PubMed Health⌕ Search

Biomedical subjects

Daniel K Benjamin

Publications and source records attributed to Daniel K Benjamin.

At least 37 records · Page 2Linked to original sources
PubMed2005

Critical appraisal of the role of Ureaplasma in the development of bronchopulmonary dysplasia with metaanalytic techniques.

BACKGROUND: Controversy exists over whether or not Ureaplasma colonization or infection of the respiratory tract contributes to the development of bronchopulmonary dysplasia (BPD). Because BPD is a major cause of morbidity and mortality in preterm infants and a potential therapeutic intervention with antimicrobials is possible, we sought to evaluate and critique the current medical literature and to document the reported association between Ureaplasma and BPD. METHODS: We analyzed all peer-reviewed articles and previous reviews including cross-references that reported Ureaplasma respiratory tract colonization or infection and development of BPD in neonates published from January 1966 to December 2004. Inclusion criteria included a cohort limited to all neonatal intensive care unit admissions or all colonized infants, articles that did not define a numerator and a denominator for BPD and Ureaplasma or that included patients from other reports were excluded from the analysis. We evaluated BPD at 28 postnatal days (BPD28) or 36 weeks post-menstrual age (BPD36). RESULTS: Twenty-three studies with an aggregate of 2216 infants reported BPD28, and 8 studies with 751 infants reported BPD36. Although there was significant association between Ureaplasma colonization and both BPD28 and BPD36, there was substantial heterogeneity (Q test statistic, P < 0.01). We therefore focused on describing the study characteristics associated with an increased relative proportion of BPD. The greatest contribution to effect was from the studies enrolling fewer than 100 infants. CONCLUSION: Ureaplasma colonization is associated with higher reported rates of BPD, but the greatest reported effect is seen in small studies; reporting bias may be partially responsible for this effect.

Bronchopulmonary Dysplasia↗
PubMed2005

New antifungal agents under development in children and neonates.

PURPOSE OF REVIEW: This review focuses on only the newest antifungal agents recently approved or still under development and the available data in pediatric and neonatal patients. The larger body of data in adult patients is used for comparative purposes only in an attempt to understand pediatric implications. RECENT FINDINGS: Pharmacokinetic data suggest differences in dosing for many newer agents in children versus adult patients, but each agent has not been fully evaluated. Voriconazole displays non-linear pharmacokinetics in adults but has linear pharmacokinetics in children, necessitating a higher dose in smaller patients and potential treatment failures using the approved adult dosing schedule. Caspofungin likewise requires higher doses relative to adult patients, and dosing in children is best accomplished on a body surface area scheme and not a body weight dosing platform. Preliminary data suggest posaconazole, an investigational triazole, in children may lead to similar levels as in adults, but very limited efficacy data are available at any dose. Micafungin dosing has been explored in neonatal patients and there is a clear trend toward lower levels obtained in the very smallest infants, highlighting the importance of the neonatal period as a separate entity to even the pediatric age group. SUMMARY: Initial data suggest dosing differences in children with some antifungals, and other newer agents have not been fully tested for the correct dosing. The underlying concern of efficacy in children compared with adult patients has never been answered as there are no randomized, phase III antifungal clinical trials from which pediatric-specific data were obtained.

Adolescent↗
PubMed2005

Cryptococcus neoformans {alpha} strains preferentially disseminate to the central nervous system during coinfection.

Cryptococcus neoformans is a fungal pathogen that has evolved over the past 40 million years into three distinct varieties or sibling species (gattii, grubii, and neoformans). Each variety manifests differences in epidemiology and disease, and var. grubii strains are responsible for the vast majority of human disease. In previous studies, alpha strains were more virulent than congenic a strains in var. neoformans, whereas var. grubii congenic a and alpha strains exhibited equivalent levels of virulence. Here the role of mating type in the virulence of var. grubii was further characterized in a panel of model systems. Congenic var. grubii a and alpha strains had equivalent survival rates when cultured with amoebae, nematodes, and macrophages. No difference in virulence was observed between a and alpha congenic strains in multiple inbred-mouse genetic backgrounds, and there was no difference in accumulations in the central nervous system (CNS) late in infection. In contrast, during coinfections, a and alpha strains are equivalent in peripheral tissues but alpha cells have an enhanced predilection to penetrate the CNS. These studies reveal the first virulence difference between congenic a and alpha strains in the most common pathogenic variety and suggest an explanation for the prevalence of alpha strains in clinical isolates.

Animals↗
PubMed2005

Neonatal candidiasis: prophylaxis and treatment.

The incidence of candidiasis has risen in neonatal intensive care units as advances in medical therapy have allowed for increased survival of extremely preterm neonates. The mortality of candidiasis has been reported to be 20% by several multi-centre studies. Definitive guidance for prophylaxis and treatment is hindered by lack of large, multi-centre, randomised controlled trials. Systemic prophylaxis is currently not recommended for any neonatal population, and amphotericin B deoxycholate continues to be used as first-line therapy for the treatment of invasive disease.

Amphotericin B↗
PubMed2004

A meta-analysis of medical versus surgical therapy for Candida endocarditis.

OBJECTIVES: The optimal management of Candida infective endocarditis (IE) is unknown. METHODS: We reviewed all 879 cases of Candida IE reported from 1966-2002 in the peer-reviewed literature to better understand the role of medical and surgical therapies. This review included 163 patients from 105 reports that met our inclusion criteria: 31 cases treated with antifungal monotherapy, 25 cases treated with medical antifungal combination therapy, and 107 cases treated with adjunctive surgical plus medical antifungal therapy. We also used meta-analytic techniques to evaluate 22 observational case-series (72 patients) of the 105 reports with two or more patients with definite Candida IE. RESULTS: We found that in patients who underwent adjunctive surgery there was a lower reported proportion of deaths [prevalence odds ratio (POR)=0.56; 95% confidence interval (CI)=0.16, 1.99)]. Higher mortality was noted in patients treated prior to 1980 (POR=2.03; 95% CI=0.55, 7.61), treated with antifungal monotherapy (POR=1.49; 95% CI=0.39, 5.81), infected with Candida parapsilosis (POR=1.51; 95% CI=0.41, 5.52), or with left-sided endocarditis (POR=2.36; 95% CI=0.55, 10.07). CONCLUSIONS: Medical antifungal therapy of Candida IE is poorly characterized, and recent antifungal developments lend promise for those patients who cannot undergo surgery.

Adolescent↗
PubMed2004

Growth as a part of the composite endpoint in paediatric antiretroviral clinical trials.

Paediatric HIV is a rapidly emerging disease in many resource-poor countries. Survival into adulthood is possible for HIV-infected children provided that they receive effective antiretroviral therapy (ART). Large trials comparing multiple regimens of ART in children of resource-poor countries have not been completed. Design of those trials will need to incorporate both lessons learned from trials completed in developed countries as well as unique aspects of the developing countries in which they are conducted. Trial design will necessarily include close attention to the endpoint, and in children, special consideration will need to be given to growth as a component of the endpoint--whether or not growth should be a component of the composite endpoint, and if so, how.

Anti-HIV Agents↗
PubMed2004

Infections due to Aspergillus terreus: a multicenter retrospective analysis of 83 cases.

Current in vitro and in vivo data indicate that invasive aspergillosis due to Aspergillus terreus is resistant to treatment with amphotericin B. Because little clinical data are available to guide therapy, we performed a retrospective cohort study of cases of invasive A. terreus infections from 1997-2002 to determine whether the use of voriconazole, compared with use of other antifungal therapies, led to an improved patient outcome. We analyzed a total of 83 cases of proven or probable invasive A. terreus infection (47% and 53%, respectively). A total of 66.3% of patients (55 of 83) died during management of IA, with 55.8% mortality (19 of 34 patients) in the voriconazole group and 73.4% mortality (36 of 49) in the group that received therapy with other antifungals. By use of Cox proportional hazards modeling, decreased mortality at 12 weeks was observed in those patients who received voriconazole (hazard ratio, 0.29; 95% CI, 0.15-0.56). Voriconazole is likely to be a better treatment choice for A. terreus infection than is a polyene.

Antifungal Agents↗
PubMed2004

Early predictors of in-hospital death in infective endocarditis.

BACKGROUND: Data on early determinants of outcome in infective endocarditis (IE) are limited. We evaluated the prognostic significance of early clinical characteristics in a large, prospective cohort of patients with IE. METHODS AND RESULTS: Two hundred sixty-seven consecutive patients with definite or possible IE by modified Duke criteria and echocardiography performed within 7 days of presentation were evaluated. Acute physiology was assessed by the Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score at the time of presentation, and early heart failure was diagnosed by Framingham criteria. In-hospital mortality rate in the cohort was 19% and similar for patients with definite or possible IE (20% versus 16%, respectively; P=0.464). Independent predictors of death determined by logistic regression modeling were diabetes mellitus (OR 2.48; 95% CI, 1.24 to 4.96), Staphylococcus aureus as causative organism (OR, 2.06; 95% CI, 1.01 to 4.20), APACHE II score (OR, 1.07; 95% CI, 1.01 to 1.12), and embolic event (OR, 2.79; 95% CI, 1.15 to 6.80). Early echocardiographic findings of the Duke criteria were not predictive of death. CONCLUSIONS: Early in the course of IE, readily available clinical characteristics that reflect the host-pathogen interaction are predictive of in-hospital death. These factors may identify those patients with IE for more aggressive treatment.

APACHE↗
PubMed2004

Active or prior GB virus C infection does not protect against vertical transmission of HIV in coinfected women from Tanzania.

To determine whether GB virus C (GBV-C) infection is associated with protection against vertical transmission of human immunodeficiency virus (HIV), we tested 186 HIV-positive pregnant women for GBV-C. Neither active nor prior GBV-C infection was associated with a lower rate of HIV acquisition among infants. Thus, GBV-C does not appear to protect against perinatal HIV acquisition.

Adult↗
PubMed2004

Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients.

BACKGROUND: Aerosolized administrations of amphotericin B deoxycholate (AmBd) and amphotericin B lipid complex (ABLC) in lung transplant recipients were compared for safety and tolerability. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined. METHODS: A prospective, randomized (1:1), double-blinded trial was conducted with 100 subjects. AmBd and ABLC were administered postoperatively by nebulizer at doses of 25 mg and 50 mg, respectively, which were doubled in mechanically ventilated patients. The planned treatment was once every day for 4 days, then once per week for 7 weeks. Treatment-related adverse events and invasive fungal infections were quantitated for 2 months after study drug initiation. RESULTS: Intent-to-treat analysis revealed study drug was discontinued for intolerance in 6 of 49 (12.2%) and 3 of 51 (5.9%) patients in the AmBd- and ABLC-treated groups, respectively (p=0.313). Subjects receiving AmBd were more likely to have experienced an adverse event (odds ratio 2.16, 95% confidence interval 1.10, 4.24, p=0.02). Primary prophylaxis failure within 2 months of study drug initiation was observed in 7 of 49 (14.3%) AmBd-treated patients and 6 of 51 (11.8%) ABLC-treated patients. No fungal pneumonias were observed. Only two (2%) patients experienced documented primary prophylaxis failure with Aspergillus infections within the follow-up period. CONCLUSIONS: Both aerosol AmBd and ABLC appear to be associated with a low rate of invasive pulmonary fungal infection in the early posttransplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event.

Adolescent↗
PubMed2004

Role of complement receptors 1 and 2 (CD35 and CD21), C3, C4, and C5 in survival by mice of Staphylococcus aureus bacteremia.

Complement-mediated opsonization and phagocytosis of encapsulated serotype 5 Staphylococcus aureus are essential to host defense. We describe the effects of complement depletion and deficiencies of C4, C5, and complement receptors 1 and 2 on mouse survival after intravenous exposure to S aureus. Depletion of complement proteins in C57BL/6 mice with the use of cobra-venom factor decreased survival compared with that of controls after the induction of bacteremia with mucoid (90% mortality), encapsulated (73%), and unencapsulated (59%) S aureus strains. In this model complement is even more important in the control of infection with encapsulated S aureus (80% of clinical isolates) than in the control of infection by unencapsulated strains. C4-deficient mice demonstrated similar mortality from bacteremia caused by encapsulated S aureus compared with controls, suggesting that in the unimmunized animal the alternative complement pathway contributes more to control of bacteremia caused by encapsulated S aureus than the classical complement pathway or mannan-binding lectin pathway. C5-deficient mice (B10.D2-H2(d) H2-T18(c) Hc(0)/oSnJ) showed similar mortality when subjected to bacteremia caused by encapsulated S aureus compared with C5-sufficient (B10.D2-Hc(1) H2(d) H2-T18(c)/nSnJ) mice, suggesting that in this model the anaphylatoxin C5a and the late complement cascade are not critical to survival of bacteremia induced with the use of these strains. However, C5-deficient mice depleted of C3 with the use of cobra-venom factor had 60% decreased survival compared with untreated C5-deficient mice with bacteremia induced by encapsulated S aureus, suggesting that in this model C3 is more critical than C5 in controlling S aureus bacteremia. Complement receptor 1 (CD35) is the primary receptor for the opsonin C3b. Mice deficient in CD35/CD21 showed a 67% decrease in survival compared with normal mice, suggesting that CD35/CD21 is of major importance in the control of S aureus-induced bacteremia.

Animals↗
PubMed2004

Postconception age and other risk factors associated with mortality following Gram-negative rod bacteremia.

BACKGROUND: Neonatal nosocomial Gram-negative rod bacteremia (GNR-b) is considered ominous. DESIGN: Multi-center cohort study of premature infants (N=6172) who had a blood culture after day of life 3 and whose birthweight was < or =1250 g. RESULTS: A total of 437 neonates developed GNR-b; most commonly with Klebsiella (122/437; 28%), Enterobacter (97/437; 22%), Escherichia coli (90/437; 21%), Pseudomonas (63/437; 14%), and Serratia (49/437; 11%). Neonates infected with Pseudomonas were more likely to die (21/63; 33%) than infants infected with other GNR (50/374; 13%). In multivariable logistic regression, infection with Pseudomonas, mechanical ventilation, and race were associated with subsequent mortality. Postconception age (PCA) was most strongly associated with mortality. Using neonates with >34 weeks PCA at the time of the first blood culture as the reference category, mortality was higher in neonates <26 weeks PCA (odds ratio (OR)=9.21; 95% confidence interval (CI)=2.79, 30.44), and in neonates 26 to 28 weeks PCA (OR=3.94; 95% CI=1.29, 12.03). CONCLUSIONS: Among premature infants, much of the mortality experienced in GNR-b is due to infection with Pseudomonas rather than enteric GNR. Race, the need for mechanical ventilation, and younger PCA when the blood culture was obtained were also strongly associated with mortality.

Age Factors↗
PubMed2004

Mortality following blood culture in premature infants: increased with Gram-negative bacteremia and candidemia, but not Gram-positive bacteremia.

OBJECTIVE: To describe survival following nosocomial bloodstream infections and quantify excess mortality associated with positive blood culture. STUDY DESIGN: Multicenter cohort study of premature infants. RESULTS: First blood culture was negative for 4648/5497 (78%) of the neonates--390/4648 (8%) died prior to discharge. Mortality prior to discharge was 19% in the 161 infants with Gram-negative rod (GNR) bacteremia, 8% in the 854 neonates with coagulase negative staphylococcus (CONS), 6% in the 169 infants infected with other Gram-positive bacteria (GP-o), and 26% in the 115 neonates with candidemia. The excess 7-day mortality was 0% for Gram-positive organisms and 83% for GNR bacteremia and candidemia. Using negative blood culture as referent, GNR [hazard ratio (HR)=2.61] and candidemia (HR=2.27) were associated with increased mortality; CONS (HR=1.08) and GP-o (HR=0.97) were not. CONCLUSIONS: Nosocomial GNR bacteremia and candidemia were associated with increased mortality but Gram-positive bacteremia was not.

Bacteremia↗
PubMed2004

Nosocomial infection in the NICU: a medical complication or unavoidable problem?

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. As it is associated with increases in mortality, morbidity, and prolonged length of hospital stay, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to review the topic of nosocomial infections in neonates.

Bacterial Infections↗
PubMed2004

Prevention and treatment of nosocomial sepsis in the NICU.

Nosocomial sepsis is a serious problem for neonates who are admitted for intensive care. It is associated with an increase in mortality, morbidity, and prolonged length of hospital stay. Thus, both the human and fiscal costs of these infections are high. Although the rate of nosocomial sepsis increases with the degree of both prematurity and low birth weight, no specific lab test has been shown to be very useful in improving our ability to predict who has a "real" blood-stream infection and, therefore, who needs to be treated with a full course of antibiotics. As a result, antibiotic use is double the rate of "proven" sepsis and we are facilitating the growth of resistant organisms in the neonatal intensive care unit. The purpose of this article is to describe simple changes in process, which when implemented, can reduce nosocomial infection rates in neonates and improve outcomes.

Anti-Bacterial Agents↗
PubMed2004

Value of an inhalational model of invasive aspergillosis.

Animal models of invasive aspergillosis have been used for virulence studies and antifungal efficacy evaluations but results have been inconsistent. In an attempt to reproduce human infection, many Aspergillus animal models have utilized a 'pulmonary route' for delivery of conidia, largely through intranasal instillation. However, several radiolabeled particle studies have shown that aerosol delivery is preferable to intranasal instillation to create a more homogenous delivery to the lungs. We hypothesized that an inhalational model would be more robust for studies of invasive aspergillosis pathogenesis and antifungal therapy. We developed an inhalational model of Aspergillus fumigatus infection using a Hinners inhalation chamber and demonstrated by quantitative polymerase chain reaction that this new inhalational model creates a more homogenous murine pneumonia, facilitating analysis of mutant strains and treatment regimens.

Administration, Inhalation↗
PubMed2004

Disseminated Candida tropicalis in a patient with chronic mucocutaneous candidiasis.

Chronic mucocutaneous candidiasis is a heterogeneous group of immunodeficiencies associated with persistent candidal infections. Patients with chronic mucocutaneous candidiasis are rarely associated with systemic infections caused by other fungi, but almost never by Candida. The authors report a case of a 16-year-old with chronic mucocutaneous candidiasis who developed a fungemia with Candida tropicalis.

Adolescent↗