Search PubMed⌕ Search

Biomedical subjects

W M Scheld

Publications and source records attributed to W M Scheld.

At least 163 records · Page 9Linked to original sources
PubMed1979

Influence of preformed antibody on experimental Streptococcus sanguis endocarditis.

The influence of preformed, anti-whole organism antibody on the development of Streptococcus sanguis endocarditis was examined in both in vivo and in vitro systems. Antibody prevented, rather than potentiated, endocarditis in rabbits. The infectious dose in 30 control animals was 10(6.5) +/- 0.33 (mean +/- standard deviation); this increased to 10(7.71 +/- 0.05 in 36 immunized animals (P less than 0.01). No differences in bacterial clearance mechanisms were apparent between groups. Antibody also prevented the adherence of S. sanguis to the constituents of nonbacterial thrombotic endocarditis (fibrin and platelets) in vitro. When preincubated in high-titer antisera, adherence of S. sanguis was reduced compared with controls (adherence ratio mean +/- standard error of the mean, X 10(4): 174 +/- 5 versus 427 +/- 10, P less than 0.001). Preadsorption of immune sera with intact S. sanguis restored adherence to normal values, whereas preadsorption with dextran was partially effective. These studies demonstrate that preformed antibody had a protective role in vivo and suggest that a possible mechanism is blockade of adherence, a crucial early step in the pathogenesis of endocarditis.

Animals↗
PubMed1979

Enzyme-linked immunosorbent assay for detection of Streptococcus pneumoniae antigen.

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of Streptococcus pneumoniae polysaccharide antigen in cerebrospinal fluid and serum. Sensitivity and specificity were determined for purified antigen preparations. Specificity was also evaluated in the rabbit meningitis model, and the sensitivity was compared to counterimmunoelectrophoresis, using the infected rabbits' cerebrospinal fluid and serum. The ELISA was a specific technique for detecting S. pneumoniae antigen. ELISA was 25 times more sensitive than counterimmunoelectrophoresis for purified antigen and resulted in an increased positivity of the cerebrospinal fluid and serum from infected rabbits. ELISA should prove very useful in the diagnosis of pneumococcal infections.

Animals↗
PubMed1978

Comparison of netilmicin with gentamicin in the therapy of experimental Escherichia coli meningitis.

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental Escherichia coli meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10(5)E. coli colony-forming units. The minimum bactericidal concentration was 2 mug/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) x 100%] was 22.5 +/- 6.0 and 20.6 +/- 7.2 for netilmicin and gentamicin, respectively (P = 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 mug/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 mug of netilmicin per ml as compared to 14.1 mug of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.

Animals↗
PubMed1978

Bacterial adherence in the pathogenesis of endocarditis. Interaction of bacterial dextran, platelets, and fibrin.

The role of dextran in the pathogenesis of bacterial endocarditis was investigated by studying the adherence of dextran producing oral streptococci to the constituents of nonbacterial thrombotic endocarditis (NBTE) in vitro and in vivo. The adherence of Streptococcus sanguis to fibrin and platelets was determined in an in vitro assay system simulating nonbacterial thrombotic endocarditis. Adherence was increased when the organisms were grown in sucrose-supplemented media (adherence ratio X 10(4), 177 +/- 6 in 5% sucrose vs. 140 +/- 7 in 0.5% sucrose, P less than 0.001), and decreased by incubating the organisms in dextranase (adherence ratio X 10(4), 117 +/- 16, P less than 0.001), an effect which was nullified by heat inactivating this enzyme (adherence ratio X 10(4), 192 +/- 7, P less than 0.001). The amount of dextran produced in broth by three different oral streptococci correlated directly with the adherence observed to fibrin and a fibrin-platelet matrix in vitro (P less than 0.001). These organisms adhered more readily to a fibrin-platelet matrix than to fibrin alone (adherence ratio X 10(4), 455 +/- 30 vs. 177 +/- 6, respectively, P less than 0.001). The role of dextran formation was also examined in vivo in rabbits with preexisting NBTE. After injection of 10(7) S. sanguis, 12 of 17 animals developed endocarditis. In contrast, when the organisms were pretreated with dextranase (an enzyme that removes dextran from the bacterial cell surface), the same inoculum resulted in endocarditis in only 5 of 19 animals (P less than 0.05). In addition, a fresh strain of S. sanguis that produced high levels of dextran (1,220 +/- 50 microgram/ml) and adhered avidly to fibrin (adherence ratio X 10(4), 220 +/- 11) produced endocarditis in 12 of 18 rabbits after injection of 10(7) organisms. Another isolate of the same strain that had been passed repeatedly in the laboratory produced less dextran (400 +/- 30 microgram/ml), adhered poorly to fibrin (adherence ratio X 10(4), 140 +/- 7), and produced endocarditis in only 3 of 14 rabbits under identical conditions (P less than 0.05). This study demonstrates that dextran production is important in the adherence of oral streptococci to the constituents of NBTE and may play a role in the pathogenesis of bacterial endocarditis by oral streptococci.

Animals↗
PubMed1977

Comparative pharmacology of cefaclor and cephalexin.

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 +/- 0.55 (standard deviation [SD]) mug/ml compared with 9.43 +/- 2.36 mug/ml for cephalexin (P < 0.01). The half-lives were 0.58 +/- 0.07 (SD) h and 0.80 +/- 0.12 (SD) h, and elimination constants were 1.22 +/- 0.15 and 0.88 +/- 0.13 h(-1) for cefaclor and cephalexin, respectively (P < 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated.

Adult↗
PubMed1977

In vitro susceptibility studies with cefaclor and cephalexin.

The in vitro activity of cefaclor and cephalexin against clinical isolates of four bacterial genera was compared. Both agents had a similar range of activity, but cefaclor was significantly more active by weight than cephalexin for most isolates tested.

Bacteria↗
PubMedDate not supplied

Recent development of rigors during infusion of urokinase: is it related to an endotoxin?

PURPOSE: This study was undertaken to determine the prevalence of rigors associated with the use of urokinase (UK) and to assay for the presence of an endotoxin in the UK solution. PATIENTS AND METHODS: Records of 75 patients who underwent 86 UK infusions between January 1988 and July 1992 were reviewed to evaluate for the development of UK-associated rigors. A modified chromogenic limulus amebocyte lysate (LAL) test was performed to determine the presence of endotoxin in four samples of UK from lots associated with rigors, one sample of UK not associated with rigors, sterile water, nonionic contrast medium, and ionic contrast medium. RESULTS: Between January 1, 1988, and July 10, 1990, 43 patients underwent 46 UK treatments (group 1) with no documented rigors (0% prevalence). In 45 of these 46 treatments, a standard, non-pulse-spray bolus of 75,000-500,000 IU of UK (mean dose, 182,222 IU) was used. Between July 11, 1990, and July 6, 1992, 38 patients underwent 40 UK treatments (group 2). In 33 of these 40 treatments, a standard bolus was given. Five patients received a pulse-spray bolus. The mean bolus was 213,768 IU (range, 100,000-500,000 IU). Eleven group 2 patients developed rigors (28% prevalence; P = .0005 vs group 1). The chromogenic LAL tests demonstrated no endotoxin in sterile water, nonionic contrast media, or ionic contrast media. Endotoxin was detected in small concentrations in the four samples of UK associated with rigors and in the UK sample not associated with rigors. CONCLUSION: The increase in the prevalence of rigors associated with the use of UK does not appear to be related to an endotoxin in UK, since the concentration of endotoxin detected is well below the threshold pyrogenic dose in humans.

Contrast Media↗
PubMedDate not supplied

Quinolone therapy for infections of the central nervous system.

The rationale for use of quinolones in the treatment of central nervous system (CNS) infections is reviewed. Quinolones exert potent activity in vitro against many gram-negative meningeal pathogens. Given the concentrations attained in cerebrospinal fluid (CSF), however, activity against gram-positive organisms is marginal. As a group, the quinolones enter (penetrate) the CSF better than do any other class of antimicrobial agents. The percentage penetration into CSF is remarkably similar in animal models and in humans with meningitis receiving concurrent therapy. The relative rank order for CSF penetration is as follows: enoxacin and pefloxacin (approximately 50%) greater than ciprofloxacin and ofloxacin (approximately 20%-30%). Certain quinolones have proven to be equivalent to conventional agents (e.g., third-generation cephalosporins) in the rate with which they eradicate bacterial gram-negative organisms from the CSF in experimental animal models of meningitis, but the serum concentrations have usually been higher than those achieved in humans. Despite these advantages, the concentrations in CSF remain low (e.g., ciprofloxacin, approximately 0.25-0.5 mg/L; pefloxacin, 4-8 mg/L) in humans because of the relatively low concentrations attained in serum. Thus, quinolones will continue to be most useful in the treatment of infections due to problem pathogens or to multiresistant pathogens (e.g., Pseudomonas species). Although quinolones appear to enter brain tissue readily, it is unlikely that they can be used as single agents for the treatment of brain abscess because of poor activity against anaerobes and streptococci, and no animal or human studies have been reported. A single dose of ciprofloxacin administered orally appears promising for use in eradication of the meningococcal carrier state.

4-Quinolones↗
PubMedDate not supplied

Drug delivery to the central nervous system: general principles and relevance to therapy for infections of the central nervous system.

Drug delivery to the central nervous system (CNS) is of vital concern to the therapy for primary CNS disorders and the development of drug neurotoxicity. The factors influencing drug entry into the CSF include the status of the blood-brain barrier (BBB) and lipid solubility, molecular weight, pKa, protein binding, and removal of the drug from the CSF by an exit pump in the choroid plexus. The most important of these factors is the status of the complex BBB systems. The morphologic equivalent of the BBB and its specialized functions (e.g., transport of D-glucose, amino acids, and ions) are discussed in depth. Methods developed for increasing drug delivery to the CNS by circumvention and/or manipulation of the BBB have included direct injection into the CSF, administration of prodrugs or chemical delivery systems, or reversible "opening" of the BBB by hyperosmotic agents, pentylenetetrazole, etoposide, DMSO, or other agents. The relevance of these general principles to selected examples of CNS infections (i.e., gram-negative aerobic bacillary meningitis and subacute encephalopathy associated with AIDS) is emphasized.

Anti-Infective Agents↗
PubMedDate not supplied

Etiology and mortality of bacterial meningitis in northeastern Brazil.

Little is known of the current incidence and mortality of meningitis in developing nations, especially in Latin America. We reviewed all cases of meningitis in an isolation-fever hospital in Salvador, Brazil, for the decade 1973-1982. Of all admissions, 6,751 (27%) were for meningitis; 4,100 (61%) of these cases were of definite or probable bacterial etiology. Children younger than 15 years accounted for 79% of cases, and 45% of cases were in children under 2 years. The overall case fatality rate was 33%, with 50% of these deaths occurring within 48 hours of hospitalization. Neisseria meningitidis was the etiologic agent in 32% of the cases, with a case fatality rate of 14%. Epidemics caused by N. meningitidis group C, then group A, in 1974-1978 accounted for 60% of the cases. Streptococcus pneumoniae caused 17% of cases, with a case fatality rate of 59%. Haemophilus influenzae type b, the most common cause of nonepidemic meningitis, caused 23% of all cases, with a case fatality rate of 38%. Enterobacteriaceae were the etiology in only 3.6% of patients, but the case fatality rate was 86%. Cultures were negative in 18% of cases with purulent cerebrospinal fluid. A total of 84% of H. influenzae, 40% of S. pneumoniae, 78% of Enterobacteriaceae, and 15% of N. meningitidis cases occurred in children less than 2 years of age. Case fatality rates were highest in this group. Vaccines protective for this age group are urgently needed.

Adolescent↗
PubMedDate not supplied

Nosocomial pneumonia: pathogenesis and recent advances in diagnosis and therapy.

Despite recent progress in the prevention and treatment of hospital-acquired infections, nosocomial pneumonia remains an important problem among critically ill patients. Nosocomial pneumonia develops in five to 10 patients per 1,000 admissions and has a mortality rate of 20%-50%. This review focuses on three areas of nosocomial pneumonia that have been the subject of investigation in recent years: (1) pathogenesis, especially the role of gastric colonization with gram-negative bacilli in retrograde pharyngeal spread; (2) diagnosis, particularly by means of bronchoalveolar lavage and the protected specimen brush during bronchoscopy; and (3) therapy with extended-spectrum penicillins, third-generation cephalosporins, imipenem, aztreonam, and quinolones.

Anti-Bacterial Agents↗
PubMedDate not supplied

Intermittent or continuous therapy of experimental meningitis due to Streptococcus pneumoniae in rabbits: preliminary observations on the postantibiotic effect in vivo.

The relative effectiveness of bolus vs. constant intravenous administration of equivalent doses of penicillin G in killing bacteria in vivo was studied in a rabbit model of meningitis due to Streptococcus pneumoniae. Samples of cerebrospinal fluid (CSF) and serum were obtained from 30 rabbits at intervals of less than or equal to 8 hr after treatment for determination of antibiotic concentrations and titers of viable bacteria in the CSF. When penicillin G was given by continuous infusion (10(5) units/hr after an initial 10(5)-unit loading dose), concentrations of drug in serum and CSF reached a steady state in 1 hr. With intermittent bolus administration of 4 x 10(5) units every 4 hr, higher peak and lower trough concentrations were achieved, and these concentrations paralleled those in the CSF. Although an initial acceleration in bactericidal rate was observed with the bolus infusion between the first and second hour of therapy, after the second hour the rate of bacterial killing was identical for the two methods of administration. The duration of therapy required for sterilization of the CSF was dependent only on the bacterial count before treatment and not on the mode of drug administration. The effect of single bolus intravenous administration of ampicillin was examined in experimental pneumococcal meningitis. Ampicillin was given at various dosages (3.25-62.5 mg/kg), and frequent samples of CSF were obtained for determination of concentrations of pneumococci and ampicillin. A long postantibiotic effect was observed in the CSF of all animals, and this effect consistently was longer than that observed in vitro.

Adult↗
PubMedDate not supplied

Rifampin in experimental endocarditis due to Staphylococcus aureus in rabbits.

Rifampin possesses unique activity against Staphylococcus aureus. It is the most active antistaphylococcal antibiotic currently available and has been shown to be particularly effective in eradicating S. aureus from abscess cavities in experimental infections. However, resistance develops rapidly in vitro and in vivo when large numbers of organisms (10(6)-10(7)) are present, and use of combination therapy has been recommended. The use of combination therapy is complicated by the finding that in vitro the addition of rifampin may reduce (antagonize) the bactericidal effect of the beta-lactam antibiotics. This study examines the in vivo effect of treatment with a beta-lactam agent (cloxacillin), rifampin, or the combination on the eradication of S. aureus from cardiac vegetations in experimental endocarditis. Five different dosage combinations of the beta-lactam agent and rifampin were administered for a three-day period, and an attempt was made to correlate peak serum bactericidal titers with results of quantitative cultures of vegetations after therapy. In two of five regimens the combination of rifampin and cloxacillin produced enhanced efficacy in vivo (synergism); in two regimens the effect was no greater than the effect of either drug alone (indifference), and in one regimen the combination was less effective than either single-drug regimen alone (antagonism). Peak serum bactericidal titers often were predictive of the in vivo effect when high doses of cloxacillin were used but were not consistently predictive of in vivo results when rifampin was the agent responsible for the major therapeutic effect. Rifampin-resistant strains did not emerge in animals receiving combination therapy but were isolated from vegetations from several animals receiving rifampin alone.

Animals↗
PubMedDate not supplied

Evaluation of rifampin and other antibiotics against Listeria monocytogenes in vitro and in vivo.

The activity of rifampin and other antibiotics against Listeria monocytogenes in vitro and in experimental animal models of listeriosis is reviewed. Rifampin appears to be bacteriostatic against Listeria in vitro, and it is reported to be no more effective than penicillin against experimental listeria meningitis in the rabbit. However, because of insufficient clinical data, the optimal antibiotic regimen for listeriosis in humans remains conjectural. At present, the most frequently recommended regimen is combination therapy with ampicillin and gentamicin; trimethoprim-sulfamethoxazole may prove useful in the penicillin-allergic individual.

Animals↗
PubMedDate not supplied

Comparative evaluation of aztreonam in therapy for experimental bacterial meningitis and cerebritis.

Aztreonam (SQ 26,776), a new monocyclic beta-lactam agent, was compared with several frequently used antibiotics in therapy for three types of experimental meningitis in rabbits and for experimental Escherichia coli cerebritis in rats. Aztreonam was highly active against common gram-negative meningeal pathogens in vitro (all minimal bactericidal concentrations less than or equal to 0.125 microgram/ml), including ampicillin-sensitive and ampicillin-resistant strains of Haemophilus influenzae, E. coli, and meningococci. In both rabbits and rats, serum concentrations of all antibiotics evaluated closely approximated concentrations found in humans receiving standard parenteral regimens. The percent penetration of aztreonam into purulent rabbit cerebrospinal fluid was 23%. In experimental meningitis, aztreonam was more rapidly bactericidal than ampicillin in meningitis due to ampicillin-sensitive H. influenzae, than ampicillin or chloramphenicol in meningitis due to ampicillin-resistant H. influenzae, and than gentamicin in meningitis due to E. coli. Aztreonam also reduced concentrations of E. coli in rat brain as rapidly as did gentamicin during therapy for experimental cerebritis, the early stage of brain abscess formation.

Ampicillin↗