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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 73 records · Page 4Linked to original sources
PubMed1993

In vitro activity of biapenem against clinical isolates of gram-positive and gram-negative bacteria.

The in vitro activity of biapenem, a new carbapenem previously designated L-627, was compared with those of imipenem and several other antimicrobial agents against 771 clinical bacterial isolates. Against gram-positive organisms, biapenem was found to be approximately as active as imipenem, inhibiting 90% of isolates of most species at concentrations within one dilution of the MIC of imipenem for 90% of the isolates. Against gram-negative organisms and Bacteroides fragilis, biapenem was at least as active as and often more active than imipenem, with MICs for 90% of the isolates two- to eightfold lower than those of imipenem.

Anti-Bacterial Agents↗
PubMed1992

In vivo activity of the combination of daptomycin and fosfomycin compared with daptomycin alone against a strain of Enterococcus faecalis with high-level gentamicin resistance in the rat endocarditis model.

The in vivo activity of the combination of daptomycin and fosfomycin against a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis in a relapse model of rat endocarditis was studied. Minimum inhibitory concentrations (MICs) (micrograms per milliliter) for these agents against this strain were 4 (daptomycin) and 16 (fosfomycin). Time-kill studies demonstrated synergistic bactericidal activity when daptomycin (0.5 micrograms/ml) and fosfomycin (32 micrograms/ml) were combined. There was no significant difference between the number of valves sterilized by daptomycin alone [six (35%) of 17 valves sterilized] and daptomycin+fosfomycin [ten (59%) of 17 valves sterilized] p = 0.3. These results suggest that the in vitro bactericidal synergism demonstrable between these two agents against strains of enterococci will not necessarily translate into greater therapeutic efficacy in clinical infections.

Animals↗
PubMed1992

Contribution of animal models in the search for effective therapy for endocarditis due to enterococci with high-level resistance to gentamicin.

Earlier studies suggest that ampicillin and amoxicillin are more effective than other beta-lactam agents in killing enterococci, although beta-lactam agents are slowly and incompletely bactericidal against most strains of Enterococcus faecalis. We previously showed that continuous infusion of ampicillin is more effective than intermittent administration in decreasing the number of enterococci in valvular vegetations of rats with catheter-induced endocarditis that are treated for 5 days. In this model, we found ampicillin plus sulbactam more effective than ampicillin alone against a beta-lactamase-producing enterococcal strain with high-level resistance to gentamicin. Daptomycin therapy produced results approximately equal to those of ampicillin plus sulbactam. Vancomycin and teicoplanin given for 5 days at doses producing equivalent serum levels had approximately equal efficacy. However, 10-day therapy with low-dose teicoplanin was considerably more effective than similar treatment with vancomycin. High-dose teicoplanin for 5 days produced sterile valves in 82% of the animals studied.

Ampicillin↗
PubMed1992

Antimicrobial susceptibility changes in Enterococcus faecalis following various penicillin exposure regimens.

Penicillin-"virgin" strains of Enterococcus faecalis collected from a population of individuals with no previous antibiotic exposure were subjected in vitro to penicillin delivered as repeated pulses, stepwise increasing concentrations, or sustained levels of a single concentration. Changes in resistance to penicillin were assessed by determination of MICs, and time-kill studies were performed to evaluate changes in tolerance to the bactericidal effects of penicillin. Isogenic clones, derived from various exposure regimens, which exhibited changes in either resistance or tolerance were further examined for changes in penicillin-binding proteins. Exposure to repeated pulses of penicillin resulted in the development of tolerance to penicillin without changes in the level of resistance. Clones derived from a regimen of stepwise increases in the penicillin concentration acquired both increased penicillin resistance and tolerance. Clones selected after prolonged continuous exposure to a fixed concentration of penicillin displayed minimally increased resistance to penicillin, but they retained the lytic, nontolerant response to the bactericidal effect of penicillin. Clones which acquired tolerance to the bactericidal effect of penicillin without changes in penicillin resistance exhibited a penicillin-binding protein pattern identical to that of the parental strain. Increased labeling of several penicillin-binding proteins accompanied the development of increased penicillin resistance in both penicillin-tolerant and nontolerant strains. Exposure of E. faecalis to penicillin in repeated pulses of brief duration, for prolonged periods at a constant concentration, or in stepwise graded concentrations can result in the selection of clones with increased resistance to the inhibitory or bactericidal effects of penicillin, or both. These observations may be relevant to the selection of dosing regimes for penicillin in the treatment of enterococcal infections, when bactericidal synergism cannot be achieved with penicillin-aminoglycoside combinations.

Bacterial Proteins↗
PubMed1992

Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci.

The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates. Using both the checkerboard technique and time-kill curves, we examined 28 strains of enterococci (17 Enterococcus faecalis and 11 Enterococcus faecium strains) with different levels of resistance to vancomycin. Of these, 15 strains were also highly gentamicin resistant, and 9 demonstrated resistance to ampicillin. Only seven strains of E. faecalis were inhibited synergistically by the combination of vancomycin with ampicillin, and even then, the concentrations of vancomycin at which synergism was demonstrated were above levels achievable in serum. None of the ampicillin-resistant isolates (all E. faecium) were inhibited synergistically at any concentration of the drugs. In no instance was bactericidal synergism observed, and in most cases the combination resulted in less killing than with ampicillin alone. Antagonism was not observed at clinically relevant concentrations. The results of this study suggest that the combination of vancomycin with ampicillin has little to offer against these emerging pathogens.

Ampicillin↗
PubMed1992

Influence of high-level gentamicin resistance and beta-hemolysis on susceptibility of enterococci to the bactericidal activities of ampicillin and vancomycin.

The bactericidal activities of ampicillin and vancomycin against 40 recent isolates of Enterococcus faecalis were examined by kill-kinetic studies at concentrations of 4 x the MIC and 20 micrograms/ml. Greater killing was seen with ampicillin (3.57 +/- 0.87 and 2.50 +/- 1.09 log10 CFU/ml, respectively; mean +/- standard deviation) than with vancomycin (1.23 +/- 0.65 and 1.05 +/- 0.57 log10 CFU/ml, respectively). Highly gentamicin-resistant strains showed a tendency toward reduced susceptibility to killing; beta-hemolytic strains were more susceptible than nonhemolytic strains when exposed to ampicillin at 20 micrograms/ml. Within each group, individual isolates demonstrated great variability in susceptibility to killing by the drugs.

Ampicillin↗
PubMed1991

Increasing resistance to beta-lactam antibiotics among clinical isolates of Enterococcus faecium: a 22-year review at one institution.

To identify any change in the antibiotic resistance of Enterococcus faecium, we examined the antibiotic susceptibilities of clinical strains (n = 84) isolated at one institution during the 22 years since 1968. A significant increase in resistance to penicillin was observed during the study period: the MICs of penicillin for 50 and 90% of isolates tested were 16 and 64 micrograms/ml, respectively, from 1969 to 1988 (n = 48; geometric mean MIC, 14 micrograms/ml) , whereas they were 256 and 512 micrograms/ml, respectively, from 1989 to 1990 (n = 36; geometric mean MIC, 123 micrograms/ml) (P less than 0.001). A comparable increase in resistance to ampicillin was also noted (P less than 0.001). No strains produced detectable beta-lactamase. In contrast, susceptibilities to vancomycin, teicoplanin, and ciprofloxacin remained stable. High-level resistance to gentamicin was observed in none of 48 isolates from 1969 to 1988, but was present in 22 of 36 strains (61%) from 1989 to 1990 (P less than 0.001) and was significantly associated with resistance (MIC, greater than or equal to 128 micrograms/ml) to penicillin (P less than 0.001). To assess the potential evolution of antibiotic resistance in this species, clinical isolates (n = 24) were compared with strains isolated in 1968 from a human population in the Solomon Islands that was never exposed to antibiotics. Solomon Island isolates were significantly more susceptible than all clinical strains to penicillin, ampicillin, and vancomycin (P less than 0.001 for each), but they exhibited no differences in susceptibility to teicoplanin or ciprofloxacin. The penicillin-binding affinity of penicillin-binding protein 5 (PBP 5) in penicillin-resistant clinical strains (MIC, 512 micrograms/ml) was notably lower than that in strains with more typical susceptibilities, suggesting an alteration in this PBP as a possible mechanism for increased penicillin resistance. Solomon Island strains most susceptible to penicillin demonstrated a prominent PBP 5* and the absence of PBP 5. These changes in the antibiotic resistance of E. faecium emphasize the importance of identifying this species in patients with serious enterococcal infections and the necessity of assessing its susceptibility to both beta-lactams and aminoglycosides if effective therapy is to be identified.

Anti-Bacterial Agents↗
PubMed1991

Chromosomally mediated beta-lactamase production and gentamicin resistance in Enterococcus faecalis.

We have analyzed four distinct strains of multiply resistant, beta-lactamase-producing enterococci isolated during an outbreak of colonization with these strains on an infant-toddler surgical ward at The Children's Hospital in Boston, Mass. All four strains were resistant to erythromycin, penicillin, and tetracycline and to high levels of gentamicin and streptomycin. One strain was also resistant to chloramphenicol. Plasmid profiles revealed four different plasmid patterns, with the number of identified plasmids ranging from zero to three. The gene coding for beta-lactamase production could be transferred at low frequency (less than 10(-8)) to an enterococcal recipient from one strain in conjunction with all of the other resistance determinants. Probes derived from the staphylococcal beta-lactamase gene and gentamicin resistance gene failed to hybridize with any of the detectable plasmids, but both genes were present on restriction fragments of genomic DNA in all strains. Our results indicate that the beta-lactamase genes and gentamicin resistance genes in these strains are integrated into the bacterial chromosome. The cotransmissibility of the resistance determinants raises the possibility of their incorporation into a multiresistance transposable genetic element.

Conjugation, Genetic↗
PubMed1991

Efficacy of different beta-lactams against an extended-spectrum beta-lactamase-producing Klebsiella pneumoniae strain in the rat intra-abdominal abscess model.

Although standard-inoculum MICs were within the susceptible range for all compounds, cefoperazone, cefotaxime, and cefpirome were significantly less effective than imipenem or the combination of cefoperazone and sulbactam in the treatment of rat intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae.

Abdomen↗
PubMed1991

Comparison of Enterococcus raffinosus with Enterococcus avium on the basis of penicillin susceptibility, penicillin-binding protein analysis, and high-level aminoglycoside resistance.

We reidentified our laboratories' collections of 57 enterococcal isolates previously classified as Enterococcus avium by the API Rapid Strep identification system (Analytab Products, Plainview, N.Y.) with the identification criteria recommended by Facklam and Collins (R. R. Facklam and M. D. Collins, J. Clin. Microbiol. 27: 731-734, 1989). Thirty isolates were identified as true E. avium, 25 isolates were identified as E. raffinosus, and 2 isolates were identified as E. pseudoavium. E. raffinosus could be differentiated from E. avium on the basis of penicillin susceptibility, as follows: MIC for 50% of E. raffinosus isolates tested (MIC50), 32 micrograms/ml; MIC90, 64 micrograms/ml (range, 4 to 64 micrograms/ml); E. avium MIC50, 1 microgram/ml; MIC90, 2 micrograms/ml (range, 0.5 to 2 micrograms/ml). No strains produced detectable beta-lactamase. Penicillin-binding protein (PBP) analysis of all E. raffinosus isolates demonstrated the unique pattern reported previously (M. D. Collins, R. R. Facklam, J. A. E. Farrow, and R. Williamson, FEMS Microbiol. Lett. 57:283-288, 1989); however, a number of newly identified PBPs were noted. Of 25 isolates, 13 had an additional PBP of 77 kDa (designated PBP 6*), while all isolates possessed a 52-kDa PBP (PBP 7) and a 46-kDa PBP (PBP 8). The presence or absence of PBP 6* did not correlate with penicillin susceptibility; however, PBP 7 demonstrated many features suggestive of low penicillin-binding affinity and may represent a possible mechanism for the relative resistance of this species to penicillin, although this hypothesis remains speculative since attempts to develop a penicillin-hypersusceptible E. raffinosus mutant were unsuccessful. E. raffinosus isolates were significantly more likely to exhibit high-level resistance to kanamycin than E. avium strains were (P < 0.001; chi-square); however, no strains demonstrated high-level resistance to gentamicin. No trend toward increasing penicillin resistance was noted among this collection of E. avium and E. raffinosus isolates collected over the past 35 and 14 years, respectively. Relative resistance to penicillin may be a helpful differentiating feature between E. avium and E. raffinosus when assessment of raffinose metabolism is not possible or is indeterminant.

Aminoglycosides↗
PubMed1990

Outbreak of ceftazidime resistance caused by extended-spectrum beta-lactamases at a Massachusetts chronic-care facility.

During a 4-month period in late 1988, we isolated ceftazidime-resistant strains of Klebsiella pneumoniae and other members of the family Enterobacteriaceae from 29 patients at a chronic-care facility in Massachusetts. Ceftazidime resistance resulted from two distinct extended-spectrum beta-lactamases of the TEM type which efficiently hydrolyzed the cephalosporin: YOU-1 with a pI of 5.57 and YOU-2 with a pI of 5.2. Genes encoding these enzymes were present on different but closely related high-molecular-weight, multiple antibiotic resistance plasmids of the H12 incompatibility group and were transferable by conjugation in vitro. Agarose gel electrophoresis of extracts from clinical isolates indicated that this outbreak arose from plasmid transmission among different strains of the family Enterobacteriaceae rather than from dissemination of a single resistant isolate. Isolation rates of ceftazidime-resistant organisms transiently decreased after use of this drug was restricted, but resistant isolates continued to be recovered 7 months after empiric use of ceftazidime ceased.

Ceftazidime↗