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C C Sanders

Publications and source records attributed to C C Sanders.

At least 19 recordsLinked to original sources
PubMed1992

beta-Lactam resistance in gram-negative bacteria: global trends and clinical impact.

Microbial drug resistance is an inescapable consequence of the utilization of antimicrobial agents in a given environment. Nowhere is the importance of resistance more evident than among agents of the beta-lactam family. Trends toward increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae, where ampicillin resistance varies from 1% to 64% globally. For Escherichia coli, ampicillin resistance has risen to > or = 50% in high-risk populations, and resistance to third-generation cephalosporins is now being seen in certain areas. Inducible beta-lactamases have been responsible for increasing multiple beta-lactam resistance among certain Enterobacteriaceae and Pseudomonas aeruginosa, and this has been associated with increased use of newer cephalosporins. Xanthomonas maltophilia with its two inducible beta-lactamases is becoming an increasingly important nosocomial pathogen, especially in areas of heavy imipenem utilization. Only through the recognition of factors associated with increasing resistance and the mechanisms responsible can strategies be designed for minimizing beta-lactam resistance.

Ampicillin Resistance↗
PubMed1992

Review of preclinical studies with ofloxacin.

Most Enterobacteriaceae, enteropathogens, and fastidious gram-negative bacteria are highly susceptible to ofloxacin, a new tricyclic fluoroquinolone. Aerobic gram-negative bacilli and gram-positive bacteria are generally not as susceptible to ofloxacin. Obligate anaerobes are generally resistant to ofloxacin, while many mycobacteria, chlamydiae, legionellae, and mycoplasmas are susceptible. Ofloxacin is generally less active than ciprofloxacin against gram-negative bacteria, is similarly active against gram-positive bacteria, mycobacteria, legionellae, and mycoplasmas, and is more active against chlamydiae. However, numerous animal studies have shown these two fluoroquinolones to be similar. Ofloxacin inhibits DNA synthesis, is rapidly bactericidal, and is 1,000-2,400 times more potent against prokaryotic gyrase than against eukaryotic gyrase. The bactericidal effect of ofloxacin is not completely neutralized by inhibitors of protein or RNA synthesis. Resistance to ofloxacin arises from mutations within chromosomal genes involved with DNA gyrase and drug permeation. Selection of resistant mutants by ofloxacin is not as frequent as that seen with nalidixic acid. However, due to the cross-resistance between ofloxacin and other fluoroquinolones, all of these drugs should be used judiciously to preserve their clinical utility.

Animals↗
PubMed1992

beta-Lactamases of gram-negative bacteria: new challenges for new drugs.

The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor. The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria. These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases. In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids. There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance. Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance.

Anti-Bacterial Agents↗
PubMed1992

Long term epidemiological analysis of Citrobacter diversus in a neonatal intensive care unit.

A prolonged outbreak of Citrobacter diversus central nervous system infection among hospitalized term infants, peaking in 1979, ceased with establishment of nurse-patient cohorting. The outbreak was attributed to dissemination of an epidemic strain among infants in an antiquated neonatal intensive care unit. When C. diversus colonization recurred within the new neonatal intensive care unit in 1984, cohorting and bacteriologic surveillance were reinstituted. By utilizing biotypes, plasmid profiles and antibiograms, four different C. diversus strains were identified circulating during 1979. Strains recovered between 1984 and 1988 from neonatal intensive care unit infants were similar to those from community-acquired sources. A strain considered avirulent in 1979 was found causing bacteremia in two infants (one with central nervous system disease) in 1984 to 1988. During cohorting C. diversus acquisition was 0.019/patient-month; after cohorting ceased it was 0.017/patient-month. Multiple source introductions appeared to occur with different C. diversus strains, some causing infant disease. No efficacy of cohorting was evident.

Citrobacter↗
PubMed1992

Lack of evidence of efficacy of cohorting nursing personnel in a neonatal intensive care unit to prevent contact spread of bacteria: an experimental study.

Nurse cohorting was investigated in a modern neonatal intensive care unit (NICU). During 99 days bacterial infection and colonization rates were determined in 100 infants experimentally assigned cohort or noncohorted care. Colonizing isolate identity was determined by plasmid profile analyses and biotyping in weekly surveillance cultures. Between Days 2 and 7, 3 infections occurred in cohorted infants but none in noncohorted ones. No secondary spread of infection or definitive colonization cluster occurred. The first colonization rate, at any site, was 0.53/patient-week in the noncohorted and 0.3 to 0.4 in the cohorted units (P greater than 0.05). Colonization ratios with species other than usual skin bacteria in the respiratory tract and with species other than Escherichia coli in the rectum were lower for noncohorted infants. Effective infection control practices in a modern NICU, including alcohol hand antisepsis, should obviate a need for cohorting.

Bacterial Infections↗
PubMed1992

Use of a predictor panel for development of a new disk for diffusion tests with cefoperazone-sulbactam.

The proper disk mass for diffusion susceptibility tests with cefoperazone-sulbactam was determined by using a predictor panel of clinical isolates that included staphylococci and gram-negative bacteria intrinsically susceptible, intrinsically resistant, and of various susceptibilities because of the production of different types and amounts of beta-lactamase. A primary panel of 24 isolates was used to screen various disk masses of cefoperazone and sulbactam in disk diffusion susceptibility tests. Regression analyses were performed for each combination by comparing MICs to zone diameters. Analysis of each component demonstrated that decreasing the disk mass of cefoperazone shifted the regression line to the left while decreasing the disk mass of sulbactam diminished the slope of the line. Ten candidate disks that adequately separated susceptible and resistant strains among the primary panel were identified, and these 10 disks, along with the previously proposed 75/30-micrograms disk, were then tested against an expanded panel of 265 isolates. Results indicated that a 30/20-micrograms cefoperazone-sulbactam disk provided the best separation between susceptible and resistant strains when interpretive criteria of less than or equal to 15 mm for resistance, 16 to 19 mm for moderate susceptibility, and greater than or equal to 20 mm for susceptibility were used. They also identified discrepancies between agar and broth microdilution MICs of sufficient size to warrant separate interpretive criteria for the two methods. Overall, the use of a predictor panel to develop interpretive criteria for susceptibility tests appeared to be a very useful approach, especially when antibiotics designed to be used against drug-resistant organisms are involved.

Bacteria↗
PubMed1992

Detection of extended-spectrum beta-lactamases in members of the family Enterobacteriaceae: comparison of the double-disk and three-dimensional tests.

The three-dimensional and clavulanate double-disk potentiation tests were compared as procedures for the detection of extended-spectrum beta-lactamase production in 32 strains of Escherichia coli and Klebsiella pneumoniae, 31 of which produced TEM-1, TEM-2, TEM-3, TEM-4, TEM-5, TEM-7, TEM-8, TEM-9, TEM-10, TEM-12, TEM-101, SHV-1, SHV-2, SHV-3, SHV-4, SHV-5, CAZ-2, MIR-1, or an unidentified extended-spectrum beta-lactamase with a pI of 5.95, with some strains producing multiple beta-lactamases. The three-dimensional test, which was performed in conjunction with a routine disk diffusion test, detected extended-spectrum beta-lactamase production in 26 of 28 (93%) of the strains that produced extended-spectrum beta-lactamases. The clavulanate double-disk potentiation test detected extended-spectrum beta-lactamases in only 22 of the 28 strains (79%) when it was performed as currently recommended. The three-dimensional test, when performed in conjunction with the disk diffusion test, offered the advantages of providing simultaneous information about both antibiotic susceptibility and extended-spectrum beta-lactamase production, coupled with a greater sensitivity and earlier detection of extended-spectrum beta-lactamases.

Anti-Bacterial Agents↗
PubMed1992

Therapeutic and epidemiologic recommendations to reduce the spread of type-I beta-lactamase resistance.

The objectives of this United States Consensus Panel meeting were to evaluate the effectiveness of current surveillance systems for the detection of bacterial resistance as well as to formulate recommendations that can assist hospitals in determining actions that should be taken when a resistance problem is detected. These recommendations may be particularly helpful in controlling the emergence and spread of type-I beta-lactamase resistance. Numerous case reports of antimicrobial resistance among Enterobacter species, Pseudomonas aeruginosa, and other Gram-negative nosocomial pathogens known to produce type-I beta-lactamases have appeared in the literature since the introduction of the newer "third-generation" cephalosporins. The widespread use of these newer antimicrobial agents, often selected as standard therapy for serious hospital-acquired infections, has been associated with a corresponding increase in resistance to them. The failure of hospitalwide surveillance methods to describe the scope of this problem, especially among the most critically ill patients, may have resulted in a false sense of security among some infectious disease specialists and clinicians prescribing these antimicrobials as empiric therapy. High-level resistance in individual hospital units may be masked in hospitalwide antibiograms. A variety of conclusions and recommendations were formulated based on the collective experiences of the Consensus Panel members. Microbiology laboratories must make it a high priority to identify markers that will assist in rapidly identifying resistant organisms. Cooperative efforts are needed among users of commercial and automated microbiology test instruments to standardize results and to improve quality control, thereby making the data more directly comparable between laboratories.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1991

In vitro studies with five quinolones: evidence for changes in relative potency as quinolone resistance rises.

A panel of 203 staphylococci, Enterobacteriaceae, Pseudomonas aeruginosa, and miscellaneous nonfermentative gram-negative bacilli were chosen for their various susceptibilities to ciprofloxacin. On the basis of agar dilution susceptibilities, each of the four taxonomic groups was divided into ciprofloxacin-susceptible, moderately resistant, and highly resistant subgroups, and each subgroup was then further analyzed for its susceptibility to the fluoroquinolones CI-960, CI-990, sparfloxacin, and ofloxacin. Although the MICs of each quinolone increased as ciprofloxacin resistance increased, the potency of CI-960 appeared to increase relative to the potencies of the other quinolones. Similarly, the MICs of sparfloxacin and ofloxacin appeared to be less affected by ciprofloxacin resistance than were the MICs of ciprofloxacin or CI-990. Single-step mutants of representative clinical isolates with different levels of ciprofloxacin resistance were selected to determine whether the study quinolones differed in their propensity to select resistant mutants and whether the presence of preexisting ciprofloxacin resistance influenced the subsequent development of resistance. Each of the five fluoroquinolones and nalidixic acid selected mutants that exhibited generally modest decreases in quinolone susceptibility (4- to 16-fold). However, CI-960 inhibited significantly more mutants (80%) than did the other quinolones (39 to 59%) at a concentration of 1 microgram/ml. The presence of preexisting ciprofloxacin resistance appeared to be associated with higher mutational frequencies in coagulase-negative staphylococci exposed to each of the fluoroquinolones and in Serratia marcescens exposed to nalidixic acid. Preexisting ciprofloxacin resistance did not influence the development of resistance in the strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, or Pseudomonas aeruginosa that were studied. The results of this study suggest that quinolones are not affected equally by all resistance mechanisms, and although each one can select mutants, some quinolones may be active against these mutants at clinically achievable concentrations.

Anti-Infective Agents↗
PubMed1991

Altered phenotypes associated with ampD mutations in Enterobacter cloacae.

A study was done to determine the genetic locus responsible for altered expression of AmpC beta-lactamase in Enterobacter cloacae 1194E and several mutants derived from E. cloacae 029. These phenotypes were defined by units of enzyme activity found in sonic extracts of cells before and after induction with cefoxitin and included (units uninduced/units induced) the wild-type (7/219), high-level constitutive (10,911/10,862), temperature-sensitive (at 30 degrees C 82/706 and at 42 degrees C 5,031/6,020), and hyperinducible (19/1,688) phenotypes. When the ampD region of each E. cloacae strain was cloned and introduced into an ampD mutant Escherichia coli strain, the altered phenotypes were found to reside within this locus. Furthermore, transformants containing wild-type ampD were poorly inducible at 42 degrees C while those with high-level constitutive or hyperinducible ampD were unaffected by temperature. Since the source of ampD was the only variable in these E. coli transformants, these results suggested that ampD encodes a protein that is involved in sensing the inducer. To test this possibility, the responses to different inducers of E. coli transformants containing various ampD regions were assessed. In the presence of wild-type ampD, transformants responded equally to cefoxitin and cefotetan, regardless of temperature. In the presence of temperature-sensitive ampD, induction by cefotetan was similar to that by cefoxitin at 30 degrees C but greater than that by cefoxitin at 42 degrees C. These results suggest that ampD encodes a protein involved in induction of AmpC beta-lactamase in E. cloacae.

Anti-Bacterial Agents↗
PubMed1991

Influence of beta-lactamase inhibitors on the potency of their companion drug with organisms possessing class I enzymes.

The ability of beta-lactamase inhibitors to induce class I beta-lactamases in certain organisms in vitro suggests a potential for antagonism in vivo. Therefore, a study was designed to assess the ability of sulbactam and clavulanate to induce beta-lactamases in two strains each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Pseudomonas aeruginosa both in vitro and in vivo. Induction in vitro was observed only with S. marcescens and P. aeruginosa and generally only when inhibitor concentrations greater than 2 micrograms/ml were examined. A mouse model of lethal infection, designed to detect in vivo antagonism arising from beta-lactamase induction, was used to determine what effect sulbactam and clavulanate would have on the 50% protective doses (PD50s) of cefoperazone and ticarcillin. Antagonism (a significant increase in the PD50) was observed in only 4 of 32 tests. Three of these involved antagonism of cefoperazone by clavulanate, and one involved antagonism of cefoperazone by sulbactam. In 6 of 32 tests, enhancement of efficacy (a significant decrease in PD50) was observed. In four of these, sulbactam enhanced cefoperazone; in one, sulbactam enhanced ticarcillin; and in one, clavulanate enhanced ticarcillin. Four of the six cases of enhancement occurred when the beta-lactamase inhibitor was given at the time of challenge. None of these positive or negative in vivo effects were predicted by in vitro tests. These data suggest that beta-lactamase inhibitors can influence the in vivo potency of their companion drug in both a beneficial and detrimental fashion against organisms with class I beta-lactamases and that these effects cannot be predicted from in vitro assays.

Animals↗
PubMed1991

In vitro studies with Bay V 3522, a new oral cephalosporin.

The in vitro activities of Bay v 3522, cefaclor, cephalexin, cefuroxime, cefixime, amoxicillin/clavulanate (2:1) and reference penicillins were compared against 314 clinical isolates of Gram-positive and Gram-negative bacteria and nine strains of Escherichia coli that differed in their outer membrane proteins in agar dilution tests with an inoculum of 10(4) cfu/spot. The beta-lactamase stabilities of the cephalosporins were also evaluated by spectrophotometric assay using 21 different beta-lactamases. Bay v 3522 was the most potent cephalosporin overall against Gram-positive pathogens, but slightly less active than amoxicillin/clavulanate. In addition to being highly active against streptococci (MIC90 = 0.25 micrograms/ml) and methicillin-susceptible staphylococci (MIC90 = 1.0 micrograms/ml), Bay v 3522 was markedly more active than the other cephalosporins against Enterococcus faecalis (MIC90 = 4 micrograms/ml). Bay v 3522 was less potent against Gram-negative pathogens, especially nosocomial isolates of Escherichia coli and Klebsiella pneumoniae (MIC90 greater than 64 micrograms/ml), but was active against Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and beta-lactamase-negative Neisseria gonorrhoeae (MIC90 = 1.0 micrograms/ml0. Hydrolysis of Bay v 3522 by most beta-lactamases examined was significantly less than that observed for cephalothin and cefaclor; similar to that observed with cephalexin; and less than that observed with cefixime and cefuroxime. None of the beta-lactamases examined hydrolysed Bay v 3522 at a rate greater than 20 nmol/min/mg. The in vitro potency of Bay v 3522 against Gram-positive and fastidious Gram-negative pathogens and its resistance to hydrolysis by beta-lactamases produced by them support further investigation of this cephalosporin as a new oral therapeutic agent.

Anti-Bacterial Agents↗
PubMed1990

Isolation of Enterobacter aerogenes susceptible to beta-lactam antibiotics despite high level beta-lactamase production.

This report describes a patient with nosocomial meningitis from whom four distinct isolates of Enterobacter aerogenes were recovered over a complicated course of chemotherapy. The initial isolate was susceptible to expanded spectrum beta-lactams despite constitutive production of high levels of beta-lactamase. Resistant isolates recovered during antibiotic therapy had lost a 42,000 outer membrane protein. These data suggest that b-lactam susceptibility in the original isolate was due to "hyperpermeability" mediated by the 42,000 Dalton protein.

Anti-Bacterial Agents↗