Antibiotics exam 1 Flashcards
In doctor’s offices antibiotics have been over prescribed, specifically for what two infections?
upper respiratory tract infections
bronchitis
SCIP which was based on SIP was designed to combat a perceived national crisis, what was that crisis?
preventable surgical site infections
In relation to mortality, spending time in the ICU, and readmission, what were the % risks associated with surgical site infections in the 1990s?
double the risk of mortality
60% increase to spend time in the ICU
and fivefold risk of readmission
The original goal of the SCIP was 25% reduction in surgical site infections by 2010. Was the goal met?
No
However a new goal of 25% was set for 2013 and the goal may have been met with a 20% reduction by 2012.
Patient-related risk factors for surgical site infections include?
extremes of age (less than 5 and greater than 65) poor nutritional status obesity diabetes peri-operative glycemic control peripheral vascular disease tobacco use coexisting infection altered immune response corticosteroid therapy pre-operative skin preperation (hair removal, surgical scrub) length of pre-operative hospitalization.
Institutional variables for surgical site infections include?
surgical experience technique (open vs laproscopic) duration of procedure hospital environment sterilization of equipment peri-operative normothermia
True or False
Good peri-operative glucose control can reduce infection risk.
True
Peri-operative glucose control has been studied predominantly in the cardiothoracic surgery population where it is associated with what % decrease in what kind of infections?
50% decrease in deep sternal infections
Which form of insulin control has been associated with additional reduction in surgical site infections? (cardiothoracic patient presumed)
continuous insulin infusion was associated with additional reduction in surgical site infections compared to intermittent subq injection.
Tell me what type of glucose control post surgery is best for bowel surgery patients?
glucose control of BELOW 200 mg/dL for 48 hours after surgery has shown an infection risk of about 14.3% compared to glucose control of patients greater than 200 mg/dL post surgery with an infection risk of 29.7%.
(the lower glucose post surgery was obviously better for infection risk)
If keeping bowel patients glucose below 200 mg/dL post surgery is good, then can it be concluded that keeping the blood sugar ultra low would be even better? why or why not?
intensive insulin regimens designed to keep blood sugar ultra low have shown higher hypoglycemia and mortality compared to conventional treatment.
(thus ultra low is not better)
Should we even bother telling people to quit smoking before surgery?
smoking cessation is a peri-operative goal. Surgeons and anesthesia providers alike should use the peri-operative setting as a “teachable moment” and even brief smoking cessation CAN reduce infection risks.
what time period of smoking cessation has demonstrated a risk reduction of approximately 50% in infections?
4-8 weeks of cessation
that is basically quitting for a smoker lol
There are 7 SCIP measures laid out for the prevention of surgical site infections, what are they?
- prophylactic antibiotics received within 1 hour prior to surgical incision.
- prophylactic antibiotic selection for surgical patients (the right antibiotic per the surgery being performed).
- prophylactic antibiotic dc’d within 24 hours after surgery end time (48 hours for cardiac patients).
- cardiac surgery patients with a controlled 0600 post-op serum glucose (less than or equal to 200 mg/dL).
- post-op wound infection diagnosed during index hospitalization.
- Surgical patient with appropriate hair removal.
- Colo-rectal surgical patients with immediate post-op normothermia.
Logically hypothermia in the surgical patient will cause what?
peripheral vasoconstriction
decreased wound oxygen tension
recruitment of leukocytes
ALL favoring INFECTION and IMPAIRED WOUND HEALING
Intraoperative warming of patients compared to controls (no intraoperative warming or normal conditions) shows us what about surgical site infections?
when patients were intraoperatively warmed there was an associated decrease of 64% in surgical site infections.
what are some advantages of prewarming patients?
placement of intravenous lines is easier because of vasodilation.
also, active prewarming of 2 hours results in the patient maintaining a core temp. above 36 C for 60 min. under GA with ambient temperatures.
Does long term corticosteroid use contribute to surgical site infections?
This has not been proven. It was for a long time considered a risk factor but there are no studies to definitively prove this claim.
What effect does long term steroid use have on surgical patients?
Long term steroid use has been associated with anastomotic leaks in bowel surgery.
(but not an increase in surgical wound infection as a whole)
If you give a patient a single dose of a corticosteroid for the prevention of N&V, will this increase their likelihood of surgical site infection?
No, there is no evidence to support this claim.
What is the reasoning for SCIP measure 1?
tissue concentration of the antibiotic should exceed the minimum inhibitory concentration (MIC) associated with the procedure and or patient characteristics from the time of incision to the completion of surgery.
(measure 1 is to give prophylactic antibiotics within 1 hour prior to surgical incision.)
Are their any antibiotics that require re dosing during the course of a surgery?
If the antibiotics chosen are short acting and the surgery is long then yes, re dosing may occur.
Why is prophylactic antibiotic use for surgery infection prevention not recommended to go past 24 hours post surgery? (cardiac is 48 hours)
There is no benefit to prolonged dosing but rather an increased incidence of drug-resistance organisms.
The antibiotic chosen should be appropriate for the most likely microorganism related to the procedure and patients characteristics, what SCIP measure is this?
2
If the patient is having a clean elective procedure performed in which no tissue (other than the skin) carrying an indigenous flora is penetrated, will they likely have prophylactic antibiotic use?
No, the risk of routine antibiotic prophylaxis outweighs the possible benefits.
What are the two predominant organisms causing surgical site infections after clean procedures (skin flora)?
Staphylococcus aureus
Staphylococcus epidermidis
In clean-contaminated procedures, including abd procedures and solid organ transplantation, the most common organisms include what?
gram-negative rods and enterococci in addition to skin flora.
(skin flora is S. aureus and S. epidermidis)
Which antibiotics have a recommended re-dosing interval of 6 hours? (2 answers)
Clindamycin (half life = 2-4 hrs)
Cefotetan
Which antibiotics have a recommended re-dosing interval of 4 hours (3 answers)
Aztreonam
CEFAZOLIN (half life =1-2 hrs)
Cefuroxime
Which antibiotic has a recommended re-dosing interval of 3 hours?
Cefotaxime
Which antibiotics have a recommended re-dosing interval of 2 hours? (3 answers)
AMPICILLIN and ampicillin- sulbactam
Cefoxitin
PIPERACILLIN-TAZOBACTAM (Zosyn)
Cipro, Fluconazole, Gentamicin, Levofloxacin, Metronidazole, Vancomycin, Erythromycin, and Neomycin all have recommended re-dosing intervals of what?
NA
(this means that based on the “normal” case length that re-dosing is not recommended, BUT if it is a long surgery then you need to look at the half life and decide from there in order to re-dose)
What is the “interval to re-dose” based on?
re-dosing in the OR is recommended at an interval approx. two times the half-life of the agent in patients with normal renal function.
What are the antimicrobials of choice for surgical procedures in which skin flora and normal flora of the GI and GU are the most likely pathogens?
cephalosporins (most often a cost effective first-generation cephalosporin such as CEFAZOLIN)
What is the likelihood of a patient having a documented IgE reaction to a cephalosporin?
Rare
What is a more likely explanation for a patients reaction to cephalosporins than IgE reaction?
Far more common intolerance such as nausea or yeast infections.
IgE-mediated anaphylactic reactions to antimicrobials usually occur in what time period after dosing and what kind of reactions would you see?
30-60 minutes after dosing and often include urticaria, bronchospasm, and hemodynamic collapse. (life-threatening emergency)
Can cephalosporins safely be given to patients with allergic reactions to Penicillins?
Yes, as long as the reaction of the patient was not an IgE-mediated reaction.
That would mean it could not have been anaphylaxis, urticaria, bronchospasm, or exfoliative dermatitis (Stevens-Johnson syndrome, toxic epidermal necrolysis).
What is the actual % of cros-reactivity with cephalosporins and penicillins?
1%
The original reports of higher cross-sensitivity was due to contaminated drug lots.
What can we do as anesthesia providers to accurately know what a persons true reaction to antibiotic was?
patients should be carefully questioned about the nature of any drug allergy.
Recommended agent (no B-lactam allergy obviously) for cardiac, thoracic, Gastroduodenale, biliary tract, high-risk laparoscopic, small intestine, hernia repair, head and neck that is not clean, neurosurgery, orthopedics requiring an agent, vascular, heart and lung transplant, pancreases and plastics?
(this should tell you to learn the exceptions, and if Hammon is not talking about an exception that you have learned then go with this answer)
CEFAZOLIN
The main recommended agent is cefazolin and at times depending on procedure will have other agents in addition but the common thread is cefazolin. Feel free to learn all details, but the above is the only one I am placing here for simplicity.
Procedures that do NOT require antibiotics? (3 answers)
elective low-risk laparoscopic
Clean head and neck
clean operations involving the hand, knee, or foot not involving implantation of foreign materials.
What is the most common substitute antibiotic agent if someone has a B lactam allergy?
Clindamycin or/then Vancomycin
Appendectomy for uncomplicated appendicitis - what is the recommended agent?
Cefoxitin, cefotetan, cefazolin + metronidazole
Recommended agent for Ophthalmic procedures?
What is the B lactam allergy alternative?
Topical neomycin- polymyxin B-gramicidin or fourth generation topical fluoroquinolones given as one drop every 5-15 min. for five doses.
Addition of cefazolin 100mg b subconjunctival injection or intracameral cefazolin or cefuroxime at the end of the procedure is optional.
There is no B lactam allergy alternative for ophthalmic procedures.
Recommended agent for urologic lower tract instrumentation?
what is the B lactam allergy alternative agent?
Fluoroquinoline, trimethoprim-sulfamethoxazole, cefazolin.
B-lactam allergy = aminoglycoside with or without clindamycin.
Liver transplantation recommended agent?
piperacillin-tazobactam, cefotaxime + ampicillin
If a patient has a documented IgE- mediated anaphylactic reaction then what antibiotics can be substituted in place of the typically recommended agent?
B-lactam antibiotics can usually be substituted with clindamycin or vancomycin.
If MRSA is considered likely then what antibiotic will you use?
Vancomycin
What nasal application has been found to be effective in elimination of MRSA colonization?
Mupirocin
Why is routine prophylaxis with Vancomycin not recommended?
(unless you have documented or highly suspected colonization with MRSA or known IgE-mediated response to B-lactam antibiotics)
risk of inducing hemodynamic instability due to histamine release (red man syndrome), if given rapidly.
also, evidence that vancomycin is less effective than cephazolin in methicillin-susceptible S. aureus.
Clean-contaminated procedures such as colorectal and abdominal surgeries require additional coverage for gram-negative rods and anaerobes in addition to skin flora, what antibiotics would this be?
Metronidazole can be added to cefazolin or cefoxitin, cefotetan, ampicillin-sulbactam, ertapenem, or ceftriaxone.
what is the most frequent complication of prophylactic antimicrobials, including the IV cephalosporins?
Pseudomembranous colitis
Oral antibiotics only vs IV antibiotics prophylactically have shown what?
If oral only is given compared to oral and IV or IV only, the oral only group tends to have higher rates of infections, disproportionately high.
To treat an ongoing infection what is it essential to identify?
identification of the causative organism is essential for appropriate antimicrobial drugs to treat the ongoing infection.
A patient has pneumonia behind a blocked bronchus, what must be done for antibiotic therapy to work in this situation?
the obstruction must be relieved or therapy will not be effective, there will be no response to the antibiotics.
The drug toxicity of hyperkalemia is associated with which antibiotic?
Trimethoprim-sulfamethoxazole
Nearly 80% of nosocomial infections occur in three sites?
urinary tract
respiratory tract
bloodstream
The incidence of nosocomial infections is highly associated with the use of what types of devices? (3 answers)
ventilators
vascular access catheters
urinary catheters
(correlates with the most common sites for infections (resp. tract, bloodstream, and urinary tract))
Intravascular access catheters are the most common cause of what two infections in the hospitalized patient?
bacteremia
fungemia
The organism infecting access catheters most commonly come from what two locations on the catheter?
what does this reflect?
colonized hub or lumen and reflects skin flora (S. aureus and S. epidermidis).
Initial therapy of suspected IV catheter infection usually includes what antibiotic and why?
vancomycin because of the high incidence of MRSA and methicillin-resistant S. epidermidis in the nosocomial environment.
Drug toxicity - allergic reactions is most often associated with which antibiotic(s)?
All antimicrobials but most often with B-lactam derivatives.
does Bowel prep reduce infection?
No
What is the good and bad about vancomycin as an oral antibiotic?
Vancomycin would be active against MRSA but would affect gram-positive flora which plays an important role in resistance to colonization.
Drug toxicity- Nephrotoxicity is due to what antimicrobials? (3 answers)
Aminoglycosides
Polymyxins
Amphotericin B
Drug toxicity- Neutropenia is due to what antimicrobials? (3 answers)
Penicillins
Cephalosporins
Vancomycin
Drug toxicity- Leukopenia and thrombocytopenia (folate deficiency) is due to what antimicrobial?
Trimethoprim
Drug toxicity- Seizures is due to what antimicrobials? (2 answers)
Penicillins and other B-Lactams (high doses, azotemic patients, history of epilepsy)
Metronidazole
Drug toxicity- Neuromuscular Blockade is due to what antimicrobial?
Aminoglycosides
Drug toxicity- GI irritation is due to what antimicrobial?
Tetracyclines
Drug toxicity- Prolonged QT interval is due to what antimicrobials? (2 answers)
Erythromycin
Fluoroquinolones
Drug toxicity- Tendinitis is due to what antimicrobial?
Fluoroquinolones
What five antibiotics are known to have a drug toxicity of Teratogenicity?
Tetracyclines Metronidazole Rifampin Trimethoprim Fluoroquinolones
If a patient has an infected prosthetic then what needs to happen for the antibiotic therapy to be effective?
The prosthetic will need to be removed for therapy to be likely effective.
What three antibiotics are considered safe to use in pregnancy?
Penicillins
Cephalosporins
Erythromycin base
What is the one antibiotic that is labeled as “avoid” during pregnancy?
Metronidazole
Name some antibiotics that should be used cautiously in pregnancy?
Aminoglycosides
Clindamycin
Rifampin
Sulfonamides
Name some antibiotics that are CONTRAINDICATED during pregnancy?
Erythromycin estolate; fluoroquinolones; tetracyclines; trimethoprim
In the elderly patient who is taking antibiotics, what two things might you want to monitor in order to know if they can handle certain antibiotic dosing?
measure plasma concentrations of antimicrobials and monitoring of renal function may be indicated.
What two antibiotics due to their large therapeutic index, obviate the need for significant changes in dosage schedules in the elderly who have normal serum creatinine concentrations?
Penicillins and Cephalosporins.
What two antibiotics may require adjustments in dosing regimens in elderly?
Aminoglycosides and vancomycin
CH2 R group onto a penicillin structure will yield what drug?
Penicillin G
CH2–O R group onto a penicillin structure will yield what drug?
Penicillin V
CH– NH2 R group onto a penicillin structure will yield what drug?
Ampicillin
CH–NH2 and then OH R group onto a penicillin structure will yield what drug?
Amoxicillin
Two CH3O R groups onto a penicillin structure will yield what drug?
Methicillin
Where on the general structure of penicillin do you find the Beta - Lactam Ring?
B-lactam ring is shaped like a square, next to the 5 sided shape that is the Thiazolidine ring.
Penicillins may be classified into subgroups based on what?
their structure
B-lactamase susceptibility
spectrum of activity
The basic structure of penicillins is what?
a dicyclic nucleus (aminopenicillanic acid) consisting of a thiazolidine ring connected to a beta-lactam ring
PCN has a bactericidal action that reflects it’s ability to do WHAT, which is an essential component of cell walls of susceptible bacteria.
interfere with the synthesis of peptidoglycan
Why are some gram-negative bacteria resistant to PCN?
they prevent access to sites where synthesis of peptidoglycan is taking place.
Clinical indications for PCN, Drug of choice for treating?
3 examples (there are more than 3)
Pneumococcal
Streptococcal
Meningococcal
Will PCN treat Gonococci?
Yes, but it has become gradually more resistant to PCN thus higher doses are needed for adequate treatment.
Treatment of syphilis would be?
PCN, highly effective against syphilis.
What is the drug of choice for treating all forms of actinomycosis and clostridial infections causing gas gangrene?
PCN
Transient bacteremia occurs in the majority of patients undergoing dental extractions, emphasizing prophylactic need of what medication for those patient with cardiac issues and tissue implants.
PCN
Transient bacteremia can accompany procedures such as?
T&A, GU, GI, dental extractions, and vaginal deliveries
Penicillin G IV 10 million U contains what?
why is this significant?
16 mEq of potassium
Thus patients with renal dysfunction may result in neurotoxicity and hyperkalemia
If a patient is needing Penicillin G but does not need the dose of potassium bc it could cause demise/risk, what will you use instead?
a sodium salt of PCN G or a similar medication such as ampicillin or carbenicillin can be used.
Can you mix other drugs with Penicillin?
You should not mix other meds with PCN, combinations may inactivate the antimicrobial effects.
Can PCN be administered intrathecally?
Not recommended bc PCN given this route is a potent convulsant!
What will increase the elimination half-time of PCN G approximately 10 fold?
Anuria
How much of PCN is excreted renally in the first hour when given IM?
60-90% IM excreted in first hour
What % of PCN is eliminated by glomerular filtration and what % is by renal tubular secretion.
Approximately 10% eliminated by glomerular filtration and 90% by renal tubular secretion.
What drug can be used to prolong PCN by blocking its renal tubular secretion?
Probenecid
What is the point of procaine PCN?
The mixture is used to try and slow the absorption of PCN and thus prolong the DOA.
Is the renal excretion of PCN slow or rapid?
rapid
What is the ratio of LA to U of antimicrobials when talking about Procaine PCN?
Procaine PCN contains 120mg of LA for every 300,000 U of antimicrobial
*What is the major mechanism of resistance to the penicillins?
bacterial production of B-lactamase enzymes that hydrolyze the B-lactam ring, rendering the antimicrobial molecule inactive.
Drugs not susceptible to hydrolysis by staphylococcal penicillinases that would otherwise hydrolyze the cyclic amide bond of the B-lactam ring and render the antimicrobial inactive? (five answers)
Methicillin Oxacillin Nafcillin Cloxacillin Dicloxacillin
What antimicrobial can penetrate into the CNS sufficient to treat staphylococcal meningitis?
NAFCILLIN
high-dose oxacillin therapy can cause what?
Hepatitis
Infections caused by staphylococci known to produce the staphylococcal penicillinases enzyme, what antibiotics would you use to fight this type of infection?
Methicillin Oxacillin Nafcillin Cloxacillin Dicloxacillin
Hemorrhagic cystitis and an allergic interstitial nephritis (hematuria, proteinuria) can be caused by what Penicillinase-resistant PCN?
Thus this drug has been replaced by what two other Penicillinase-resistant PCN?
Methicillin
superseded by oxacillin and nafcillin
More than 80% of an IV dose of this drug is excreted in the bile, which may be an advantage when high-dose therapy is needed in a pt. with impaired renal function?
Nafcillin
What two Penicillinase-resistant PCN are available ONLY as oral preparations and may be preferred due to higher blood levels that result after taking?
Cloxacillin
Dicloxacillin
What three Penicillinase-resistant PCN have extensive renal excretion?
Methicillin
Oxacillin
cloxacillin
What two Penicillinase-resistant PCN are relative stable in an acidic medium and adequately works as a PO medication?
oxacillin and nafcillin
Broad spectrum PCN 2nd generation, name them?
Ampicillin
Amoxicillin
(Carbenicillin listed under this header as well as 3rd generation)
2nd generation PCN are Bactericidal against what types of bacteria?
both gram positive and gram negative bacteria
What inactivates 2nd generation PCN?
All inactivated by penicillinase produced by certain gram positive and negative bacteria.
What are 2nd generation PCN NOT effective against?
These drugs are not effective against most staphylococcal infections
What 2nd generation PCN has a broader range of activity than PCN G?
Ampicillin
Among PCNs associated with the highest incidence of skin rash (9%) which typically appears 7-10 days after initiation therapy, what drug am I?
Ampicillin
This 2nd generation PCN:
Covers pneumocci, meningococci, gonococci, and various streptococci
Also covers some gram negative bacilli such as: Haemophilus influenza and Escherichia coli
Ampicillin
Ampicillin PO dose, how much is excreted from the kidneys unchanged in the first how many hours?
50% of PO dose is excreted in kidney unchanged in the first 6 hours
Chemically identical to ampicillin except for an OH substituent instead of an H on the side chain?
Amoxicillin
Spectrum of activity of Amoxicillin is identical to ampicillin but what two things are better about Amoxicillin?
more efficiently absorbed from GI
Effective concentrations are present in circulation 2x as long
Carbenicillin is a derivative of what other PCN?
Ampicillin
Principle advantage of Carbenicillin is what?
its effectiveness in Tx of infections caused by Pseudomonas aeruginosa and certain Proteus strains resistant to ampicillin.
Is carbenicillin penicillinase susceptible? What strains is it not effective against?
Yes, and ineffective against most strains of S. aureus.
How must Carbenicillin be given?
Must be given parenterally because it is not absorbed in the GI
elimination half time of carbenicillin?
1 hour, prolonged in the presence of hepatic or renal dysfunction = 2 hour half time.
what patients may not need to take carbenicillin and why?
CHF patients or patients in which CHF can develop because the sodium load with a large dose of Carbenicillin is considerable.
(5mEq/g of sodium and a large dose of Carbenicillin is 30-40g) 10% of the drug is sodium.
non-reabsorbable carbenicillin can result in what?
Hypokalemia and metabolic alkalosis may occur d/t obligatory excretion of K+ with the large amounts of nonreabsorbable carbenicillin.
How does carbenicillin effect someone’s blood?
Interferes with normal platelet aggregation and prolongs bleeding time even when platelet count remains the same.
What two meds share a common B-Lactam ring?
PCNs and cephalosporins
4th Generation PCN known as Acylaminopenicillins, three examples would be?
Mezlocillin
Piperacillin
Azlocillin
Broadest spectrum of all PCNs would be?
4th generation PCN (acylamino like piperacillin)
Which generation of PCNs have lower sodium load than carboxypenicillins but similar side effects?
4th generation PCNs = acylaminopenicillins
Are 4th generation PCNs are they effective against penicillinase-producing strains of S aureus?
No, they are ineffective
4th generation PCNs are derivatives of what PCN?
ampicillin
What are some examples of PCN Beta lactamase inhibitors?
Clavulanic acid, sulbactam, and tazobactam
What do Beta lactamase inhibitors do?
Bind irreversibly to Beta-lactamase enzyme.
Inactivates these enzymes and rendering the organism sensitive to Beta-lactamase-susceptible PCN
Do Beta lactamase inhibitors have antimicrobial activity?
very little antimicrobial activity, they must be combined with PCNs
Clavulanic acid is available with what PO PCN?
Amoxicillin
Subactam is typically combined with what PCN and what route?
Parenteral ampicillin
Like PCN these antibiotics are bactericidal antimicrobials that inhibit bacterial cell wall synthesis and have a low intrinsic toxicity, what antibiotic would that be?
Cephalosporins
What can bacteria produce that disrupts the Beta-lactam structure of cephaosporins?
cephalosporinases
What are the two reasons for resistance to cephalosporins?
- bacteria producing cephalosporinases
2. cephalosporins inability to penetrate the bacteria to its site of action.
Newer cephalosporins have broader spectrums but may not be used why?
more expensive
IV administration of any cephalosporin can cause what? (key word IV)
thrombophlebitis
Which antibiotic can produce diacetyl metabolites which are associated with decreased antimicrobial activity?
Cephalosporins
Large doses of cephalosporins can cause what test to show up positive?
positive Coombs’ reaction, but hemolysis is rare
With the exception of cephaloridine, cephalosporins have less frequency of WHAT compared to aminoglycosides or polymyxins.
Nephrotoxicity
Majority of allergic reactions to Cephalosporins are what kind of reactions, and occur at within what time period?
Majority of reactions are cutaneous and occur 24 hours after exposure
What is the percentage of life-threatening anaphylaxis occurring due to cephalosporins?
0.02%
If you are allergic to one cephalosporin will you likely be allergic to others?
All share immunologic cross-reactivity: Allergic to one probably allergic to all
Is there cross-reactivity between cephalosporins and PCN?
INFREQUENT
What antibiotic may be used as an alternative to those with PCN allergies?
some cephalosporins may be used!
incidence of allergic reaction with cephalosporins and PCNs is?
1-10%
Considered the most allergic of all drugs?
PCNs
What is the most common adverse reaction for Beta-lactams?
hypersensitivity
Most often is allergic reaction delayed or immediate? what would that reaction look like?
delayed reaction: maculopapular rash and/or fever
Less often but more serious: immediate hypersensitivity that is mediated by IgE characterized by what three symptoms?
Laryngeal edema
Bronchospasm
CV collapse
It is said that a reaction to PCN can occur without prior known exposure, this is thought to occur due to what?
unrecognized exposure due to ingestion of foods
Is any route of administration of PCN more likely to cause an allergic reaction?
All routes can cause an allergic reaction.
Anaphylactic reactions are more associated with parenteral than oral administration.
If you have a cutaneous reaction to PCN once does it mean you will have that reaction every time and you can never take it again?
patients with cutaneous reactions may continue to take PCN in the future without a similar response.
How is an allergy to PCN formed?
The ring structure of PCN is opened to form a hapten metabolite: penicilloyl
what is penicilloyl?
The hapten metabolite that is formed when the ring structure of PCN is opened.
Why does a hapten metabolite like penicilloyl matter?
Haptens act as antigens. When bound to a protein may cause an immune response.
(does not induce formation of antibodies like an antigen, just the possibility of immune response when bound to a protein)
what do 95% of patients allergic to PCN have in common?
They form the penicilloyl-protein conjugate (major antigenic determinant)
5% patients allergic to PCN form 6-aminopenicillic acid and benzylpenamaldic acid, is this a major or minor antigenic determinant?
minor antigenic determinant.
How can you find out if someone will have an allergic reaction to PCN?
Skin test with penicilloyl-polylysine antigen can detect those who would have an allergic reaction to PCN.
Are both major and minor antigenic determinants detected by the penicilloyl polylysine antigen skin test?
Minor antigenic determinants are not detected with the skin test. But a patient with the minor antigen could still develop sever allergic reactions.
*From first generation cephalosporins to 3rd generation, how does the activity against gram-positive cocci and gram-negative cocci change?
In general activity against gram-positive cocci decreases, and activity against gram-negative cocci increases from first to third generation cephalosporins.
Price and toxicity of 1st gen. cephalosporins?
inexpensive and low toxicity
1st gen. cephalosporins are as active as 2nd and 3rd gen. against what two bacterium?
staphylococci and nonenterococcal streptococci
1st. generation cephalosporins are commonly used as prophylaxis in patients under going surgeries such as? (5 answers)
Intraabdominal Biliary CV Orthopedic Pelvic
What is the prototype drug for 1st generation cephalosporins?
Cephalothin
Cefazolin is what type/class of drug specifically?
1st generation cephalosporin
What are cephalosporins derived from?
7-aminocephalosporanic acid
Is cephalothin recommended for meningitis?
No, it does not enter CSF.
Drug of choice for surgical prophylaxis?
Cefazolin
This drug has essentially the same antimicrobial spectrum as cephalothin?
Cefazolin
Why does Cefazolin have the advantage of achieving higher blood levels than cephalothin?
due to slower renal elimination
Which routes is Cefazolin well tolerated?
IM and IV
recommended dose for cefazolin for surgical prophylaxis?
2g, but 3g for pts weighing greater than or equal to 120kg
recommended re-dosing interval for cefazolin?
4 hours
half life of cefazolin?
1-2 hours
pharmacologically similar to cefoxitin except has a methylthiotetrazole side chain which has a risk of bleeding and disulfiram like reactions with concurrent use of ETOH.
Cefamandole
Which 2nd generation cephalosporin is resistant to cephalosporinases produced by gram-negative bacteria.
Cefoxitin
What two 2nd generation cephalosporins have extended activity against gram-negative bacteria?
Cefoxitin and Cefamandole
more effective than cefamandole against H. influenza and is ONLY 2nd generation effective in treatment of meningitis.
Cefuroxime
Have enhanced ability to resist hydrolysis by the Beta-lactamases of many gram-negative bacilli including E. coli, Klebsiella, Proteus, and H. influenza.
3rd generation cephalosporins
Can achieve therapeutic levels in the cerebrospinal fluid and can be used to treat meningitis? (what group of drugs as a whole)
3rd generation cephalosporins
Cefotaxime is the first of the 3rd generation cephalosporins. Effective in a broad range of infections including?
meningitis caused by gram-negative bacilli other than Pseudomonas
What is the elimination half time of cefotaxime?
1 hour
30% is excreted as a desacetyl derivative that has antibacterial activity and is synergistic with parent compound, what drug am I?
Cefotaxime
Other name for Rocephin?
Ceftriaxone
has longest elimination ½ time of any 3rd generation. Highly effective against gram-negative bacilli including Neisseria and Haemophilus, what drug am I?
Ceftriaxone
effective 3rd generation PO medication. As active as other cephalosporins against: Pneumococci Group A streptococci H. influenza What drug am I?
Cefixime
Less effective against S. aureus and NOT active against anaerobes such as Pseudomonas, what antibiotic am I?
Cefixime
What antimicrobial drug is lacking the thiazolidine ring present in PCN and the dihydrothiazine ring found in cephalosporins?
Aztreonam
Is Aztreonam limited to gram positive or gram negative activity?
gram negative only
Disadvantages of Aztreonam is?
may develop enterococcal superinfections and significantly more expensive than aminoglycosides.
Unique advantage of Aztreonam is?
the absence of any cross-reactivity between aztreonam and circulating antibodies of PCN or cephalosporin allergic patients.
How should Aztreonam be given and why?
IV or IM if you want therapeutic blood levels, does not absorb from GI tract.
Which antimicrobials are Poorly lipid soluble but bactericidal for aerobic gram-negative bacteria?
Aminoglycosides
Aminoglycosides has extensive renal excretion, almost exclusively what?
glomerular filtration
Elimination half time of aminoglycosides is what? and in the presence of renal failure how does it change?
Elimination half time is 2-3 hours and prolonged 20-40 fold in presence of renal failure
How do you guide safe administration of aminoglycosides?
use plasma concentration measurements of the drug
Do aminoglycosides absorb well in the GI?
No, less than 1% absorbed into circulation when given PO.
What side effects limit aminoglycosides clinical usefulness?
Ototoxicity
nephrotoxicity
skeletal muscle weakness
potentiation of NMB drugs
Resistant organisms, frequent occurrence of vestibular damage with prolonged tx, and availability of less toxic antimicrobials are all things that limit the use of this antimicrobial today?
Streptomycin
First parenterally administered aminoglycoside that was active against gram-negative bacilli and Mycobacterium tuberculosis?
Streptomycin
This aminoglycoside Penetrates pleural, ascetic, and synovial fluids in presence of inflammation?
Gentamicin
at what mcg/mL concentration is Gentamicin toxic?
greater than 9 mcg/mL
What aminoglycoside is active against P. aeruginosa and gram-negative bacilli?
Gentamicin
Similar incidence of nephrotoxicity and ototoxicity as gentamicin?
Amikacin
A semisynthetic with advantage of not being associated with the development of resistance.
Used to treat infections caused by gentamicin or tobramycin resistant gram negative bacilli?
Amikacin
What medication should Amikacin not be used with and why?
Should not use with PCN d/t resulting antagonism of the bactericidal actions of PCN against some strains of Enterococcus faecalis.
Topical aminoglycoside used to treat infection of the after burns?
Neomycin
Neomycin is used as an adjunct to the therapy of hepatic coma why?
decreases ammonia concentrations
Oral form does not undergo systemic absorption and thus is used to decrease bacterial flora in the intestines before GI surgery?
Neomycin
What medications accentuate the ototoxic effects of aminoglycosides?
diuretics such as furosemide or mannitol.
If you are taking an aminoglycoside and you have nystagmus, vertigo, nausea, and acute onset of Meniere’s syndrome then what toxicity is occurring?
Vestibular toxicity
If you are taking an aminoglycoside and you have tinnitus or a sensation of pressure or fullness in the ears then what is taking place?
Auditory dysfunction
Which aminoglycoside is the MOST nephrotoxic and therefore is not administered by the parenteral route?
Neomycin
How do aminoglycosides cause nephrotoxicity?
aminoglycosides accumulate in the renal cortex and can produce acute tubular necrosis.
aminoglycosides can inhibit the prejunctional release of Ach while also decreasing postsynaptic sensitivity to the NT, but what medication can you give to overcome this effect?
IV calcium
A patient with what disease is uniquely susceptible to the skeletal muscle weakness if treated with aminoglycosides?
Myasthenia gravis
All macrolides are well absorbed where and why?
GI tract because they are stable in the presence of acidic gastric fluid.
Erythromycin is effective against what type of bacteria?
most gram positive bacteria
Most common side effect of Erythromycin is what, which severely limits it’s use?
GI intolerance
Erythromycin or clindamycin is an effective alternative to PCN or Cephalosporins for the treatment of what three things?
Streptococcal pharyngitis
Bronchitis
Pneumonia
Does Erythromycin need to have the dose altered in patients with renal failure?
No
Prolonged use of Erythromycin can results in what issues?
Thrombophlebitis at the injection site.
Tinnitus
Hearing loss
severe N/V
What macrolide is associated with Torsade’s de pointes?
Erythromycin
If you are giving a patient erythromycin and ketoconazole what can occur and why?
Increased plasma concentration of erythromycin increases the risk of ventricular dysrhythmias and sudden death. This is because erythromycin is metabolized by CYP3A and ketoconazole inhibits CYP3A, thus increasing the plasma concentration of erythromycin.
Azithromycin resembles erythromycin in its antimicrobial activity but has a different elimination half time, what would that be?
68 hours
How is azithromycin dosed?
1 time a day for five days
When should you take azithromycin?
take 1 hour before or 2 hours after a meal bc bioavailability is decreased by foods.
how long do tissues levels remain therapeutic with azithromycin after the five days of treatment?
4-7 days after the five day treatment course
Severe pseudomembranous colitis can be a complication of therapy, should be used only to treat infections that cannot be adequately treated by less toxic antimicrobial.
Clindamycin
Significant diarrhea caused by this drug suggest stopping and evaluation for pseudomembranous colitis.
Clindamycin
Clindamycin’s pre and postjunctional effects at the NMJ can it be treated like aminoglycosides?
No, calcium nor anticholinesterase drugs cannot fix.
What drug can induce profound and long lasting neuromuscular blockade in the absence of nondepolarizing muscle relaxants and after full recovery from the effects of Sch has occurred?
Clindamycin
prolongs NDMB even after reversal?
clindamycin
percentage of people that have skin rashes with clindamycin?
10%
How does Vancomycin work?
Bactericidal glycopeptide antimicrobial that impairs cell wall synthesis of gram-positive bacteria
Vancomycin according to our book is used PO ONLY for the treatment of what bacterium?
staphylococcal enterocolitis and antimicrobial associated pseudomembranous enterocolitis.
When allergic to PCN and/or Cephalosporin IV Vancomycin treats what bacterial infections?
Severe staphylococcal infections
Streptococcal
Enterococcal endocarditis
When using Vancomycin to treat enterococcal endocarditis what else should be given with the Vanc?
aminoglycosides are often needed
what is the drug of choice to treat MRSA?
Vancomyocin
Recommended infusion mg/Kg and time for vancomycin and why?
10-15 mg/Kg over 60 minutes over an hours to minimized to minimize occurrence of drug induced histamine release and hypotension.
What antibiotic may be given 2 hours prior to surgery for prophylaxis?
Vancomycin
If you give Vanc. in less than 30 min. what can happen? (has been reported)
profound hypotension and even cardiac arrest
elimination half time of Vanc. is?
6 hours
What is the ideal plasma level of Vancomycin?
20-30 mcg/mL
If a patient is on Vanc. with renal failure how prolonged can elimination be?
up to 9 days
at what plasma concentration of Vancomycin is ototoxicity likely to occur?
greater than 30 mcg/mL
Does Vancomycin produce direct myocardial depression?
Yes, but it is not the myocardial depression that is responsible for hypotension in humans, instead it is the histamine release that eventually causes the hypotension.
Histamine release caused by Vanc. can cause what syndrome?
Red man syndrome
What can be given before Vancomycin to decrease the effects of histamine release?
Oral H1 (diphenhydramine 1 mg/kg) and H2 (cimetidine 4 mg/kg) receptor antagonists administered 1 hour before induction of anesthesia decreased histamine –related side effects of rapid vancomycin infusion (1 gm over 10 min).
What can happen if you give Vancomycin to a patient recovering from Sch.- induced NMB?
has been known to result in return of neuromuscular blockade
Bacitracins is limited to what kind of antibacterial route?
topical application in ophthalmologic and dermatologic ointments.
Which antibiotic is bactericidal against Clostridium and most gram-neg. bacilli?
Metronidazole
What oral antibiotic is useful for treating pseudomembranous colitis?
Metronidazole
This antibiotic is associated with increased risk of tendinitis and tendon rupture that is enhanced in patients older than 60, with kidney, heart, or lung transplant and taking corticosteroids?
Fluoroquinolones
