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Year 3 - infection > Antimicrobial Chemotherapy > Flashcards

Antimicrobial Chemotherapy Flashcards

1
Q

Paradox - Antibiotics increase infections - how?

A
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2
Q

paradox - Antibiotics increase infection…and mortality in uninfected patients?

A

excessive antimicrobial usage causes measurable harm to patients and ar emor elikely to get infections like C. diff

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3
Q

With current trends in antimicrobial use, new _________ and increasing numbers of _________ (new clones) will be generated at home and abroad and spread internationally

Current control efforts are “firefighting”

Prevention requires a new attitude to Antibiotic Stewardship, requiring major _______ in antibiotic ___ and “antibiotic holidays”

A

resistances

infections

decline

use

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4
Q
  • Patients with infections caused by ___________ _______ are generally at ________ risk of worse clinical outcomes and death, and consume ____ healthcare resources than patients infected with the ____ bacteria that are not _______. (WHO 2014)
  • The use and misuse of antimicrobials __________ the emergence of drug-resistant strains
A
  • Patients with infections caused by drug-resistant bacteria are generally at increased risk of worse clinical outcomes and death, and consume more healthcare resources than patients infected with the same bacteria that are not resistant. (WHO 2014)
  • The use and misuse of antimicrobials accelerates the emergence of drug-resistant strains
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5
Q

There is a high correlation between antibiotic ___ and __________

A

use

resistance

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6
Q

how would you do IV to Oral Switch Therapy (IVOST)?

A

Consider switching patients from IV to oral antibiotics after 48hrs, provided that: the patient is improving clinically and is able to tolerate an oral formulation

i.e. if all the criteria below are met:

Able to swallow and tolerate fluids

Temp. 36-38°C for at least 48 hours

Heart rate < 100bpm for previous 12 hours

WCC between 4 and 12x109L

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7
Q

Healthcare workers can help tackle AMR by…

A
  • Practicing effective infection prevention & control
  • Prescribing and dispensing antibiotics only when truly needed
  • Prescribing & dispensing the right antibiotic(s) for the right duration to treat the illness

“Our mission is not to prescribe as few antibiotics as possible but to identify that small group of patients who really need antimicrobial treatment and to explain reassure and educate the large group of patients who do not.”

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8
Q

Everybody can help tackle resistance! How?

A
  • Use antibiotics only when prescribed
  • Complete the full course
  • Never share antibiotics or use leftover prescriptions
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9
Q

are all antiviral virustatic or virucidal?

A

All are virustatic, none are virucidal

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10
Q

• Viruses are _______ intracellular parasites

A

obligate

a parasitic organism that cannot complete its life-cycle without exploiting a suitable host

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11
Q
  • As viruses utilise host cell enzymes in order to _______, there are limited viral proteins that are potential _______ for antiviral drugs
  • Toxicity to host cell ___ uncommon: side effects
  • Only used in a _______ of viral infections
A

replicate

targets

not

minority

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12
Q

what stage of the virus life cycle is the target?

A
  • Several stages of the virus life cycle are targets
  • Most target intracellular stages
  • Greater effect on viral replication than on the host cell function
  • Most antivirals are nucleoside analogues - inhibit nucleic acid synthesis
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13
Q

what may the treatment of antivirals be used for?

A

Prophylaxis (to prevent infection)

Pre-emptive therapy (when evidence of infection detected, but before symptoms apparent)

Overt disease

Suppressive therapy (to keep viral replication below the rate that causes tissue damage in asymptomatic infected patient)

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14
Q

Do antivirals eradicate the virus from latently infected cells?

A

Antivirals do NOT eradicate virus from latently infected cells, e.g. herpes viruses

Therefore, after successful treatment of an episode of overt infection, suppressive (maintenance) treatment may be needed

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15
Q

what can antivirals be used for in practice?

A

Herpesviruses: HSV 1 & 2, VZV, CMV

HIV

Hepatitis: hepatitis B, hepatitis C

Respiratory: influenza, respiratory syncytial virus (RSV)

Use of Antivirals for HSV & VZV

Herpes simplex: Mucocutaneous: oral, genital, eye, skin, Encephalitis, Immunocompromised: any site

Chickenpox: in those at increased risk of complications, neonate, immunocompromised, pregnant, immunocompetent adult…only if begun within 24 hours of onset of rash

Shingles: Only decreases post-herpetic neuralgia in the immunocompetent host if begun within 72 hours of onset of symptoms

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16
Q

How are each of the following taken:

aciclovir

valaciclovir

famciclovir

foscarnet

A

aciclovir - oral, IV, eye ointment, cream

valaciclovir - oral

famciclovir - oral

foscarnet - IV

aciclovir-like drugs are only active in herpes infected cell - low toxicity for uninfected cells

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17
Q

what is the mode of action of aciclovir?

A
  • Aciclovir is converted by viral thymidine kinase to ACVMP,
  • ACVMP then converted by host cell kinases to ACV-TP
  • ACV-TP, in turn, competitively inhibits and inactivates HSV-specific DNA polymerase
  • preventing further viral DNA synthesis
  • without affecting the normal cellular processes
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18
Q

Antivirals and CMV - All available drugs have significant toxicity

when should they be used?

A

• Only treat life- or sight-threatening CMV infections

e.g. HIV patients: CMV retinitis, colitis, Transplant recipients: pneumonitis

  • May also be used to treat neonates with symptomatic congenital CMV infection
  • ganciclovir - IV, ocular implant
  • valganciclovir - Oral
  • cidofovir - IV
  • foscarnet - IV
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19
Q

what is the use of antivirals in influeza?

A

Influenza A or B: oseltamivir, zanamivir

  • Role in both treatment and prophylaxis
  • Not always indicated, but if used, should usually start within 48 hours of onset of symptoms/contact
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20
Q

onto main antimicrobial chemotherapy powerpoint

A
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21
Q

what are the different locations that a drug can act in an orgamism?

A
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22
Q

Penicillins

A
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23
Q

Cephalosporins

A
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24
Q

Aminoglycosides

A
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25
Macrolides
26
Quinolones
27
Glycopeptides
28
Other antibiotics (1)
Other antibiotics (2)
29
Other
30
what are the 4 principles of prescribing?
1. Indications for antimicrobials 2. Diagnosis 3. Patient Characteristics 4. Antimicrobial selection
31
what does empiric and directed mean?
vempiric - without microbiology results directed - based on microbiology results
32
what are 2 indications for antimicrobials?
therapy prophylaxis
33
what ar ethe types of prophylaxis?
Primary: - anti-malarial; immunosupressed patients - pre-operative surgical - post-exposure e.g. HIV, meningitis Secondary - To prevent a second episode e.g. PJP
34
how is the diagnosis made
Diagnosis of Infection: - Clinical - Laboratory - None (no treatment) Severity assessment: ? Sepsis (qSOFA: syst BP\<100, altered mental, RR\>22) ? Septic shock
35
what are important Patient Characteristics to think about when prescribing?
age renal function liver function immunocompromised pregnancy known allergies
36
when prescribing, how is antimicrobial selection done and hwat needs to be thought about?
Guideline or “individualised” therapy ? likely organism(s) empirical therapy or result-based therapy bactericidal vs. bacteriostatic drug single agent or combination potential adverse effects
37
Clinical scenario 1: Mrs S 84 year old lady admitted with falls due to postural hypotension. ACE inhibitor stopped and fit for discharge. On doing the IDL you come across the following result Urine microscopy pus cells 84 Urine culture 105 growth of E.coli Sensitive to Amoxicillin, Co-amoxiclav, Trimethoprim, Nitrofurantoin, Gentamicin, Temocillin, Fosfomycin, Ciprofloxacin What do you do?
38
Clinical Scenario 2: Mrs S 84 year old lady admitted with falls due to postural hypotension. ACE inhibitor stopped and fit for discharge. On doing the IDL you come across the following result Urine microscopy pus cells 84 Urine culture 105 growth of E.coli Resistant to Amoxicillin, Co-amoxiclav, Trimethoprim, Nitrofurantoin, Fosfomycin, Ciprofloxacin Sensitive to Temocillin, Gentamicin, Meropenem What do you do?
39
Antimicrobial Prescribing Facts: The 30% Rule: ➤ 30% of all hospitalised inpatients at any given time receive \_\_\_\_\_\_\_\_ ➤ Over 30% of antibiotics are prescribed ___________ in the community ➤ Up to 30% of all surgical __________ is inappropriate ➤ 10-30% of pharmacy costs can be saved by antimicrobial __________ programs
antibiotics inappropriately prophylaxis stewardship
40
Antibiotic Resistance: \_\_\_\_\_\_\_ phenomenon Bacteria adapt to \_\_\_\_\_\_ Bacteria rapidly multiply and can generate ________ very quickly
Natural survive resistance
41
What is the Sensitivity Testing Disk Defusion method?
a test of the antibiotic sensitivity of bacteria. It uses antibiotic discs to test the extent to which bacteria are affected by those antibiotics
42
what are 4 Main Mechanisms of Resistance?
Enzymatic inactivation of drug Modified targets for drugs Reduced permeability to drug Efflux of drug
43
Genetics of resistance can be mediated by what 2 things?
Chromosomally mediated Plasmid mediated
44
what is Chromosomally Mediated Resistance?
Mutation in gene coding for drug target or membrane transport system Frequency of spontaneous mutations 10-7 to 10-9 Much lower than frequency of acqusition of plasmids Less of a problem clinically Basis for using multi-drug therapy eg TB.
45
what is Binary Fission?
DNA replicates Cell elongates Divides in 2 2 identical bacteria
46
what is the process of Plasmid Mediated Resistance?
Plasmids are extra-chromosoamal strands of DNA Replicate independent of cell chromosome Carry genes for enzymes which degrade antibiotics and modify membrane transport systems May carry 1 or more resistance gene Bacteria have ability to conjugate Therefore they can transfer resistance genes to other species of bacteria Can be cross species Certain bacteria can take up plasmids by transformation
47
what are some exaples of Medically Important Resistant Organisms?
MRSA VRE ESBL CPE Clostridium difficile
48
what is MRSA resistant to
Methicillin is a penicillinase resistant penicillin ie similar to flucloxacillin MRSA has an altered binding protein compared with MSSA Resistant to flucloxacillin
49
what can MRSA be used in the lab for?
Used in lab to determine whether organisms are sensitive to flucloxacillin
50
Can MRSA colonise without infection?
Most often colonisation without infection
51
What can the effects of MRSA be?
Can cause severe invasive infections eg osteomyelitis, endocarditis Mortality in patients with MRSA bacteraemia is twice that of MSSA bacteraemia
52
Carriage of MRSA is promoted by what?
Carriage of MRSA is promoted by antibiotic use
53
what is VRE?
Vancomycin resistant enterococci Enterococci are intrinsically only sensitive to a limited number of antitbiotics VRE are only sensitive to 1 or 2 antibiotics
54
where do VRE colonise and what effects can they cause?
VRE colonise GI tract in patients exposed to multiple antibiotics Can cause invasive disease eg endocarditis especially in patients with prosthetic devices
55
What is ESBL producing Enterobacteraciae?
ESBL – extended spectrum beta-lactamase Confer a range of resistance mechanisms, enzymatic degradation of antibiotic, reduced porins, increased efflux Resistant to beta-lactam antibiotics, often cephalosporins May be associated with further resistance mechanisms such as resistance to aminoglycasides and carbapenems (CPE)
56
CPE - Carbapenem producing enterobacteriacae what is effective against it?
Multiply resistant bacteria Typically only sensitive to a few antibiotics of last resort When associated with infection few treatment options
57
where can CPE – Carbapenem producing enterobacteriacae colonise and what is its effects?
Can colonise gut of healthy individuals Can colonise healthcare environment
58
what are Factors Influencing Antibiotic Resistance?
Widespread antibiotic use encouraging selective pressure (i.e surviving bacteria develop resistance) Antibiotic use by medical professions, veterinary practices, farming Patients surviving longer with more medical conditions and hospital contact More invasive procedures and prosthetic devices eg dialysis patients In UK increased bed pressure encourages spread of resistant organisms
59
has antibiotic use and prescribing decreased or increased?
decreased
60
who prescribes the most antibiotics?
61
what is a type 1 hypersensitivity reaction?
Type I – IgE mediated specific immunoglobulin, stimulates pro-inflammatory release resulting in urticarial, laryngeal oedema, bronchospasm/circulatory collapse - Anaphylaxis occurs in 4 to 15 of every 100,000 penicillin treatment courses
62
what is a type 2 hypersensitivity reaction?
Type II - Beta lactam specific IgG or IgM antibodies bind to circulating blood cell resulting in haematological reactions or interstitial nephritis
63
what is a type 3 hypersensitivity reaction?
Type III- Circulating beta-lactam specific IgG or IgM bind to beta-lactam antigens fixing complement and lodging in tissues resulting in serum sickness and drug related fever
64
what is a type 4 hypersensitivity reaction?
Type IV – Not antibody mediated but T-cell recognises antigen leading to localised inflammation eg contact dermatitis
65
what is the Management of patient with beta-lactam allergy?
5-20% of patients give history of beta-lactam allergy Less than 1% of those will have Type I penicillin allergy Difficult to confirm lack of availability of testing Taking a good history is important
66
Clinical Scenario 4: 64 year old man presents with hip pain and fever 2 months after hip replacement surgery Staph aureus grows in blood cultures Initially responds well to if flucloxacillin treatment however after 10 days has ongoing fever and high inflammatory markers What do you do?
67
Resistance vs Failure of Therapy - what is the difference
Resistance = inabilitiy of antibiotic to kill bacteria Resistance can be detected in the lab by measuring MIC levels (Minimum Inhibitory Concentration) Clinical failure may occur despite lab reports of sensitivity especially if what (next slide)
68
what are reasons for failure of therapy?
Inadequate dose of antibiotic Inappropriate route Non-compliance with antibiotic Bacteria walled off in abscess cavity Foreign bodies eg surgical implants/prosthesis Poor penetration of drug to site of infection
69
Antibiotic Stewardship - what advice is given in regards to the use of antibiotics
Using the right antibiotic for the right indication for the right duration of time Use an antibiotic only if suspected or proven bacterial infection Use antibiotics as per guidelines and review with results of microbiology Review antibiotic prescriptions regularly and stop as soon as possible Limit use of broad-spectrum blind antibiotic therapy to seriously ill patients
70
IV to Oral Switch Therapy (IVOST) - when would this occur?
Consider switching patients from IV to oral antibiotics after 48hrs, provided that: the patient is improving clinically and is able to tolerate an oral formulation i.e. if all the criteria below are met: Able to swallow and tolerate fluids Temp. 36-38°C for at least 48 hours Heart rate \< 100bpm for previous 12 hours WCC between 4 and 12x109L
71
how is Education done?
Regular training sessions for medical students and junior doctors ScRAP On-line resources e.g. NES, Learn Pro, TURAS European Antibiotic Awareness Day General public
72
NHS grampian successes
Reduction in CDI (C. diff) MRSA rates have fallen ESBL rates relatively stable But there is no room for complacency
73
Healthcare workers can help tackle AMR by...
Practicing effective infection prevention & control Prescribing and dispensing antibiotics only when truly needed Prescribing & dispensing the right antibiotic(s) for the right duration to treat the illness

Year 3 - infection (14 decks)

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