Alain Kentos

Impact of Infectious Diseases Specialists and Microbiological Data on the Appropriateness of Antimicrobial Therapy for Bacteremia

Antimicrobial therapy for 428 episodes of bacteremia in an 850-bed university hospital was prospectively evaluated for 1 year to measure the impact of two factors--blood culture results and the therapy chosen by infectious diseases specialists (IDSs)--on quality of treatment and outcome. Initial shock, a simplified acute physiology score of >15, and inappropriateness of the empirical treatment were independently associated with increased mortality. Empirical treatment was appropriate in 63% of the episodes. This proportion reached 78% for the episodes treated by IDSs, compared with 54% for the others (P < .001). After availability of blood culture results, the proportion of appropriate treatments increased to 94%, with 97% for IDS-treated patients and 89% for other patients (P = .008). IDSs more frequently shifted to oral antibiotics and used fewer broad-spectrum drugs. This study underlines the impact of blood culture results and of IDSs on the prescription of appropriate treatment for bacteremia and on the better use of antimicrobial drugs.

Gonadotropin-Releasing Hormone Agonist for the Prevention of Chemotherapy-Induced Ovarian Failure in Patients With Lymphoma: 1-Year Follow-Up of a Prospective Randomized Trial

PURPOSE To assess the efficacy of gonadotropin-releasing hormone agonist (GnRHa) in preventing chemotherapy-induced ovarian failure in patients treated for Hodgkin or non-Hodgkin lymphoma within the setting of a multicenter, randomized, prospective trial. PATIENTS AND METHODS Patients age 18 to 45 years were randomly assigned to receive either the GnRHa triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) concomitantly with alkylating agents containing chemotherapy. The primary end point was the premature ovarian failure (POF) rate (follicle-stimulating hormone [FSH] ≥ 40 IU/L) after 1 year of follow-up. RESULTS Eighty-four of 129 randomly assigned patients completed the 1-year follow-up. The mean FSH values were higher in the control group than in the GnRHa group during chemotherapy; however, this difference was no longer observed after 6 months of follow-up. After 1 year, 20% and 19% of patients in the GnRHa and control groups, respectively, exhibited POF (P = 1.00). More than half of patients in each group completely restored their ovarian function (FSH < 10 IU/L), but the anti-Müllerian hormone values were higher in the GnRHa group than in the control group (1.4 ± 0.35 v 0.5 ± 0.15 ng/mL, respectively; P = .040). The occurrence of adverse events was similar in both groups with the exception of metrorrhagia, which was more frequently observed in the control group than the GnRHa group (38.4% v 15.6%, respectively; P = .024). CONCLUSION Approximately 20% of patients in both groups exhibited POF after 1 year of follow-up. Triptorelin was not associated with a significant decreased risk of POF in young patients treated for lymphoma but may provide protection of the ovarian reserve.

No Evidence for the Benefit of Gonadotropin-Releasing Hormone Agonist in Preserving Ovarian Function and Fertility in Lymphoma Survivors Treated With Chemotherapy: Final Long-Term Report of a Prospective Randomized Trial

PURPOSE We have reported previously that after 1-year follow up, gonadotropin-releasing hormone agonist (GnRHa) did not prevent chemotherapy-induced premature ovarian failure (POF) in patients with lymphoma, but may provide protection of the ovarian reserve. Here, we report the final analysis of the cohort after 5 years of follow up. PATIENTS AND METHODS A total of 129 patients with lymphoma were randomly assigned to receive either triptorelin plus norethisterone (GnRHa group) or norethisterone alone (control group) during chemotherapy. Ovarian function and fertility were reported after 2, 3, 4, and 5 to 7 years of follow up. The primary end point was POF, defined as at least one follicle-stimulating hormone value of > 40 IU/L after 2 years of follow up. RESULTS Sixty-seven patients 26.21 ± 0.64 years of age had available data after a median follow-up time of 5.33 years in the GnRHa group and 5.58 years in the control group (P = .452). Multivariate logistic regression analysis showed a significantly increased risk of POF in patients according to age (P = .047), the conditioning regimen for hematopoietic stem cell transplant (P = .002), and the cumulative dose of cyclophosphamide > 5 g/m(2) (P = .019), but not to the coadministration of GnRHa during chemotherapy (odds ratio, 0.702; P = .651). The ovarian reserve, evaluated using anti-Müllerian hormone and follicle-stimulating hormone levels, was similar in both groups. Fifty-three percent and 43% achieved pregnancy in the GnRHa and control groups, respectively (P = .467). CONCLUSION To the best of our knowledge, this is the first long-term analysis confirming that GnRHa is not efficient in preventing chemotherapy-induced POF in young patients with lymphoma and did not influence future pregnancy rate. These results reopen the debate about the drugs benefit in that it should not be recommended as standard for fertility preservation in patients with lymphoma.

Rituximab in auto-immune haemolytic anaemia and immune thrombocytopenic purpura: A Belgian retrospective multicentric study

Objectives.  For better characterizing the effect of anti‐CD20 therapy, we analysed the use of rituximab in Belgian patients experiencing auto‐immune haemolytic anaemia (AIHA) and immune thrombocytopenic purpura (ITP).

Ceftazidime- and Imipenem-Induced Endotoxin Release During Treatment of Gram-Negative Infections

Abstract. To determine whether ceftazidime and imipenem, which target two different penicillin-binding proteins, result in different amounts of endotoxin and cytokine release in patients with gram-negative infection, plasma endotoxin, interleukin-6, and tumor necrosis factor alpha were measured during the first 24 h of antibiotic therapy in 27 patients with gram-negative infection who had been randomized to receive either ceftazidime 2 g t.i.d. (n=12) or imipenem/cilastatin 1 g t.i.d. (n=15). The source of infection was the digestive tract (n=13), the urinary tract (n=5), the respiratory tract (n=2), soft tissue (n=2), i.v. line (n=2), or other (n=3). After the first antibiotic injection, a significant increase in the median concentration of plasma interleukin-6 and plasma tumor necrosis factor alpha was noted, without significant differences related to the antibiotic administered. Antibiotic-induced endotoxemia was detectable in nine patients (including 7 with bacteremia). In conclusion, ceftazidime and imipenem had similar effects on endotoxin and cytokine release during the treatment of gram-negative infections.

Subcutaneous panniculitis-like T-cell lymphoma: further evidence for a distinct neoplasm originating from large granular lymphocytes of T/NK phenotype

We report the case of a 20 year‐old caucasian woman who presented a primary subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) as an invasive tumor of the chest wall. Herein, the neoplastic cells were found to express a CD3+CD8+ phenotype but also displayed variably the natural killer (NK)‐associated antigens CD56 and CD57 as well as granzyme B. On cytological examination, these cells showed a large granular lymphocyte (LGL)‐like morphology with presence of azurophilic granules in their cytoplasm. Electron dense and membrane bound granules like those found in cytotoxic T lymphocytes (CTL) were also demonstrated by electron microscopy. Neither rearrangement of the T‐cell receptor subunits nor Epstein‐Barr virus (EBV) genome was observed at the molecular level. The LGL‐like features of the neoplastic cells found in this case and the presence of NK‐associated antigens provide additional support to the cytotoxic derivation of most SPTCL.

Post-transplant lymphoproliferative disorders after lung transplantation: first-line treatment with rituximab may induce complete remission.

Abstract: Background: Post‐transplant lymphoproliferative disorders (PTLD) are potentially lethal complications of solid organ transplantation. We, here, report on our experience with rituximab, an anti‐CD20 monoclonal antibody, as first‐line treatment for PTLD in six lung transplant recipients.

Bacillus cereus pneumonia in a patient with acute lymphoblastic leukemia

Reported here is a case of Bacillus cereus pneumonia that occurred in a patient with acute lymphoblastic leukemia. The presentation was severe, essentially marked by respiratory distress and pleuritic chest pain. Classic empirical treatment initiated for febrile neutropenia did not cover this rare pathogen and appropriate therapy was therefore delayed. B. cereus is most often a culture contaminant, but it can also be responsible for self-limited gastrointestinal intoxication and, more rarely, severe systemic diseases. Virulence in the case of systemic disease is attributed to tissue necrosis mediated by toxin release. B. cereus pneumonia, as described in the English-language literature, mainly affects immunocompromised patients and most often has a fatal outcome. Thus, the identification of B. cereus in clinical specimens of severely ill immunocompromised patients should lead physicians to question its clinical significance.

The role of rituximab in adults with warm antibody autoimmune hemolytic anemia

Warm antibody hemolytic anemia is the most common form of autoimmune hemolytic anemia. When therapy is needed, corticosteroids remain the cornerstone of initial treatment but are able to cure only a minority of patients (<20%). Splenectomy is usually proposed when a second-line therapy is needed. This classical approach is now challenged by the use of rituximab both as second-line and as first-line therapy. Second-line treatment with rituximab leads to response rates similar to splenectomy (∼70%), but rituximab-induced responses seem less sustained. However, additional courses of rituximab are most often followed by responses, at the price of reasonable toxicity. In some major European centers, rituximab is now the preferred second-line therapy of warm antibody hemolytic anemia in adults, although no prospective study convincingly supports this attitude. A recent randomized study strongly suggests that in first-line treatment, rituximab combined with steroids is superior to monotherapy with steroids. If this finding is confirmed, rituximab will emerge as a major component of the management of warm antibody hemolytic anemia not only after relapse but as soon as treatment is needed.

Prevotella bivia as an unusual cause of endocarditis.

A case of monomicrobial endocarditis due toPrevotella bivia in a 60-year-old man without previous cardiac lesions is reported. The extremely indolent course with multiple systemic emboli as the only clinical manifestation occurring at least seven months before diagnosis and the persistently negative blood cultures were remarkable features of this case. The incidence, clinical characteristics, treatment and outcome of published cases of infective endocarditis due to anaerobic bacteria are briefly reviewed.