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Ask the Expert
Is amoxicillin still appropriate for
the treatment of infections caused by non-susceptible isolates?
Donald E Low, MD
Department of Microbiology, Mount Sinai Hospital, Toronto, Ontario, Canada
Amoxicillin is commonly used in both pediatric and adult patients for the treatment of upper and lower respiratory
tract infections. With the emergence and increase in the prevalence of Streptococcus
pneumoniae with a reduced susceptibility to penicillin,
the question often arises as to whether or not amoxicillin is still appropriate for the treatment of infections
due to non-susceptible isolates, and if so, should the dosage be modified and for what conditions.
Penicillin resistance in pneumococci is due to altered penicillin binding proteins (PBP) to which the penicillins
have a decreased affinity and as a result, an increase in their minimum inhibitory concentration (MIC). As altered
PBPs evolved and the MICs increased to 0.6 mg/L, it was no longer possible to achieve adequate levels of penicillins
in the CSF when treating meningitis, especially when the MIC reached 1.0 mg/L. This resulted in the current NCCLS
breakpoints for penicillin; penicillin non-susceptible S.
pneumoniae were defined as MIC 0.6 mg/L and penicillin-resistant
S. pneumoniae
as MIC 1mg/L. The same resistant breakpoints were given for amoxicillin.
The therapeutic efficacy of beta-lactam antibiotics correlates best with the duration of time that levels exceed
the MIC for the infecting organism. With the penicillins, maximum bacteriologic efficacy is seen when the levels
remain above the MIC for 40% of the dosing interval. Today in North, Central and South America, although the rates
of penicillin resistance in pneumococci are increasing, it is rare to isolate a strain with a MIC of 8 mg/L. Therefore,
in non-meningeal infections it is still possible to achieve effective concentrations for treating even resistant
strains, especially in sites where the drugs are well distributed (e.g., serum, lung and sinuses). However, there
is an exception, the middle ear. It is more difficult to achieve adequate concentrations of beta-lactam antibiotics
in middle ear fluid than other body sites. Therefore, with the increasing prevalence of resistance and increase
in the number of cases of acute otitis media due to non-susceptible pneumococci, the Centers for Disease Control
and Prevention assembled their Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group. This group recommends
that for first-line therapy in otitis media, amoxicillin remains the drug of choice, but now at a dose of 60 to
90 mg/kg/day. Because adequate concentrations can be achieved at other respiratory sites for infections due to
S. pneumoniae
with MICs <16 mg/L, it is not necessary to change the dose. Because amoxicillin is not used to treat meningitis,
the National Committee for Clinical Laboratory Standards will be changing the breakpoints of amoxicillin to susceptible:
<4 mg/L, intermediate: 4 mg/L, and resistant: >4 mg/L. This change will have a dramatic effect on the reported
rates of amoxicillin resistance in penicillin-resistant pneumococci. |
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