Review of the spectrum and potency of orally administered cephalosporins and amoxicillin/clavulanate

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Abstract

The antimicrobial spectrum and in vitro potency of the most frequently prescribed orally administered cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil, cephalexin) and amoxicillin/clavulanate are reviewed. These β-lactam agents have been widely used in the outpatient arena for the treatment of community-acquired respiratory tract and other mild-to-moderate infections. The data presented here were obtained from critical review articles on each of these compounds. Cephalexin and cefaclor were among the least potent and had the narrowest antimicrobial spectrums against the pathogens evaluated. In contrast, cefdinir, cefpodoxime, cefprozil, and cefuroxime were highly active against penicillin-susceptible Streptococcus pneumoniae and retained some activity against penicillin-intermediate strains, whereas amoxicillin/clavulanate was the most active against S. pneumoniae, including most penicillin nonsusceptible strains. Amoxicillin/clavulanate and cefdinir were the most potent compounds against methicillin (oxacillin)-susceptible Staphylococcus aureus, whereas cefpodoxime was the most potent compound against Haemophilus influenzae. Amoxicillin/clavulanate, cefdinir, and cefpodoxime were also active against Moraxella catarrhalis, including β-lactamase–producing strains. In summary, orally administered “3rd-generation” or extended spectrum cephalosporins exhibited more balanced spectrums of activity against the principal bacterial pathogens responsible for outpatient respiratory tract and other infections when compared with other widely used oral cephalosporins of earlier generations or amoxicillin alone.

Introduction

Several classifications of the cephalosporins have been proposed with the most practical and commonly used being based on the timing of introduction for the parenteral agents in clinical practice, which usually corresponds to their advancing antibacterial spectrums. Using this approach, many publications classify the orally administered cephalosporins by generations, similar to the parenteral cephalosporin classification (“1st-, 2nd-, and 3rd-generation” agents). However, it is difficult or impossible to classify several of these oral compounds based on variations in in vitro potency and the limitations imposed on levels achievable in vivo with oral administration.

Using an alternative approach, one can simply divide these agents between “older cephems”, which include compounds with more limited potencies and spectrums, and “advanced-generation cephems”, which include more potent compounds with expanded antibacterial spectrums against some respiratory tract pathogens (Table 1). Among the older cephems, we have included only cephalexin in this review, an agent still widely used for uncomplicated skin and skin structure infections (uSSSIs) and pharyngitis. The so-called advanced-generation cephems were then divided into 3 distinct groups on the basis of antimicrobial potency and spectrum. Group I includes cephalosporins with more limited spectrums, but that also include Neisseria gonorrhoeae and a few enteric Gram-negative bacilli, such as Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Groups II and III include compounds with more extended or potent antibacterial activity targeting Enterobacteriaceae; however, compounds in group II show limited activity against Staphylococcus aureus and penicillin-nonsusceptible Streptococcus pneumoniae (Table 1).

In this report, we review the antimicrobial spectrums and in vitro potencies of selected oral cephalosporins (cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime axetil and cephalexin) and amoxicillin in comparison with amoxicillin/clavulanate, which has been available for over 20 years and remains widely used, particularly for the treatment of respiratory tract infections (White et al., 2004).

Section snippets

Background

Brotzu (1948) discovered cephalosporins in 1945 as naturally occurring substances produced by the fungus Cephalosporium acremonium, now known as Acremonium chrysogenum. The first widely used cephalosporin was cephalothin, introduced to the market in 1962 and was available only for parenteral use. Among the first semisynthetic modifications of the C-7 side chain of the cephem nucleus was the addition of a d-phenylglycyl moiety that produced cephalexin, the first oral cephalosporin (Wick, 1967).

In vitro testing

The categoric breakpoints established by the Clinical and Laboratory Standards Institute (CLSI, formerly, National Committee for Clinical Laboratory Standards) are used in comparing the antimicrobial spectrum and activity for the compounds evaluated in this review. These breakpoints are used in most studies that compare and contrast in vitro activity of orally administrated β-lactams. Use of pharmacokinetic/pharmacodynamic (PK/PD) derived breakpoints is also offered as an alternative to those

Discussion

The analysis of the large amount of data summarized in Table 4, Table 5 indicates that cefdinir and cefuroxime among the orally administered cephalosporins have more balanced spectrums against the principal pathogens responsible for respiratory tract infections when compared with the other advanced-generation cephems evaluated. Cefdinir and cefuroxime also showed higher potency and a wider spectrum against pathogens (mainly S. pneumoniae) compared with cefaclor and cephalexin. Furthermore,

Conclusions

The advanced-generation cephems (Table 1) have a history of a wider spectrum, higher potency, and better side-effect profiles compared with older agents (cefaclor, loracarbef, and cephalexin). The in vitro summary presented in this review shows the strengths and weaknesses that these compounds and amoxicillin/clavulanate possess against the pathogens responsible for community-acquired respiratory infections and other indications such as uSSSI.

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