Antibiotics NURS 305

Define selective toxicity

The ability of a drug to injure a targeted cell or target organism without injuring other cells or organisms

In what three ways is antibiotic selective toxicity achieved?

Disruption of bacterial cell wall

Inhibition of an enzyme unique to bacteria

Disruption of bacterial protein synthesis

Why do antibiotics not cause much toxicity?

Aspects they target are only fond in bacteria; highly selective

Do human cells have peptidoglycan? Why is this important?

No; antibiotics can only penetrate the peptidoglycan layer found in bacteria

What are the five main mechanisms of action of antibiotics?

Inhibit bacterial ell wall synthesis

Increase cell membrane permeability

Inhibit bacterial protein synthesis

Inhibit bacterial synthesis of nucleic acids

Inhibit specific biochemical reactions

What is the main disadvantage of broad-spectrum antibiotics?

Extensively affects body flora

Bactericidal vs bacteriostatic

"cidal": kills bacteria directly

"static": halts bacterial growth without killing bacteria

What happens over time with repeated exposure to antibiotics?

Resistance

What are some bacteria that have microbial drug resistance?

S. aureus, enterobacter, pseudomonas aeruginosa, C. diff

What are the four basic mechanisms of microbial drug resistance?

Decrease concentration of drug at its site of action

Inactivate a drug

Alter structure of drug target molecules

Produce a drug antagonist

How do resistant microbes decrease antibiotic concentration inside bacterial cells?

Pump antibiotic outside the cell via p-glycoprotein pump

What are the two main mechanisms of acquired antibiotic resistance?

Spontaneous mutation, conjugation

What causes multi-drug resistance?

Conjugation; DNA is being transferred to other bacteria

Which gram of bacteria most commonly undergo conjugation?

Gram-negative

Which mechanism for acquired resistance usually causes resistance to one drug?

Spontaneous mutation

Which type of antibiotics does the most to facilitate the emergence of resistance?

Broad-spectrum

The more that antibiotics are used, the (faster/slower) drug-resistant organisms emerge

Faster

What are the three main types of infections that result from drug resistance?

Nosocomial, superinfection, community-acquired

What is a superinfection?

New infection that appears during the course of treatment for a primary infection

Why are superinfections usually difficult to treat?

They are cased by drug-resistance microbes

What are examples of superinfections?

Candida, C. diff

What can result from ending a medication regimen early?

Resistance

What is empiric therapy?

Antibiotic therapy for patients before causative organism is positively identified

What should be done before giving empiric therapy?

Collect culture and sensitivity

Should a C&S or med be done first?

C&S

What are the main host factors that determine which med will be given?

Host defenses (skin, mucous membranes, etc), site of infection, previous allergic reactions, genetic mutations

What is a common mutation that influences how individuals metabolize meds?

G6PD

When combining two antibiotics with different MOA's, which types of drug-drug interactions can occur?

Additive, synergistic

What are some indications for combining multiple antibiotics?

Mixed infections, prevention of resistance, decreased toxicity, enhanced bacterial action

In what medical cases are antibiotics given for prevention rather than to treat an established infection?

Surgery, bacterial endocarditis, neutropenia, heart valve issues

What are some common misuses of antibiotics?

Attempted treatment of viruses, treatment of fever of unknown origin, improper dosages, treatment in the absence of adequate bacteriologic information, omission of surgical drainage

A patient has a fever. The cause is unknown. What must the doctor NOT do?

Prescribe an antibiotic

If a patient has an abscess, should the abscess be drained or should an antibiotic be given first?

Abscess should be drained, THEN antibiotic

What are common examples of gram-positive bacteria?

Staphylococcus, streptococcus, enterococcus

What are common examples of gram-negative bacteria?

E. coli, proteus, pseudomonas, enterobacter, klebsiella, shigella

Are gram-negative or gram-positive bacteria more dangerous? Why?

Gram-negative; three-layered wall and production of toxins

What are the four beta-lactam classes of antibiotics?

Penicillins, cephalosporins, carbapenems, monobactams

Penicillins, cephalosporins, carbapenems, monobactams are known as what type of antibiotics?

Beta-lactam

What is the MOA of penicillins?

Inhibit cell wall synthesis

Where are most penicillins excreted?

Kidneys

Penicillins are what type of antibiotic?

Beta-lactam

Cephalosporins are what type of antibiotic?

Beta-lactam

Carbapenems are what type of antibiotic?

Beta-lactam

Monobactams are what type of antibiotic?

Beta-lactam

Which penicillin is NOT excreted by the kidneys?

Nafcillin

What are the four types of penicillins?

Narrow-spectrum, anti-staphylococcal, broad-spectrum, antipseudomonas

What is the spectrum of penicillinase-sensitive antibiotics?

Narrow-spectrum

What are examples of narrow-spectrum penicillins?

PCN V and PCN G

PCN V and PCN G are examples of what kind of penicillin?

Narrow-spectrum/penicillinase-sensitive

What is the spectrum of penicillinase-resistant antibiotics?

Antistaphylococcal

What are examples of antistaphylococcal penicillins?

Nafcillin, Methicillin, Oxacillin, Cloxacillin, Dicoxacillin

Which PCN specifically targets S. aureus?

Oxacillin

Nafcillin - what type of PCN?

Antistaphylococcal/penicillinase-resistant

Methicillin - what type of PCN?

Antistaphylococcal/penicillinase-resistant

Oxacillin - what type of PCN?

Antistaphylococcal/penicillinase-resistant

Which bacteria has a very low acceptance of beta-lactams?

S. aureus

How many cell layers does gram-negative bacteria have?

3

What are the components of a gram-negative cell envelope?

3-layers; thin cell wall, additional outer membrane that is difficult to penetrate

What are the components of a gram-positive cell envelope?

2-layers; relatively thick cell wall that is easy to penetrate

What are beta-lactamases?

Enzymes produced by bacteria that render penicillins inactive (and other beta-lactam antibiotics)

What are the enzymes produced by bacteria that render penicillins inactive (and other beta-lactam antibiotics)?

Beta-lactamases

What are examples of broad-spectrum penicillins?

Ampicillin, amoxicillin

What are broad-spectrum penicillins aka?

Aminopenicillins

Ampicillin - which type of PCN?

Broad-spectrum/aminopenicillin

Amoxicillin - which type of PCN?

Broad-spectrum/aminopenicillin

Which infections are aminopenicillins active against?

Same as PCN G, plus influenza, enterococcus, E. coli, salmonella, shigella

Which antibiotic is most effective against E. coli?

Amoxicillin, ampicillin

Are broad-spectrum/aminopenicillins affected by beta-lactamases?

Yes

What are examples of antipseudomonal PCN's?

Piperacillin, ticarcillan

Which infections are antipseudomonal PCN's active against?

Same as aminopenicillins, plus enterobacter, proteus, klebsiella

Are antipseudomonal PCN's affected by beta-lactamases?

Yes

How are the actions of beta-lactamases prevented when giving a PCN?

Giving with a beta-lactamase inhibitor

When are beta-lactamase inhibitors used?

When infection is more serious or resistance is more prevalent in the person or facility

What might amoxicillin be switched to if it becomes ineffective?

Augmentin (amox. with a beta-lactamase inhibitor)

What is the most common adverse effect to PCNs?

Hypersensitivity rxn

Are PCN adverse rxns very common? Why or why not?

No; they are very selective

How does PCN anaphylaxis affect risks for superinfections?

30% increased risk for MRSA or c. diff

What are contraindicated with PCN anaphylaxis?

Cephalosporins

If a person "might be allergic to PCN's" but they aren't sure, what should the nurse do?

PCN skin test

What are S/Sx of PCN allergy?

Uticarial rash, flushing, diaphoresis, tachycardia, respiratory difficulties

What are S/Sx of PCN anaphylaxis?

Hypotension, severe respiratory distress, laryngeal edema, tachycardia, cyanosis, seizures

What are the three main body systems that can be adversely affected by penicillins?

Neuro (toxicity), kidneys (nephropathy), hematologic (eosinophilia, hemolytic anemia, leukopenia, bone marrow depression)

What is the MOA of cephalosporins?

Bond to penicillin-binding proteins, disrupt cell wall synthesis, cause cell lysis

When are cephalosporins most effective?

Cells undergoing active growth and division

Describe how each of the five generations of cephalosporins responds to beta-lactamases

First generation are destroyed, second generation is less sensitive, third-fifth are much more resistant than the first two

What are the three rules of thumb as you move up in cephalosporin generations?

1. Increasing activity against gram-negative bacteria

2. Increased resistance to destruction by beta-lactamases

3. Increased ability to reach the CSF

When might cephalosporins be given?

Surgical prophylaxis, RTI's, skin/soft tissue infections, bones/joints, UTI, septicemia

What are the first generation cephalosporins?

Cefazolin, cephalexin