PBL 2 Determinates of judicious antimicrobial use (adapted from TG and lecture
notes)
There are numerous reasons why antibiotic use needs to be regulated, monitored
and directed including emerging patterns of resistance, cost, indication, contraindications,
drug/ disease/ patient interactions, empiric/ prophylactic/ sensitivity directed therapy, and
the first question ‘is this antimicrobial even essential for treatment?’
Is an antimicrobial needed?
Unnecessary antimicrobial use exposes patients to potential side effects, and
monitory burden. It also helps create an environment promoting the selection of resistant
strains of bacteria in the community (and hospital). Most viral illnesses like the common cold
and bacterial diseases like otitis media are self-limiting and do not benefit from antibiotic
use.
Antimicrobial Resistance
Antimicrobial resistance is steadily increasing in many pathogens including:
 Streptococcus pneumoniae
 Methicillin-resistant staph aureus (MRSA)
 Vancomycin-resistant enterococci (VRE)
 Klebsiella (beta-lactamase resistance)
 Escherichia coli (beta-lactamase resistance)
 Acinetobacter (multiresistant)
 Pseudomonas aeruginosa (multiresistant)*
Judicious use of antibiotics will both reduce the occurrence of new resistance strains but will
curb resistance prevalence after its emergence.
Antimicrobial Choice
Choice of antibiotic must be made on a list of factors:
 Spectrums of activity in relation to known/ suspected causative microbes – if in
doubt ask!
 Side effects – eg. Ototoxicity and nephrotoxicity of aminoglycosides
 Therapeutic drug monitoring (TDM) – eg. 6-14hr post dose monitoring of
aminoglycosides
 Risk of superinfection – eg. Pseudomembranous colitis (C. difficile)
 Adverse drug events (ADE’s)/ Hypersensitivity – eg. Sulphur allergy in pt receiving
Bactrim forte
Prophylactic Therapy
Prophylactic therapy in the absence of active infection should only be reserved for
situations proven to show benefit or when consequences of any infection would be
disastrous. Most surgical prophylaxis antimicrobials consist of a single dose given about an
hour before surgery via IM or IV to provide cover during the procedure, whereas Candida
prophylaxis in HIV patients may continue for a few months. Antibiotic choice should be
based on known or likely target pathogen that normally causes problems without
prophylaxis.
Empirical Therapy “Use of antibiotics before the aetiology of the infection is known”
When immediate antibiotic treatment is indicated, empirical therapy should be
based on local epidemiology and on potential pathogens and their developing resistance
patterns. Wherever possible though, culture and sensitivity testing should be done before
commencing antimicrobial therapy; since non-infective diagnosis may be confirmed and
PBL 2 Determinates of judicious antimicrobial use (adapted from TG and lecture
notes)
monitory and resistance costs reduced, or in the case of unestablished infective cause,
continue therapy for more than 48 hours. (eg. Trimethoprim for UTI, ceftriaxone for
bacterial meningitis etc)
Directed Therapy
When culture and sensitivity results come back from pathology and the results give
some antibiotic choices, it is important to acknowledge that organisms isolated may not
necessarily be responsible for the clinical picture. To reduce risk of superinfection with
resistant micro-organisms, the chosen antimicrobial should be the:
 Most effective
 Least toxic
 Narrowest spectrum
 Most cost effective
Directed therapy can be sensitivity directed or pathogen directed. Pathogen directed
therapy is a less accurate way to prescribe since need to consider
 Likely antibiotic resistance profile in that particular patient
 What antibiotics has the patient recently received?
 What resistant organisms have been cultured from the patient previously?
 Likely resistance profile in that particular geographic area or ICU
Topical Therapy
Topical antibiotic therapy should be restricted to a few conditions proven to benefit
(eg. Conjunctivitis) and should be from different antibiotic classes than those used for
systemic therapy.
Combination Therapy
Generally speaking, only use combinations for antimicrobials to:
 Extend the spectrum (eg. mixed infections like PID)
 Achieve synergy that is known to improve outcomes (eg. enterococcal endocarditis
with gent and amoxy or H.pylori with clarithromycin and amoxy)
 Prevent emergence of resistant strains (eg. TB treatment)
Duration of Therapy
To minimise resistance and development of drug adverse effects, it is important to
limit duration of therapy. Some infections have well documented timelines, while others rely
on clinical signs to guide duration. Duration of therapy also depends on what kind of killing
type the antimicrobial exhibits:
•Concentration dependent (eg. Aminoglycosides and Quinolones)
–Maximal killing at maximal concentrations
–Upper concentration limit is the concentration that will produce toxicity
Note: it is better to give a 7mg/kg once daily dose of gentamicin for 3 days than to give a 3.5mg/kg
once daily dose for a week; since killing is concentration dependent, and ototoxicity and
nephrotoxicity are related to total AUC and not concentration so the longer the time on gent the
higher the risk of side effects. So shorter duration of therapy reduces side effects and resistance and
increases bacterial kill BUT Dr’s are still so scared of dosing gentamicin correctly!!! Aargh!
•Time dependent (Penicillins and Cephalosporins)
–Do not get greater killing at high concentrations
–Time above MIC is the important consideration