Oxford Manual of Childhood Infections Third Edition

Oxford Manual of Childhood Infections Third Edition

Oxford Manual of Childhood Infections Third Edition

Oxford Manual of Childhood Infections Third Edition Antimicrobial agents target sites or pathways that are unique
to the bacterium in order to achieve maximum toxicity for the
microorganisms and minimal toxicity to humans.  • All antibiotics produce human toxicity to varying degrees and the
therapeutic index (maximal tolerated dose divided by the minimum
effective dose) provides a numerical expression of this. Some
antibiotics, such as penicillins, are very safe and thus have a very high
therapeutic index. Others, e.g. gentamicin, have a low maximum
tolerated dose and thus a therapeutic index that is low.

• Antimicrobials alter the host’s normal fl ora (e.g. ampicillin or
amoxicillin/clavulanate are re-excreted into the gastrointestinal tract)
and affect the predominantly anaerobic fl ora of the large bowel
resulting in antibiotic-associated diarrhoea or promoting colonization
by Clostridium difficile.
• ‘Use it and lose it!’ Use and misuse of antibiotics contribute to
development of antimicrobial resistance. There is reasonably good
evidence that rational use of antibiotics can prevent or decrease the
development of resistance.
• Choosing the right antibiotic for therapy of a given infection is more
challenging than ever and following the key steps listed below will
allow for a systematic approach to antibiotic selection:
• What is (are) the most likely causative pathogen(s) for the
diagnosed clinical syndrome?
• What is the probable susceptibility of the isolated (or suspected)
pathogen based on lab results or local epidemiological parameters?
• What is the appropriate dose and duration of therapy according to
the host and the site of infection.

• Presumptive and empirical therapy:
• Initial choice of antibiotic is usually based on a clinical syndrome
and anatomical site of infection. The initial antibiotic choice can
often later be changed to the most narrow-spectrum, yet effective,
antibiotic with activity against the identifi ed organism.• For suspected (unproven) infections presumptive therapy may be

Oxford Manual of Childhood Infections Third Edition



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