No abstract

In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 (COX-2) over cyclooxygenase-1 (COX-1). Gastrointestinal (GI) tolerability of meloxicam 7.5 and 15 mg vs piroxicam 20 mg was evaluated in a 4-week, double-blind, parallel group, placebo-controlled study in 51 healthy male volunteers, using a combination of oesphago-gastro-duodenal endoscopy, faecal blood loss measurement and symptom evaluation. Analysis of covariance found no significant difference in faecal blood loss between the groups. However, significantly higher bleeding was found with piroxicam 20 mg compared with placebo using a Student's t-test on the weighted means. Endoscopy score were significantly higher with piroxicam than with meloxicam 7.5 mg or placebo (P < 0.01). A significant difference from baseline was observed in the meloxicam 15 mg and piroxicam groups (P < 0.05), but not in the meloxicam 7.5 mg and placebo groups. Six piroxicam-treated volunteers were withdrawn following a poor endoscopic score, but no such withdrawals occurred in the meloxicam and placebo groups (P < 0.01). Meloxicam 7.5 mg caused less GI damage compared with piroxicam 20 when administered to healthy young volunteers for 28 days; a possible dose dependency effect in GI tolerability was also suggested for meloxicam 7.5 and 15 mg, in relation to endoscopic findings.

IntroductionNosocomial legionellosis has generally been described in immunodepressed patients, but Legionella pneumophila serogroup 3 has rarely been identified as the causative agent.Case presentationWe report the case of nosocomial L. pneumophila serogroup 3 pneumonia in a 70-year-old Caucasian man with non-Hodgkin lymphoma. Diagnosis was carried out by culture and real-time polymerase chain reaction of bronchoalveolar lavage fluid. The results of a urinary antigen test were negative. A hospital environmental investigation revealed that the hospital water system was highly colonized by L. pneumophila serogroups 3, 4, and 8. The hospital team involved in the prevention of infections was informed, long-term control measures to reduce the environmental bacterial load were adopted, and clinical monitoring of legionellosis occurrence in high-risk patients was performed. No further cases of Legionella pneumonia have been observed so far.ConclusionsIn this report, we describe a case of legionellosis caused by L. pneumophila serogroup 3, which is not usually a causative agent of nosocomial infection. Our research confirms the importance of carrying out cultures of respiratory secretions to diagnose legionellosis and highlights the limited value of the urinary antigen test for hospital infections, especially in immunocompromised patients. It also indicates that, to reduce the bacterial load and prevent nosocomial legionellosis, appropriate control measures should be implemented with systematic monitoring of hospital water systems.

The object of this work was to compare the efficacy of antibiotic combinations including ceftriaxone with that of combinations including an antipseudomonal beta-lactam for the empirical treatment of febrile neutropenia in cancer patients. We identified all published randomised trials comparing two antibiotic combinations differing only in the beta-lactam, being ceftriaxone in one treatment group and an antipseudomonal beta-lactam in the other. The quality of individual trials was formally evaluated. A meta-analysis was performed using the Peto-modified Mantel-Haenszel method for combining binary data. Primary analysis was done, for both febrile episodes and bacteraemic episodes, using failure of empirical antibiotic treatment defined as modification of the initial allocated regimen or death during treatment. Secondary analysis was done using death from any cause in the two treatment groups. Data relating to 1,537 febrile neutropenic episodes recorded in eight randomised clinical trial were pooled s. Overall, there were 256 treatment failures out of 782 febrile episodes treated with ceftriaxone-containing combinations (32.7%), and 243 out of 755 treated with antipseudomonal beta-lactam regimens (32.1%). The pooled odds ratio of failure for ceftriaxone-containing combinations for febrile episodes was 1.04, with the 95% confidence interval ranging from 0.84 to 1.29, and that for bacteraemic episodes was 0.93 (95% confidence interval 0.58-1.49). With regard to overall mortality, there were 54 deaths among 782 febrile episodes treated with ceftriaxone-containing combinations (6.9%) and 62 deaths among 755 febrile episodes treated with antipseudomonal beta-lactam-containing regimens (8.2%). The pooled odds ratio of death for ceftriaxone regimens was 0.84 (95% confidence interval 0.57-1.24). Results of this meta-analysis show that in the empirical treatment of febrile neutropenia, antibiotic combinations containing ceftriaxone are as effective as those in which the beta-lactam has specific activity against Pseudomonas aeruginosa, such as ureidopenicillin or ceftazidime.