minocycline and Hematologic-Neoplasms

Empiric antibiotic monotherapy is considered the standard of treatment for febrile neutropenic patients with cancer, but this approach may be inadequate because of the increasing prevalence of infections caused by multidrug resistant (MDR) bacteria.. In this multicenter, open-label, randomized, superiority trial, adult, febrile, high-risk neutropenic patients (FhrNPs) with hematologic malignancies were randomly assigned to receive piperacillin/tazobactam (4.5 g intravenously every 8 hours) with or without tigecycline (50 mg intravenously every 12 hours; loading dose 100 mg). The primary end point was resolution of febrile episode without modifications of the initial allocated treatment.. Three hundred ninety FhrNPs were enrolled (combination/monotherapy, 187/203) and were included in the intention-to-treat analysis (ITTA). The ITTA revealed a successful outcome in 67.9% v 44.3% of patients who had received combination therapy and monotherapy, respectively (127/187 v 90/203; absolute difference in risk (adr), 23.6%; 95% CI, 14% to 33%; P < .001). The combination regimen proved better than monotherapy in bacteremias (adr, 32.8%; 95% CI, 19% to 46%; P < .001) and in clinically documented infections (adr, 36%; 95% CI, 9% to 64%; P < .01). Mortality and number of adverse effects were limited and similar in the two groups.. The combination of piperacillin/tazobactam and tigecycline is safe, well tolerated, and more effective than piperacillin/tazobactam alone in febrile, high-risk, neutropenic hematologic patients with cancer. In epidemiologic settings characterized by a high prevalence of infections because of MDR microorganisms, this combination could be considered as one of the first-line empiric antibiotic therapies.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Chemotherapy-Induced Febrile Neutropenia; Drug Combinations; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Minocycline; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Risk Factors; Tigecycline; Young Adult

Topics: Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Hematologic Neoplasms; Humans; Minocycline; Retrospective Studies; Tigecycline

Tigecycline (TGC) is a first-in-class glycylcycline with an expanded spectrum of activity. Although TGC has not been prospectively studied in febrile neutropenia (FN), we observed that occasionally critically ill neutropenic patients unresponsive to other antibiotics were treated with TGC in our departments. The aim of our study was to analyse effectiveness and toxicity of TGC in FN.. Data of infectious episodes treated with TGC were retrospectively collected. Baseline data of patients, haematological malignancy, infection and adverse events were documented. Success was defined as defervescence (≥7 days) in the absence of any sign of persistent infection.. Data of 35 patients with haematological malignancies and FN were evaluated. Median duration of neutropenia was 25 days (range 6-69 days). The type of infection was pneumonia in 24 patients, four microbiologically documented infections, three clinically documented infections and four with fever of unknown origin. The TGC was administered after a median of two (range 1-5) prior antibiotic regimens. Treatment was successful in 15 (43 %) patients. In patients with prolonged neutropenia (≥28 days), response was significantly lower (13 vs. 79 %; p =0.001). Eight (23 %) patients died during the fever episode. Grade 3-4 toxicity occurred in five (14 %) patients.. Our results showed promising response rates to TGC and very low toxicity rates compared to the generally low response rate of third-line antibiotic therapies, indicating that TGC may be a successful alternative for salvage treatment of febrile neutropenia, but further study is needed.

Topics: Adult; Aged; Anti-Bacterial Agents; Chemotherapy-Induced Febrile Neutropenia; Drug-Related Side Effects and Adverse Reactions; Female; Hematologic Neoplasms; Hospitals, University; Humans; Male; Middle Aged; Minocycline; Retrospective Studies; Tigecycline; Treatment Outcome

Bacterial infections in patients with hematological neoplasms carry high morbidity and mortality. Gram-positive microorganisms can cause more than half of the bacterial infections in patients with febrile neutropenia, especially bacteremias. Effective coverage against these infections in these hosts, especially the immunodepressed, is required.. We reviewed the literature published in the last decade on infections in patients with hematological malignancies, with or without febrile neutropenia. Emphasis was placed on publications analyzing the processes caused by Gram-positive microorganisms and the management of these infections (whether bacteremic or otherwise) through traditional drugs (glycopeptides) and the new antibiotics (linezolid, tigecycline and daptomycin).. There was a notable scarcity of studies on the treatment of infections due to Gram-positive microorganisms in patients with cancer through treatment with the new antimicrobial drugs. Especially striking was the lack of comparative studies. Specifically, in the case of daptomycin, there were no randomized comparative trials in patients with febrile neutropenia, although there were observational retrospective studies or case studies [European Cubicin(®) Outcome Registry and Experience (EUCORE)] with a large number of patients (around 200) with oncological malignancies. In the three main studies, the overall favorable response rates were between 65% and 90%, with a therapeutic success rate of 85% in patients with severe febrile neutropenia. At the same time, the safety profile of daptomycin was shown to be highly favorable with good tolerability and a low rate of adverse effects (< 10% for those directly related to the antibiotic) which, on very few occasions, were severe or led to treatment withdrawal. The nephrotoxicity rate was much lower than that caused by vancomycin in historical control groups, although there were no statistically significant differences.. Daptomycin is a safe and effective therapeutic alternative in the treatment of bacterial infections due to Gram-positive microorganisms in patients with cancer, with or without neutropenia. However, further studies are required to support the use of this drug in the empirical treatment of febrile neutropenia.

Topics: Acetamides; Anti-Bacterial Agents; Antineoplastic Agents; Daptomycin; Databases, Factual; Europe; Glycopeptides; Gram-Positive Bacterial Infections; Hematologic Neoplasms; Humans; Immunocompromised Host; Kidney Diseases; Linezolid; Microbial Sensitivity Tests; Minocycline; Multicenter Studies as Topic; Neutropenia; Oxazolidinones; Registries; Retrospective Studies; Risk Factors; Tigecycline; Treatment Outcome

Multi-resistant coagulase-negative staphylococci (CNS) may cause systemic infections in patients undergoing bone marrow transplantation. Daptomycin, a new lipopeptide, and tigecycline, a new glycylcycline, have excellent activity against Gram-positive bacteria including methicillin-resistant staphylococci. This study presents the in vitro activity of daptomycin and tigecycline compared to vancomycin and fosfomycin against 105 CNS isolated from 76 bone marrow transplant patients with symptomatic bacteremia.. Blood stream isolates of Staphylococcus epidermidis (n = 102) and Staphylococcus haemolyticus (n = 3) from bone marrow transplant patients were collected from 2000 to 2006. The susceptibility of all isolates was tested using methods of the Clinical Laboratory Standards Institute.. The minimal inhibitory concentrations MIC(50) and MIC(90) were 0.125 microg/mL and 0.25 microg/mL for daptomycin, 0.25 and 0.5 microg/mL for tigecycline, 1 microg/mL and 2 microg/mL for vancomycin, and 8 microg/mL and >256 microg/mL for fosfomycin, respectively. MIC values of tested agents were similar for both methicillin-sensitive and methicillin-resistant S. epidermidis strains.. All CNS isolates were susceptible to the new antistaphylococcal agents daptomycin and tigecycline. Although vancomycin had been used over the past 30 yr at our bone marrow transplant unit all CNS were still susceptible to vancomycin.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bone Marrow Transplantation; Coagulase; Daptomycin; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Hematologic Neoplasms; Humans; In Vitro Techniques; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Staphylococcal Infections; Staphylococcus; Staphylococcus epidermidis; Staphylococcus haemolyticus; Tigecycline; Vancomycin