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Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 55 records · Page 3Linked to original sources
PubMed1996

The place of quinolones in everyday clinical practice.

The new fluoroquinolones have many attributes and relatively few drawbacks. As a result, they have been rapidly adopted for the treatment of serious bacterial infections. The currently available fluoroquinolones are particularly effective for the treatment of urinary tract infections, bacterial diarrhea, enteric fever, gonorrhea, chancroid, skin and soft tissue infections, acute and chronic gram-negative osteomyelitis, gram-negative pneumonias, serious infections due to a variety of gram-negative bacilli, and in the eradication of the meningococcal carrier state. As we learn more about the properties of these compounds, the number and variety of infections for which they are useful continues to expand.

Anti-Infective Agents↗
PubMed1995

Characterization of vancomycin resistance in Enterococcus durans.

During investigation of an outbreak of vancomycin resistant Enterococcus faecium in a paediatric hospital, an isolate of Enterococcus durans resistant to vancomycin, teicoplanin, ampicillin and highly resistant to gentamicin and streptomycin was found in the stools of a patient also colonized with a strain of E. faecium with the same resistance pattern. Minimal inhibitory concentrations of vancomycin and teicoplanin were 512 and 64 mg/mL, respectively. Resistance to vancomycin as well as high-level resistance to gentamicin was transferable to an E. faecium recipient strain. Both multiresistant E. faecium and E. durans isolates as well as the transconjugant presented only one plasmid. The vanA gene was detected and localized to the high molecular weight plasmid by DNA hybridization with a vanA gene probe. Growth in vancomycin resulted in induction of an approximately 40 kDa protein visible in membrane preparations from these cells. Genetic linkage between vancomycin and gentamicin resistance genes in the same plasmid is suggested.

Anti-Bacterial Agents↗
PubMed1995

In vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent.

This study evaluated the in vitro activity of A-86719.1, a novel 2-pyridone antimicrobial agent. The drug inhibited all tested members of the family Enterobacteriaceae at < or = 0.5 microgram/ml and all tested Pseudomonas aeruginosa, Burkholderia (Pseudomonas) cepacia, and Xanthomonas maltophilia strains at < or = 2 micrograms/ml. All but two strains of gram-positive bacteria were inhibited by < or = 1 microgram of the new drug per ml, including isolates highly resistant to ciprofloxacin.

Anti-Bacterial Agents↗
PubMed1995

Comparative in vitro activities of L-695,256, a novel carbapenem, against gram-positive bacteria.

The in vitro activity of a prototype 2-aryl carbapenem, L-695,256, against gram-positive bacteria was examined. All streptococci and oxacillin-susceptible and -resistant staphylococci were inhibited at concentrations of < or = 0.125, < or = 0.125, and 4 micrograms/ml, respectively. The activity of L-695,256 was superior to that of imipenem against other organisms intrinsically resistant to beta-lactams.

Anti-Bacterial Agents↗
PubMed1994

Comparative activities of piperacillin and tazobactam against clinical isolates of Legionella spp.

We evaluated the in vitro activity of piperacillin alone or in combination with the beta-lactamase inhibitor tazobactam against clinical isolates of Legionella species. At an inoculum of approximately 10(4) CFU, tazobactam, piperacillin, and the 8:1 combination had equivalent activities against Legionella spp. At an approximately 10-fold higher inoculum, the following results were obtained, expressed as MICs for 50 and 90% of strains tested (MIC range): piperacillin, 4 and 16 (0.25 to 32) micrograms/ml; tazobactam, 0.5 and 1 (0.125 to 2) micrograms/ml; and piperacillin-tazobactam (expressed in terms of MIC of piperacillin) 0.5 and 1 (0.03 to 2) micrograms/ml. Tazobactam alone and the combination with piperacillin were more active than piperacillin alone at the higher inoculum.

Drug Synergism↗
PubMed1994

Activity of fleroxacin alone and in combination with clindamycin or metronidazole in experimental intra-abdominal abscesses.

To assess the potential efficacy of fleroxacin in combination with clindamycin or metronidazole in mixed aerobic and anaerobic infections, we used a rat model of intra-abdominal abscesses in which the inoculum consisted of pooled rat feces mixed with BaSO4. Two hours after bacterial challenge, antimicrobial therapy was begun intravenously with regimens designed to stimulate human pharmacokinetics. A combination of clindamycin and gentamicin was included as an established treatment regimen. After 8.5 days of therapy, final bacterial counts in abscesses showed that fleroxacin alone or combined with metronidazole or clindamycin effectively eradicated Escherichia coli, with bacterial densities of < or = 2.84 +/- 0.1, < or = 2.9 +/- 0.1, and < or = 2.9 +/- 0.1 (mean +/- standard error of the mean) log10 CFU/g, respectively. The addition of either clindamycin or metronidazole to fleroxacin substantially enhanced the effectiveness of the regimens against Bacteroides fragilis, with bacterial counts of < or = 3.0 +/- 0.1 or < or = 2.9 +/- 0.1 log10 CFU/g, respectively, versus 9.2 +/- 0.2 log10 CFU/g for fleroxacin alone. The combination of metronidazole and fleroxacin also resulted in a significantly greater reduction of peptostreptococci and Bacteroides thetaiotaomicron than fleroxacin alone (< or = 2.9 +/- 0.1 versus 6.1 +/- 0.9 log10 CFU/g and 3.3 +/- 0.4 versus 8.3 +/- 0.1 log10 CFU/g, respectively). Except for those of B. fragilis, counts of other anaerobes were reduced to a greater extent by metronidazole plus fleroxacin than by clindamycin plus fleroxacin, although differences were not always significant. Metronidazole plus fleroxacin was at least as active a clindamycin plus gentamicin against all species and was significantly more active against Clostridium spp. No regimen effectively eradicated enterococci from the abscesses. These results suggest that the addition of either metronidazole or clindamycin would effectively enhance the spectrum of fleroxacin for treatment of mixed aerobic and anaerobic infections.

Abdomen↗
PubMed1994

In vitro activities of two glycylcyclines against gram-positive bacteria.

The glycylcyclines designated CL 329,998 and CL 331,002 are N,N-dimethylglycylamido derivatives of minocycline and 6-demethyl-6-deoxytetracycline, respectively. In vitro activities of these two antimicrobial agents were compared with those of tetracycline, minocycline, and seven other antimicrobial agents against 412 gram-positive organisms. Both new drugs were significantly more active than minocycline against methicillin-resistant Staphylococcus aureus (MICs for 90% of isolates tested, 0.25 and 0.5 microgram/ml versus 4 micrograms/ml). CL 329,998 inhibited all streptococci, lactobacilli, and Leuconostoc spp. at concentrations of < or = 0.5 microgram/ml, with CL 331,002 slightly less active against some species. All enterococci, including minocycline-resistant and multidrug-resistant isolates, were inhibited at < or = 0.5- and < or = 1.0-microgram/ml concentrations of the new drugs, respectively. Only bacteriostatic activity was evident by time-kill curves. The two glycylcyclines demonstrated activities in vitro that were superior to those of minocycline against several gram-positive bacterial species, and at relatively low concentrations, they inhibited isolates resistant to both tetracycline and minocycline.

Anti-Bacterial Agents↗
PubMed1993

Effect of pH variation on the susceptibility of Helicobacter pylori to three macrolide antimicrobial agents and temafloxacin.

The in vitro susceptibility of 27 clinical isolates of Helicobacter pylori to erythromycin, clarithromycin, azithromycin and temafloxacin under various pH conditions was evaluated. Clarithromycin (MIC90 0.03 micrograms/ml) was found to be significantly more active than either erythromycin (MIC90 0.125 micrograms/ml) or azithromycin (MIC90 0.25 micrograms/ml) at a neutral pH. Lowering the pH to 5.75 resulted in a loss in efficacy from 8- to 32-fold for all three macrolides studied. The MIC90 of clarithromycin (0.5 micrograms/ml) remained lower than those of azithromycin (2 micrograms/ml) and erythromycin (4 micrograms/ml). No synergism or antagonism was observed with combinations of clarithromycin and temafloxacin at either the neutral or lower pH values.

Anti-Bacterial Agents↗
PubMed1993

Meeting the challenges of beta-lactamases.

A wide variety of beta-lactamases are found in clinical isolates of bacteria and, when present, these enzymes often result in resistance to one or more beta-lactam antibiotics. The prevalence of organisms with these enzymes has increased as beta-lactams have been increasingly used in clinical practice. This paper defines the nature of these enzymes and details the attempts to overcome the problem of resistance mediated by beta-lactamase, efforts which have culminated in the development of a series of effective beta-lactamase inhibitors which can be combined with beta-lactam antibiotics. The currently available compounds, clavulanic acid, sulbactam, and tazobactam are very effective inhibitors of many types of beta-lactamases, but there are additional enzymes which are resistant even to these inhibitors and which pose continuing challenges for the pharmaceutical chemist and clinician alike.

Animals↗
PubMed1993

Efficacy of ceftriaxone plus tazobactam in a rat model of intraabdominal abscess due to Bacteroides fragilis.

Using a rat model of intraperitoneal abscess due to Bacteroides fragilis, we evaluated therapy with the combination of ceftriaxone plus the beta-lactamase inhibitor tazobactam in comparison with ceftriaxone or cefotaxime alone. When treatment was begun five hours after bacterial challenge, final bacterial counts within abscesses at 3.5 days of treatment were as follows (mean +/- S.D., log10 cfu/g): ceftriaxone plus tazobactam, 4.15 +/- 1.25; cefotaxime, 4.77 +/- 1.80; ceftriaxone alone, 5.68 +/- 1.04; untreated controls, 9.14 +/- 1.13. In spite of pharmacokinetic differences between the two drugs, coadministration of tazobactam significantly enhanced activity of ceftriaxone in this model.

Abdomen↗
PubMed1993

In vitro activity of CP-99,219, a new fluoroquinolone, against clinical isolates of gram-positive bacteria.

The in vitro activity of the fluoroquinolone CP-99,219 against gram-positive bacteria was compared with those of five other antimicrobial agents. Against ciprofloxacin-susceptible staphylococci and against streptococci, MICs were < or = 0.12 and < or = 0.5 microgram/ml, respectively. CP-99,219 was also more active than ciprofloxacin against ciprofloxacin-resistant staphylococci, most enterococci, Leuconostoc spp., and lactobacilli.

Anti-Bacterial Agents↗
PubMed1993

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

Using a rat model of aortic valve infective endocarditis, we previously found that oxacillin was equally effective against an oxacillin-susceptible strain of Staphylococcus aureus and a beta-lactamase-hyperproducing borderline oxacillin-susceptible strain of S. aureus; also, ampicillin-sulbactam was less effective than oxacillin against both isolates and at low doses was less effective against the borderline-susceptible strain than against the fully oxacillin-susceptible strain (C. Thauvin-Eliopoulos, L. B. Rice, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 34:728-732, 1990). In the present study, we extended this work, using alternative treatment schedules and additional bacterial strains. Extending treatment with low doses of ampicillin-sulbactam (500 and 250 mg/kg of body weight per day, respectively) to 6.5 days resulted in equalization of effectiveness against the previously studied strains BOSSA-1 and OSSA-1 (3.75 +/- 1.61 log10 and 4.71 +/- 1.79 log10 CFU of residual viable bacteria per g, respectively). Against the borderline oxacillin-susceptible strain BOSSA-1, increasing the sulbactam dosage from 500 to 2,000 mg/kg/day while maintaining a fixed dose of ampicillin (1,000 mg/kg/day) by continuous infusion resulted in lower bacterial counts (4.93 +/- 1.84 log10 versus 3.65 +/- 1.26 log10 CFU of residual viable bacteria per g, respectively), but this difference was of only borderline significance; differences in efficacy between the low-dose and high-dose sulbactam regimens were exaggerated when intermittent intravenous administration was used (6.19 +/- 1.90 log10 versus 3.37 +/- 1.41 log10 CFU/g, respectively; P < 0.001). However, for any individual sulbactam dosage, the model of administration (continuous versus intermittent infusion) did not affect the activity of the regimen. When additional strains were used in the model, oxacillin and ampicillin-sulbactam (1,000 plus 2,000 mg/kg/day) were equally effective against both oxacillin-susceptible and borderline oxacillin-resistant strains of S. aureus. These results support the predictions that oxacillin would be clinically effective in the treatment of infections caused by borderline oxacillin-susceptible strains of S. aureus and that, except at very low doses, ampicillin-sulbactam would also be as effective against borderline-susceptible strains as against fully oxacillin-susceptible strains of S. aureus.

Ampicillin↗
PubMed1993

In vitro activity of RP59500, an injectable streptogramin antibiotic, against vancomycin-resistant gram-positive organisms.

The in vitro activity of RP59500, a streptogramin antibiotic, against 146 clinical isolates of vancomycin-resistant gram-positive bacteria was examined. Five strains of the species Enterococcus casseliflavus and Enterococcus gallinarum, for which the MIC of vancomycin was 8 micrograms/ml, were also studied. Twenty-eight vancomycin-susceptible strains of Enterococcus faecalis and Enterococcus faecium were included for comparison. The drug was highly active against Leuconostoc spp., Lactobacillus spp., and Pediococcus spp. (MICs, < or = 2 micrograms/ml). RP59500 was more active against vancomycin-susceptible strains of E. faecium than E. faecalis (MICs for 90% of the strains [MIC90s], 1.0 versus 32 micrograms/ml). Vancomycin-resistant strains of E. faecalis were as resistant to RP59500 as vancomycin-susceptible strains (MIC90, 32 micrograms/ml), but some vancomycin-resistant E. faecium strains were relatively more resistant to the new agent (MIC90, 16; MIC range, 0.5 to 32 micrograms/ml) than were vancomycin-susceptible organisms of this species.

Drug Resistance, Microbial↗
PubMed1993

In vitro activity of ramoplanin against vancomycin-resistant gram-positive organisms.

In vitro activity of ramoplanin, a cyclic lipoglycopeptide, against 92 vancomycin-resistant gram-positive organisms was evaluated. Ramoplanin demonstrated potent activity against many highly vancomycin-resistant organisms including enterococci (MICs for 90% of strains tested of 0.5 micrograms/ml) and against Lactobacillus spp., Leuconostoc spp., and Pediococcus spp., all of which were inhibited at concentrations of < or = 0.25 micrograms/ml. This drug or a derivative compound merits further investigation as a potential therapeutic agent for infections due to vancomycin-resistant enterococci.

Anti-Bacterial Agents↗
PubMed1993

A gene conferring resistance to vancomycin but not teicoplanin in isolates of Enterococcus faecalis and Enterococcus faecium demonstrates homology with vanB, vanA, and vanC genes of enterococci.

We report the sequence of a 630-bp fragment of a gene associated with resistance to high levels of vancomycin in a clinical isolate of Enterococcus faecalis which retained susceptibility to teicoplanin. This gene was similar to the recently sequenced vanB and partially homologous with vanA, but it showed less-marked similarity to vanC. A DNA probe, derived from this polymerase chain reaction-amplified gene fragment, hybridized specifically with genomic DNA from Enterococcus faecium and E. faecalis isolates which were vancomycin resistant (MICs ranged from 8 to 512 micrograms/ml) but susceptible to teicoplanin. Curing of vancomycin resistance was associated with loss of DNA hybridization with the gene probe. Transfer of DNA which hybridized with the probe accompanied transfer of vancomycin resistance to a susceptible recipient strain. Neither curing nor transfer of vancomycin resistance was consistently related to loss or acquisition, respectively, of plasmid DNA.

Amino Acid Sequence↗