Showing papers by "Robert C. Moellering published in 1992"

Emergence of Enterococcus as a Significant Pathogen

Abstract: Enterococci are components of the normal bowel flora of humans and other animals. They are often found as part of a mixed flora in intraabdominal and pelvic infections, but their role in these settings has been difficult to assess; early studies suggested that they were not important pathogens under these circumstances. Indeed, it was thought that treatments eliminating most of the other organisms from these sites of mixed infection would often lead to "spontaneous" eradication of the enterococcal component as well. As a result, the enterococci were generally considered harmless commensals. Recent studies, however, have documented the pathogenic potential of these organisms and in fact have shown convincingly that they are significant nosocomial pathogens. Enterococci are also capable of causing a variety of community-acquired infections.

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

Abstract: 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.

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

Abstract: 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.

Contribution of Animal Models in the Search for Effective Therapy for Endocarditis Due to Enterococci with High-Level Resistance to Gentamicin

Abstract: 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.

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

Abstract: 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 (357 +/- 087 and 250 +/- 109 log10 CFU/ml, respectively; mean +/- standard deviation) than with vancomycin (123 +/- 065 and 105 +/- 057 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

29th annual meeting of the Infectious Diseases Society of America.

Abstract: I am pleased to welcome you to the 29th annual meeting of the Infectious Diseases Society of America (IDSA). I will begin my comments by examining a series of problems that face medicine in general and the specialty of infectious diseases in particular. Because of my own parochial vantage point, I will look initially at problems that are unique to infectious disease specialists in the United States, although many have broader implications. I will also state at the outset that the specific problems I will address do not represent a comprehensive list of all of the ills facing American or worldwide medicine or infectious diseases. After briefly examining some of these issues, I will try to place them into a broader context of problems facing medicine throughout the world. In my initial discussion, I will deal with six issues that vary greatly in their importance and impact. These include, first, the practical question of the timing and format of the annual meeting of the IDSA. I will then discuss problems relating to reimbursement for specialists who work in clinical areas, such as infectious disease, in which there are no "gimmicks" or procedures. I will follow with a brief look at some of the issues of satisfaction with lifestyle and practice style among those of us who are primarily in the business of treating patients. Threats to medical research, the loss of prestige of US medicine, and problems in controlling even common infections in the United States round out the eclectic list of topics that form the basis for my initial discussion. As most of you know, the Council of the IDSA at its spring meeting in April 1991 voted to change the format of the annual meeting and to move toward a separation in place and time of the annual meeting from the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). The secretary of the IDSA then sent two letters to the membership requesting input concerning these decisions. Almost 500 letters were received. Most IDSA members supported a change in format of the annual meeting, but a clear majority