Antibiotics and Antibiotic Resistance Flashcards
What are the 3 antimicrobial agents
- Disinfectants
- Antiseptics
- Antibiotics
What are disinfectants?
Antimicrobial agents that are applied to inanimate objects (e.g. floors, tables, walls etc.)
What are antiseptics?
Antimicrobial agents that are sufficiently non-toxic to be applied to living tissues (e.g. hand sanitizers)
What are antibiotics?
antimicrobial agents produced by bacteria and fungi that are exploited by humans (delivered topically and internally)
Describe what antibiotics are useful for
- very effective therapeutic against bacterial infections
- availability of antibiotics enable cancer chemotherapy, organ transplantation, all invasive surgeries, and the treatment of premature infants
What are the 2 major problems when dealing with antibiotics?
- Bacterial resistance to antibiotics always happens
- Diminished interest fro pharmaceutical companies to develop new antibiotics
Describe the types of misuse of antibiotics
- Empiric use (blinded use)
- Increased use of broad-spectrum agents
- Pediatric use for viral infections
- Patients who do not complete course
- Antibiotics in animal feed
What are the different ways we can measure antibiotic activity?
- minimum inhibitory concentration (MIC)
What is minimum inhibitory concentration?
- series of culture tubes with varying concentration of agent
- check for visible growth
- the lowest concentration of agent that inhibits the growth
- antibiotic strips
- faster, multiple antibiotics
How do antibiotics works?
- target essential bacterial components
- cell wall synthesis
- protein synthesis
- DNA/RNA synthesis
- foliate synthesis
- cell membrane alteration
- targets are not present (or different) in eukaryotic cells
What is a penicillin-like “beta” lactam antibiotic?
- contains a “B lactam ring”
- function to inhibit cell wall synthesis in bacteria
- bind the bacterial “penicillin-binding proteins (PBPs)
- some bacteria can produce a B lactamase
What are penicillin-binding proteins
- are transpeptidases
- no peptide cross-links
- weak cell wall
- cell death
What is B lactamase?
- an enzyme that destroys the ring and thus the antibiotic
What is a methicillin-like “beta” lactam antibiotic?
- contains a “B lactam ring”
- chemically modified penicillin
- can’t be cleaved by B lactamases
- some bacteria can produce a different “penicillin-binding protein” (e.g. PBP2a)
- encoded by ‘mec’
- PBP2a doesn’t bind methicillin (or other B lactams)
What is Vancomycin?
- a glycopeptide antibiotic
- inhibits cell wall synthesis in gram positives
- often a drug of “last resort”
- binds the peptide linkage at terminal D-ala-D-ala residues and inhibits transpeptidation
- resistance genes change theses to D-ala-D-Lac and vancomycin can no longer bind
- resistance is encoded by the van genes
What are the bacterial strategies for antibiotic resistance
Prevention of antibiotic entry
- gram-negative outer membrane and mycobacteria cell wall
Antibiotic modification
- B lactamase
Efflux of antibiotic
- actively pump out the antibiotic
Alteration of antibiotic target
- PBPs, ribosome modifications
Bypassing the antibiotic action
- use environmental folic acid
Antibiotic resistance genes
- many mechanisms of antibiotic resistance are genetically encoded
- can produce very high levels of antibiotic resistance
- often encoded on mobile genetic elements (plasmids) allowing for horizontal gene transfer -> “superbugs”
What is horizontal gene transfer?
- rather than alter gene function through mutations, new genes are acquired from another source
- transformation
- transduction
- conjugation
What is klebsialla pneuomoniae
- gram-negative
- an important cause of nosocomial pneumonia
- produces a capsule and is commonly resistant to multiple antibiotics
- first documented source of “NDM-1”
What is NDM-1
- New Delhi Metallo-beta-lactamase-1
- also known as a carbapenemase
- carbapenem antibiotics are B-lactamase resistance B-lactams with broad-spectrum activity
- is now widespread in other gram-negatives
- CRE (carbapenem-resistant Enterobacteriaceae)
What are clostridia?
- gram-positive
- rod-shaped
- endospore-formers
- strict anaerobes, vegetative cells killed by O2
- generally found in soil and intestinal tracts of animals
- can cause life-threatening disease mediated by exotoxins
What are some important clostridia human pathogens?
C. difficile
- pseudomembranous colitis
C. tetani
- tetanus
C. botulinum
- botulism
C. perfringens
- food-borne illness and gas gangrene
What can C. difficile exist as
- asymptomatic carrier state in the large intestine
- cause of mild to moderate diarrhea
- cause of life-threatening pseudomembranous colitis
Where can C. difficile be found in?
- nursing home and hospital environments
- nosocomial pathogen
C. difficile endospores
- can be very difficult to eradication from the environment
- culture from the floor, bedpans, toilets, hands and clothing of medical personnel
What is the mode of transmission of C. difficile
- through the spore: fecal-oral route
What is pseudomembranous colitis?
- most symptomatic patients have recently revived an antimicrobial agent
- an inflammatory condition of the large intestine
- offensive smelling diarrhea, abdominal pain, fever, nausea dehydration
- symptoms may occur 1-2 days after antibiotics or several weeks after the antibiotic is discontinued
Pseudomembranous colitis lesions
- show characteristic yellow lesions
- ## can enlarge to cover substantial portion s of inflamed mucosa and can be stripped off from the pseudomembrane
Pseudomembranous colitis treatment
- antibiotics are used to cure infections, but they also kill the normal microbiota
- suppression of normal microbiota and persistence of C. difficile endospores
- after the antibiotic is stopped, spores germinate, overgrowth of C. difficile occurs with the production of toxins
- does not itself invade, but the toxins damage the intestinal lining of the large intestine
What are the toxins produced by C. diff
- A-B toxins called the large clostridial cytotoxins
- serves to designate two domains
What does the A domain do?
Denotes the active portion of the toxin that carries the enzymatic activity
- function to inactivate key regulatory protein of host cells
- causes dysregulation of multiple cellular processes including cytoskeletal rearrangements, cell death and inflammation
What does the B domain do?
Denotes the portion of the toxin molecule responsible for binding and uptake by the host cell
Diagnosis and treatment
- history (antibiotic use), symptoms and laboratory test to confirm C. difficile
- endoscopy and toxin detection assay
- discontinue inciting antibiotic if still being used
- fluids for treatment
- antibiotics more specific for “C. diff” - oral vancomycin or I.V. metronidazole
- avoid antidiarrheal agents - would cause decreased toxin clearance
