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Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

120 records · Page 7Linked to original sources
PubMed1974

Microbiological characterization of everninomicins B and D.

Everninomicins B and D are components of a complex of antibiotic substances produced by Micromonospora. Both were shown to be highly active inhibitors of growth of all gram-positive bacteria, Neisseria, and Bacteroides studied in vitro. Potency of activity appeared to be greater than that of chloramphenicol, but less than that of penicillin G, when assayed against strains susceptible to each of the drugs. The everninomicins were bacteriostatic for all strains tested, except group A streptococci. No facultatively anaerobic gram-negative bacilli were susceptible. Resistant mutants were selected with difficulty from susceptible staphylococci in the laboratory, and these demonstrated no cross-resistance to available antimicrobial agents. Most variations in media, growth conditions, or procedure of assay had little or no effect on antimicrobial activity. Only addition of serum or increase in inoculum size reduced antibacterial activity. Significant differences in activity of the two components were encountered infrequently; the B component was four- to sixfold more active against gonococci and group A streptococci, whereas the D component was fourfold more active against enterococci. Because of the high degree of in vitro activity and lack of resistance among susceptible genera of bacteria, the everninomicins clearly merit further careful study as potential therapeutic agents.

Aminoglycosides↗
PubMedDate not supplied

Efficacy, safety, and potential economic benefits of oral ciprofloxacin in the treatment of infections.

Ciprofloxacin is a new 4-quinolone carboxylic acid derivative with a broad spectrum of activity against gram-positive and gram-negative bacteria, chlamydiae, rickettsiae, and related organisms. The drug has been administered orally to 2,018 patients, primarily in the United States. In open trials oral ciprofloxacin has been shown to constitute effective therapy for osteomyelitis, gonorrhea, and infections of the urinary and gastrointestinal tracts, respiratory tree, and skin and soft tissues. In controlled comparative trials, most of which were doubly blinded, oral ciprofloxacin was equal in terms of safety and therapeutically equal or superior to oral trimethoprim-sulfamethoxazole in urinary and gastrointestinal infections, to oral ampicillin in respiratory infections, and to parenteral cefotaxime in skin and soft tissue disease. Adverse reactions were infrequent and generally mild. The emergence of resistance was encountered rarely; the organisms implicated were usually those for which initial minimal inhibitory concentrations were high, albeit in the sensitive range (such as Pseudomonas aeruginosa). Ciprofloxacin potentiates the toxicity of theophylline. Concurrent administration of antacids may diminish gastrointestinal absorption of the drug.

Bacterial Infections↗
PubMedDate not supplied

Heterogeneity in ampR-ampC gene interaction in Enterobacter cloacae.

The ampR gene and its regulation of AmpC beta-lactamase synthesis were investigated for Enterobacter cloacae 1194E, a wild-type strain producing a group A (pI 8.7) enzyme. Expression of the cloned E. cloacae 1194E ampR-ampC region was examined initially in Escherichia coli HB101. However, transformants showed only constitutive beta-lactamase expression. For study of enzyme expression in a more closely related host, the cloned E. cloacae 1194E ampR-ampC region was transformed into E. cloacae 55, a wild-type strain producing a group B (pI 7.8) enzyme. Results indicated a functional E. cloacae 1194E ampR gene that could not be transcomplemented by E. cloacae 55. A comparative analysis of ampR nucleotide and amino acid-sequence data from E. cloacae 1194E and E. cloacae MHN1 revealed related but divergent genes. Thermal induction studies of AmpC beta-lactamase also indicated a difference between E. cloacae 1194E and E. cloacae 55 in ampR-ampC interaction. Thus, it appears that, in at least some strains of Enterobacter, significant intraspecies divergence of ampR has occurred. This heterogeneity in ampR would not have been detected with beta-lactamase expression studies conducted exclusively in E. coli.

Amino Acid Sequence↗
PubMedDate not supplied

Inducible beta-lactamases: clinical and epidemiologic implications for use of newer cephalosporins.

The emergence of resistance to multiple beta-lactam antibiotics is a major problem in patients infected with organisms that characteristically produce inducible beta-lactamases--e.g., species of Pseudomonas, Enterobacter, Serratia, Citrobacter, indole-positive Proteus, and Providencia. Resistance has emerged in 14%-56% of patients infected with these organisms and treated with one of the newer cephalosporins. The emergence of resistance has been associated with clinical failure or relapse in 25%-75% of these patients. Combination therapy appears to have little impact on rates of resistance or its clinical consequences. Multiply resistant organisms have spread widely in some hospitals, and this trend has been correlated closely with the extent of use of the newer cephalosporins. The magnitude of the problem is frequently underestimated because many properly performed susceptibility tests fail to detect resistance when it is actually present and because some methods used to calculate rates minimize the impact of the emergence of resistance among organisms with inducible beta-lactamases.

Adolescent↗
PubMedDate not supplied

Sisomicin: a review of eight years' experience.

Sisomicin is a new broad-spectrum aminoglycoside most closely related structurally to gentamicin C1a. In vitro and in experimental infections, sisomicin has been found to be more potent than or nearly as potent as the most active of the other available aminoglycosides. Although susceptible to many (but not all) aminoglycoside-inactivating enzymes, sisomicin is active against many microorganisms that are resistant to other aminoglycosides by nonenzymatic mechanisms. Sisomicin has been shown to interact synergistically with various beta-lactam antibiotics against enterococci, staphylocicci, Enterobacteriaceae, and nonfermentative gram-negative bacilli. The pharmacokinetics and toxicity of sisomicin in humans appear to be similar to those of gentamicin, despite earlier reports of greater acute toxicity in animals. Sisomicin has been shown to be effective for treatment of severe infections in humans, including some infections caused by gentamicin-resistant bacteria.

Animals↗
PubMedDate not supplied

Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future.

A number of beta-lactam antibiotics that are relatively resistant to hydrolysis by beta-lactamases have been developed. This characteristic has expanded the antibacterial spectrum of the drugs beyond that of their progenitors. However, it also appears responsible for several problems that have been observed with the new drugs, including the development of microbial cross-resistance to multiple beta-lactam antibiotics and occasionally to the aminoglycosides. Strains most often involved are Enterobacter, Serratia, and Pseudomonas-genera that characteristically possess inducible beta-lactamases. Derepression of these enzymes is one mechanism shown to be responsible for the development of resistance to multiple beta-lactam antibiotics. Since in most instances the drugs are not susceptible to hydrolysis by these enzymes, resistance is produced by a nonhydrolytic barrier mechanism; i.e., the beta-lactamases bind the drugs, thus preventing their access to target proteins. Alterations in permeability and in penicillin-binding proteins are other possible mechanisms by which resistance may develop; however, these have not been investigated extensively. In addition to the problem of emergence of resistance, potential problems include the impact of multiply beta-lactam-resistant strains as nosocomial pathogens and antagonism between beta-lactam antibiotics used in combination. Only through a careful assessment of the relative advantages and disadvantages of these new beta-lactam antibiotics can their appropriate place in chemotherapy and chemoprophylaxis be identified.

Anti-Bacterial Agents↗