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Biomedical subjects

C C Sanders

Publications and source records attributed to C C Sanders.

At least 109 records · Page 6Linked to original sources
PubMed1987

Selective ceftazidime resistance in Escherichia coli: association with changes in outer membrane protein.

A strain of Escherichia coli (MG/32) was recovered from the blood of a patient who had received ceftazidime for eight weeks. The isolate was resistant to ceftazidime but susceptible to other third-generation cephalosporins. Alterations in outer membrane proteins were implicated in this selective ceftazidime resistance. As ceftazidime susceptibility was regained, the quantity of outer membrane proteins of 37,000 and 39,000 molecular weight increased. Although the isolate possessed a TEM-1 beta-lactamase, this enzyme was not involved in the selective resistance to ceftazidime; it did not disappear on reacquisition of ceftazidime susceptibility and did not hydrolyze the drug. Potassium clavulanate enhanced the activity of ceftazidime against E. coli strain MG/32, but this enhancement was due to a direct effect on outer membrane proteins and not to beta-lactamase inhibition.

Anti-Bacterial Agents↗
PubMed1987

Leakage of beta-lactamase: a second mechanism for antibiotic potentiation by amdinocillin.

Discrepancies were observed between results of different beta-lactamase induction tests with amdinocillin, which appeared to be a strong inducer in whole-cell assays but a weak inducer in assays with cell-free sonic extracts. Results of a nitrocephin-disk test with constitutive beta-lactamase producers indicated that the positive results obtained in whole-cell assays were due to drug-produced leakage of enzyme from the cell and not to induction. Imipenem was also found to cause leakage of beta-lactamase from a similar number of constitutive enzyme producers, while cefoxitin was much less likely to cause leakage. A split-dose regimen was employed to treat mice infected with a strain of Enterobacter cloacae which appeared to leak enzyme on exposure to amdinocillin. Results indicated that prior treatment with amdinocillin significantly enhanced (P less than 0.025) the efficacy of azlocillin, an enzyme-labile drug, but did not affect the efficacy of cefotaxime, a relatively enzyme-stable drug. Conversely, prior treatment with amdinocillin did not potentiate the efficacy of either azlocillin or cefotaxime in the treatment of mice infected with an Escherichia coli strain that was highly susceptible to all three drugs. Thus, it appears that amdinocillin may potentiate the activity of other beta-lactam drugs not only by binding to a complementary penicillin-binding protein but also by causing leakage of beta-lactamase from the cell. This effect may be related to its ability to bind to penicillin-binding protein 2 and subsequently produce changes in outer membrane permeability.

Amdinocillin↗
PubMed1986

Type I beta-lactamases of gram-negative bacteria: interactions with beta-lactam antibiotics.

The interaction of type I beta-lactamases with diverse beta-lactam compounds representing cephalosporins, cephamycins, penicillins, penams, penems, carbapenems, monobactams, and clavams was examined by using various Enterobacteriaceae and Pseudomonas aeruginosa as sources of the enzymes. The ability of a given drug to reversibly induce beta-lactamase was unrelated to its ability to select mutants stably derepressed for beta-lactamase production. Imipenem was one of the most-potent enzyme inducers, yet it did not select derepressed mutants. Many of the newer cephalosporins were poor enzyme inducers but readily selected derepressed mutants. Resistance to hydrolysis did not predict a drug's inhibitory activity against derepressed mutants. The activity of the penems, penams, and carbapenems was least affected by derepression of beta-lactamase, whereas the activity of anionic cephalosporins and aztreonam was most affected.

Anti-Bacterial Agents↗
PubMed1986

Randomised comparison of ceftriaxone and cefamandole therapy in lower respiratory tract infections in an elderly population.

Patients with pneumonia or bronchitis were randomized to receive ceftriaxone or cefamandole. A total of 30 of 38 patients were evaluable, 16 in the ceftriaxone group (average age 66.3 years) and 14 in the cefamandole group (average age 69.4 years). All but one had underlying diseases. Patients usually received 1 g of ceftriaxone intravenously every 12 h (mean duration 8.7 days) or 1.5 g of cefamandole intravenously every 6 h (mean duration 8.2 days). Adverse experiences attributable to the drugs were confined to one episode of discomfort at the infusion site in each group. Bacteriological results with ceftriaxone were 83% cured, 11% superinfected after eradication of pretherapy isolate, and 6% failed. Bacteriological results with cefamandole were 76% cured, 24% failed. Clinical results with ceftriaxone were 38% cured, 56% improved, 6% failed. Clinical results with cefamandole were 57% cured, 21% improved, 21% failed. Emergence of a resistant Serratia marcescens was seen in a ceftriaxone-treated patient. Disc diffusion susceptibility testing identified six of the seven pretherapy nonfastidious Gram-negative isolates as susceptible; however, two of the six could not be eradicated with the assigned drug and another two were eradicated with ensuing super-infection with susceptible isolates of Pseudomonas aeruginosa. In contrast, MBCs were an accurate guide to clinical outcome with nonfastidious Gram-negative bacilli.

Adult↗
PubMed1986

Evidence for multiple forms of type I chromosomal beta-lactamase in Pseudomonas aeruginosa.

The multiple stages of derepression of the type I chromosomal beta-lactamase in Pseudomonas aeruginosa were examined. Mutants partially and fully derepressed for beta-lactamase were selected from a wild-type clinical isolate. An analysis of the beta-lactamase produced by these mutants and the induced wild type revealed significant differences in the products of derepression at each stage. Beta-lactamase produced by the fully derepressed mutant showed a lower affinity (Km, 0.113 mM) for cephalothin than that produced by the partially derepressed mutant (Km, 0.049 mM). However, due to a very large Vmax, the former possessed a much greater hydrolytic efficiency. Differences in substrate profile were also noted. Only beta-lactamase from the fully derepressed mutant hydrolyzed cefamandole, cefoperazone, and cefonicid. The partially derepressed mutant possessed a single beta-lactamase band with a pI of 8.4. The fully derepressed mutant possessed this band and an additional major band with a pI of 7.5. Induction of the wild type with cefoxitin produced both bands. The changes in physiologic parameters of the enzymes produced in the different stages of derepression suggest a complex system for beta-lactamase expression in P. aeruginosa. This may involve at least two distinct structural regions, each of which is under control of the same repressor.

Chromosomes, Bacterial↗
PubMed1986

Characterization of beta-lactamases in situ on polyacrylamide gels.

An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteria.

Clavulanic Acids↗
PubMed1985

Microbial resistance to newer generation beta-lactam antibiotics: clinical and laboratory implications.

Certain nonfastidious, gram-negative bacilli possess the ability to rapidly develop resistance to many of the newer "enzyme stable" beta-lactam antibiotics. This finding poses many clinical problems including emergence of resistance during therapy with the drugs. Therapeutic alternatives for patients are severely limited when this problem occurs because multiple drug resistance may arise simultaneously. To date, two mechanisms have been found to be responsible for this resistance. The first, which produces multiple beta-lactam resistance, is the induction of chromosomal beta-lactamases that mediate resistance to nonsubstrate drugs by the creation of a nonhydrolytic barrier that blocks access to target proteins within the cell. The second mechanism, which produces beta-lactam/aminoglycoside resistance, involves a change in outer membrane permeability. Outbreaks of nosocomial infections with these multiple drug-resistant organisms and spread of the strains throughout the hospital are already being seen. Control of these problems can only be achieved through the judicious and restricted use of these new antibiotics.

Aminoglycosides↗
PubMed1985

Role of beta-lactamases and outer membrane proteins in multiple beta-lactam resistance of Enterobacter cloacae.

The chromosomal beta-lactamase and outer membrane proteins of Enterobacter cloacae were examined to determine their relative contributions to multiple antibiotic resistance in this organism. Mutants altered in beta-lactamase expression, whether derived in the laboratory or recovered from patients treated with one of the new beta-lactam antibiotics, were found to have no detectable alterations in outer membrane proteins. Derepression of beta-lactamase in these mutants was associated with high-level resistance to multiple beta-lactam antibiotics, while loss of inducible beta-lactamase (i.e., production of basal enzyme levels only) was associated with acquisition of susceptibility to many beta-lactam antibiotics, including cephalothin. In contrast, alteration in outer membrane proteins was associated with only moderate-level resistance to beta-lactam antibiotics. However, this included resistance to such drugs as amdinocillin and Sch 34343, which were unaffected by derepression of beta-lactamase. Resistance to chloramphenicol and tetracycline also accompanied changes in outer membrane proteins. Although the outer membrane proteins of various strains of E. cloacae were similar, there did appear to be some major strain-to-strain variations. Thus, it appears that alterations in both beta-lactamase and outer membrane proteins can affect the susceptibility of E. cloacae to many antibiotics. However, alterations in beta-lactamase alone are sufficient to produce high-level multiple beta-lactam resistance in this organism.

Anti-Bacterial Agents↗
PubMed1985

Randomized, double-blind comparison of ceftazidime and moxalactam in complicated urinary tract infections.

Sixty-seven patients with complicated urinary tract infections were randomized in double-blind fashion to ceftazidime or moxalactam (MOX). A total of 54 patients were evaluable, 27 in each group. Patients received 500 mg of antibiotic intravenously every 12 h, except for those with Pseudomonas aeruginosa randomized to MOX who received 2 g intravenously every 12 h. Toxic effects with ceftazidime were experienced by the following number of patients: pain with infusion, one; posttherapy diarrhea, one; liver function test elevations, two; and neutropenia, one. Toxic effects with MOX were experienced by the following number of patients: liver function test elevations, two; and prolonged prothrombin time, one. All resolved. At 1 week posttherapy, bacteriologic results were 74% cured, 11% relapsed, 15% reinfection with ceftazidime and 52% cured, 33% relapsed, and 19% reinfection with MOX. Ceftazidime was effective for infections caused by MOX-resistant P. aeruginosa. P. aeruginosa resistant to MOX and other beta-lactams was isolated from one patient after MOX therapy. Enterococcal reinfection was common in both groups.

Adult↗
PubMed1984

Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes.

The ability of three quinolones, two beta-lactams, and one aminoglycoside to select resistant mutants was examined in tests with 30 isolates of commonly encountered nosocomial pathogens. Ciprofloxacin and norfloxacin, two new quinolone derivatives, were no more likely to select resistant mutants than amikacin, whereas nalidixic acid, an older quinolone derivative, was the most likely of the six drugs examined to select resistant mutants. Mutational frequencies of 10(-7) to 10(-8) were observed in most instances. In general, the mutants were 8 to 16 times less susceptible to the drug used for selection. Although most quinolone-selected mutants were cross-resistant only to other drugs within this class, certain mutants of Klebsiella pneumoniae selected by nalidixic acid, ciprofloxacin, or norfloxacin were also less susceptible to beta-lactam antibiotics. This unusual pattern of multiple drug resistance was associated with changes in outer membrane proteins of the organism. Multiple drug resistance was also observed in beta-lactam-selected mutants of Enterobacter cloacae and Pseudomonas aeruginosa (beta-lactams), amikacin-selected mutants of Providencia stuartii and P. aeruginosa (aminoglycosides), and beta-lactam- or amikacin-selected mutants of Serratia marcescens (beta-lactams plus aminoglycosides). These results underscore the need to examine carefully the frequency with which resistance to any new antibiotic develops, as well as the patterns of multiple drug resistance which may occur simultaneously.

Amikacin↗
PubMed1983

Vitamin B6-dependent Streptococcus mimicking fungi in a patient with endocarditis.

A patient was referred to our hospital with a tentative diagnosis of fungal endocarditis based upon clinical symptoms, suggestive travel history, and microscopic visualization in blood cultures of gram-negative bulbous filaments that appeared to be fungal elements. Subcultures of the blood culture bottles were unsuccessful on all media with the exception of blood agar plates, which had been cross-streaked with Staphylococcus aureus. These plates grew vitamin B6-dependent streptococci. This nutritionally variant organism was determined by biochemical tests to be Streptococcus mitis (mitior). It had a penicillin MIC and MBC of 0.015 micrograms/mL and 0.03 micrograms/mL, respectively and streptomycin MIC and MBC of 0.78 micrograms/mL and 1.56 micrograms/mL, respectively. The patient was treated with these two agents and recovered. We stress the importance of suspecting vitamin B6-dependent streptococci, even when gram stains may suggest presence of other microorganisms.

Diagnosis, Differential↗