Many strains of bacteria have been shown to be resistant to the tetracyclines. These include certain strains of streptococci, staphylococci, pneumococci, gonococci, and many other gram-negative organisms. Therefore, culture and sensitivity testing are advised to determine the susceptibility of the infecting organisms to tetracyclines. Chemotherapy should not be initiated until all the necessary bacteriological investigations have been started.

Microorganisms that have become insensitive to one tetracycline invariably exhibit cross resistance to other tetracyclines.

Some cross resistance between the tetracyclines and chloramphenicol for gram-negative organisms but not for gram-positive ones has been reported. Tetracycline resistant organisms are most likely to be acquired from other individuals in a population where tetracyclines have been widely used.

The tetracyclines are indicated in infections caused by the following microorganisms:

Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox, tick fevers), M. pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of L. venereum and G. inguinale, and the spirochetal agent of relapsing fever (B. recurrentis).

The following gram negative organisms: H. ducreyi (chancroid), Y. pestis and F. tularensis, B. bacilliformis, Bacteroides spp., Vibrio comma and V. fetus, and Brucella organisms (in conjunction with streptomycin).

The following gram negative organisms, when bacteriologic testing indicates appropriate susceptibility to the drug: E. coli, E. aerogenes, Shigella spp., Mima spp., Herellea spp., H. influenzae (respiratory infections), and Klebsiella infections (respiratory and urinary).

The following gram positive organisms when bacteriologic testing indicates appropriate susceptibility to the drug: anaerobic streptococci, S. pyogenes (For upper respiratory infections due to Group A beta hemolytic streptococci, penicillin is the drug of choice including prophylaxis of rheumatic fever), S. pneumoniae, and S. aureus. The frequency of resistance to tetracyclines in hemolytic streptococci is highest in strains from infections of the ear, wounds and skin. Tetracyclines should not be prescribed for acute throat infections; also, they are not the drug of choice in any staphylococcal infection.

When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of infections due to: N. gonorrhoeae, T. pallidum and T. pertenue (syphilis and yaws), L. monocytogenes, Clostridium spp., B. anthracis, Fusobacterium fusiform (Vincent's infection), and Actinomyces.

In acute intestinal amebiasis, the tetracyclines may be a useful adjunct to amebicides. In severe acne the tetracyclines may be useful adjunctive therapy.

Tetracyclines are indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence.

Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral and topical agents.

Because tetracycline tends to accumulate in certain neoplastic cells and to exhibit a brilliant, yellowish gold fluorescence when exposed to ultraviolet light, it may be useful in experienced hands for the diagnosis of malignancy.