Antibacterials Flashcards
bacteriostatic
inhibits bacterial growth without causing death. MIC= minimum inhibitory concentration.
bactericidal
rapidly kills bacteria by disrupting synthesis or integrity of the cell wall. MBC for 99.9% death
5 bactericidal mechanisms of action
- -cell wall synthesis
- -protein synthesis
- -nucleic acid synthesis
- -antimetabolites
- -bacterial membrane disruption
2 classes of antibiotics that inhibit cell wall synthesis
beta-lactams (penicillins, cephalosporins, carbapenems, monobactams) and glycopeptides
Penicillin mechanism
- -bind PBPs to inhibit cell wall synthesis of peptidoglycan layer
- -beta-lactam ring is antibacterial
- -side chains dictate spectrum
Penicillin side effects
Results from hypersensitivity
- -Morbilliform rash (most common) due to IgM response
- -Anaphylaxis (rare) IgE mediated leads to angioedema, bronchospasm, hypotension
Cephalosporin mechanism
- -inhibit peptidoglycan synthesis by binding PBPs
- -compared to penicillin: wider spectrum, can kill many beta-lactamase bacteria, improved pharmacokinetics
Cephalosporin coverage and side effects
- -better coverage of Gram (-) with later generations
- -can be useful for penicillin hypersensitivity unless they have a history of anaphylaxis runs
Carbapenem mechanism
- -inhibit peptidoglycan synthesis by binding PBPs
- -compared to penicillin: wider spectrum, can kill many beta-lactamase bacteria, improved pharmacokinetics
Carbapenem coverage and side effects
- -very wide coverage, antipseudomonal
- -seizures is main side effect
- -avoid giving to CNS compromised pts.
Monobactams (aztreonam) mechanism and side effects
- -reserved for penicillin allergic patients
- -ONLY active against Gram (-) aerobic bacteria
- -no major side effects
Beta-lactam resistance mechanisms
(1) beta-lactamases (degradative enzymes)
(2) PBPs (cell wall resistant transpeptidases)
(3) efflux pumps
Beta-lactamase inhibitor mechanisms
- -weak antibactericidal, must combine with penicillins
- -irreversibly bind/inactivate beta-lactamses of bacteria
Glycopeptide mechanism
(Vancomycin)
- -inhibits cell wall formation by interacting with D-alanine-D-alanine termini of pentapeptide side chains in the cell wall
- -no beta-lactam cross resistance
- -ONLY active against Gram (+) organisms
Vancomycin side effects
- -**Red Man’s: histamine release from rapid AB infusion –> anaphylaxis
- -administer more slowly
- -neutropenia & nephrotoxicity
Vancomycin resistance
- -molecule is too large to penetrate outer membrane of Gram (-) bacteria
- -also unable to bind to bacteria from changes in pentapeptide side chain terminus
Protein synthesis inhibitors (30S ribosome)
- -aminoglycosides (streptomycin)
- -tetracyclines
Protein synthesis inhibitors (50S ribosome)
- -clindamycin
- -macrolides (erythromycin)
- -chloramphenicol
- -linezolid
- -streptogramins (quinupristin/dalfopristin)
Aminoglycoside mechanism
- -Gram (-) rods
- -irreveribly bind to 30S ribosomes
- -commonly used in syngery with beta-lactam or vancomycin for Gram(+) treatment
Aminoglycoside side effects
- -nephrotoxicity (dose > 1/day or treatment > 3 days)
- -ototoxicity (often irreversible)
Aminoglycoside resistance
- -*mutation of 30S ribosome binding site
- -decreased AB uptake
- -enzymatic modification of AB
- -efflux pump
Tetracyclines mechanism
- -**bacteriostatic binding to 30S ribosome
- -effective against variety of typical and atypical organisms
Tetracycline side effects
- -teeth discoloration given to children
- -brown skin discoloration
- -dark melanin deposits on skin
Tetracyclne resistance
- -decreased penetration into bacteria
- -efflux pump
- -*30S ribosome allows binding but protein synthesis continues
Macrolide mechanism
–**bacteropstatic against atypicals, gram (+), and some mycobacteria
Macrolide side effects
- -(enteric like) abdominal cramps, nausea, vomitting, diarrhea
- V tach with QT prolongation
Macrolide resistance
- -*methylation of 50S ribosome binding site
- -efflux pump
- -enzyme modification of AB
- -decreased permeability of outer envelope
Lincosamide mechanism
(Clindamycin)
- -**bacteriostatic against Gram (+) AND anaerobes 50S ribosome
- -used to prevent toxin formation (TSS)
Lincosamide side effects
(Clindamycin)
- -20% diarrhea
- -rare C. difficile colitis
Clindamycin resistance
- -alteration of 50S protein receptor
- -methylation of 50S subunit binding site (**cross-resistance with macrolides)
- -decreased penetration
Oxazolidinones (Linezolid)
–**Bacteriostatic against resistant Gram (+) 50S
Oxazolidinones (Linezolid) side effects
- -lactic acidososis
- -neuropathy
- -cytopenias
Chloramphenicol mechanism
- -*static or cidal depending on bacteria
- -Salmonella
- -50S ribosome target
Chloramphenicol side effects
–Disrupts protein synthesis in bone marrow cells
Chloramphenicol resistance
- -*production of chloramphenicol acetytransferase, catalyzes AB
- -decreased permeability
Nucleid acid synthesis antibiotics
- -DNA replication: quinolones & metronidazole
- -RNA replication: rifamycins
Quinolone mechanism
- -inhibit DNA gyrases -> breaks in DNA
- -active against Gram (+) and (-)
Quinolone side effects
- -tendonitis with rupture
- -headache dizzine, insomnia
- -QT prolongation
Metronidazole mechanism
- -bacteria reduce AB nitro groups resulting in toxic compounds that disrupt DNA
- -activae against anaerobic bacteria and some parasites
Metronidazole side effects
- -neuropathy
- -ataxia, dysarthria, cerebellar dentae lesions
Metronidazole resistance
- -reduced AB activation
- -elimination of compounds before DNA interaction
Rifamycin mechanism
- -bind to RNA polymerase inhibiting intiation of RNA synthesis
- -Gram (+) and mycobacteria
- -single-step mutation resistance
Rifamycin side effects
- -1% hepatitis
- -uveitis
Antimetabolite antibiotics
sulfonamides and trimethoprim
Trimethoprim/Sulfonamide mechanism
- -**bacteriostatic that prevents the synthesis of folic acid
- -active against Gram + and Gram - and some protozoa
- -Resistance occurs through alteration of the folate pathway
TMP-SMX side effects
–Enteric
–Hypersensitivity
…
Bacterial membrane disruption
lipopolypeptides and polymyxins
Lipopolypeptide (Daptomycin) mechanism
- -binds to membranes causing rapid depolarization and cell death
- -Active against Gram (+) and anaerobes
Lipopolypeptide (Daptomycin) side effects
- -elevated creatine phosphokinase
- -NO PNEUMONIA (binds surfactant)
Polymyxin mechanism, side effect, and resistance
- -acts as a detergent that interacts with phospholipids ad disrupts the cell membrane
- -active against many GNRs
- -nephro/neurotoxicity
- -resistance by decreased permeability