Laboratory Evaluation of Antimicrobial Agents

LABORATORY EVALUATION OF ANTIMICROBIAL AGENTS

INTRODUCTION

Laboratory evaluation of antimicrobial agents remains a cornerstone of clinical microbiology and antimicrobial/ biocide discovery and development. The development of robust and reproducible assays for determining microbial susceptibility to antimicrobial agents is of fundamental importance in the appropriate selection of therapeutic agents and biocides for use in infection control, disinfection, preservation and antifouling applications. Such laboratory assays form the basis for high-throughput screening of compounds or biological extracts in the discovery, isolation and development of new antimicrobial drugs and biocides. Such assays facilitate identification of antimicrobial agents from various sources and in lead antimicrobial compound optimization. In the control of human and animal infection, laboratory evaluation of candidate agents yields crucial information which can inform choice of antimicrobial agent(s) where the causative organism is known or suspected. As the number of microorganisms exhibiting resistance to conventional antimicrobial agents increases, laboratory evaluation of antimicrobial susceptibility is increasingly important for the selection of appropriate therapeutic antimicrobials. Evaluation of the potential antimicrobial action and nature of the inhibitory or lethal effects of established and novel therapeutic agents and biocides are important considerations in the success of therapeutic interventions and infection/contamination control procedures.

Significant concerns that the extensive use of biocidal agents may be linked to the development of antimicrobial resistance exist. Recent concerns regarding significant global public health issues such as the increasing threat of bioterrorism, the prevalence of healthcare associated infections, severe acute respiratory syndrome (SARS), avian influenza (H5N1) and the 2009 World Health Organization declaration of the swine flu (H1N1) pandemic (the first pandemic of the 21st century) have seen global demand for biocides increase dramatically. In addition, the emergence of new infectious agents (e.g. prions) and the increasing transmission rates of significant blood-borne viruses (e.g. HIV, hepatitis B and C) which may readily contaminate medical instruments or the environment has focused attention on the need for effective and proven disinfecting and sterilizing agents.

Finally, increasing appreciation of the role played by microbial biofilms in human and animal infectious diseases and their ubiquitous distribution in natural ecosystems has led to the development of novel approaches for the laboratory evaluation of antimicrobial susceptibility of microorganisms growing as surface-adhered sessile populations. These studies have demonstrated that microorganisms in the biofilm mode of growth are phenotypically different from their planktonic counterparts and frequently exhibit significant tolerance to antimicrobial challenge. This has implications for the environmental control of microorganisms and in the selection of appropriate concentrations of antibiotic or biocide necessary to eradicate them. As such, biofilms may constitute a reservoir of infectious microorganisms which may remain following antimicrobial treatment, even if antimicrobial selection is based on standard laboratory evaluations of antimicrobials which are based on planktonic cultures of microorganisms. Tests for evaluating candidate antimicrobial agents to be used in human and animal medicine as well as environmental biocides remain significant laboratory considerations.