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
What are the sepsis treatment steps?
High flow oxygen when required take a blood culture, IV antibiotic Fluid resuscitation check and repeat lactate after 2 hours monitor urine output hourly for 2 hours
How should you manage antibiotics for sepsis?
IV broad spectrum within one hour based on local guidelines and patient specific parameters
Then focus, review every 24-48 hours, and tailor to a known pathogen once identified.
Switch to oral Abx as soon as possible
What is the fluid challenge with relation to sepsis and how/why is it important?
Give a high volume of fluids within initial period then adjust according to fluid balance.
If the lactate level is above 4 mmol/L or the patient is hypotensive, give IV fluids to expand circulating fluid volume and restore perfusion pressure
Describe and discuss supportive therapies for sepsis
Vasopressors and iontropic agents, given if there is still a low BP despite fluid resuscitation. Example: norepherine
Corticosteroids
How should critically ill patients with covid-19 be managed?
Ventilation fluid resuscitation dexamethasone antivirals paracetamol vte prophylaxis antibiotic therapy - 2ndry infection
How can sepsis be prevented?
vaccination, good hygiene, PPE, antibiotic stewardship and education
What is a lower respiratory tract infection?
An acute illness usually presenting with a cough and fever/sputum/breathlesness/chest pain/discomfort
What is pneumonia?
Inflammation of the lung characterised by consolidation of the affected area. Can limit oxygen intake
What causes pneumonia?
Bacteria, virus, funghi
How is pneumonia diagnosed? Compare pre/post pandemic
Post pandemic, diagnosed using CRB score
Pre pandemic: CURB score
Physical examination, observations, x rays
What is the CURB 65 score?
Used to diagnose likelihood of pneumonia C = confusion U = urea R = Resp rate B = BP 65 - AGE
What is the difference between the presentation of bacterial and covid-19 pneumonia?
bacterial = rapidly unwell patient, no history of covid 19, purulent sputum
covid 19 - history of covid, severe muscle pain, loss of sense of smell, history of exposure
What are the presenting symptoms of pneumonia leading to diagnosis?
Use of accessory respiratory muscles crackles wheeze dullness decreased intensity of breath sounds hyper/hypo thermia RR >18 Tachycardic Cyanosis Consolidation on chest x ray If severe shortness of breath at rest, hypoxic
How should severe pneumonia be managed?
Admission to hospital for IV fluids, and an IV oral antibiotic.
IV co-amoxiclav + clarithromycin
How should moderate pneumonia be managed?
Oral doxycycline at home
When should a patient with severe pneumonia be switched to an oral antibiotic from IV?
Upon: resolution of fever reduction in pulse rate resolution of tachypnoea once well hydrated and taking oral fluids absence of hypoxia improved white cell count
What is bacterial endocarditis?
Infection of the lining of the heart and cardiac valves. It is a rare infection in the community and can be potentially fatal
Describe right sided bacterial endocarditis
Infection involves the pulmonary valve and the tricuspid valve. Usually common in IV drug users
Describe left sided bacterial endocarditis
Infection involves the mitral and aortic valve. This infection is the most common.
What are the risk factors for bacterial endocarditis?
Congenital valve disease ventricular septal defects degenerative valve disease mitral thrombus Older patients replacing damaged valves having central lines for a long period of time