Search PubMed⌕ Search

Biomedical subjects

W M Scheld

Publications and source records attributed to W M Scheld.

At least 145 records · Page 8Linked to original sources
PubMed1981

A multivariate approach to prognostication in experimental bacterial meningitis.

Known concentrations of type III pneumococci were inoculated into eighty-one rabbits by cisternal puncture. Antibiotic therapy was started the following day. Aliquots of cerebrospinal fluid (CSF) and plasma were sampled on day one immediately before therapy was started and at regular intervals thereafter for up to eight days. Samples were analyzed for glucose, lactate, lactic dehydrogenase, and creatine kinase in various combinations. Leukocyte counts were performed on all CSF specimens. The timing of the specimens proved critical to the prognostic utility of the analyses performed. Day two plasma glucose was the most important single measurement for prognostication. Day one values for CSF glucose, lactate, and leukocyte count were also important. Substantial gains in prognostic accuracy were achieved when clinical laboratory measurements were used in combination by discriminant function analysis.

Animals↗
PubMed1981

Moxalactam and cefazolin: comparative pharmacokinetics in normal subjects.

Moxalactam, a new beta-lactam antibiotic with a wide in vitro spectrum of activity, was compared with cefazolin after intravenous and intramuscular administration of 1.0 g in a double-blind crossover design in 21 adult male subjects with normal renal function. Serum samples were obtained at 0.5, 1, 2, 3, 4, 6, 8, and 12 h, and urine was collected at 0 to 2, 2 to 4, 4 to 6, 6 to 8, and 8 to 12 h after dosing. Intravenous kinetics were described by a linear two-compartment model. For moxalactam, the drug clearance and volume of distribution were larger (115.2 versus 75.9 ml/min per 70 kg, P = 0.001, and 0.44 versus 0.19 liter/kg, P less than 0.001, respectively), and the t1/2beta was longer (3.47 versus 2.18 h, P = 0.01), with correspondingly smaller area under the curve (151 versus 236 h x mg/ml, P = 0.003) and lower serum concentration at 30 min (62 versus 106 micrograms/ml, P = 0.003) than cefazolin. Intramuscular kinetics were similar and were well described by a single-compartment model. Urinary recovery was essentially identical for both drugs: 55 to 75% in 8 h. Consistent departures from the two-compartment model for moxalactam (not noted for cefazolin) suggested enterohepatic recirculation of moxalactam. Both drugs were well tolerated, and no adverse reactions were noted.

Adult↗
PubMed1981

Pharmacokinetics of cefoperazone in normal volunteers and subjects with renal insufficiency.

We examined the pharmacokinetics of the new beta-lactam agent, cefoperazone, in normal and functionally anephric dialysis subjects with normal liver function. All subjects received 3 g of cefoperazone intravenously, and serial serum and urine samples were taken thereafter for up to 36 h. The serum levels, volume of distribution (0.22 liter/kg, normal; 0.19 liter/kg; dialysis), beta half-life (2.07 h, normal; 2.03 h, dialysis), and total body clearance (96.2 ml/min, normal; 92.9 ml/ min, dialysis) were all not significantly different between the two groups. Cefoperazone may be administered without adjustment of dose for any degree of renal dysfunction to patients with normal hepatic function.

Adult↗
PubMed1981

Bacterial adhesion in the pathogenesis of infective endocarditis. Effect of subinhibitory antibiotic concentrations on streptococcal adhesion in vitro and the development of endocarditis in rabbits.

Bacterial adhesion to the constituents of nonbacterial thrombotic endocarditis (NBTE) is important in the pathogenesis of endocarditis. Subinhibitory concentrations (subMIC) of some antibiotics decrease bacterial adhesion to epithelial cells in vitro. We utilized an in vitro assay system to study the effect of subMIC of various antibiotics on streptococcal adhesion to a fibrin-platelet matrix (simulating NBTE). The results were (a) bacterial adhesion of Streptococcus sanguis and Streptococcus faecalis to NBTE was significantly reduced by vancomycin, penicillin, tetracycline, chloramphenicol and streptomycin (P less than 0.01 vs. controls) but not rifampin or trimethoprimsulfametrole; (b) the effect was dose-dependent and increased with duration of exposure to antibiotic; (c) reduction in bacterial adhesion did not correlate with altered retention by hydrophobic-interaction chromatography. This reduction in adhesion correlated with a diminished capacity of subMIC exposed Streptococcus sanguis (1/4 vancomycin minimum inhibitory concentration (MIC) X 4 h) to produce endocarditis in vivo. After intravenous inoculation of 10(6) colony-forming units of preincubated organisms into rabbits with traumatized aortic valves, 6 of 22 developed endocarditis vs. 17 of 22 controls (P = 0.03). These results may be relevant to prophylaxis of endocarditis since exposure of bacteria to subMIC of various antibiotics may reduce bacterial adherence both, to mucosal surfaces, and to damaged cardiac valves.

Animals↗
PubMed1980

Pharmacokinetics of moxalactam in subjects with various degrees of renal dysfunction.

We have examined the pharmacokinetics of moxalactam (LY127935) in 36 subjects with various degrees of renal dysfunction. Creatinine clearance (Ccr)/1.73 m2 ranged from zero to 135.8 ml/min. After a 1-g administration of moxalactam intravenously, the volume of distribution was 20.6 /+- 9.5 liters (0.28 liter/kg), and the mean half-life ranged from 3.1 h for subjects with Ccr greater than 65 ml/min to 19.3 h for subjects with Ccr less than 10 ml/min. The moxalactam clearance was closely correlated to Ccr (r = 0.93, P less than 0.0001) and excretion of antibiotic was 73.6 +/- 13% in normal subjects. Renal clearance accounted for 90% of moxalactam clearance in the normal subjects. A dosage schedule for administering moxalactam to patients with various degrees of renal dysfunction is provided.

Adolescent↗
PubMed1980

Detection of circulating antigen in experimental Candida albicans endocarditis by an enzyme-linked immunosorbent assay.

A double-antibody sandwich enzyme-linked immunosorbent assay was developed for the detection of circulating Candida albicans antigen during the course of experimental C. albicans endocarditis. The enzyme-linked immunosorbent assay was positive in 75% of rabbits with polyethylene catheter-induced experimental aortic valve C. albicans endocarditis but was negative in all controls, including catheterized animals that received intravenous Candida or catheterized but uninfected animals, and in rabbits with experimental fungal or bacterial endocarditis of other etiologies. The enzyme-linked immunosorbent assay was much more sensitive than blood culturing or fever determinations in experimental C. albicans endocarditis. This assay is more sensitive than currently available serological techniques, is highly specific, and deserves further study in the diagnosis of invasive, disseminated C. albicans infections, including endocarditis.

Animals↗
PubMed1980

Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure.

Animals↗
PubMed1980

Combination antibiotic therapy of bacterial endocarditis.

A penicillin-aminoglycoside regimen is accepted therapy for enterococcal endocarditis, but use of combinations of antibiotics in other forms of bacterial endocarditis is controversial. This review analyzes in-vitro, experimental animal model, and clinical studies of combination "synergistic" antibiotic treatment for enterococcal, viridans streptococcal, staphylococcal, and gram-negative aerobic bacillary endocarditis. Current recommendations for treatment of these entities are discussed.

Aminoglycosides↗
PubMed1979

Pulmonary infection with capsule-deficient cryptococcus neoformans.

A case of bilateral lobar pneumonia due to Crytococcus neoformans is presented. The capsule-deficient fungal organisms within tissue were suggestive of Histoplasma capsulatum. Cultures grew Cryptococcus neoformans and there was cryptococcal antigen in the serum. Pulmonary cryptococcosis and the occurrence of unencapsulated cryptococci are reviewed. The important role both culture and the latex agglutination test for cryptococcal antigen play in the differential diagnosis of systemic fungal infections with over-lapping histopathology are discussed.

Adult↗
PubMed1979

Response to therapy in an experimental rabbit model of meningitis due to Listeria monocytogenes.

A uniformly fatal, reproducible model of experimental meningitis due to Listeria monocytogenes was developed in rabbits for study of the natural progression of the disease and was used to evaluate treatment regimens. Bacterial titers in cerebrospinal fluid and pleocytosis approximated those found in humans. Therapeutic studies in vivo revealed that rifampin was less rapidly bactericidal than ampicillin or penicillin, the agents usually recommended for treatment of meningitis; that penicillin plus rifampin was no more efficacious than penicillin alone; that ampicillin demonstrated greater bactericidal activity in vivo than did penicillin; and that addition of an aminoglycoside (gentamicin) to either penicillin or ampicillin significantly enhanced their bactericidal activity in vivo. Ampicillin plus gentamicin was the most effective combination in vivo and may represent the preferred mode of therapy for listeria meningitis.

Ampicillin↗
PubMed1979

Simultaneous disseminated aspergillosis and zygomycosis in a leukemic patient.

Although the incidence of fungal infections is increasing, infections caused by more than one fungus are rare. We have described the clinical, pathologic, and mycologic findings in a leukemic patient with simultaneous pulmonary infection and systemic dissemination caused by Aspergillus fumigatus and Rhizopus sp.

Adult↗
PubMed1979

Citrobacter freundii meningitis in an adult.

We have described the first case of an adult patient with Citrobacter freundii meningitis, which was successfully treated without administration of intrathecal aminoglycoside.

Adult↗
PubMed1979

Mecillinam-ampicillin synergism in experimental Enterobacteriaceae meningitis.

The in vitro activities of mecillinam, a new beta-amidinopenicillin, and ampicillin, alone and in combination, against an Escherichia coli strain and a Klebsiella pneumoniae strain were compared, and these results were correlated with their respective activities in vivo in experimental meningitis. The mecillinam-ampicillin combination was synergistic in vitro against both strains when tested by a modified checkerboard technique (bacteriostatic synergy). However when quantitative bactericidal synergy studies were made, the relative bactericidal rate of the combination was more rapid than that of either drug alone ("bactericidal synergy") against the Escherichia coli isolate only. In a rabbit model of Enterobacteriaceae meningitis, in vivo bactericidal activity correlated with results obtained in vitro. Both drugs were administered by continuous intravenous infusion for 8 h. Serum and cerebrospinal fluid antibiotic levels were similar to those achieved in humans. Cerebrospinal fluid bacterial concentrations (colony-forming units [CFU] per milliliter) were quantitatively titrated at 2-h intervals. Both drugs, alone or the combination, were ineffective against the K. pneumoniae strain in vivo (change in titer <1 log in 8 h). In contrast, the combination produced a markedly enhanced bactericidal effect against the E. coli strain (mean +/- standard deviation, decrease of log(10) CFU per milliliter of 3.65 +/- 1.02) compared with those of ampicillin alone (decrease of log(10) CFU per milliter of 0.07 +/- 0.8) and mecillinam alone (decrease of log(10) CFU per milliliter of 1.6 +/- 0.05) (P < 0.001). When bactericidal synergism can be demonstrated for mecillinam-ampicillin in vitro in a case of gram-negative-bacillary meningitis this combination may be useful in the therapy of the illness.

Amdinocillin↗
PubMed1979

Clearance of bacteria from cerebrospinal fluid to blood in experimental meningitis.

The occurrence and importance of secondary bacteremia in the pathogenesis of and response to therapy in meningitis is uncertain. Streptococcus pneumoniae type III was injected into the cerebrospinal fluid of the cisterna magna in anesthetized, curarized dogs, and sequential simultaneous samples were obtained from the superior sagittal sinus, cisterna magna, and peripheral blood. The results show that: (i) bacteria are rapidly transported from the cerebrospinal fluid to blood but only after active multiplication within the cerebrospinal fluid, and (ii) entrance into the blood from the cerebrospinal fluid occurs before the height of the febrile response or cerebrospinal fluid pleocytosis.

Animals↗