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D R Snydman

Publications and source records attributed to D R Snydman.

At least 55 records · Page 3Linked to original sources
PubMed1997

Epidemiology of sepsis syndrome in 8 academic medical centers.

CONTEXT: Sepsis syndrome is a leading cause of mortality in hospitalized patients. However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. OBJECTIVE: To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. DESIGN: Prospective, multi-institutional, observational study including 5-month follow-up. SETTING: Eight academic tertiary care centers. METHODS: Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. RESULTS: From January 4, 1993, to April 2, 1994, 12759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean+/-95% confidence limit) of sepsis syndrome was 2.0+/-0.16 cases per 100 admissions, or 2.8+/-0.17 per 1000 patient-days. The unadjusted attack rate for sepsis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Bloodstream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. CONCLUSIONS: Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs. An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available.

Adult↗
PubMed1997

Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients.

Cytomegalovirus (CMV) is a cause of considerable morbidity and mortality among orthotopic liver transplant (OLT) recipients. To study the impact of CMV on cost and hospital length of stay in this population, we undertook an analysis of a cohort of OLT recipients from four transplant centers in Boston who participated in a CMV prophylaxis trial. First posttransplant year hospital length of stay (including the hospital stay after transplantation and readmissions within 1 year after transplantation) was available for all 141 patients included in the study. In a multiple linear regression model bacteremia (P=0.0001), CMV disease (P=0.0007), abdominal reexploration (excluding retransplantation) (P=0.0070), recipient age < or = 16 years (P=0.0352), and the number of units of blood products (red blood cells, platelets, or fresh frozen plasma) administered during transplantation (P=0.0523) were shown to be independently associated with longer first posttransplant year hospital length of stay. Cost data for in-hospital care for the year beginning with admission for liver transplantation were available for 66 OLT recipients. Using a multiple linear regression model, development of CMV disease (P=0.0001), the number of units of blood products administered during transplantation (P=0.0001), bacteremia (P=0.0002), decreased pretransplant renal function (estimated by creatinine clearance) (P=0.0109), and need for retransplantation (P=0.0619) were shown to be independently associated with higher cost. These data strongly suggest that CMV disease has a direct impact on cost and hospital length of stay in liver transplantation.

Adolescent↗
PubMed1997

Effect of cytomegalovirus infection status on first-year mortality rates among orthotopic liver transplant recipients. The Boston Center for Liver Transplantation CMVIG Study Group.

BACKGROUND: To reduce the mortality rate associated with liver transplantation, it is important to identify the risk factors for increased mortality among liver transplant recipients. It has been suggested that cytomegalovirus (CMV) infection is one such risk factor, but no studies have examined mortality rates associated with the CMV serologic status of the donor and recipient by using multivariate techniques. OBJECTIVE: To study the effect of CMV on 1-year mortality rates in orthotopic liver transplant recipients. DESIGN: Intention-to-treat analysis of a cohort. PATIENTS: 146 liver transplant recipients who were enrolled in a multicenter, randomized, placebo-controlled intervention trial. SETTING: Four university-affiliated transplantation centers. RESULTS: 1-year mortality rates for the four strata of donor and recipient CMV serologic status before transplantation were as follows: seronegative donor and recipient, 11%; seronegative donor and seropositive recipient, 22%; seropositive donor and recipient, 30%; and seropositive donor and seronegative recipient, 44% (P = 0.0091). Multivariate analysis using a time-dependent Cox proportional hazards model showed that retransplantation (relative risk, 4.6 [95% CI, 1.9 to 10.7]; P < 0.001); total number of units of blood products administered during transplantation (relative risk, 1.006 per unit [CI, 1.003 to 1.010]; P < 0.001); and presence of CMV disease (relative risk, 3.9 [CI, 1.8 to 8.5]; P < 0.001), invasive fungal disease (relative risk, 3.3 [CI, 1.5 to 7.1]; P = 0.0020), and bacteremia (relative risk, 2.5 [CI, 1.2 to 5.2]; P = 0.0136) were independently associated with higher mortality rates. If post-transplantation variables that were highly correlated with donor and recipient CMV serologic status were restricted from the model, donor and recipient CMV serologic status was the only pretransplantation variable independently associated with higher mortality rates (P = 0.002). CONCLUSION: Donor and recipient CMV serologic status is a significant pretransplantation determinant for death in liver transplant recipients.

Adult↗
PubMed1997

The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, Maryland.

PURPOSE: To assess impact of cytomegalovirus (CMV) donor-recipient serostatus, infection, or disease on development of invasive fungal infection in orthotopic liver transplant recipients. PATIENTS AND METHODS: An analysis of prospectively collected data in 146 liver transplant recipients (intention to treat cohort) from 4 tertiary care, university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). Patients were observed for 1 year after transplantation for the development of CMV infection, CMV disease, CMV pneumonia, as well as for the development of opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine and throat and every other week of buffy coat for CMV for 2 months, then monthly for 6 months, at 1 year, and at the time of any clinical illness. Pre- and posttransplant variables including CMV-serostatus of donor and recipient, fungal isolation from sterile body sites, fungemia, bacteremia, antibiotic use, immunosuppression, treatment for rejection, and volumes of blood products were measured. RESULTS: Survival analysis demonstrated that 36% of patients with CMV disease developed invasive fungal disease within the first year post-transplant compared with 8% of those without CMV disease (P < 0.0001). One-year mortality in patients with invasive fungal disease was 15 of 22 (68%) compared with 23 of 124 (19%) in those without invasive fungal disease (P < 0.001). A multivariable, time-dependent analysis demonstrated that being a CMV-seronegative recipient of a CMV-seropositive donor organ (P < 0.001), having bacteremia (P = 0.001), UNOS (United Network for Organ Sharing) status 4 (need for life support measures) at transplant (P = 0.002), and volume of platelets (P = 0.002) were independently associated with invasive fungal disease. Restriction of cases of invasive fungal disease to those that occurred more than 2 weeks after transplant demonstrated an association with CMV disease (P = 0.003), bacteremia (P = 0.003), need for life support (P = 0.03), and volume of blood products transfused (P = 0.02). CONCLUSION: CMV disease or being a CMV-seronegative recipient of a CMV-seropositive donor organ is an important predictor for invasive fungal disease following orthotopic liver transplantation.

Adolescent↗
PubMed1997

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗
PubMed1997

Clinical and epidemiological predictors of recurrent cytomegalovirus disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

Predictors of recurrent cytomegalovirus (CMV) disease after the first episode of successfully treated CMV disease in orthotopic liver transplant recipients were studied. Recurrent CMV disease was defined as disease diagnosed > 14 days after the end of a minimum 8-day course of ganciclovir therapy for the first episode and was classified as early or late if it occurred within or after 90 days, respectively, after completion of ganciclovir treatment. Eleven (27%) of 41 patients had recurrent CMV disease (nine early recurrences and two late recurrences). Death was more likely to occur in patients with recurrent CMV disease than in those without it (55% vs. 13%, respectively; P = .006). Initial episodes of multiorgan CMV disease (P = .001) and CMV pneumonia (P = .012) were associated with early recurrence. Multivariate analysis showed that multiorgan CMV disease was independently associated with early recurrence (P = .003; odds ratio, 13.5; 95% confidence interval, 2.4-76.8). Recognition of risk factors for recurrent CMV disease may help identify patients for whom a more intensive therapeutic or diagnostic approach is needed.

Antiviral Agents↗
PubMed1997

Surveillance cultures of blood, urine, and throat specimens are not valuable for predicting cytomegalovirus disease in liver transplant recipients. Boston Center for Liver Transplantation Cytomegalovirus Immune Globulin Study Group.

The role of markers of cytomegalovirus (CMV) infection, such as the isolation of CMV, the presence of CMV antigenemia, or detection of viral DNA by polymerase chain reaction (PCR) assay, as predictors of subsequent CMV disease has been examined in recent studies. We studied the value of performing surveillance cultures of blood, urine, and throat specimens in a cohort of 156 liver transplant recipients who had participated in clinical trials and had received ganciclovir only for documented CMV disease. Cultures of urine and throat specimens for detection of CMV were performed every week, and cultures of blood specimens were performed every other week for the first 2 months after transplantation, then monthly for 6 months. Eighty-nine (57%) of 156 patients developed CMV infection, 41 (46%) of whom developed clinical CMV disease (36 had organ involvement and five had CMV syndrome). Fifty (32%) of 156 patients had positive blood cultures, 35 (22%) had positive urine cultures, and 41 (26%) had positive throat cultures. The positive and negative predictive values of surveillance cultures for predicting CMV disease were as follows: blood cultures, 46% and 83%, respectively; urine cultures, 26% and 74%, respectively; and throat cultures, 32% and 76%, respectively. These data indicate that such cultures are not useful in predicting CMV disease in liver transplant recipients. Future studies should examine the value of alternative markers, such as CMV antigenemia or the detection of viral DNA by PCR, for predicting CMV disease in this setting.

Adult↗
PubMed1997

Effect of pH on in vitro antimicrobial susceptibility of the Bacteroides fragilis group.

We studied the effect of pH (7.1, 6.3, and 5.8) on the in vitro susceptibilities of 59 isolates of Bacteroides fragilis and 60 isolates of other B. fragilis group species to trovafloxacin, ciprofloxacin, clindamycin, ampicillin-sulbactam, piperacillin-tazobactam, imipenem, and meropenem. For each agent tested the geometric mean MIC was highest at pH 5.8, intermediate at pH 6.3, and lowest at pH 7.1. The magnitude of the pH effect varied greatly among different antibiotics. These data show that an acidic pH decreases the in vitro susceptibilities of the B. fragilis group to several antibiotics.

Ampicillin↗
PubMed1997

Cytomegalovirus immune globulin (CMVIG) prophylaxis is associated with increased survival after orthotopic liver transplantation. The Boston Center for Liver Transplantation CMVIG Study Group.

Cytomegalovirus (CMV) causes considerable morbidity and mortality in orthotopic liver transplant (OLT) recipients. Several prophylactic strategies against CMV have been studied in solid organ transplant recipients, including cytomegalovirus immune globulin (CMVIG). We examined the effect of CMVIG prophylaxis on first-year and long-term survival after liver transplantation. Data were analysed for 162 OLT recipients from four transplant centers in Boston who participated in two CMVIG prophylaxis trials. Ninety patients received CMVIG (median follow-up 5.6 yr), and 72 patients received placebo (median follow-up 5.4 yr). CMVIG prophylaxis was shown to be associated with increased first-year (86% vs. 72%, p = 0.029) and long-term (68% vs. 54%, p = 0.055) survival. The distribution of baseline characteristics including donor and recipient demographics, donor CMV serostatus, United Network for Organ Sharing (UNOS) status, pre-transplant renal and liver function tests, transplantation surgical time, number of units of blood products administered during transplantation, primary immunosuppressive regimen, use of solumedrol or antilymphocyte therapy for induction of immunosuppression or treatment of rejection, and surgical complications was similar for CMVIG and placebo recipients. CMVIG recipients were more likely to have primary biliary cirrhosis than placebo recipients (21% vs. 8%, p = 0.025). Using a Cox proportional hazards multivariate model to control for pre-transplant liver disease, CMVIG was shown to be independently associated with increased first-year survival (p = 0.042); a trend toward association with increased long-term survival (p = 0.098) was also shown. These data support that CMVIG prophylaxis, beyond its proven efficacy in decreasing the incidence of severe CMV-associated disease, is associated with increased survival when used prophylactically in OLT recipients.

Adolescent↗
PubMed1996

Incidence and predictors of cytomegalovirus pneumonia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

The incidence, predictors, and outcome of cytomegalovirus pneumonia in OLT recipients have not been well defined. We conducted an analysis of prospectively collected data from 141 OLT recipients who were included as part of a randomized, placebo-controlled trial of CMV immune globulin prophylaxis. Cytomegalovirus pneumonia was diagnosed in 13 of 141 (9.2%) OLT recipients during the first year posttransplant and was associated with a higher 1-year mortality compared with those recipients without CMV pneumonia (84.6 vs. 17.2%, P=0.0001). Univariate analysis demonstrated that CMV viremia (P=0.001), invasive fungal disease (P=0.0001), donor(+)/pretransplant recipient(-) CMV serologic status (P=0.013), abdominal operation (excluding retransplantation) after liver transplantation (P=0.0027), bacteremia (P=0.0105), and advanced United Network of Organ Sharing status (P=0.023) were associated with CMV pneumonia. Cytomegalovirus viremia was diagnosed in 11 of 13 patients with CMV pneumonia at a median of 11 days (range 1-66 days) before diagnosis of CMV pneumonia. In a multivariate analysis using a time-dependent, Cox proportional hazards model, CMV viremia (RR=8.6, 95% CI 1.8-39.7, P=0.0012), invasive fungal disease (RR=6.5, 95% CI 2.1-20.3, P=0.0001), and abdominal reoperation (RR=4.4, 95% CI 1.4-13.1, P=0.0043) were found to be independent predictors of CMV pneumonia. The attributable mortality associated with CMV pneumonia within the first year after liver transplantation for the patients with CMV pneumonia was 67.4%. Intensified measures for prevention of CMV should be considered for patients at high risk of developing CMV pneumonia.

Adult↗
PubMed1996

Risk factors leading to clinical failure in the treatment of intra-abdominal or skin/soft tissue infections.

A study of determinants of outcome in adult patients with intra-abdominal or skin/soft tissue infections treated with cefotetan, cefoxitin, or ampicillin/sulbactam monotherapy was undertaken. Patients were matched for principal infectious process, surgery performed for the management of the infection, year of hospital admission, age, and sex. The criteria for inclusion, exclusion, and matching of patients and assignment of clinical and microbiological outcome were based on the 1992 Infectious Diseases Society of America/Federal Drug Administration guidelines for the evaluation of anti-infective drug products. One hundred and thirty-seven cases of intra-abdominal or skin and soft tissue infections treated with cefotetan (n = 47), cefoxitin (n = 43), or ampicillin/sulbactam (n = 47) monotherapy were selected without knowledge of outcome and analyzed using a single blinded analysis. The baseline characteristics did not differ between the treatment groups, nor did the rates of clinical or microbiological failure. A multivariate analysis showed that isolation of an organism resistant to the treatment regimen, including Pseudomonas spp., [odds ratio (OR) = 14.9, p = 0.001], being on antibiotic therapy at the time of admission (OR = 4.5, p = 0.007), and diagnosis of a complicated intra-abdominal infection (OR = 3.5, p = 0.014) were independently associated with clinical failure. These data support the assertion that antibiotic resistant organisms in mixed anaerobic/aerobic infections are associated with clinical failure and suggest that the antibiotic regimen should be modified to include Pseudomonas spp. in its spectrum when this organism is isolated from patients with such infections.

Abdominal Abscess↗
PubMed1996

The changing face of candidemia: emergence of non-Candida albicans species and antifungal resistance.

OBJECTIVES: To assess the changing epidemiology of candidemia in the 1990s, to evaluate the clinical implications for the presence of non-Candida albicans in blood, and to evaluate the presence of antifungal resistance in relation to prior antifungal administration. DESIGN: Multicenter prospective observational study of patients with positive blood cultures for Candida species or Torulopsis glabrata. SETTING: Four tertiary care medical centers. RESULTS: Four hundred twenty-seven consecutive patients were enrolled. The frequency of candidemia due to non-C. albicans species significantly increased in each hospital throughout the 3.5-year study period (P = 0.01). Thirteen percent of candidemias occurred in patients who were already receiving systemic antifungal agents. Candidemias developing while receiving antifungal therapy were more likely caused by non-C. albicans species than by C. albicans species (P = 0.0005). C. parapsilosis and C. krusei were more commonly seen with prior fluconazole therapy, whereas T. glabrata was more commonly seen with prior amphotericin B therapy. Candida species isolated during episodes of breakthrough candidemia exhibited a significantly higher MIC to the antifungal agent being administered (P < 0.001). CONCLUSION: In this large scale study, the non-C. albicans species, especially T. glabrata, emerged as important and frequent pathogens causing fungemia. This finding has major clinical implications given the higher complication and mortality rate associated with the non-C. albicans species. The change in the pattern of candidemia might be partly attributed to the increase in number of immunocompromised hosts and the widespread use of prophylactic or empiric antifungal therapy. This is an ominous sign given the in vitro resistance of the non-C. albicans species to currently available antifungal agents.

Amphotericin B↗
PubMed1996

Primary cytomegalovirus infection in liver transplant recipients: comparison of infections transmitted via donor organs and via transfusions. Boston Center for Liver Transplantation CMVIG Study Group.

Primary cytomegalovirus (CMV) infection in liver transplant recipients generally occurs following transmission via a CMV-seropositive donor organ. Occasionally primary infection arises in recipients of CMV-seronegative donor organs through blood transfusions. We studied the differences in clinical manifestations of primary CMV infection associated with these two modes of transmission, among 40 liver transplant recipients who had documented primary CMV infection post-transplantation. Thirty-one of 40 patients received a CMV-seropositive donor organ; CMV infection in the other nine patients was transfusion related. Symptomatic CMV disease (22 of 31 vs. 4 of 9; P = .06), CMV hepatitis (20 of 31 vs. 1 of 9; P = .007), invasive fungal disease (13 of 31 vs. 0 of 9; P = .03), and death (16 of 31 vs. 1 of 9; P = .06) were more likely to occur in patients with donor organ-associated primary CMV infection. The incubation period between transplantation and onset of CMV infection, a possible marker for viral load, was shorter in recipients of donor organ-transmitted CMV infection (median, 44 vs. 137 days; P = .004). Controlling for potential confounders such as immunosuppression did not alter these associations. Primary CMV infection associated with the donor organ has a more profound impact than primary infection associated with transfusion. These differences may be due to dissimilarities in the viral load associated with donated livers and transfused blood products.

Adolescent↗
PubMed1996

Exposure to cytomegalovirus from the donated organ is a risk factor for bacteremia in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

To define predictors of bacteremia and to assess the potential role of exposure to cytomegalovirus (CMV) as a risk factor for bacteremia in liver transplant recipients, an intention-to-treat analysis of data for 146 orthotopic liver transplant recipients who participated in a multicenter, randomized, intervention trial was undertaken. Fifty-eight episodes of bacteremia occurred in 40 (27.4%) of 146 patients within 1 year after transplantation. Bacteremia was diagnosed a median of 39.5 days (range, 1-325 days) after transplantation. One-year mortality rates were higher among patients with bacteremia than among those without bacteremia (47.5% [19 of 40] vs. 18% [19 of 106], respectively; P = .001). A time-dependent multivariate analysis of variables that were significantly (P < or = .05) associated with bacteremia in the univariate analysis showed that donor CMV seropositivity (relative risk [RR], 3.4; 95% confidence interval [CI], 1.6-6.6; P = .0005), age of younger than 16 years (RR, 2.6; 95% CI, 1.3-5.2; P < .0059), and a major abdominal operation after transplantation excluding retransplantation (RR, 3.8; 95% CI, 1.8-8.0; P = .0004) were independently associated with bacteremia. These epidemiologic data suggest that exposure to CMV from the donated organ is an independent risk factor for bacteremia in orthotopic liver transplant recipients.

Bacteremia↗
PubMed1996

Analysis of trends in antimicrobial resistance patterns among clinical isolates of Bacteroides fragilis group species from 1990 to 1994.

Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.

Bacteroides↗