1
Q
What are the goals of administering antimicrobials?
A
- 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
2
Q
what are some types of adverse reactions that can be had with antimicrobials?
A
- hypersensitivity reaction (dose dependent)* direct organ toxicity (dose related)* potential for superinfections* cross-reactions with other medications we give
3
Q
What is an SSI? How is it defined?
A
- 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
4
Q
What specific aspects of a surgery can increase the risk of infection?What surgeries have the highest incidence of infection?
A
- procedure type* skill of surgeon* use of foreign meterial or implantable device* degree of tissue trauma* highest incidence: Carotid endarterectomy, urologic, colon
5
Q
What patient traits increase the risk of surgical site infection?
A
- DM* smoking* obesity* malnutrition* systemic steroid use* immunosuppressive therapy* intraoperative hypothermia* trauma* prosthetic heart valves
6
Q
What adverse outcomes are associated with hypothermia?
A
- 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
7
Q
What are the appropriate antibiotics for Cardiothoracic and vascular surgery?What if the pt has a b-lactam allergy?
A
- Cefazolin, cefuroxime, or vancomycin* b-lactam allergy: vancomycin or clindamycin
8
Q
What is the difference between bacteriocidal and bacteriostatic?
A
- 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
9
Q
What are some bacteriocidal antibiotics?
A
- PCNs and cephalosporins* Isoniazid* metronidazole* polymyxins* rifampin* bacitracin* aminoglycosides* vancomycin* quinolones* PIMP-R-BAVQ (this mneumonic has been censored due to adult content)
10
Q
What are some bacteriostatic antibiotics?
A
- 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
11
Q
What is the structure of Penicillin?-
A
- dicyclic nucleus that has a thiazolidine ring connected to a B-lactam ring
12
Q
Is Penicillin bacteriocidal or bacteriostatic?MOA?What kind of organisms can affect?
A
- interferes with the synthesis of peptidoglycan which is an essential component to cell walls of susceptible bacteria* Organisms: * pneumococcal * meningococcal * streptococcal * actinomycosis
13
Q
How is Penicillin excreted?What can increase the E 1/2t?
A
- 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
14
Q
Penicillin adverse reactions
A
- 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
15
Q
Why is there cross sensitivity between PCN and cephalosporins?How common is it?
A
Because both classes have a b-lactam ringanywhwere from 2-8% of people with PCN allergy are also allergic to cephalosporins
16
Q
What is the difference between 1st and 2nd generation PCNs?Examples?
A
- The later generations are also efective on some gram- bacilli * haemophilus influenza * E coli* Examples: Amoxicillan, ampicillin
17
Q
If your patient is allergic to 1st generation PCN, can you give them a 2nd?
A
No! You should substitue it with clindamycin or vancomycin
18
Q
Are cephalosporins (Cefazolin) -cidal or -static?MOA?
A
- Bactericidal- inhibits bacterial cell wall synthesis and have low toxicity
19
Q
Facts about Cefazolin:spectrum of activity?allergy incidence?excretion?
A
- Broad spectrum activity* allergy incidence is 1-10% * anaphylaxis is 0.02%, * PCN and cephalosporin allergy 1-3%* Renal excretion
20
Q
Which generation of cephalosporin is best for Menningitis?
A
- 3rd generation* achieves therapeutic levels in the CSF and they also have lower toxicity than earlier generations
21
Q
What is the structure of Macrolides?two examples?Which is the prototype?
A
- macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached* Erythromycin, Azithromycin* Prototype: erythromycin
22
Q
Is Erythromycin -cidal or -static?MOA?What kinds of bacteria is it effective against?
A
- 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
23
Q
How is Erythromycin metabolized?How might this effect other meds?
A
- 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
24
Q
What are the side effects of Erythromycin?
A
- 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
25
Clindamycinclass?-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
26
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
27
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
28
Vancomycin:structure-cidal or -static?MOA
* Glycopeptide derivative* Bacteriocidal* impairs cell wall synthesis
29
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
30
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
31
What is the dose of Vanco?
* 10-15 mg/kg over 60 minutes* 1 gram mixed in 250 ml
32
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
33
When is the combination of vancomycin and aminoglycosides indicated?
* endocarditis caused by strep. viridans or enterococci(combo increases risk of otoxicity and nephrotoxcity\*\*)
34
Vancomycin:excretionDoes it penetrate the CSF?
* Renal excretion by glomerular filtration (80-90% is 24 hours* Slow CSF penetration unless there is meningeal inflammation
35
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
36
What antibiotic can be used to treat hepatic coma? How?
Neomycin- used to bring down ammonia levels
37
Aminoglycosides-cidal or -static?what kind of bacteria?excretionE1/2t?
* Bactericidal * effective for aerobic gram - and + bacteria* Extensive renal excretion through glomerular filtration* E1/2t 2-3 hours * increased 20-40x with renal failure
38
Which antibiotics potentiate NDMRs?
* Aminoglycosides * can be reversed with neostigmine or calcium gluconate* Clindamycin * cannot be reversed with reversal agents or calcium
39
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
40
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
41
Fluoroquinolones:-cidal or -static?effective against what kind of bacteria?
* Bactericidal- broad spectrum* effective for enteric gram - bacilli and mycobacterium * GI/GU infections
42
FluoroquinolonesExcretionE1/2t?
* Renal excretion, through glomerular filtration and renal tubular secretion * decrease dose in renal dysfunction* E1/2t: 3-8 hours* **can inhibit CYP450**
43
Sulfonamides:-cidal or -static?MOA?
* Bacteriostatic* prevent normal use of PABA by bacteria to synthesize folic acid
44
Sulfonamides:clinical useelimination
* 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
45
Sulfonamides Side effects
* skin rash* anaphylaxis* photosensitivity* allergic nephritis* drug fever* hepatotoxicity* acute hemolytic anemia* thrombocytopenia* increased effect of PO anticoagulant
46
Metronidazole-cidal or -static?types of bacteriaClinical 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
47
Metronidazoleadministrationside effects
* PO or IV * well absorbed orally and widely distributed in tissue including CNS* Side effects * dry mouth * metallic taste * nausea * avoid alcohol
48
What are the 1st line antimycobacterial agents?
* Isoniazid- bacterio**static,** -cidal if bacteria are dividing * hepato-renal toxicity* Rifampin- bacterio**cidal** * Induces CYP450 * hepato-renal toxicity, thrombocytopenia, anemia* Ethambutol- bacterio**static** * optic neuritis* Pyrazinamide- bacterio**static** * liver toxicity
49
Amphotericin BUseelimination
* Given for yeasts and fungi* slow renal excretion * renal function is impaired in **80%** of pts * most recover, some have permanent decrease in GFR
50
Amphotericin BSide effects
* fever, chills, dyspnea, hypotension during infusion* impaired hepatic function* hypokalemia* allergic reactions* seizure* anemia* thrombocytopenia
51
Acyclovirusesside effects
* used to treat herpes* may cause renal damage if infused rapidly* thrombophlebitis* HA during infusion
52
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
53
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
54
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
55
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%
56
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
57
What anesthesia interactions can you expect with **integrase strand transfer inhibitors**?
none
58
What kind of anesthesia interactions can you expect with **early inhibitors**?
* changes clearance and effect of **midazolam**
59
Which antimicrobials are safe in pregnancy?
* PCNs* cephalosporins* erythromycin
60
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
61
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)
62
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
63
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
64
Aminoglycoside pharmacokinetics
* VD = 25% of body weight* adjust maintenance dosing based upon creatinine* plasma monitoring necessary
65
Which antimicrobials are CYP450 inhibitors?
SulfonamidesErythromycinFluroquinolones
66
Which antimicrobials cause muscle weakness?
CiprofloxacinClindamycin(moxifloxacin causes peripheral neuropathy)
67
Which antimicrobials will you decrease your dose for if the pt has renal disease?
SulfonamidesFluroquinolonesVancPCNcephalosporinsaminoglycosides
68
Which antimicrobials increase QT interval?
moxifloxacinmacroglides
69
Which surgeries require cefazolin **+ Metronidazole**?
Head and neck ( with entry into orpharynx)Colorectal (emergency surgery or obstruction)Appendectomy
NRP 507
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