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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
Q

Macrolides

A
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26
Q

Quinolones

A
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27
Q

Glycopeptides

A
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28
Q

Other antibiotics (1)

A

Other antibiotics (2)

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29
Q

Other

A
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30
Q

what are the 4 principles of prescribing?

A
  1. Indications for antimicrobials
  2. Diagnosis
  3. Patient Characteristics
  4. Antimicrobial selection
31
Q

what does empiric and directed mean?

A

vempiric - without microbiology results

directed - based on microbiology results

32
Q

what are 2 indications for antimicrobials?

A

therapy

prophylaxis

33
Q

what ar ethe types of prophylaxis?

A

Primary:

  • anti-malarial; immunosupressed patients
  • pre-operative surgical
  • post-exposure e.g. HIV, meningitis

Secondary - To prevent a second episode e.g. PJP

34
Q

how is the diagnosis made

A

Diagnosis of Infection:

  • Clinical
  • Laboratory
  • None (no treatment)

Severity assessment:

? Sepsis (qSOFA: syst BP<100, altered mental, RR>22)

? Septic shock

35
Q

what are important Patient Characteristics to think about when prescribing?

A

age

renal function

liver function

immunocompromised

pregnancy

known allergies

36
Q

when prescribing, how is antimicrobial selection done and hwat needs to be thought about?

A

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
Q

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?

A
38
Q

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?

A
39
Q

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

A

antibiotics

inappropriately

prophylaxis

stewardship

40
Q

Antibiotic Resistance:

_______ phenomenon

Bacteria adapt to ______

Bacteria rapidly multiply and can generate ________ very quickly

A

Natural

survive

resistance

41
Q

What is the Sensitivity Testing Disk Defusion method?

A

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
Q

what are 4 Main Mechanisms of Resistance?

A

Enzymatic inactivation of drug

Modified targets for drugs

Reduced permeability to drug

Efflux of drug

43
Q

Genetics of resistance can be mediated by what 2 things?

A

Chromosomally mediated

Plasmid mediated

44
Q

what is Chromosomally Mediated Resistance?

A

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
Q

what is Binary Fission?

A

DNA replicates

Cell elongates

Divides in 2

2 identical bacteria

46
Q

what is the process of Plasmid Mediated Resistance?

A

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
Q

what are some exaples of Medically Important Resistant Organisms?

A

MRSA

VRE

ESBL

CPE

Clostridium difficile

48
Q

what is MRSA resistant to

A

Methicillin is a penicillinase resistant penicillin ie similar to flucloxacillin

MRSA has an altered binding protein compared with MSSA

Resistant to flucloxacillin

49
Q

what can MRSA be used in the lab for?

A

Used in lab to determine whether organisms are sensitive to flucloxacillin

50
Q

Can MRSA colonise without infection?

A

Most often colonisation without infection

51
Q

What can the effects of MRSA be?

A

Can cause severe invasive infections eg osteomyelitis, endocarditis

Mortality in patients with MRSA bacteraemia is twice that of MSSA bacteraemia

52
Q

Carriage of MRSA is promoted by what?

A

Carriage of MRSA is promoted by antibiotic use

53
Q

what is VRE?

A

Vancomycin resistant enterococci

Enterococci are intrinsically only sensitive to a limited number of antitbiotics

VRE are only sensitive to 1 or 2 antibiotics

54
Q

where do VRE colonise and what effects can they cause?

A

VRE colonise GI tract in patients exposed to multiple antibiotics

Can cause invasive disease eg endocarditis especially in patients with prosthetic devices

55
Q

What is ESBL producing Enterobacteraciae?

A

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
Q

CPE - Carbapenem producing enterobacteriacae

what is effective against it?

A

Multiply resistant bacteria

Typically only sensitive to a few antibiotics of last resort

When associated with infection few treatment options

57
Q

where can CPE – Carbapenem producing enterobacteriacae colonise and what is its effects?

A

Can colonise gut of healthy individuals

Can colonise healthcare environment

58
Q

what are Factors Influencing Antibiotic Resistance?

A

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
Q

has antibiotic use and prescribing decreased or increased?

A

decreased

60
Q

who prescribes the most antibiotics?

A
61
Q

what is a type 1 hypersensitivity reaction?

A

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
Q

what is a type 2 hypersensitivity reaction?

A

Type II - Beta lactam specific IgG or IgM antibodies bind to circulating blood cell resulting in haematological reactions or interstitial nephritis

63
Q

what is a type 3 hypersensitivity reaction?

A

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
Q

what is a type 4 hypersensitivity reaction?

A

Type IV – Not antibody mediated but T-cell recognises antigen leading to localised inflammation eg contact dermatitis

65
Q

what is the Management of patient with beta-lactam allergy?

A

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
Q

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?

A
67
Q

Resistance vs Failure of Therapy - what is the difference

A

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
Q

what are reasons for failure of therapy?

A

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
Q

Antibiotic Stewardship - what advice is given in regards to the use of antibiotics

A

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
Q

IV to Oral Switch Therapy (IVOST) - when would this occur?

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

71
Q

how is Education done?

A

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
Q

NHS grampian successes

A

Reduction in CDI (C. diff)

MRSA rates have fallen

ESBL rates relatively stable

But there is no room for complacency

73
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

Year 3 - infection (14 decks)

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