Clinical Approach To Antimicrobial Therapy Flashcards
Factors involved in choosing abx: infective agent
Pathogenicity; virulence; invasiveness; adherence; toxin production; transmissibility; growth requirements; antibiotic susceptibility in vitro.
Factors involved in choosing antibiotics: host resistance
State of health or debility; nutritional state; immune status; underlying illness; implants/foreign bodies; portal of entry; normal flora; antibiotic therapy augment host resistance
Define sepsis
Combination of symptoms and signs of a localised primary site of infection
Define SIRS
Systemic inflammatory response syndrome
What is SIRS the first sign of?
That infection is spreading form the primary site of infection and the patient may be bacteraemic.
Other non infective causes of SIRS
Trauma, chronic inflammation, malignancy
What are the criteria for SIRS (at least 2 of)?
Temperature: >38C (febrile/pyrexial) or 90 beats/min (tachycardia)
Respiratory rate: >20 breaths/min or PaCO2 12000 cells/mm3 or
What are the features of SEVERE sepsis?
Temperature: >38C (febrile/pyrexial) or 90 beats/min (tachycardia)
Respiratory rate: >20 breaths/min or PaCO2 12000 cells/mm3 or
When is prophylactic use of antibiotics indicated?
When infection is a serious complication of surgery or of a medical condition e.g. If a non-sterile site will be breeched in surgery
When is therapeutic use of antibiotics indicated?
When infection is suspected or confirmed by:
- Clinical diagnosis (disease or site) or
- microbiological diagnosis I.e. laboratory confirmed
What information is necessary when deciding what antibiotics to use on a patient with suspected or confirmed bacterial infection?
- location/source of infection
- severity of infectious process
- epidemiological setting of patient
- pre-existing medical contain or problems that could pre-dispose patient to an infection
What information does the anatomical location of an infection give when prescribing antibiotics?
Allows most likely organism to be determined and allows pattern of susceptibility to be reasonably predicted (local surveillance)
Allows use of appropriate empirical therapy.
Also determines route if therapy administration .
What are some examples of the epidemiological factors of a patient that impact on the likelihood of an organism?
Age; sex; location; travel; IVDU; pets;
What are some pre-existing medical conditions that could pre-dispose a patient to infection?
Prosthesis; valvular heart disease; immunosuppressions; diabetes mellitus
What are the implications for a narrow spectrum abx?
Targeted therapy - organism defined
What are the implications for use of broad spectrum abx?
Empirical or best guess therapy - microbiology is uncertain.
Site directed.
Associated side effects: spread of resistance etc
Factors involved in shaping guidelines for choosing empirical antibiotic treatment
Site of infection Seriousness Likely organisms Patient factors & circumstances Cost Toxicity and side effects Local/national resistance rates Other underlying medical conditions Contraindications
Why is picking the correct route of abx administration essential?
To ensure effective drug concentrations at the site of infection.
Choices for route if administration of abx
Oral
IV
IM
Topical
What can effect oral absorption of abx?
Food - abx poorly absorbed or less stable
Drugs - calcium antacids and iron interfere with tetracycline uptake
What are the pharmacokinetic factors that can effect can an abx and its usefulness?
Serum concentrations Half life (t 1/2) Tissue concentrations Protein binding Crossing natural boundaries e.g CSF, joint fluid Metabolism Excretion. (Liver/kidney)
Situations where cidal agents preferred
Immunocompromised- seriously ill or steroid therapy
Immunodeficiency - neutropenia, HIV
Difficult sites - endocarditis and meningitis
NEED TO KNOW KILLING ORGANISM NOT JUST INHIBITING GROWTH
How long to treat a UTI/cystitis for
3 days
How long to treat streptococcal pharyngitis for?
10 days
How long to treat pulmonary TB for?
6 months
How long to treat endocarditis for?
4-6 weeks
Most infections responds to how many days treatment according to severity of condition?
5-7 (10) days
What signs should be looked for to show treatment of micro-orgs can be stopped?
Clinical observations
Resolution of inflammatory process (WBC, CRP, temp = normal)
Repeat micro cultures clear
Imaging to see if abscess/ collection resolved
Advantages of IV to oral switch
Reductions in HA- bacteraemias and infected lines
Saves medical and nursing time
Reduces discomfort of patients and enables improved mobility and earlier discharge
Reduced treatment costs
Patient more likely to receive abx at correct time
Potential to reduce risk of adverse effects (more error in parental drugs)
Why might deep seated infections require initial 2 weeks of IV therapy? Examples
Allows correct concentration to reach deep areas Liver abscess Osteomyelitis, septic arthritis Empyema, Cavitating pneumonia
Advantages of using tWo drugs together (synergy)
To prevent relapse
To prevent resistance arising
Provides broad spectrum cover
Some examples where two abx are used synergistically in the treatment of infection to prevent resistance or relapse
TB: isoniazid and Rifampicin 6 months
Endocarditis : penicillin and Aminoglycoside
Deep bone and joint: Rifampicin and anti-staph agent
Enterococcal infections: penicillin and gentamicin
High risk infections requiring prolonged IV therapy
S.aureus bacteraemia Severe necrotising soft tissue infection Infected implants/prosthesis Meningitis/encephalitis Intracranial abscess Endocarditis Exacerbation of CF/ Bronchiectasis Inadequately drained abscess or empyema Severe infections related to chemotherapy induced neutropenia
OPAT
Outpatient parental antimicrobial therapy
What is OPAT?
Allows safe administration of IV drugs at home using once daily agents
What are the requirements for OPAT?
Patient: clinical stable, capable of self management, good IV access.
Need to be reviewed once a week and managed by MDT
Advantages of OPAT
Reduce the no of hospital bed days e.g. CF children or adults with endocarditis
Patient care in their own home
Reduction in the risk of acquisition of nosocomial infection
Disadvantages of OPAT
Risk of developing acute, sub-acute or life threatening complications e.g. Anaphylaxis, other drug toxicity, line infection.
Failure to resolve underlying infection.
Disadvantage of using two drugs together
Increases cost
Increased risk of toxicity
What should be considered in terms of drug safety in patient?
Known hypersensitivity or intolerance
Impaired excretion (renal/liver failure)
Drug interactions e.g. Ciprofloxacin and theophylline
Higher risk of toxicity e.g. BM toxicity effects in transplant patients; pre existing liver disease; CNS toxicity in epilepsy
Risk of antibiotic associated diarrhoea
What causes antibiotic associated diarrhoea?
Abx can disrupt normal flora of gut -> germination of C. Difficile spores -> diarrhoea and colitis caused by toxin positive c.diff.
Who are at high risk of antibiotic associated diarrhoea or c.diff?
In patients and elderly
What is a penicillin intolerance and what implications does it have?
GI upset, sickness.
Very common
Penicillins and beta lactams can be used
What is penicillin anaphylaxis and what are its consequences?
Severe and immediate skin rash, other anaphylactic symptoms.
All beta lactams should be avoided. Replace with Macrolide/quinolone/glycopeptide
What are the implications of a skin rash after penicillin
No penicillins but may use other beta lactams I.e. cephalosporins, monobactams and carbapenems, as low risk of cross reaction occurring.
What are the possible causes of antibiotic treatment failure ?
Wrong diagnosis (not infectious or could be viral/fungal)
Wrong choice of abx - reconsider site and possible orgs; ?source
Inadequate dose
Antibiotic given by wrong route - IV/ oral vanc
Host factors - neutropenic patient require cidal agent
Drug resistance developing during treatment (repeat AST)
Pus requiring drainage; necrotic material with bio films or foreign body needs removing
What are the two goals of antimicrobial stewardship “start smart, then focus” guidance
Effective, timely treatment of infection
Minimise collateral damage of abx use.
Principles of “start smart”
Take hx of relevant allergies
Prompt effective abx treatment within one hour of dx or ASAP if life threatening
Comply with local prescribing guidelines
Document clinical indication and dies on drug chart AND in clinical notes
Include review/stop date or duration
Relevant micro samples taken
Principles of “then focus”:
Clinical review and decision at 48 hours:
1. STOP - not infections
2. IV/oral switch - nice clinical response
3. Change to narrow spectrum abx
4. Continue and review again after 24 hours
5. OPAT
DOCUMENT DECISION
Define selective toxicity
Therapeutic agents that target pathogenic organisms, not pathological processes from cells/tissues.
Which special groups of patients require different prescribing guidelines?
Newborns; Pregnant; Lactating; Elderly; Immunosuppressed.
Why do newborns, the elderly, pregnant or breastfeeding women and immunosuppressed patients require special prescribing?
There are specific infectious processes which may be specific to these people.
They have different physiologies therefore agents are ltd.
Which special group of Patients are the most complicated for prescribing and why?
Elderly.
Least homogenous; comorbidities; drug interactions; physiology; compliance and need for written directions.
Principles of of prescribing in community care
Empirical treatment, syndrome based.
Minimise emergence of bacterial resistance - simple generic agents, avoid broad spectrum abx.
Safe, effective and economic use of abx - limit telephone prescribing; no or delayed abx strategy I.e. Frequently viral
Referral to hospital if GP suspects immunosuppressive illness or if requires further investigations/hospital admission.
