Treatment with oral CMX001 at a dose of 100 mg twice weekly significantly reduced the incidence of CMV events in recipients of hematopoietic-cell transplants. Diarrhea was dose-limiting in this population at a dose of 200 mg twice weekly. (Funded by Chimerix; CMX001-201 ClinicalTrials.gov number, NCT00942305.).
The anti-cytomegalovirus (CMV) activity and safety of oral maribavir in CMVseropositive allogeneic stem-cell transplant recipients were evaluated in a randomized, double-blind, placebocontrolled, dose-ranging study. After engraftment, 111 patients were randomized to receive CMV prophylaxis with maribavir (100 mg twice daily, 400 mg once daily, or 400 mg twice daily) or placebo. Within the first 100 days after transplantation, the incidence of CMV infection based on CMV pp65 antigenemia was lower in each of the respective maribavir groups (15%, P ؍ .046; 19%, P ؍ .116; 15%, P ؍ .053) compared with placebo (39%). Similarly, the incidence of CMV infection based on plasma CMV DNA was lower in each of the respective maribavir groups (7%, P ؍ .001; 11%, P ؍ .007; 19%, P ؍ .038) compared with placebo (46%). Anti-CMV therapy was also used less often in patients receiving each respective dose of maribavir (15%, P ؍ .001; 30%, P ؍ .051; 15%, P ؍ .002) compared with placebo (57%). There were 3 cases of CMV disease in placebo patients but none in the maribavir patients. Adverse events, mostly taste disturbance, nausea, and vomiting, were more frequent with maribavir. Maribavir had no adverse effect on neutrophil or platelet counts. These results show that maribavir can reduce the incidence of CMV infection and, unlike ganciclovir, does not cause myelosuppression. This trial is registered at www. ClinicalTrials.gov as #NCT00223925.
This cross-sectional and prospective one year study evaluated adults admitted to an inner city hospital with community-acquired pneumonia. The study used extensive diagnostic methods to evaluate the etiologies of community-acquired pneumonia in hospitalized patients with differing immunologic status. Of 385 study patients, concurrent problems associated with immunosuppression were noted in 221 (57%) patients, 180 of whom were human immunodeficiency virus (HIV)-infected. The five most common causes of community-acquired pneumonia were: Streptococcus pneumoniae, Pneumocystis carinii, aspiration, Hemophilus influenzae, and gram-negative bacilli. Only 8.3% of patients had either Legionella, Chlamydia pneumoniae or Mycoplasma pneumoniae. Despite use of state-of-the-art diagnostic techniques, no diagnosis was made in 46 of 180 (25.6%) HIV-infected patients, 56 of 164 (34.1%) immunocompetent patients, and 20 of 41 (48.8%) non-HIV-infected immunosuppressed patients. The diagnostic yield of pre-antibiotic sputum culture for conventional bacteria was 99/155 (63.9%) compared to 52 of 169 patients (32.7%) with adequate post-antibiotic sputum culture (p < 0.0001). Although S. pneumonia continues to be the most commonly identified etiologic agent of community-acquired pneumonia, it is surpassed by P. carinii in the HIV-infected patient population. The apparent decline in the frequency of S. pneumoniae in our series presumably reflects administration of antibiotics prior to procurement of sputum culture. The paucity of atypical agents in this study support the current American Thoracic Society guidelines for selective use of macrolide therapy in immunocompetent adults hospitalized with community-acquired pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)
We conducted a prospective study of 385 patients who had community-acquired pneumonia with use of a modified polymerase chain reaction (PCR) assay that detects amplified DNA by enzyme immunoassay (EIA). We used PCR-EIA to improve detection of Chlamydia pneumoniae infection and to differentiate C. pneumoniae infection from other chlamydial infections. Cultures of throat swab specimens from four patients yielded Chlamydia species (C. pneumoniae, one patient; Chlamydia species, two patients; and C. psittaci, one patient). C. pneumoniae was repeatedly detected by PCR-EIA for thirteen (3.4%) of these 385 patients. Six of these 13 patients were infected with the human immunodeficiency virus. Ten (76.9%) of the patients who were positive by PCR-EIA had IgG titers of > or = 1:16, and two (15.4%) of the 13 patients had IgG titers of < 1:16; no sera was available in one case. Other pathogens were recovered in eight (61.5%) of the 13 cases in which C. pneumoniae was detected by PCR-EIA. In addition, for 46 (11.9%) of the 385 patients the titers of antibody were considered diagnostic of C. pneumoniae infection; however, as 36 of the 46 patients were infected with the human immunodeficiency virus (which may have affected their serological response to C. pneumoniae), interpretation of these titers was problematic. As PCR-EIA was more sensitive than was culture for detecting C. pneumoniae infection in this study, this method may be a valuable tool for the prompt diagnosis of this infection.
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