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Biomedical subjects

David R Snydman

Publications and source records attributed to David R Snydman.

At least 19 recordsLinked to original sources
PubMed2006

Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients.

OBJECTIVE: Vancomycin resistant enterococcal (VRE) blood stream infection (BSI) in neutropenic patients is associated with poor outcome. We report our experience in treating VRE BSI in febrile, neutropenic patients with daptomycin, a recently licensed lipopeptide with bactericidal activity against VRE. PATIENTS AND METHODS: Patients with fever, neutropenia and VRE BSI were treated with more than one dose of daptomycin (either 6 mg/kg/day or 4 mg/kg/day) in an open label, emergency-use trial. Patients were then assessed for clinical and microbiological cures and survival. MIC's of isolates to daptomycin were determined. RESULTS: Nine febrile, neutropenic patients with VRE BSI received daptomycin. Four of 9 courses (44%) had clinical and/or microbiologic cure. Two of the 5 who failed cure died within 3 days of initiation of daptomycin. Five subjects survived to 30 days after the onset of BSI. CONCLUSIONS: Use of daptomycin in neutropenic patients with VRE BSI deserves further study as a treatment for VRE BSI in neutropenic patients.

Adult↗
PubMed2006

Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies.

BACKGROUND: Cytomegalovirus (CMV) causes significant morbidity and mortality in transplant recipients, but there is no consensus regarding the most appropriate prevention method. The goal of this meta-analysis was to compare the efficacy of universal prophylaxis and preemption using ganciclovir. METHODS: Literature searches for randomized and nonrandomized controlled trials of ganciclovir prophylaxis and preemption were conducted. Because of the lack of head-to-head trials, indirect comparisons of meta-analyses of the prevention strategies were performed. Meta-analyses were conducted using a random effects model to estimate the overall risk ratios for various clinical outcomes. We assessed the event rates for control groups across the trials for comparability. RESULTS: Literature searches identified 17 universal prophylaxis trials and 9 preemption trials with 1560 and 457 subjects, respectively. Overall event rates for CMV disease in control groups across the studies were similar (approximately 26%). The relative risk of CMV disease in prophylaxis trials was 0.34 (95% confidence interval, 0.24-0.48) when trials of patients with prophylaxis of short duration and trials that only evaluated patients with high-risk serostatus were excluded. The relative risk of CMV disease for study subjects in all preemption trials was 0.30 (95% confidence interval, 0.15-0.60), compared with that for control subjects. There was no statistically significant difference in CMV disease between prevention strategies. Similarly, no differences between strategies were found for all-cause mortality or rejection. There were insufficient data to adequately evaluate graft loss and opportunistic infection. CONCLUSIONS: On the basis of indirect comparisons of meta-analyses of prevention strategies, universal prophylaxis and preemption are equally effective in reducing the incidence of CMV disease.

Antiviral Agents↗
PubMed2006

Hypogammaglobulinemia in liver transplant recipients: incidence, timing, risk factors, and outcomes.

BACKGROUND: Recent studies suggest a substantial incidence of posttransplant hypogammaglobulinemia and an association with infection. METHODS: We conducted a retrospective analysis of immunoglobulin (Ig) G levels from blood prospectively collected during a randomized double-blind placebo-controlled trial of cytomegalovirus (CMV) immune globulin that included 146 patients who underwent liver transplantation between December 1987 and June 1990. Serum samples collected at baseline and approximately weeks 4, 8, 12, 16, 24, and 32 posttransplant were analyzed. Hypogammaglobulinemia was defined as having at least one IgG level below 560 mg/dl. A variety of variables were analyzed as potential risk factors and outcomes of hypogammaglobulinemia. RESULTS: A total of 613 samples from 112 patients were analyzed. Twenty-nine (26%) patients had posttransplant hypogammaglobulinemia. Fourteen (12.5%) had hypogammaglobulinemia at the time of their baseline measurement. There was a strong association between hypogammaglobulinemia and both one-year (P=0.0490) and five-year mortality (P=0.0187), even when adjusted for variables known to be associated with mortality (HR for one-year mortality 3.08, confidence interval 1.20, 7.91). Risk factors for hypogammaglobulinemia included only non A/non B hepatitis and "other diagnosis" (a category made up of rare causes of liver disease). None of the infectious outcomes examined, including CMV infection, CMV disease, bacteremia or invasive fungal disease, or rejection were significantly associated with hypogammaglobulinemia. CONCLUSIONS: In orthotopic liver transplant recipients we found a 26% incidence of posttransplant hypogammaglobulinemia. Approximately half of these patients were hypogammaglobulinemic at baseline. A strong association between hypogammaglobulinemia and mortality was seen. Prospective studies are needed to further elucidate the risk factors and outcomes of posttransplant hypogammaglobulinemia.

Adult↗
PubMed2005

The impact of gown-use requirement on hand hygiene compliance.

BACKGROUND: Hand hygiene compliance remains low, despite its effectiveness in preventing infections. Gowns are routinely used to reduce dissemination of organisms within hospitals. Use of gowns is time consuming and costly, and their effectiveness, compared with that of hand hygiene alone, is debated. Among the arguments supporting a gown-use requirement is the potential to boost awareness of infection control, leading to improved hand hygiene compliance. METHODS: Hand hygiene compliance was recorded in a 14-month crossover trial comparing compliance at 2 intensive care units during periods with and without a gown-use requirement. RESULTS: During 170 h of observation, 1619 hand hygiene opportunities were recorded. Compliance was 10% before care was given and 36% after care was given. Compliance with glove and gown use was 62% and 63%, respectively. After-care hand hygiene compliance for nurses, physicians, and therapists was 40%, 38%, and 22%, respectively. Compliance after patient contact, body fluid contact, and other in-room activity was 42%, 48%, and 22%, respectively. For periods with and without a gown-use requirement, overall after-care compliance (37% vs. 34%) and rates by personnel and activity type were similar. In the subgroup of patients on contact precautions, hand hygiene compliance during the period with a gown-use requirement versus the period without a gown-use requirement was 11% versus 10% (P=.85) before care was given and 45% versus 39% (P=.09) after care was given. In this subgroup, after adjustment for type of in-room activity, medical personnel, intensive care unit, and observer, the predicted after-care hand hygiene compliance during periods with and without a gown-use requirement was 48% versus 41% (P=.02). CONCLUSIONS: The hypothesis that a gown-use requirement might improve hand hygiene compliance in the intensive care unit could not be confirmed. In the subgroup of patients on contact precautions, improvement in hand hygiene compliance associated with the gown-use requirement was small and did not affect precare rates.

Guideline Adherence↗
PubMed2005

Evaluation of the in vitro activity of NVP-LMB415 against clinical anaerobic isolates with emphasis on the Bacteroides fragilis group.

OBJECTIVES: To compare the in vitro activity of NVP-LMB415 (formerly referred to as NVP-PDF 713) with that of other agents with anti-anaerobe activity against clinical anaerobic isolates, with emphasis on the Bacteroides fragilis group. METHODS: The MICs for 405 B. fragilis group and 102 Gram-positive anaerobic isolates were determined using NCCLS-recommended procedures. The activity of NVP-LMB415 was compared with that of cefoxitin, clindamycin, imipenem, garenoxacin, linezolid, moxifloxacin and tigecycline. Vancomycin was included in the evaluation of the Gram-positive organisms. RESULTS: NVP-LMB415 showed excellent in vitro activity against all the species of the B. fragilis group isolates (MIC range < or = 0.03-0.5 mg/L and MIC(90) 0.5 mg/L). NVP-LMB415 was active against B. fragilis group strains resistant to beta-lactams, quinolones or clindamycin, and the MICs were much lower than those of newer agents such as linezolid, tigecycline and garenoxacin. The MICs of NVP-LMB415 ( > or = 4 mg/L) for Clostridium species were higher than the MICs for other anaerobes. CONCLUSIONS: Given the frequency of isolation of anaerobic bacteria and their increasing resistance to all classes of antibiotics, NVP-LMB415 is an ideal agent for potential use against mixed infections caused by resistant anaerobic pathogens such as of B. fragilis and Gram-positive aerobic strains such as methicillin-resistant staphylococci, streptococci and enterococci.

Amidohydrolases↗
PubMed2005

Impact of cytomegalovirus prophylaxis on rejection following orthotopic liver transplantation.

With improved cytomegalovirus (CMV) prophylaxis, CMV disease after liver transplantation has decreased dramatically, and patient and graft survival have improved. We examined the impact of CMV prophylaxis on biopsy proven rejection after orthotopic liver transplantation by analyzing data on 192 liver recipients over 5 years (1994-1999). Risk factors assessed for biopsy proven rejection including donor and recipient age, CMV serostatus; CMV prophylaxis; immunosuppression; bacteremia and blood product use were examined over a 2-year follow-up. Multivariate analysis of risk factors for rejection showed that bacteremia (HR 3.57, 95% CI 1.39-9.36, P=0.008), donor age (HR 1.20, 95% CI 1.06-1.36, per 10 year increase, P=0.004), and use of cyclosporine as initial immunosuppression compared to tacrolimus (HR 1.98, 95% CI 1.27-3.09, P=0.003) were associated with increased risk; ganciclovir prophylaxis for 3 months (HR 0.51, 95% CI 0.33 to 0.79, P=0.003) and recipient age (HR 0.78; 95% CI 0.63-0.96, for each 10 year increase, P=0.03) were associated with decreased risk. We conclude that, the use of CMV prophylaxis with ganciclovir significantly reduces the incidence of biopsy proven rejection in liver transplant recipients.

Antiviral Agents↗
PubMed2005

Transmission of vancomycin-resistant enterococcus in a neonatal intensive care unit.

An outbreak of vancomycin-resistant Enterococcus transmission in our neonatal intensive care unit persisted despite strict contact precautions and cohorting of colonized neonates and their caregivers. After terminal cleaning was performed, incubators were found to harbor the neonates' clone of vancomycin-resistant Enterococcus. Transmission ceased after cohorting of incubators, suggesting the effectiveness of infection control measures targeting environmental contamination.

Disease Outbreaks↗
PubMed2005

Fluconazole MIC and the fluconazole dose/MIC ratio correlate with therapeutic response among patients with candidemia.

We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (</=200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 mug/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 mug/ml and 219.36 [P = 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC </= 8 mug/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 mug/ml), and resistant (MIC >/= 64 mug/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio </=50 (P = 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.

Adolescent↗
PubMed2004

The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection or receipt of a CMV-seropositive donor liver has been shown to be an independent predictor of bacteremia in orthotopic liver transplant (OLT) recipients. However, prevention of CMV infection through use of intense CMV prophylaxis has not been examined to assess the impact on bacteremia in liver transplant recipients. METHODS: We analyzed the impact of CMV prophylaxis on rates of bacteremia by examining 192 consecutive OLT recipients during a 2-year follow-up period. RESULTS: There were 29 episodes of bacteremia. Univariate analysis of risk factors for bacteremia showed that invasive fungal disease, initial anti-lymphocyte immunosuppression, treatment for rejection, and use of solumedrol were significantly associated with increased risk. Receipt of >or=14 days of ganciclovir prophylaxis (hazard ratio [HR], 0.40; 95% CI [confidence interval], 0.18-0.87; P=.02), end-to-end biliary anastomosis, and receipt of <10 units of red blood cells (RBCs) were significantly associated with a decreased risk. Three-variable analysis controlling for end-to-end anastomosis and use of <10 units of RBCs, showed that use of >or=14 days of ganciclovir was still associated with a reduced risk of bacteremia (HR, 0.44; 95% CI, 0.20-0.98; P=.0437). CONCLUSIONS: Among factors associated with bacteremia, use of prophylactic ganciclovir is independently associated with a significant reduction of bacteremia in OLT recipients.

Adult↗
PubMed2004

Combination antibiotic therapy lowers mortality among severely ill patients with pneumococcal bacteremia.

Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combination antibiotic therapy versus monotherapy on mortality was examined by univariate analyses and by logistic regression models. The 14-day mortality was not significantly different for the two groups. However, among critically ill patients, combination antibiotic therapy was associated with lower 14-day mortality (23.4 versus 55.3%, p = 0.0015). This improvement in survival was independent of country of origin, intensive care unit support, class of antibiotics, or in vitro activity of the antibiotics prescribed. Combination antibiotic therapy improved survival among critically ill patients with bacteremic pneumococcal illness.

Adolescent↗
PubMed2004

Iron storage indices: novel predictors of bacteremia in hemodialysis patients initiating intravenous iron therapy.

Bacterial sepsis is the second leading cause of death among hemodialysis (HD) patients. Iron overload and intravenous iron therapy are linked to bacterial infection. This study examined iron stores, intravenous iron dosing, and bacteremic risk in HD patients. Retrospectively, 132 HD patients receiving their first course of intravenous iron were studied. Baseline laboratory values, including transferrin saturation (TSAT) value and ferritin level, were measured before initiating intravenous iron therapy. Patients were followed for up to 1 year after the initiation of iron therapy for the outcome of bacteremia by Cox proportional hazards regression analysis. Iron-replete patients (those with a TSAT value > or =20% and a ferritin level > or =100 ng/mL) had a significantly higher risk of bacteremia (hazard ratio [HR], 2.5). Venous catheter users (HR, 4.9) and those with diabetes mellitus (HR, 2.2) were also at increased risk. Modest iron storage levels may increase the risk of bacteremia among HD patients initiating intravenous iron therapy. Additional studies are needed to confirm these relationships.

Bacteremia↗
PubMed2004

Intra-abdominal infections: review of the bacteriology, antimicrobial susceptibility and the role of ertapenem in their therapy.

Complicated intra-abdominal infections require a combination of surgery/drainage and antimicrobial therapy that is active against both the aerobic and the anaerobic bacteria that comprise the intestinal flora. Ertapenem, a parenteral carbapenem, is highly resistant to a wide variety of beta-lactamase enzymes, and has a broad spectrum of activity against bacteria associated with community-acquired infections including those of complicated intra-abdominal conditions. This article reviews the bacteriology of complicated intra-abdominal infections, their antimicrobial susceptibility, especially to anaerobes, the utility of animal models in these mixed infections, and the supportive clinical trials and in vitro susceptibility data that show ertapenem to be generally well tolerated and as effective as either piperacillin-tazobactam or ceftriaxone plus metronidazole in the therapy of complicated intra-abdominal infections.

Abdomen↗
PubMed2004

Viral prophylaxis in organ transplant patients.

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu season'.

Antiviral Agents↗
PubMed2003

Role of environmental contamination as a risk factor for acquisition of vancomycin-resistant enterococci in patients treated in a medical intensive care unit.

BACKGROUND: Colonization pressure, proximity to another case, exposure to a nurse who cares for another case, enteral feeding, and the use of sucralfate, vancomycin hydrochloride, cephalosporins, or antibiotics are among the defined risk factors for acquisition of vancomycin-resistant enterococci (VRE) in the intensive care unit (ICU) setting. However, the role of rooms with contaminated environmental surfaces has not been well delineated. METHODS: Retrospective case-control study conducted on patients admitted to the medical ICU (MICU) of a tertiary-care, university-affiliated medical center during a 9-month period. Patients who acquired VRE (cases) were matched with 2 randomly selected control subjects who did not acquire VRE and had been in the MICU for at least the same number of days. RESULTS: Thirty cases were matched with 60 appropriate controls. Cases were more likely to have been in the hospital for longer than 7 days before MICU admission (P =.009); to have occupied a specific room with persisting contaminated surfaces (P =.06); to have had a central venous catheter (P =.05); to have received vancomycin (P =.02), cephalosporins (P =.03), and quinolones (P =.006) before MICU admission; and to have received vancomycin (P =.02) and metronidazole sodium phosphate (P =.03) after MICU admission. Multivariate analysis showed that a hospital stay of longer than 1 week before MICU admission (P =.04), use of vancomycin before or after MICU admission (P =.03), use of quinolones before MICU admission (P =.03), and placement in a contaminated room (P =.02) were the best predictors of VRE acquisition. CONCLUSIONS: Among all other factors associated with VRE transmission, VRE acquisition may depend on room contamination, even after extensive cleaning. This study underscores the need for better cleaning and the role of the environment in transmission of VRE.

Aged↗