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Biomedical subjects

D R Snydman

Publications and source records attributed to D R Snydman.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cytomegalovirus immune globulin after liver transplantation: a cost-effectiveness analysis.

OBJECTIVE: Cytomegalovirus (CMV) immune globulin (CMVIG) has been shown to significantly reduce severe CMV-associated disease complicating orthotopic liver transplant (OLT). We evaluated the economic impact of severe CMV-associated disease and calculated the marginal cost-effectiveness (C/E) of routine prophylaxis with CMVIG after OLT. DESIGN: C/E analysis. SETTING: Four teaching hospitals in Boston. PATIENTS: Patients who underwent OLT from January 1988 through June 1990. MEASUREMENTS: We gathered actual cost data of hospital care for patients enrolled in a clinical trial of CMVIG prophylaxis in OLT. We calculated average outpatient expenses from a separate group of patients undergoing OLT and developed a regression model to estimate costs during the first year post-transplant (R2 = 0.77). Based on this model, we calculated variable costs (in 1999 US dollars) for all patients in the randomized trial. From the published literature we obtained the probability of CMV outcomes and of long-term survival after OLT. We then developed a decision analytical model to determine an incremental C/E ratio, using a Markov simulation to estimate long-term survival and long-term costs. We discounted costs and life-years at 3% and 5% per yr. RESULTS: Based on the efficacy rate of 54% in the controlled trial, we estimate that CMVIG will increase life expectancy by 0.65 discounted years at an additional cost of $11,600, providing a marginal C/E ratio of $17,900/yr life saved. Examining the confidence limits of efficacy, we estimate that CMVIG will have a marginal C/E ratio of $66,200 gained/yr at an efficacy of 11% and $14,000 gained/yr at an efficacy of 83%. CONCLUSION: After OLT, prophylactic CMVIG has an incremental C/E ratio comparable to that of other well-accepted medical therapies and should be used routinely in these patients.

Cost-Benefit Analysis↗
PubMed2000

Comparative In vitro activities of daptomycin and vancomycin against resistant gram-positive pathogens.

The in vitro activity of daptomycin against 224 current gram-positive clinical isolates including vancomycin-resistant Enterococcus faecium (VREF), methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus spp. (MRSS), and penicillin-resistant Streptococcus pneumoniae (PRSP) was evaluated. The MICs at which 90% of isolates are inhibited for daptomycin and vancomycin, respectively, were as follows: MRSA, 1 and 2 microg/ml; MRSS, 1 and 4 microg/ml; PRSP, 1 and 0.5 microg/ml; and VREF, 2 and >64 microg/ml. Daptomycin was bactericidal against 82% of 17 VREF isolates. The antibacterial activity of daptomycin was strongly dependent on the calcium concentration of the medium. Daptomycin was active against all gram-positive cocci tested.

Colony Count, Microbial↗
PubMed2000

Comparative in vitro activities of clinafloxacin and trovafloxacin against 1,000 isolates of bacteroides fragilis group: effect of the medium on test results.

The in vitro antibacterial activities of clinafloxacin, trovafloxacin, ciprofloxacin, and cefoxitin against 1,000 clinical isolates of Bacteroides fragilis group were compared by agar dilution in brucella blood agar (BBA) and Wilkins Chalgren agar (WCA). Significantly higher geometric mean MICs for the three quinolones and cefoxitin (P<0.001) were obtained in BBA than in WCA. Regardless of medium, clinafloxacin was slightly more active than trovafloxacin. The activity of clinafloxacin and trovafloxacin was greater than that of cefoxitin against B. distasonis, B. ovatus, and B. thetaiotaomicron but lower against B. vulgatus. High cross resistance between trovafloxacin and clinafloxacin was observed.

Anti-Infective Agents↗
PubMed1999

Clinical utility of blood cultures drawn from indwelling central venous catheters in hospitalized patients with cancer.

BACKGROUND: Because of concern about low specificity, the American College of Physicians guidelines and expert opinion discourage the use of a central venous catheter when obtaining blood for culture for bacteremia or fungemia. However, data on the reliability of cultures done with blood obtained from a central venous catheter are conflicting. OBJECTIVE: To determine the sensitivity, specificity, and positive and negative predictive values of cultures done with blood obtained through a central venous catheter compared with peripheral venipuncture. DESIGN: Retrospective cohort study of hospitalized patients with cancer in whom samples for paired cultures were drawn through a central venous catheter and peripheral venipuncture. SETTING: Tertiary care, university-affiliated medical center. PATIENTS: 185 patients hospitalized on a hematology-oncology ward between August 1994 and June 1996. MEASUREMENTS: Blinded assessments of culture results done by infectious disease experts were used as the gold standard. Sensitivity, specificity, and positive and negative predictive values were compared for culture of blood from central catheters and culture of blood from peripheral venipuncture. RESULTS: Of 551 paired cultures, 469 (85%) were catheter-negative/venipuncture-negative, 32 (6%) were catheter-positive/venipuncture-positive, 17 (3%) were catheter-negative/venipuncture-positive, and 33 (6%) were catheter-positive/venipuncture-negative pairs. For the 82 paired cultures with at least one positive result, blinded determination of true bacteremia or fungemia was made by two infectious disease specialists. For catheter draw compared with peripheral venipuncture, sensitivity was 89% (95% CI, 79% to 98%) and 78% (CI, 65% to 90%) (difference, 11 percentage points [CI, -6 to 28 percentage points]), specificity was 95% (CI, 93% to 97%) and 97% (CI, 96% to 99%) (difference, -2 percentage points [CI, -5 to 0.2 percentage points]), positive predictive value was 63% (CI, 50% to 75%) and 73% (CI, 60% to 86%) (difference, -10 percentage points [CI, -26 to 5 percentage points]), and negative predictive value was 99% [CI, 97% to 100%]) and 98% (CI, 96% to 100%) (difference, 1 percentage point [CI, -0.5 to 3 percentage points]). CONCLUSIONS: In hospitalized hematology-oncology patients, culture of blood drawn through either the central catheter or peripheral vein shows excellent negative predictive value. Culture of blood drawn through an indwelling central venous catheter has low positive predictive value, apparently less than from a peripheral venipuncture. Therefore, a positive result from a catheter needs clinical interpretation and may require confirmation. However, the use of a catheter to obtain blood for culture may be an acceptable method for ruling out bloodstream infections.

Anti-Bacterial Agents↗
PubMed1999

Outcome of transplantation of organs procured from bacteremic donors.

BACKGROUND: Transplantation of organs from donors who are bacteremic is controversial. We examined the outcome of recipients of solid organs from donors with bacteremia and/or fungemia at the time of organ recovery. METHODS: All organ donors from a single organ procurement organization between January 1990 and December 1996 were retrospectively analyzed. We calculated rates of transmission from bacteremic or fungemic donors to their recipients and compared the graft and patient survival rates for recipients of these organs with those for recipients of organs from non-bacteremic donors. RESULTS: There were 95 (5.1%) bacteremic donors from a total of 1775, from whom 212 recipients received organs. Forty-six (48%) of the bacteremic donors had pathogens in their blood. Among the 101 recipients of organs from these, no evidence of transmission could be documented. (0% transmission rate, 95% CI 0-3). The remaining 49 donors had either Staphylococcus epidermidis or other unlikely pathogens recovered from the blood. Examination of the 111 recipients of organs from these donors also found no evidence for transmission (0% transmission rate, 95% CI 0-3). Of the 212 recipients, 193 (91%) received a mean of 3.8+/-2.5 days of antibiotics postoperatively. The 30-day graft and patient survival for recipients of organs from bacteremic donors was not significantly different from recipients of organs from nonbacteremic donors (P = 0.695 for patient survival, and P = 0.310 for graft survival). CONCLUSIONS: Organs transplanted from bacteremic donors do not transmit bacterial infection or result in poorer outcomes. Use of organs from these donors could help increase organ availability.

Adult↗
PubMed1999

Infection in solid organ transplantation.

Infection in the organ transplant recipient is a major determinant of the outcome of transplantation. The attributable mortality from invasive fungal disease and cytomegalovirus disease has been 50 and 30%, respectively. Determinants of infection include epidemiologic exposures to environmental pathogens or exposure to latent infection in the donated organ or recipient, and changes in the net state of immunosuppression. For the past two decades significant improvements have been made in the recognition, prevention and treatment of infections, such as cytomegalovirus and P. carinii. Future research will need to focus on treatment of invasive mold infections, and the management of hepatitis B and C in liver transplantation. In addition, improvement in the prevention of the post-transplant lymphoproliferative disease syndrome will be necessary.

Cytomegalovirus Infections↗
PubMed1999

Multicenter study of in vitro susceptibility of the Bacteroides fragilis group, 1995 to 1996, with comparison of resistance trends from 1990 to 1996.

Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most beta-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within the B. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilis group species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the beta-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.

Anti-Bacterial Agents↗
PubMed1998

Significance of cytomegalovirus for long-term survival after orthotopic liver transplantation: a prospective derivation and validation cohort analysis.

BACKGROUND: Cytomegalovirus (CMV) infection and disease has been found to be associated with decreased graft and patient survival among heart transplant recipients. We sought to explore the effect of CMV infection and disease on long-term survival in orthotopic liver transplant (OLT) recipients using a derivation and validation cohort. METHODS: For derivation-validation modeling, we used data collected from two prospectively followed cohorts as the basis for multivariate analyses: 167 OLT recipients from the Boston Center for Liver Transplantation (the derivation set; median follow-up: 5.5 years, mortality: 40%) and an independent cohort of 294 OLT recipients from the Mayo Clinic (the validation set; median follow-up: 4.8 years, mortality: 27%). RESULTS: Underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis, number of units of red blood cells administered during transplantation, and donor CMV seropositivity were the pre- and intratransplant variables independently associated (P<0.01) with decreased long-term survival in the derivation cohort. For variables collected up to 1 year after transplantation, the need for retransplan. tation, CMV pneumonia, invasive fungal disease, and underlying liver disease other than primary biliary cirrhosis or sclerosing cholangitis were independently associated (P<0.01) with decreased long-term survival in the derivation cohort. The magnitude of the relationship of each pre-, intra-, and posttransplant factor with survival, as measured by the relative risk, did not significantly differ between the derivation and validation cohorts. The derivation model, incorporating pre-, intra-, and posttransplant factors, had receiver operating characteristic areas of 73% and 74% for 5-year mortality in the derivation and validation cohorts, respectively. CONCLUSIONS: Data from a derivation and an independent validation cohort demonstrate that CMV factors (reflected by either donor CMV seropositivity at transplantation, CMV pneumonia, or CMV disease within the first posttransplant year) are independently associated with decreased long-term survival in OLT recipients.

Adolescent↗
PubMed1998

Utility of serial rectal swab cultures for detection of ceftazidime- and imipenem-resistant gram-negative bacilli from patients in the intensive care unit.

Forty-four patients receiving intensive care were studied prospectively to assess the utility of serial rectal swab cultures and clinical correlates of resistance for Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., Morganella morganii, and Serratia marcescens strains resistant to ceftazidime or imipenem. Strains of Pseudomonas aeruginosa, Enterobacter spp., Citrobacter spp., or Morganella morganii were found in 26 of 44 (59%) patients: 17 (65%) in clinical sites (11 with concomitant rectal isolates) and nine (35%) in a rectal site only. Of 49 total isolates, 13 (26.5%) were resistant: 10 (20.4%) to ceftazidime and three (6.1%) to imipenem. Surveillance rectal swabs from 27 patients without a clinical isolate identified two patients with resistant organisms (15% of all resistant isolates). The majority of resistance to ceftazidime or imipenem among Pseudomonas or Enterobacter can be detected by the use of clinical specimens alone.

Adult↗
PubMed1998

Vancomycin-resistant enterococcal infections in bone marrow transplant recipients.

Vancomycin-resistant enterococci (VRE) infections have been increasingly reported in immunosuppressed individuals over the past decade. Emergence of this pathogen in the bone marrow transplantation (BMT) setting, in the form of bacteremia or positive stool cultures, is of concern because of lack of effective antimicrobial therapy. We report episodes of vancomycin-resistant E. faecium bacteremia in two patients undergoing BMT including the first case of VRE meningitis observed in this setting. Since the outcome in these patients undergoing matched unrelated donor BMT was fatal, we believe that routine screening for VRE in high risk patients should be considered. Management of VRE carrier state in BMT candidates is unclear at present.

Adult↗
PubMed1998

Human herpesvirus 6 reactivation is associated with cytomegalovirus infection and syndromes in kidney transplant recipients at risk for primary cytomegalovirus infection.

A potential association between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) following kidney transplantation was explored by retrospectively testing serial serum specimens for HHV-6 IgG and IgM antibody. HHV-6 reactivation occurred in 35 (66%) of 53 transplant recipients. Fungal or parasitic opportunistic infections, graft rejection or loss, and mortality were not associated with HHV-6 reactivation. HHV-6 reactivation was associated with primary CMV infection (P=.001) and CMV syndrome (P=.003) and with trends for CMV-related hepatitis (P=.095), CMV-related neutropenia (P=.104), and serious CMV disease (P=.085). After controlling for CMV immune globulin (CMVIG) prophylaxis, the association between HHV-6 reactivation and primary CMV infection and syndrome remained significant (P=.002 and 0.006, respectively). The reduction in CMV syndrome among those receiving CMVIG prophylaxis remained significant (P=.007) after controlling for HHV-6 reactivation. HHV-6 reactivation in kidney transplant recipients at risk for primary CMV infection is associated with CMV infection and CMV-related disease, and these effects are independent of CMVIG prophylaxis.

Adult↗
PubMed1998

Do in vitro susceptibility data predict the microbiologic response to amphotericin B? Results of a prospective study of patients with Candida fungemia.

Outcome for 105 patients with candidemia treated with amphotericin B was correlated with amphotericin B in vitro susceptibility results. Thirty-three patients had microbiologic failure, which was defined as persistence of Candida in the bloodstream despite > or = 3 days of amphotericin B. Amphotericin B minimum inhibitory concentrations (MICs) were determined by the National Committee for Clinical Laboratory Standards methodology. After determination of MICs, the minimal lethal concentrations (MLCs) were determined. The isolates tested yielded a narrow range of amphotericin B MICs (0.06-2 microg/mL); only 5% (5/105) exhibited MICs > or = 1 microg/mL. The MLC range, on the other hand, was significantly broader (0.125 to > 16 microg/mL); 24% (25/105) exhibited MLCs > or = 1 microg/mL. The strongest predictor for microbiologic failure was 48-h MLC (P < .001), followed by 24-h MLC (P = .03) and 48-h MIC (P = .11). A resistant break point for amphotericin B of > 1 microg/mL for MLC and > or = 1 microg/mL for MIC could be inferred from this study.

Amphotericin B↗
PubMed1998

Infective endocarditis in solid organ transplant recipients.

Infective endocarditis, defined as pathologically or clinically definite by the Duke criteria, was observed in 14 transplant recipients at our institutions. In addition, we reviewed 32 previously reported cases in solid organ transplant recipients. The spectrum of organisms causing infective endocarditis was clearly different in transplant recipients than in the general population; 50% of the infections were due to Aspergillus fumigatus or Staphylococcus aureus, but only 4% were due to viridans streptococci. Fungal infections predominated early (accounting for six of 10 cases of endocarditis within 30 days of transplantation), while bacterial infections caused most cases (80%) after this time. In 80% (37) of the 46 cases in transplant recipients, there was no underlying valvular disease. Seventy-four percent (34) of the 46 cases were associated with previous hospital-acquired infection, notably venous access device and wound infections. Three patients with S. aureus endocarditis had had an episode of S. aureus bacteremia > 3 weeks prior to the diagnosis of endocarditis and had received treatment for the initial bacteremia of < 14 days' duration. The overall mortality rate was 57% (26 of 46 patients died), with 58% (15) of the 26 fatal cases not being suspected during life. Endocarditis is an underappreciated sequela of hospital-acquired infection in transplant recipients.

Adult↗
PubMed1998

Limulus amebocyte lysate assay for detection of endotoxin in patients with sepsis syndrome. AMCC Sepsis Project Working Group.

Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection.

Bacteremia↗
PubMed1998

Late incidence of cancer after metronidazole use: a matched metronidazole user/nonuser study.

In vitro mutagenic activity and carcinogenic potential of metronidazole in certain animals raised concerns about its possible carcinogenicity in humans. We studied the late incidence of cancer after metronidazole use among persons enrolled in the Group Health Cooperative of Puget Sound, Seattle, a health maintenance organization. Randomly selected nonusers were matched on a one-to-one basis for age, gender, and year of enrollment to persons who used metronidazole on an outpatient basis during the period January 1975 to December 1983; 5,222 metronidazole user/nonuser pairs, for whom the median follow-up was 12.6 years, were analyzed. Forty-nine percent, 39.2%, 9.8%, and 2% of users had 1, 2-4, 5-9, and > or = 10 prescriptions or refills of metronidazole filled, respectively. The late (after the first 7 years of follow-up) incidence of cancer was nearly identical among users and nonusers (652 and 662 per 100,000 person-years, respectively; relative risk, 0.98; 95% confidence interval, 0.80-1.20). Age-gender stratified analysis did not reveal any association between metronidazole use and cancer. These data support no association between short-term exposure to metronidazole and cancer in humans. Although the results are reassuring, they may not extend to subjects who have used metronidazole for prolonged periods; further epidemiological studies should focus on these individuals.

Adolescent↗
PubMed1998

Adenovirus infection in adult orthotopic liver transplant recipients: incidence and clinical significance.

Adenovirus infection occurs in 10% of pediatric orthotopic liver transplant recipients; however, no cases have been described in adult liver transplant recipients. A retrospective review of 191 adults who underwent liver transplantation from January 1988 through October 1995 was done to describe the incidence and clinical significance of adenovirus infection in this population. There were 11 (5.8%) patients with 16 cultures positive for adenovirus. Sites of isolation were urine (9), blood (2), liver biopsy (2), colonic biopsy (1), lung biopsy (1), and stool (1). Adenovirus infection was classified as either disease or asymptomatic infection. There were 7 cases of adenovirus disease (2 definite, 1 probable, and 4 possible). Disease was disseminated in 3 patients: All had pneumonia and 2 died. Of the 3 patients with pneumonia, 2 had evidence of multiorgan involvement. Adenovirus disease occurs in adult orthotopic liver transplant recipients and may be associated with significant morbidity and occasional mortality.

Adenoviridae↗