Antimicrobial Chemotherapy Flashcards
Paradox - Antibiotics increase infections - how?
paradox - Antibiotics increase infection…and mortality in uninfected patients?
excessive antimicrobial usage causes measurable harm to patients and ar emor elikely to get infections like C. diff
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”
resistances
infections
decline
use
- 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
- 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
There is a high correlation between antibiotic ___ and __________
use
resistance
how would you do IV to Oral Switch Therapy (IVOST)?
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
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
“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.”
Everybody can help tackle resistance! How?
- Use antibiotics only when prescribed
- Complete the full course
- Never share antibiotics or use leftover prescriptions
are all antiviral virustatic or virucidal?
All are virustatic, none are virucidal
• Viruses are _______ intracellular parasites
obligate
a parasitic organism that cannot complete its life-cycle without exploiting a suitable host
- 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
replicate
targets
not
minority
what stage of the virus life cycle is the target?
- 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
what may the treatment of antivirals be used for?
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)
Do antivirals eradicate the virus from latently infected cells?
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
what can antivirals be used for in practice?
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
How are each of the following taken:
aciclovir
valaciclovir
famciclovir
foscarnet
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
what is the mode of action of aciclovir?
- 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
Antivirals and CMV - All available drugs have significant toxicity
when should they be used?
• 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
what is the use of antivirals in influeza?
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
onto main antimicrobial chemotherapy powerpoint
what are the different locations that a drug can act in an orgamism?
Penicillins
Cephalosporins
Aminoglycosides
Macrolides
Quinolones
Glycopeptides
Other antibiotics (1)
Other antibiotics (2)
Other
what are the 4 principles of prescribing?
- Indications for antimicrobials
- Diagnosis
- Patient Characteristics
- Antimicrobial selection
what does empiric and directed mean?
vempiric - without microbiology results
directed - based on microbiology results
what are 2 indications for antimicrobials?
therapy
prophylaxis
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
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
what are important Patient Characteristics to think about when prescribing?
age
renal function
liver function
immunocompromised
pregnancy
known allergies
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
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?
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?
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
Antibiotic Resistance:
_______ phenomenon
Bacteria adapt to ______
Bacteria rapidly multiply and can generate ________ very quickly
Natural
survive
resistance
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
what are 4 Main Mechanisms of Resistance?
Enzymatic inactivation of drug
Modified targets for drugs
Reduced permeability to drug
Efflux of drug
Genetics of resistance can be mediated by what 2 things?
Chromosomally mediated
Plasmid mediated
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.
what is Binary Fission?
DNA replicates
Cell elongates
Divides in 2
2 identical bacteria
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
what are some exaples of Medically Important Resistant Organisms?
MRSA
VRE
ESBL
CPE
Clostridium difficile
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
what can MRSA be used in the lab for?
Used in lab to determine whether organisms are sensitive to flucloxacillin
Can MRSA colonise without infection?
Most often colonisation without infection
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
Carriage of MRSA is promoted by what?
Carriage of MRSA is promoted by antibiotic use
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
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
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)
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
where can CPE – Carbapenem producing enterobacteriacae colonise and what is its effects?
Can colonise gut of healthy individuals
Can colonise healthcare environment
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
has antibiotic use and prescribing decreased or increased?
decreased
who prescribes the most antibiotics?
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
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
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
what is a type 4 hypersensitivity reaction?
Type IV – Not antibody mediated but T-cell recognises antigen leading to localised inflammation eg contact dermatitis
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
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?
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)
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
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
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
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
NHS grampian successes
Reduction in CDI (C. diff)
MRSA rates have fallen
ESBL rates relatively stable
But there is no room for complacency
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
