Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 91 records · Page 5Linked to original sources

PubMed1990

Efficacy of oxacillin and ampicillin-sulbactam combination in experimental endocarditis caused by beta-lactamase-hyperproducing Staphylococcus aureus.

Optimal therapy of infections caused by borderline oxacillin-susceptible, beta-lactamase-hyperproducing Staphylococcus aureus has not been established. We used a rat model of aortic valve endocarditis to examine efficacies of antibiotic regimens against a borderline oxacillin-susceptible strain as compared with a fully susceptible S. aureus strain. Animals were treated with oxacillin alone or in combination with sulbactam or with ampicillin-sulbactam combinations at two dose levels. Infections caused by the borderline susceptible and fully susceptible strains responded equally well to oxacillin alone, with residual bacterial titers in vegetations falling to 4.8 +/- 1.6 and 4.4 +/- 1.7 (mean +/- standard deviation) log10 CFU/g, respectively. Addition of sulbactam to oxacillin (1:2) did not enhance the efficacy of oxacillin against either strain in the animal model. A high-dose regimen of ampicillin-sulbactam (2:1) yielding mean (+/- standard deviation) levels in serum of 16.8 +/- 7.4 and 9.5 +/- 1.1 micrograms/ml, respectively, proved equally effective against both strains (bacterial titers, 6.6 log10 CFU/g). However, at lower doses (8.3 +/- 2.6 and 5.9 +/- 2.4 micrograms/ml, the combination showed greater efficacy against the fully susceptible strain, with residual titers of 7.1 +/- 2.0 versus 9.0 +/- 1.6 log10 CFU/g (P less than 0.05). In vitro studies revealed that the beta-lactamase inhibitor sulbactam was also a potent inducer of staphylococcal beta-lactamase at clinically relevant concentrations. Based on this short-term in vivo therapy study, oxacillin would be predicted to be clinically effective in the therapy of infections caused by borderline oxacillin-susceptible strains of S. aureus, while the combination of ampicillin with sulbactam appears to be inferior to oxacillin alone against such infections.

Ampicillin↗

PubMed1990

Efficacy of teicoplanin in two dosage regimens for experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.

Optimal therapy for the treatment of infections caused by strains of enterococci demonstrating high-level resistance to gentamicin and other aminoglycosides has not been established. The present study examined the efficacy of teicoplanin, a glycopeptide antibiotic active against gram-positive bacterial infections in various animal models, in the treatment of experimental endocarditis due to a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin. Vancomycin was used as a comparative antibiotic. In the first set of experiments, both antimicrobial agents were administered by continuous intravenous infusion for 5 days at dosages which yielded comparable mean levels in serum (plus or minus the standard deviation) of 14.6 +/- 4.3 micrograms/ml for teicoplanin and 14.3 +/- 2.2 micrograms/ml for vancomycin. These regimens proved similarly effective in sterilizing cardiac vegetations (38 versus 50% of treated animals, respectively; P greater than 0.05). Mean (plus or minus the standard deviation) residual bacterial titers within vegetations were reduced to 3.2 +/- 1.2 log10 CFU/g and 3.4 +/- 1.7 log10 CFU/g, respectively. In separate experiments, the potential of teicoplanin to cure endocarditis was assessed, using two dosage regimens: (i) 30 mg/kg per day (mean level in serum, 13 micrograms/ml) for 10 days or (ii) 150 mg/kg per day (mean level in serum, 84 micrograms/ml) for 5 days. Surviving animals were sacrificed 10 days after the discontinuation of therapy. Both teicoplanin regimens were more effective than the comparative vancomycin (150 mg/kg per day) regimen: 92 versus 43% cured (P =0.025) in the standard-dose group, and 82 versus 37% cured (P = 0.015) in the high-dose group. Results in this rat model of enterococcal endocarditis show that teicoplanin may prove useful in the treatment of serious infections due to high level-gentamicin-resistant enterococci in humans.

Animals↗

PubMed1990

Comparative in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent.

The in vitro activity of WIN 57273, a new fluoroquinolone antimicrobial agent, was evaluated against approximately 600 bacterial isolates. The new drug was 4- to 128-fold more active than ciprofloxacin against a broad range of gram-positive organisms, with the new drug inhibiting 90% of strains of each species except Enterococcus faecium at concentrations of less than or equal to 0.25 microgram/ml. WIN 57273 was four- to eightfold less active than ciprofloxacin against many members of the family Enterobacteriaceae, but the MICs of the new drug for 90% of strains tested (MIC90s) were less than or equal to 8 micrograms/ml (range, 0.25 to 8 micrograms/ml) for all species. Branhamella catarrhalis, Haemophilus influenzae, Neisseria gonorrhoeae, and Legionella spp. were highly susceptible (MIC90s, less than or equal to 0.06 microgram/ml). WIN 57273 demonstrated excellent activity against anaerobes (MIC90s, less than or equal to 0.25 microgram/ml), and the drug was also more active than ciprofloxacin against 30 strains of Mycobacterium avium-M. intracellulare (MIC, 0.1 to 1.0 microgram/ml). The activity of WIN 57273 against gram-positive organisms was minimally affected by pH and increased at low pH (5.4) against gram-negative organisms. The bactericidal activity of WIN 57273 was demonstrated by time-kill techniques against selected organisms. The frequencies of spontaneous resistance to the new agent were low, but resistant colonies could be selected after serial passage of initially susceptible organisms through incremental concentrations of the drug.

4-Quinolones↗

PubMed1990

Failure of trimethoprim-sulfamethoxazole therapy in experimental enterococcal endocarditis.

To assess the potential efficacy of trimethoprim-sulfamethoxazole (TMP-SMX) against serious enterococcal infections, we used a rat enterococcal endocarditis model comparing TMP-SMX therapy (500 mg of TMP plus 2,500 mg of SMX per kg of body weight per day given every 8 h by intragastric gavage) with intravenous ampicillin therapy (1,000 mg/kg per day). Despite concentrations of active drug in serum well in excess of the MIC and MBC, the mean residual vegetation bacterial titer in TMP-SMX-treated rats was similar to that in untreated controls (8.4 +/- 1.1 versus 8.6 +/- 1.3 log10 CFU/g) and significantly higher than that in the ampicillin-treated group (3.6 +/- 1.5 log10 CFU/g; P less than or equal to 0.001). This demonstrates discordance between in vitro activity and in vivo efficacy of TMP-SMX in serious enterococcal infection.

Ampicillin↗

PubMed1990

In vitro activity of BAY v 3522, a new cephalosporin for oral administration.

The activity of BAY v 3522 was tested against over 500 clinical bacterial isolates and compared with the activities of ampicillin, amoxicillin-clavulanate, cefaclor, cefixime, cefuroxime, cephalexin, and/or ciprofloxacin, erythromycin, and metronidazole. BAY v 3522 activity against staphylococci and streptococci equaled or exceeded those of the other agents. BAY v 3522 exhibited no significant advantage over cefaclor, cefuroxime, or cephalexin against gram-negative bacilli.

Administration, Oral↗

PubMed1990

Interaction between antimicrobial consumption and selection of resistant bacterial strains.

The relationship between the consumption of antimicrobial agents and the emergence of resistance in bacteria is complex. However, there is clear-cut evidence that the therapeutic and prophylactic use of antimicrobials is associated with the emergence of resistance in the individual patient, in the hospital setting, and in the worldwide community as a whole.

Anti-Bacterial Agents↗

PubMed1989

Ofloxacin.

Explore the source record for details and available documents.

Humans↗

PubMed1989

Effect of varying pH on the susceptibility of Campylobacter pylori to antimicrobial agents.

The susceptibility of 22 clinical isolates of Campylobacter pylori to eight antimicrobial agents was studied under varying pH conditions. Macrolides (erythromycin, dirythromycin), clindamycin and to a lesser extent quinolones lost efficacy at lowered pH. The activity of ampicillin and metronidazole remained relatively stable throughout the pH range tested. The effect of pH an antimicrobial efficacy may warrant consideration when selecting an antibiotic to clear Campylobacter pylori in vivo, since the pH of the gastric submucous environment is not known for certain.

Anti-Bacterial Agents↗

PubMed1989

In vitro activity of cefoperazone-sulbactam combinations against cefoperazone-resistant clinical bacterial isolates.

From July 1987 to January 1988, 452 cefoperazone-resistant bacterial isolates were identified among strains subjected to routine susceptibility testing in a clinical microbiology laboratory. The 452 isolates were tested for susceptibility to cefoperazone, sulbactam, and a 2:1 combination of these drugs by agar dilution techniques. The greatest benefit of the cefoperazone-sulbactam combination was noted against Bacteroides spp. and Acinetobacter spp. The combination demonstrated clinically significant synergism against approximately 20% of strains of Pseudomonas aeruginosa.

Acinetobacter↗

PubMed1989

The carbapenems: new broad spectrum beta-lactam antibiotics.

The carbapenems differ from the penicillins (penams) in having an unsaturated bond between C2 and C3 and a carbon atom replacing sulphur at position 1 of the thiazolidine ring. The various carbapenems differ primarily in the configuration of the side chains at C2 and C6. Carbapenems include the thienamycins, olivanic acids, carpetimycins, asparenomycins, pluracidomycins, and other natural and semi-synthetic compounds. Carbapenems vary in their stability and resistance to beta-lactamases, ability to inhibit and to induce beta-lactamases, and in-vitro spectra of activity. Many are highly unstable in solution. Some are degraded by mammalian dehydropeptidases in vivo. The hydroxyethyl side chain in the alpha or trans-configuration at C6 in thienamycin provides striking resistance to beta-lactamases, but this compound is highly unstable in concentrated solution and the solid state. The N-formimidoyl derivative of thienamycin (imipenem) is more stable in solution and has broad-spectrum activity against aerobic and anaerobic bacteria. However, imipenem is not stable to renal dehydropeptidases and its degradation products are nephrotoxic in certain animals. It is thus administered with the dehydropeptidase inhibitor cilastatin. High serum levels of imipenem (especially in patients with renal failure and central nervous system disease) have been associated with seizures. The drug is therefore not appropriate for meningitis. Meropenem is a new carbapenem which has the same side chain as imipenem at C6. Its unique side chain at C2 assures a broad spectrum of activity which includes Pseudomonas aeruginosa and other aerobic and anaerobic organisms. Only Ps. (Xanthomonas) maltophilia is generally resistant. This species is resistant also to imipenem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

In vitro synergism between daptomycin and fosfomycin against Enterococcus faecalis isolates with high-level gentamicin resistance.

Daptomycin and fosfomycin are two agents which inhibit different steps in peptidoglycan synthesis. We studied the in vitro activities of these drugs, alone and in combination, by time-kill techniques against 21 clinical isolates of Enterococcus (Streptococcus) faecalis demonstrating high-level resistance to gentamicin. Combinations of fosfomycin and daptomycin exhibited synergistic bactericidal activity (100-fold decrease in CFU per milliliter at 24 h compared with daptomycin alone) against all strains (mean +/- standard deviation of increment in killing = 2.7 +/- 0.7 log10 CFU/ml). In a subgroup of strains against which daptomycin (5 micrograms/ml) alone was bactericidal (greater than 3 log10 killing), synergistic activity was demonstrable only when the concentration of daptomycin was lowered to 0.25 to 0.5 microgram/ml. A 50% dilution of human serum diminished the bactericidal activity of daptomycin alone at 24 h but did not affect killing observed with the daptomycin-fosfomycin combination. The inhibition of peptidoglycan synthesis by the combination was greater than the inhibition observed with either drug alone. The combination of daptomycin and fosfomycin exhibited consistent synergistic bactericidal activity against strains of E. faecalis possessing high-level resistance to gentamicin. This synergism may be the result of sequential inhibition of early steps in peptidoglycan synthesis.

Anti-Bacterial Agents↗

PubMed1989

In vitro activity of SK&F 104662, a new glycopeptide antibiotic.

The in vitro activity of SK&F 104662, a new glycopeptide antibiotic, against gram-positive bacteria was evaluated. Activity was comparable to those of teicoplanin and vancomycin against most organisms. SK&F 104662 inhibited diphtheroids at concentrations of less than or equal to 0.5 microgram/ml. Addition of human serum to the test medium lowered the inhibitory activity of this glycopeptide against some organisms by as much as eightfold.

Anti-Bacterial Agents↗

PubMed1989

Treatment of experimental endocarditis caused by a beta-lactamase-producing strain of Enterococcus faecalis with high-level resistance to gentamicin.

Several antimicrobial regimens were evaluated in the treatment of experimental enterococcal endocarditis due to a beta-lactamase-producing, highly gentamicin-resistant strain of Enterococcus faecalis. Ampicillin alone cleared bacteremia in the majority of rats and reduced titers of bacteria within vegetations (6.84 versus 8.80 log10 CFU/g in controls) but did not sterilize valves. Ampicillin-sulbactam combinations, vancomycin, daptomycin, and imipenem each reduced residual bacterial titers within vegetations to 4.01 log10 CFU/g or less; in 26 to 43% of animals receiving 5 days of therapy, titers of bacteria were reduced to undetectable levels. In a separate experiment, rats received ampicillin-sulbactam, daptomycin, or vancomycin for 10 days and were then observed for 10 days after termination of therapy for evidence of relapse. In surviving rats, valves remained sterile in four of five rats treated with ampicillin-sulbactam, in five of seven treated with daptomycin, but in only one of eight receiving vancomycin.

Animals↗

PubMed1989

Comparative in vitro activity of SM7338, a new carbapenem antimicrobial agent.

The comparative in vitro activity of SM7338 was tested against 670 routine clinical isolates and 130 cefoperazone-resistant isolates of bacteria by agar dilution methods. SM7338 was at least as active as imipenem against gram-negative organisms but was slightly less active against gram-positive organisms. SM7338 was particularly active against members of the family Enterobacteriaceae, with MICs for 90% of strains of less than or equal to 0.125 micrograms/ml for all species tested. Differences in activity between SM7338 and imipenem were particularly striking against Proteus vulgaris, Proteus mirabilis, and Morganella morganii, against which MICs of SM7338 and imipenem for 90% of strains were 0.125 and 4 micrograms/ml, respectively. The presence of unique plasmid-mediated beta-lactamases in Pseudomonas aeruginosa PU21 transconjugants did not affect activity substantially, except in the case of OXA-2 (eightfold-increased MIC) and OXA-3 (fourfold-increased MIC). SM7338 was also active against a laboratory-derived strain of P. aeruginosa which hyperproduced chromosomal beta-lactamase, inhibiting both the wild type and the mutant at a concentration of 1.0 micrograms/ml.

Anti-Bacterial Agents↗

PubMed1989

Effects of clindamycin and gentamicin and other antimicrobial combinations against enterococci in an experimental model of intra-abdominal abscess.

A model was developed to permit direct assessment of antibiotic efficacy against Enterococcus species in experimental intra-abdominal abscess. Abscesses yielded Enterococcus faecalis in pure culture. Antimicrobials were delivered by precisely controlled continuous intravenous infusion. After five days of therapy, ampicillin alone or in combination with gentamicin reduced residual bacterial titers from 7.93 +/- 1.05 (untreated) to 3.51 +/- 1.07 and 3.52 +/- 0.81 log10 colony forming units per gram, respectively. Both the clindamycin and gentamicin combination (6.49 +/- 1.33) and metronidazole and gentamicin combination (6.79 +/- 0.90) significantly suppressed the growth of enterococci (p less than 0.01). Combined clindamycin and aztreonam was ineffective, as were any of the agents used alone (except ampicillin). These results may explain, in part, the clinical efficacy of certain drug combinations against the enterococcal component of polymicrobial abscesses despite the apparent lack of in vitro activity of individual agents.

Abdominal Muscles↗

PubMed1988

Activity and mechanism of action of DuP 105 and DuP 721, new oxazolidinone compounds.

The in-vitro activities of DuP 721 and DuP 105, new oxazolidinone antibacterials, were compared with those of cefazolin, cephalexin, ciprofloxacin, clindamycin, oxacillin, penicillin, and vancomycin against Gram-positive cocci. DuP 721 was approximately four-fold more active than DuP 105 with an MIC of 2.0 mg/l for 90% of the Staphylococcus aureus, beta-haemolytic streptococcus and Streptococcus faecalis strains tested, and an MIC of 4.0 mg/l for 90% of the Str. faecium, penicillin-resistant Str. pneumoniae and viridans streptococcus strains tested. DuP 105 was most active against strains of Staph. epidermidis with an MIC of 4.0 mg/l for 90% of the strains tested. There was no cross resistance between these and the other antibacterial agents that were tested. Both oxazolidinones had bacteriostatic activity in broth against susceptible organisms. Both DuP 721 and DuP 105 inhibited ribosomal protein synthesis in a cell-free system. These synthetic, orally absorbable compounds represent a new series of antibacterial agents unrelated by chemical structure to any other currently available antimicrobial agents.

Anti-Bacterial Agents↗

PubMed1988

High-level resistance to gentamicin in clinical isolates of Streptococcus (Enterococcus) faecium.

During a 14-month period beginning in July 1986, three distinct clinical isolates of Streptococcus (Enterococcus) faecium demonstrating high-level resistance (MIC, greater than 2,000 micrograms/ml) to gentamicin, kanamycin, tobramycin, and streptomycin were recovered from individual patients at one institution. Combinations of ampicillin with any of these agents failed to show bactericidal synergism. By filter-mating techniques, high-level gentamicin resistance could be transferred into a susceptible recipient of the same species at frequencies as high as 1 x 10(-4); transfer into Streptococcus faecalis JH2-7 occurred at lower frequencies (less than 2 x 10(-7). Aminoglycoside substrate profile analysis of clinical isolates as well as of laboratory-derived cured strains and transconjugants revealed 2"-aminoglycoside phosphotransferase and 3'-aminoglycoside phosphotransferase (III) phosphorylating enzymes, AAC-6' acetylating activity above that attributable to the intrinsic activity characteristic of S. faecium, and a streptomycin adenylylating enzyme. All three isolates carried a 51-megadalton plasmid. Curing of this plasmid or conjugative transfer into susceptible recipients was associated with the loss or acquisition of high-level gentamicin resistance, respectively. Loss of high-level gentamicin resistance was also observed when curing techniques resulted in a decrease in the size of this plasmid equivalent to a 10-megadalton deletion. Transferable, high-level resistance to gentamicin and other aminoglycosides, which was previously recognized in S. faecalis, has now emerged in clinical isolates of S. faecium, with the attendant concerns for possible spread.

Ampicillin↗

PubMed1988

Synergistic activity between vancomycin or teicoplanin and gentamicin or tobramycin against pathogenic diphtheroids.

The in vitro activities of vancomycin and teicoplanin alone and in combination with gentamicin or tobramycin were studied by time-kill techniques with 11 strains of pathogenic diphtheroids (Corynebacterium group JK). The activities of vancomycin and teicoplanin were similar (MIC for 90% of strains tested [MIC90], 1 microgram/ml), as were those of gentamicin and tobramycin (the MIC90 was 1 microgram/ml for five aminoglycoside-susceptible strains, and the MIC90 was greater than 1,024 micrograms/ml for six aminoglycoside-resistant strains). No consistent synergistic killing could be demonstrated by the combination of glycopeptide and aminoglycoside antibiotics at arbitrarily chosen concentrations within the range of clinically achievable levels. However, by careful adjustment of both vancomycin and gentamicin concentrations within a narrow range below the MIC of each antibiotic, synergistic killing could be seen with an aminoglycoside-susceptible strain but not with an aminoglycoside-resistant strain. Synergism between glycopeptide and aminoglycoside antibiotics occurs with some diphtheroid organisms, but it may not be clinically relevant.

Corynebacterium↗