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Biomedical subjects

T W Williams

Publications and source records attributed to T W Williams.

At least 55 records · Page 3Linked to original sources
PubMed1979

Synergy of vancomycin plus cefazolin or cephalothin against methicillin-resistance Staphylococcus epidermidis.

The in vitro activity of cephalothin, cefazolin, and vancomycin against 25 isolates of methicillin-resistant Staphylococcus epidermidis was determined by means of a broth dilution technique with two sizes of inoculum. The size of the inoculum had a marked effect on the minimal inhibitory concentrations and the minimal bactericidal concentrations of all three antibiotics. With a small inoculum, 100% of the isolates were inhibited by 3.12 micrograms of vancomycin/ml, 76% by 12.5 micrograms of cephalothin/ml, and 64% by 12.5 micrograms of cefazolin/ml. With a large inoculum 100% of the isolates were inhibited by 200 micrograms of vancomycin/ml, 40% by 12.5 micrograms of cephalothin/ml, and 12% by 12.5 micrograms of cefazolin/ml. As determined by a tube dilution checkerboard technique for both sizes of inoculum, the combination of vancomycin plus cephalothin was synergistic against methicillin-resistant S. epidermidis in 45 of 50 cases, and the combination of vancomycin plus cefazolin was synergistic in 39 or 50 cases. These data from in vitro studies suggest that these antibiotic combinations should be evaluated clinically in patients with severe infections caused by methicillin-resistant S. epidermidis.

Cefazolin↗
PubMed1979

Susceptibility and synergy studies of methicillin-resistant Staphylococcus epidermidis.

Methicillin-resistant Staphylococcus epidermidis is an important cause of cerebrospinal fluid shunt infections and prosthetic valve endocarditis. Agar dilution minimum inhibitory concentrations were determined for 100 strains of methicillin-resistant S. epidermidis which were isolated from clinical specimens. Vancomycin inhibited all 100 strains at </=3.12 mug/ml, whereas clindamycin inhibited only 46 strains at </=12.5 mug/ml. Methicillin-resistant S. epidermidis strains were resistant to achievable levels of erythromycin, with 90 strains having a minimum inhibitory concentration of >/=3.12 mug/ml. Of the five cephalosporins and one cephamycin tested, cefamandole was the most active in vitro, inhibiting 97 strains at </=25 mug/ml. Antibiotic synergism was examined by a quantitative bacterial time-kill method. Synergism (>/=10(2) kill by the combination over the most effective single antibiotic at 24 h) was demonstrated with vancomycin (1.56 mug/ml) plus cefamandole (6.25 mug/ml) in 14 of 14 strains, vancomycin plus cephalothin (6.25 mug/ml) in 14 of 14 strains, vancomycin plus rifampin (0.008 to 0.012 mug/ml) in 6 of 12 strains, rifampin plus cefamandole in 9 of 12 strains, and rifampin plus cephalothin in 10 of 12 strains. The emergence of populations of bacteria resistant to 0.2 mug of rifampin per ml developed in three of five methicillin-resistant S. epidermidis strains tested. The addition of either vancomycin, cephalothin, or cefamandole to the rifampin prevented the emergence of resistance in these three strains. Clinical trials of synergistic antibiotic combination therapy for serious methicillin-resistant S. epidermidis infections are indicated.

Anti-Bacterial Agents↗
PubMed1979

Clavulanic acid and penicillin treatment of Staphylococcus aureus renal infection in mice.

Clavulanic acid, an inhibitor of beta-lactamase, was used together with penicillin to treat infection caused by a penicillinase-producing Staphylococcus aureus. Clavulanic acid + penicillin administered to mice, prophylactically or in treatment of established infection, reduced morbidity, bacterial counts in the kidneys, and/or mortality; these differences were statistically significant when compared with those obtained by using penicillin or clavulanic acid alone.

Animals↗
PubMed1979

Allergic bronchopulmonary aspergillosis-like syndrome consequent to aspergilloma.

Two patients who represent the first well-documented cases of an allergic bronchopulmonary aspergillosis-like syndrome developing consequent to an aspergilloma are reported. These patients experienced both subjective and objective evidence of improvement after the initiation of corticosteroid therapy. Literature relevant to the combined occurrence of aspergilloma and allergic bronchopulmonary aspergillosis and their immunology is reviewed.

Adult↗
PubMed1978

Agranulocytosis during therapy with orally administered cloxacillin.

Agranulocytosis developed in a patient with staphylococcal osteomyelitis after 35 days of treatment with orally administered cloxacillin. The patient had fever, prostration, pharyngitis, and profound leukopenia, which subsequently abated upon withdrawal of the drug. Cloxacillin should be included in the growing list of drugs capable of producing leukopenia and agranulocytosis.

Administration, Oral↗
PubMed1978

Methicillin-resistant Staphylococcus epidermidis.

Staphylococcus epidermidis is frequently associated with infection of prosthetic heart valves, prosthetic orthopedic devices, and neurosurgical shunts. Penicillinase-resistant semisynthetic penicillins, such as methicillin, have been the therapeutic and prophylactic agents of choice for S epidermidis infection. However, more S epidermidis isolates are now resistant to methicillin and other penicillins. In our laboratory 41% of S epidermidis isolates were resistant to methici-lin. All of the methicillin-susceptible isolates and 82% of the methicillin-resistant isoates were susceptible to cephalothin. Cephalothin should replace methicillin as the prophylactic and therapeutic agent of choice in institutions with a high percentage of methicillin-resistant S epidermidis.

Cephalothin↗
PubMed1978

Prosthetic valve endocarditis.

PVE is increasingly frequent and often lethal. The classic features of infective endocarditis may be absent early in the course of the illess. Therefore, patients with prosthetic heart valves and fever must be considered candidates for this infection until another cause for the fever can be established. Five to six blood cultures will document the persistent bacteremia of PVE in most cases. Treatment consists of parenteral penicillins for sensitive organisms plus valvular re-replacement for intractable heart failure mechanical malfunction of the valve, persistent sepsis, or multiple major emboli. In spite of aggressive therapy, the mortality remains high. Therefore, appropriate prophylaxis is warranted in patients with prosthetic valves who must undergo procedures that might lead to bacteremia.

Anti-Bacterial Agents↗
PubMed1977

Gastroenteritis in children: a two-year review in Manitoba. I. Etiology.

During two years, 1,217 children hospitalized with gastroenteritis at the Children's Centre in Winnipeg, Manitoba, Canada were studied. Bacterial pathogens were present in 25% of these children: enteropathogenic Escherichia coli in 120, Shigella in 139, Salmonella in 24, and multiple pathogens in 18. Rotavirus was detected in 54 (11%) of 472 patients examined. Rotavirus and enteropathogenic E. coli were the most common pathogens in infants, and Shigella was the most common in older children. Bacterial diarrhea occurred more commonly in summer, whereas rotavirus infection occurred more commonly in winter. Among 276 children screened, enterotoxigenic E. coli was found in three, and Aeromonas shigelloides that produced a similar toxin in two others. Enteroinvasive E. coli was not detected in 70 children. Organisms producing toxins "cytotoxic" to HeLa cells were isolated from three of 90 children. Screening for enterotoxigenic or enteroinvasive organisms was not productive of a significant number of pathogens, and, although screening for rotavirus did improve the number of etiologic diagnoses, the etiology of the majority of cases of diarrhea remained unknown.

Age Factors↗
PubMed1977

Resistance to gentamicin: a growing concern.

Gentaminic was introduced in 1969 as a broad-spectrum aminoglycoside effective in vitro against a majority of aerobic gram-negative bacilli. In recent years gentamicin-resistant clinical isolates have become more prevalent. In our laboratory in 1975, 32% of Pseudomonas sp and 44% of indole-negative Proteus sp isolates were resistant to gentamicin. Resistance to tobramycin is also increasing; 24% of Escherichia coli and 28% of indole-negative Proteus sp isolates were found to be tobramycin-resistant. In addition, isolation of previously uncommon gentamicin-resistant species, ie, Proteus rettgeri and other indole-positive Proteus sp, from clinical specimens has increased dramatically in the past five years. This increase in gentamicin and tobramycin-resistant gram-negative bacilli serves as a constant stimulus for the development of new antimicrobial agents.

Drug Resistance, Microbial↗
PubMed1977

In vitro lysis of target cells by rat polymorphonuclear leukocytes isolated from acute pyelonephritic exudates.

Polymorphonuclear (PMN) leukocytes from acute pyelonephritic exudates of rats were examined for cytoxicity against various target cells. Pyelonephritic PMN leukocytes caused lysis in vitro of syngeneic renal epithelial cells in 24 to 48 hr. They also caused lysis of allogeneic and xenogeneic target cells. The susceptibility to PMN-induced cytolysis was different among various target cell lines. Cell lysis proceeded at low ratios of effector to target cells and was not dependent on the addition of antibody or lectins. PMN isolated from peritoneal exudates (starch or endotoxin induced) were also cytoxic for the target cells. Cell-free supernatants from pyelonephritic PMN-target cell mixtures, or pyelonephritic PMN leukocytes cultured alone contained cytolytic substances which were nondialyzable and heat stable Finally, the urine of pyelonephritic rats was cytotoxic. These results suggest that PMN leukocytes and their cytotoxic mediators are directly involved in the pathogenesis of renal injury in pyelonephritis.

Animals↗
PubMed1976

Comparison of thrombophlebitis associated with three cephalosporin antibiotics.

A double-blind study with volunteers was performed to determine the incidence and severity of thrombophlebitis associated with cephalothin, cephapirin, cefamandole, and a water control. Although there were no statistical differences in the incidence of thrombophlebitis, cephalothin resulted in significantly more severe thrombophlebitis compared with the other agents.

Cephalosporins↗
PubMed1976

Bone concentrations of antimicrobial agents after parenteral administration.

Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindamycin were detected in bone with greatest frequency. Cefazolin and gentamicin were each detected in bone specimens from only one of four patients. Neither penicillin G nor cephalothin was present in bone in sufficient quantity to be measurable. These data suggest that a number of factors, in addition to serum concentration, affect concentration of antimicrobial agents in bone. The clinical significance of the relationship between bone concentrations of antibiotics and therapeutic outcome is not certain.

Adult↗
PubMed1976

Influence of cephalosporin antibiotics on blood coagulation and platelet function.

Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics.

Blood Coagulation↗
PubMed1976

In vitro activity of josamycin against aerobic gram-positive cocci and anaerobes.

Josamycin, a new macrolide antibiotic, was compared with ampicillin, erythromycin, and clindamycin in vitro against 25 isolates each of pneumococci, enterococci, Staphylococcus aureus, S. epidermidis, and nonenterococcal hemolytic streptococci and against 25 anaerobes including 10 Bacteroides fragilis. Minimal inhibitory concentration and minimal bactericidal concentration data were obtained for the aerobic organisms, using serial twofold tube dilutions in Mueller-Hinton broth. Minimal inhibitory concentrations were determined for the anaerobes by the agar dilution technique. Josamycin was comparable to erythromycin and clindamycin in activity against the pneumococci, streptococci, and staphylococci and was more active than clindamycin against enterococci. It was somewhat less active than ampicillin against enterococci and S. epidermidis and showed its greatest in vitro activity against anaerobes, being comparable to clindamycin.

Ampicillin↗
PubMed1976

Cellular immunity in pyelonephritis: identification of suppressor cell activity of spleen cells in response to concanavalin A and inhibition of lymphocyte-mediated L cell cytotoxicity.

A population of fast sedimenting spleen cells was identified as the cause of impaired in vitro response of spleen cells to concanavalin A (Con A) in acute pyelonephritis in rats. These fast-sedimenting cells responded to Con A by suppressing the DNA synthetic response of normal spleen cells to Con A. In addition, spleen cells from acute pyelonephritis rats were significantly less able to mediate in vitro cell destruction in xenogeneic aggressor lymphocyte: target L cell mixtures. On the basis of these findings, the hypothesis is proposed that a suppressor cell can protect the pyelonephritic kidney against immunologically mediated tissue damage.

Animals↗
PubMed1976

Defective platelet function following the administration of penicillin compounds.

Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP-induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP.

Adenosine Diphosphate↗