Lecture 14 - Antibiotics Flashcards
What are some common diseases caused by pathogenic bacteria?
- Bacteremia
- Pneumonia
- Meningitis
- Tuberculosis
- Epiglottitis
- Gonorrhoeae
What are some factors that influence development of infection?
- Systemic – disease and drugs
- Local – cleaning, closure of wound, contraction of vessels
- Virulence, number, host resistance
What determines the selection of antibiotic?
- Identification of organism
- Susceptibility of organism to a particular agent
- Site of infection
- Drug characteristics (lipid solubility, molecular weight, protein binding)
___ soluble antibiotics penetrate the lung tissue better
Lipid
What is an advantage and disadvantage to protein binding?
- Can increase half-life
- More protein binding means less efficient diffusion
When is the oral route chosen for antibiotics?
Infections that are mild and can be treated on an outpatient basis
When is the intravenous route chosen for antibiotics?
Most serious infections
What is an example of an antibiotic that is poorly absorbed by the intestine?
Vancomycin
What patient factors affect selection of antimicrobial agent?
- Immune system
- Renal function
- Hepatic function
- Poor perfusion
- Age
- Pregnancy/lactation
What is empiric therapy?
- Initiation of treatment before a firm diagnosis
- Usually use broad spectrum antibiotics
What is directed therapy?
Choose treatment based on knowledge of the organism that is the cause of the infection
What factors influence the choice of empiric therapy?
- Site of infection
- Immunocompromised
- Neutropenia
- Community vs. hospital acquired infection
- Age
What is neutropenia?
Low levels of neutrophils
When would antibiotics be used for suppression?
Px may have a chronic bacterial infection in a place of the body that is hard for antibiotics to penetrate, so would use antibiotics to prevent a systemic infection
What does bactericidal mean?
Kills bacteria at concentrations achievable in the patient
What does bacteriostatic mean?
Arrests the growth and replication of organisms, limiting the spread of infection
What is concentration-dependent killing?
Significant increase in the rate of bacterial killing w/ higher concentrations of the drug
When is concentration-dependent killing useful?
Rapid killing of infective pathogens
What are narrow spectrum antimicrobial agents?
Act on a limited group of microorganisms
What are extended spectrum antimicrobial agents?
Effective against one class of organisms as well as a significant number in a different class
What are broad spectrum antimicrobial agents?
Kill a range of antimicrobial species
When are antimicrobial combinations used?
- Unknown organism
- Polymicrobial infection
- Antibiotic synergy
- Patient/population factors
What are disadvantages to antimicrobial combinations?
- Superinfection
- Eradication of normal microflora
- Resistance
- Adverse effects (greater toxicity)
- Patient adherence to therapy
- Increased cost
Define antibiotic synergism
When the effect of 2 drugs in combination is greater than the sum of the effect when 2 drugs are administered independently
Define antibiotic antagonism
When the effect of 2 drugs in combination is less than the sum of the effect when 2 drugs are administered independently
What are the mechanisms of antibiotic synergy?
- One drug enhances uptake of the second
- One drug enhances the metabolic effect of the other
- Drugs act sequentially in a common pathway
- Drugs inhibit the same target but in different ways
- 2 or more drugs inhibit targets in different pathways
What are mechanisms of antibiotic antagonism?
Not well studied b/c disadvantageous for clinical therapy
What is one of the most widely effective and least toxic antibiotic strategies?
Targeting synthesis of bacterial cell walls
Cell wall inhibitors are only effective against _____
Actively growing bacteria
What is the mechanism of penicillin?
- Blocks last step of bacterial cell wall synthesis
- Inhibits transpeptidases
- Causes osmotic pressure on cells, resulting in cell lysis
What do transpeptidases do?
Form cross-links between peptidoglycan chains that are essential for cell wall integrity
What enzymes do gram positive bacteria produce and why is this important to cell walls?
- Autolysins, which break down the cell wall
- Without active cell wall synthesis autolysins can damage the cell
What are 2 examples of penicillinase-resistant penicillins?
Methicillin and cloxacillin
What are 2 examples of extended spectrum penicillins?
Ampicillin and amoxicillin
Which portion of penicillin is critical to inhibit the transpeptidase enzyme?
Beta lactam ring
What type of side effects will all antibiotics that are administered orally have?
GI effects
What is needed to be considered bacteriocidal?
At least 3log10 killing
What are some adverse effects of penicillins?
- GI effects
- Allergy to metabolites
- Cross allergy w/in penicillin class
- Reduced coagulation for px receiving anticoagulants
Is penicillin safe for pregnant and breastfeeding women?
Yes
Cephalosporins are structurally similar to _____
Penicillins
What are some adverse effects of cephalosporins?
- Cross resistance and cross allergic potential w/ each other and w/ penicillins
- Allergy and GI effects less common than w/ penicillins
What is the mechanism of protein synthesis inhibitors?
Bind to 70S ribosomes, which are only found in bacteria
Which microorganisms are protein synthesis inhibitors effective against?
Gram positive and gram negative
What are examples of protein synthesis inhibitors?
- Tetracyclines
- Aminoglycosides
- Macrolides
- Chloramphenicol
- Clindamycin
What is the mechanism of tetracyclines?
- Bind irreversibly to 30S ribosome
- Blocks acyl-tRNA access to the ribosome
Tetracyclines are _____ spectrum
Broad
Are tetracyclines bacteriostatic or bactericidal?
Bacteriostatic
What are some adverse effects of tetracyclines?
- GI discomfort
- Deposition in bones and teeth of growing children
- Hepatotoxicity
- Increased UV sensitivity
- Dizziness, nausea, vomiting
- Resistance is common
Which patients shouldn’t get tetracyclines?
- Kidney/liver disease
- Pregnant/lactating
What is the mechanism of aminoglycosides?
- Bind irreversibly to 30S ribosome
- Blocks functional assembly of ribosome
Which bacteria are aminoglycosides effective against?
Aerobic gram negative bacteria
Are aminoglycosides bactericidal or bacteriostatic?
Bactericidal
Which aminoglycosides are derived from streptomyces?
Streptomycin and kanamycin
Which aminoglycosides derived from micromonospora?
Gentamicin and amikacin
What are some adverse effects of aminoglycosides?
- Nephrotoxicity
- Ototoxicity (deafness)
- Neuromuscular paralysis
- Allergic reactions (contact dermatitis)
What is the mechanism of macrolides?
- Bind irreversibly to 50S ribosome
- Block peptidyl transfer
Are macrolides broad or narrow spectrum and which bacteria are they effective against?
- Broad spectrum
- Gram positive
Are macrolides bacteriostatic or bactericidal?
Bacteriostatic, but bactericidal at high doses
Which macrolides are derived from streptomyces?
Erythromycin, clarithromycin, and azithromycin
What are some adverse effects of macrolides?
- GI problems
- Jaundice
- Ototoxicity
- Prolonged QTc interval in px w/ existing arrythmias
- Myopathy (interactions w/ statins)
When is quinupristin/dalfopristin used?
For treatment of vancomycin resistant enterococcus
What is quinupristin/dalfopristin?
Mixture of 2 drugs in a ratio of 70:30
What is the mechanism of quinupristin?
Binds to 50S subunit preventing peptide elongation
What is the mechanism of dalfopristin?
Binds to 23S subunit preventing peptidyl transfer
Is quinupristin/dalfopristin bacteriostatic or bactericidal?
Bactericidal w/ long post-antibiotic effect
What are some adverse effects of quinupristin/dalfopristin?
- Venous irritation when given IV
- Joint/muscle ache in px w/ high doses
- Hyperbilirubinemia
- Inhibits cytochrome P450
What is the mechanism of DNA/RNA synthesis inhibitors?
- Inhibit enzymes required for bacterial DNA synthesis
- Inhibit bacterial topoisomerase or DNA gyrase
- Block synthesis of DNA/RNA and growth of cells
DNA/RNA synthesis inhibitors are only effective against _____
Actively growing bacteria
What are 2 examples of DNA/RNA synthesis inhibitors?
Fluoroquinolones and rifamycin
What is the mechanism of fluoroquinolones?
1) Inhibit DNA gyrase
2) Prevent DNA replication
3) Bactericidal
What are some adverse effects of fluoroquinolones?
- GI (nausea, vomiting, diarrhea)
- CNS (dizziness)
- Phototoxicity
- Cartilage erosion
Are fluoroquinolones safe to use in pregnant or nursing women?
No
What is the most commonly prescribed fluoroquinolone?
Ciprofloxacin
Which infections is ciprofloxacin used for?
- Bones/joints
- Respiratory tract
- Urinary tract
What are some interactions w/ ciprofloxacin and levofloxacin?
- Alters levels of drugs metabolized by CYP 1A2
- Warfarin levels increased
- Increased seizure risk when used w/ NSAIDs
Which infections is moxifloxacin used for?
- Respiratory tract and tuberculosis
- Endocarditis
- Meningitis
- Conjunctivitis
What is the most common adverse effect of moxifloxacin?
May prolong QTc interval
What does moxifloxacin interact w/?
Warfarin
What is the mechanism of metabolite synthesis inhibitors?
- Competitive inhibitors of essential metabolites
- Structurally similar to metabolite but doesn’t fulfill its metabolic function w/in the bacteria
What are 2 examples of metabolite synthesis inhibitors?
Sulfonamides and trimethoprim
What is the mechanism of sulfonamides?
Inhibit synthesis of bacterial dihydrofolic acid
Are sulfonamides broad or narrow spectrum and which bacteria are they effective against?
- Broad spectrum
- Effective against more gram positive and many gram negative bacteria
Which bacteria are resistant to sulfonamides?
Bacteria that obtain folates from the environment
What are some short acting sulfonamides?
Sulfamethoxazole and sulfadiazine
What is a long acting sulfonamide?
Sulfadimethoxine
What are common adverse effects of sulfonamides?
- Allergies (rashes)
- Kernicterus, especially newborns (bilirubin-induced brain dysfunction)
- Nephrotoxicity
- Hemolytic anemia
What is the mechanism of trimethoprim?
Inhibit synthesis of bacterial tetrahydrofolic acid
Is trimethoprim broad or narrow spectrum and which bacteria is it effective against?
- Broad spectrum
- Effective against most gram positive and many gram negative
Is trimethoprim bacteriostatic or bactericidal?
Bacteriostatic
What infections is trimethoprim used for?
- UTI’s
- Vaginal infections
- Bacterial prostatitis
- Prophylaxis
Can trimethoprim be used in pregnant women?
No
What does trimethoprim interact with?
Warfarin
What is cotrimoxazole composed of?
Trimethoprim:sulfonamethoxazole in 1:5 ratio
What is cotrimoxazole used for?
Inhibition of folate synthesis
What is cotrimoxazole used for?
- UTI’s
- Respiratory tract infections
- Kidney infections
- GI tract infections
- Septicemia
- Prophylaxis in HIV px
Is cotrimoxazole widely used? Why or why not?
No b/c of high level of adverse reactions
Can cotrimoxazole be used in pregnant women?
No
What are some adverse effects of cotrimoxazole?
- Skin rashes
- Nausea, vomiting
- Jaundice, renal damage/failure
How long does it take for relief of symptoms when taking antibiotics?
Usually 48-72 hours
What is the common duration of antibiotic therapy?
7-14 days, but longer for tuberculosis (months)
Why does the full course of antibiotics need to be finished even if the px is feeling better?
Reduce the risk of developing a secondary infection and reduces selection of resistant bacteria
How can GI and vaginal side effects be minimized or prevented?
Take oral antibiotics w/ food
