Antimicrobials 2 Flashcards
How are antimicrobials commonly misused?
No infection present
Selection of incorrect drug
Inadequate or excessive dose
Inappropriate duration of therapy
Expensive agent used when cheaper is available
(In short: Incorrect dose, duration, diagnosis and drug/ cost)
What does resistance cost?
Suffering and money:
Re-operation, abscess, wound infection
What % of people in hospital suffer an adverse event and which AEs do they suffer?
5%
GI upset
Fever & rash
Renal dysfunction
Acute anaphylaxis
Hepatitis
Why are antimicrobials CHAOS?
CHOICE of antimicrobial based on:
HOST characteristics
ANTIMICROBIAL susceptibilities
ORGANISM itself
SITE of infection
How are drugs chosen?
Narrow and bactericidal if possible
Ideally based on bacteriological diagnosis (or best guess)
Sensitivity pattern
Patient characteristics
Cost
What theoretical considerations must be made to choose a drug?
Pharmacokinetics (absorption, distribution, elimination)
Route of administration (IV if not PO or access deep site/ CNS)
Dosage (Age (+weight), Renal/ Hepatic function, monitoring)
What host factors affect choice?
Allergy
Age
Genetics
Hepatic function
Renal function
What is the MIC?
Minimum inhibitory Concentration
How does the agar disc diffusion method work?
Antibiotic-impregnated disc absorbs moisture from the agar; antibiotic diffuses into the agar medium.
As distance from the disc increases, there is a logarathmic reduction in the [antibiotic].[diffused antibiotic] at the interface of growing and inhibited bacteria ~ MIC
When do we do blood cultures?
Prior to antibiotics
How do we use empirical cover?
broad-spectrum agent that is likely to “cover” the likely organisms, given the differential
After culture: narrow it down
When is an empiric antibiotic appropriate?
Nosocomial infections (pneumonia) and severe sepsis
The best antibiotic should be prescribed first, based on the patient’s risk factors, suspected pathogen and local resistance patterns.
How do we identify the infecting organism?
Gram stain (CSF/ joint aspirate/ pus)
Rapid antigen detection (immunofluorescence and PCR)
Why should we consider the site of infection?
The local concentration of the antimicrobial will be affected by factors such as:
pH at the infection site
Lipid-solubility of the drug
Ability to penetrate the blood-brain barrier (CNS infections)
Special considerations required for Rx endocarditis or osteomyelitis
How do we determine if a patient truly requires an antimicrobial?
Evidence of systemic response (fever, raised CRP, raised WBC or really low WBC)
Considering duration, RFs, source, exclusion of other proinflammatory disease
When do we use IV?
Serious (or deep-seated) infection
When do we use PO?
Usually easy, but avoid if poor GI function or vomiting
Different classes of antimicrobial have different oral bioavailabilities
When do we use IM?
Not an option for long-term use
Avoid if bleeding tendency or drug is locally irritant
When do we use Topical?
Limited application and may cause local sensitisation
When is IV to PO switch recommended?
i.v. to p.o. switch is recommended in hospital for most infections if the patient has stabilised after 48 hours i.v. therapy
What is Type I pattern of activity and which antibiotics are useful?
Concentration-dependent killing and Prolonged persistent effects
Aminoglycosides
Daptomycin
Fluoroquinolones
Ketolides
What is the goal of therapy with Type I pattern?
Maximise concentrations
What is the PK/PD parameter in Type I patterns?
24h-AUC/MICPeak/MIC
What is Type 2 pattern of activity and which antibiotics are useful?
Time-dependent killing and Minimal persistent effects
Carbapenems
Cephalosporins
Erythromycin
Linezolid
Penicillins
What is the goal of therapy with Type 2 pattern?
Maximisation of duration of exposure
What is the PK/PD parameter in Type 2 patterns?
T>MIC
What is Type 3 pattern of activity and which antibiotics are useful?
Time-dependent killing and Moderate to prolonged persistent effects
Azithromycin
Clindamycin
Oxazolidinones
Tetracyclines
Vancomycin
What is the goal of therapy with Type 3 pattern?
Maximise amount of drug
What is the PK/PD parameter in Type 3 patterns?
24h- AUC/MIC
How long do you give Abx for?
Based on clinical markers
How long should you treat N. meningitidis meningitis?
7 days
How long should you treat Acute osteomyelitis?
6 weeks
How long should you treat Bacterial endocarditis?
4-6 weeks
How long should you treat GpA Streptococcal pharyngitis?
10 days
How long should you treat Simple cystitis in women?
3 days
How do you treat skin infections and why?
Flucloxacillin (except allergy or MRSA)
Impetigo/ cellulitis/ wound infections are normally due to Staph aureus and beta haemolytic strep which responds to penicillin
What is iGAS treatment?
Aggressive and early debridement
Antibiotics – adjunctive use of protein synthesis inhibitors esp. clindamycin (also has good skin & soft tissue penetration)
Use of IVIg
What is the Eagle effect?
High doses of penicillin have a worse bactericidal effect.
Originally referred to the paradoxically reduced antibacterial effect of penicillin at high doses, though recent usage generally refers to the relative lack of efficacy of beta-lactam antibacterial drugs on infections having large numbers of bacteria.
What is the proposed mechanism of the eagle effect?
Penicillin is a bactericidal antibiotic (inhibiting cell wall synthesis) but this synthesis only occurs when bacteria are actively replicating (or in the log phase of growth).
In cases of extremely high bacterial burden (such as with Group A Strep), bacteria may be in the stationary phase of growth.
In this instance since no bacteria are actively replicating (presumably due to nutrient restriction) penicillin has no activity.
How do you treat pharyngitis?
Benzylpenicillin 10 days
How do you treat mild CAP?
Amoxicillin
How do you treat severe CAP?
Co-amoxiclav and clarithromycin
How bad is hospital acquired respiratory tract infections?
Second most common HAI
23% mortality
Greatest likelihood of tracheal intubation and mechanical ventilation
How do you treat a HA RTI?
Cephalosporins, ciprofloxacin, piperacillin/ tazobactam
If MRSA consider Vanc addition
What are the main pathogens of bacterial meningitis and how do we treat them?
N. Meningitidis
S. pneumoniae
+/- Listeria in the very young/elderly/immuno-compromised
Ceftriaxone (+/- amoxycillin if Listeria likely)
How do you treat meningitis in babys?
Baby less than 3 months: Cefotaxime PLUS Amoxicillin (to cover for listeriosis)
Note: Ceftriaxone not used in neonates as displaces bilirubin from albumin and because it can cause biliary sludging
Neisseria meningitidis: Benzylpenicillin (high dose) or Ceftriaxone/Cefotaxime
How does penicillin resistance happen in N meningitidis?
The mechanism of relative resistance to penicillin involves, at least in part, the production of altered forms of one of the penicillin-binding proteins.
Although treatment with penicillin is still effective against these relatively resistant strains, there is evidence that low-dose treatment regimens can fail.
Beta-Lactamase production in meningococci is extremely rare but has been reported
How do you treat simple cystitis?
Trimethoprim 3 days
How do you treat HA UTI (commonest type of HAI)?
Cephalexin or Augmentin
How do you treat an infected urinary catheter?
Change under gentamicin cover
How do you treat C difficile colitis
STOP the offending antibiotic (usually a cephalosporin);
If severe, Rx with p.o. metronidazole;
If above fails, use p.o. vancomycin
How are antibiotics usage monitored?
Antibiotic policy/guidelines drawn up in consultation with other specialists in the Antibiotic Review Group
Microbiologist /pharmacist review of complex cases or inappropriate antimicrobial usage
If there is no response within 48 hours what should you consider?
Is it really bacterial? Are there cultures?
Is there a persistent focus present (e.g. an infected vascular or urinary catheter)?
Is there a deep-seated collection (e.g. intra-abdominal) that requires drainage?
Could the patient have bacterial endocarditis?
Correct dose?
Is another infection present (esp consider Candida)?
Summarise antibiotic prescribing
Get blood culuture (or appropriate culutre)
Prescribe empirical Abx on most likely Ddx.
Monitor clinical status and response (48-72h)- re-evaluate when microbiology has got results
Tailor therapy to more narrow Abx based on Micro and pt response.
If patient has been well then evaluation may result in discontinuation of treatment.
Is resistance increasing?
Yes
How are carbapenemases changing?
KPC was high during an outbreak in NW England
OXA-48 is also high
What is a MIC breakpoint and how is it used?
The point at which the there is therapeutic success
MIC>breakpoint - resistant
MIC
