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Biomedical subjects

M E Levison

Publications and source records attributed to M E Levison.

At least 37 records · Page 2Linked to original sources

Assessing diagnostic criteria for active infective endocarditis.

A study was performed to describe agreement among experts on their classification of patients, in the absence of information concerning risk factors, as to the presence of infective endocarditis (IE). The study also assessed the clinical characteristics that enabled the experts to determine that a patient had IE. All patients with a discharge diagnosis of IE were identified prospectively from 54 hospitals in the Delaware Valley over a 3-year period. Patients were part of a case-control study of risk factors for IE. Three infectious disease experts independently reviewed abstracted hospital records and classified each of 151 eligible patients as a definite, probable or possible case, or a probable noncase, both based on clinical judgement and using a modified standard definition. Experts were more likely to classify a patient as a definite case of IE on the basis of clinical judgement than by using the modified standard definition. Agreement between reviewers was 92 to 95% when they were distinguishing only probable non-cases from others. Agreement between reviewers on specific categories was lower (40 to 58%). The number of positive blood cultures was a strong predictor of a patient's being classified as a case, as was the type of infecting organism. It is concluded that experts are willing to make a definitive diagnosis of IE on the basis of blood culture information alone. Further supporting evidence, such as the presence of vegetation on an echocardiogram, is needed when blood culture results are ambiguous.

Adult↗

The bactericidal activity of magainins against Pseudomonas aeruginosa and Enterococcus faecium.

The antimicrobial activities of two synthetic magainins, MSI 94 and MSI 93, were investigated in vitro against 20 clinical isolates each of Pseudomonas aeruginosa and Enterococcus faecium. The ranges of the MICs of both agents were 6.25-50 mg/L for P. aeruginosa and 3.13-12.5 mg/L for E. faecium. In time-kill studies, the magainins demonstrated rapid, concentration-dependent bactericidal activity against selected isolates of both species. This bactericidal effect was inoculum-dependent for P. aeruginosa in both the logarithmic and stationary phases of growth. Bacterial regrowth was regularly observed after 24 h of incubation in the time-kill studies; this was due to loss of antimicrobial activity during overnight incubation rather than to the development of resistance. More rapid and sustained bactericidal activity was noted when the magainins were combined with either silver nitrate (AgNO3) or gentamicin against P. aeruginosa and with gentamicin against E. faecium. Neither agent produced a post-antibiotic effect on P. aeruginosa.

Animals↗

Antibiotic treatment of experimental endocarditis due to vancomycin- and ampicillin-resistant Enterococcus faecium.

We compared ciprofloxacin, rifampin, and gentamicin treatments, alone and in combination, for 5 days in the therapy of experimental aortic valve endocarditis in rats caused by a clinical isolate of vancomycin-resistant Enterococcus faecium. The MICs and MBCs of vancomycin, ciprofloxacin, rifampin, and gentamicin were 250 and > 1,000, 3.1 and 6.3, 0.098 and 1.6, and 12.5 and > 50 micrograms/ml, respectively. Infected rats were sacrificed after completing 5 days of therapy. Additional rats within each treatment group were followed for 5 days beyond the last dose of antibiotic therapy. Although survivals in the different groups were not significantly different after 5 days of therapy, survival was significantly better 5 days beyond the last dose of antibiotic therapy in rats treated with rifampin-containing regimens. The combination of ciprofloxacin and gentamicin was bactericidal in vitro and in vegetations from rats with enterococcal endocarditis. Rifampin alone was similarly bactericidal in vivo, but it was not significantly better than rifampin in combination with other antibiotics. Subpopulations resistant to rifampin, but not ciprofloxacin, were detected in the inoculum and in most vegetations during therapy. However, the combination of ciprofloxacin plus both gentamicin and rifampin reduced both the rifampin-susceptible and -resistant population in vegetations of 9 of 10 animals below the level of detection after 5 days of therapy. Nevertheless, a residual enterococcal population apparently remained in numbers of < 2 log10 CFU/g after 5 days of therapy, which resulted in relapse. Perhaps a longer course of therapy would have eliminated this residual population and improved efficacy.

Ampicillin Resistance↗

Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers.

OBJECTIVES: To describe an epidemic of vancomycin-resistant Enterococcus faecium causing bacteremia and bacteriuria, to identify the source of infection, to delineate risk factors associated with acquisition of the organism, and to determine antibiotic sensitivities for the organism. DESIGN: Investigation of an epidemic, including a case-control study. SETTING: Medical-surgical intensive care unit and ward in a university medical center. PATIENTS: Nine patients infected or colonized with vancomycin-resistant Enterococcus faecium and 20 noninfected controls. MEASUREMENTS: Clinical data, environmental surveillance cultures, and in-vitro microbiologic studies. RESULTS: Colonization or infection by vancomycin-resistant E. faecium was associated with an increased duration of treatment with ceftazidime, 13.2 compared with 4.6 days, and a greater number of nonisolated days of hospitalization in the intensive care unit, 19.9 compared with 6.4 days for infected and noninfected patients, respectively (P less than 0.05). Environmental surveillance cultures recovered the organism repeatedly from the rectal probe handles of three electronic thermometers used exclusively on nonisolated patients in the intensive care unit. Restriction endonuclease analysis of plasmid DNA showed that all clinical and environmental isolates were identical. Infection control measures, including isolation of colonized or infected patients and removal of the rectal thermometer probes suspected to be responsible for transmission, resulted in termination of the outbreak. In-vitro, time-kill studies showed that the combination of ciprofloxacin, rifampin, and gentamicin resulted in bactericidal activity against the organism. CONCLUSIONS: This nosocomial outbreak of infection due to a highly vancomycin-resistant strain of Enterococcus is the first epidemic in which an electronic thermometer has been implicated as the vehicle of transmission for an infectious agent.

Adolescent↗

Bactericidal activity of ramoplanin against antibiotic-resistant enterococci.

Ramoplanin, a new lipoglycodepsipeptide antibiotic, was uniformly active against 65 strains of enterococci, including strains highly resistant to vancomycin, penicillin G, and gentamicin. MBCs were usually within a fourfold dilution of the MICs. In time-kill studies, ramoplanin alone demonstrated dose-dependent bactericidal activity against enterococcal strains that resisted killing by vancomycin or penicillin in combination with gentamicin.

Anti-Bacterial Agents↗

Host defense mechanisms in the pathogenesis of urinary tract infection.

Certain microorganisms have a propensity for causing urinary tract infection, and the route (either ascending or hematogenous) by which microorganisms contaminate the urinary tract from external sources is frequently characteristic of the microorganism. There are local defense mechanisms both in the urine and at each anatomic site in the urinary tract (urethra, bladder, ureter, and kidney). The defense mechanisms at one site may have opposing effects on microbial growth at other sites in the urinary tract. The outcome following entrance of microorganisms into the urinary tract is a result of competing forces, which consist of these local urinary defense mechanisms, the initial numbers of microorganisms contaminating the urinary tract, and microbial virulence factors.

Aged↗

Synergistic bactericidal activity of rat serum with vancomycin against enterococci.

Animal models of infectious diseases may not predict clinical efficacy when species-related factors come into play. Recently, unexpected bactericidal activity of vancomycin alone against enterococci was observed in a rat model of endocarditis. A factor or factors in rat serum, but not rabbit or human serum, enhanced in vitro killing by vancomycin in four of five clinical isolates of enterococci. Bactericidal activity was maintained on dilution of rat serum to 5.0% and after exposure of serum to 56 degrees C for 30 min. Activity was lost by heating at 60 degrees C for 2 h, ultrafiltration, or absorption with bentonite or heat-killed bacteria. Rat serum appears to contain a factor or factors that contribute bactericidal activity to vancomycin, a drug normally bacteriostatic for these enterococci. The mechanism by which this factor enhances killing of enterococci by vancomycin is unknown.

Animals↗

In vitro susceptibilities of oral pigmented Bacteroides species to trospectomycin and other selected antimicrobial agents.

The in vitro activity of trospectomycin against 97 clinical isolates of oral pigmented Bacteroides species was compared with the activities of five other antimicrobial agents. At 4 micrograms/ml, more than 90% of isolates were inhibited by trospectomycin. Overall, strains that produced beta-lactamase (n = 41) were more resistant to trospectomycin, penicillin G, cefoxitin, piperacillin, and tetracycline but not to clindamycin. In this study, trospectomycin had excellent in vitro activity against oral pigmented Bacteroides species.

Anti-Bacterial Agents↗

High-level penicillin resistance among isolates of enterococci. Implications for treatment of enterococcal infections.

STUDY OBJECTIVE: To determine the extent and clinical significance of high-level penicillin-resistant Enterococcus faecium at our institution. DESIGN: Surveillance of clinical enterococcal isolates, in-vitro susceptibility and timed survival studies, and determination of antibiotic efficacy in an experimental model of enterococcal endocarditis. MEASUREMENTS AND MAIN RESULTS: For a 6-month period, 14% of enterococcal isolates (30 of 212) were identified as E. faecium. One third of the isolates were highly resistant to penicillin G (minimum inhibitory concentration [MIC], greater than or equal to 200 micrograms/mL) but did not produce beta-lactamase. The findings from in-vitro survival studies showed that this high-level resistance resulted in the loss of bactericidal activity normally observed when an aminoglycoside antibiotic agent is combined with penicillin. An experimental rat model of endocarditis provided in-vivo data that confirmed our in-vitro observations. After the rats received therapy for 72 hours, penicillin G either alone or in combination with gentamicin did not significantly decrease the numbers of enterococci in vegetations on heart valves compared with untreated controls (P = 0.62 and P = 0.58, respectively). CONCLUSIONS: Enterococcus faecium accounts for a notable proportion of clinical enterococcal isolates. Many strains from patients at our institution, as well as from patients at other institutions throughout the country, are highly resistant to penicillin. Because high-level penicillin resistance has important therapeutic implications, periodic surveillance and MIC testing of significant enterococcal isolates, especially E. faecium, are suggested.

Animals↗

Postantibiotic effect of penicillin plus gentamicin versus Enterococcus faecalis in vitro and in vivo.

A persistent suppression of bacterial growth following a brief exposure to an antibiotic (postantibiotic effect [( PAE]) has been described for a variety of antibiotics and microorganisms. If a PAE is present in vivo, antibiotic levels in tissue at the site of infection may decrease below the MIC without bacterial regrowth in the latter portion of the dosing interval. In the present studies, a PAE was sought in vitro and in vivo for penicillin G plus gentamicin versus Enterococcus faecalis. The studies demonstrated that increasing concentrations of gentamicin caused an increased rate of bactericidal action and an increasingly prolonged PAE in vitro. The combination of penicillin and gentamicin, in addition to more rapid killing, exhibited a more prolonged PAE than did penicillin alone. However, unlike these in vitro findings, no PAE could be demonstrated in vivo in rats with experimental left-sided enterococcal endocarditis treated with penicillin plus gentamicin. This suggests that antibiotic vegetation levels should be maintained above the MIC throughout the dosing interval to prevent loss of efficacy as a result of bacterial regrowth.

Animals↗

Pharmacodynamics of antimicrobial agents. Bactericidal and postantibiotic effects.

The effectiveness of antibiotic dosing regimens may be strongly influenced by the effects that drug concentrations at the site of infection have on bacterial population dynamics during the interval after a single dose and the cumulative effects after multiple, intermittent doses. These pharmacodynamic effects involve: (1) the rate and extent of bactericidal action and suppression of bacterial growth in tissues, and (2) persistent postantibiotic antibacterial effects. Antimicrobial agents may each exhibit unique pharmacodynamic effects that can vary with the site of infection and species of microorganism.

Anti-Bacterial Agents↗

Absence of a postantibiotic effect in experimental Pseudomonas endocarditis treated with imipenem, with or without gentamicin.

We found an in vitro postantibiotic effect (PAE) of 3-4 h for imipenem and of approximately 5 h for imipenem plus gentamicin against Pseudomonas aeruginosa. We therefore evaluated these antibiotics in a rat model of pseudomonas endocarditis. A rapid bactericidal effect was initially observed in vegetations from rats treated with imipenem alone or in combination with gentamicin. Bacterial counts rose rapidly, however, as soon as levels of imipenem in vegetations fell below the minimal inhibitory concentration (i.e., no PAE was demonstrated). Levels of gentamicin in vegetations were similar to those that had enhanced the bactericidal effect of imipenem and had resulted in a 5-h PAE in vitro. The presence in vitro of a PAE for imipenem, with or without gentamicin, does not necessarily predict its presence in vivo in pseudomonas endocarditis in the rat.

Animals↗

Antibiotic selection and pharmacokinetics in the critically ill.

In critically ill patients, a good outcome of an infection episode often requires early institution of appropriate antimicrobial therapy. The choice of one specific antimicrobial agent or combination of agents over another requires consideration of the nature of the etiologic organism, the host, and the drug(s).

Anti-Bacterial Agents↗

Therapy vs no therapy for bacteriuria in elderly ambulatory nonhospitalized women.

This prospective randomized study was undertaken to determine the efficacy of antimicrobial therapy compared with no therapy for bacteriuria in elderly ambulatory nonhospitalized women. Sixty-one women (mean age, 85.8 years) with bacteriuria were in the no therapy control group and 63 women (mean age, 85.8 years) with bacteriuria were in the therapy group; none had symptoms of urinary tract infection. One short course of antimicrobial therapy achieved a cure rate of 68.3% (43 of 63 women cured) two weeks after treatment. During the six-month follow-up period, ten (16.4%) of 61 women in the no therapy group and five (7.9%) of 63 women in the therapy group developed symptomatic urinary tract infection. At the time of six-month follow-up, 19 (34.5%) of 55 women in the no therapy group and 35 (63.6%) of 55 women in the therapy group did not have bacteriuria. We conclude that for asymptomatic bacteriuria in elderly ambulatory nonhospitalized women, short-course antimicrobial therapy is effective at two-week follow-up and that antimicrobial therapy can eliminate bacteriuria in most of these women for at least a six-month period.

Aged↗