Roger L. Nichols

Development of Resistance and Cross-Resistance in vitro to Erythromycin, Carbomycin, Spiramycin, Oleandomycin and Streptogramin.∗

Summary and conclusions Four strains of M. aureus were rendered resistant to erythromycin, carbomycin, oleandomycin, spiramycin and streptogramin by repeated subcultures in the presence of increasing concentrations of these antibiotics. Cross-resistance to about the same degree developed to all of these agents except to streptogramin; the latter produced homologous resistance at a slower rate than the others, but this was associated with a corresponding increase in cross-resistance to the other 4 antibiotics.

Sulfamethoxypyridazine: preliminary observations on absorption and excretion of a new, long-acting antibacterial sulfonamide.

Summary and conclusions Concentrations of sulfamethoxypyridazine in blood and urine of 6 normal adult males were determined after a single oral dose of 4 g. The drug was well absorbed, yielding high levels of free drug and only small amounts in acetylated form in the plasma. Little if any of the drug diffuses into the blood cells. The drug is cleared slowly from the plasma, the acetylated form being cleared by the kidney about 11 times as fast as the free drug. Urine concentrations varied up to about 200 mg %, between 35 and 60% being in the conjugated form. Significant levels were still present in the blood and urine 105 hours after the dose. This prolonged action should be of clinical interest and suggests that further exploration of the potentialities of this new sulfonamide drug is warranted.

In vivo evaluation of ocular inserts of hydrogel impregnated with antibiotics fop trachoma therapy

Sustained release of antibiotics from hydrogel matrices in the eye was studied for the purpose of developing a new method for trachoma therapy. Copolymers of N-vinylpyrrolidone were moulded into an ocular insert and impregnated with erythromycin or erythromycin estolate. The antibiotic-hydrogel inserts completely suppressed the chlamydia trachomatis infection in the owl monkey eyes. The drug elution rates were a little lower in vivo than in vitro. By comparison of the drug elution rate in the human eye with that in the owl monkey eye, similar therapeutic effect is expected in the treatment of human trachoma.

Immunology of Chlamydial Infections

With its long recorded history, its high global prevalence, and its potential for causing partial or total blindness, trachoma ranks as one of the major afflictions of humanity (Bietti, 1974; Jones, 1975; Locatcher-Khorazo and Seegal, 1972; Nataf, 1952; Thygeson, 1971). The principal etiological agent of trachoma is an intracellular parasitic prokaryote, currently assigned to the genus Chlamydia (Becker, 1974, 1978; Moulder, 1964, 1966; Page, 1968; Storz, 1971; E. Weiss, 1971). The species designation of the trachoma organism is C. trachomatis (Page, 1968). Various serotypes of C. trachomatis also cause, besides trachoma-inclusion conjunctivitis (TRIC), some cases of nongonococcal Urethritis and Cervicitis (Dunlop, 1975; Fritsch et al., 1910; Hobson and Holmes, 1977; Jones et al., 1964; Lindner, 1910; Oriel et al., 1978; Richmond and Sparling, 1976; Schachter et al., 1976), some cases of infant pneumonia (Beem and Saxon, 1977; Frommell et al., 1977; Schachter et al., 1975), and lymphogranuloma venereum (LGV) (Abrams, 1968; Meyer, 1953; Rake and Jones, 1942; Willcox, 1975). Organisms assigned to the species C. psittaci are distinguished by their failure to store glycogen during growth (Becker, 1978; Gordon and Quan, 1965; Jenkin and Fan, 1971): divers strains cause ornithosis (Bedson, 1958) and various diseases in nonhuman mammals, such as pneumonia, encephalitis, conjunctivitis, enteritis, abortion, and polyarthritis (Storz, 1971).

Plasma Penicillin Levels from Oral Penicillins V and G and Intramuscular Penicillin G.

Summary Oral penicillin V gave higher and better sustained levels of penicillin activity in the plasma than oral buffered potassium penicillin G at each of 3 dosage levels, viz. 200000, 400000 and 1 million units. Intramuscular penicillin G yielded higher and better sustained levels than oral penicillin V in equivalent doses given at levels of 400000 or 1 million units. An i. m. dose of 200000 units of penicillin G produced higher peak levels and these occurred earlier but they were less well sustained than with this amount of oral penicillin V; the total amount of penicillin absorbed from this amount of penicillin was not significantly different for these 2 dosage forms. Persons over 60 years of age attained peak levels later; in general they had higher and better sustained levels of penicillin in the plasma from any given dose than did younger individuals.

Trachoma in a Rural Haitian Community

We selected 43 patients, aged 15 days to 57 yesrs, for intensive study after screening 975 people for clinical evidence of trachoma in rural Haiti. Trachoma was present in Haiti with low endemicity and was followed by relatively mild sequelae. Laboratory studies confirmed the disease through demonstration of conjunctival inclusion bodies by immunofluoresence and serotyping of antibody in sera or eye secretions, or both. Of 23 patients (age 1 to 36 years) with active trachoma, all had serum antibody to chlamydia (range 1:10 to 1:640), nine had eye secretion antibody (range 1:10 to 1:1280), and one was inclusion positive. The remaining 20 patients (age 15 days to 57 years) had the following diagnosis: atypical follicles (eight), conjunctivitis with or without mucopurulent discharge (ten) innactive pannus only (one), and severe anemia (one). Only 16 of the 20 were tested for serum antibody and all were positive (1:10 to 1:5,120), 11 of 20 had eye secretion antibody (1:10 to less than or equal to 1:640), and one was inclusion positive. Serotyping attempted on 22 patients yielded 16 patients with antibodies specific for type A, one patient with type B, and five who were not typed.