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Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

At least 91 records · Page 5Linked to original sources
PubMed1983

Influence of clindamycin on derepression of beta-lactamases in Enterobacter spp. and Pseudomonas aeruginosa.

Previous studies in this and other laboratories have shown that derepression of beta-lactamases in strains of Enterobacter and Pseudomonas spp. is responsible for the rapid development of resistance to a variety of beta-lactam antibiotics. The purpose of the current study was to evaluate the effects of clindamycin on derepression of beta-lactamases in these two genera. In tests with four strains of each genus, clindamycin diminished derepression in one isolate of each genus and completely prevented derepression in a second Enterobacter isolate (strain 55). Additional tests with strain 55 revealed that other inhibitors of macromolecular synthesis did not completely prevent derepression of beta-lactamase when tested at concentrations that did not inhibit replication. However, clindamycin did not affect synthesis of beta-lactamase that was constitutively produced in a mutant of this strain (55M). It also did not inhibit derepression of beta-galactosidase in either strain 55 or 55M. Clindamycin did not diminish the bactericidal effects of beta-lactam antibiotics against Enterobacter or Pseudomonas spp. However, it enhanced the bactericidal activity of cefamandole against strain 55. These in vitro effects of clindamycin on strain 55 that were related to prevention of derepression of beta-lactamase were confirmed in vivo with an animal model of infection. These results indicate that in some strains, clindamycin can specifically prevent derepression of beta-lactamases without inhibiting growth. Such a selective effect may provide a new approach for the enhancement of the antibacterial activity of certain beta-lactam antibiotics.

Cefamandole↗
PubMed1982

Toxic shock syndrome: an ecologic imbalance within the genital microflora of women?

Epidemiologic data suggested that toxic shock syndrome (TSS) may be caused by an imbalance among the flora of the female genital tract. Since natural defense mechanisms often involve antagonistic interactions between the flora and potential pathogens, the ability of genital lactobacilli to inhibit Staphylococcus aureus was determined in agar overlay assays. Lactobacilli were chosen for study because previous investigations had suggested an important role for this genus in maintenance of health of the female genital tract. Fourteen of 50 strains of lactobacilli and Lactinex inhibited the growth of certain staphylococci, including strains from cases of TSS. The inhibitory activity of some lactobacilli was variable and could be enhanced by exogenously supplied substrates. Growth of one consistently inhibitory lactobacillus was inhibited by Staphylococcus aureus. A model for the etiology of toxic shock syndrome in menstruating women is proposed. The model includes antagonistic interactions between lactobacilli and staphylococci and the influence of tampons on these interactions to favor the staphylococcus.

Ecology↗
PubMed1982

Activity of amikacin against Mycobacteria in vitro and in murine tuberculosis.

Amikacin was found to be a potent inhibitor of clinical isolates of Mycobacterium tuberculosis in vitro. The drug was also active against some, but not all, strains of M. intracellulare, M. kansasii and rapidly growing mycobacteria in concentrations that may be attained clinically. Activity was independent of susceptibility or resistance of the isolates to commonly used antituberculosis agents. Groups of mice were infected intravenously with M. tuberculosis H37Rv and then treated daily with amikacin, streptomycin, isoniazid or kanamycin. One third of the mice in each group were killed 30, 60 and 90 days after infection. Extent of pulmonary disease was recorded and tubercle bacilli were enumerated in lungs. Isoniazid eradicated tubercle bacilli from the lungs within 90 days. The remaining drugs were suppressive. Amikacin was more efficacious than streptomycin or kanamycin given in equivalent or greater dosages. Because of its potent activity in vitro, efficacy in experimental tuberculosis and activity against drug resistant mycobacteria, amikacin merits further study as a potential therapeutic agent for tuberculosis and other mycobacterial infections.

Amikacin↗
PubMed1982

Resistance to cefamandole: a collaborative study of emerging clinical problems.

Cefamandole resistance in five patients was studied. Microorganisms emerged resistant to cefamandole during therapy with the drug in three patients with complicated infections. This resistance was associated with an enhanced production of beta-lactamase and/or with a change in the substrates and the isoelectric focusing patterns of the enzymes. Cross-resistance to other beta-lactam antibiotics developed concurrently in isolates from these patients. Disk diffusion tests did not detect resistance to cefamandole in the pretreatment isolate from the fourth patient; this isolate produced inactivating enzymes, and resistance was detected only in broth dilution tests. In the fifth patient, infection with a cefamandole-resistant Enterobacter developed during postoperative therapy with the drug. Resistance to cefamandole in the isolate from this patient was unstable and was associated with inducible beta-lactamase activity. These examples emphasize the need for close monitoring of patients who are given cefamandole and for thorough in vitro evaluation of isolates from the patients both before and after treatment.

Adult↗
PubMed1982

Enocin: an antibiotic produced by Streptococcus salivarius that may contribute to protection against infections due to group A streptococci.

Clinical studies have indicated that certain constituents of the normal throat flora may play a role in resistance to group A streptococcal infections. Strains of Streptococcus salivarius were among the most active components of this protective flora. The present studies were designed to determine the mechanism responsible for the antagonism of group A streptococci by S. Salivarius. Cell-free filtrates made at the end of the logarithmic growth phase of S. salivarius inhibited the growth of group A streptococci. The only other organisms susceptible to inhibition by these filtrates were those that require exogenous pantothenate, as group A streptococci do. The activity of filtrates was primarily bacteriostatic and could be specifically reversed by pantothenate. Activity was not due to a simple depletion of the vitamin but rather to the presence of a substance that interfered with the utilization of pantothenate. This substance, given the name enocin, was heat labile but was unaffected by proteolytic enzymes. Thus, strains of S. salivarius that appear to enhance the resistance of certain individuals to streptococcal infection may exert their protective effect through in situ production of the antibiotic enocin.

Bacteriocins↗
PubMed1982

Antagonism of carbenicillin and cefamandole by cefoxitin in treatment of experimental infections in mice.

The ability of cefoxitin to antagonize the in vivo efficacy of cefamandole and carbenicillin as predicted by in vitro assays was analyzed in experimental infections in mice. Cefoxitin was administered in a nonprotective dose either at the time of challenge or simultaneously with the protective drug, 1 and 3.5 h postchallenge. In mice infected with Enterobacter cloacae, median 50% protective doses of cefamandole and carbenicillin were markedly increased by cefoxitin, especially when the latter was given at the time of challenge. The antagonistic effect was also associated with increased numbers of challenge bacteria present in animal heart blood within a 6.5-h period after infection. In infections with Pseudomonas aeruginosa, cefoxitin antagonized carbenicillin; however, the effect was less dramatic than that seen with E. cloacae. Antagonism in this model was pronounced with simultaneous administration of antagonizing and protective drugs. The antagonistic effects observed in all in vivo tests were not due to the selection of stable resistance to the protective drugs, but appeared to be due to a reversible induction of beta-lactamases by cefoxitin.

Animals↗
PubMed1982

In vitro antagonism of beta-lactam antibiotics by cefoxitin.

We assessed the extent and mechanisms of antagonism of beta-lactam antibiotics by cefoxitin. In tests with 41 gram-negative isolates, cefoxitin antagonized cephalothin, cefamandole, cefsulodin, cefotaxime, moxalactam, ampicillin, carbenicillin, piperacillin, mezlocillin, and azlocillin, but not cephalexin, mecillinam, or N-formimidoyl thienamycin. The extent of antagonism varied with the beta-lactam and genus studied. However, antagonism occurred most often with strains possessing inducible cephalosporinases. Antagonism of cephalothin and cefamandole correlated closely with the induction of beta-lactamases capable of inactivating these drugs. Although antagonism of the remaining drugs occurred more often with strains possessing inducible beta-lactamases, these enzymes did not inactivate the drugs. Morphological studies revealed that cefoxitin inhibited filamentation and lysis produced by various beta-lactam drugs. Results of this investigation suggest that cefoxitin antagonizes beta-lactams via (i) induction of drug-inactivating beta-lactamases, and (ii) the induction of beta-lactamases that cannot inactivate the drug but serve as barriers against access to target proteins. This barrier appears most efficient for drugs that bind to penicillin-binding proteins 1 and 3.

Anti-Bacterial Agents↗
PubMed1982

Development and evaluation of a biochemical scheme for identification of endocervical lactobacilli.

A biochemical scheme for the species identification of endocervical lactobacilli was developed and evaluated with 10 isolates obtained from the American Type Culture Collection (ATCC) and 106 endocervical isolates obtained from women reporting to a local venereal disease clinic and a local hospital clinic. The scheme consisted of two stages. Stage I included six tests and was tested and modified with results obtained with ATCC strains. From the modified stage I, stage II was developed. Tests to be performed in this stage were determined from expected characteristics of lactobacilli. Stage II was also tested with the ATCC strains. Of the 106 endocervical isolates, 78 (74%) were identified with the two-stage scheme as developed with the ATCC strains. Unexpected results were obtained in one or both stages with the other 28 isolates. For 10 isolates, the final species identified were not previously expected to be recovered. A "best-fit" method was used to determine the most likely identification of the remaining 18 isolates. In a few instances, the use of a third stage was necessary to reach an identification. The final identification scheme, although complicated in appearance, generated a species identification with a total of 12 tests with a range of 7 to 10 tests per isolate.

Cervix Uteri↗
PubMed1981

In vitro studies with Win 42122-2: comparison with gentamicin, netilmicin, and amikacin.

The in vitro activity of Win 42122-2 against gram-negative clinical isolates was compared in serial twofold broth dilution tests with gentamicin, netilmicin, and amikacin. Against 173 gentamicin-susceptible Enterobacteriaceae, the activity of Win 42122-2 was generally twofold less than those of gentamicin or netilmicin and similar to that of amikacin. Against 60 gentamicin-susceptible nonfermentative gram-negative bacilli, including P. aeruginosa, the activity of Win 42122-2 was four- to eightfold less than that of gentamicin or netilmicin and two- to fourfold less than that of amikacin. Minimal bacterial concentrations for Win 42122-2 were usually similar to minimal inhibitory concentrations. Win 42122-2 was not highly active against gentamicin-resistant bacteria. Win 42122-2 was as active as gentamicin against Mycobacterium tuberculosis but was less active than gentamicin or amikacin against atypical mycobacteria. Win 42122-2 interacted synergistically with penicillin G against enterococci, including strains highly resistant to streptomycin.

Amikacin↗
PubMed1980

Antagonism of cefamandole by cefoxitin in routine disk susceptibility tests.

Cefoxitin was found to antagonize cefamandole in standardized disk diffusion susceptibility tests. This antagonism increased as the distance between the two disks decreased, and was most frequently observed in tests with cephalothin-resistant Enterobacteriaceae. It occurred in tests with 68 of 98 (69%) cephalothin-resistant isolates, one of six (17%) cephalothin-intermediate isolates, and one of 40 (3%) cephalothin-susceptible isolates. Clinical laboratories that use both disks in routine susceptibility tests should be aware of this anatagonism and should ensure that the disks are not placed in proximity to each other.

Cefamandole↗
PubMed1979

In vitro activity of furazlocillin (Bay k 4999) compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics.

The activity of furazlocillin (Bay k 4999) was compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics against a number of gram-positive and gram-negative organisms. These new expanded-spectrum penicillins were less active than penicillin G against most gram-positive organisms. Furazlocillin, mezlocillin, and piperacillin showed activity comparable to ampicillin and penicillin G against Haemophilus influenzae and penicillin-susceptible neisseriae, respectively. None of the drugs tested was effective against penicillin-resistant gonococci. The activity of furazlocillin was greater than that of mezlocillin, piperacillin, ampicillin, or carbenicillin against many Enterobacteriaceae. However, certain beta-lactam-resistant strains among these organisms were not highly susceptible to any of the three new penicillins. Furazlocillin was less active than piperacillin against Pseudomonas aeruginosa but was more active than carbenicillin or mezlocillin. Inoculum effects and discrepancies between minimal inhibitory concentrations and minimal bactericidal concentrations were observed with furazlocillin, mezlocillin, and piperacillin against several genera. The kinetics of bacterial killing by the new penicillins were often slow and incomplete over 24 h, especially in tests with Enterobacter and P. aeruginosa. Synergy was demonstrated between furazlocillin and aminoglycosides against a variety of gram-negative bacilli and Streptococcus faecalis.

Aminoglycosides↗
PubMed1979

Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases.

Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain Enterobacteriaceae that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147 Enterobacteriaceae for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of Enterobacter, indole-positive Proteus, and Serratia. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.

Cefamandole↗