L25- Antibacterial Therapy I, background Flashcards
list the different ways Antibacterials can be classified
- MOA
- spectrum of activity
- clinical uses
- selective toxicity / AEs
- contraindications
- mechanism of resistance
define the following:
- (1) antimicrobial
- (2) antibacterial
- (3) antibiotic
1- inhibits growth of micro-organisms
2- inhibits growth of bacteria
3- inhibits growth of micro-organisms- made by other micro-organisms [but now its extended to include synthetic drugs]
list the main MOAs of antibacterials
- cell wall synthesis
- protein synthesis inhibitors
- drugs affecting nucelic acid synthesis
- urinary antiseptics
- Misc.
compare and contrast the effect and use of antibacterials that are Bacteriostatic and Bacteriocidal
Static:
- reversible inhibition of growth - growth returns once drug is removed, does not dec bacterial numbers
- used in immunocompetent patients –> immune system recovers and prepares for microbial removal
- used in minor infections
Cidal:
- irreversible inhibition of growth - destroys present bacteria
- used in immunocompromised patients
- used in life-threatening infections
define Selective Toxicity, include the two main mechanisms to achieve it
Defn: ability to injure/kill an invading micro-organism w/o harming host
i) ideally target sites unique to infecting organism (sites not in host): eg. cell walls / peptidoglycan
ii) alternatively target sites different to the host equivalent: eg. prokaryotic v eukaryotic ribosomes
define Postantibiotic effect and some of the mechanism that cause this effect
Defn: killing action of drug continues once plasma levels are below measurable
- lag time: if irreversible enzyme inhibitors – time it takes to synthesize new proteins
- persistence of agent in target site (outside of plasma)
- enhanced susceptibility of bacteria to phagocytosis or other defense mechanisms
list the antibacterial spectums
Broad
Narrow
Extended (in between)
Broad Spectrum antibacterials:
- (1) uses
- (2) disadvantages
1- empiric therapy, mixed infections
2:
- selection for MDR bacteria (resistant)
- disruption of normal flora
Narrow Spectrum antibacterials:
- (1) uses
- (2) disadvantages
1- treats infections of known origin (requires culture)
2- must know causal agent, not useful for empiric treatment
Extended Spectrum antibacterials:
- (1) uses
- (2) disadvantages
1- empiric therapy, mixed infections
2:
- selection for MDR bacteria (resistant)
- disruption of normal flora
Define MIC and MBC
MIC- minimum inhibitory concentration, lowest [antibiotic] that prevents VISIBLE growth
MBC- minimum bactericidal concentration, lowest [antibiotic] that yields 99.9% decline in colony count
Note- MBC is slightly greater than MIC
describe how MIC and MBC are determined
Dilution Method
1) MIC: serial dilutions of antibiotic, MIC = the tube with least [antibiotic] w/o visible growth
2) MBC: dilutions + agar, use all the dilutions and place on agar to culture, MBC = dilution area w/o colony formation
Disk Sensitivity Test- MIC only
-place antibacterial disks of differing concentrations of growth plate with bacteria –> MIC = lowest concentration with clear zone around disk
list the factors to consider when selecting Antibacterials
- organism identity
- organism susceptibility to an agent
- necessity of empiric therapy (out-patient)
- site of infection
- pharmacological factors
- patient factors
- cost of therapy
______ is the best test / most common test for identifying organisms in bacterial infections since cultures can take too long, include:
- structural difference
- test result differences
- Tx differences
Gram Stain
Pos:
-thick-mesh like cell wall made of peptidoglycan
-purple on microscopy
-easier for antibacterials to traverse cell wall
Neg:
- narrow cell wall, outer membrane
- pink on microscopy
- hard for antibacterials to enter organism, must utilize porin system
describe how antibiotics enhance bacterial resistance
1) initial infectious population has rare resistant bacteria
2) antibiotic given –> kills non-resistant bacteria
3) resistant bacteria multiply => infection that is more difficult to treat
describe the mechanisms of resistance to antibiotics (hint- 3)
- altered antibiotic uptake: dec permeability, dec uptake mechanisms, or inc in multi-drug resistant pumps
- altered target: change in receptor structure and drug affinity or modification of targeted metabolic pathway
- drug inactivation: eg. bacterial enzymes altering and inactivating drug
define primary and acquired drug resistance
Primary (no target): structural absence of target for drug to act on; eg. mycoplasma lack cell wall => penicillin resistance
Acquired (genetic changes):
- spontaneous DNA mutations
- DNA transfer of drug resistance (plasmid)
- altered expression of proteins in drug-resistant organisms (epigenetics)
(1) therapy is either initiated in patients with minor infections or (2) situations. Selection of (1) therapy is influenced by (3) and (4). (5) is often the initial type of therapy used in (1) therapy.
1- empirical therapy
2- urgency or immediate therapy is required and cultures are too slow, eg. meningitis
3- site of infection
4- Pt Hx: HA or CA infections
5- broad spectrum therapy
what are the drug qualities that determine its ability to penetrate BBB
- lipid solubility (inc –> more able to diffuse across BBB)
- MW (smaller the better)
- protein binding of drug (low affinity for plasma proteins better, higher affinity for transport proteins better)
list the many pharmacological factors that influence drug selection
- route of administration
- route of elimination (liver, kidney- eg. UTI agents must be eliminated thru renal system)
- 1/2 life affected by disease or other drugs (contraindications)
- drug interactions
- dosing schedule (out-patient, not an issue for in-patient)
- AEs and idiosyncratic responses
oral administration of antibacterials is preferred in (1) situations
parenteral administration is preferred in (2) situations
1- mild infections
2- serious infections, or if oral bioavailability via GIT is poor
list the common complications of antibiotic therapy
- Hypersensitivity: frequently, ranges from urticaria –> anaphylaxis
- Direct toxicity: directly affects host cellular processes
- Superinfection: new or secondary infection during therapy of initial / primary infection
what are the patient factors to consider when selecting antibacterials
- immune system status (competent, compromised)
- renal and or hepatic dysfunction
- poor perfusion
- age
- pregnancy, lactation
list the advantages of combination antibacterial therapy
- achieves synergistic effects
- good in emergency situations
- delays resistance
- treats mixed infections
- treats immunocompromised / immunosuppressed
what are the mechanisms of synergistic effects among antibacterials
- Sequential blockade in pathways (eg. Sulfamethoxazole + Trimethoprim)
- Blockade of drug-inactivating enzymes (eg. Augmentin = clavulanic acid + amoxicillin)
Enhanced drug uptake
list the disadvantages of combination antibacterial therapy
- some agents only work on multiplying/dividing bacteria –> so if one agent causes baceteriostasis than the other may be less effective (eg. β-lactams + tetracyclines)
- may select for MDR bacteria
list some of the guidelines for antimicrobial chemoprophylaxis
- always directed towards specific pathogen (narrow spectrum)
- no development of resistance
- limited duration of use
- conventional therapeutic doses should be used
- only in situations with proven drug efficacy
list some non-surgical situations when antimicrobial chemoprophylaxis may be employed
- prevention of CMV, HIV, influenza, meningococcal infections, TB
- animal or human bite
- chronic bronchitis
describe the use of antimicrobial chemoprophylaxis in terms of surgical prophylaxis
limited to procedures where infections occur in >50% of untreated cases under optimal conditions
eg. GI procedures, vaginal hysterectomy, C-section, joint replacement, open fracture surgery
