Exam 1 Antibiotics and Respiratory Flashcards
Goals and General Rules for Antibiotics
inhibit organisms at concentrations that are tolerated by the host
seriously ill/immunocompromised- bactericidal
narrow spectrum before broad spectrum or combination therapy to preserve normal flora
Why does anesthesia care about antimicrobals
timely administration
reimbursement for quality care
potential for adverse reactions
cross reactions with other medications we administer
Potential for adverse reactions with abx
hypersensitivity reaction (dose dependent)
direct organ toxicity (dose dependent)
potential for superinfections
identify patient at risk for complications
SSI are the ____ most common healthcare associated infection
second
SSI develop in ____ of 30 million surgical patients
2-5%
Represent approx. _____ of all hospital acquired infections annually in the US and cost ___ dollar/year
14-16%
1 billion
SSIs account for __ of surgical mortality and lead to
3%
increased readmissions
increased LOS
increased hospital costs
SSI defined
as an infection related to a operative procedure that occurs at or near the surgical incision within 30 days of the procedure
Additional details of SSI
purulent exudate draining from a surgical site
+ culture obtained form a surgical site that was closed initally
surgeon’s diagnosis of infection
surgical site that requires re-opening to at least one of the following signs or symptoms: tenderness, swelling , reddness, heat
Surgical Risks for Infection
procedure type
skill of surgeon
use of foreign material or implantable device
degree of tissue trauma
Patient Risks for SSI
diabetes smoking obesity malnutrition systemic steroid use immunosuppressive therapy intraop hypothermia trauma prosthetic heart valves
Anesthesia providers use of antibiotics can decrease infection with
timely and appropriate use of antibiotics
maintenance of normothermia
proper syringe/med administration practices
SSI Prevention Antibiotic Timing
antibiotic prophylaxis 1 hour before incision
30-60 min before incision is the ideal window for drug administration
hypothermia is associated with
increased Blood loss, increased transfusions requirement prolonged PACU stay impaired immue dysfunction compromised neutrophil function leads to vasoconstriction tissue hypoxia and increased SSI
SBE Prophylaxis
amoxicillin 2gm PO
IV ampicillin 2 gm IV
Pencillin Allergy: Ceftriaxone 1gm IV
cefazolin 1gm IV (not in patients with hypersensitivity to PCN)
ceftazolin, cefuroxime or vancomycin
if B lactam allergy, vancomycin or clindamycin
cardiothoracic and vascular surgery
Cefetan, cefazolin, cefoxitin, cefuroxime, ampillicin/bactrim
B lactam allergy: clinda + gent or cipro or met +gent or clindamycin monotherapy
hysterectomy
Cefazolin or cefuroxime
B lactam- vancomycin or clindamycin
hip or knee anthroplasty
Cefotetan, cefoxitin + met or amp/sulbactam
Colon
Bactericidal antibiotics
kill the susceptible bacteria
bacteriostatic antibiotics
reversibly inhibit the growth of bacteria
duration of therapy must be sufficient to allow cellular and humoral defense mechanism to eradicate the bacteria
Bactericidal Antibiotics
pencillins & cephalosporins isoniazid metronidazole polymyxins rifampin vancomycin aminoglycosides quinolones
Bacteriostatic Antibiotics
chloramphenicol clindamycin macroslides sulfonamides tetracyclines trimepthoprim
Structure and Organism of Pencillin
basic structure of dicyclic nucleus with thiazolidine ring connected to B-lactam ring Bactericidal pneumococcal meningococcal streptococcal actinomycosis
MOA of Pencillin
interacts with synthesis of peptidoglycan which is essential to component of cell walls of susceptible bacteria
Excretion of Pencillin
renal excreted rapidly, plasma concentration decrease 50% in first hour
10% glomerular filtration/90% renal tubular secretion
anuria increases elimination half time by 1/2fold
DOA of Pencillin
administration of probenecid will reduce renal excretion and prolong action
Adverse Reactions of Penicillin
hypersensitivity most allergenic of antimicrobals rash/fever hemolytic anemia maculopapular rash
What drugs is common with cross senisitivity with pencillin?
3% B-lactam ring
Penicillin Uses
otitis media meningitis sore throat pneumonia & respiratory infections septicemia gonorrhea/UTIs
Organisms treated by Second Gen Penicillin
pneumoncoccal meningococcal streptococcal actinomycosis wider range of activity (gram - H. influenza and Ecoli
Second Generation Penicillins Examples
amoxicillin
ampicillin
Cefazolin
bactericidal antimicrobals that inhibtit bacterial cell wall synthesis and have low toxicity
broad spectrum activity
low allergy incidence (1-10%)
anaphylaxis is 0.02% (due to B lactam ring)
cross sensitivity with other Cephalosporins
RENALLY EXCRETED
Generations of Cephalosporins
Start with stronger GRam + coverage then increase Gram - coverage as increase class
Macrolides Examples
Erythromycin and Azithromycin
Macrolides
compounds characterized by a macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached
Erythromycin protype
Macrolides are effective against
gram + bacilli, pneumococci, streptococci, staphylococci, mycoplasma and chlamydia
Erythromycin
bacteriostatic or bactericidal depending on dose
Metabolism of Erythromycin
CYP 450 system and thus increase concentration of theophylline, warfin, cyclosporin, methylpredinisone and digoxin
Excretion of Erythromycin
bile
Do you alter erythromycin dose for renal patients?
no
Side effects of Erythromycin
GI intolerance (due to increase peristalsitis)
severe NV after IV infusion
gastric emptying
cholestastic hepatitis
QT effects- prolongs cardiac repolarization
reports of torsades de pointes
thrombophelitis
Clindamycin
linomycins
bacteriostatic
similar to erythromycin in antimicrobal activity
more active with anerobes
pseudomembranous colitis-> severe diarrhea should indicate discontinuation of therapy
Dosing of Clindamycin
only 10% administered dose is excreted unchanged in urine, rest is inactive
Decrease Clindamycin dose with
severe liver disease
Clinda is common for
female GU surgeries
Side Effects of Clindamycin
Rapid IV dose: Hypotension
skin rash
prolonged pre and post junctional effects at NMJ in the absence of ND NMB
not antagonized with anticholinesterases or calcium
concurrent administration with NDMR can produce long lasting profound NM
Vancomycin- Glycopeptide Derivative
Bacteriocidal impairs cell wall synthesis
effective for gram + bacteria (severe staph infections)– streptococcal, enterococcal, endocarditis
DOC for Methicillin resistant staph aureus (MRSA)
Vanco is administered with for
aminoglychoside for endocarditis
Vancomycin is excreted
via kidney 90% unchanged in urine
Elimination 1/2 time of Vanco
6 hours but can be prolonged in renal failure patients
S/E of vancomycin
rapid infusion- red man’s syndrome
ototoxicity/nephrotoxicity/ return of NMB
Dose of Vancomycin
10-15mg/kg over 60 mins
1 gm mixed in 250ml
Vanco is used for
cardiac/orthopedic procedures using prosthetic devices and CSF, shunt related infections
Indications for Vancomycin
MRSA, endocarditis due to strep. v or enterococci
patients allergic to B lactams
pharmacokinetics of vancomycin
poor oral absorption
IV administration
renal excretion by glomerular filtration (80-90%) in 24hr
slow CSF penetration unless there is meningeal inflammation
Side effects of Vancomycin
phlebosclerotic (irritating to tissue) nephrotoxicity rare unless with other drugs ototoxicity > 300mcg/ml hypersensitivity hypotension & red mans
Red Man’s syndrome
flushing due to histamine release
Administer diphenhydramine and cimetidine 1 hour before induction to limit histamine related effects
1mg/kg
4mg/kg
Aminoglycoside Drug Examples
Streptomycin &Kanamycin
Gentamycin
Amikacin
Neomycin
Streptomycin & Kanamycin
limited uses
frequent occurance of vestibular damage
Gentamicin
broader spectrum
toxic level >9mcg/ml
Amikacin
derivative of kanamycin
treatment of infections caused by gentamicin or tobramycin resistant gram negative bacilli
Neomycin
treatment for skin, eye and mucous membrane infections
adjunct therapy to hepatic coma
administered to decrease bacteria in intestine before GI surgery
most nephrotoxic
Aminoglycosides
bactericidal (effective for gram negative and gram +)
generally prescribed combination therapy with beta lactam antibiotic for Gram -
Mycobaterium Tuberculosis
Excretion for Aminoglycosides
extensive renal excretion through glomerular filtration
Elimination time of Aminoglycosides
2-3 hours that can be increased with renal failure (20-40x)
Side effects of Aminoglycosides
limited by toxicity ototoxicity nephrotoxicity skeletal muscle weakness potentiation of NDMR blockade
Muscle weakness of Aminoglycosides
inhibit the pre-junctional release of Ach and decreases post-synaptic sensitivity to the NT
most impt with neuromuscular path patients (MG)
Potentiation of NMR with aminoglycosides with Depolarizing or ND?
Non-depolarizing drugs
result can be reversed with calcium gluconate or neo but it will not be sustained
Examples of Fluroquinolones
ciprofloxacin
moxifloxacin
Ciprofloxacin
treats respiratory infections, tuberculosis and anthrax
Moxifloxacin
suitable for long acting treatment of acute sinusitis, bronchitis, complicated Ab wounds QT prolongation peripheral neuropathy psychosis SJS
Fluroquinolones
broad spectrum, bactericidals
effective for gram - bacilli and myobactrium
useful for treatment of complicated GI GU infections
Cipro useful in treatment of
variety of systemic infections including bone, soft tissues, and resp tract
Pharmacokinetics of Fluroquinolones
Rapid GI absorption and penetrates fluids and tissues well
renally excreted, through glomerular filtration and renal tubular secretion
Renal Dosing Required
Elimination 1/2 time: 3-8 hours
can inhibit CYP 450 enzymes
Side effects of Fluoroquinolones
Mild GI disturbances N/V CNS dizziness, insomnia, Tendon or Achilles rupture muscle weakness in patients in MG
Sulfonamides, Sulfamethoxazole and trimethoprim
Bacteriostatic
antimicrobial activity due to the ability of these drugs to prevent normal use of PABA by bacteria to synthesize FA
inhibits microbial synthesis of folate production
portion of drug is acetylated in the liver and other is renally excreted
Renal Dosing required
Clinical Uses of Sulfonamides, Sulfamethoxazole and trimethoprim
urinary tract infections
inflammatory bowel disease
burns
Side Effects of Sulfonamides, Sulfamethoxazole and trimethoprim
skin rash to anaphylaxis photosensitivity allergic nephritis drug fever hepatotoxicity acute hemolytic anemia thrombocytopenia increase effect of pro anticoagulant
Metronidazole
Bactericidal
anaerobic gram negative bacilli clostridum
What drug is useful for: CNS infections, abdominal and pelvic sepsis, pseudomembranous colitis (CDiff), and endocarditis?
metronidazole
recommended for colorectal surgery
Pharmacokinetics of Metronidazole
well absorbed orally and widely distributed in tissue including CNS
PO IV
Side effects of Metronidazole
dry mouth
metallic taste
nausea
avoid alcohol
Antimycobacterial Agents (1st line)
isoniazid rifampin ethambutal pyrazinamide used in combination therapy (3 4 agents) for 2 months followed by minimum of 4 months of therapy with 2 agents
Isoniazid
bacteriostatic
bactericidal if bacteria are dividing
hepato-renal toxicity
decrease platelets and anemia
Rifampin
bacteriocidal
hepatic enzyme induction
hepat-renal toxicity, thrombocytopenia, anemia
very potent, inducer of hepatic enzyme, increase NDMR , re-dose alot
Ethambutol
bacteriostatic
optic neuritis
Pyrazinamide
bacteriostatic
liver toxicity
Side Effects of Amphotericin B
fever, chills, dyspnea, hypotension, can occur during infusion impaired hepatic function hypokalemia allergic reactions seizure anemia thrombocytopenia
Amphotericin B
given for yeast and fungi
poor PO absorption
slow renal excretion
Renal Function and Amphotercin B
renal function is impaired in 80% of patients treated wiith this drug
most recover after drug is stopped but some result in permenant decrease in GFR
watch Cr levels
Acyclovir
used to treat herpes
may cause renal damage if infused rapidly
thrombophlebitis
patients may complain of headache during infusion
Interferons
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 (degradation of viral mRNA)
enhance tumoricidal activities of macrophages
treatment for chronic hepatitis B and C
nasal spray
Side effects of Antivirals
flu like symptoms hematologic toxicity depression, irritability decreased mental concentration development of autoimmune conditions rashes alopecia changes in CV thyroid and hepatic function
Triple Therapy
Drugs chosen from 6 classes
Importance of CRNA to note with antiretrovirals
existence of adverse effects (liver toxicity, peripheral neuropathy, nephro-toxicity, neuromuscular weakness)
interactions with other medications) proton pump inhibitors, cimetidine, NMDR, benzo)
Six Classes of antiretrovirals:
nucleoside/non nucleotide reverse transcriptionast inhibitors (NRTI & NNRTIs) delaviridine Protease Inhibitors- ritonavir fusion inhibitors- enfuvirtide CCR5 receptors antagonist integrase inhibitors- lamivudine
Take Aways of Antimicrobals
appropriate stewardship of antimicrobal use
infection prevention- SCIP
types of antibiotics cidal vs static
antibiotic classes and ATB: b lactams, linomycins, vancomycin, aminoglycosides
muscular weakness
anti-virals side effects
S/E of antiretrovirals
pancreatitis hepatotoxicity lactic acid fat re-distribution increase plasma concentration of Ca blockers, NMB, and