Two patients with colonic adenocarcinoma and Streptococcus bovis endocarditis suggested a possible association between the two. Non-enterococcal Group D streptococci were isolated from fecal cultures of 11 of 105 controls, 35 of 63 patients with carcinoma of the colon, seven of 25 with inflammatory bowel disease, four of 21 with non-colonic neoplasms and five of 37 with other gastrointestinal disorders. All such streptococci examined for lactose fermentation were S. bovis. The prevalence of S. bovis in fecal cultures from patients with carcinoma of the colon was significantly increased (P less than 0.001) as compared to that in controls, and also to all other groups (P less than 0.001). No other group had results significantly different from those of controls (P less than 0.05) although patients with inflammatory bowel disease were more frequently carriers. The carrier state was unrelated to age, hospitalization status, colonic stasis, gastrointestinal bleeding or recent barium-enema examination. The implications of this association are unknown.

Gentamicin uptake and killing were studied in aminoglycoside-susceptible wildtype Staphylococcus aureus strains and aminoglycoside-resistant small-colony mutants selected by gentamicin from these strains. In wild-type S. aureus three phases of gentamicin accumulation were noted, and killing occurred during the last and most rapid phase of uptake. Uptake and killing were abolished by anaerobic growth and sodium azide, suggesting that energy-dependent active drug transport required respiration. Treatment ofwild-type strains with the uncouplers N,N'-dicyclohexyl carbodiimide (DCCD) and carbonyl cyanide-m-chlorophenyl hydrazone showed disparate effects on gentamicin uptake, producing enhanced and diminished accumulations, respectively. Small-colony mutants demonstrated markedly deficient uptake compared with the wild-type strains and were not killed by gentamicin in concentrations up to 10 ,Lg/ml. Several classes of aminoglycoside-resistant mutant strains are described. One mutant strain was a menadione auxotroph which, when grown in the presence of menadione, exhibited normal gentamicin uptake and killing. Gentamicin uptake and killing in this strain were abolished by KCN (21,24). The decreased susceptibilities to a wide variety of aminoglycosides observed in these mutant strains suggest a more general mechanism of resistance than specific enzymatic modification or altered ribosomal binding of particular aminoglycosides. In view of data indicating that similar small-colony variants of S. aureus have impairments in oxidative processes (19,20) and the demonstration that oxidatively generated energy is required for aminoglycoside uptake in gram-negative bacilli (4-6), we were interested in studying gentamicin accumulation and its relationship to oxidative metabolism in wild-type and aminoglycoside-resistant small-colony mutants of S. aureus.

We studied 1309 dental professionals (1132 dentists, 131 hygienists, and 46 assistants) without behavioral risk factors for the acquired immunodeficiency syndrome (AIDS) to determine their occupational risk for infection with human immunodeficiency virus (HIV). Subjects completed questionnaires on behavior; type, duration, and location of their dental practice; infection-control practices; and estimated numbers of potential occupational exposures to HIV. Serum samples were tested for antibodies to HIV and to hepatitis B surface antigen (unvaccinated subjects). Fifty-one percent of the subjects practiced in locations where many cases of AIDS have been reported. Seventy-two percent treated patients who had AIDS or were at increased risk for it. Ninety-four percent reported accidental puncturing of the skin with instruments used in treating patients. Adherence to recommended infection-control practices was infrequent. Twenty-one percent of unvaccinated subjects had antibodies to hepatitis B surface antigen. Only one dentist without a history of behavioral risk factors for AIDS had serum antibodies to HIV. We conclude that despite infrequent compliance with recommended infection-control precautions, frequent occupational exposure to persons at increased risk for HIV infection, and frequent accidental puncturing of the skin with sharp instruments, dental professionals are at low occupational risk for HIV infection.

The efficacy of nafcillin and gentamicin used alone and in combination at doses giving serum concentrations comparable to those achieved in patients was studied in rabbits with experimental Staphylococcus aureus endocarditis. The organism used was a penicillinase-producing, methicillin-susceptible, clinical isolate. The addition of gentamicin to nafcillin significantly increased the rate of killing of organisms in valvular vegetations, compared to the effect of nafcillin alone. Gentamicin alone delayed mortality but was not effective in reducing the bacterial populations of the vegetations. Bacteremia persisted in the animals treated with gentamicin alone, in contrast to the groups treated with nafcillin or the combination. Selection of a subpopulation of aminoglycoside-resistant small-colony variants occurred in animals treated with gentamicin alone. This variant was subsequently employed in the rabbit model and produced endocarditis, metastatic infection, and bacteremia comparable to those caused by the parent strain. Animals with infection produced by the variant died later than animals infected by the parent strain. Nafcillin was equally effective in reducing the population of both parent and variant strains in vitro and in therapy of the infected animals. Population studies showed the variant to be a mutant emerging at a rate of 1.9 X 10-7. It was shown to differ from the parent strain in coagulase and hemolysin production, colonial morphology, and aminoglycoside susceptibility, but was similar by light and electron microscopy and in phage type, pigmentation of colonies, deoxyribonuclease production, mannitol fermentation, and growth rate.In vitro time-kill studies with blood culture isolates of penicillinase-producing, methicillinsusceptible S. aureus have demonstrated that gentamicin at a concentration of 5 ,ug/ml is rapidly bactericidal and reduces the bacterial population at a rate greater than that achieved by nafcillin at 20 jig/ml (N. H. Steigbigel, J. I.Casey, and B. J. Heeter, Clin. Res. 21:976, 1973). The initial rate of killing at a lower concentration of gentamicin (0.5 ,ug/ml) was similar to that obtained with 5 ,ug/ml but was associated with the later overgrowth, in each of 24 strains tested, of a small-colony variant which showed increased resistance when rechallenged with aminoglycosides. The combination of nafcillin and gentamicin (0.5 yg/ml) demonstrated the initial rapid killing without the subsequent emergence of the variant strain. Studies using a high inoculum of organisms, 109 colony-forming units (CFU) per ml, demonstrated that gentamicin alone or in combination with nafcillin was significantly active, whereas nafcillin alone did not decrease the population. The relevance of these in vitro observations was studied in a model of S. aureus endocarditis in rabbits.This study was presented in part at the 16th Interscience Conference on Antimicrobial Agents and Chemotherapy, October, 1976

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