Antimicrobial Therapy Flashcards
Goals & general rules of antimicrobial therapy include:
Inhibit microorganisms at concentrations that are tolerated by the host
Seriously ill/immunocompromised select bactericidal
Narrow spectrum before broad spectrum or combination therapy to preserve normal flora (target organism)
Adverse reactions with antimicrobial therapy includes:
hypersensitivity reaction (dose independent), direct organ toxicity (dose related), potential for superinfections, identify patients at risk for complications (elderly or parturients)
Another concern when incorporating antimicrobials into our care plan includes
cross-reactions with other medications given
Providing prophylaxis before surgery is important
because it keeps patients safe and allows for reimbursement for quality care
Surgical site infections are defined as
an infection related to an operative procedure that occurs at or near the surgical incision within 30 days of the procedure
It is considered a surgical site infection when
purulent exudate drains from a surgical site, a positive culture obtained from a surgical site that was closed initially, a surgeon’s diagnosis of infection, a surgical site that requires reopening due to a least one of the following signs or symptoms: tenderness, swelling, redness, or heat
SSI are the second most common
healthcare associated infection
they develop in 2-5% of 30 million surgical patients
The cost of SSIs per year equates to
1 billion dollars/year
SSIs account for 3% of surgical mortality and lead to
increased re-admissions, increased length of stay (7-10 days), and increased hospital costs (additional $3,000-29,000/per SSI diagnosis)
What are the two types of risk for development of SSIs?
Surgical Risk
Patient risks
Surgical risks for SSIs include
procedure type, skill of surgeon, use of foreign material or implantable device, degree of tissue trauma
Patient risks for SSIs include
diabetes, smoking use, obesity, malnutrition, systemic steroid use, immunosuppressive therapy, intraoperative hypothermia, trauma, prosthetic heart valves
Anesthesia providers can make an impact on prevention through:
timely and appropriate use of antibiotics, maintenance of normothermia, and proper syringe/med administration practices
SCIP measures related to antibiotics include:
prophylactic antibiotic received within one hour prior to surgical incision, prophylactic antibiotic selection for surgical patients, prophylactic antibiotics discontinued within 24 hours after surgery end time
SCIP measures include
controlled blood glucose in cardiac patients, appropriate hair removal, urinary catheter removal on postop day 1 or 2, periop temperature management, patients receiving beta-blocker dose, patients with DVT prophylaxis
The timing of antibiotics for surgery is
1 hour before incision; 30-60 minutes before incision is the ideal window for drug administration
Hypothermia is associated with adverse outcomes which include:
increased blood loss, increased transfusion requirements, prolonged PACU stay, post-op pain, impaired immune function (compromised neutrophil function–> vasoconstriction–> tissue hypoxia and increased incidence of SSI)
What drug is given most frequently preoperatively?
cefazolin
The standard general prophylaxis for SBE is:
amoxicillin 2 gms PO
IV- Ampicillin 2 gms IV
SBE prophylaxis for an individual with a penicillin allergy is:
clindamycin 600 mg IV
cefazolin 1 gm IV
Antibiotics are classified as
bactericidal or bacteriostatic
Bactericidial means
they kill the susceptible bacteria
Bacteriostatic means
if they reversibly inhibit the growth of bacteria
When a bacteriostatic antibiotic is used, the duration of therapy must be sufficient to allow
cellular and humoral defense mechanisms to eradicate the bacteria
Bactericidal drugs include
penicillins, cephalosporins, isoniazid, metronidazole, polymyxins, rifampin, vancomycin, aminoglycosides, bacitracin, quinolones
Bacteriostatic drugs include
chloramphenicol, clindamycin, macrolides, sulfonamides, tetracyclines, trimethoprim
Penicillin is considered a
bactericidal drug that interferes with the synthesis of peptidoglycan which is an essential component to cell walls of susceptible bacteria
Penicillin target organisms include
pneumococcal, meningococcal, streptococcal, and actinomycosis
Penicillin structure is
basic structure is a dicylic nucleus that consists of a thiazolidine ring connected to a beta-lactam ring
Penicillin is excreted by
renal excretion
anuria increases elimination half-time by 10 fold
This drug can be administered with penicillin to reduce renal excretion and prolong action
probenecid
Adverse reactions from penicillins include
hypersensitivity- most allergenic of all the antimicrobials (up to 10%): rash, fever, hemolytic anemia, maculopapular rash, immediate sensitivity: anaphylaxis
Penicillin has cross-sensitivity with
all penicillin drugs and cephalosporins (3%) due to the common beta-lactam ring
Routes of penicillin include
PO & IV
Mechanism of action of penicillin includes
inhibits transpeptidation of cell wall
bactericidal
Penicillin can be used to treat
otitis media, meningitis, sore throat, pneumonia and respiratory infections, septicemia, peritonitis, gonorrhea, UTIs
Known issues of penicillin include:
resistance, allergic reactions, and cross hypersensitivity
Second generation penicillins target these organisms
pneumococcal, meningococcal, streptococcal, actinomycosis, Wider range of activity (e coli, gram negative bacilli–> haemophilus influenze)
Second generation penicillins include
amoxicillin & ampicillin
For patients with documented IgE mediated anaphylactic reactions with B-lactum antibiotics
clindamycin or vancomycin can be substituted
Cephalosporin antibiotics include
cefazolin
Cephalosporin antibiotics are
bactericidal antimicrobials that inhibit bacterial cell wall synthesis and have low toxicity
Cephalosporin antibiotics are excreted
renally
Cephalosporin is what kind of spectrum of antibiotic?
broad spectrum activity
Cephalosporin has cross reactivity
with other cephalosporins, anaphylaxis is 0.02%, and penicillin and cephalosporin allergy is 1-3% (don’t give it if it was an anaphylaxis reaction)
Cephalosporins can penetrate
the joints and cross the placenta
Cephalosporins are more effective as
you go up in generation
Examples of macrolides include
erythromycin & azithromycin
Macrolides are particularly useful for patients with
sensitivities to penicillins and cephalosporin drugs
The chemical structure of macrolides is
a macrolytic lactone ring containing 14-16 atoms with a deoxy sugar attached
Macrolides are effective against
gram positive bacilli, pneumoccoci, streptococci, staphylococci, mycoplasma, chlamydia
Routes of macrolides include
oral and IV
Macrolide uses include
URI (pharyngitis, tonsillitis, sore throat), otitis media, uncomplicated skin infections (staph), ulcers (h. pylori), STDs (chlamydia, gonorrhea), lower respiratory tract infections (MAC, pneumonia, Legionnaire’s, anthrax)
The mechanism of action of macrolides
bind to 50 S and block translocation step in protein synthesis
Macrolides are considered to be
bacteriostatic
The half life of azithromycin is
3 days
Erythromycin is considered to be
bacteriostatic or bactericidial
Erythromycin works by
inhibiting bacterial protein synthesis
Erythromycin is excreted in
bile
Erythromycin is metabolized by
cytochrome P-450 system and thus increase serum concentration of theophylline, warfarin, cyclosporine, methylprednisone, and digoxin
The dose in renal disease for erythromycin
does not need to be altered
Side effects of erythromycin include
GI intolerance, severe N/V with IV infusion, gastric emptying with increased peristalsis, cholestasic hepatitis, thrombophlebitis, QT effects (prolongs cardiac repolarization & torsades de pointes)
Clindamycin is (class & type)
linomycins- class bacteriostatic
Complications of clindamycin include
pseudomembranous colitis–>severe diarrhea should indicate discontinuation of therapy
Severe GI complications limit its use to infections that are difficult to treat
Clindamycin is most commonly used in
female GU surgeries
The mechanism of action of clindamycin is
similar to emycin in antimicrobial activity
When administering clindamycin, the dose
needs to be decreased with severe liver disease
Side effects of clindamycin include
skin rash, prolonged pre & post junctional effects at NMJ in the absences of NMDR
Clindamycin is not antagonized with
anticholinesterases or calcium- concurrent administration with NMDR can produce long lasting, profound neuromuscular blockade
Routes of clindamycin include
PO & IV
The mechanism of clindamycin is
Binds to 50S & inhibits peptidyl transferase and transduction
Vancomycin (class & type)
glycopeptide derivative
bacteriocidal- impairs cell wall synthesis
Vancomycin is excreted
renally & can be prolonged (up to 9 days) with renal failure patients
Vancomycin is effective for
gram positive bacteria, severe staph infections, streptococcal, enterococcal, endocarditis, drug of choice for MRS, penicillin/cephalosporin allergy, administered with aminoglycoside for endocarditis
Rapid infusion of vancomycin can cause
profound hypotension
Side effects of vancomycin include
red man syndrome- intense facial & truncal erythema from histamine release; ototoxicity/nephrotoxicity, return of NMJ blockade
Vancomycin is used for
CSF & shunt related infections, cardiac/orthopedic procedures using prosthetic devices
The use of vancomycin is typically reserved for
Rx of bacterial infections resistant to other antibiotics, or patients with severe hypersensitivity to other indicated antibiotics; if bacteria become resistant to vancomycin, there are only a few other drugs that may be effective in treating the patient
Administration of vancomycin consists of
IV slowly over 1 hour
Vancomycin has synergistic actions with
aminoglycosides against susceptible gram positives
Indications of vancomycin include
MRSA, endocarditis due to strep or enterococci, patients allergic to Beta lactams
Side effects of vancomycin include
phlebosclerotic (vanc is irritating to tissue), nephrotoxicity rare unless concomitant tx with other nephrotoxic drugs such as aminoglycosides, ototoxicity when concentrations are >30 mcg/ml, hypersensitivity (maculopapular skin rash), hypotension & red man syndrome if given IV in less than 30 minutes, administration of benadryl 1 hour before induction limits histamine related effects
Aminoglycosides include
streptomycin, kanamycin, gentamicin, amikacin, neomycin
The most nephrotoxic aminoglycoside is
neomycin
Neomycin can be used to treat
skin, eye and mucous membrane infections
adjunct therapy to hepatic coma
administered to decrease bacteria in intestine before GI surgery
Amikacin is used to treat
infections caused by gentamicin or tobramycin resistant gram negative bacilli
it is a derivative of kanamycin
Vestibular damage can occur with use of these aminoglycosides
streptomycin & kanamycin
also has limited uses
Routes for aminoglycosides include
IM, IV or topical
Mechanism of action for aminoglycosides include
irreversible inhibition of protein synthesis
Adverse effects of aminoglycosides include
ototoxicity (rev vestibular & irreversible auditory), nephrotoxicity (reversible), NMJ blockade (high dose), pregnancy category C
Adverse side effects of antiretroviral drugs include
liver toxicity, peripheral neuropathy, nephro-toxicity, neuromuscular weakness
Antiretroviral drugs have interactions with
proton-pump inhibitors, cimetidine, NDMR, opioids, benzos
Treatments for HIV typically consist of
“triple therapy” and include nucleosides/non nucleotide reverse transcriptase inhibitors, protease inhibitors, fusion inhibitors, CCR5 receptors antagonists, integrase inhibitors
Side effects of antivirals include
flu like symptoms, hematologic toxicity, depression, irritability, decreased mental concentration, development of autoimmune conditions, rashes, alopecia, changes in CV, thyroid, hepatic function
Interferons definition
term used to designate glycoproteins produced in response to viral infections
Antivirals work by
binding 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
Antivirals are used for the treatment of
chronic hepatitis B & C
Acyclovir can be used
to treat herpes, may cause renal damage if infused rapidly, thrombophlebitis, patients may complain of HA during IV infusion
Viruses are obligate
intracellular parasites & it is difficult to kill virus and not host cell
some cell surface receptors are unique for viruses and this gives a location for potential drug therapy
Example of antifungals include
amphotericin B
Amphotericin B is given for
yeasts and fungi
Amphotericin is given via
IV as it has poor PO absorption
Amphotericin is excreted by
renal excretion & renal function is impaired in 80% of patients treated with this drug (most recover but it could be lasting)
Side effects of antifungals include
fever, chills, dyspnea, hypotension (can occur during infusion), impaired hepatic function, hypokalemia, allergic reactions, seizure, anemia, thrombocytopenia
Antimyobacterial agents are distributed through
tissues, CSF
Which antimycobacterial agents are bacteriostatic?
isoniazid, ethambutol, pyrazinamide
Which antimycobacterial agents are bacteriocidal?
rifampin
side effects: hepato-real toxicity, thrombocytopenia, anemia
causes hepatic enzyme induction
Antimycobacterial agents are used in
combination therapy (3 or 4 agents) for 2 months, followed by minimum of 4 months of therapy with 2 agents
List the side effects of antimycobacterial agents
isoniazid-hepato-renal toxicity
ethambutol- optic neuritis
pyrazinamide- liver toxicity
Metronidazole is (type)
bactericidal- targeting anaerobic gram negative bacilli clostridium
Metronidazole is useful for treating
CNS infections, abdominal & pelvic sepsis, pseudomembranous colitis (c. diff.), and endocarditis
Side effects of metronidazole include
dry mouth, metallic taste, nausea, avoid alcohol
Metronidazole can be used
PO or IV
well absorbed orally and widely distributed in tissue including CNS
Metronidazole is recommended for
pre-op prophylaxis for colorectal surgery
Side effects of sulfonamides include
skin rash to anaphylaxis, photosensitivity, allergic nephritis, drug fever, hepatotoxicity, acute hemolytic anemia, thrombocytopenia, increase effect of PO anticoagulant
Clinical uses of sulfonamides include
urinary tract infections, inflammatory bowel disease, and burns
Sulfonamides are excreted
via renal & liver
dose is reduced in renal disease
Sulfonamide examples include
sulfamethoxazole and trimethoprim
Sulfonamides work by
bacteriostatic
antimicrobial activity is due to the ability of these drugs to prevent normal use of PABA by bacteria to synthesize folic acid
inhibits microbial synthesis of folate production
Aminoglycoside side effects include
limited by their toxicity, ototoxicity, nephrotoxicity, skeletal muscle weakness, potentiation of NMDR blockade, muscle weakness: inhibit the pre-junctional release of Ach and decreases post-synaptic sensitivity to the neurotransmitter (impact on patients with neuromuscular pathology i.e. myasthenia gravis)
Aminoglycosides have increased elimination half-time
in the setting of renal failure
extensive renal excretion through glomerular filtration
Aminoglycosides are (type)
bactericidal and effective for aerobic gram negative and positive bacteria
also used to treat mycobacterium tuberculosis
Aminoglycosides are prescribed as
combination therapy with beta-lactam antibiotic for gram negative
Aminoglycosides & NMDBs
have potentiation, paralysis is usally reversible with calcium gluconate or neostigmine, effect may not be sustained
Examples of fluroquinolones include
ciprofloxacin and moxifloxacin
Ciprofloxacin is used to treat
respiratory infections, TB & anthrax
Moxifloxacin is used to treat
acute sinusitis, bronchitis, & complicated abdominal infections
Moxifloxacin side effects include
QT prolongation, peripheral neuropathy, pscyhosis, Stevens-Johnson syndrome
Fluroquinolones work by
inhibiting DNRA Gyrase and Toposomerase IV
Side effects of fluoroquinolones include
mild GI disturbances, N/V, CNS dizziness, insomnia, tendon or achilles rupture, muscle weakness in patients with myasthenia gravis
Fluoroquinolones are (type)
broad spectrum and bactericidal
Fluoroquinolones are excreted via
renal excretion- decrease dose in renal dysfunction
Fluoroquinolones can inhibit
P450 enzymes
Fluorquinolones can be used to treat
GI & GU infections
ciprofloxacin is useful in treatment of systemic infections including bone, soft tissue, and respiratory tract
Fluoroquinolones are effective in (type of bacteria)
treating enteric Gram negative bacilli and mycobacterium
