Search PubMed⌕ Search

Biomedical subjects

R C Moellering

Publications and source records attributed to R C Moellering.

At least 37 records · Page 2Linked to original sources
PubMed1999

Activities of the oxazolidinones linezolid and eperezolid in experimental intra-abdominal abscess due to Enterococcus faecalis or vancomycin-resistant Enterococcus faecium.

The in vivo effectiveness of oxazolidinones eperezolid (U-100592) and linezolid (U-100766) against one strain each of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium was examined in a rat model of intra-abdominal abscess. MICs of both drugs were 2 microg/ml for each strain. At doses of 25 mg/kg of body weight twice daily intravenously or orally, linezolid produced small but statistically significant reductions in abscess bacterial density for E. faecalis. The reduction in viable cells observed would not likely be clinically relevant. Eperezolid was ineffective at this dose. At a dosage of 100 mg/kg/day, linezolid treatment led to an approximately 100-fold reduction in viable cells per gram of abscess. Against E. faecium infections, intravenous eperezolid and oral linezolid were effective, reducing densities approximately 2 log(10) CFU/g. Both oxazolidinones demonstrated activity against enterococci in this model. However, results were modest with the dosing regimens employed.

Abdominal Abscess↗
PubMed1998

The specter of glycopeptide resistance: current trends and future considerations.

Two glycopeptide antibiotics, vancomycin and teicoplanin, are currently available for clinical use in various parts of the world, whereas a third, avoparcin, is available for use in agricultural applications and in veterinary medicine in some countries. Because of their outstanding activity against a broad spectrum of gram-positive bacteria, vancomycin and teicoplanin have often been considered the drugs of "last resort" for serious infections due to drug-resistant gram-positive pathogens. Glycopeptides had been in clinical use for almost 30 years before high-level resistance, first reported in enterococcal species, emerged. More recently, there have been disturbing reports of low- and intermediate-level resistance to vancomycin in strains of Staphylococcus aureus. A review of earlier reports reveals, however, that S. aureus strains with reduced susceptibility to glycopeptides were first identified >40 years ago. Such strains may occur in nature or may have developed low-level mutational resistance in response to the selection pressure of glycopeptide therapy. Of considerably greater concern is the possibility that vancomycin resistance genes found in enterococci may be transferred to more virulent organisms such as staphylococci or Streptococcus pneumoniae.

Anti-Bacterial Agents↗
PubMed1998

Perspectives on switching oral acyclovir from prescription to over-the-counter status: report of a consensus panel.

The proposed switching of oral acyclovir from prescription to over-the-counter (OTC) status for the 5-day episodic treatment of genital herpes was considered by a consensus panel. It was concluded that self-diagnosis/misdiagnosis, misuse, and adverse drug effects were potential problems with the OTC use of acyclovir. While acyclovir reduces asymptomatic shedding of herpes simplex virus type 2, the reduction in transmission of virus potentially resulting from increased acyclovir use was felt to be of unknown extent but likely to be of benefit overall. The availability of acyclovir would likely be improved. There were differences in opinion as to whether widespread availability of acyclovir (prescription or OTC) may speed the development of viral resistance. However, all panel members felt that granting OTC status may set an undesirable precedent for the switch from prescription to OTC use of other systemically administered antiinfective agents. The effect of this precedent, in terms of accelerating development of multidrug-resistant bacteria, was a major concern of all panel members. The consensus was that the switch of acyclovir to OTC status could not be supported.

Acyclovir↗
PubMed1998

Antibiotic resistance: lessons for the future.

It is clear that emergence of resistant bacterial strains will continue to be a problem as long as clinicians use the currently available antimicrobial agents. Past and current policies for dealing with resistance have, at best, been only partially effective. Thus, novel approaches to the problem of antimicrobial resistance are badly needed. Development of novel "classic" antimicrobial agents, chemical modification of currently known agents to overcome resistance, and the development of potentiators of known antimicrobials represent three areas that have been partially exploited in the past and continue to represent fertile fields for additional investigation. In addition, a number of investigators are working to develop inhibitors of new bacterial targets and to develop inhibitors of genes relating to virulence or pathogenesis. Although the deployment of antisense nucleotides as antimicrobial agents is theoretically appealing, to date, it has not been possible to develop any of these agents for clinical use.

Anti-Bacterial Agents↗
PubMed1998

Vancomycin-resistant enterococci.

Enterococci, a part of normal gut flora, are not particularly pathogenic organisms in humans. For example, they do not cause respiratory tract infections. The most frequent enterococcal infections are urinary tract infections. Despite their lack of pathogenicity, enterococci have emerged as significant nosocomial pathogens in the United States and elsewhere. Enterococci are formidable pathogens because of their resistance to antimicrobial agents. Enterococci are intrinsically resistant to beta-lactam agents and aminoglycosides and were the first bacteria to acquire vancomycin resistance. Infection control measures have been far from effective at preventing the dissemination of vancomycin-resistant enterococci in the hospital. Therapy for infections due to vancomycin-resistant enterococci presents real challenges. Most isolates remain susceptible to nitrofurantoin, but this agent is useful only for urinary tract infections. The greatest threat posed by vancomycin-resistant enterococci is the potential to transfer their resistance genes to more pathogenic gram-positive bacteria, which could produce truly frightening pathogens.

Anti-Bacterial Agents↗
PubMed1998

Problems with antimicrobial resistance in gram-positive cocci.

The development of antimicrobial resistance has almost invariably accompanied the therapeutic use of antimicrobial agents. Newer antimicrobials have succeeded partly but not entirely in overcoming the problem of resistance. Antimicrobial resistance in gram-positive cocci has achieved its greatest prominence in the past 15 years. There has been a steady erosion of antimicrobial activity against gram-positive cocci. The presentations in this symposium dealt with some of the important problems of antimicrobial resistance in gram-positive cocci, including methicillin resistance and multidrug resistance in staphylococci, penicillin resistance in pneumococci, and vancomycin resistance in enterococci. A related problem that warrants attention is the potential for explosive development of macrolide resistance in gram-positive cocci. This potential is particularly pertinent because the popularity of a number of new macrolides has led to a striking increase in their use. This occurrence will almost certainly be accompanied by a generalized increase in resistance in gram-positive cocci.

Anti-Bacterial Agents↗
PubMed1998

In-vitro activity of the new ketolide antibiotic HMR 3647 against gram-positive bacteria.

The comparative in-vitro activity of HMR 3647, a new ketolide antibiotic, was investigated against 492 clinical isolates of gram-positive bacteria, including multiply resistant strains, by an agar-dilution technique. All streptococci tested were inhibited by the new ketolide at concentrations < or = 0.5 mg/L. HMR 3647 was more potent than erythromycin against staphylococci. For enterococci the new compound yielded an MIC90 of 8 mg/L. Erysipelothrix spp., Pediococcus spp., Leuconostoc spp., Lactobacillus spp., JK diphtheroids and Listeria monocytogenes were also susceptible to the new ketolide.

Anti-Bacterial Agents↗
PubMed1998

Characterization of vancomycin-resistant Enterococcus faecium isolates from the United States and their susceptibility in vitro to dalfopristin-quinupristin.

In the course of clinical studies with the investigational streptogramin antimicrobial dalfopristin-quinupristin, isolates of vancomycin-resistant Enterococcus faecium were referred to our laboratory from across the United States. Seventy-two percent of the strains were of the VanA type, phenotypically and genotypically, while 28% were of the VanB type. High-level resistance to streptomycin or gentamicin was observed in 86 and 81%, respectively, of the VanA strains but in only 69 and 66%, respectively, of the VanB strains. These enterococci were resistant to ampicillin (MIC for 50% of the isolates tested [MIC50] and MIC90, 128 and 256 microg/ml, respectively) and to the other approved agents tested, with the exception of chloramphenicol (MIC90, 8 microg/ml) and novobiocin (MIC90, 1 microg/ml). Considering all of the isolates submitted, dalfopristin-quinupristin inhibited 86.4% of them at concentrations of < or = 1 microg/ml and 95.1% of them at < or = 2 microg/ml. However, for the data set comprised of only the first isolate submitted for each patient, 94.3% of the strains were inhibited at concentrations of < or = 1 microg/ml and 98.9% were inhibited at concentrations of < or = 2 microg/ml. Multiple drug resistance was very common among these isolates of vancomycin-resistant E. faecium, while dalfopristin-quinupristin inhibited the majority at concentrations that are likely to be clinically relevant.

Anti-Bacterial Agents↗
PubMed1998

Susceptibilities of Legionella spp. to newer antimicrobials in vitro.

The in vitro activities of 13 antimicrobial agents against 30 strains of Legionella spp. were determined. Rifapentine, rifampin, and clarithromycin were the most potent agents (MICs at which 90% of isolates are inhibited [MIC90s], < or = 0.008 microgram/ml). The ketolide HMR 3647 and the fluoroquinolones levofloxacin and BAY 12-8039 (MIC90s, 0.03 to 0.06 microgram/ml) were more active than erythromycin A or roxithromycin. The MIC90s of dalfopristin-quinupristin and linezolid were 0.5 and 8 micrograms/ml, respectively. Based on class characteristics and in vitro activities, several of these agents may have potential roles in the treatment of Legionella infections.

Anti-Bacterial Agents↗
PubMed1997

Influence of erythromycin resistance, inoculum growth phase, and incubation time on assessment of the bactericidal activity of RP 59500 (quinupristin-dalfopristin) against vancomycin-resistant Enterococcus faecium.

RP 59500, a mixture of two semisynthetic streptogramin antibiotics (quinupristin and dalfopristin), is one of a few investigational agents currently in clinical trials with inhibitory activity against multiple-drug-resistant strains of Enterococcus faecium. We evaluated the bactericidal activity of this antimicrobial against 30 recent clinical isolates of vancomycin-resistant E. faecium, including 23 erythromycin-resistant (MIC, >256 microg/ml) and 7 erythromycin-intermediate (MIC, 2 to 4 microg/ml) strains. All isolates were inhibited by RP 59500 at 0.25 to 1.0 microg/ml. The bactericidal activity of RP 59500 was markedly influenced by the erythromycin susceptibility of the strains and by several technical factors, such as inoculum growth phase and time of incubation of counting plates. As determined by time-kill methods, RP 59500 at a concentration of 2 or 8 microg/ml failed to kill erythromycin-resistant organisms under any conditions. Bactericidal activity was observed against all seven erythromycin-intermediate isolates when log-phase inocula were used and the cells were counted after 48 h of incubation (mean reductions in viable bacteria for RP 59500 at concentrations of 2 and 8 microg/ml, 3.45 and 3.50 log10 CFU/ml, respectively), but killing was diminished when the plates were examined at 72 h (mean killing, 3.06 and 2.95 log10, CFU/ml, respectively). No bactericidal activity was observed when stationary-phase cultures were used. On the basis of these data, we expect that bactericidal activity of RP 59500 against the multiple-drug-resistant E. faecium strains currently encountered would be distinctly uncommon.

Anti-Bacterial Agents↗
PubMed1997

Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae.

The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76; piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34; cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93. Imipenem was more effective than either of the inhibitor combinations (P < 0.05). Cefotaxime was unexpectedly effective given its poor in vivo activity against this organism in our earlier studies, which used a different dose and total duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These observations suggest that the effectiveness of cephalosporins in the treatment of experimental infections caused by extended-spectrum beta-lactamase-producing K. pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection.

Abdominal Abscess↗
PubMed1997

In vitro activity of RU 64004, a new ketolide antibiotic, against gram-positive bacteria.

The comparative in vitro activity of RU 64004 (also known as HMR 3004), a new ketolide antibiotic, was tested by agar dilution against approximately 500 gram-positive organisms, including multiply resistant enterococci, streptococci, and staphylococci. All streptococci were inhibited by < or = 1 microg of RU 64004 per ml. The ketolide was more potent than other macrolides against erythromycin A-susceptible staphylococci and was generally more potent than clindamycin against erythromycin A-resistant strains susceptible to this agent. Clindamycin-resistant staphylococci (MIC, > 128 microg/ml) proved resistant to the ketolide, but some erythromycin A- and clindamycin-resistant enterococci remained susceptible to RU 64004.

Anti-Bacterial Agents↗
PubMed1996

Comparative in vitro activity of levofloxacin and ofloxacin against gram-positive bacteria.

The in vitro activity of levofloxacin against 506 Gram-positive bacteria was compared with those of D(-)-ofloxacin, ofloxacin, ciprofloxacin, and sparfloxacin. Levofloxacin was generally twice as active as ofloxacin against these organisms (range, 0-3 twofold dilutions). Sparfloxacin appeared to have the greatest activity overall, but for several groups of organisms minimum inhibitory concentrations (MIC90s) of this compound were within one twofold dilution of those of levofloxacin. Resistance to levofloxacin (MIC > or = 8 micrograms/ml) was not encountered among streptococcal species, was rare in methicillin-susceptible staphylococci (1.7%), and was infrequent in vancomycin-susceptible Enterococcus faecalis and Enterococcus faecium (8.7%). Resistance was more common among vancomycin-resistant enterococci and methicillin-resistant staphylococci.

Anti-Bacterial Agents↗
PubMed1996

In vitro activities in new oxazolidinone antimicrobial agents against enterococci.

The comparative in vitro activities of two new oxazolidinone antimicrobial agents, U-100592 and U-100766, against 180 isolates of enterococci representing several resistance profiles were examined by using an agar dilution technique. The two oxazolidinones inhibited all isolates, including strains resistant to vancomycin, ampicillin, and minocycline, at concentrations between 1 and 4 micrograms/ml.

Acetamides↗