
Erythromycin
Fluroquinolones
Which antimicrobials cause muscle weakness?
Ciprofloxacin
Clindamycin
(moxifloxacin causes peripheral neuropathy)
Which antimicrobials will you decrease your dose for if the pt has renal disease?
Sulfonamides
Fluroquinolones
Vanc
PCN
cephalosporins
aminoglycosides
Which antimicrobials increase QT interval?
moxifloxacin
macroglides
Which surgeries require cefazolin + Metronidazole?
Head and neck ( with entry into orpharynx)
Colorectal (emergency surgery or obstruction)
Appendectomy
