trimethoprim--sulfamethoxazole-drug-combination and Rodent-Diseases

Trimethoprim-sulfamethoxazole (TMP-SMX) medication in the feed or water is commonly administered to immunocompro mised mice to prevent the occurrence of Pneumocystis murina (formerly P. carinii) pneumonia. Therapeutic doses of SMX can cause decreased total and free thyroxine (T4) levels in dogs and thyroid hypertrophy and hyperplasia in mice, rats, and dogs. Our primary objective was to determine whether SMX at doses present in commercially available rodent TMP-SMX feed would pro duce hypothyroidism in mice. Plasma T4 levels were determined prior to and after placement of Brand A TMP-SMX feed (daily SMX dose, 240 mg/kg), Brand B TMP-SMX feed (daily SMX dose, 2400 mg/kg), and their respective controls (doses calculated for a 25-g mouse according to vendor's information). T4 levels in the mice fed Brand B TMP-SMX feed were significantly decreased by 2 wk after feed placement. Levels of thyroid stimulating hormone in male and female mice given Brand B TMP-SMX feed were significantly elevated compared with those of control groups at 6 wk after feed placement, when only these mice showed evidence of thyroid hypertrophy and hyperplasia. No significant change in T4 levels occurred over the course of 11 wk in mice given the Brand A TMP-SMX chow or either control feed. In light of the significant clinical hypothyroidism that occurred in our mice while receiving Brand B TMP-SMX diet, we recommend SMX levels more similar to that of Brand A to avoid such unwanted effects which could confound research data.

Topics: Animal Feed; Animals; Body Weight; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Female; Fertility; Hypothyroidism; Male; Mice; Mice, Inbred C57BL; Rodent Diseases; Thyroid Gland; Thyrotropin; Thyroxine; Trimethoprim, Sulfamethoxazole Drug Combination

The clinical presentation, diagnosis, histopathologic findings, and elimination of dual respiratory tract infection with Pasteurella pneumotropica and Pneumocystis carinii were studied in 100 adult barrier-reared C.B17 and MRL- lpr mice homozygous for a targeted mutation of the JH region of the immunoglobulin heavy chain.. Necropsy, aerobic bacteriologic culture of hematogenous and pulmonary tissues, histochemical staining of pulmonary tissues, polymerase chain reaction analysis of pulmonary tissues and feces, and viral serologic testing were performed on 19 clinically affected mice and 8 clinically normal mice, then later on antibiotic-treated and caesarian re-derived mice. Therapeutic strategies included sequential administration of trimethoprim/ sulfamethoxazole and enrofloxacin or enrofloxacin administration and caesarian rederivation.. Clinically affected mice had diffuse, nonsuppurative, interstitial pneumonia with superimposed pyogranulomatous lobar pneumonia that was detected microscopically. Affected lung tissue yielded pure culture of P. pneumotropica. Aged-matched, clinically normal mice of both genotypes had interstitial histiocytic pneumonia without lobar pneumonia, and P. pneumotropica was not isolated. Histochemical staining of lung tissues from normal and clinically affected mice revealed scattered cysts consistent with P. carinii, principally in the interstitium. Treatment with sulfamethoxazole/trimethoprim and enrofloxacin eliminated bacteriologic detection of P. pneumotropica, decreased mortality from 50% to 6%, and improved breeding performance.. A successful antibiotic therapy and rederivation approach, incorporating enrofloxacin, cesarian section, and isolator rearing, was developed for B cell-deficient mice with opportunistic infections.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; B-Lymphocytes; Cesarean Section; DNA, Bacterial; Enrofloxacin; Feces; Female; Fluoroquinolones; Immunohistochemistry; Lung; Male; Mice; Mice, Inbred ICR; Pasteurella; Pasteurella Infections; Pneumocystis; Pneumonia, Bacterial; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Quinolones; Rodent Diseases; Trimethoprim, Sulfamethoxazole Drug Combination

Two sources of rats free of latent Pneumocystis carinii are described. First, rats from a virus-free colony failed to develop infection after 8 weeks of immune suppression unless they were housed with previously infected rats. Second, pregnant rats (non-virus free) received trimethoprim-sulfamethoxazole from day 10 of gestation until the pups were weaned. Pups raised in filter-topped cages and immunosuppressed for 8 weeks were free of P. carinii infection.

Topics: Animals; Disease Models, Animal; Drug Combinations; Female; Immunosuppression Therapy; Pneumonia, Pneumocystis; Pregnancy; Rats; Rats, Inbred Strains; Rodent Diseases; Specific Pathogen-Free Organisms; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination