Susceptibility of herpesviruses to three nucleoside analogues and their combinations and enhancement of the antiviral effect of acid pH.
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Biomedical subjects
Publications and source records attributed to L B Guze.
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Susceptibility of 64 clinical isolates of Neisseria gonorrhoeae to metronidazole was determined by the agar dilution technique using Mueller-Hinton and chocolate agar media. All isolates were resistant to metronidazole at 12.5 mug/ml in either medium. This lack of activity of metronidazole against N. gonorrhoeae would suggest that the ability to recover N. gonorrhoeae in patients being treated with metronidazole for concurrent Trichomonas vaginalis infections should not be hampered.
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The effect of antimicrobial therapy on the histopathologic progression of experimental hematogenous pyelonephritis induced in rats by Streptococcus faecalis was studied. Treatment sufficient to render the renal parenchyma sterile strikingly decreased the incidence and severity of calyceal lesions, delayed the progression of papillary lesions but had little effect on the severity of cortical interstitial and tubular alterations. L-forms could not be demonstrated to participate in the pathogenesis of these lesions. Kanamycin had an independent nephrotoxic effect which complicated interpretation of the effect of therapy in animals receiving this agent.
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Two neonates and four adults with herpes simplex virus (HSV) encephalitis were treated with cytosine arabinoside (Ara-C). A low dose of 40 to 160 mg per m(2) per day was given for 4 to 6 days by continuous intravenous infusion and, except in two cases, by intrathecal administration. In one patient, idoxuridine (IUdR) at the dose of 1 g every 4 h was also administered after 4 days of Ara-C therapy. Both neonates and two of four adults survived. Their clinical improvement was closely related in time to the onset of therapy with Ara-C (cases 1, 2, 3) and with IUdR (case 4). In one adult who died on the 27th day of illness of a massive pulmonary embolus, postmortem examination of the brain did not disclose viral inclusions, and viral culture was negative. In the other patient who died, however, brain culture postmortem was still positive for HSV despite 4 days of Ara-C therapy. Ara-C, in addition to IUdR, may be effective in HSV encephalitis treatment, but double-blind, controlled studies appear to be necessary with these agents.
Earlier workers suggested that synergism of polymyxin and sulfonamides occurred because sulfonamides produced changes in the cell wall which permitted the more ready access of polymyxin. We tested this hypothesis by using L-forms, which lack cell wall. The demonstration that synergism of polymyxin and sulfonamides occurs in L-forms of Proteus mirabilis and Staphylococcus aureus suggested that the synergism is a result of some mechanism other than alterations of the cell wall.
Minimum inhibitory and bactericidal concentrations of four antibiotics and their combinations were determined for 38 strains of enterococci by a microtitration tube dilution technique. The drugs were ampicillin, vancomycin, gentamicin, and streptomycin; the combinations were ampicillin-gentamicin, ampicillin-streptomycin, vancomycin-gentamicin, and vancomycin-streptomycin. At achievable serum concentrations, ampicillin alone killed 60% of strains, whereas combination with streptomycin increased this to 90% and with gentamicin to 100%. Vancomycin alone showed striking inhibitory activity, but very poor bactericidal activity at achievable concentrations. Combination with one of the aminoglycosides increased the bactericidal activity substantially. When combined with ampicillin, gentamicin was both more active and showed synergistic bactericidal activity significantly more often (P < 0.01) than streptomycin.
The fatty acid composition of the membranes of three different penicillin-produced L-forms of Streptococcus faecalis was determined: (i) a stable (nonreverting) L-form (T(53)) cultured in brain heart infusion (BHI) with 0.5 M sucrose; (ii) a stable L-form (T(531)) cultured in BHI without sucrose; and (iii) an unstable L-form (T(9)) cultured in BHI with 0.5 M sucrose and 1,000 U of penicillin per ml. L-forms were obtained by centrifugation and lysed by washing in 1 mM tris(hydroxymethyl)aminomethane-hydrochloride buffer. The parent S. faecalis was also cultured in BHI and BHI containing 0.5 M sucrose, and washed with buffer. The fatty acid composition of L-forms of S. faecalis cultured in BHI without sucrose (370 mosmol) had higher C(18:1) and lower C(18) than L-forms cultured in the same media with added 0.5 M sucrose (950 mosmol) in both exponential and stationary cultures. In the stationary phase of growth, C(19) was reduced in the L-forms cultured without sucrose. Similar changes were seen in the parent S. faecalis cultured in the two types of media. These changes in membrane fatty acids may relate to osmo-regulation of the L-forms.