1s: Antimicrobials 2

Question 1

Give examples of antibiotic misuse

Answer 1

• no infection present
• inaequate/excessive dose
• selection of incorrect drug
• inappropriate drug therapy
• expensive agent used when cheaper is available

Question 2

CHAOS = things to consider when prescribing antimicrobials

Answer 2

• C - choice of correct antimicrobial depends upon the…
• H - host characteristics (i.e. renal failure, pregnancy, allergy, age, genetics, hepatic function)
• A - antimicrobial susceptibilities of the…
• O - organism itself and also the…
• S - site of infection (i.e. bone, CSF, urine)

Question 3

Guidelines for choice of drug

Answer 3

• use NARROW spectrum if possible
• use BACTERICIDAL drugs if possible
• ideally, choice based on bacteriological diagnosis (or best guess based on DDX)
• consider local sensitivity patterns
• patient characteristics
• cost

Other factors to consider:

• pharmacokinetics (absorption, distribution, elimination)
• route of administration (e.g. sepsis → low BP → perfusion of intestines low → oral drug absorption compromised.)
• IV recommended if = infection is serious, deep infection, patient not absorbing orally, treat CNS infection
• dosage (age, renal/hepatic function, drug monitoring)

Question 4

What is MIC?

Answer 4

Minimum inhibitory concentration

• minimum drug concentration needed to inhibit growth of organism in a culture
• guidelines = if MIC is higher than X, the organism is resistant

Question 5

Agar Disc Diffusion Method

Answer 5

• Time-consuming
• The disc is impregnated with abx which diffuses out from the disc
• as distance from disc increases, concentration of abx decreases logarithmically
• the border of the clear zone is the MIC

Question 6

Empirical therapy

Answer 6

• It is important to collect specimens for culture BEFORE starting empirical antibiotic therapy if possible
• Empirical cover can then be changed based on the culture results
• Empirical therapy covers the most likely organism (even before you know the exact one)

In patients with nosocomial infections, appropriate initial ABx is associated with higher survival rates

• So, broad spectrum ABx are an optimal initial choice for nosocomial pneumonia and severe sepsis
• Septic shock is a particularly important indication for broad-spectrum antibiotics

Question 7

Identification of organisms ix

Answer 7

• Gram-staining (send as much specimen as possible  higher volume of sample means higher sensitivity)
• Rapid antigen detection
  
  • Immunofluorescence
  • PCR

Question 8

Site of infection factors

Answer 8

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

Special considerations are needed for endocarditis and osteomyelitis

Question 9

Need for antimicrobials: check for evidence of a systemic response, route of administration

Answer 9

• 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

Question 10

PK/PD predictors of efficacy

Answer 10

Question 11

3 patterns of antimicrobial activity: type 1

Answer 11

Peak above MIC (Cmax) is the MOST IMPORTANT FACTOR (as concentration-dependent effects)

→ aminoglycosides given as one big dose a day to get max Cmax

however, adverse effects (ototoxicity and nephrotoxicity)

• also measure trough concentrations to ensure drug is being eliminated
• accumulation of drug is associated with toxicity

→ PEAK influence dose of drug give, TROUGH, determines frequency

• NOTE: if a patient has renal failure than you may be worried about giving a full dose of aminoglycosides however, if their renal failure is caused by the sepsis then you would want to start off with the full dose and worry about the nephrotoxicity and accumulation later

Question 12

3 patterns of antimicrobial activity: type 2

Answer 12

Type II (e.g. Penicillins)

• These are time-dependent, so you want to maximise the time above the MIC
• The concentration above the MIC is NOT very important
• So, with penicillins, you tend to take them quite frequently (3-4 times per week)

Question 13

3 patterns of antimicrobial activity: type 2

Answer 13

Type II (e.g. Penicillins)

• These are time-dependent, so you want to maximise the time above the MIC
• The concentration above the MIC is NOT very important
• So, with penicillins, you tend to take them quite frequently (3-4 times per week)

Question 14

3 patterns of antimicrobial activity: type 3

Answer 14

Type III (e.g. Vancomycin)

• Sort of a combination of Type I and Type II
• The AUC above the MIC is the MOST IMPORTANT factor (both concentration and time-dependent effects)
• Infusions can maintain an AUC above the MIC

Question 15

Length of treatment decision

Answer 15

Question 15

Length of treatment decision

Answer 15

Question 16

Common skin infection organisms and treatment for these

Answer 16

Common organisms

• staphylococcus aureus
• B-haemolytic streptococci (GBS)

Tx = flucloxacillin (unless penicillin or MRSA allergic)

iGAS (invasive Group A streptococcus)

• aggressive and early debridement
• abx - adjunctive use of protein synthesis inhibitors (e.g. clindamycin)
• use of IVIG

Question 17

Eagle effect

Answer 17

• Describes the relative lack of efficacy of beta-lactams on infections having large numbers of bacteria
• Penicillin works by inhibiting cell wall synthesis, but cell wall synthesis only occurs when the bacteria are dividing
• In cases of extremely high bacterial burden, bacteria may be in the stationary phase of growth
• In this case, as no bacteria are actively replicating, penicillin has NO activity

Question 18

Respiratory Tract Infections

Answer 18

Examples and treatment:

• pharyngitis = benzylpenicillin (20 days) phenoxymethylpenicillin (10 days)
• CAP (mild) = amoxicillin
• CAP (severe) = co-amoxiclav and clarithromycin

Common organisms:

• streptococcus pneumonia
• haemophilia influenza
• mortadella catarralis
• Atypicals: legionella, mycoplasma, chlamydia

Question 19

Hospital acquired pneumonia

Answer 19

• Second most common cause of HAI (HAI = >48 hours after admission)
• highest mortality
• greatest risk associated with tracheal intubation and mechanical ventilation
• organisms = S. aureus, Klebsiella, Pseudomonas, Haemophilus

Mx:

• co-amox AND
• gentamicin or tazocin

Question 20

Main pathogens for bacterial meningitis

Answer 20

• Neisseria meningitides
• Streptococcus pneumonia
• Listeria monocytogenes = in very young, elderly or immunocompromised

Question 21

Tx for bacterial meningitis

Answer 21

Neisseria, S. pneumonia → benzylpenicillin (high dose) or ceftriaxone

Listeria → amoxicillin/ampicillin

Baby <3 months -→ cefotaxime + amoxicillin (covers listeria)

Question 22

top 2 most common HAI

Answer 22

1. HA UTI
2. HA Pneumonia

Question 23

UTIs

Answer 23

Question 24

C. diff colitis

Answer 24

Question 25

If no response within 48 hours, consider the following…

Answer 25

* Does the patient have a bacterial infection? * Is there a persistent focus present (e.g. urinary catheter)? * Is there a deep-seated collection (e.g. intra-abdominal) that requires drainage? * Could the patient have bacterial endocarditis? * Am I using the correct dose of antimicrobial? * Is there another infection present (consider Candida)?