5_Antibiotics Flashcards
3 possible outcomes if antibiotic is added to bacteria
-
Resistant:
- Bacteria are resistant and continue to grow.
-
Bacteriostatic:
- Bacterial growth stops but the bacteria are not killed and growth will resume after removal of the antibiotic (bacteriostatic). Killing of the bacteria depends on the immune system.
-
Bactericidal:
- Bacteria are killed (bactericidal).
minimum inhibitory concentration (MIC):
define, and which types of Abx have this?
- the lowest concentration at which bacterial growth is inhibited.
- Both bacteriostatic and bactericidal antibiotics have MICs.
minimal bactericidal concentration (MBC):
define
- the lowest concentration at which bacteria are killed.
- A bactericidal antibiotic is where the MBC and MIC are close.
what determines if an Abx is bactericidal or bacteriostatic?
dependent on drug dose and bacterial species and needs to be empirically determined.
how does the MIC (min. inhibitory conc)
Disc Diffusion Assay work? (aka Kirby-Bauer)
- Abx diffuses out of the disk at a set rate –> forming a gradient of Abx conc.
- The surface of the plate is inoculated with bacteria and the bacteria grow overnight.
- The agar will be clear at concentrations of antibiotic that inhibit bacterial growth (zone of inhibition). The more sensitive the bacteria, the larger the zone of inhibition:
- small zone = resistant
- large zone = sensitive
- The exact size of resistant zones varies depending on the Abx.
what does size of “zone of inhibition” correlate to in a disc diffusion assay?
correlates to the antibiotic concentration (differs between antibiotics).
what determines resistance?
determined by the achievable clinical dose
define:
sensitive, intermediate, and resistant
- Sensitive = inhibited by 1/2 of the achievable clinical dose or lower.
- Intermediate = inhibited by concentrations higher than 1/2 the achievable dose.
- Resistant = cannot be inhibited by an achievable dose.
natural intrinsic resistance:
define and examples
- These are properties that make the bacteria more resistant.
- Gram-negative membrane
- efflux pumps (Type I secretion)
- proteases that destroy drugs
3 main types of resistance
- natural (intrinsic)
- mutational
- acquired
mutational resistance:
define
- These arise from mutation of the chromosome.
- Spread is clonal or vertical (through spreading the resistant strain).
acquired resistance:
define
- These are acquired on mobile genetic elements from other bacteria.
- Spread can be by spread of resistant bacteria AND spread of the resistance gene
how do random chromosomal mutations occur?
what increases the frequency of such mutations?
- Chromosomal mutations occur when DNA polymerase makes errors.
- Under stress the error rate increases (can affect error prone polymerases)
combination antibiotics:
function
useful for treating bacteria w/ high mutation rates;
(e.g. Mycobacterium tuberculosis)
how do resistant clone mutants spread?
resistant clones w/ chromosomal mutations are spread by clonal (vertical) spread/ transmission
efflux pumps:
function
Type I secretion; modified version on in Gram-positive bacteria
Efflux pumps remove the drug from the bacteria.
- They can be non-specific or specific
- They can be intrinsic, acquired, or mutational (depression of pump expression)
two principles of antibiotic exclusion:
define
Size exclusion
- particularly important for Gram-negative bacteria where the antibiotic has to pass through outer membrane porins
Active transport
- through the cytoplasmic (plasma, inner membrane) of Gram negative and Gram positive bacteria
- oxidative phosphorylation
- slow growth states (SCVs) or bacteria in biofilms
what produces beta-lactamases?
and function?
- gram-negative and gram-positive bacteria produce beta-lactamase
- beta-lactamase inactivates penicillin by cleaving a beta-lactam ring
beta-lactamase inhibitors can be co-administered with penicillin;
what it the purpose of this?
- The inhibitors are harder to cleave –> the b-lactamase remains bound to the inhibitor essentially keeping it from being available to bind to and cleave the b-lactam antibiotic.
beta-lactamase resistant drugs:
what do these do?
- there are beta-lactamase resistant forms of beta-lactam antibiotics
- emerging beta-lactamases destroy resistant forms (ESBL) extended spectrum beta-lactamases
fosfomycinase:
function
antibiotic that cleaves fosfomycin
modification/and inactivation of aminoglycosides
Aminoglycosides are inactivated by modification by the bacteria. There are 3 basic modifications that will inactivate Aminoglycosides:
- N-acetylation
- O-phosphorylation
- O-adenylation
what can inactivate chloramphenicol?
Chloramphenicol can be inactivated by acetylation (acetyl transferase)
what is the purpose of target site modifications?
- these target site modifications will prevent Abx action
- these include mutation to specific targets that are either acquired or mutational
what does MRSA (methicillin resistant S. aureus) mecA gene do?
encodes a new beta-lactam resistance PBP (PBP2a)
what does beta-lactam resistant S. pneumoniae do?
(specifically, PBP2X and PBP2B)
- Penicillin-binding protein 2x (PBP2X) – low and high level resistance
- Penicillin-binding protein 2x (PBP2B) – low and high level resistance
how do MLS (macrolide-lincosamide-streptogramin) strains work?
- MLS strains have a erthromycin methyltransferase gene that methylates 23S rRNA –>
- prevents interaction of macrolides and lincosamides/clindamycin with the 23S rRNA and the 50S ribosomal subunit
how do target site modifications effect changes in RNA polymerase structure?
prevent interaction of rifampicins with RNA polymerase
how is vancomycin resistance acquired and encoded?
what do these do?
- acquired and encoded by 7 genes.
- These genes change the D-Ala-D-Ala pentapeptide –>
- D-Ala-D-Ser or,
- D-Ala-D-Lac
- There are 3 types of Vancomycin resistance operons: VanA, VanB, VanC.
metabolic bypass:
define
- There are either modification or complete substitution of Dihydropteroic acid synthetase and Dihydrofolate reductase.
- Among these are unique bypass mechanisms such as the synthesis of drugresistant, plasmid-coded dihydrofolate reductase or dihydropteroate synthetase
why is infection control important?
to protect yourself and others!
sources of infectious agents?
- Person to person including skin contact
- Fomites (surfaces) including any surface in contact with people or droplets (patient coughing or sneezing)
- Instruments
standard sterilizatoin/disinfection precautions
- handwashing (hand hygiene)
- use of personal protective equipment (gloves, masks, eye protection, & gown)
- patient care equipment
- environmental surfaces
- injury prevention
types of hand hygiene
-
Handwashing
- Washing hands with plain soap and water
-
Antiseptic handwash
- Washing hands with water and soap or other detergents containing an antiseptic agent
-
Alcohol-based handrub
- Rubbing hands with an alcohol-containing preparation
-
Surgical antisepsis
- Handwashing with an antiseptic soap or an alcohol-based handrub before operations by surgical personnel
what is the best type of hand hygiene?
- handwashing is better than alcohol-based rubs;
- should be used when visibly dirty;
- after touching contaminated objects with bare hands
types of personal protective equipment (PPE)
- Gloves: exam, over-gloves, sterile surgical, and utility
- Face masks: various levels of protection depending on type of mask
- Eye protection: safety glasses, chin-length face shield
- Clinical jacket: disposable or reusable
types of patient care equipment?
define & examples of:
- critical instruments,
- semi-critical instruments,
- non-critical instruments and devices
-
Critical Instruments
- Penetrate the skin
- Heat sterilize between uses or use sterile single-use, disposable devices
- Ex: include surgical instruments, scalpel blades
-
Semi-critical Instruments
- Contact skin do not penetrate soft tissue
- Heat sterilize or high-level disinfect
- Ex: include instruments for nail care
-
Non-critical Instruments and Devices
- Contact intact skin
- Clean and disinfect using a low to intermediate level disinfectant
- Ex: exam tables, ultrasound treatment equipment
what is the difference between sterilization and disinfection?
define
- Sterilization: complete killing/removal of all organisms from a location or material
- Disinfection: destruction (reduction) of pathogenic organisms by processes that fail to meet the criteria for sterilization
sterilization is the complete killing/removal of all organisms from a location or material;
what are the different techniques?
-
Autoclaves: uses steam pressure to sterilize equipment
- does not inactivate prions, like those associated with Creutzfeldt-Jakob disease
- inactivates: bacteria, viruses, fungi, spores
-
Dry heat:
- High temperature (>300oC) for prolonged periods (>90 mins)
- used only for solid items (e.g. metal instruments)
- Chemical vapor: this process uses a mixture of chemicals, (incl. alcohol, formaldehyde, ketone, acetone, and water) that are heated under pressure to form a sterilizing gas
disinfection is the destruction/ reduction of pathogenic organisms by processes that fails to meet the criteria for sterilization;
what are the different methods of disinfection?
-
physical methods:
- flushing, washing
- microwaves
- sonication
-
chemical methods: (bacteria only)
- biguanide - damages cell membranes
- alcohol - damages proteins, membranes, collapses cell wall
- QACS (quaternary active compounds) - disrupt cell membrane
- Phenolics - denatures proteins, and damages membranes
-
chemical methods (bacteria + viruses + spores)
- chlorine
- hydrogen peroxide - damages essential cell components DNA and protein
-
UV (bacteria and viruses)
- damages DNA
- only acts on surfaces (UV does not penetrate)
what are the factors affecting the killing of microorganisms?
-
Killing agent
- Nature of killing agent
- Intensity or conc.: higher conc. gives greater effect.
- Duration of action (exposure time): longer time gives greater effect.
- Temp. of action-higher temp: gives greater effect.
-
Organisms Being Killed or Inactivated
- Resistance by kind of organism: bacterial endospores > Mycobacterium tuberculosis (TB) > non-enveloped (hydrophilic) viruses > fungi > vegetative cells > enveloped (lipid) viruses > bacteria
- Number of organisms: higher numbers, longer time required.
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Extrinsic Conditions
- pH: better at other than neutral; chemical considerations.
- Physical and chemical barriers to effective sterilization.
disinfection of environmental surfaces is important where?
- housekeeping surfaces
- clinical contact surfaces
- waiting room
what are the bloodborne pathogens associated with needlesticks?
- HBV
- clinical hepatitis
- serological evidence of HBV infection
- HCV
- HIV
how to reduce risk of transmitting MRSA?
cover open skin wounds;
reduce MRSA transmission risk
(MRSA survives on surfaces)
