Susceptibility testing of Chlamydia trachomatis: from eggs to monoclonal antibodies

Chlamydia trachomatis is thought to be the most common sexually transmitted agent in the United States, an assertion which has received further support as laboratory diagnostic tests become more widely used. Chlamydial infections are of major concern because peak incidence rates are found in adolescents and young adults of child-bearing age and because of their propensity to cause serious complications such as pelvic inflammatory disease, tubal infertility, ectopic pregnancy, and neonatal pneumonitis. Although the potential for the development of antimicrobial resistance seems limited, the frequent occurrence of C. trachomatis with Neisseria gonorrhoeae in which both chromosomeand plasmid-mediated resistances are rapidly becoming more prevalent demands continued surveillance of susceptibility to older antimicrobial agents, as well as evaluation of newer ones. Historically, the antimicrobial susceptibility of C. trachomatis has been predictable. When comparable methods are used, MICs usually fall within a narrow range. Reasons for this are suggested by the nature of the organism and its life cycle. The infectious form, or elementary body, is adapted to extracellular transit and is protected by a thick, rigid, trilaminar cell wall. After attachment to susceptible cells, elementary bodies are ingested into phagosomes (cytoplasmic vacuoles formed by invagination of cellular plasma membranes), where they remain during their intracellular phase. Within 24 h of phagocytosis, the elementary body develops into the reproductive form, or reticulate body, the cell wall becomes porous, and binary fission occurs, with the formation of new elementary bodies and eventual rupture of the host cell. Compared to most other procaryotes, chlamydiae have a relatively small genome, which consists of a double-stranded DNA molecule with a molecular mass of 4 x 10 to 6 x 108 daltons (6 x 105 nucleotide pairs) (18, 25), approximately one-half the size of N. gonorrhoeae DNA (18). Chlamydiae also possess a small (4.4-megadalton) cryptic plasmid (25). A new capacity for bacterial resistance must arise either through chromosomal mutation or through genetic transfer from another organism. The small chromosome limits the number of base pairs available for mutagenesis, while gene transfer by conjugation, transformation, or transduction is relatively unlikely because extracellular, thick-walled, metabolically inert elementary bodies probably are incapable of receiving genetic material from the many bacteria which they come in contact with and because intracellular, metabolically active, and dividing reticulate bodies rarely encounter other bacteria in the highly restrictive environment