No abstract

The urgent need to treat presumptive bacterial or fungal infections in neutropenic patients has meant that initial therapy is empiric and based on the pathogens most likely to be responsible, and drug resistance. The traditional empirical treatment in Norway has been penicillin G and an aminoglycoside, and this combination has been criticized over recent y. We wished to analyse the microbiological spectrum and susceptibility patterns of pathogens causing bacteraemia in febrile neutropenic patients. This was a prospective multicentre study. During the study period of 2 y, a total of 282 episodes of fever involving 243 neutropenic patients was observed. In 34% of episodes bacteraemia was documented. Overall, 40% of the episodes were caused by Gram-positive organisms, 41% by Gram-negative organisms and 19% were polymicrobial. The most frequently isolated bacteria were Escherichia coli (25.6%), a- and non-haemolytic streptococci (15.6%), coagulase-negative staphylococci (12.4%) and Klebsiella spp. (7.4%). None of the Gram-negative isolates was resistant to gentamicin, meropenem, ceftazidime or ciprofloxacin. Only 5 coagulase-negative staphylococci isolates were resistant to both penicillin G and aminoglycoside. The overall mortality rate was 7%, and 1.2% due to confirmed bacteraemic infection.

A mixture of 7a-3H-and 4-'4C-labeled cholesterol was administered intravenously to rats. Cholestanol with 20-30% lower ratio between 3H and '4C than in cholesterol could be isolated from different organs. In a healthy human control, cholestanol isolated from feces had a 3H/'4C ratio which was 28% lower than in administered cholesterol. Cholesterol and coprostanol reisolated in these experiments had the same ratio between 3H and 14C as in the precursor. A previously unknown pathway for formation of cholestanol, involving 7a-hydroxylated intermediates, may explain these results. Under normal conditions, this pathway is responsible for at most 30% of the cholestanol synthesized from cholesterol.Intravenous administration of the 7a-3H-and 4-'4C-labeled cholesterol to a patient with cerebrotendinous xanthomatosis (CTX) resulted in formation of cholestanol which had 70-75% lower 3H/'4C ratio. It is concluded that the novel pathway involving 7a-hydroxylated intermediates is accelerated in patients with CTX. This acceleration may contribute essentially to the accumulation of cholestanol, which is a predominant feature of this disease.7a-Hydroxycholesterol and 7a-hydroxy4-cholesten-3-one might be intermediates in the novel pathway to cholestanol. After intravenous administration of 7_-3H-labeled 7a-hydroxycholesterol in a patient with CTX, significant amounts of 3H were incorporated into plasma and fecal cholestanol. Only small amounts of 7a-hydroxycholesterol and 7a-hydroxy-4-cholesten-3-one are excreted into the intestine, and we therefore conclude that the 7a-dehydroxylation step mainly occurs in the liver. In CTFX, the synthesis of cholestanol may be accelerated because the concentrations of 7a-hydroxylated bile acid intermediates in the liver are increased. A possible mechanism for the conversion of a minor fraction of 7a-hydroxycholesterol into cholestanol is suggested.

No abstract

In Norway, the use of chemoprophylaxis after cases of meningococcal disease is not recommended. Instead, household members less than 15 years are treated with penicillin for 7 days. Failures of this treatment have been reported. We therefore used DNA fingerprinting to identify the disease-causing strain in healthy contacts combined with selective rifampicin prophylaxis to these carriers to prevent secondary cases. During a 2-year period (1987-89) there were 13 cases of meningococcal disease in the County of Telemark (165000 inhabitants). 65 (14.7%) out of 441 contacts to these 13 patients harbored meningococci in their throat; 16 (3.6%) carried the disease-causing strain. Only 1 carrier fulfilled the criteria for being treated with penicillin; 8 were adults and the remaining 7 were not household members. No secondary cases of meningococcal disease occurred during the study period or the following 12 months. During the 4-year period (1984-87) preceding the study period there were 39 cases of meningococcal disease in Telemark; 7 of them were index cases for 12 bacteriologically verified and 4 clinically suspected secondary cases of meningococcal disease. We conclude that selective prophylaxis with rifampicin seems to be more efficient that penicillin treatment of household members less than 15 to prevent secondary cases of meningococcal disease.