1 General + disinfectants and antiseptics Flashcards
1
Q
What are the general terms of antimicrobial therapy?
A
- Bactericidal: kill target bacteria
- Bacteriostatic: stop or delay the growth of bacteria
- Sporocidal: agent that destroys spores, the reproductive element of fungi, protozoa, …
- Combination:
- Additive
- Synergistic (penicillins + aminoglycosides)
- Antagonistic (penicillin + tetracyclines)
- You can block the growth of some bacteria with bacteriostatic drugs, which won’t allow the production of a specific protein, which might be the target of the bactericidal drugs ==> useless!
- Antibiotics: produced by microorganisms
- Chemotherapeutics: produced by chemical synthesis
2
Q
What are the different mechanism of actions of the antibacterials?
A
3
Q
What are the characteristics of antibiotic therapy?
Types of therapies?
A
- Causative therapy
- Pathogens actively respond to the challenge
- Antibiotic use is a permanent interference with the environment
Types of antibiotic therapy:
-
Empiric:
- In critically ill patients, when there is no time to identify the microorganism responsible for detection or establishing its drug susceptibility.
-
Sensitivity based (definitive):
- Some pathogens, like S. Pyogenes and N. Meningitidis, have predictable susceptibility patterns to certain antibiotics, while others (e.g. most gram negative bacilli, enterococci and staphylococci species) often show unpredictable susceptibility patterns
- Prophylactic
4
Q
Which are the basic conditions of an effective therapy?
A
- The pathogens have to be sensitive to the antimicrobial agent
- The antimicrobial agents have to be in effective concentration at the site of infection, which depends on:
- Pharmacokinetics of the drug
-
Route of administration:
- Some can only be used parenterally (e.g. Aminoglycosides). This shows that they are for severe infections, within the hospital.
-
Dose:
- Don’t need to know it! (Thank you Jesus)
- The dose doesn’t depend on the severity of the infection
-
Duration of the therapy:
- Should only last a couple days, but some exceptions where we have shorter treatments (know these)
5
Q
What are the considerations in choice of antimicrobial agents?
A
- Antibacterial spectrum
- Site of infection
- Pharmacokinetics of the antimicrobial agents
- Inactivation Vs no inactivation
- Long Vs short half-life
- Adverse effects
- Presence of renal or hepatic failure:
- Antibiotics that are concentrated or eliminated by the liver (e.g. erythromycin and doxycycline) must be used carefully in patients with hepatic dysfunction
- Poor kidney function may cause accumulation of certain antibiotics –> direct monitoring of serum levels of some antibiotics is preferred to identify the max and/or min values to prevent potential toxicities
- Drug interaction
- Severity of infection
- General condition of the patient (concomitant disease, state of immune system, age, pregnancy)
- In pregnancy: Penicillins (1st choice), b-lactams or macrolides.
- Cost
6
Q
What is the post-antibiotic effect (PAE)?
A
- Suppression of bacterial growth after short exposure of organisms to antibiotics (how long the action remains) when it falls below the MIC
- PAE = T – C
- T = time required for the exposed culture to increase 1 log10 above the count observed immediately after drug removal
- C = corresponding time for the unexposed control
- PAE = T – C
- Antimicrobial drugs with a long PAE often require only 1 dose/day, particularly against gram (-) bacteria
- Agents with relatively long (≥ 1.5h) against gram (-) bacteria:
- Aminoglycosides
- Carbapenems
- Quinolones/Fluoroquinolones
- Rifampin
- Tetracyclines
- Agents with relatively long (≥ 1.5h) against gram (-) bacteria:
7
Q
What is the relationship between AUE and MIC?
A
Minimal bactericidal concentration (MBC):
It is the lowest concentration of antimicrobial agent that results in 99.9% decline in colony count after overnight broth dilution incubations
Minimal inhibitory concentration (MIC):
- It is the lowest antimicrobial concentration that prevents visible growth of an organism after 24h of incubation
- This serves as a quantitative measure of in vitro susceptibility and is commonly used in practice to streamline therapy.
Cmax/MIC – Concentration-dependent antibacterial activity:
- Certain antimicrobial agents, like Aminoglycosides and Daptomycin, show a significant increase in the rate of bacterial killing as the concentration of antibiotic increases.
- Giving drugs that exhibit this concentration-dependent activity by once-a-day bolus infusion achieves high peak levels, favoring rapid killing of the infecting pathogen.
- High dose once-a-day is not always used!!!
T > MIC – time-dependent antibacterial activity:
- On the other hand, b-lactams don’t show concentration-dependent activity
- The clinical efficacy of these antibiotics is best predicted by the percentage of time that blood concentration of a drug remains above MIC.
- This is the so-called time-dependent antibacterial activity
- The serum concentration should exceed MIC for at least 40-60 % of dose interval
- Multiple dosing or continuous infusion will ensure the prolonged time with antibiotic serum concentration above MIC
AUC/MIC:
- Fluoroquinolones have a high AUC/MIC ==> good activity
8
Q
What can you say about combining antimicrobial agents?
A
- Not routinely recommended (e.g. you don’t put 2 bacteriostatic agents together)
- Instead, it is therapeutically advised to treat patients with a single agent that is most specific to the infecting organism.
- This strategy reduces the possibility of superinfections, decreased apparition of resistant organisms and minimizes toxicity
- However, some situations require combination of antimicrobial drugs (e.g. tuberculosis treatment)
Aim:
- To assure a synergistic effect
- β-lactams + aminoglycosides
- To extend the antibacterial spectrum
- Sulfonamides + trimethoprim
- Penicillins + lactamase inhibitors
- To prevent the development of resistance???
- E.g. Pseudomonas Aeruginosa, Acinetobacter infection; antimycobacterial agents (min 3-4 drugs)
9
Q
What are the indications of prophylactic treatment?
A
-
Surgical prophylaxis:
- Cephalosporins
- Treatment prior to most surgical procedures can decrease the incidence of infection afterwards.
- It is directed against the most likely organisms, not eradication of every potential pathogen.
- E.g. patients with endocarditis, non-sterile abdominal surgery, dental extractions, …
-
Non-surgical prophylaxis:
- Individuals with high risk:
- E.g. Immunocompromised patients, patients with endocarditis
- Recurrent infections
- E.g. urinary, genital herpes, otitis media
- Close contacts
- E.g. meningococcal infection, tuberculosis, pertussis, plague, Hemophilus influenza
- Risk of infection:
- E.g. malaria, anthrax
- Individuals with high risk:
10
Q
What are the different antibacterial spectra?
A
-
Narrow spectrum:
- E.g. G-penicillin, vancomycin, oxazolidine, lincosamide, fuzidic acid
-
Extended spectrum:
- E.g. Aminoglycosides, aminopenicillines, 2nd and 3rd generation cephalosporins, some fluoroquinolones, macrolides
- Broad spectrum:
E.g. Tetracyclines, carbapenems, 4th generation fluoroquinolones, chloramphenicol, piperacilline + tazobactam
11
Q
What can be the complications of antibiotic therapy?
A
-
Hypersensitivity:
- Frequently occurs with metabolic products of antimicrobial drugs
- E.g. penicillins can cause serious hypersensitivity reactions, ranging from urticarial to anaphylactic shock.
-
Direct toxicity:
- High serum level of certain antibiotics may cause toxicity by directly affecting cellular processes of the host.
- E.g. aminoglycosides can cause ototoxicity by interfering with membrane function in the auditory cells.
-
Superinfection:
- Drug therapy, particularly with broad-spectrum antibiotics or combinations of agents can lead to alterations of the normal microbial flora of the upper respiratory, oral, intestinal and genitourinary tracts, permitting overgrowth of opportunistic organisms, especially fungi or resistant bacteria.
- These infections usually require secondary treatments using specific anti-infective agents.
12
Q
What are the general definitions of:
disinfectant
antiseptic
sterilization
phenol-coefficient?
A
Disinfectant: Used to kill microorganisms in an inanimate environment
Antiseptic: inhibit bacterial growth both in vitro and in contact with the surfaces of living tissues (skin, mucous membranes)
Sterilization: Elimination of all form of microbial life (fungi, bacteria, viruses, spores, …)
Phenol-coefficient: measure of the bactericidal activity of a chemical compound in relation to phenol (5%)
13
Q
What are the mechanisms of action and general features of disinfectants?
A
Mechanism of action of disinfectants:
- Protein denaturation
- Membrane disruption
- Nucleic acid damage
General features of disinfectants:
- Against parasites, bacteria, fungi, viruses ++
- Always applied locally
- Not selective
- Antibacterial and antifungal efficiency is always combined to phenol (the first disinfectant used)
- Can be:
- Bacteriostatic or bactericidal
- Fungistatic or fungicidal
- Virocidal and sporocidal
- Depends on:
- Concentration
- Temperature
- Time
- pH
- Number of bacteria: the less the better
- Ideal antiseptics (Doesn’t really exist):
- Effective in high dilution ® homeopathic antiseptic.
- No tissue damaging effect
- Odorless
- Stable (except oxidizing agents ® they should be unstable)
- Water soluble
- Effect not inhibited by proteins, fibers, exudates, pus
- Cheap
14
Q
Types of disinfectants and antiseptics?
A
- Aclcohol
- Aldehydes
- Phenol and derivatives
- Acids
- Halogens
- Oxidizing agents
- Heavy metals
- Quaternary ammonium compounds (detergents and soaps)
- Physical antimicrobials
15
Q
Alcohol!
A
Types:
- Ethanol (70%)
- Propanol (70%)
- Isopropanol (60-70%) (nail polish remover)
Features of ethanol:
- Around 70% concentration ==> bactericidal, not sporicidal
- Mechanism: water withdrawal, protein denaturation
- Synergy with other antiseptic
- Usually used for superficial skin-infections
-
Problems:
- Inflammable
- Make the skin very dry
