Microbiology 1S: Antimicrobials 2

Question 1

Name some common examples of antibiotic misuse

Answer 1

• No infection present
• Selection of incorrect drug
• Inadequate or excessive dose
• Inappropriate drug therapy
• Expensive agent used when cheaper is available

Question 2

what % of those with bacteraemia will get better by themselves?

Answer 2

50%

Question 3

What is empirical therapy?

Answer 3

Treatment given without knowledge of the cause or nature of the disorder and based on experience rather than logic

• 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)

Question 4

What % of those given antimicrobial will experience an adverse event?

Answer 4

5%

Question 5

Name some examples of adverse reactions to antimicrobials

Answer 5

• GI upset
• Fever and rash
• Renal dysfunction
• Acute anaphylaxis
• Hepatitis

Question 6

What is the acronym to remember when prescribing antibiotics? What does it stand for?

Answer 6

• CHAOS – things to consider when prescribing antimicrobials
  
  • 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 7

What are some more specific guidelines for choice of antibiotic?

Answer 7

• Use NARROW SPECTRUM if possible
• Use BACTERICIDAL drugs if possible
• Ideally, choice based on a bacteriological diagnosis (or the best guess based upon the differential diagnosis)
• Consider local sensitivity patterns
• Patient characteristics
• Cost

Question 8

What are some other factors to consider when choosing an antibiotic?

Answer 8

• Pharmacokinetics (absorption, distribution, elimination)
• Route of administration
  
  • NOTE: in patients who are septic, their blood pressure is likely to be low, hence perfusion of their intestines will be low and so drug absorption per orally may be compromised
  • IV is recommended if:
    
    • The infection is serious Patient is not absorbing orally
    • There is a deep infection Treat CNS infection
• Dosage (age, renal/hepatic function, drug monitoring)

Question 9

Describe the Agar Disc Diffusion Method when it comes to calculating the MIC?

Answer 9

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

Question 10

What is the MIC?

Answer 10

• MIC = minimum inhibitory concentration
  
  • This is the minimum drug concentration that is required to inhibit the growth of the organism in a culture
  • There are regulatory bodies that set an MIC cut-off (i.e. if the MIC is higher than X, the organism is resistant)

Question 11

What type of Abx is the best for nosocomial (hospital acquired) pneumonia and severe sepsis?

Answer 11

• broad spectrum ABx are an optimal initial choice
• Septic shock is a particularly important indication for broad-spectrum antibiotics

Question 12

How are patients’ infective organism identified?

Answer 12

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

Question 13

Local concentration of the antimicrobial will be affected by factors such as…

Answer 13

• pH at the infection site
• Lipid-solubility of the drug
• Ability to penetrate the blood-brain barrier

Question 14

Which infections require special considerations when it comes to how the antimicrobial will reach the site of infection?

Answer 14

• Special considerations are needed for endocarditis and osteomyelitis
• 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 15

What are the indications for an antimicrobial?

Answer 15

• Check for evidence of a systemic response
  
  • Fever ± raised CRP
  • High WBC (mainly neutrophils; may be LOW WBC in severe infection)
  • Also consider:
    
    • Duration of symptoms
    • Underlying risk factors
    • Likely source of infection
    • Exclude other pro-inflammatory disease

Question 16

What are the routes of administration of antimicrobials and why are each used?

Answer 16

• IV –> serious (or deep-seated) infection
• PO –> usually easy, but avoid if poor GI function or vomiting
  
  • Different classes of antimicrobial have different oral bioavailabilities
• IM –> not an option for long-term use
  
  • Avoid if bleeding tendency or drug is locally irritant
• Topical –> limited application and may cause local sensitisation
  
  • NOTE: putting topical antibiotics on sloughing tissue will not be very effective

Question 17

When would one switch from IV to PO for antimicrobial Tx?

Answer 17

• IV to PO switch is recommended in hospital for most infections if the patient has stabilised after 48 hours of IV treatment

Question 18

Describe the patterns of activity of different antibiotic classes

Answer 18

Question 19

Describe type I antibiotics

Answer 19

• Type I (e.g. Aminoglycosides)
  
  • Peak above the MIC (Cmax) is the MOST IMPORTANT factor (these drugs have concentration-dependent effects)
  • Therefore, aminoglycosides are given as one big dose once a day, to try and get the Cmax as high as possible
  • The higher the Cmax the better the clinical outcome for infections treated with aminoglycosides
  • However, achieving high Cmax must be balanced with the risk of adverse effects (ototoxicity and nephrotoxicity)
    
    • You also measure the trough concentration to ensure that the drug is being eliminated
    • Accumulation of the drug is associated with toxicity
    • If the trough is too high, you will adjust the frequency of the doses being given so that you do not compromise the Cmax but do reduce accumulation of the drug
  • I.E. the peak will influence the dose of the drug given, whereas the trough will determine the 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 20

Describe type II antibiotics

Answer 20

• 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 21

Describe type III antibiotics

Answer 21

• 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 22

What is the length of antibiotic Tx guided by?

Answer 22

• Guided by the clinical response and improvement in inflammatory markers
• Not very well defined for most infections

Question 23

Name some Tx times for specific infections:

• N. meningitidis
• Acute osteomyelitis (adult)
• Bacterial endocarditis
• Group A Strep Pharyngitis
• Simple cystitis

Answer 23

• Recommended treatment duration for specific infections:
  
  • N. meningitidis 7 days
  • Acute osteomyelitis (adult) 6 weeks
  • Bacterial endocarditis 4-6 weeks
  • Group A Strep Pharyngitis 10 days to prevent sequelae like rheumatic fever
  • Simple cystitis 3 days

Question 24

Name some common organisms that cause skin infections

Answer 24

• Staphylococcus aureus
• Beta-haemolytic Streptococci (GBS)

Question 25

What is the Tx for skin infections?

Answer 25

• Treatment: flucloxacillin
  
  • Unless:
    
    • penicillin allergy → Clarithromycin/Erythromycin/Doxycycline
    • MRSA → Vancomycin

Question 26

What is the Tx for iGAS (invasive Group A Streptococcus)?

Answer 26

• Aggressive and early debridement
• Antibiotics – adjunctive use of protein synthesis inhibitors (e.g. clindamycin)
• Use of IV Ig

Question 27

Describe the eagle effect

Answer 27

• 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 28

What are some examples of Respiratory Tract Infections and give their Tx

Answer 28

Question 29

What are some common organisms that cause respiratory tract infections?

Answer 29

Question 30

Describe Hospital-Acquired Pneumonia

Answer 30

• Second most common cause of HAI
• Associated with highest mortality (23%)
• Greatest risk associated with tracheal intubation and mechanical ventilation

Question 31

What is the Tx for Hospital-Acquired Pneumonia?

Answer 31

• Cephalosporin
• Ciprofloxacin
• Piperacillin/tazobactam
• (If MRSA, consider addition of vancomycin)

Question 32

What are the main pathogens implicated in Bacterial Meningitis ?

Answer 32

• Neisseria meningitidis
• Streptococcus pneumoniae
• Listeria monocytogenes – in very young, elderly or immunocompromised

Question 33

What is the Tx for Bacterial Meningitis ?

Answer 33

• Treatment – generic
  
  • Neisseria, S. pneumoniae –> Benzylpenicillin (high dose) or ceftriaxone/cefotaxime
    
    • Neisseria can be resistant to penicillin through altered production of penicillin-binding proteins
    • Treatment with penicillin can still work but it needs to be at a high dose
  • Listeria –> Amoxicillin / ampicillin
  • Baby < 3 months –> Cefotaxime + amoxicillin (covers listeria)
    
    • IMPORTANT: ceftriaxone is NOT used in neonates because it displaces bilirubin from albumin and can cause biliary sludging

Question 34

What is the Tx for UTIs?

Answer 34

• Simple cystitis –> Trimethoprim 3 days
• Hospital-acquired UTI –> cephalexin / augmentin
  
  • MOST COMMON type of HAI
• Infected urinary catheter –> change under gentamicin cover

Question 35

What is the Tx for Clostridium difficile Colitis?

Answer 35

• STOP the offending antibiotic (usually a cephalosporin)
• If SEVERE, treat with:
  
  • Metronidazole (PO)
  • If above fails, use vancomycin (PO)
• NOTE: antimicrobial usage should be monitored

Question 36

What should you think about if there is no response within 48hrs to initial Clostridium difficile Colitis tx?

Answer 36

• 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)?