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Biomedical subjects

D R Snydman

Publications and source records attributed to D R Snydman.

At least 19 recordsLinked to original sources
PubMed2006

Endocarditis and pericarditis complicating pneumococcal bacteraemia, with special reference to the adhesive abilities of pneumococci: results from a prospective study.

The incidence of pneumococcal cardiac infections is unknown and the pathogenicity of such complications is poorly understood. In a prospective, international, observational study, eight of 844 patients hospitalised with Streptococcus pneumoniae bacteraemia developed endocarditis (n = 5) or pericarditis (n = 3). The clinical and microbiological characteristics of these patients were compared with those of control patients. The corresponding incidence of pneumococcal endocarditis was c. 1-3/1 million inhabitants/year. There was no common pattern in the medical history of patients with an infectious cardiac complication. The severity of illness upon admission was comparable with that for patients without infectious cardiac complications, as was the 14-day mortality rate (25% and 17%, respectively). For encapsulated S. pneumoniae, no significant differences were found between patients with infectious cardiac complications and controls in adherence assays. However, non-encapsulated S. pneumoniae showed higher hydrophobicity and increased adherence to human epithelial cells.

Adolescent↗
PubMed2005

Daptomycin-resistant, methicillin-resistant Staphylococcus aureus bacteremia.

We describe a patient who developed daptomycin-resistant, methicillin-resistant Staphylococcus aureus (MRSA) during an episode of presumed septic thrombophlebitis of the portal vein. Although daptomycin is an alternative agent for treatment of drug-resistant gram-positive bacterial infections, development of resistance during prolonged use may occur with MRSA bacteremia from a persistent focus.

Anti-Bacterial Agents↗
PubMed2005

Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam antibiotics against Staphylococcus aureus and Enterococci by FIC index and timed-kill curves.

The interactions of daptomycin with gentamicin and 5 beta-lactam agents were determined by checkerboard and timed-kill studies. Eighty isolates were tested by checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and VRE. Checkerboard results showed highest frequency of synergistic effects against VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a modest effect with most combinations against VRE and MRSA (5-20%); and indifference with daptomycin and most agents against MSSA (0-5%); except with daptomycin with oxacillin where 10-20% synergy was observed. Synergistic interaction was confirmed by time kill studies in seven of ten isolates where checkerboard suggested synergy. A bactericidal effect was exerted in 5/7 synergistic combinations. The in vitro data suggest that daptomycin combined with other antibiotics may be microbiologically beneficial and not antagonistic.

Anti-Bacterial Agents↗
PubMed2004

In vitro activities of tigecycline against the Bacteroides fragilis group.

The in vitro activities of tigecycline were tested against 831 isolates of the Bacteroides fragilis group representing all of the species within the group. On a weight-to-weight basis (8 microg/ml), tigecycline was more active than clindamycin, minocycline, trovafloxacin, and cefoxitin and less active than imipenem or piperacillin-tazobactam against all isolates of the B. fragilis group. Tigecycline geometric mean MICs were statistically higher against B. distasonis than other Bacteroides species (P value of 0.0001).

Anti-Bacterial Agents↗
PubMed2002

National survey on the susceptibility of Bacteroides Fragilis Group: report and analysis of trends for 1997-2000.

The results of a multicenter US survey using the National Committee for Clinical Laboratory Standards currently recommended methodology for measuring in vitro susceptibility of 2673 isolates of Bacteroides fragilis group species were compared from 1997 to 2000. The test panel consisted of 14 antibiotics: 3 carbapenems, 3 beta-lactam-beta-lactamase inhibitors, 3 cephamycins, 2 fluoroquinolones, clindamycin, chloramphenicol, and metronidazole. Declines in the geometric mean minimum inhibitory concentrations were seen with imipenem, meropenem, ampicillin-sulbactam, and the cephamycins. Increased geometric means were observed with the fluoroquinolones and were usually accompanied by an increase in resistance rates. Bacteroides distasonis shows the highest resistance rates among beta-lactam antibiotics, whereas Bacteroides vulgatus shows the highest resistance levels among fluoroquinolones. B. fragilis shows the lowest resistance rates for all antibiotics. All strains were susceptible to chloramphenicol and metronidazole concentrations <8 microgram/mL. The data underscore the need for species identification and continued surveillance to monitor resistance patterns.

Anti-Bacterial Agents↗
PubMed2002

In vitro activities of newer quinolones against bacteroides group organisms.

The activities of BMS-284576, clinafloxacin, moxifloxacin, sitafloxacin, trovafloxacin, imipenem, cefoxitin, and clindamycin against 589 Bacteroides fragilis group isolates were determined. The activity of BMS-284576 was comparable to that of trovafloxacin. Sitafloxacin and clinafloxacin were the most active quinolones, and moxifloxacin was the least active. B. fragilis was the most susceptible of the species, and Bacteroides vulgatus was the most resistant. Association of specific antibiotic resistance with Bacteroides species was noted for all quinolones.

Anti-Infective Agents↗
PubMed2001

Determinants of vancomycin resistance and mortality rates in enterococcal bacteremia. a prospective multicenter study.

BACKGROUND: Enterococcus species are major nosocomial pathogens and are exhibiting vancomycin resistance with increasing frequency. Previous studies have not resolved whether vancomycin resistance is an independent risk factor for death in patients with invasive disease due to Enterococcus species or whether antibiotic therapy alters the outcome of enterococcal bacteremia. OBJECTIVE: To determine whether vancomycin resistance is an independent predictor of death in patients with enterococcal bacteremia and whether appropriate antimicrobial therapy influences outcome. DESIGN: Prospective observational study. SETTING: Four academic medical centers and a community hospital. PATIENTS: All patients with enterococcal bacteremia. MEASUREMENTS: Demographic characteristics; underlying disease; Acute Physiology and Chronic Health Evaluation (APACHE) II scores; antibiotic therapy, immunosuppression, and procedures before onset; and antibiotic therapy during the ensuing 6 weeks. The major end point was 14-day survival. RESULTS: Of 398 episodes, 60% were caused by E. faecalis and 37% were caused by E. faecium. Thirty-seven percent of isolates exhibited resistance or intermediate susceptibility to vancomycin. Twenty-two percent of E. faecium isolates showed reduced susceptibility to quinupristin-dalfopristin. Previous vancomycin use (odds ratio [OR], 5.82 [95% CI, 3.20 to 10.58]; P < 0.001), previous corticosteroid use (OR, 2.43 [CI, 1.22 to 4.86]; P = 0.01), and total APACHE II score (OR, 1.06 per unit change [CI, 1.02 to 1.10 per unit change]; P = 0.003) were associated with vancomycin-resistant enterococcal bacteremia. The mortality rate was 19% at 14 days. Hematologic malignancy (OR, 3.83 [CI, 1.56 to 9.39]; P = 0.003), vancomycin resistance (OR, 2.10 [CI, 1.14 to 3.88]; P = 0.02), and APACHE II score (OR, 1.10 per unit change [CI, 1.05 to 1.14 per unit change]; P < 0.001) were associated with 14-day mortality. Among patients with monomicrobial enterococcal bacteremia, receipt of effective antimicrobial therapy within 48 hours independently predicted survival (OR for death, 0.21 [CI, 0.06 to 0.80]; P = 0.02). CONCLUSIONS: Vancomycin resistance is an independent predictor of death from enterococcal bacteremia. Early, effective antimicrobial therapy is associated with a significant improvement in survival.

APACHE↗
PubMed2001

Association of human herpesvirus 6 reactivation with severe cytomegalovirus-associated disease in orthotopic liver transplant recipients.

To explore the possible interaction between human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) in patients who have undergone organ transplantation, stored serum samples from 139 orthotopic liver transplant recipients were tested for HHV-6 immunoglobulin (Ig) G and IgM antibodies. HHV-6 reactivation occurred in 87 patients (62.6%) and was associated with CMV disease (P=.01), severe CMV-associated disease (P=.01), older age (P=.005), and use of muromonab-CD3 (Orthoclone; Orthobiotech) as treatment for rejection (P=.02). Trends for an association between HHV-6 reactivation and invasive fungal disease (P=.12), bacteremia (P=.10), and graft loss (P=.12) were seen. In a multivariate analysis of risk factors for severe CMV-associated disease, HHV-6 reactivation (relative risk [RR], 3.5; 95% confidence interval [CI], 1.2-10.2; P=.02), CMV donor-positive-recipient-negative match (RR, 5.7; 95% CI, 2.5-13.2; P<.001), and elevated serum creatinine level (P<.0001) were independent predictors. HHV-6 reactivation is associated with severe CMV-associated disease in liver transplant recipients.

Adult↗
PubMed2001

Late and atypical cytomegalovirus disease in solid-organ transplant recipients.

Posttransplantation cytomegalovirus (CMV) disease typically occurs 1-4 months after solid-organ transplantation. The case definition invariably includes unexplained fever for > or =3 days, often with leukopenia. Late and atypical presentation of CMV disease has been rarely reported. Five cases of late and atypical CMV disease in heart (n = 1), liver (n = 1), and kidney (n = 3) transplant recipients occurred within a 4-month period in early 1999. These patients presented at a median of 25 months after organ transplantation (range, 6 months to 22 years). Atypical findings included absence of fever in 3 patients, elevated white blood cell counts in 4 patients, and normal platelet counts in 4 patients. Four patients were at risk for primary CMV infection, and 3 received ganciclovir prophylaxis for 3 months. One patients was treated for rejection, and 2 patients had induction muromonab-CD3 (Orthclone; Orthobiotech). Two of the patients had pulmonary CMV disease, but neither of these patients had hypoxia. Two patients had enterocolitis, one of whom had chronic colitis for a year. These cases may represent a changing epidemiology and clinical presentation of CMV disease in solid-organ transplant recipients in an era of changing immunosuppression and improved CMV disease prevention in the early posttransplantation period.

Adult↗
PubMed2001

Epidemiology of infections after solid-organ transplantation.

Infections are a major determinant of the outcome of solid-organ transplantation. Their incidence varies because of a number of factors. The type of organ transplanted, the degree of immunosuppression, the need for additional antirejection therapy, and the occurrence of technical or surgical complications all affect the incidence of infection after transplantation. There are 3 general time frames to consider. In the first month, bacterial and candidal infections predominate. From the second through the sixth months, infections "classically" associated with transplantation become manifest. Beyond the sixth month, the clinical course is largely determined by the presence or absence of chronic rejection.

Cross Infection↗
PubMed2001

Posttransplant microbiological surveillance.

Posttransplant microbiological surveillance should be used when the likelihood of infection in a transplant recipient is high and the sensitivity and specificity of the test can provide a high positive or negative predictive value. Testing is also performed in some instances to monitor the patient's response to therapy. Examples of successful posttransplant microbiological surveillance include molecular detection of cytomegalovirus and Epstein-Barr virus and virus load determinations, as well as hepatitis B and C detection and virus load testing. Routine fungal and bacterial surveillance are generally not necessary, except for Candida colonization detection or vancomycin-resistant enterococcal detection in high-risk subgroups. The organ transplanted may also play a role in the type of routine surveillance recommended.

Humans↗
PubMed2001

Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection.

Highly active antiretroviral therapy has decreased human immunodeficiency virus (HIV)-associated mortality; other comorbidities, such as chronic liver disease, are assuming greater importance. We retrospectively examined the causes of death of HIV-seropositive patients at our institution in 1991, 1996, and 1998-1999. In 1998-1999, 11 (50%) of 22 deaths were due to end-stage liver disease, compared with 3 (11.5%) of 26 in 1991 and 5 (13.9%) of 36 in 1996 (P=.003). In 1998-1999, 55% of patients had nondetectable plasma HIV RNA levels and/or CD4 cell counts of >200 cells/mm(3) within the year before death. Most of the patients that were tested had detectable antibodies to hepatitis C virus (75% of patients who died in 1991, 57.7% who died in 1996, and 93.8% who died in 1998-1999; P=NS). In 1998-1999, 7 patients (31.8%) discontinued antiretroviral therapy because of hepatotoxicity, compared with 0 in 1991 and 2 (5.6%) in 1996. End-stage liver disease is now the leading cause of death in our hospitalized HIV-seropositive population.

Adult↗
PubMed2001

Historical overview of the use of cytomegalovirus hyperimmune globulin in organ transplantation.

A historical review of the development of cytomegalovirus hyperimmune globulin (CMV-IG, CytoGam) shows its increasing use in solid organ transplant (SOT) recipients, either alone or in combination with ganciclovir. A review of clinical trials of CytoGam in renal transplant recipients shows reductions in CMV-associated syndromes and fungal and parasitic superinfections, and increases in graft survival, while CytoGam prophylaxis trials in orthotopic liver transplant (OLT) recipients have produced reductions in severe CMV-associated disease and invasive fungal disease. A combination of CytoGam plus ganciclovir in OLT recipients has resulted in reductions in CMV hepatitis and infection, and CMV disease and viremia, plus a trend in improved 1- and 2-year survival rates.

Antiviral Agents↗
PubMed2000

Antimicrobial resistance and clinical outcome of Bacteroides bacteremia: findings of a multicenter prospective observational trial.

There is debate regarding the correlation between in vitro susceptibility testing and clinical response to therapy for Bacteroides bacteremia. We conducted a prospective multicenter observational study of 128 patients with bacteroides bacteremia. Outcome was correlated with results of in vitro susceptibility testing of Bacteroides isolates recovered from blood and/or nonblood sites, determined with use of 3 end points: mortality at 30 days, clinical response (cure vs. failure), and microbiological response (eradication vs. persistence). The mortality rate among patients who received inactive therapy (45%) was higher than among patients who received active therapy (16%; P=.04). Clinical failure (82%) and microbiological persistence (42%) were higher for patients who received inactive therapy than for patients who received active therapy (22% and 12%, respectively; P=.0002 and.06, respectively). In vitro activity of agents directed at Bacteroides species reliably predicts outcome: the specificity was 97%, and positive predictive value was 82%. Antimicrobial susceptibility testing may be indicated for patients whose blood specimens yield Bacteroides species.

Adolescent↗
PubMed2000

Clinical manifestations and molecular epidemiology of late recurrent candidemia, and implications for management.

The aim of this study was to define the epidemiology and clinical manifestations of late recurrent candidemia. For this purpose, late recurrent candidemia was defined as an episode of candidemia occurring at least 1 month after the apparent complete resolution of an infectious episode caused by the same Candida sp. A total of five patients with recurrent candidemia were investigated. For all patients, isolates from the initial and recurrent episodes of candidemia were available for in vitro susceptibility testing and genetic characterization by DNA-based techniques. The results revealed the following salient features: prolonged duration between the initial and recurrent episodes (range, 1-8 months); recurrence of candidemia despite anti-fungal therapy; importance of retained intravascular catheters, neutropenia, and corticosteroids as factors predisposing to recurrence; high morbidity and mortality; no emergence of antifungal drug resistance between the initial and recurrent episodes; and relapse of infection due to the original infecting strain, rather than reinfection with a new strain. These findings raise several issues about the management and follow-up of patients with candidemia, which require assessment in future studies.

Aged↗
PubMed2000

Varicella zoster virus infections following allogeneic bone marrow transplantation: frequency, risk factors, and clinical outcome.

Reactivation of varicella zoster virus (VZV) is a common event in patients undergoing allogeneic bone marrow transplantation (BMT) and may lead to life-threatening complications. We retrospectively analyzed the incidence, clinical outcome, and risk factors for VZV infections occurring within the first 5 years of transplantation in 100 consecutive adults undergoing allogeneic BMT between 1992 and 1997. Forty-one patients (41%) developed VZV reactivation a median of 227 days (range 45-346 days) post-transplantation. Twelve percent of VZV reactivation occurred in the first 100 days and 88% within the first 24 months. Among those who survived for 2 or more years after transplantation (n = 47), 59% developed VZV infection. Forty percent of patients with VZV reactivation required admission with a mean hospital stay of 7.2 days. Two patients developed encephalitis, and 1 died despite antiviral therapy. The most frequent complications were post-herpetic neuralgia and peripheral neuropathy (68%). Thoracic dermatomal zoster represented 41% of the infections; disseminated cutaneous involvement was observed in 17% of patients. No clinical or epidemiologic risk factors were associated with recurrence. Administration of ganciclovir for prevention of cytomegalovirus infection delayed the onset of VZV infection beyond 4 months (P = .06). In a further subset analysis, patients with a limited chronic graft-versus-host disease (GVHD) had a lower estimated incidence of VZV reactivation compared with those with extensive chronic GVHD (P = .11). We conclude that complications from reactivation of VZV infection are common and associated with considerable morbidity and mortality in patients undergoing allogeneic BMT.

2-Aminopurine↗