PubMed Health⌕ Search

Biomedical subjects

D R Snydman

Publications and source records attributed to D R Snydman.

At least 73 records · Page 4Linked to original sources
PubMed1995

Preemptive ganciclovir therapy to prevent cytomegalovirus disease in cytomegalovirus antibody-positive renal transplant recipients. A randomized controlled trial.

OBJECTIVE: To determine whether preemptive ganciclovir therapy administered daily during antilymphocyte antibody therapy can prevent cytomegalovirus disease in renal transplant recipients who are positive for cytomegalovirus antibody. DESIGN: Randomized, controlled, multicenter trial. SETTING: 6 university-affiliated transplantation centers. PATIENTS: 113 renal transplant recipients who were positive for cytomegalovirus antibody. INTERVENTION: Patients were randomly assigned to receive either 1) ganciclovir, 2.5 mg/kg body weight administered intravenously on every day that antilymphocyte antibody therapy was administered or 2) no anticytomegalovirus therapy. MEASUREMENTS: Patients were observed for 6 months after completion of antilymphocyte antibody therapy for development of cytomegalovirus disease and cytomegalovirus viremia. RESULTS: Cytomegalovirus disease occurred in 14% of patients (9 of 64) who received preemptive ganciclovir therapy and in 33% of controls (16 of 49) (P = 0.018). Cytomegalovirus was isolated from buffy-coat specimens from 17% of patients (11 of 64) receiving preemptive ganciclovir and from 35% of controls (17 of 49) (P = 0.03). Controlling for the reason (induction or treatment of rejection) for using antilymphocyte antibodies in a Cox proportional hazards model, we found that preemptive ganciclovir still protected against cytomegalovirus disease (adjusted relative risk, 0.27; 95% CI, 0.12 to 0.64). No adverse events were attributed to preemptive ganciclovir therapy during or within 6 months of its administration. CONCLUSIONS: Preemptive ganciclovir therapy administered daily during courses of treatment with antilymphocyte antibodies reduced the excessive occurrence of cytomegalovirus disease in renal transplant recipients who were positive for cytomegalovirus antibody. This approach, which links the most potent immunosuppression to intensive antimicrobial therapy, allows preventive therapy to be given to those patients at greatest risk for developing infectious complications. These patients are likely to benefit most from the preventive strategy.

Adolescent↗
PubMed1995

Attributable mortality of bacteremia associated with the Bacteroides fragilis group.

Uncontrolled studies have suggested that Bacteroides fragilis group bacteremia has an attributable mortality rate between 13% and 33%. To determine the true attributable mortality rate and the mortality risk ratio associated with bacteremia due to the B. fragilis group, we conducted a matched-pair study in which cases were matched to controls for age, gender, year of admission, principal discharge diagnosis, and types of major surgery by an investigator blinded to survival status. Cases and controls were comparable in demographic and clinical characteristics. Cases had a significantly higher mortality rate (28% vs. 8.7%, P = .002, McNemar's test), with an attributable mortality rate of 19.3% (95% CI, 8%-30%; P = .003) and a mortality risk ratio of 3.2. In a multivariate analysis, three clinical factors were independently correlated with mortality: the presence of B. fragilis group bacteremia (RR: 4.9; 95% CI: 3.7-6.0; P = .009), congestive heart failure (RR: 8.0; 95% CI: 6.6-9.3; P = .003) or chronic liver disease (RR: 6.3; 95% CI: 4.8-7.7; P = .01). Cases also had a 16-day-longer stay in the hospital (P = .0007, Wilcoxon's signed rank test) compared with controls. Thus, B. fragilis group bacteremia contributes significantly to morbidity and mortality.

Bacteremia↗
PubMed1995

Spectrum and significance of bacteremia due to Moraxella catarrhalis.

Fifty-eight cases of bacteremia due to Moraxella catarrhalis, including seven that occurred in patients treated at our facilities, are analyzed. The host's medical history plays a major role in the presentation and outcome of M. catarrhalis bacteremia. Bacteremia is typically accompanied by pneumonia in adults with underlying respiratory disease. Many neutropenic patients do not manifest a focus of infection; in contrast, the source identified in healthy, immunocompetent patients is usually the upper airway or the ears. In the recent literature, it has been reported that a rash is typically absent in adults with bacteremic pneumonia and in immunocompetent hosts and that only some neutropenic patients have a rash. The prognosis is grave for patients with endocarditis and for patients with immunoglobulin deficiency or neutropenia not related to a hematologic malignancy. In addition, mortality is substantial among bacteremic patients with respiratory conditions or other chronic debilities, especially when respiratory copathogens are present. The prognosis is good for febrile neutropenic patients with underlying leukemia or lymphoma when the neutropenia resolves. When healthy, immunocompetent individuals are affected with M. catarrhalis bacteremia, their presentations range from self-limited febrile illness to life-threatening disease.

Adult↗
PubMed1995

Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates.

We undertook a randomized, placebo-controlled, double blind trial of cytomegalovirus (CMV) immunoglobulin (CMVIG) for prevention of CMV-associated disease in 183 multiply transfused, premature neonates. CMVIG (150 mg/kg) or placebo was given within 24 hours of the first transfusion and at Day 10. If an intravenous catheter was still in place an additional dose was given between Days 20 and 30. The globulin and placebo groups were well-matched with respect to birth weight, gestational age, Apgar score, birth to a CMV-seropositive mother, requirement for assisted ventilation and exposure to CMV-positive, unscreened blood products. Among infants followed for more than 10 days, 18 (10.5%) developed CMV infection; 9 had symptomatic CMV disease (5 placebo; 4 CMVIG). Among infants born to a CMV-seropositive mother, CMVIG use was associated with a CMV syndrome rate of 3.2% (95% confidence interval, 0.2 to 18.5%) compared to 12.5% (95% confidence interval, 4.5 to 27.6%) among placebo recipients (P = 0.163). Among placebo recipients infants born to CMV-seropositive mothers were more likely to have a virologically confirmed CMV syndrome than those born to a CMV-seronegative mother, despite receipt of blood not screened for CMV antibody (P = 0.012). Multivariate analysis demonstrated that two factors were independently associated with CMV acquisition: the volume of CMV-seropositive blood products transfused (P = 0.005); and birth to a CMV-seropositive mother (P = 0.006). Infusions of CMVIG were well-tolerated. This study reaffirms that perinatally acquired CMV disease is more common among infants born to CMV-seropositive mothers than CMV-seronegative mothers, even without use of CMV-screened blood products.

Antibodies, Viral↗
PubMed1995

Antiviral antibodies in transplantation.

Antiviral antibodies clearly play a role in organ transplantation. The only antibody with a licensed indication for this population is CMVIG; however, the use of HBIG has become the standard of care for those patients at risk for HBV recurrence, and the use of VZIG would appear to be indicated for exposures to varicella-zoster in patients lacking immunity. Future studies defining the role of antiviral antibodies for therapy are necessary, and the role of antibody to prevent the EBV PTLD remains to be explored.

Antibodies, Viral↗
PubMed1995

Recurrent cytomegalovirus disease in solid-organ transplant recipients.

Recurrent CMV disease has been reported to occur in 6% to 59% of solid-organ transplant recipients. The consequences of recurrent CMV disease after the treatment of the first CMV disease episode in patient and graft survival have not been fully elucidated. Additionally, few epidemiologic data are available regarding predictors of recurrent CMV disease. In three of four studies that investigated predictors for recurrent CMV disease, primary CMV infection (D+/R-) was associated with a higher rate of recurrent CMV disease among liver, intestinal, and solid-organ transplant recipients in general. Antirejection therapy was associated with recurrent CMV disease in two of three studies that examined this variable as a possible predictor of recurrent CMV disease. Further studies are needed to define the subgroup of solid-organ transplant recipients at higher risk for recurrent CMV disease, for whom more intensive or novel prophylactic, therapeutic, or diagnostic cost-effective strategies are warranted.

Cytomegalovirus Infections↗
PubMed1995

Cytomegalovirus infection in organ transplant recipients.

Cytomegalovirus (CMV) continues to be responsible for a substantial fraction of the morbidity and mortality that follows organ transplantation. The three major consequences of CMV infection are CMV disease (encompassing a range of clinical illness), superinfection with opportunistic pathogens, and injury to the transplanted organ. In the last decade, considerable progress has been made in elucidating risk factors for CMV disease, in rapid detection of CMV in clinical specimens, and in the use of antiviral chemotherapy and immunoglobulin to prevent and treat CMV disease after transplantation. This article discusses the impact of these advances on patient outcome following transplantation and the challenges for the next decade.

Antiviral Agents↗
PubMed1994

Treatment of severe pneumonia in hospitalized patients: results of a multicenter, randomized, double-blind trial comparing intravenous ciprofloxacin with imipenem-cilastatin. The Severe Pneumonia Study Group.

Intravenously administered ciprofloxacin was compared with imipenem for the treatment of severe pneumonia. In this prospective, randomized, double-blind, multicenter trial, which included an intent-to-treat analysis, a total of 405 patients with severe pneumonia were enrolled. The mean APACHE II score was 17.6, 79% of the patients required mechanical ventilation, and 78% had nosocomial pneumonia. A subgroup of 205 patients (98 ciprofloxacin-treated patients and 107 imipenem-treated patients) were evaluable for the major efficacy endpoints. Patients were randomized to receive intravenous treatment with either ciprofloxacin (400 mg every 8 h) or imipenem (1,000 mg every 8 h), and doses were adjusted for renal function. The primary and secondary efficacy endpoints were bacteriological and clinical responses at 3 to 7 days after completion of therapy. Ciprofloxacin-treated patients had a higher bacteriological eradication rate than did imipenem-treated patients (69 versus 59%; 95% confidence interval of -0.6%, 26.2%; P = 0.069) and also a significantly higher clinical response rate (69 versus 56%; 95% confidence interval of 3.5%, 28.5%; P = 0.021). The greatest difference between ciprofloxacin and imipenem was in eradication of members of the family Enterobacteriaceae (93 versus 65%; P = 0.009). Stepwise logistic regression analysis demonstrated the following factors to be associated with bacteriological eradication: absence of Pseudomonas aeruginosa (P < 0.01), higher weight (P < 0.01), a low APACHE II score (P = 0.03), and treatment with ciprofloxacin (P = 0.04). When P. aeruginosa was recovered from initial respiratory tract cultures, failure to achieve bacteriological eradication and development of resistance during therapy were common in both treatment groups (67 and 33% for ciprofloxacin and 59 and 53% for imipenem, respectively). Seizures were observed more frequently with imipenem than with ciprofloxacin (6 versus 1%; P = 0.028). These results demonstrate that in patients with severe pneumonia, monotherapy with ciprofloxacin is at least equivalent to monotherapy with imipenem in terms of bacteriological eradication and clinical response. For both treatment groups, the presence of P. aeruginosa had a negative impact on treatment success. Seizures were more common with imipenem than with ciprofloxacin. Monotherapy for severe pneumonia is a safe and effective initial strategy but may need to be modified if P. aeruginosa is suspected or recovered from patients.

Adult↗
PubMed1993

Cytomegalovirus immune globulin prophylaxis in liver transplantation. A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To study the effect of cytomegalovirus immune globulin (CMVIG) on prevention of cytomegalovirus (CMV) disease and its complications in patients receiving liver transplants. DESIGN: Randomized, multicenter, placebo-controlled, double-blind trial. SETTING: Four university-affiliated transplant centers in Boston (Boston Center for Liver Transplantation). PATIENTS: One hundred forty-one liver transplant recipients completed the study. INTERVENTION: CMVIG or placebo (1% albumin) given in a dose of 150 mg/kg body weight within 72 hours of the transplant, then at weeks 2, 4, 6, and 8, and at 100 mg/kg at weeks 12 and 16. MEASUREMENTS: Patients were observed for 1 year after transplantation for the development of CMV infection, disease, pneumonia, as well as for opportunistic fungal infections, graft survival, and mortality. Weekly cultures were taken of urine, buffy coat, and throat wash for CMV for 2 months, then monthly, and at any clinical illness. RESULTS: Using a Cox proportional hazards model, CMVIG was shown to reduce severe CMV-associated disease (multi-organ CMV disease, CMV pneumonia, or invasive fungal disease associated with CMV infection) from 26% to 12% (relative risk, 0.39; 95% CI, 0.17 to 0.89). When we controlled for the use of monoclonal antibodies to T cells (OKT3), CMVIG use was still protective (relative risk, 0.39; CI, 0.17 to 0.90). Rates of CMV disease were reduced from 31% to 19% (relative risk, 0.56; CI, 0.3 to 1.1) in CMVIG recipients although no effect on rates of CMV infection, graft survival, or patient survival at 1 year were shown. When we controlled for the urgency of transplantation and OKT3 use, a reduction in CMV disease (relative risk, 0.22; CI, 0.06 to 0.81) was shown for globulin recipients for all serologic groups except for the highest risk group (the CMV-seropositive donor, CMV-seronegative group). CONCLUSION: CMVIG reduced the rate of severe CMV-associated disease in patients undergoing orthotopic liver transplantation. No effect of CMVIG on CMV donor-positive, recipient-negative liver transplant recipients was shown, suggesting a need for additional prophylactic strategies.

Acyclovir↗
PubMed1993

New developments in cytomegalovirus prevention and management.

The use of CMVIG, approved in 1990 for prophylactic administration in seronegative recipients of kidneys from seropositive donors, has been shown to be extremely effective in preventing the considerable morbidity and mortality associated with CMV disease. While the complex interactions between CMV and the immune system, including the effects of immunosuppressive therapy, are still under investigation, passive immunization with CMVIG offers a practical, safe, and cost-effective means of clinical intervention in renal transplant patients known to be at risk for CMV disease. Further clinical studies will need to explore the mechanisms of interaction of CMVIG with reactivation of latent infection and superinfection and with allograft dysfunction and antirejection therapy. Studies that evaluate the use of CMVIG in combination with other pharmacologic and immunologic interventions, both for prevention and treatment of CMV disease, will guide the use of the drug. CMVIG promises to be most helpful in reducing morbidity and mortality in transplant recipients and other particularly at-risk populations such as those who are immunosuppressed iatrogenically.

Antibodies, Viral↗
PubMed1993

Controlled trial to evaluate protection of high-risk infants against respiratory syncytial virus disease by using standard intravenous immune globulin.

We performed a randomized, controlled trial of intravenous immune globulin (respiratory syncytial virus [RSV] neutralizing [Nt] antibody titer of 1:950 in 5% solution) to evaluate protection against RSV-induced disease over two respiratory virus seasons. Forty-nine children (mean age at enrollment, 4.5 months) with severe congenital heart disease or bronchopulmonary dysplasia were randomized as follows. Twenty-four patients were followed as controls and received no immune globulin. Twenty-five patients received monthly infusions of immune globulin at a dose of 500 mg/kg of body weight. There was a similar distribution between groups of patients with heart disease and bronchopulmonary dysplasia. There were 12 culture-proven RSV infections, 6 in the prophylaxis group and 6 in the control group. There was a trend toward less severe RSV illness in immune globulin recipients, as measured by length of hospitalization. Four of the six immune globulin recipients were hospitalized for a total of 35 days (mean, 8.8 +/- 5.0 days) because of RSV illness, in contrast to 51 hospital days (mean, 12.8 +/- 7.6 days) among RSV-infected controls. We conclude that monthly infusions of standard immune globulin containing RSV Nt antibodies may be safely administered to high-risk children, but that standard intravenous immune globulin does not contain sufficient RSV Nt antibody titer to fully protect against severe RSV illness.

Humans↗
PubMed1993

Viral infections in the intensive care unit.

Serious viral infections requiring intensive care generally occur in immunocompromised patients and in those patients with underlying cardiopulmonary disease. However, occasional cases may occur in normal hosts. This article reviews the serious viral diseases that are commonly encountered in the adult ICU, including viral pneumonia, encephalitis, and hepatitis, and focuses on diagnostic techniques and management principles. A separate section is devoted to cytomegalovirus infection, given the prominent role that this virus plays in the immunocompromised host receiving intensive care.

Adult↗
PubMed1993

Monotherapy is appropriate for nosocomial pneumonia in the intensive care unit.

The antibiotic therapy of pneumonia in the patient receiving intensive care has traditionally required the use of two agents, usually a beta-lactam or other broad spectrum agent and an aminoglycoside. A large body of data is now available indicating that initial empiric therapy with a broad spectrum agent (third-generation cephalosporin, carbapenem or fluoroquinolone) is as efficacious as combination therapy in the treatment of critically ill patients with pneumonia. If Pseudomonas aeruginosa is isolated, a second antibiotic may need to be added. Overall, approximately 60% of patients can be successfully treated with any of these regimens. The historic reasons that established antibiotic combinations as the standard for therapy are critically examined and put into perspective. Studies of pharmacokinetics, experimental pneumonia and clinical trials completed in the last decade show that for most cases of nosocomial pneumonia, monotherapy is an acceptable regimen.

Anti-Bacterial Agents↗