Principals of Antimicrobial Use Flashcards
1
Q
Define Stewardship
A
Careful and responsible management of natural resources
2
Q
List the stepwise systemic approach to antimicrobial use
A
- Confirm presence of infection (Risk factors, subjective evidence, objective evidence, possible sites of infection)
- Identification of pathogen (likley pathogen, microbiological tests)
- Selection of antimicrobial and regimen
- Empiric, definitive, prophylaxis
- Consider organism, host and drug factors
- Decide on choice of agent, route, dosage and duration - Monitor response
- Therapeutic response
- ADRs
Step 1 and 2 = Indication for Use
Step 3 = Regimen
Step 4 = Monitoring and Plan
3
Q
Definition of Infection ?
A
Infection is when an organism causes damage to host resulting in altered physiology, s/sx of disease
4
Q
List the Risk Factors for Infection
A
- Disruption of natural protective barriers
- Skin/mucous membranes
- CIlia of respiratory tract - Age
- Immunosuppression
- Malnutrition
- Underlying diseases (e.g. HIV)
- Drugs (Immunosuppressive, chemotherapy, steroids) - Alterations in normal flora of host
- e.g. Hospital or use of antibiotics
5
Q
What are the subjective evidences for infection?
A
- Localised symptoms
- Diarrhea, nausea, vomiting, abdominal distention
- Cough, purulent sputum
- Dysuria, frequency, urgency
- etc - Systemic symptoms
- Feverish, chills, rigors
- Malaise
- Fast Heart Rate
- Shortness of breath
6
Q
What are the OBJECTIVE evidences of infection?
A
Changes in vital signs, for example
- Fever (temperature > 38 degrees)
- Hallmark of infection
- May be masked by antipyretics, also may have non-infectious causes - Hypotension (SBP < 100)
- Tachypnea (Increased RR > 22 bpm)
- Heart Rate (> 90bpm)
- Altered Mental Status (esp in elderly)
- Drop in Glasgow Coma scale
Changes in Lab test (elevated/depressed total whites, neutrophils, INCREASED Procalcitonin, CRP, Erythrocyte sedimentation rate, ESR)
- CRP is not so specific for infection (only indicates inflammation)
- Procalcitonin more specific for infection (higher = presence of infection)
7
Q
At what level of Procalcitonin is starting Abx encouraged?
A
> = 0.5ug/L
Strongly encouraged if >= 1ug/L
8
Q
At what level of Procalcitonin should we consider stopping Abx?
A
When procalcitonin levels decrease by 80% from peak concentration, OR concentration <0.5ug/L
9
Q
At what level of Procalcitonin should we consider changing Abx?
A
When procalcitonin increases, and concentration remains above 0.5ug/L
Remember: Threshold to continue Abx is always 0.5ug/L
10
Q
At what level of Procalcitonin should we consider CONTINUING abx?
A
When there is a decrease of more than 80% of Procalcitonin BUT concentration remains above 0.5ug/L
11
Q
What are the common sites of infection?
A
Urinary tract, Respiratory tract, Skin/soft tissues, Intra-abdominal (cavity of the abdomen)
12
Q
Define Sepsis
A
Life threatening organ dysfunction caused by dysregulated host response to infection
13
Q
Follow up cultures are less reliable than pre-treatment cultures because…
A
It may result in false negative results
- Need to obtain cultures before administration, because organisms may already be killed by empiric Abx
14
Q
Once you obtain the results of culture test, what are the kinds of pathogen that is possible that we have to consider? (Hint: True pathogens or…)
A
Pathogens possible: Contamination, Colonizers or True pathogen
Streamline therapy if true pathogen is indeed isolated
15
Q
Intraabdominal infections and DM foot infections is an example of
A
Anaerobic Infections
16
Q
List some sites on the body that are usually sterile (anatomically)
A
CNS, Cardiovascular system, Lower respiratory tract, Bones and Joint, Kidney and bladder (but not urethra)
17
Q
Most common pathogen that is found for UTI is
A
Ecoli
18
Q
Can commensals and colonisers cause infection?
A
Usually no.
But there is a need to assess the situation and exclude other factors. (Do not discount commensals and colonisers completely)
19
Q
Define True Pathogen
A
Causes true infection , capable of damaging host tissue and eliciting host response and s/sx of infection (Aka causes disease)
Can be acquired from environment or part of normal flora or even commensals
20
Q
Define Colonisers
A
Presence of normal flora or pathogen organisms but usually does not elicit host response
21
Q
Define contaminants
A
Presence of microorganisms typically acquired during collection or processing of host specimens without evidence of host response
22
Q
What is a likely contaminant for blood cultures?
A
Staphylococcus Epidermidis (Coagulase Negative Staphylococcus) , Bacillus spp
Note: They may sometimes still be a true pathogen esp in cases of catheter-related infections or ports going into bloodstream
23
Q
What is a likely COLONISER from urine culture?
A
Yeast
24
Q
What must be considered during selection of Abx? (3 factors)
A
- Empiric, Definitive (Culture-directed) or Prophylaxis
- Which agent, route of adm, dosing, duration? (Appropriate Agent, Duration and Route)
- Organism, host and drug factors
25
Define empiric therapy
Abx use based on:
1. Clinical presentation
2. Site of infection
3. Likely organism causing infection at that site
4. Likely resistant pattern
26
Define Definitive therapy
Aka culture directed therapy
| Abx choice is based on microbiological results
27
Define prophylactic therapy
Abx given to prevent an infection
| - e.g. Surgical Prophylaxis and Post-exposure prophylaxis
28
What are the consequences of overtreatment of Abx?
Abx associated toxicities (Side effects)
CDAD / Superinfections
Resistance
Cost
29
What is the conseuqence of undertreatment of Abx?
1. Ineffectiveness
2. Mortality
3. Increased length of stay in hospital
4. Cost (wastage due to ineffectiveness)
30
What are the three most important principles of Abx use to achieve improved patient outcomes?
1. Timely initiation of appropriate agents (most effective, least toxic and narrowest spectrum)
2. Administration of dosage individualised to patient and appropriate to organism and site of infection
3. Timely and appropriate alteration in response to clinical responses and microbiological data
(Shortest course of Abx as much as possible)
31
Why must active Abx be administered asap esp for severely ill patients
Increased mortality due to non-timely treatment
32
What are the benefits of Combination Therapy for Abx?
1. Extend specturm of activity (esp for severely ill patients)
- Piptazo + Vancomycin to cover (-) and (+) respectively
- Piptazo + Ciprofloxacin to cover Pseudomonas ventilated associated pneumonia
2. Achieve synergistic bactericidal effect
- Ampicillin + Gentamicin for Enterococcus Endocarditis
- Trimethoprim + Sulfamethoxazole
3. Prevent development of resistance
33
What are the possible disadvantages of combination therapy?
1. Increased risk of toxicity and allergic reactions
2. Increased risk of drug interactions
3. Increased cost
4. Increased selection for MDR organisms
5. Increased risk of Superinfections
- E.g. CDAD on top of primary infections (due to Clindamycin use), disruption of natural flora leading to increased risk of fungal infections
6. Possible antagonistic effect concerns
- Bactericidal Abx cannot be combined with bacteriostatic, the antagonistic effect is theoretical. Best to avoid
34
What are the host factors to consider in Abx use?
1. Age
2. History of Allergies and ADR
3. G6PD (e.g. Bactrim - Sulfa drugs, Nitrofurantoin)
4. Pregnancy/lactation
5. Renal/Hepatic impairment
6. Status of host immune function
7. Severity of Illness
8. Recent antimicrobial use (Superinfections possible?)
9. Healthcare associated risk factors (Nosocomical Infections possible?)
35
What antibiotics are generally avoided in children?
Fluoroquinolone, Tetracyclines
- Fluoroquinolone: Bone deformities in young children
- Tetracyclines = affect bone and teeth development, can cause tooth discoloration
36
What are the possible beta lactams that can cross react with penicillins allergies?
Cephalosporins, Carbapenems
Can still be considered if patient established that he/she will only have very mild reactions (itchiness etc) with consideration of other Abx first (e.g. Macrolides) but....
Avoid them ESPECIALLY for patients with severe hypersensitivity reactions (e.g. immediate IgE mediated Allergic reactions, SJS, TEN)
Mild reactions = can still consider case by case
37
What is G6PD a concerning factor in Abx selection?
Concern about hemolysis of RBC
To avoid sulfonamides, nitrofurantoin
38
What are the Abx that may cause Hemolysis in G6PD patients?
Sulfonamides (Sulfamethoxazole in Co-trimoxazole), Nitrofurantoin
39
Name the Abx generally safe for pregnancy
Beta lactams, Macrolides
40
Name the Abx to be avoided in pregnancy
Bactrim, Fluoroquinolones, Tetracyclines
Fluoroquinolones and Tetracyclines to be avoided in children anyway
Bactrim = Avoid in 1st and 3rd trimester due to concerns over G6PD in 1st and 3rd trimester, and Kernicterus in fetus for 3rd trimester
41
What are the Abx that can cause nephrotoxicity (kidney impairment)?
Aminoglycosides
| High Dose Vancomycin
42
What are the Abx that can cause Hepatotoxicity?
Pyrazinamide, Rifmapicin Isoniaizd (Pyrazinamide most toxic)
Amoxi-clav etc
43
For immunocompromised patients, it may be better to use.....
Bactericidal drugs (BQAV)
- Beta Lactams
- Quinolones
- Aminoglycosides
- Vancomycin (Glycopeptide)
Consider combination therapy for polymicrobial/multiple infections, or in cases of Pseudomonas (Piptazo + Cipro for Pseudomonas-causing Pneumonia)
44
If patient is severely ill....
1. Timely treatment with Abx essential +
| 2. Consider Broader spectrum coverage like for Pseudomonas (e.g. Piptazo + Ciprofloxacin, Piptazo + Vanco etc)
45
What if a patient fails to get better with the Abx
Do not continue with same Abx and
Consider that recent Abx use is a risk factor for drug resistant organism
But consider other factors like compliance, administration issues or whether is the culture test is still valid (may need to redo culture test again)
46
What are the MDR organisms found in healthcare setting?
MRSA
ESBLs
Drug Resistant Pseudomonas & Acinetobacter Baumannii
47
List the Healthcare-associated risk factors
1. Hospitalisation in recent 90 days
2. Current hospitalisation for more than 2 days
3. Residence in nursing homes
4. Abx use in last 90 days
5. Home infusion therapy
6. Chronic dialysis
48
What Abx work for MRSA?
Vancomycin, Linezolid, Daptomycin, Ceftaroline (5th gen Cephalosporin)
(Also possible: Bactrim, Doxycycline, Clindamycin)
49
What Abx works for Pseudomonas?
| Hint: PCCC LAGAMI
```
Ceftazidime
Cefepime
Piptazo
Ciprofloxacin
Levofloxacin
Amikacin
Gentamicin
Aztreonam
Meropenem
Imipenem
```
50
What Abx works against ESBL producing Enterobactericeae?
Meropenem
Imipenem
Ertapenem
Aminoglycosides
=> Carbapanams and Aminoglycosides
51
What Abx work against Anaerobics?
| CMAPC
```
Clindamycin
Metronidazole
Amoxiclav (addition of Clavulanic acid to Amoxicillin causes Amoxicillin to be active against Anaerobes, similarly for Piptazo's case)
Piptazo
Carbapenems
```
52
Which Abx cmi for CSF penetration? (Low CSF concentration)
1st and 2nd generation Cephalosporins
Aminoglycosides
Macrolides
Clindamycin
53
What can be used for CSF infections?
Penicillins
Ceftriaxone (3rd gen cephalosporins onwards)
Cefepime
Ceftazidime
Meropenem
Vancomycin
54
Why is Daptomycin not used for pneumonia? (Pneumonia caused by ventilator associated MRSA)
Inactivated by lung surfactant
55
For treatment of abscesses, avoid....
Aminoglycosides
56
Abx good for concentrating in prostate?
Ciprofloxacin and Bactrim
57
What is a surrogate marker for PK-PD relationship?
Minimum Inhibitory Concentration (MIC)
58
Name the two main categories of Pk-PD characteristics that Abx may fall under (2 types of Abx)
1. Concentration dependent Abx
| 2. Time dependent Abx
59
Define time-dependent Abx
Time that Abx is ABOVE MEC
AUC over MIC is also used = A certain AUC over MIC is needed
Killing is more correlated to duration of exposure, NOT concentration
60
Example of time-dependent Abx?
Beta Lactams (Penicillins etc)
61
Define concentration dependent Abx
Abx where a certain level of Cmax above MEC must be obtained (A high Cmax peak that is way above MEC is desired)
Rate and extent of bacterial killing is a function of Abx concentration (higher conc = rapid and more extensive killing)
62
Example of concentration dependent Abx?
Aminoglycosides, Fluoroquinolones
63
Post antibiotic effect is....
the ability of Abx to persistent suppress bacterial growth, EVEN at LOW/UNDETECTABLE concentrations
64
State the dosing strategy for Concentration dependent Bacterial Killing?
Optimise Peak:MIC ratio
- Peak/Cmax is usually 8 to 10x above MIC (IMPT)
- Give Larger doses at extended intervals
- *Quantity is more important* to achieve higher Cmax (peak)
- E.g. For Ciprofloxacin, Choose 500mg Q24H OVER 250mg every 12 hours to achieve greater Cmax
65
Aminoglycosides are given
Once daily doses, to achieve 8 to 10x above MIC levels
- Cmax of 16 to 20 ug/mL usually
- Follow the Hartford's Nomogram
66
Why are Aminoglycosides given once daily usually?
| 5 reasons
Because it has concentration dependent killing
+
Post antibiotic effect
+
Prevents adaptive resistance (selection of more resistant mutants)
+
Less nephrotoxicity (due to once a day only, nephrotoxicity associated with duration of exposure rather than concentration)
+
Lowered cost
67
Starting dose for Aminoglycosides under the hartford Monogram?
Always start with 7mg/kg
Dosing frequency depends on how much is left after a certain duration (Maintainance dose frequency)
- Dose is correlated with renal function (CrCl)
68
Describe the steps to derive Aminoglycoside dosage regimen under the Hartford Nomogram?
1. Start with 7mg/kg
2. Take serum concentration of drug 6 to 14 hours after the dose (usually 8 hrs)
3. Plot the nomogram
69
What is the Dosing strategy for Time dependent bacterial killing?
Percentage of time above MIC must be at least 40-70% of the time
(40-70% of dosing interval above MIC)
More frequent dosage adm
Continuous IV infusion/prolonged intermittent infusion
Block excretion (using PROBENECID)
70
Starting dose for Aminoglycosides?
7mg/kg
71
What drug can block excretion of Penicillin?
Probenecid
72
Total time above MIC for Continuous, Traditional and Prolonged Administration for time-dependent killing...
Total time above MIC:
| Continuous > Prolonged > Traditional
73
What is the Abx with time dependent bacterial killing + PAE effect or long half life?
Vancomycin (400-600 AUC:MIC ratio for MRSA).
Rate and extent of bacterial killing depends on overall drug exposure (AUC) vs MIC (AUC vs MIC)
Note: Beta Lactams only has TIME DEPENDENT killing, no PAE
74
Dosing strategy for Abx (e.g. Vancomycin) with Time dependent bacterial killing + Persistent effect (due long t1/2 or PAE?)
Optimise AUC:MIC Ratio (e.g. Vancomycin - 400 to 600 for MRSA)
*Dependent on Total Daily Dose (impt)*
Vancomycin 500mg every 12 hours vs 1g every 24 hours
- Just choose 1g every 24 hours since TDD is more impt and clearance is same for 1 patient
75
Route of Adm for severe infections/hospitalisation/rapid blood concentration needed?
IV
Change to oral once patient can tolerate/where suitable
76
Advantage of oral route includes
Avoidance of catheter/line/blood infections, and irritation to veins causing Thrombophlebitis
77
What are some Abx with good bioavailability for BOTH oral and IV?
(F BLM)
Fluoroquionolones, Metronidazole, Linezolid, Bactrim
Administration of IV vs Oral may not be so important (Oral bioavailability, F > 0.8)
78
Considerations for Route of administration....
PO - Choose Abx with Good oral bioavailability
(e.g. Fluoroquinolones, Metronidazole, Linezolid, bactrim)
IM - Community based, less common and less painful (than IV) = e.g. IM Ceftriaxone, Streptomycin, Benzathine Penicillin for Syphilis
Topical: For skin/localised infections
Aerolised/nebulised - E.g. Nebulised CMS (Colistin Methanesulfonate) for MDR Pseudomonas (not common but may be used)
79
What drug lowers Valproate (Antiepileptic) concentrations?
Carbapenems
80
CYP450 inhibitors?
Azoles (Systemic - Fluconazole, Itraconazole, Voriconazole)
| Macrolides (Erythromycin, Clarithromycin, Azithromycin)
81
CYP450 Inducers?
Rifampicin
82
Examples of infections that may take months to resolve
TB, chronic suppression of other infections
83
Example of infections that is lifelong
HIV
84
Infections that take 4-6 weeks of Abx therapy?
Endocarditis (Infection of the Endocardium of the heart)
| Osteomyelitis
85
Common ADRs for patients new to Abx?
Angioedema, Rashes, Itch
86
What are the notable side effects for Vancomycin?
Flushing, Hypotension, itch are common side effects
Red man syndrome may be observed (esp with Rapid Infusion)
- Vancomycin is a time dependent Abx with PAE effect
- Prioritise Total Daily Dose (TDD) to achieve a certain amount of AUC/MIC ratio (400-600)
- Since TDD is used, Vancomycin can be considered for Continuous/prolonged infusion to slow down rate of infusion and reduce Red Man's Syndrome
To note: Continuous infusion = Can take whole day
Prolonged infusion = Just lengthening the typical infusion time
87
If patient has satisfactory response to an Abx (e.g. Empirics), what are the possible steps to take next?
1. Convert IV to oral if applicable
2. Deescalate/streamline broad spectrum to narrower spectrum
3. Stop if completed adequate duration (e.g. Procalcitonin levels <0.5ug/L , possibly with >80% decrease from previous levels)
- Note: Continue if there is a drop in 80% of Procalcitonin but levels still remain above 0.5ug/L. Change if there is an increase in Procalcitonin levels, with levels remaining above 0.5ug/L.
88
Possible causes of unsatisfactory response to Abx includes:
1. Inappropriate diagnosis (noninfectious causes, non-bacterial)
2. Inappropriate choice of Abx (Resistance, development of resistance0
3. Subtherapeutic concentrations (Non-compliance, IMPROVING RENAL FUNCTION, drug interactions)
4. Abscess/collections that need drainage/surgery to remove
5. Impaired host defense
6. Superinfection (CDAD/fungal infections)
7. Toxicity of Abx
89
3 Most important principles of Abx use to improve patient outcomes?
1. Timely initiation of appropriate agents
2. Administration of dosage individualised and appropriate to organism and site of infection
3. Timely and appropriate ALTERATION in response to clinical responses and microbiological data (Give Abx for shortest duration possible)
90
What is the MINDME Acronym for Antimicrobial Stewardship under WHO?
Microbiology guides therapy whenever possible
Indications should be evidence based
Narrowest spectrum required
Dosage appropriate to site & type of infection
Minimise duration of therapy
Ensure Monotherapy
91
Major objectives of Antimicrobial Stewardship Programme?
1. Achieve best clinical otucomes
2. Minimise toxicity/other adverse events
3. Limit selective pressure on emergence of Abx-resistant strains
4 Reduce excessive costs attributable to suboptimal antimicrobial use
