Effect of warfarin on the induction and course of experimental endocarditis.
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The effect of warfarin treatment on an experimental endocarditis was studied in rabbits. Warfarin had no effect on the induction of a Streptococcus sanguis infection in catheter-induced endocardial vegetations, and the course of this infection was also unaltered. However, warfarin treatment resulted in rapidly progressive bacteremia, probably due to impaired circulation in clearing organs such as the lungs, liver, and spleen. Warfarin also reduced the survival time of the infected rabbits, in which pulmonary edema and extensive lung hemorrhages may have been a contributory factor. (+info)
pKa calculations for class A beta-lactamases: influence of substrate binding.
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Beta-Lactamases are responsible for bacterial resistance to beta-lactams and are thus of major clinical importance. However, the identity of the general base involved in their mechanism of action is still unclear. Two candidate residues, Glu166 and Lys73, have been proposed to fulfill this role. Previous studies support the proposal that Glu166 acts during the deacylation, but there is no consensus on the possible role of this residue in the acylation step. Recent experimental data and theoretical considerations indicate that Lys73 is protonated in the free beta-lactamases, showing that this residue is unlikely to act as a proton abstractor. On the other hand, it has been proposed that the pKa of Lys73 would be dramatically reduced upon substrate binding and would thus be able to act as a base. To check this hypothesis, we performed continuum electrostatic calculations for five wild-type and three beta-lactamase mutants to estimate the pKa of Lys73 in the presence of substrates, both in the Henri-Michaelis complex and in the tetrahedral intermediate. In all cases, the pKa of Lys73 was computed to be above 10, showing that it is unlikely to act as a proton abstractor, even when a beta-lactam substrate is bound in the enzyme active site. The pKa of Lys234 is also raised in the tetrahedral intermediate, thus confirming a probable role of this residue in the stabilization of the tetrahedral intermediate. The influence of the beta-lactam carboxylate on the pKa values of the active-site lysines is also discussed. (+info)
Pneumococcal psoas abscess.
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A 47-year-old woman was admitted to our hospital because of severe low back pain. A computed tomography (CT) scan revealed a left sided psoas muscle abscess. On the first hospital day, US-guided drainage was performed. Streptococcus pneumoniae was isolated from the pus. Thereafter, the open drainage of the abscess and antibiotic treatment were given with subsequent clinical improvement. Only 10 cases of pneumococcal psoas abscess have been previously reported in the world literature. (+info)
Sublethal heat stress of Vibrio parahaemolyticus.
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When Vibrio parahaemolyticsu ATCC 17802 was heated at 41 degrees C for 30 min in 100 mM phosphate-3% NaCl buffer (pH 7.0), the plate counts obtained when using Trypticase soy agar containing 0.25% added NaCl (0.25 TSAS) were nearly 99.9% higher than plate counts using Trypticase soy agar containing 5.5% added NaCl (5.5 TSAS). A similar result was obtained when cells of V. parahaemolyticus were grown in a glucose salts medium (GSM) and heated at 45 degrees C. The injured cells recovered salt tolerance within 3 h when placed in either 2.5 TSBS or GSM at 30 degrees C. The addition of chloramphenicol, actinomycin D, or nalidixic acid to 2.5 TSBS during recovery of cells grown in 2.5 TSBS indicated that recovery was dependent upon protein, ribonucleic acid (RNA, and deoxyribonucleic acid (DNA) synthesis. Penicillin did not inhibit the recovery process. Heat-injured, GSM-grown cells required RNA synthesis but not DNA synthesis during recovery in GSM. Chemical analyses showed that total cellular RNA decreased and total cellular DNA remained constant during heat injury. The addition of [6-3H]uracil, L-[U-14C]leucine, and [methyl-3H]thymidine to the recovery media confirmed the results of the antibiotic experiments. (+info)
Enterococcal endocarditis: duration and mode of treatment.
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This report summarizes data on sixteen patients with enterococcal endocarditis treated with penicillin and streptomycin. The experience reported suggests that a four week period is adequate for routine therapy in these patients, as in other forms of streptococcal endocarditis. It provides an additional group of patients successfully treated with penicillin and streptomycin. Two relapses were encountered. One of these received inadequate daily doses of penicillin. The other patient was clearly a failure of penicillin and streptomycin, but the failure in this instance could not be attributed to foreshortened treatment (6 weeks) or to high level streptomycin resistance of the infecting strain of Enterococcus. (+info)
Characterisation of penicillin G uptake in human small intestinal brush border membrane vesicles.
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BACKGROUND: Many beta lactams are well absorbed by the small intestine, although the reasons for this are poorly understood. AIMS: To characterise the uptake of penicillin G into human small intestinal brush border membrane vesicles (BBMV) and to compare the uptake characteristics to those of rabbit BBMV. METHODS AND RESULTS: Uptake of penicillin G was studied in human BBMV. Penicillin G was actively transported into the lumen of BBMV via an H+ dependent, Na+ independent uptake system. The carrier mediated process was saturable and adhered to Michaelis-Menten kinetics (Vmax 52 nmol penicillin G per mg protein per 30 seconds, Km 13.9 mM). These results are similar to those previously reported in rabbit BBMV. CONCLUSIONS: It is suggested that penicillin G can be used as a model molecule for peptide and beta lactam transport studies as it is cheap and readily available in isotopically labelled form. Furthermore, rabbit BBMV may be used as an acceptable substitute for human BBMV for the study of penicillin transport. (+info)
Efficacy of beta-lactam antibiotics combined with gentamicin against penicillin-resistant pneumococcal pneumonia in CBA/J mice.
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We examined the efficacy of gentamicin combined with beta-lactam antibiotics against penicillin-resistant Streptococcus pneumoniae (PRSP) in a noncompromised mouse model of pneumonia. In the presence of 8 mg/L (0.25 x MIC) and 16 mg/L (0.5 x MIC) of gentamicin, MICs of penicillin G against 23 strains of PRSP decreased from 1-4 mg/L to 0.03 mg/L in 14 (61%) and 23 strains (100%), respectively. A short-time killing study using strain 741 showed that 8 mg/L of gentamicin (0.25 x MIC) increased the killing activity of penicillin G, cefotaxime and imipenem (at 0.25, 1 and 4 x MIC) during a 6 h incubation period. Survival studies showed that the combined treatment of penicillin-G (160 mg/kg) and gentamicin (10 mg/kg), which commenced 2 days after infection (twice a day for 5 days), provided complete protection, while no animal survived when either antibiotic was used alone. A significant improvement in mortality was observed when a small dose of imipenem (2.5 and 10 mg/kg) was used with gentamicin. Our results suggest that gentamicin, when combined with beta-lactam antibiotics, especially imipenem, may be potentially useful against PRSP pneumonia in noncompromised individuals. (+info)
beta-lactamase production and antimicrobial susceptibility of oral heterogeneous Fusobacterium nucleatum populations in young children.
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Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp. vincentii (J. L. Dzink, M. T. Sheenan, and S. S. Socransky, Int. J. Syst. Bacteriol. 40:74-78, 1990). In vitro susceptibility of these beta-lactamase-producing and 26 non-beta-lactamase-producing F. nucleatum isolates was tested with penicillin G, amoxicillin-clavulanic acid, tetracycline hydrochloride, metronidazole, trovafloxacin, and azithromycin. Except for penicillin G, the antimicrobials exhibited good activity against all F. nucleatum isolates. (+info)