A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.

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.

Ceftriaxone versus beta-lactams with antipseudomonal activity for empirical, combined antibiotic therapy in febrile neutropenia: a meta-analysis.

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.

Double-blind, placebo-controlled study on effects of diclofenac sodium and indomethacin on postprandial gastric motility in man.

Data from animal studies suggest that NSAIDs-induced gastric damage may be due to increased gastric motility. Such a mechanism, however, has never been tested or demonstrated in man. We evaluated the effects of two frequently prescribed NSAIDs, indomethacin and diclofenac sodium, on postprandial gastric motor activity (a physiologically reproducible stimulus) in healthy volunteers to see whether these compounds increase gastric motility. Twenty-four healthy volunteers of both sexes, 21-35 years of age, underwent a basal gastric motility recording. Thereafter, they were randomized in three groups to receive either placebo, indomethacin (50 mg three times a day) or diclofenac sodium (50 mg three times a day) for a week. At the end of the week, they underwent an identical manometric study. Analysis of the motility tracings showed no difference in gastric antral motility index and in amplitude of gastric antral contractions after NSAIDs with respect to the basal study and to the placebo group. About 50% of subjects (two in the placebo group) complained of side effects. These were transient and mild, except in two subjects taking indomethacin, in whom endoscopy was necessary; one of these had a small prepyloric ulcer. It is concluded that in man NSAID-related gastric damage is unlikely to be due to increased gastric motility.

A 4-week, double-blind, parallel-group study to compare the gastrointestinal effects of meloxicam 7.5 mg, meloxicam 15 mg, piroxicam 20 mg and placebo by means of faecal blood loss, endoscopy and symptom evaluation in healthy volunteers.

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.

[Cervical osteolysis. Initial manifestation of embryonal rhabdomyosarcoma]. / Ostéolyse cervicale. Manifestation inaugurale d'un rhabdomyosarcome embryonnaire.

Initial manifestations in a patient with an embryonic rhabdomyosarcoma were signs of cervical spine osteolysis. Initial histological diagnosis of a chordoma was rejected on the basis of the site of the tumor and then eliminated by a second histological study. The course was fulminating over a period of 8 months. Comparison between this case and intracranial localizations of the tumor are possible because of mild initial involvement of the soft tissues.

[Acute primary infection due to slow-growing anaerobes after total hip arthroplasty (author's transl)]. / Infection aiguë précoce primitive à germes anaérobies à croissance lente après chirurgie prothétique de la hanche. Trois observations.

Most early post-operative infections in total hip arthroplasty are due to aerobic bacteria. Anaerobes infections are less common and less easy to diagnose since the organisms are growing slowly. In the three patients reported the responsible organisms were detected by a strict bacteriological technique including cultures lasting more than 48 hours. Treatment consisted of re-operation and appropriate antibiotic therapy. The slow development of anaerobic bacteria makes antibiotic sensitivity tests particularly difficult to read. The need for cultures prolonged beyond 48 hours partly explains the frequency of overt suppuration in cases where standard bacteriological methods had given negative results.

Fractures of cervical spine with neurological lesion treated by reduction and fixation with plates.

A series of 61 cases of cervical spine fracture and dislocation with neurological deficit treated operatively were reviewed. All were reduced and internally fixed with plates and screws. The operative technique was not easy and required a great deal of care and experience. Surgery did not significantly alter the neurological recovery in 12 cases with root involvement and 23 cases with complete tetraplegia. Neurological recovery seemed to be better after surgical intervention in the case of incomplete tetraplegias; 18 out of 26 being able to walk eventually. The main value of surgical fixation of these injuries was to allow early rehabilitation without any external cervical support. However, intensive care of the neuro-cardio-respiratory complications in the post-operative period was necessary to evert the high risk of mortality and morbidity from surgery.

Treatment of infected pseudoarthrosis of limbs.

It was not difficult to treat an infected pseudoarthrosis without loss of bone substance by "excision-decortication-drainage" in one stage. Union was obtained in 90% of the cases. The rest required additional bone grafts. In only one case out of 41 was there persistent infection. The problem of infected pseudoarthrosis with loss of bone substance and a sizeable defect was more difficult to solve. None of the several methods of treatment employed were without complications. When the overlying skin defect was large and impossible to close in the presence of persistent sepsis at the pseudoarthrosis defect, Papineau's two stage technique of wide excision first followed by insertion of spongious autologous grafts through the granulating defect, appeared secure with minimal risk of residual osteitis in nearly 90% of the cases. 15% of the cases had poor skin healing, requiring further treatment and 20% (nearly one in five) had a stress fracture through the grafted area. One out of 35 cases had persistent pseudoarthrosis and two had persistent infection. In ten selected cases of infected pseudoarthrosis of the tibia with large skin and bone defect, a one stage method of excision, bone grafting and primary skin cover with a local gastrocnemius flap was attempted. In seven cases, primary skin healing and bone union was achieved, one patient required further bone grafting and two had recurrence of sepsis. If properly planned, this one stage method may be indicated in selected cases of infected pseudoarthrosis of the tibia.