Synergy between a non-neuroleptic thioxanthene stereo-isomer and penicillin in vivo.

Some neuroleptic drugs of the phenothiazine and thioxanthene groups have an antimicrobial effect in vitro. This is also true for neuroleptically inactive stereo-isomeric analogs of the thioxanthenes e.g. trans(E)-clopenthixol (t-CPT). In a murine pneumococcus peritonitis model t-CPT demonstrated a slight, but non-significant antibacterial effect in doses of 0.3-0.9 mg per mouse, while higher doses seemed to enhance the bacterial virulence. If combined with subtherapeutic doses of penicillin, a significantly higher survival rate was obtained compared with either drug given alone. In vitro studies demonstrated a similar synergistic effect. These results indicate that at least one non-neuroleptic thioxanthene stereo-isomer has an antibiotic potential also in vivo. The mechanism of action is not known.

Peroperative penicillins, bacteremia, and pelvic inflammatory disease in association with induced first-trimester abortion.

In a clinical, controlled trial including 474 women, 250 were randomised to prophylactic treatment with penicillin/pivampicillin and 224 to placebo treatment. Cervical, uterine, and blood cultures were obtained at abortion. In the treatment group, 13 percent developed bacteremia versus 14 percent in the placebo group. The distribution of species cultured from the cervix and uterus was not significantly different from that of the species recovered in the blood. A previous report found that women with a history of pelvic inflammatory disease (PID) carried a higher risk of contracting postabortal genital infection. However, the frequency of bacteremia in these women was not significantly different from the frequency in women without previous PID (p greater than 0.3). In women with and without postabortal infection, no significant differences were observed between the frequencies of bacteremia, either in the antibiotic group (p greater than 0.9) or in the placebo group (p greater than 0.7), suggesting that the release of bacteria into the blood stream from the instrumented tissues is without pathogenetic importance in postabortal infection.

The pneumococcus and the mouse protection test: importance of the lag phase in vivo.

During development of a mouse protection test with a pneumococcus type 3 we noted the importance of the immediate post-challenge lag phase of the bacteria in vivo for the effective timing of treatment with different antibiotics. The lag phase, lasting 6-8 h after intraperitoneal challenge and parallel in peritoneum and blood, was reproducible with the same and three other strains of pneumococcus type 3. Penicillin administration during the lag phase had no effect upon survival of the mice, while a significantly improved effect was obtained after treating the mice with penicillin during the bacterial growth phase. In contrast, treatment with gentamicin or erythromycin during the bacterial lag phase was significantly more effective than administration of either drug after initiation of growth of the pneumococcus.

Pseudomonas cepacia in 16 non-fatal cases of postoperative bacteremia derived from intrinsic contamination of the anaesthetic fentanyl. Clinical and epidemiological observations in Denmark and Holland.

From Nov. 15 to Dec. 17, 1977, Pseudomonas cepacia was isolated from the blood of 16 patients in Odense, Denmark, and Nijmegen, Holland, 2--5 days after an operation with general anaesthesia. The fever started 14--70 h after operation and lasted 2--4 days. All patients recovered. 14/15 patients examined 7--51 days later had agglutinating antibody titres of 400-3,200 against the epidemic strain. Ps. cepacia with identical biochemical characters and sensitivity pattern was isolated from unbroken vials containing the anaesthetic fentanyl, which had been given to all 16 patients. Two batches were contaminated, one heavily so (10(4)--10(5) cfu/0.1 ml). Seven other batches examined yielded no growth. The preservative added to the vials was a mixture of methyl- and propyl-p-hydroxybenzoates which not only allowed growth of the Ps. cepacia strain but could also serve as a carbon source as did citric and malonic acids. The concentration of preservative was not reduced in contaminated vials. The vials had not been sterilized after closure; too much reliance had been placed on an aseptic technique and insufficient preservatives.