Chapter 10: Antimicrobial Agents
Vancomycin
Glycopeptide (polypeptide antibiotic) - hinders peptidoglycan elongation - antibiotic of last resort - used for MRSA - toxic and costly - strains have developed that are resistant to VRSA, antibiotic Synercid rushed through FDA approval - Synercid resistance leads to Linezolid development
Nucleic acid inhibitors
Rifampin Quinolones Fluoroquinolones
Which antibiotic causes a misread of mRNA because it alters the shape of the bacterial ribosome? Cipro Oxazolidinones Streptomycin Sulfanilamides
Streptomycin
What is meant when a bacterium is said to become "resistant" to an antibiotic? The antibiotic kills or inhibits the bacterium. The antibiotic is metabolized by the bacterium, providing more energy for growth of the cell. The bacterium is neither killed nor inhibited by the antibiotic. The antibiotic mutates in a way that benefits the bacterium.
The bacterium is neither killed nor inhibited by the antibiotic.
Some bacterial cells are resistant to a variety of antimicrobials because they actively pump the drugs out of the cell. True False
True
Which of the following is NOT a beta-lactam antibiotic? methicillin vancomycin cephalothin penicillin G
Vancomycin
Why is it difficult to find good chemotherapeutic agents against viruses? Viruses are not cells, and therefore not sensitive to such compounds. Viruses depend on the host cell's machinery, so it is hard to find a viral target that would leave the host cell unaffected. Viruses infect both bacteria and human cells. There is no effective way to deliver the drug to the virus.
Viruses depend on the host cell's machinery, so it is hard to find a viral target that would leave the host cell unaffected.
Ethambutol
Mycolic acid inhibitor - inhibits incorporation of mycolic acid into cell wall - anti-TB drug
Isoniazid hydrazide
Mycolic acid inhibitor - inhibits synthesis of mycolic acids and is used in combination with other drugs to treat TB (takes months to adminster) - oral antibiotic
Competition between beneficial microbes and potential pathogens is called microbial (synergy/antagonism).
antagonism
Bacillus licheniformis secretes a compound that inhibits the growth of other Gram-positive bacteria. This is an example of a(n) ________. antibiotic. porin. toxin. chemotherapeutic. analog.
antibiotic.
selective toxicity
antimicrobial agent kills pathogenic microbe without harming the host a. Historically reminiscent of the magic bullet of Paul Ehrlich b. used arsenical compound (eg. rat poison) called Salvarsan to treat syphilitic patients
Antimicrobials
antimicrobial compounds synthesized in the laboratory (eg. sulfadiazine)
Penicillins
bactericidal; cell lysis occurs; bind and block peptidases involved in cross bridges linking the NAM subunits; both contain beta lactam ring; extracted entirely from mold
If a particular bacterial species is resistant to beta-lactam antibiotics, which of the following might you expect to find inside the bacterial cells? DNA polymerase beta lactamase transpeptidase RNA polymerase
beta lactamase
Chlorampenicol
binds with 50s ribosomal subunit and inhibits peptide bond formation - broad spectrum - cheap synthetic antimicrobial - side effects: suppresses bone marrow - aplastic anemia
Erythromycin
binds with 50s ribosomal subunit and prevents ribosomal translocation - macrolide (large molecule containing lactone ring) - bactericidal - does not penetrate cell wall of Gram - bacteria - used to treat penicillin resistant strains - only effective against Gram + bacteria - side effects: GI disturbance
Inhibitors of Cell wall synthesis
Penicillin Cephalosporins Polypeptide antibiotics Mycolic acid inhibitors
Which antibiotic disrupts cell membranes? Polymyxin Vancomycin Augmentin Cipro
Polymyxin
Cell membrane damagers
Polymyxins
Bacitracin
Polypeptide antiobiotic - produced by Bacillus sublitis - blocks transport of NAG and NAM from cytoplasm - very toxic - applied only topically - effective against Gram + cocci
An antimicrobial drug that blocks the transport of NAG and NAM from the cytoplasm is targeting which of the following cellular processes? nucleic acid synthesis cell wall synthesis cytoplasmic membrane synthesis protein synthesis
cell wall synthesis
Quinolones
inhibit DNA synthesis/gyrases eg. Ciprofloxacin - oral antibiotic used for UTIs - useful for prophylaxis - treatment of Anthrax - crosses blood brain barrier
The mechanism of action of the antibiotic vancomycin is __________ inhibition of cell wall synthesis. inhibition of nucleic acid synthesis. inhibition of a metabolic pathway. inhibition of protein synthesis. disruption of cytoplasmic membranes.
inhibition of cell wall synthesis.
Which of the following is NOT a direct mode of action of antimicrobial drugs? inhibition of cell wall synthesis inhibition of protein synthesis inhibition of nucleic acid synthesis inhibition of flagella formation
inhibition of flagella formation.
The mechanism of action of erythromycin is _______________. inhibition of a metabolic pathway. disruption of cytoplasmic membranes. inhibition of protein synthesis. inhibition of cell wall synthesis. inhibition of nucleic acid synthesis.
inhibition of protein synthesis.
Bacteriostatic
inhibits growth and reproduction of the microbe; best administered in immunocompetent individuals; allows for immune system to work against microbes; less costly, fewer side effects
Tetracycline
interferes with tRNA attachment - broad spectrum - superinfections often happen (eg. Candida albicans - yeast infections_ - penetrates tissues well, valuable against Chlamydia infections - side effects: discoloration of teeth in children, liver damage, use contraindicated for pregnant women
Narrow spectrum antibiotics
more specific approach; targeted therapy
Eukaryotic pathogens
much more difficult because cells are similar with host's
An antibiotic that inhibits cell wall synthesis will result in which of the following? Ribosomes lose their function. Possible lysis prevention theta replication Plasmolysis Cells cannot attach to their hosts.
Possible lysis
TB treatment
Requires combined therapy - use of drugs of diff. modes of action (eg. INH + Streptomycin + Pyrazinamide + Cycloserine -> due to emergence of resistance of TB bacterium)
When a patient is treated with antibiotics, __________. mutations occur in all of the bacterial cells sensitive bacterial cells multiply uncontrollably the drug will kill or inhibit the growth of the sensitive bacterial cells the drug will kill or inhibit the growth of the resistant bacterial cells mutations will occur in the sensitive bacterial cells, but not in the resistant bacterial cells
the drug will kill or inhibit the growth of the sensitive bacterial cells
Antimicrobial drugs are selectively toxic. This means _____. the drugs will not have toxic effects on a patient the drugs should be toxic to the pathogens and not the patient the drugs will affect only a particular type of pathogen the drugs are reactive within a specific part of the patient's anatomy (for example, the inner ear).
the drugs should be toxic to the pathogens and not the patient
Chemotherapy
use of chemical compounds to treat infectious (microbial) and non-infectious (eg. cancer) diseases
Penicillin V
oral; stays longer (~24 hours)
Which antibiotic prevent initiation and block ribosome assembly? oxazolidinones Chloramphenicol tetracyclines Rifamycin
oxazolidinones
semi-synthetic penicillin
partially synthesized; retains core penicillin molecule eg. Oxacillin - resistant to penicillinase eg. Ampicillin - extended spectrum penicillin
Most drugs that inhibit the synthesis of the cell wall act by _________. preventing the formation of β-lactamases. disrupting the formation of the mycolic acid layer of the cell wall. blocking the secretion of cell wall molecules from the cytoplasm. preventing the formation of alanine-alanine bridges. preventing the cross-linkage of NAM subunits.
preventing the cross-linkage of NAM subunits.
Chloramphenicol as an antibiotic: prevents the attachment of tRNA to a ribosome prevents the formation of peptide bonds prevents a large subunit from attaching to a small subunit changes the shape of the ribosome
prevents the formation of peptide bonds
Penicillin G
requires injection, destroyed by stomach acid, does not stay long enough in blood circulation to be effective (~2 hours)
Which of the following is NOT a direct possible side effect of antibiotic use? toxicity resistance allergies disruption of normal flora
resistance
An antimicrobial disk on a Kirby-Bauer plate that shows no zone of inhibition indicates that the microbe being tested is __________ to the drug. resistant susceptible synergistic intermediate
resistant
Bacterial DNA replication requires the enzyme gyrase, but eukaryotic replication does not. Ciprofloxacin ("Cipro") inhibits gyrase activity. This is an example of _______. antimicrobial resistance. synergism. selective toxicity. use of an analog. an antimetabolite.
selective toxicity.
Which of the following activities can be shown to increase resistance among microbial populations? developing second- and third-generation versions of antimicrobial drugs taking a combination of antimicrobial drugs taking antibacterial drugs for viral infections taking an antimicrobial drug for the entire prescribed time
taking antibacterial drugs for viral infections
Selman Waksman
discovered Streptomycin derived from Streptomyces bacteria
Alexander Fleming
discovered penicillin extracted from Penicillium notatum
Gerhard Domagk
discovered sulfanilamides
Paul Ehrlich
dreamt of "magic bullets"; arsenical compounds that killed microbes
Broad spectrum antibiotics
effective against Gram + and Gram - bacteria; used if bacterium causing infection is unknown; shotgun approach; disadvantage normal microbiota are also destroyed encouraging growth of opportunists (potential pathogens that are part of the normal human microbiota). If they survive and their competitors are affected, superinfection occurs (eg. Candida albicans - yeast infection); once figure out what cause of illness is, switch to narrow spectrum antiobiotics
Penicillinase
enzyme produced by bacteria that deactivates penicillin penicillin hydrolyzed into penicilloic acid (no antimicrobial activity); beta lactam ring broken by enzyme
Which antibiotic prevents translocation of the ribosome? erthromycin tetracyclines chloramphenicol streptomycin
erthromycin
Drug-resistant populations of microbes arise when ___________. exposure to drugs causes mutations that produce resistance. synergy between medications occurs. the patient becomes immune to the drug. resistant cells become numerous in a population due to their greater vigor. exposure to drugs selectively kills sensitive cells, allowing overgrowth of resistant cells.
exposure to drugs selectively kills sensitive cells, allowing overgrowth of resistant cells.
Howard Florey and Ernst Chain
extracted and mass produced penicillin from penicillium chryseogenum
Aminoglycosides
- alters shape of 30s ribosomal subunit - significant activity against Gram - infections - broad spectrum - can cause permanent damage to auditory nerve (tinnitus) - toxic to kidneys - important to monitor aminoglycoside levels of patient
Streptogramins
- binds with 50s ribosomal subunit - inhibits translation - Synercid - used for Vancomycin resistant bacteria, synergistic effect
Oxazolidinones
- binds with 50s ribosomal subunit - prevents formation of 70s ribosome - bactericidal - affect Gram + (eg. Linezolid)
Cephalosporins
- derived from Cephalosporium acremonium - beta lactam antibiotic like penicillin - main ring different from penicillin, 2 sites for R groups - Broad spectrum or extended spectrum antibiotic - 2nd, 3rd, 4th, 5th generations more effective against Gram-negatives (eg. Keflex, Cefoxitin)
Rifampin
- inhibits mRNA synthesis - treatment for TB and INH
Polymyxins
- interact with membrane phospholipids - Topical - combined with bacitracin and neomycin as over the counter antibiotic
Sulfanomides
- synthetic drug from dyes - synergistic combination as trimethoprim/sulfamethoxazole - treatment of UTI and pneumocystis pneumonia in AIDS patients - analogs of important metabolites (folic acid) - competitive enzyme inhibitors -> prevents the metabolism of DNA, RNA, and amino acids
Inhibitors of Protein synthesis
Aminoglycosides Tetracyclines Chloramphenicol Eryhthromycin Streptogramins Oxazolidinones
Clavulanic acid could be used to protect which of the following antibiotics in a drug formulation? Amoxycillin bacitracin sulfanilamide erythromycin
Amoxycillin
Imipenem
Carbapenem - broad spectrum - highly resistant to beta lactamases - good against Pseudomonas aeroginosa
Which antibiotic blocks peptide bond formation in translation? Streptomycin Erythromycin Chloramphenicol Penicillin
Chloramphenicol
Ciprofloxacins act against what bacterial target? Bacterial ribosomes DNA gyrase Cell walls Cell membranes Metabolic pathways unique to bacteria
DNA gyrase
The outer membrane of Gram-negative bacteria enables many antimicrobial drugs to enter the cell more easily. True False
False
Why are antibiotics that work on the peptidoglycan cell wall of bacteria a good choice of drug? Bacteria are especially sensitive to these compounds. They are less expensive that other antibiotics Humans and other animal hosts lack peptidoglycan cell walls. The drugs also work against DNA gyrase.
Humans and other animal hosts lack peptidoglycan cell walls.
Modes of Action
Inhibition of cell wall synthesis (eg. Penicillin & cephalosporins) Inhibition of protein synthesis (eg. Aminoglycosides & tetracycline) Injury to plasma membrane (eg. Polymyxin & amphotericin B) Inhibition to nucleic acid synthesis (eg. ciprofloxacin & nalidixic acid) Inhibition of folic acid synthesis (eg. trimethoprim-sulfamethoxazole)
The abbreviation (MIC/MID/MBC) stands for the smallest amount of a drug that will inhibit the growth and reproduction of a pathogen.
MIC
Aztreonam
Monobactam - beta lactam ring is alone and not fused with another ring - especially useful in treating P. aeruginosa infections
Viral pathogens
difficult, intracellular and controls host's genetic functions
Penicillin and beta lactamase inhibitors
good against penicillinase producing bacteria; beta lactamase inhibitors include clavulanic acid and sulbactam eg. Augmentin - amoxacillin + clavulanic acid, preferred antibiotic for pediatric patients eg. Timentin - ticarcillin + clavulanic acid; same as Augmentin
Porins
gram negative cells, allow only small and hydrophilic molecules
Bacteriocidal
lethal to microbes; advisable for immunocompromised individuals (eg. oncology & AIDS patients)
Which category of antimicrobial drug works by changing the shape of a ribosome? tetracyclines streptomycin chloramphenicol oxazolidinones
streptomycin
Antibiotics
substances produced by some microbes that inhibit or kill other microbes (eg. Penicillin)
Which of the following is NOT associated with the work of Paul Ehrlich? sulfanilamide the concept of the "magic bullet" arsenic compounds the concept of chemotherapy
sulfanilamide
Folic Acid Synthesis Inhibitors
sulfanomides
Gram positives
susceptible to penicillin
