Deja Ch 2.1 Antibacterial Flashcards
What is a bacteriostatic antibiotic?
An antibiotic that causes reversible inhibition of growth. The bacteria are still present and able to replicate should the bacteriostatic antibiotic be removed. A bacteriostatic antibiotic therefore prevents the exponential growth of bacteria, allowing the host immune system better chances of clearing the bacteria that is present in the body.
What is a bactericidal antibiotic?
An antibiotic that causes irreversible inhibition of growth, therefore directly killing the bacteria
Why should bacteriostatic and bactericidal antibiotics not be given together?
Bacteriostatic drugs will antagonize the effects of bacteriocidal drugs which rely on the active replication and utilization of environmental resources by bacteria.
Which antibiotic inhibits bacterial cell wall synthesis by blocking glycopeptide polymerization through binding tightly to the D-alanyl-D-alanine portion of the cell wall (peptidoglycan) precursor?
Vancomycin
Vancomycin-resistant bacteria change their D-ala-D-ala terminus of the peptide side chain to what?
To D-ala-D-lactate; this change prevents the cross linking reaction necessary for elongation of the peptide side chain, weakening the cell wall and making the bacteria susceptible to lysis
Vancomycin is most commonly used to treat what types of infections?
Gram-positive infections. Vancomycin is only effective against gram-positive bacteria, and is particularly useful for infections due to methicillin resistant Staphylococcus aureus (MRSA) infections.
Does vancomycin have good oral bioavailability?
No. Vancomycin can be given orally to treat Clostridium difficile enterocolitis because the drug stays in the gastrointestinal tract (it is poorly absorbed from the GI tract).
What are the adverse effects of vancomycin?
Hyperemia, or “red man” syndrome (see following questions); ototoxicity (rare, but it must be used with caution when coadministered with other drugs having ototoxicity, such as aminoglycosides); nephrotoxicity (similar situation as described for ototoxicity); phlebitis at site of injection
Release of what substance is responsible for “red man” syndrome?
Histamine
How can vancomycin-induced “red man” syndrome be prevented?
By slowing the infusion rate. Infusion over 1 to 2 hours is normally sufficient. Additionally, antihistamines may be coadministered.
Which antibiotic inhibits the phosphorylation/dephosphorylation cycling of the lipid carrier required in the transfer of peptidoglycan to the cell wall?
Bacitracin (used topically only due to severe nephrotoxicity if given systemically)
Sulfonamide antibiotics antagonize what compound?
Para-aminobenzoic acid (PABA) (see next answer)
What is the mechanism of action of sulfonamide antibiotics?
Sulfonamides are structural analogs of PABA. This class of antibiotics is effective against bacteria that must use PABA to synthesize folate de novo. Sulfonamides work by inhibiting dihydropteroic acid synthase, the enzyme that catalyzes the condensation reaction between PABA and dihydropteridine to form dihydropteroic acid, the first step in the synthesis of tetrahydrofolic acid.
Do humans possess dihydropteroic acid synthase?
No. Therefore sulfonamides are selectively toxic to bacteria and other microorganisms.
Against which microorganisms are sulfonamides effective?
Gram-positive and gram-negative bacteria, Nocardia, Chlamydia trachomatis, some protozoa (malaria), Escherichia Coli, Klebsiella, Salmonella, Shigella, Enterobacter
Are sulfonamide antibiotics bactericidal or bacteriostatic?
Primarily bacteriostatic
What are the adverse effects of sulfonamide antibiotics?
Nausea; vomiting; diarrhea; phototoxicity; hemolysis (in individuals having glucose-6-phosphate dehydrogenase (G6PD) deficiency); hypersensitivity; Stevens-Johnson syndrome (incidence and severity of adverse effects greatly increase immunocompromised in AIDS patients)
Why are sulfonamide antibiotics contraindicated in neonates?
They displace bilirubin from albumin thereby causing kernicterus in neonates.
Give examples of sulfonamide antibiotics:
Sulfamethoxazole; sulfacetamide; sulfisoxazole; sulfadiazine (only available in the United States in combination with pyrimethamine); sulfadoxine in combination with pyrimethamine (the antimalarial “Fansidar”)
Name antibiotics that works synergistically with sulfonamides by preventing the next reaction in folate synthesis:
Trimethoprim or pyrimethamine
What is the mechanism of action of trimethoprim?
Competitive inhibitor of dihydrofolic acid reductase (DHFR), the enzyme that converts dihydrofolic acid to tetrahydrofolic acid
What are the adverse effects of trimethoprim?
Leukopenia; granulocytopenia; thrombocytopenia; megaloblastic anemia
The trimethoprim-sulfamethoxazole combination is most commonly used to treat what type of infections?
Urinary tract infections (UTI) primarily caused by E. coli as well as many upper respiratory infections (URI) such as Pneumocystis jiroveci pneumonia, some nontuberculous mycobacterial infections, most S. aureus strains, Pneumococcus, Haemophilus sp, Moraxella catarrhalis, and Klebsiella pneumoniae infections. However, up to 30% of UTI and URI pathogenic strains are resistant to this antibiotic combination.
Give examples of how bacteria may become resistant to sulfonamide antibiotics:
Increased concentrations of PABA; decreased binding affinity of target enzymes; uptake and use of exogenous sources of folic acid
What is the mechanism of action of fluoroquinolone antibiotics?
Inhibition of two DNA gyrases (bacterial DNA topoisomerase II and IV) which in turn prevents relaxation of supercoiled DNA inhibiting DNA replication and transcription
Give examples of fluoroquinolone antibiotics:
Ciprofloxacin, moxifloxacin, gemifloxacin, levofloxacin, lomefloxacin, norfloxacin, ofloxacin, gatifloxacin. All are fluorinated derivatives of nalidixic acid giving them the ability to be active systemically.
What types of bacteria are susceptible to quinolone antibiotics?
Many gram-positive and gram-negative bacteria. Examples include Shigella, Salmonella, toxigenic E. Coli, Campylobacter, Pseudomonas, Enterobacter, chlamydial urethritis or cervicitis, and atypical mycobacterial infections
What are the adverse effects of fluoroquinolone antibiotics?
Generally are well tolerated, but nausea, vomiting, and diarrhea are the most common adverse effects. Dizziness, insomnia, headache, photosensitivity, QT interval prolongation also occur with certain quinolones. Gatifloxacin causes hyperglycemia in diabetics and hypoglycemia when used in combination with oral hypoglycemics, and therefore is only available for ophthalmic use in the United States.
Why are fluoroquinolone antibiotics contraindicated in children?
They have deleterious effects on cartilage development, thereby causing tendonitis and possible tendon rupture.
Are fluoroquinolone antibiotics bactericidal or bacteriostatic?
Bactericidal
Give examples of how bacteria may become resistant to fluoroquinolone antibiotics:
Reduced drug penetration (drug efflux pumps); mutations in DNA gyrases result in decreased binding affinity of bacterial target enzymes for fluoroquinolones
What is the mechanism of action of b-lactam antibiotics?
They weaken the cell wall by inactivating transpeptidases (penicillin-binding protein [PBPs]), thereby inhibiting transpeptidation reactions necessary in the cross-linking of peptidoglycan subunits in the bacterial cell wall.
Name the four main classes of b-lactam antibiotics:
- Penicillins 2. Cephalosporins 3. Carbapenems 4. Monobactams
Give examples of how bacteria may become resistant to b-lactam antibiotics?
Production of b-lactamases (cleaves the b-lactam ring; the most common mechanism); alteration of PBPs; inhibition of drugs to reach PBPs; downregulation of porin structure (only in gram-negative organisms since gram-positive organisms lack the outer cell wall where porins are located); development of efflux pumps in gram-negatives
Which class of b-lactam antibiotics is resistant to b-lactamases?
Monobactams
Give an example of a monobactam antibiotic:
Aztreonam. This is the only monobactam available in the United States.
What organisms are monobactams active against?
Aerobic gram-negative rods, including pseudomonas
Can a monobactam be used in a penicillin-allergic patient?
Yes. This makes monobactams a good choice for patients with a penicillin allergy and a serious gram- negative infection.
Give examples of antibiotics that belong to each of the following penicillin classes: _-lactamase susceptible; narrow spectrum
Penicillin G (intravenous); penicillin V (oral)
Give examples of antibiotics that belong to each of the following penicillin classes: _-lactamase susceptible; broad spectrum
Amoxicillin; ampicillin; piperacillin; ticarcillin
Give examples of antibiotics that belong to each of the following penicillin classes: _-lactamase resistant; narrow spectrum
Methicillin; nafcillin; dicloxacillin; oxacillin
Penicillins are synergistic with what other antibiotic drug class in the treatment of enterococcal and pseudomonal infections?
Aminoglycosides. Aminoglycosides are very polar molecules that cannot easily cross the cell wall. With inhibition of cell wall formation by penicillins, aminoglycosides are then able to enter cells and exert their effects.
Name three _-lactamase inhibitors that can be used in combination with penicillins:
- Clavulanate 2. Sulbactam 3. Tazobactam
What are the adverse effects of the penicillin antibiotics?
Hypersensitivity; acute interstitial nephritis (common with methicillin); nausea; vomiting; diarrhea; hepatitis (oxacillin); hemolytic anemia; pseudomembranous colitis (ampicillin)
What is the mechanism of methicillin resistance by S. aureusl?
Production of an alternative PBP 2a
Does Streptococcus make b-lactamase?
No (mechanism of resistance is via altered PBPs)
Are b-lactam antibiotics effective in treating Mycoplasma infections?
No (Mycoplasma have no cell walls)
Give examples of medications in each of the following cephalosporin classes: First generation
Cefazolin; cephalexin; cefadroxil; cephapirin; cephradine
Give examples of medications in each of the following cephalosporin classes: Second generation
Cefuroxime; cefotetan; cefaclor; cefoxitin; cefprozil; cefpodoxime; cefamandole; cefmetazole; loracarbef; cefonicid
Give examples of medications in each of the following cephalosporin classes: Third generation
Cefotaxime; Ceftazidime; Ceftriaxone; Cefpodoxime; cefdinir; cefditoren; ceftibuten; cefixime; cefoperazone; ceftizoxime; moxalactam
Give examples of medications in each of the following cephalosporin classes: Fourth generation
Cefepime (only representative drug of this generation)
Which cephalosporin has the broadest spectrum of activity and is resistant to _-lactamases?
Cefepime
How does the antibiotic spectrum of activity of cephalosporins vary by generation, that is, how does the coverage of second-generation drugs compare to first generation and so on?
Second generation: increased gram-negative coverage as compared to first generation. Third generation: continued increase in gram-negative coverage and greater ability to cross blood-brain barrier as compared to second generation drugs. Fourth generation: increased _-lactamase resistance as compared to third-generation drugs
Give examples of carbapenem b- lactams:
Imipenem; meropenem; ertapenem; doripenem
Why is cilastatin given concomitantly with imipenem?
Cilastatin (a dipeptidase inhibitor) inhibits renal dihydropeptidases in the renal tubules which inactivate imipenem, thereby allowing imipenem to exert its effects.
What is the difference in microbial coverage between imipenem and ertapenem?
Ertapenem does not cover Acinetobacter species and pseudomonal species.
What is the mechanism of action of aminoglycoside antibiotics?
Binds to 3OS ribosomal subunit to prevent formation of initiation complex, thereby inhibiting bacterial protein synthesis; incorporation of incorrect amino acids in the growing peptide chain
Are aminoglycoside antibiotics bactericidal or bacteriostatic?
Bactericidal
Give examples of aminoglycoside antibiotics:
Gentamicin; tobramycin; streptomycin; amikacin; neomycin
What is streptomycin commonly used to treat?
Tuberculosis infections
Why might the efficacy of an aminoglycoside be increased when given as a single large dose as opposed to multiple smaller doses (two reasons)?
- Concentration-dependent killing: increasing concentrations of aminoglycosides kill a greater proportion of bacteria more quickly. ; 2. Postantibiotic effect: the antibacterial activity of aminoglycosides lasts longer than detectable levels of the drug are found in the bloodstream.
Against which organisms are aminoglycosides effective?
Gram-negative aerobes. Aminoglycosides passively diffuse across porins in the outer membrane of gram- negatives and their entry across the inner membrane is oxygen dependent. Use with a (_-lactam increases gram- positive coverage.
