Clinical Application of Antimicrobials Flashcards
What is the choice of antibiotics based on?
Severity of infection, pathogen type, site of infection, patient specific characteristics, specific guidelines
What is a bactericidal antibiotic? Give examples
An antibiotic that kills bacterial cells. Examples: aminoglycosides, beta lactams, vancomycin, quinolones, rifampicin, metronidazole
What is a bacteriostatic antibiotic? Give examples
antibiotics which inhibit cell growth, they are sufficient for non life threatening infections. EXAMPLES: chloramphenicol, eythromycin, sulfonamides, trimethoprim, tetracyclines
What is the post antibiotic effect?
PAE: antibacterials continue to supress growth of bacterials after exposure
What is the MIC?
Minimum inhibitory concentration, the concentration that inhibits visible bacteria growth at 24 hours
What is the MBC?
Minimum bactericidal concentration, the concentration of antibiotic that results in 1000 fold reduction in bacterial density after 24 hours. Concentration of the drug must be more than the minimum bactericidal concentration for effective bacterial kill
What is the relationship between MBC and MIC?
If the ratio of minimum bacterial concentration to minimum inhibitory concentration is less than 4, agent is bactericidal, more than 4, agent is static.
What is a time dependant antibiotic?
For a time dependant antibiotic, once the drug concentration is above the MBC, the time the drug is in contact with bacteria is the most important factor
What is a concentration dependent antibiotic
The absolute concentration of the drug is the most important factor, the rate of kill is increased if the concentration of the drug is consistently above the minimum bactericidal concentration. One single large dose is often therapeutic
Discuss pharmacokinetics in relation to antibiotics
Absorption: route of administration (oral/IV?), Bioavailability, counselling, interactions
Distribution: antibiotic relevant to time
Metabolism/elimination: route and effects, interactions, is there a need for a dose adjustment for renal/hepatic impairment?
What is a type 1 antibiotic and give examples
Concentration dependent antibiotics with significant post antibiotic effect. For example, aminoglycosides, metronidazole, gentamicin. Peak/minimum inhibition concentration relates to efficacy
What is a type 2 antibiotic and give examples
Time dependent, low post antibiotic effect. Time above minimum inhibitory concentration relates to efficacy. EXAMPLES: beta lactams, erythromycin
What is a type 3 antibiotic and give examples
Time and concentration dependent antibiotics. They have mixed properties such as time dependent killing. Ideal dosing regimine maximises the amount of drug. 24 hour area under the curve to minimum inhibitor concentration ratio leads to good efficacy. EXAMPLES: vancomycin and tetracyclines
Discuss some challenges with antibiotics
Resistance, superinfection, adverse effects, allergy, interactions
Describe some key pharmacodynamic interactions with antibiotics
Macrolides and drugs that prolong QT interval: prolonged QT interval
Quinolones and epilepsy: reduced seizure threshold
Linezolid and drugs that increase serotonin: increased risk of serotonin syndrome
Trimethoprim and co trimoxazole/methotrexate: risk of bone marrow suppression
Describe some key pharmacokinetic interactions with antibiotics
Absorption reduced with cations: tetracyclines, fluoroquinolones
metabolism via CYP450: macrolides, fluoroquinolones, metronidazole, sulfonamides (inhIbitors of CYP450)
Rifampicin - induces CYP450
high risk drugs with narrow TI
nitrofurantoin requires good kidney function in order to be effective
What is sepsis?
A life threatening organ dysfunction caused by a dysregulated organ response to infection
What is septic shock?
A medical emergency. Persistent hypotension requiring vasopressors to maintain mean arterial pressure >65mmHg and serum lactate >2mmol/L
Describe the symptoms of sepsis
Fast breathing, skin rash/clammy sweaty skin, fast heart beat, weakness or aching muscles, not passing much urine, confused or disorientated and slurring speech, feeling very hot/cold/shivering, feeling very unwell
Describe the pathophysiology of sepsis
A pro-inflammatory response which leads to vasolidation and disturbances in the microcirculation. Theres a mismatch in o2 supply and demand, which leads to mitochondrial dysfunction and cell apoptosis. This leads to tissue hypoxia and organ dysfunction.
How is sepsis diagnosed clinically?
History taking, clinical signs/symptoms.
FBC, U&Es, lactate level
blood cultures
arterial blood gasses
How does lactate level aid in the diagnosis of sepsis?
Lactate is an indicator of cellular hypoxia. It is a predictor of mortality and poor outcomes. The degree of lactate reduction following resuscitation predicts survival likelihood
Describe and discuss the screening tools used to detect sepsis
Sequential organ failure assessment: estimates the risk of morbidity/mortality. Lower BP, higher HR, altered mental state are predictors of poorer outcomes
NEWS2: used to asses patients that are acutely unwell
What are the goals of sepsis treatment?
Resuscitate the patient and restore haemodynamic stability
identify the source of the infection, contain and treat
start an IV antibiotic within an hour
Switch to a targetted antibiotic once pathogen is confirmed
Maintain organ system function