Antimicrobial Agents Flashcards
antibiotic
chemical produced by one microbe and has the ability to harm other microbes
antimicrobial drug
any agent, natural or synthetic, that has the ability to kill or suppress microorganisms
bacteriocidal
directly lethal to bacteria at clinically achievable concentrations
bacteriostatic drugs
slow bacterial growth but do not cause cell death
Selective toxicity
ability of a drug to injure a target cell or target organism without injuring other cells or organisms that are in the intimate contact with the target
narrow-spectrum antibiotics
active against only a few species of microorganisms
broad-spectrum antibiotics
active against a wide variety of microbes
Four basic mechanisms for drug resistance from microbes
- decrease concentration of a drug at its site location.
- alter the structure of drug target molecules.
- produce a drug antagonist.
- cause drug inactivation.
causes random changes in a microbe’s DNA
spontaneous mutations
process by which extrachromosomal DNA is transferred from one bacterium to another.
conjugation
R factor (resistance factor)
- code for mechanism of drug resistance.
- cod for sexual apparatus for DNA transfer.
Conjugation takes place in primarily what bacteria?
Gram-negative
multiple drug resistance
transferring DNA that codes for several different drug-metabolizing enzymes to a single bacterium
which antibiotic agents promore the emergence of resistance
broad-spectrum agents
Superinfection
new infection that appears during the course of treatment for a primary infection, ridding inhibitory nature of normal flora, allowing infectious agent to flourish
superinfections are more likely in which type of patients
those receiving broad-spectrum agents
therapeutic objective when treating an infection
produce maximal antimicrobial effects, while causing minimal harm to the host
factors considered when prescribing a new antibiotic
- identity of the infecting organism.
- drug sensitivity of the infecting organism.
- host factors, site of the infection and the status of host defenses.
why will one drug of first choice be chosen over another one
greater efficacy, lower toxicity, more narrow spectrum
conditions ruling out first choice drug of choice
- allergies to drug.
- inability of drug of choice to penetrate to the side of infection.
- heightened susceptibility of the patient to toxicity of the first-choice drug.
two host factors that influence the selection of antibiotics
host defense and infection site.
Also: age, pregnancy, previous drug reactions.
host defenses
primarily of the immune system and phagocytic cells - antimicrobial therapy would be rare without it (concert).
minimum inhibitory concentration (MIC)
amount of bacteriocide at the site of infection
Antimicrobial concerns in infants
vulnerable to drug toxicity. Eliminate drugs slowly. No sulfonamides, kernicterus.
Antimicrobial concerns in children/adolescents
tetracyclines bind to developing teeth, causing discoloration.A
Antimicrobial concerns in pregnant women.
Placental crossing. Gentamicin, irreversible hearing loss. Also risk to mother
Antimicrobial concerns in breastfeeding women
enter breast milk. Sulfas cause kernicterus in infants
Antimicrobial concerns in older adults
reduced metabolism and excretion can result in accumulation
desirable concentrations for antibiotics
4-8x the MIC
Antimicrobial effect of 2 drugs is equal to the sum f the effects of the two drugs alone
additive response
the effect of the combination is grater than the sum of the effects of the individual agents
potentiative interaction
less effective therapy with 2 drugs than the use of one by itself
antagonism
most common indication for using multiple antibiotics
initial therapy for severe infection of unknown etiology, especially in the neutropenic host.
indications for antibiotic combinations
- initial therapy of severe infection.
- mixed infections.
- preventing resistance.
- decreased toxicity.
- enhanced antibacterial action.
locations susceptible to mixed infections
brain abscesses, pelvic infections, abd perf organs
infectious disease treated by multiple antibiotic combination
tuberculosis
combining amphotericin B with flucytosine does what
decreases toxicity - decreases risk of amphotericin-induced damage to kidneys
antibiotic treatment for enterococcal endocarditis
penicillin (weakens wall) and aminoglycoside (supress protein synthesis) - enhanced bacterial action
percentage of antibiotics used for prophylaxis
30-50%
surgical cases considered 100% infection risk, for which antibiotics is a treatment
contaminated surgery - perforated abdominal organs, compound fractures, lacerations from animal bites
most operations antibiotic choice
first-generation cephalosporin
bacterial endocarditis
congenital or valvular heart disease with prosthetic heart valves - unusually susceptible. Dislodge bacteria into bloodstream. AHA - much less often than previously prescribed.
much smaller number of neutrophils, which indicates for prophylactic antibiotic use
neutropenia
neutropenia prophylactic antibiotic use increases risk for
fungal infections - killing normal flora that suppresses fungal growth
prophylaxis for recurrent UTI
trimethoprim/sulfamethoxazole
prophylaxis against influenza
oseltamivir
bactericidal that disrupt the bacterial cell wall
beta-lactam
rigid, permeable, mesh-like structure that lies outside the cytoplasmic membrane
bacterial cell wall
penicillin mechanism of action
weakens bacterial cell wall, cell takes up water and bursts
penicillin is only effective against bacteria
undergoing growth and division
how does penicillin weaken the cell wall
- inhibition of transpeptidases
- disinhibition (activation) of autolysins
factors to determine bacterial resistance to penicillins
- inability of penicillins to reach their targets (PBPs)
beta-lactamases
enzymes that cleave the beta-lactam ring rendering beta-lactam antibiotics inactive
beta-lactamases that act selectively on penicillins
penicillinases
produce large amounts of penicillinases and export them into the surrounding medium
gram-positive bacteria
produce small amounts of penicillinases and secrete them into the periplasmic space
gram-negative bacteria
penicillin derivative resistant to actions of beta-lactamases
methicillin
mechanism of resistance for methicillin resistant staph. aureus
production of PBPs with low affinity for penicillins and almost all other beta-lactam antibiotics
PBPs
Penicillin-binding proteins - high affinity to penicillin, constituent in many bacteria
Four major groups of penicillins
- narrow-spectrum, penicillinase sensitive
- narrow-spectrum, penicillinase resistant (antistaphylococcal penicillins)
- broad-spectrum penicillins (aminopenicillins)
- extended-spectrum penicillins (antipseudomonal penicillins)
Examples of narrow-spectrum, penicillinase sensitive penicillins
Penicillin G, Penicillin V.
Streptococcus species, Neisseria species, many anaerobes, spirochetes.
Examples of narrow-spectrum, penicillinase resistant (antistaphylococcal) penicillins
Nafcillin, Oxacillin, Dicloxacillin.
Staphylococcus aureus.
Examples of broad-sprectrum penicillins (aminopenicillins)
Ampicillin, Amoxicillin.
Haemophilum influenzae, E. coli, Proteus mirabilis, enterococci, Neisseria gonorrhoeae
Examples of extended-spectrum penicillin (antipseudomonal) penicillin
Piperacillin.
Same as aminopenicillins plus more.
First penicillin available
Penicillin G (benzylpenicillin)
Penicillin G is first drug of choice for
pharyngitis and infectious endocarditis, also staph. aureus that don’t produce penicillinase.
Penicillin is preferred agent
for several gram-positive bacilli - gas gangrene and anthrax
pharmacokinetics of penicillin
available in 4 salts, all absorb to release penicillin G.
intramuscular administration of penicillin
all 4 salts may be administered, but different absorption rates
intravenous administration of penicillin
when high blood levels are needed rapidly. only potassium or sodium salts.
distribution of penicillin
distributes well to most tissues and fluids. varies in inflammation for penetration to cerebrospinal fluid, joints, and eyes.
metabolism of penicillin
minimal metabolism, eliminated by kidneys unchanged.
least toxic of all antibiotics
penicillin G
effective and safe alternatives for patients with penicillin allergies
vancomycin, erythromycin, clindamycin
examples of beta-lactamase resistant penicillin
nafcillin, oxacillin, dicloxacilin
what do beta-lactamase resistant penicillins treat
penicillinase-producing staph aureus and staph epidermidis
treatment of choice for MRSA
vancomycin
therapeutic goal of penicillins
treatment of infections caused by sensitive bacteria
baseline data of penicillin administration
tests to identify infection organisms and its drug sensitivity. microscopic culture before starting treatment. skin allergy test for hx of penicillin allergy.
high-risk patients for penicillin administration
hx of severe allergic reaction to penicillins, cephalosporins, or carbapenems
PO administration of penicillins with meals
one hour before or two hours after
evaluating therapeutic effects of penicillins
monitor for indications of antimicrobial effects
monitoring kidney function
measuring intake and output in kidney disease, acutely ill patients, and very old and young
minimizing adverse effects of penicillin
allergy skin test.
monitor sodium levels in sodium loaded.
monitor potassium levels and cardiac status in K loaded.
drug that is bactericidal, often resistant to beta-lactamases, active against broad spectrum of pathogens, low toxicity,
cephalosporin
mechanism of action of cephalosporin
- disrupt cell wall synthesis
- activate autolysins (cleave bonds in cell walls)
cephalosporin is most effective against cells
undergoing active growth and division
main form of resistance for cephalosporin
beta-lactamases
how many generations of cephalosporin are there
5
absorption of cephalosporin
most are parenterally
distribution of cephalosporin
well in pleural, pericardial, peritoneal fluids
metabolism of cephalosporin
kidney elimination
adverse reaction of cephalosporin
bleeding - cefotetan and ceftriaxone - interference with vitamin K metabolism.
thrombophlebitis - rotating infusion site and dilute med.
immune mediated hemolytic anemia- d/c.
differences when choosing which of the many cephalosporin to employ
antimicrobial spectrum and phamacokinetics
antimicrobial spectrum for cephalosporin
no broader than required
pharmacokinetic properties of interest in cephalosporin
- route of admin.
- duration of action.
- distribution of the CSF.
- route of elimination.
beta-lactam antibiotics with very broad antimicrobial spectra - none active against MRSA
cabapenems
four available cabapenems
imipenem, meropenem, ertapenem, doripenem
most widely used antibiotic in US hospitals
vancomycin
primary indications for vancomycin
C. diff, MRSA, serious infections with allergies to penicillin. only gram-positive
major toxicity of vancomycin use
renal failure
mechanism of action of vancomycin
inhibits cell wall synthesis - binding to molecules that serve as precursors for cell wall biosynthesis
high-risk patients for cephalosporins
history of allergic reactions to cephalosporins or other penicillins. Ceftriaxone for neonates reaching IV calcium.
how long do you bolus a cephalosporin injection to a continuous IV infusion
3 to 5 minutes
Vancomycin therapeutic goal
CDI, infection with MRSA, allergies to penicillin
red man syndrome
rapid infusion of vancomycin - flushing, rash, pruritus, urticaria, tachycardia, and hypotension.
second line agents used to treat infections resistant to first-line agents
bacteriostatic inhibitors
bacteriostatic inhibitors
tetracycline, macrolines, clindamycin
Four tetracyclines available for systemic therapy
tetracycline, demeclocycline, doxycycline, minocycline
mechanism of action for tetracyclines
suppress bacterial growth by inhibiting protein synthesis
Tetracyclines are first-line therapy for what infectious disorders
- rickettsial diseases.
- Chlamydia trachomatis.
- brucellosis.
- cholera.
- pneumonia by Mycoplasma pneumonia.
- Lyme disease.
- Anthrax.
- Gastic infection by H. pylori.
how are tetracyclines eliminated
liver and kidneys - liver bilee
tetracyclines bind to what in the teeth
calcium - yellow discoloration. darker is longer
clinical manifestations of hepatoxicity
lethargy and jaundice
vestibular toxicity has occurred with what tetracycline
minocycline
photosensitivity occurs with what antibiotic
tetracyclines
least expensive and most widely used member of the tetracycline family
tetracycline hydrochloride
Oldest member of the macrolides family
erythromycin
broad-spectrum antibiotics that inhibit protein synthesis and are big
macrolides
macrolides mechanism of action
bacteriostatic protein synthesis
erythromycin is first-choice drug for what
whooping cough, acute diphtheria, certain chlamydial infections, and pneumonia
erythromycin adverse effects
cardiac death from QT prolongation
clindamycin can promote what?
severe CDAD
clindamycin mechanism of action
binds to the 50S subunit of bacterial ribosomes and inhibits protein synthesis
therapeutic goal of tetracyclines
treatment of tetracycline-sensitive infections, acne, and periodontal disease
high risk patients for tetracyclines
pregnant women and children under 8, renal impairment
wait two hours after taking tetracycline to eat what
chelators (milk, calcium, iron, magnesium, antiacids)
high-risk patients of erythomycin
QT prolongation, inhibitors of CYP3A4
Therapeutic goal of clyndamicin
treatment of anaerobic infections outside the CNS
aminoglycosides
natural and semisynthetic antibiotics, bactericidal, potent, serious toxicities
ahminoglycosides are composed of
two or more amino sugars connected by a glycoside linkage
poqtantibiotid effect
bactericidal effect several hours after serum levels have dropped below the minimal bacterial concentration
antibiotic that cannot kill anaerobes
aminoglycosides - must be transported with oxygen
adverse side effects of aminoglycosides
ototoxicity and nephrotoxicity
gentamicin oral therapy indication
suppression of bowel flora before elective colorectal surgery
gentamicin topical therapy indication
local infections of the eyes, ears, and skin
mechanism of action of sulfonamides
bacteriostatic - suppress bacterial growth by inhibiting synthesis of tetrahydrofolate
principal indication for sulfonamides
UTI
most severe hypersensitivity response to sulfonamides
stevens-johnson syndrome - widespread lesions of the skin and mucous membrane, fever, malaise, toxemia.
antibacterial agent specifically for protozoal infections caused by anaerobic bacteria
metronidazole
fluorinated analogs of nalidixic acid
fluoroquinolones
