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Biomedical subjects

C C Sanders

Publications and source records attributed to C C Sanders.

At least 91 records · Page 5Linked to original sources
PubMed1990

Diverse potential of beta-lactamase inhibitors to induce class I enzymes.

The ability of various beta-lactamase inhibitors to induce class I beta-lactamases was assessed. Clavulanate was the most active compound, inducing Morganella morganii, Aeromonas caviae, and Enterobacter aerogenes over a broad concentration range and Citrobacter freundii, Pseudomonas aeruginosa, and Serratia marcescens at high concentrations. Disk approximation tests paralleled these results, with clavulanate, but not sulbactam or tazobactam, antagonizing the activity of several beta-lactams against these organisms.

Anti-Bacterial Agents↗
PubMed1990

Purification and characterization of inducible beta-lactamases in Aeromonas spp.

beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI 8.0 and a second band at pI 7.0 for A. hydrophila. Likewise, A. sobria produced two bands, one at pI 8.4 and the other at pI 7.0. Two enzymes from each species were separated by flatbed electrofocusing gel and purified to homogeneity. The molecular weight of the pI 7.0 enzyme (A1) from both species was estimated to be 42,500, whereas the pI 8.0 (A2h) and 8.4 (A2s) enzymes of A. hydrophila and A. sobria had molecular weights of 31,500 and 35,000, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The relative Vmax values for cephalothin, penicillin, and imipenem for these enzymes indicated that A1 was primarily a cephalosporinase while A2h and A2s were penicillinases highly active against carbapenems. A1 was susceptible to inhibition by cloxacillin, while the A2 enzymes were inhibited by clavulanic acid and EDTA and required zinc for activity. Thus, there appear to be two distinct inducible beta-lactamases in A. hydrophila and A. sobria that play an important role in the beta-lactam resistance of these species.

Aeromonas↗
PubMed1990

Beta-lactamase production in members of the family Enterobacteriaceae and resistance to beta-lactam-enzyme inhibitor combinations.

Recent reports that members of the family Enterobacteriaceae that produce high levels of certain beta-lactamases are often resistant to ticarcillin-clavulanate prompted this study to assess the relationship between type and amount of enzyme produced and susceptibility to ticarcillin-clavulanate, piperacillin-tazobactam, and cefoperazone-sulbactam. Agar dilution MICs were determined by using 73 strains of Enterobacteriaceae that produced a single beta-lactamase that had been characterized and quantified and a beta-lactamase-negative control strain of Escherichia coli. For E. coli and Klebsiella pneumoniae, MICs of each combination increased as levels of TEM, SHV-1, or class IV enzymes increased. However, the percentage of strains that were resistant was highest for ticarcillin-clavulanate (32%), with only 18 and 6% resistant to piperacillin-tazobactam and cefoperazone-sulbactam, respectively. Strains producing PSE-1, regardless of level, were resistant or moderately susceptible to ticarcillin-clavulanate but were susceptible to piperacillin-tazobactam and cefoperazone-sulbactam. HMS-1 and OHIO-1 beta-lactamases were associated with resistance to ticarcillin-clavulanate and piperacillin-tazobactam, respectively. High levels of class IV enzymes in Klebsiella oxytoca were associated with resistance to all three combinations. These results indicate that the level and type of beta-lactamase produced by members of the family Enterobacteriaceae are important determinants of susceptibility to beta-lactam-inhibitor combinations, especially ticarcillin-clavulanate.

Anti-Bacterial Agents↗
PubMed1989

Meropenem: activity against resistant gram-negative bacteria and interactions with beta-lactamases.

The activity of meropenem, a new carbapenem, was determined against 82 Gram-negative bacteria in agar dilution tests. Many of these isolates were resistant to one or more beta-lactam antibiotics and the mechanisms responsible for the resistance had been characterized. The production of beta-lactamases had little influence on susceptibility to either meropenem or imipenem except in tests with Aeromonas hydrophila and Pseudomonas (Xanthomonas) maltophilia. These species produced metalloenzymes capable of hydrolyzing the carbapenems, and strains expressing high levels of these enzymes were resistant to both meropenem and imipenem. Clinical isolates of P. aeruginosa that had developed resistance to imipenem during therapy with the drug were two- to 32-fold less susceptible to meropenem than the corresponding pretreatment isolates. Alterations in outer membrane proteins were associated with this change in susceptibility to the carbapenems. Meropenem was a less potent inducer of Class I beta-lactamases than imipenem but was still a better inducer than ceftazidime or piperacillin. Overall, meropenem showed excellent activity against bacteria producing a variety of beta-lactamases, but cross-resistance between meropenem and imipenem due to enzymatic and non-enzymatic mechanisms did occur.

Carbapenems↗
PubMed1989

ampG is essential for high-level expression of AmpC beta-lactamase in Enterobacter cloacae.

Mutants of Enterobacter cloacae 55 were studied to delineate more completely the genetics of inducible expression of AmpC beta-lactamase. E. cloacae 55M-L, derived by mutagenesis from a mutant with high-level cefotaxime resistance (MIC, greater than 64 micrograms/ml), E. cloacae 55M, demonstrated a novel phenotype by producing only low levels of AmpC constitutively. Neither the parental phenotype of E. cloacae 55M nor the wild-type phenotype of E. cloacae 55 could be restored in E. cloacae 55M-L by the introduction of functional ampR, ampC, or ampD genes. Cloning each of these genes from E. cloacae 55M-L confirmed the same genotype for this mutant as for its parental strain. Mutation of E. cloacae 55M-L to the E. cloacae 55M phenotype was found to occur spontaneously at a frequency of 10(-8). All such revertants demonstrated an inducible wild-type phenotype after introduction of a functional ampD. These results suggested that the E. cloacae 55M-L phenotype was due to a mutation in an as yet unrecognized gene, designated ampG. Verification of this gene was obtained by the restoration of the E. cloacae 55M phenotype in E. cloacae 55M-L by introduction of a cloned 2.9-kilobase BamHI fragment from the E. cloacae 55 chromosome. Transformation of both ampG and ampD into E. cloacae 55M-L reconstituted the inducible wild-type phenotype. These results indicate that ampG is required for the activation of ampC by AmpR. Without ampG, neither induction nor high-level expression of AmpC is possible. It is likely that the ampG gene product and AmpD together modulate the ability of AmpR to activate ampC expression.

Ampicillin↗
PubMed1989

beta-Lactamase stability and in vitro activity of oral cephalosporins against strains possessing well-characterized mechanisms of resistance.

The in vitro activity of four oral cephalosporins was assessed in dilution tests with 50 isolates of the family Enterobacteriaceae possessing well-characterized mechanisms of resistance to beta-lactam antibiotics. The interaction of the drugs with a broad array of beta-lactamases was also determined in spectrophotometric assays and tests for enzyme induction. Overall, the percentages of strains susceptible to each of the study drugs were 82% for cefixime, 62% for cefuroxime, 58% for cephalexin, and 44% for cefaclor. The poor activity of the older cephalosporins was due to a high degree of susceptibility to hydrolysis by both plasmid-mediated and chromosomally mediated beta-lactamases. For cefaclor, higher MICs were associated with higher levels of plasmid-mediated beta-lactamases in the strains. Resistance to cefuroxime was seen primarily among strains expressing high levels of class I or IV beta-lactamase. Resistance to cefixime was seen only among strains expressing high levels of class I enzymes. Neither cefixime nor cefuroxime was a strong inducer of class I beta-lactamases, although enzyme induction did appear to play a role in cefuroxime resistance in a strain of Serratia marcescens. The consistently greater activity of cefixime over cefuroxime was found not to be due to greater drug permeation into the cell. Rather, it appeared to result from the high affinity of the drug for target enzymes.

Anti-Bacterial Agents↗
PubMed1988

Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers.

The ability of a single oral 750-mg dose of ciprofloxacin to eradicate Neisseria meningitidis from persistent nasopharyngeal carriers was prospectively evaluated in a placebo-controlled, randomized, double-blinded study. Cultures of specimens taken from all 23 ciprofloxacin-dosed subjects 1 day postdose were negative; cultures from 96% of these subjects were negative at 7 and 21 days postdose, including a specimen from a subject colonized with a minocycline-resistant strain. Of 22 placebo recipients, 20 (91%) remained culture positive. Single-dose ciprofloxacin appears efficacious for meningococcal prophylaxis.

Carrier State↗
PubMed1988

Heterogeneity of class I beta-lactamase expression in clinical isolates of Pseudomonas aeruginosa.

Expression of chromosomal beta-lactamase was examined in 85 clinical isolates of Pseudomonas aeruginosa. beta-Lactamase assays with and without cefoxitin induction revealed four phenotypes of enzyme expression: low basal, inducible; moderate basal, inducible; moderate basal, constitutive; and high basal, constitutive. The isoelectric points of the major beta-lactamase bands were 9.4, 9.2, and 8.4. These results indicate that there is a limited heterogeneity in expression of chromosomal beta-lactamase of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1988

Aminoglycoside resistance among Pseudomonas aeruginosa isolates with an unusual disk diffusion antibiogram.

In recent years, a number of clinical microbiology laboratories have isolated Pseudomonas aeruginosa with the unusual aminoglycoside disk diffusion result of resistance to both amikacin and gentamicin but susceptibility to tobramycin (ArGrTs). A total of 39 isolates of P. aeruginosa reported to have this resistance pattern were retested by the standard National Committee for Clinical Laboratory Standards disk diffusion procedure; 30 strains (77%) were confirmed to be ArGrTs. These 30 isolates were further examined for susceptibility to those aminoglycosides by agar dilution and broth micro- and macrodilution methods. Only 27, 27, and 23% of the isolates appeared to be ArGrTs by agar, broth microdilution, and broth macrodilution testing, respectively. Most of the remaining isolates were resistant to all three aminoglycosides when tested by broth dilution and resistant only to gentamicin when tested by agar dilution. The percentages of strains resistant to any particular aminoglycoside by agar dilution, broth microdilution, and broth macrodilution, respectively, were 43, 80, and 70 for amikacin, 97, 93, and 100 for gentamicin, 100, 100, and 100 for netilmicin, 30, 87, and 93 for sisomicin, and 13, 57, and 50 for tobramycin. These results indicate that strains showing the unusual aminoglycoside antibiogram are less susceptible to aminoglycosides in general and should probably be considered borderline resistant to all aminoglycosides. The efficacy of aminoglycosides in the treatment of infections produced by these strains is unknown.

Amikacin↗
PubMed1988

Beta-lactam resistance in Aeromonas spp. caused by inducible beta-lactamases active against penicillins, cephalosporins, and carbapenems.

Use of cefoperazone in a patient with Aeromonas caviae in the respiratory tract selected a mutant that constitutively produced beta-lactamase. This mutant, in contrast to its parental strain with an inducible beta-lactamase, showed enhanced resistance to newer cephalosporins and aztreonam. This observation suggested that species of Aeromonas, like those of other genera with inducible beta-lactamases, may pose therapeutic problems associated with the rapid development of multiple beta-lactam resistance. Thus, a study was designed to identify the beta-lactamases in 12 strains representing four species of Aeromonas and assess their role in drug resistance. Eleven strains possessed inducible beta-lactamases. One strain showed no detectable activity. An analysis of substrate and inhibitor profiles, isoelectric points, and beta-lactam susceptibility patterns revealed the presence of at least four distinguishable inducible beta-lactamases. These enzymes were involved in the resistance of strains within the genus to penicillins, cephalosporins, aztreonam, and imipenem but not cefoxitin. Unlike most other organisms with inducible beta-lactamases, all four strains of A. caviae, one of four strains of A. sobria, and one of three strains of A. hydrophila possessed two distinct inducible beta-lactamases. Furthermore, substrate and inhibitor profiles revealed that many of these Aeromonas beta-lactamases were distinct from inducible enzymes that have been characterized in other genera of gram-negative bacteria.

Aeromonas↗
PubMed1988

Resistance to ticarcillin-potassium clavulanate among clinical isolates of the family Enterobacteriaceae: role of PSE-1 beta-lactamase and high levels of TEM-1 and SHV-1 and problems with false susceptibility in disk diffusion tests.

Thirty-four clinical isolates of the family Enterobacteriaceae from the University of Texas M. D. Anderson Cancer Center appeared resistant to ticarcillin-potassium clavulanate in agar dilution and broth macrodilution tests. Among those isolates producing a single non-class I beta-lactamase, resistance was due to production of high levels of TEM-1, SHV-1, or class IV enzymes. In five Escherichia coli isolates, production of low levels of PSE-1 was responsible for resistance which seemed due to rapid hydrolysis of ticarcillin rather than diminished susceptibility of PSE-1 to inhibition by potassium clavulanate. Comparisons of dilution and disk diffusion tests revealed major discrepancies, with 65% false susceptibility in the disk test. Revision of the interpretive criteria used for disk diffusion tests from less than or equal to 11 to less than or equal to 18 mm for resistance is proposed to resolve these discrepancies until clinical data are obtained which can be used to determine which in vitro test is most predictive of therapeutic outcome. These new criteria would diminish false susceptibility without introducing false resistance.

Clavulanic Acid↗
PubMed1987

Overview of preclinical studies with ciprofloxacin.

Ciprofloxacin is a new 6-fluoro-7-piperazino-4-quinolone that is highly active against a broad array of microbial pathogens. Minimal inhibitory concentrations (MICs) of ciprofloxacin are generally below 0.5 micrograms/ml for Hemophilus, Neisseria, and Enterobacteriaceae and are 1.0 microgram/ml or less for many non-fermentative gram-negative bacteria. Most staphylococci, including strains resistant to methicillin, are inhibited by 1.0 microgram/ml or less of ciprofloxacin, whereas streptococci are somewhat less susceptible. Obligate anaerobes are generally not susceptible to ciprofloxacin at concentrations below 1.0 microgram/ml. The antimicrobial potency of ciprofloxacin is twofold to fourfold greater than that of norfloxacin and is considerably greater than that of cephalosporins and aminoglycosides in tests with most gram-negative bacteria. Factors diminishing the in vitro activity of ciprofloxacin include acidic pH, high levels of magnesium ions, and an inoculum size of 10(7) colony-forming units/ml or greater. Ciprofloxacin is bactericidal at concentrations near its MIC for most bacteria. In vivo tests with experimentally induced infections in animals confirm the potency of ciprofloxacin. Doses required to protect 50 percent of animals from death are generally less than 2.0 mg/kg for gram-negative infections and range from 0.7 to 7.0 mg/kg for staphylococcal infections. The antimicrobial spectrum and potency of ciprofloxacin demonstrated in these preclinical studies make this quinolone a promising new antimicrobial agent.

Animals↗
PubMed1987

Clinical importance of inducible beta-lactamases in gram-negative bacteria.

The clinical problems caused by inducible beta-lactamases in certain gram-negative bacteria are being recognized with increasing frequency. These problems include the rapid emergence of multiple beta-lactam resistance during therapy with many of the newer beta-lactam antibiotics. Such multiply resistant organisms are now spreading within the hospital and have become important nosocomial pathogens. This has been a particularly difficult problem for intensive care units, cystic fibrosis centers and burn units where there are clusters of patients who are highly susceptible to infections with organisms like Enterobacter spp., Serratia spp. and Pseudomonas aeruginosa, which possess inducible beta-lactamases. Only through an awareness of these problems, their cause, and restriction of the use of certain newer beta-lactam antibiotics can these problems be controlled.

Anti-Bacterial Agents↗
PubMed1987

Emergence of resistance in gram-negative bacteria during therapy with expanded-spectrum cephalosporins.

To assess the clinical importance of emergence of beta-lactam resistance caused by stable derepression of chromosomal beta-lactamases, sequential cultures from patients treated with expanded-spectrum cephalosporins were monitored for the persistence of bacteria possessing these enzymes. Antibiotic susceptibilities and beta-lactamase production before and after cefoxitin induction were determined in sequential isolates of individual bacterial strains. Of 49 strains isolated from 44 patients, 25 strains (51%) were eradicated by cephalosporin therapy, 17 strains (35%) persisted with unchanged susceptibility in sequential cultures, and 7 strains (14%) from 7 patients developed multiple beta-lactam resistance during cephalosporin therapy. In 6 of the 7 strains, resistance was associated with stable derepression of beta-lactamases. In the patient group whose strains developed resistance, subsequent use of non-beta-lactam antibiotics was more frequent and mortality was higher.

Bacterial Infections↗
PubMed1987

Infectious morbidity in gynecologic cancer.

A retrospective investigation of infectious morbidity in gynecologic oncology patients documented that 54 (11%) of 494 patients and 68 (6%) of 1204 patient admissions were complicated by a serious infection. The highest rate of infectious morbidity by admission was 21%, occurring in patients admitted for cancer of the vulva. The highest surgical infectious morbidity, 22%, occurred in patients admitted for cervical cancer. Important factors in determining infection risk include multiple host factors, radical surgical procedures, factors inherent in the tumor itself, and additional irradiation and chemotherapy. These serious polymicrobial infections dictate intelligent selection of antimicrobials and appropriate monitoring to anticipate complications inherent in antimicrobial therapy. beta-Lactamase induction, superinfection, nephrotoxicity, and necrotizing enterocolitis are documented problems in these patients.

Adult↗