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Key points
AJ Varley BSc MB BS MRCS FRCA
The aminoglycosides and
fluoroquinolones exhibit Jumoke Sule MB ChB MRCP FRCPath
‘concentration-dependent AR Absalom MB ChB FRCA MD
killing’ and so higher doses
are associated with greater
efficacy.
b-Lactams, erythromycin,
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009 185
Principles of antibiotic therapy
metabolic pathways or if the antibiotic cannot enter the bacterium bowel surgery is associated with heavy levels of bacterial contami-
due to impermeability. Hence, b-lactam agents with activity nation and postoperative infection rates are much higher.
against the bacterial cell wall have no effect against mycoplasma, Alternative strategies of prophylaxis such as bowel sterilization by
small bacteria that lack a cell wall. Resistance may be acquired the use of poorly absorbed oral antibiotics have been abandoned.
either by mutation or by transfer of genetic material from resistant Therefore, prophylaxis depends on reducing faecal bacterial load
to susceptible organisms. Mutations occur frequently with rifampi- by mechanical means and the administration of systemic antibiotics
cin and fusidic acid; hence, these agents should be used in combi- active against aerobic and anaerobic organisms. These should be
nation with another antibiotic for treatment of infection. Transfer administered at induction to ensure adequate antibiotic levels at the
of genetic material occurs via plasmids and transposons (small start of surgery, in accordance with local or national guidelines.5
molecules of DNA that are distinct from the bacterial chromo- Patients who are having foreign materials implanted have a
186 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009
Principles of antibiotic therapy
rule. A first dose of antibiotic should be given as soon as the diag- cerebrospinal fluid. A count of white blood cells, red blood cells,
nosis is considered, as it has been demonstrated that delays before or epithelial cells according to sample type allows an assessment
the administration of antibiotics increase the risk of mortality. of inflammation and sample quality, whereas Gram’s staining
allows a rapid division of bacteria into two large groups,
Broad spectrum vs narrow spectrum Gram-positive and Gram-negative, based on the properties of their
Broad-spectrum antibiotics such as b-lactam/b-lactamase inhibitor cell walls. Further subdivision into cocci and bacilli in conjunction
combinations (co-amoxiclav and piperacillin–tazobactam), third- with knowledge of the clinical setting can allow a reasonable
generation cephalosporins, quinolones, and carbapenems are useful assumption of the likely organism type, thus providing an early
for initial empirical therapy in critically ill patients. They allow a opportunity for the selection of empirical antibiotic therapy. For
greater range of pathogens to be covered, but should be altered to a example, the isolation of Gram-positive diplococci from blood cul-
Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009 187
Principles of antibiotic therapy
to ensure that levels are therapeutic, or to assess compliance with antibiotic usage and guides the use of correct agents and dosage to
drug regimes ( predominantly TB treatment courses). ensure efficacy and avoid toxicity.
Assays can be ‘chemical’, simple measures of the drug concen-
tration in plasma, to ensure efficacy and avoid toxicity. This is
commonly performed during aminoglycoside therapy.
References
Alternatively, they can be more complex ‘microbiological assays’ 1. Craig W. Does the dose matter? Clin Infect Dis 2001; 33: S233– 7
or ‘back-assays’ in which samples of a patient’s plasma containing 2. Malacarne P, Bergamasco S, Donadio C. Nephrotoxicity due to combi-
the administered antibiotics are combined with standardized con- nation antibiotic therapy with vancomycin and aminoglycosides in septic
critically ill patients. Chemotherapy 2006; 52: 178–84
centration of the infecting organism. Although this allows a direct
3. Niederman MS. Principles of appropriate antibiotic use. Int J Antimicrob
assessment of the efficacy of the antibiotic dose, these assays are Agents 2005; 26: S170– 5
188 Continuing Education in Anaesthesia, Critical Care & Pain j Volume 9 Number 6 2009