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ANTIBIOTICS:
BACK TO BASICS
MECHANISM OF ACTION OF THE
MAJOR ANTIBIOTIC GROUPS
CELL WALL SYNTHESIS INHIBITORS
Penicillins
Cephalosporins
• Bactericidal
• Time-dependent killing
• Examples include:
Amoxicillin, AmoxicillinClavulanate, Ampicillin
• Bactericidal
• Time-dependent killing
• Four generations with varying
antibacterial spectrums
• Examples include:
Cefalexin (first generation)
Cefovecin (third generation)
In a recent survey1, vets identified that
remembering the intricacies of every different
antibiotic could sometimes be a challenge.
This guide is intended as an antibiotic refresher,
and details a number of key factors to consider
when prescribing an antibiotic. 81% of vets
surveyed identified that antibiotic resistance is a
topic that concerns them; this guide includes a
section on fluoroquinolone resistance, and looks
at ways that this can be minimised.
NUCLEIC ACID SYNTHESIS INHIBITORS
Fluoroquinolones
• Inhibit bacterial DNA synthesis
• Bactericidal
• Concentration-dependent
killing
• Examples include:
Second generation FQs:
Enrofloxacin, Marbofloxacin,
Orbifloxacin
Third generation FQs:
Pradofloxacin
Sulphonamides and
Potentiated Sulphonamides
• Block folic acid synthesis
• Sulphonamides are
bacteriostatic, become
bactericidal when potentiated
• Examples include:
Trimethoprim Sulphadiazine
Metronidazole+
CELL MEMBRANE FUNCTION INHIBITORS
Polymyxins
• Generally used in topical medications
• Examples include: Polymyxin B
PROTEIN SYNTHESIS INHIBITORS
Lincosamides
Aminoglycosides
• Bacteriostatic
• Examples include:
Clindamycin, Lincomycin
• Bactericidal
• Concentrationdependent killing
• Examples include:
Gentamicin and Framycetin
Tetracyclines
• Bacteriostatic
• Examples include:
Oxytetracycline‡, Doxycycline
Chloramphenicol*
• Bacteriostatic
(these are licensed for topical use only)
Macrolides
• Bacteriostatic
• Examples include:
Spiramycin, Erythromycin*,
Clarithromycin*, Azithromycin*
* Not licensed for veterinary use
+
Metronidazole is not licensed for
sole use, but is licensed for oral use in
combination with spiramycin.
‡ Oxytetracycline is not licensed for
use in cats.
Refer to appropriate data sheets for
specific indications and warnings.
RESPONSIBLE CHOICE FOR SEVERE INFECTIONS
www.veraflox.co.uk
BACTERICIDAL VS.
BACTERIOSTATIC
TIME DEPENDENT VS. CONCENTRATION
DEPENDENT BACTERIAL KILLING
Bacteriostatic antibiotics inhibit the growth of bacteria,
whereas bactericidal agents cause death of the
bacteria. Bactericidal agents are sometimes preferable
in infections where the immune status of the patient
is compromised.
With time dependent antibiotics (such as penicillins and
cephalosporins), serum levels of the antibiotic should
exceed the MIC for as long as possible during each 24 hour
period; these agents usually require multiple daily doses to
achieve this. Concentration dependent antibiotics (such as
fluoroquinolones and aminoglycosides) rely on high peak
concentrations to achieve bacterial killing; dosing schedules
are usually once daily.
Distinction between these two groups is not always
clear cut however, and other factors are usually more
important in determining antibiotic choice.
FACTORS TO CONSIDER WHEN PRESCRIBING AN ANTIBIOTIC
1
Is an antibiotic definitely indicated?
What is the likely bacterial species present?
2
Use cytology and culture where appropriate. Culture is
especially important when empirical therapy has been
ineffective, and/or long antibiotic courses are required.
3
Consider the method of antimicrobial delivery:
would topical agents be effective?
Take into account the site of infection
when analysing culture and sensitivity results
4
Susceptibility results are generally based on antimicrobial
concentrations achievable in the bloodstream, and do not
take tissue levels into account. Does the antibiotic penetrate
the infected tissue and reach adequate concentrations?
5
Are there any potential toxicities or
contra-indications associated with the antibiotic
that need to be considered?
6
7
Consider the likelihood that an antibiotic
may contribute to resistance
Different members of the same antimicrobial class may
carry different risks of selecting for resistance*
Compliance
Is the owner likely to be able to give the
treatment prescribed?
DO YOU FEEL LIKE YOU KNOW ENOUGH ABOUT ANTIBIOTICS?
Why not test your knowledge and get CPD hours at the same time, using the Antibiotics Back to Basics
assessment online resource at www.veraflox.co.uk
THE MUTANT
SELECTION WINDOW
Minimum Inhibitory
Concentration (MIC)
Mutant Prevention
Concentration (MPC)
The lowest concentration of
an antimicrobial that will inhibit
the visible growth of a bacterial
isolate after incubation for
18 – 24 hours.
The lowest concentration of
an antimicrobial that will kill
not only susceptible bacteria,
but also the least susceptible
bacteria present in high
density populations.
What is a first-step mutant?
In large bacterial populations, spontaneous mutations can occur,
that render the “mutant” bacteria harder to kill. In the case of
fluoroquinolones, resistance occurs in a step-wise manner; and bacteria
that undergo these spontaneous mutations are referred to as first-step
mutants. If first-step mutants are not killed during therapy, they may
proliferate and mutate further.
Fluoroquinolones that achieve levels above the MPC are less likely
to leave first-step mutant bacteria behind during therapy.3-5
The Mutant Selection Window
This is the zone between the MIC
and MPC. If an antibiotic is able to
exceed MIC levels in the body but
does not reach MPC levels, it is in
the Mutant Selection Window. This
is the danger zone - the antibiotic
is killing susceptible bacteria but
leaving first-stage mutants behind.
Mutant Selection Window (MSW)
Blondeau et al, J. Chemo, 2004
Serum or tissue drug concentration
ANTIBIOTIC ACRONYM BUSTER
MPC
MSW
MIC
Time post-administration
FLUOROQUINOLONE MPC PROFILE
Therapeutic C max 6
Pradofloxacin
Enrofloxacin
Marbofloxacin
Orbifloxacin
Difloxacin
Cmax: maximum amount of antibiotic
achieved in the serum of the animal with
standard dosing.
0.6
* Compared to other
fluoroquinolones, Veraflox®
is the least likely to select
for resistance2
The bars represent the MPC value
for each antibiotic (i.e. the amount of
antibiotic needed to kill both susceptible
and first-step mutant bacteria)
3.5
3.5
Where the bar turns red beyond the
Cmax, this indicates that the amount
of antibiotic needed to reach MPC
(and thus kill first-step mutants) is not
achieved during normal dosing with
the FQ specified.
9
18
0 2 4 6 8 10 12 14 16 18
MPC (µg/ml)
Comparative MPC values
of veterinary fluoroquinolones
against Staphylococcus sp.
in relation to serum drug levels
reached in dogs2
• By achieving drug
concentrations that exceed
the MPC, the potential
for selection of resistant
bacteria is reduced.3-5
• When a fluoroquinolone is
indicated, choosing the one that
is the least likely to leave first-step
mutants behind is the best way
to help minimise the escalation of
fluoroquinolone resistance.
COMPLIANCE
MORE INFORMATION
• Ensure that the owner can administer the
medication - both dosing method and frequency
(demonstrate how to give medication if possible)
Bayer offer a range of resources to support
the use of antibiotics in practice...
• Advise clients on the importance of correct
treatment intervals (for example every twelve
hours is more specific than twice daily; which
is crucial for the efficacy of some antibiotics)
• Educate owner about the importance of
completing the course
ANTIBIOTIC REMINDERS
IN YOUR POCKET
CPD
Visit www.animalhealthwebinars.bayer.co.uk
to source a number of cpd webinars,
including Joe Blondeau discussing the Mutant
Prevention Concentration.
Compliance an issue?
The following tools may be useful:
Client leaflets & reminder magnets
These leaflets detail the importance
of completing the whole antibiotic course,
and offer a handy record, so your clients
can keep track of when they need to
give their pet the next dose.
App Reminders
The Jungle App now offers antibiotic
reminders for Veraflox®, Baytril
and Nisamox. All your clients need to
do is fill in the treatment, course length
and time of day for the first treatment
and the app will do the rest!
AVAILABLE ON APPLE iOS AND ANDROID!
www.veraflox.co.uk
PLEASE CONTACT
YOUR BAYER REPRESENTATIVE
FOR MORE INFORMATION
Use Medicines Responsibly (www.noah.co.uk/responsible)
Veraflox® 15 mg tablets contain 15 mg pradofloxacin. Veraflox® 60 mg tablets contain 60 mg pradofloxacin. Veraflox® 120 mg tablets contain 120 mg pradofloxacin. Veraflox®
25 mg/ml oral suspension for cats contains 25 mg/ml pradofloxacin. Please refer to appropriate data sheet at noahcompendium.co.uk. Advice should be sought from the medicine
prescriber. Further information is available on request. ® Registered Trade Mark of Bayer AG. Bayer plc, Animal Health Division, Bayer House, Strawberry Hill, Newbury, Berkshire RG14
1JA Tel: 01635 563000 POM-V Bayer Ltd, Animal Health Division, The Atrium, Blackthorn Road, Dublin 18, Ireland Tel: 01 299 9313 POM EU/2/10/107/003 EU/2/10/107/007
EU/2/10/107/009 EU/2/10/107/013. CODE
References: 1.Survey of 456 practising UK vets conducted by surveymonkey in March 2014 2.Wetzstein HG. Comparative mutant prevention concentrations of pradofloxacin and other
veterinary fluoroquinolones indicate differing potentials in preventing selection of resistance. Antimicrob Agents Chemother. 2005;49(10):4166-4173. 3.Blondeau JM. Mutant Prevention
Concentration. In STAT - Steps to Antimicrobial Therapy. North American Compendiums Inc., Port Huron, MI, USA 2009: 67 - 98.4.Blondeau JM. New concepts in antimicrobial susceptibility
testing: the mutant prevention concentration and mutant selection window approach. Vet Dermatology 2009; 20: 383 - 396. 5.Mateus A, Brodbelt D, Stark K. Evidence-based use of
antimicrobials in veterinary practice. In Practice 2011; 33: 194 - 202. 6.Heinen E. Comparative serum pharmacokinetics of the fluoroquinolones enrofloxacin, difloxacin, marbofloxacin
and orbifloxacin in dogs after single oral administration. J Vet Pharmacol Therap 2002; 25: 1-5.
RESPONSIBLE CHOICE FOR SEVERE INFECTIONS
www.veraflox.co.uk