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
Describe the pathophysiology of bacterial endocarditis?
A healthy heart lining is resistant to bacteria in the blood. If there is an endothelial injury, cytokines are recruited to the area. Bacteria aggregate and from clots, and a surface for other bacteria to bind to, which leads to an infection which is hard to penetrate with antibiotics
Describe the clinical presentation in early bacterial endocarditis
Vague symptoms, including fever, fatigue and heart murmur.
Describe the clinical presentation in late bacterial endocarditis
Microemboly or immunological factors such as:
spliinter haemorrhage, roth’s spots, nodes, finger clubbing
When/why should bacterial endocarditis be considered
After new prosthetic valve surgery, emoblic events with no origin, sepsis
fever + prosthetic devices, IV drug user or new arrythmias
What is a splinter hemorrhage?
caused by damage to capillaries
What is a roths spot
microemboly on the retina
What investigations are done prior to diagnosing/treating bacterial endocarditis?
if stable - blood culture should be done 3x prior to starting treatment echocardiograpy - vegetation chest x ray ecg urine microscopy inflammatory markers FBC/U&E, LFT
What is dukes criteria and how does it relate to bacterial endocarditis
Criteria designed to assess likelihood of bacterial endocarditis, score based on vegetation, blood culture, risk factors. Presence of 2 major criteria = positive
What is the most common pathogen responsible for bacterial endocarditis infections
Strep - gram +ve.
fungal infections - hard to identify and associated with high mortality, common in immunocompromised patients
How is bacterial endocarditis treated briefly?
Microbe eradication by antimicrobials. Bactericidal antibiotics with prolonged regimine
Why is bacterial endocarditis difficult to treat?
Due to vegetation on the heart valves/the body’s own immune system
What are the main complications of bacterial endocarditis?
heart failure, uncontrolled infection, embolic events, neurological complications.
How can bacteria endocarditis be prevented?
Prophylaxis - given according to risk factors present
What is the role of the pharmacist in bacterial endocarditis treatment?
Counselling -benefits vs risks of prophylaxis, importance of maintaining good oral health, symptoms and when to seek advice, early referral to education for at risk patients, management of antimicrobials. Gentamicin/vancomycin TDM
What is the typical treatment of prosthetic valve bacterial endocarditis
2 weeks gentamicin 3mg/kg IV in 1/2 doses. Gentamicin is only given for the shortened course as it is toxic
6 weeks vancomycin 30-60mg/kg
rifampicin iv/orally (active against MRSA - common source of infection in prosthetic valve)
Is gentamicin time or concentration dependent?
Gentamicin is a concentration dependant antibiotic, which has greater bactericidal activity at increased drug concentration.
Is gentamicin lipophilic?
No, highly hydrophilic and it is not well absorbed in obese patients as it is not well absorbed in adipose tissue, therefore this can lead to overdose.
How is gentamicin dosed?
As a once daily dose to reduce nephrotoxicity. Dose is ideal body weight. Renal function must be checked and doses adjusted accordingly
Describe extended interval gentamicin dosing and the monitoring requirements associated
Extended interval dosing (also known as “once-daily gentamicin”) involves the use of dose administered as a 30-60minute infusion.Check the trough level 18-24 hours after the last dose, if it is less than 1mg/L then the subsequent dose can be given. Take drug level after the dose and 8 hours later.
Describe multiple dosing of gentamicin and the monitoring requirements associated
Giving the gentamicin dose in 3 divided doses. Must take pre and post dose, pre dose gentamicin levels must be less than 2, and post level must be 5-10mg/L
Discuss the use of vancomycin for bacterial endocarditis and the monitoring requirements associated
Given every 12 hours IV as it is not absorbed in the gut. Post dose blood level not required, but a pre dose level must be taken within an hour to ensure the serum vancomycin level is between 10-20mg/L. Renal function must be monitored
What adverse effect is associated with vancomycin?
Red man syndrome, related to the rate of infusion
discuss the use of rifampicin for bacterial endocarditis and the monitoring requirements associated
Rifampicin is effective in killing stationary/slowly growing microorganisms, but has high levels of resistance. This medication should be taken 2-3 days after gentamicin and vancomycin. It is an enzyme inducer, so will impact warfarin levels. Can lead to the discolouration of body fluids
What is meningitis?
Inflammation of the membrane covering the brain and the spinal cord
What can cause meningitis?
Infection, fungi, trauma, drugs
How can bacterial meningitis spread?
between close contacts or in close crowds of people, meningitis will spread in droplets/secretions from the respiratory tract
Discuss the pathophysiology of meningitis
Pathogenic agents in the bloodstream penetrate the subarachnoid space and cause inflammation. Raised interchranial pressure leads to decreased cerebral perfusion and hypoxia/ischaemia.
What are risk factors for meningitis?
Can occur in anyone of any age but typically occurs in young babies/children
Discuss the clinical presentation of meningitis
Symptoms can be very non-specific and the absence of a rash is not enough to rule out meningitis
Discuss the clinical presentation of meningitis in young children
Fever, vomiting, poor feeding, irritability, sudden onset of fever, muscle/joint aches, cold extremities, non-blanching rash, severe stiffness of hamstrings/legs
How Is meningitis diagnosed?
Lumbar puncture and sent away for testing. Would not find increased white blood cells.
What are the desired features of antimicrobial agents for meningitis?
Bacericidal and RAPID IV administration as this is a life threatening bacterial infection. Needs to be broad spectrum and lipophillic
What are the first steps for treatment of meningitis
Empirical ABx stat
dexamethasone to reduce neurological complications
What are the treatment options for meningitis (discuss their pros/cons)
ceftriaxone - bactericidal, broad spec, crosses BBB
choramphenicol -lipophillic, broad spec but has adverse effects
Benzylpenicillin
How is meninigitis treated in children over 3 months
parenteral cephalasporins ceftriaxone or cefoxatime
How is meninigitis treated in children under 3 months
Ceftriaxone or cefoxamine plus ampicillin or amoxicllin
What supportive therapies can be given for meningitis?
Oxygen if hypoxic
IV fluids
manage electrolytes
What are the long-term complications associated with meningitis?
fatigue, emotional changes, septicaemia.
When is chemoprophylaxis indicated for meningitis?
Prolonged close contacts, patient.
Give ciprofloxacin first choice, or ceftriaxone, but this is only available by injection
ASAP after exposure.
rifampicin 2x day for 2 days
How are pharmacists involved in meningitis prevention?
iMMUNISATION
What is a urinary tract infection?
An infection of part of the urinary tract, uncomplicated infections tend to be bacterial in nature
Which parts of the urinary tract are typically involved in lower UTI?
Urethra/bladder
Which parts of the urinary tract are typically involved in upper UTI?
kidney/ureta
Which urinary tract infection commonly leads to sepsis?
pyelonephritis
What is cystitis?
A minor/self limiting UTI
What are some common causes of UTIs?
E.coli
pregnant patients - foetus pushing on the bladder
anything which can suppress the flow of urine
What symptoms of UTI are associated with systemic infection?
fever, systemically unwell, suprapubic pain, poor feeding, failure to thrive, vaginal discharge
What symptoms of UTI are associated with lower and upper infections?
Incomplete emptying, increased frequency, new nocturia, increased urgency, dysuria, cloudy urine, haematuria
What diagnostic testing is usually carried out for UTIs? Describe both
Mid stream - in more serious infections
dip stick - looking for white blood cells/nitrites
Which self care management options can be recommended for urinary tract infections?
Paracetamol/ibuprofen
When are NSAIDs not indicated?
Asthma, SSRIs, CV risk, blood thinners, elderly
What is the first line therapy for a lower UTI? Discuss when it is not indicated
Nitrofurantoin twice a day for 3 days. Not indicated when eGFR is less than 45ml/min. Concentrates in the urine, so needs good renal function. Does not reach high blood levels so is not suitable in upper UTI.
What counselling should be given with nitrofurantoin
Take with food to avoid GI disturbances
What is the second line therapy for UTI?
Trimethoprim, is not used often
What can be done for patients experiencing recurring UTIs? How often would they be having UTI for it it be considered as recurring?
Trimethoprim or nitrofurantoin prophylaxis, 2nd choice amoxicillin or cefalexin. 2 UTIs in 6 months or more than 3 a year
What patient groups are included in complicated UTIs?
pregnant women, men, catheterised, children
How are UTIs treated in pregnancy? Give details
Give paracetamol
Nitrofurantoin give but a longer course due to risks. Not given at full term
Trimethoprim not given as teratogenic.
2nd line: amoxicillin/cefalexin
What is fever and loin pain associated with?
Upper UTI, hospital admission and IV antibiotics recommended
How are UTIs treated in patients with a longer ureter?
Not common for anatomical reasons. Give a 7 day course of antibiotics instead of 3 of same antibiotics. Cefalexin can penetrate the prostate
How are UTIs treated in catheterized patients?
Check for blockages, remove blockage and change catheter then give a 7 day course of antibiotics
How do UTIs present in elderly people?
Atypical presentation, confusion. But must be new symptoms. Elderly patients can have nitrofurantoin as long as their eGFR is above 45ml/min
How should UTIs be treated in children?
Consider hospitalisation if they are unable to take fluids.
IV or oral co-amoxiclav
2nd line: ciprofloxacin
How should pyelonephritis be managed?
ciprofloxacin
How should pyelonephritis be managed?
Pneumonia
What is the usual first line treatment for community acquired pneumonia?
Amoxicillin + clarithromycin/erythromycin
OR doxycycline
or flucloxacillin
What is the nature of the interaction between doxycycline and anticoagulants
Doxycycline increases the anticoagulant effect, so this should be monitored and a dose adjustment should follow if required
What counselling should be given to someone taking the combined oral contraceptive and is being prescribed an antibiotic?
contraceptives go through the gi tract where they are metabolised and excreted to the liver, where they reach bile and are dissolved, bacteria in the GI reverse this to allow contraceptives to work. Antibiotics kill GI bacteria, and therefore oestrogen are metabolised and do not work
How is meningitis treated in babies under 3 months old and how does it compare with the treatment given to babies aged over 3 months?
Under 3 months: IV cefotoxime + amoxicillin and ampicillin
over 3 months: Iv ceftriaxone + amoxicllin and ampicllin
