Bacteriuria is common in chronically catheterized patients and is associated with both acute and chronic complications. Of 605 consecutive weekly urine specimens from 20 chronically catheterized patients, 98% contained bacteria at high concentrations and 77% were polymicrobial. The mean interval between new episodes of bacteriuria was 1.8 weeks. Most species of bacteria caused five to seven new episodes of bacteriuria per 100 weeks of catheterization. Even though access to the catheter lumen was similar, the duration of bacteriuric episodes varied greatly by species. Of the episodes of bacteriuria caused by nonenterococcal gram-positive cocci, greater than 75% lasted less than one week. Mean durations of episodes of bacteriuria due to Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa were four to six weeks, whereas those due to Providencia stuartii averaged 10 weeks and ranged up to 36 weeks. Thus, the very high prevalence of bacteriuria--virtually 100%--was a result of a high incidence caused by many different species combined with the prolonged residence of some gram-negative bacilli in the catheter and urinary tract.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts -1A2 and the A/Ann Arbor/6/60 cold-adapted ( ca ) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts -1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID 50 ) for each recombinant was approximately 10 5.0 50% tissue culture infective doses. The virus shed by the ts -1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts -1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID 50 and approximately 70% of ca or ts vaccinees who received 10 to 32 HID 50 of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.

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