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Worldwide Trends in Resistance

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Summary

The recent development of orally active third generation cephalosporins, such as cefdinir, has provided highly active agents for the management of outpatient infections. Resistance to these compounds can arise as a consequence of 3 principal mechanisms, i.e. production of β-lactamases, reduced permeation of the drug, and alteration of the target site. Enterobacteriaceae that have developed derepressed mutants that hyperproduce chromosomally encoded β-lactamases include Enterobacter spp., Citrobacter spp., and Serratia spp., which are largely associated with nosocomial infections. Transferable resistance to cefotaxime, ceftazidime, and some second generation cephems has been observed in clinical isolates of Klebsiella pneumoniae harbouring extended-spectrum β-lactamases. These enzymes were derived from plasmid-mediated β-lactamases TEM-1, TEM-2 and SHV-1 by point mutations in penicillinase genes.

It appears that resistance has been observed in many regions throughout Europe, in a number of Middle Eastern countries, and in Japan, South Africa and parts of North America. Current antimicrobial resistance among Haemophilus influenzae clinical isolates is a problem causing increasing concern worldwide. In the second European study investigating the prevalence of antimicrobial resistance in 2529 isolates of H. influenzae, the highest incidence of resistance to ampicillin, cefaclor, chloramphenicol, tetracycline and cotrimoxazole was reported in Spain. Orally active third generation cephalosporins would not be expected to contribute to the selection of such strains if they possessed sufficient stability against these enzymes and if they were administered at an appropriate dosage for maintaining adequate in vivo concentrations.

A review of the literature reveals that resistance of Enterobacteriaceae to cefdinir, cefixime and cefpodoxime is relatively infrequent and usually limited to Serratia marcescens and some strains of Citrobacter spp. and Enterobacter spp. While most of the clinically important non-enterobacterial aerobic Gramnegative organisms are susceptible to third generation cephalosporins, cefdinir, cefixime, cefaclor and cefadroxil demonstrated minimal or no activity against nonfermenters. The majority of clinically significant aerobic Gram-positive organisms are susceptible to the above-mentioned cephalosporins, in particular Streptococcus pneumoniae, S. pyogenes, other streptococci and most methicillinsusceptible Staphylococcus aureus isolates. However, reduced activity of penicillins and cephalosporins, especially as a result of nonenzymatic resistance, is an important problem to monitor in S. pneumoniae. Production of β-lactamase in H. influenzae seems to be stable at around 10% of strains, while nonenzymatic resistance is increasing.

The third generation cephalosporins, including the newer orally administered agents such as cefdinir, have generally maintained their clinical efficacy against a wide range of bacteria. The judicious use of these agents, combined with continual monitoring of bacterial resistance to these compounds, will ensure that community- and hospital-based treatment policies remain accurate and reliable.

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  1. Service de Microbiologie Médicale, Hôpital Saint-Joseph, Université Pierre & Marie Curie, 7, rue Pierre Larousse, 75674, Paris Cedex 14, France

    J. F. Acar

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Acar, J.F. Worldwide Trends in Resistance. Clin. Drug Invest. 9 (Suppl 3), 45–53 (1995). https://doi.org/10.2165/00044011-199500093-00007

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