MICRO: Antimicrobials 2 Flashcards
What are the main types of misuse of antibiotics?
- No infection present
- Selection of incorrect drug
- Inadequate or excessive dose
- Inappropriate duration of therapy
- Expensive agent used when cheaper is available
Which patients most benefit from antibiotics? What about bacteraemia?
- About 50% of people with bacteraemia would get better by themselves
- Patients who are hypotensive tend to do quite badly and mortality is higher- these patients need antibiotics quickly
What is the % of patients who get adverse events with antibiotics?
- About 5% of hospitalised people who are given an antimicrobial will experience an adverse event
What is the most common SE of antimicrobials?
GI upset/diarrhoea
NB: about 60% of diarrhoea post-antibiotics is due to SE and not C. diff.
What are the common adverse events with antibiotics?
- GI upset (i.e. diarrhoea)- MOST COMMON
- Fever and rash
- Renal dysfunction
- Acute anaphylaxis
- Liver dysfunction (abnormal LFTs seen), Hepatitis
Benefits should outweigh the risks
Where has antibiotic prescribing been most reduced in healthcare?
GP and dentists
What 4 factors should be considered when prescribing antibiotics?
-
Choice of the correct antimicrobial depends on the CHAOS:
- Host characteristics (e.g. age, pregnancy, renal/ liver failure, other medications, tetracyclines deposit in bone so cannot be used in children
- Antimicrobial susceptibilities (local policies)
- Organism itself
- Site of infection (e.g. bone, CSF, urine)
Why can giving narrow spectrum antibiotics be challenging? Why is it important?
Easier to give narrow spectrum if you have sensitivities/culture but this is not commonly done
Use narrow sprectrum + bactericidal if possible e.g. penicillin for tonsillitis
What 3 pharmacological factors should be considered when prescribing antibiotics?
- Pharmacokinetics (absorption, distribution, elimination)
- Route of administration - IV for serious infection or if the patient is not absorbing PO
- Dosage (age, renal/ hepatic function, drug monitoring)
When should you consider IV over PO antibiotics?
- Sepsis - BP is low, hence perfusion is low and subsequent drug absorption PO may be compromised
- If accessing a deep site (e.g. endocarditis, osteomyelitis) or CNS (only a small proportion get into the CNS effectively)
- If antimicrobial is not absorbed well orally e.g. aminoglycosides
Name 2 methods for susceptibility testing.
- Gradient MIC method
- Agar disc diffusion method
Define MIC and break point.
MIC (minimum inhibitory concentration) = this is the least amount of drug required to inhibit the growth of the organism in a culture
Break point = the point above the MIC that determines whether the organism is sensitive or resistant to the antimicrobial
Describe the agar disc diffusion method for measuring MIC.
- The disc is impregnated with antibiotic (which diffuses out from the disc)
- Distance from the disc ↑ = conc of antibiotic ↓logarithmically
- The border of the clear zone is the MIC
- The zone of inhibited antibiotic is measured and compared to guidance (as below) and reported as sensitive or resistant.
What is the difference between empirical and definitive treatments?
EMPIRICAL THERAPY: If it is necessary to treat the patient on an empirical basis, a broad-spectrum agent that is likely to ‘cover’ the most likely organism is used. Collect specimen before starting antibiotic
DEFINITIVE THERAPY: Empirical cover can be then changed based on culture results
How are break points determined?
Susceptibility is set by standard bodies e.g. European Committee on Antimicrobial Susceptibility Testing
reported as a table which gives breakpoints i.e. if MIC is greater than the breakpoint then it will be resistant. If the MIC is 8 and the breakpoint is less than or = to 8 then it will still be intermediate or sensitive.
What are the advantages of empirical therapy in nosocomial infections?
- higher survival rates
- shorter hospital stays
- lower healthcare costs
(nosocomial = hospital)
What are the only clnical situations where empirical therapy has been shown to improve survival?
Septic shock (e.g. hypotension) is a particularly important indication for broad-spectrum antibiotics
Patient age, bacteraemia, neutropenia, causative organism and source of infection are not associated with better outcome with empirical treatment at infection onset in this study.
When can gram staining(3) and rapid antigen detection (2) be used in the identification of infecting organisms?
-
Gram-staining
- CSF
- Joint aspirate
- Pus
-
Rapid Antigen Detection
- Immunofluorescence
- PCR
What 3 factors can affect the concentration of the antibiotic locally?
- pH of site
- lipid solubility of drug
- ability to penetrate BBB e.g. in CSF infections
What evidence can point towards whether a patient needs antimicrobials?
- Evidence of a systemic response, e.g.
- Fever
- Raised CRP
- High WCC (mainly neutrophils)
- NOTE: in SEVERE infections, you can get a low WCC
- Also:
- Duration of symptoms
- Underlying risk factors
- Likely source of infection
- Exclude other pro-inflammatory disease
When should IM antimicrobial administration not be used?
- Irritant antimicrobials
- If long term use required
When should you switch to PO antimicrobials? When is this not appropriate?
- IV to PO switch is recommended in hospital for most infections if the patient has stabilised after 48 hours of IV treatment
In CNS infections and severe infections such as osteomyelitis and endocarditis, you may NOT switch to PO
Describe the main factors to consider in terms of pharmacokinetics/pharmacodynamics of antimicrobials graphically.
- Peak concentration above MIC
- Time above the MIC
What are the three patterns of activity of antimicrobials? Give an example of each.
Type I - concentration dependent killing and prolonged persistent effects
Type II - time-dependent killing and minimal persistent effects
Type III - time-dependent killing and moderate-prolonged persistent effects
- Aminoglycosides, fluoroquinolones
- Carbapenes, cephalosporins, erythromycin
- Azithromycin, tetracyclines
What is the goal of therapy for type I/II/III antimicrobials?
I - concentration-dependent - maximise concentration i.e. Cmax so give as one big dose to get this as high as possible BUT remember risk of adverse effects. Trough determines the frequency, peak determines the dose given.
II - time-dependent - maximise duration of exposure - time above MIC should be maximised e.g. penicillins given frequently or infusions
III - combination of time and concentration dependent - maximise amount of drug i.e. the AUC is the most important; infusions good for this
How should aminoglycosides be given for best effect? What risks should be considered?
Type I activity so concentration-dependent killing
- Give one big dose to get Cmax as high as possible
- Risk of ototoxicity and nephrotoxicity
- Measure trough concentrations for 24 hours after the first dose to ensure elimination then adjust if necessary e.g. give more frequent (detemined by trough) lower doses (detemined by Cmax)
What are the recommended treatment durations for these specific infections?
- N. meningitidis meningitis
- Acute osteomyelitis
- Bacterial endocarditis
- Gp A streptococcal pharyngitis
- Simple cystitis
NOTE: Group A Streptococcal pharyngitis, need to be treated for 10 days to prevent sequelae such as rheumatic fever and glomerulonephritis
What organisms usually cause skin infections like impetigo/cellulitis/wound infections? What is the treatment?
Common organisms:
- Staphylococcus aureus
- Group A and B Streptococci (b-haemolytic)- e.g. S. pyogenes
TREATMENT: Flucloxacillin
- Unless penicillin allergy or MRSA- may give vancomycin to cover instead
What is the management of invasive group A streptococcal infections?
Invasive Group A Streptococcal Infection e.g. severe cellulitis, necrotising fasciitis
- Aggressive and early debridement
- Antibiotics- adjunctive use of protein synthesis inhibitors, especially clindamycin (good skin and soft tissue penetration)
- Use of IVIg
What is the eagle effect?
- Relative lack of efficacy of b-lactams on infections having large numbers of bacteria
- In cases of extremely high bacterial burden (e.g. with Group A streptococcus), bacteria may be in the stationary phase of growth.
- Penicillin works by inhibiting cell wall synthesis, but cell wall synthesis only occurs when the bacteria are dividing
- In this case, as no bacteria are actively replicating, penicillin has NO activity
Name 3 atypical causes of CAP.
Legionella,
Mycoplasma,
Chlamydia
How is pharyngitis treated?
- Pharyngitis: benzylpenicillin for 20 days//phenoxymethylpenicillin for 10days (to prevent risk of rheumatic fever and glomerulonephritis sequelae)
How are mild and severe CAP treated?
- CAP (mild): Amoxicillin – usually pneumococcus and Haemophilus
- CAP (severe): Co-amoxiclav + Clarithromycin – might worry about amoxicillin resistance
Name 3 common microorganisms causing RTIs.
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
How is HAP treated?
Usually gram negative
- TREATMENT:
- Cephalosporin
- Ciprofloxacin
- Tazocin (pip/taz)
- If MRSA, consider addition of vancomycin
What is the treatement in adults and neonates/infants for meningitis?
Adult - cefTRIAXONE +/- amox
Infant/neonate <3 months - cefoTAXIME + amox (to cover Listeria). Ceftriaxone is not used in neonates as this can cause displacement of bilirubin from albumin and cause biliary sludging.
What differentials should you consider if there is no response to antimicrobials within 48 hours?
- Cause other than bacterial
- Persistent focus of infection e.g. catheter
- Deep-seated collection requiring drainage
- Bacterial endocarditis
- Incorrect dosage
- Another infection
List 3 causes of meningitis.
- N. meningitidis
- S. pneumoniae
- Listeria monocytogenes in the very young/ elderly/ immunocompromised
What is the treatment of simple cystitis vs hospital acquired UTI? What about an infected catheter?
Simple cystitis
- Trimethoprim x 3 days
Hospital-acquired UTI
- Cephalexin or Co-amoxiclav
- Most common type of HAI
Infected urinary catheter
- Change catheter under Gentamicin cover
How is C diff colitis managed? What is the route of administration ?
Stop offending antibiotic
Give PO metronidazone or PO vancomycin if it fails
What % of patients with bacteraemia would get better by themselves?
50%
How is Listeria meningitis treated?
Amoxicillin/ampicillin
NB: amox is added onto cefotaxime in neonates <3months to cover for this.
Peak above the MIC
Time above the MIC
