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D Lew

Publications and source records attributed to D Lew.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of factors that contribute to treatment failure in patients with community-acquired pneumonia.

To determine the causes of treatment failure and to evaluate the prognostic factors in patients hospitalized for community-acquired pneumonia, a prospective, observational study of 228 adult patients hospitalized for a community-acquired pneumonia in the University Hospital of Geneva and the La Chaux-de-Fonds Community Hospital, Switzerland, was conducted. The percentage of patients who failed to improve (as defined by guidelines of the Infectious Disease Society of America) and the causes of treatment failure were assessed, and patients who failed to improve under antimicrobial therapy were compared with those who did improve. In the 54 (24%) patients who failed to improve, a mean increase in length of hospitalization of 4 days was observed. Most causes of treatment failure could be attributed to host factors (61%) rather than to the pathogen (16%) or to an inappropriate antibiotic regimen (3%). After adjusting for potentially confounding variables, concomitant neoplasia (OR 3.25; 95%CI 1.11-9.56), neurological disease (OR 2.34; 95%CI 1.07-5.13), and aspiration pneumonia (OR 2.97; 95%CI 29-6.86]) were associated with failure to improve, whereas monocytosis improved prognosis (OR 0.40; 95%CI 0.20-0.80). Almost one out of four patients hospitalized for community-acquired pneumonia failed to respond to empirical antibiotic treatment. Aspiration pneumonia, concomitant neoplasia, and neurological disease were factors positively associated with failure to improve, whereas monocytosis was linked to a better prognosis.

Adolescent↗
PubMed2006

Intracellular residency is frequently associated with recurrent Staphylococcus aureus rhinosinusitis.

AIM: The prevalence of intracellular Staphylococcus aureus organisms in the nasal mucosa of patients with recurrent infectious rhinosinusitis episodes was studied. METHOD: Twenty-seven consecutive adult patients who failed medical management of chronic rhinosinusitis (CRS) of multiple origins, associated or not with nasal polyposis, were consecutively enrolled for endonasal sinus surgery (including partial middle turbinectomy, middle antrostomy, ethmoidectomy, sphenoidotomy) and followed for a 12-month post-operative period. RESULTS: Seventeen of these patients showed the presence of intracellular S. aureus as detected by confocal laser scan immunofluorescence microscopy in epithelial cells of surgical intranasal biopsy specimens. Nine of the patients with and two without intracellular bacteria yielded S. aureus in endoscopically guided cultures of middle meatus secretions, despite the recent administration of prophylactic antibiotics. Eleven of the 17 patients with intracellular S. aureus relapsed for rhinosinusitis within the 12-month follow-up period. Molecular typing of sequential S. aureus isolates demonstrated the persistence of unique patient-specific S. aureus clonotypes in nine of the patients with intracellular bacteria during the 12-month follow-up. CONCLUSION: The presence of intracellular S. aureus in epithelial cells of the nasal mucosa is a significant risk factor for recurrent episodes of rhinosinusitis due to persistent bacterial clonotypes, which appear refractory to antimicrobial and surgical therapy.

Adolescent↗
PubMed2004

Absidia posttraumatic infection: successful treatment with posaconazole.

The class zygomycetes is a large group of filamentous fungi found ubiquitously in nature, primarily in humid soil. Their virulence in immunocompetent hosts is low; therefore, they are usually considered to be contaminants of cultures. In the present study, we describe a patient who had severe traumatic injury with an Absidia infection, who developed intolerance to antifungal treatment with amphotericin B, but responded to posaconazole treatment.

Absidia↗
PubMed2004

Severe Mycoplasma hominis infections in two renal transplant patients.

Systemic infections due to Mycoplasma hominis are rare and occur mainly in immunocompromised patients. Reported here are the cases of two renal transplant patients with peritonitis who did not respond to empirical antimicrobial treatment. Effective treatment with doxycycline was administered only after definitive identification of Mycoplasma hominis was achieved. For this identification, the new genetic amplification-sequencing method was invaluable.

Adult↗
PubMed2004

Secular trends of nocardia infection over 15 years in a tertiary care hospital.

AIMS: To assess the incidence of nocardia infection over 15 years in a tertiary care hospital. METHODS: Over a 15 year period, Nocardia spp were isolated from 20 patients hospitalised at the Geneva University Hospitals, Switzerland. RESULTS: Sixteen patients had one or more underlying conditions. The median time between symptom onset and diagnosis was 30 days. The most common initial unconfirmed diagnosis was pulmonary tuberculosis (four). The lung was involved in 16 cases, followed by the central nervous system (two) and skin (two); one patient had disseminated infection. The most common species identified was N asteroides. In vitro susceptibility testing was performed on 14 of 20 strains. All strains were susceptible to imipenem and amikacin. Initial treatment with trimethoprim/sulfamethoxazole (TMP/SMX) was started in 14 patients, although five patients had to be switched to another treatment because of side effects or lack of efficacy. A cure was observed in 15 patients, death in three, and relapse or complications in two. CONCLUSIONS: Nocardiosis can become a severe infection and mainly affects profoundly immunocompromised patients. Differential diagnosis often delays the time to diagnosis, which worsens the outcome. New diagnostic tools, such as the polymerase chain reaction, could provide more rapid and reliable results. TMT/SMX was the most commonly prescribed treatment, but needed to be changed for another treatment because of side effects or lack of efficacy in a considerable proportion of patients. Imipenem should be used as an alternative treatment for severely ill patients, and the sulfa combination for less severe infections.

Adolescent↗
PubMed2003

Serotonin syndrome after concomitant treatment with linezolid and citalopram.

Linezolid, a new synthetic antimicrobial, is an important weapon against methicillin-resistant Staphylococcus aureus (MRSA). Although there are reports of serotonin syndrome developing after concomitant use of linezolid and the selective serotonin reuptake inhibitor paroxitene, this report concerns a patient receiving citalopram who developed thrombocytopenia, serotonin syndrome, and lactic acidosis and died following long-term linezolid therapy.

Acetamides↗
PubMed2003

Successful treatment of pulmonary invasive aspergillosis with voriconazole in patients who failed conventional therapy.

BACKGROUND: The incidence of fungal infections, including those due to Aspergillosis species has continued to increase in recent years. Invasive aspergillosis remains an important cause of morbidity and mortality, despite therapeutics interventions. PATIENTS AND METHODS: We reported five cases of invasive pulmonary aspergillosis treated with voriconazole failing to respond to conventional treatments. RESULTS: The clinical and radiological resolution of pulmonary aspergillosis reported in these cases following therapy with voriconazole is remarkable, considering the infections had proved refractory to standard antifungal therapies. Long-term therapy (in two cases > or = 1 year, in one case 6 months) was very well tolerated by patients who were unable to tolerate other antifungal agents. CONCLUSION: Therapy with voriconazole offers a new therapeutic option for otherwise difficult-to-treat infections and the potential to significantly improve the management of Aspergillosis infections.

Adult↗
PubMed2003

Community-acquired pneumonia: causes of treatment failure in patients enrolled in clinical trials.

In order to determine the causes of treatment failure in community-acquired pneumonia (CAP) clinical trials, a MEDLINE search for all CAP studies published between 1990 and 1997 was performed. Prospective, randomized studies comparing the efficacy of two or more antibiotics in CAP were selected. Treatment failure was defined as persistent fever, deterioration of patient's condition, or a change in the prescribed antibiotic regimen. In 16% of the cases included in the clinical trials, the treatment of CAP is unsuccessful. A significant number of identified failure cases were owing to antibiotic side-effects. Resistant pathogens are an unusual cause of failure whatever the antibiotic used.

Aged↗
PubMed2003

Cefepime versus imipenem-cilastatin for treatment of nosocomial pneumonia in intensive care unit patients: a multicenter, evaluator-blind, prospective, randomized study.

In a randomized, evaluator-blind, multicenter trial, we compared cefepime (2 g three times a day) with imipenem-cilastatin (500 mg four times a day) for the treatment of nosocomial pneumonia in 281 intensive care unit patients from 13 centers in six European countries. Of 209 patients eligible for per-protocol analysis of efficacy, favorable clinical responses were achieved in 76 of 108 (70%) patients treated with cefepime and 75 of 101 (74%) patients treated with imipenem-cilastatin. The 95% confidence interval (CI) for the difference between these response rates (-16 to 8%) failed to exclude the predefined lower limit for noninferiority of -15%. In addition, therapy of pneumonia caused by an organism producing an extended-spectrum beta-lactamase (ESBL) failed in 4 of 13 patients in the cefepime group but in none of 10 patients in the imipenem group. However, the clinical efficacies of both treatments appeared to be similar in a secondary intent-to-treat analysis (95% CI for difference, -9 to 14%) and a multivariate analysis (95% CI for odds ratio, 0.47 to 1.75). Furthermore, the all-cause 30-day mortality rates were 28 of 108 (26%) patients in the cefepime group and 19 of 101 (19%) patients in the imipenem group (P = 0.25). Rates of documented or presumed microbiological eradication of the causative organism were similar with cefepime (61%) and imipenem-cilastatin (54%) (95% CI, -23 to 8%). Primary or secondary resistance of Pseudomonas aeruginosa was detected in 19% of the patients treated with cefepime and 44% of the patients treated with imipenem-cilastatin (P = 0.05). Adverse events were reported in 71 of 138 (51%) and 62 of 141 (44%) patients eligible for safety analysis in the cefepime and imipenem groups, respectively (P = 0.23). Although the primary end point for this study does not exclude the possibility that cefepime was inferior to imipenem, some secondary analyses showed that the two regimens had comparable clinical and microbiological efficacies. Cefepime appeared to be less active against organisms producing an ESBL, but primary and secondary resistance to imipenem was more common for P. aeruginosa. Selection of a single agent for therapy of nosocomial pneumonia should be guided by local resistance patterns.

APACHE↗
PubMed2003

Caspofungin in the treatment of oropharyngeal candidiasis.

A patient with AIDS developed oropharyngeal candidiasis. Candida albicans and C. glabrata were isolated from the patient and found to be resistant to fluconazole and itraconazole in vitro. Voriconazole therapy was initiated, but discontinued when the C. albicans strain isolated from the patient was found to be resistant to it. The patient failed to respond to subsequent therapy with a combination of amphotericin B and 5-flucytosine. Therapy with caspofungin was then initiated (70 mg loading dose, followed by 50 mg/day). The patient responded favourably to caspofungin, with complete resolution of signs and symptoms.

AIDS-Related Opportunistic Infections↗
PubMed2002

Prospective epidemiologic survey of patients with community-acquired pneumonia requiring hospitalization in Switzerland.

BACKGROUND: Community-acquired pneumonia (CAP) is a common problem and the principal infection requiring hospitalization, but its treatment is complicated by the difficulty in microbiological diagnosis and the increasing incidence of antibiotic resistance among respiratory pathogens. The purpose of this paper is to present the main epidemiologic features of patients with CAP requiring hospitalization in our country. METHODS: We enrolled three hundred and eighteen adult patients with CAP requiring hospitalization in seven large medical centers in Switzerland during two winter periods. The patients' mean age was 70.4 years. This study describes the epidemiology of these patients. Clinical, radiologic and microbiological evaluations were performed at study entry during treatment, and at 4 weeks post-therapy. For microbiological diagnostic purposes, sputum culture, throat swab culture, PCR, blood cultures, Legionella urinary antigen and serologic evaluations were also performed. RESULTS: Despite the higher mean age, the overall mortality rate was 8%, lower than in other comparable studies. The most common underlying diseases present at study entry were cardiac failure (23%), chronic obstructive pulmonary disease (20%), renal failure (15%), and diabetes (12%); 40% of the patients were smokers. Although dyspnea, cough and positive pulmonary auscultation findings were present in about 90% of patients, fever >38 degrees C was present in only 64%. The most frequently isolated respiratory pathogens were Streptococcus pneumoniae (12.6%), Haemophilus influenzae (6%), Staphylococcus aureus (1.6%), and Moraxella catarrhalis (1.6%). Atypical pathogens were frequently found, with the following distribution: Mycoplasma pneumoniae, 7.5%; Chlamydia pneumoniae, 5.3%; and Legionella pneumophila, 4.4%. The mean duration between onset of symptoms and hospital admission was 4.8 days, and the mean treatment duration was 12.1 days. Two weeks after the start of therapy, although clinical symptoms were absent, radiologic infiltrates were still present in 24% of patients. CONCLUSIONS: The microbiological diagnosis in CAP can be established in only about 50% of cases with the combination of several diagnostic tools. Epidemiologic surveys of CAP should be performed on a regular basis, regionally, as a way to improve the management of these infections.

Aged↗
PubMed2001

Role of nasopharyngeal culture in antibiotic prescription for patients with common cold or acute sinusitis.

The aim of the present study was to assess the hypothesis that, when present in nasopharyngeal secretions, Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis play a pathogenic role early in the course of an upper respiratory tract infection. Adults with a clinical diagnosis of acute sinusitis or common cold were enrolled. Participants were randomly assigned in a double-blind manner to receive azithromycin 500 mg daily or placebo for 3 days. The effect of treatment on symptom evolution in the predefined subset of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis in their nasopharyngeal secretions was assessed. Of 265 patients enrolled, 132 received placebo and 133 azithromycin. Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis was identified in nasopharyngeal secretions of 77 patients (29%). In this predefined subgroup of patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 occurred in 73% of those treated with azithromycin compared with 47% of those who received placebo (P=0.007). The median time before resolution of symptoms was 5 days in the azithromycin group compared to 7 days in the placebo group. Respiratory complications requiring antibiotic treatment occurred in 19% of patients in the placebo group and in 3% of the azithromycin group (P=0.025). In the remaining 188 patients without Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, resolution of symptoms by day 7 was similar in both groups (69% in the placebo group vs. 64% in the azithromycin group [P=0.75]). Antibiotic treatment is of clinical benefit for patients with acute sinusitis or common cold when Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis is present in nasopharyngeal secretions. This observation provides new insights into the pathogenic role of these bacteria in the early stage of the common cold.

Acute Disease↗
PubMed2001

Phase II evaluation of suramin in advanced renal cell carcinoma. A Southwest Oncology Group study.

Twenty-two eligible patients with advanced renal carcinoma were treated with suramin utilizing a fixed dose regimen. Therapy was reasonably well tolerated with 3 of 22 patients (14%) developing grade 4 toxicity and 11 of 22 patients (50%) having a maximum toxicity of grade 3. There were no responders; median survival was 10 months. Suramin is not an active agent in advanced renal carcinoma.

Journal Article↗
PubMed2001

Experimental validation of a finite element model of the temporomandibular joint.

PURPOSE: A 2-dimensional finite model of the temporomandibular joint (TMJ) was previously developed to provide a way of studying the specific roles of individual components as well as the overall dynamics of joint motion. This study was undertaken to show that the previously reported finite element model provides results that are consistent with the experimentally obtained results. MATERIALS AND METHODS: The upper compartment of a TMJ of a fresh cadaver specimen was exposed to allow the insertion of a small strip of pressure-sensitive film. Measured loads were applied to the chin and angle of the mandible, pressing the condyle into the glenoid fossa. The resulting stresses in the joint stained the film, providing a way to determine their magnitude. Similar loads were applied to the finite element model and the stresses in the TMJ were mathematically calculated. RESULTS: Experimental results were successfully obtained in 4 separate attempts, recording maximum stresses of 5.6, 8.6, 6.4, and 9.9 MPa (megapascals), respectively. The corresponding finite element model predictions were 7.3, 6.9, 6.4, and 8.2 MPa, respectively. CONCLUSIONS: This study indicates that the results of the previously reported finite element model of the TMJ provide a reasonable approximation of the actual physical situation.

Aged↗
PubMed2001

Fungemia in HIV-infected patients: a 12-year study in a tertiary care hospital.

Opportunistic infections caused by fungi are common in human immunodeficiency virus (HIV)-infected patients. We focused on severe infections as indicated by detectable fungemia. Medical charts available for patients having positive blood cultures with fungi at the University of Geneva Hospital were retrospectively (1989 to 2000) reviewed. Of 328 patients with fungemia during the study period, 315 (96%) medical charts were accessible. Of these 315 patients, 37 (12.2%) were HIV-positive, and 13 (35.1%) died within 6 months from their episode of fungemia. This was a lower mortality rate than for the HIV seronegative patients (45.8%). The median and average age of the 34 HIV-positive patients was 37.2 years, and 24 (64.9%) were males. Cryptococcus neoformans (n = 14) and Candida albicans (n = 12) were the most frequently identified species, followed by Candida glabrata (n = 3), of which 3 were mixed C. albicans + C. glabrata, Histoplasma capsulatum (n = 2), and Penicillium marneffei (n = 2). The frequency decreased significantly (p < 0.007) from the time period 1993 to 1996 (n = 21) to the period 1997 to 2000 (n = 6). Fungemias in HIV-infected patients have declined significantly since 1996. This coincides with the introduction of highly active antiretroviral therapy (HAART).

AIDS-Related Opportunistic Infections↗
PubMed2001

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

OBJECTIVE: Phase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DESIGN: Multicenter, double-blind, phase III, placebo-controlled, randomized study. SETTING: A total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PATIENTS: A total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. INTERVENTION: After randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17-96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor alpha concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. CONCLUSION: Lenercept had no significant effect on mortality in the study population.

APACHE↗