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Is Amoxicillin still appropriate for the treatment of infections caused by non-susceptible isolates?
For the treatment of upper and lower respiratory tract infections Amoxicillin is commonly used in both pediatric and adult patients. 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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