minocycline and Neutropenia

Invasive fungal infection (IFI) is a serious complication of chemotherapy for hematological malignancies and autologous/allogeneic hematopoietic stem cell transplantation in children and shows a high mortality rate. We performed a randomized trial comparing micafungin (MCFG), a new anti-fungal agent, with fosfluconazole, a prodrug of fluconazole (FF) conventionally used as a prophylactic agent, for prophylaxis against IFI. Cefpirome was administered as prophylaxis against bacterial infection, and meropenem+minocycline as an empiric window therapy for febrile neutropenia. MCFG 2 mg/kg/day (max 100 mg/day) and FF 10 mg/kg/day (max 400 mg/day) were both safe and effective (event free ratio of IFI, MCFG 94.4% vs FF 94.3%) without significant difference. Thus, MCFG is safe and can be used for prophylaxis against IFI in children.

Topics: Adolescent; Child; Child, Preschool; Drug Therapy, Combination; Echinocandins; Female; Fluconazole; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lipopeptides; Male; Meropenem; Micafungin; Minocycline; Mycoses; Neutropenia; Opportunistic Infections; Organophosphates; Prodrugs; Thienamycins

Febrile neutropenic patients are at a high risk of life-threatening bacterial infections. Tigecycline was developed to treat multidrug-resistant isolates, however resistance to tigecycline in Klebsiella pneumoniae has been reported. Here, we investigated tigecycline resistance among K. pneumoniae isolated from febrile neutropenic patients admitted to Hematology ICU, Egypt. Out of 75 enrolled febrile neutropenic patients, 48 cases showed bacteriologically confirmed infection. The majority of cases were infected with K. pneumoniae, of which nine were tigecycline non-susceptible. Expression levels of the efflux pump genes acrB and oqxB and their regulatory genes ramA and rarA were analysed. Six isolates had overexpression of the four efflux-related genes while one showed baseline expression. This study emphasizes the importance of growing tigecycline resistance in K. pneumoniae infecting febrile neutropenic patients. Concerning the mechanism of resistance, it was clear that the ramA gene plays the major role, although alternative resistance mechanisms may also exist.

Topics: Adult; Animals; Anti-Bacterial Agents; Bacterial Proteins; Drug Resistance, Bacterial; Egypt; Female; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Neutropenia; Tigecycline; Young Adult

Tigecycline is the first available drug of glycylcycline family. Because of recent introduction, some of its adverse effects could be still unexplored.. We report the cases of 2 boys who underwent an allogenic bone marrow transplantation for acute myeloid leukemia and were treated with tigecycline. Erythrocyte and platelet engraftment followed a normal course, but the neutrophil count remained low despite the increase in leukocyte count. After tigecycline interruption, the neutrophil count rapidly raised in both cases.. Neutropenia was suspected to be secondary to tigecycline exposure. In vitro experiments were performed, which suggested tigecycline influence on myeloid cells survival.

Topics: Adolescent; Anti-Bacterial Agents; Bone Marrow Transplantation; Child; Combined Modality Therapy; Female; Graft Survival; Humans; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Minocycline; Myeloid Cells; Neutropenia; Neutrophils; Prognosis; Tigecycline; Transplantation Conditioning; Transplantation, Autologous

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

An 18-year-old patient is described who presented with febrile neutropenia and hepatitis caused by minocycline therapy. This rare complication of minocycline-induced lupus syndrome is discussed here.

Topics: Acne Vulgaris; Adolescent; Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Humans; Lupus Erythematosus, Systemic; Male; Minocycline; Neutropenia

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Topics: Adult; Anti-Bacterial Agents; Antibiotics, Antitubercular; Bone Marrow Transplantation; Catheterization, Central Venous; Catheters, Indwelling; Cohort Studies; Cross Infection; Drug Delivery Systems; Drug Resistance; Female; Humans; Infection Control; Leukemia; Male; Middle Aged; Minocycline; Neutropenia; Rifampin; Staphylococcal Infections; Texas

The in vivo pharmacodynamic activities of two glycylcyclines (GAR-936 and WAY 152,288) were assessed in an experimental murine thigh infection model in neutropenic mice. Mice were infected with one of several strains of Streptococcus pneumoniae, Staphylococcus aureus, Escherichia coli, or Klebsiella pneumoniae. Most infections were treated with a twice-daily dosing schedule, with administration of 0.75 to 192 mg of GAR-936 or WAY 152,288 per kg of body weight. A maximum-effect dose-response model was used to calculate the dose that produced a net bacteriostatic effect over 24 h of therapy. This dose was called the bacteriostatic dose. More extensive dosing studies were performed with S. pneumoniae 1199, E. coli ATCC 25922, and K. pneumoniae ATCC 43816, with doses being given as one, two, four, or eight equal doses over a period of 24 h. The dosing schedules were designed in order to minimize the interrelationship between the various pharmacokinetic and pharmacodynamic parameters studied. These parameters were time above 0.03 to 32 times the MIC, area under the concentration-time curve (AUC), and maximum concentration of drug in serum (C(max)). The bacteriostatic dose remained essentially the same, irrespective of the dosing frequency, for S. pneumoniae 1199 (0.3 to 0.9 mg/kg/day). For E. coli ATCC 25922 and K. pneumoniae ATCC 43816, however, more frequent dosing led to lower bacteriostatic doses. Pharmacokinetic studies demonstrated dose-dependent elimination half-lives of 1.05 to 2.34 and 1.65 to 3.36 h and serum protein bindings of 59 and 71% for GAR-936 and WAY 152,288, respectively. GAR-936 and WAY 152,288 were similarly effective against the microorganisms studied, with small differences in maximum effect and 50% effective dose. The glycylcyclines were also similarly effective against tetracycline-sensitive and tetracycline-resistant bacteria. Time above a certain factor (range, 0.5 to 4 times) of the MIC was a better predictor of in vivo efficacy than C(max) or AUC for most organism-drug combinations. The results demonstrate that in order to achieve 80% maximum efficacy, the concentration of unbound drug in serum should be maintained above the MIC for at least 50% of the time for GAR-936 and for at least 75% of the time for WAY 152,288. The results of these experiments will aid in the rational design of dose-finding studies for these glycylcyclines in humans.

Topics: Animals; Anti-Bacterial Agents; Area Under Curve; Colony Count, Microbial; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Half-Life; Mice; Mice, Inbred ICR; Minocycline; Muscle, Skeletal; Neutropenia; Survival Analysis; Tigecycline

Minocycline can cause various types of hepatotoxicity. We report an 18-year-old male who developed a delayed onset of minocycline-induced cholestatic hepatitis with autoimmune features and neutropenia. He responded to withdrawal of the drug and a short course of corticosteroids. If minocycline is to be administered, then periodic monitoring for hepatoxicity is recommended.

Topics: Acne Vulgaris; Adolescent; Anti-Bacterial Agents; Chemical and Drug Induced Liver Injury; Hepatitis, Autoimmune; Humans; Male; Minocycline; Neutropenia

Minocycline is a tetracycline agent frequently used for acne therapy. It has a few rare but severe side effects that are not widely known but should be recognized early as drug related. These include acute hepatitis and liver failure; a Löffler-like syndrome with pulmonary infiltrates, wheezing, fever, and eosinophilia; skin eruptions, eosinophilic cellulitis, and pustular folliculitis with eosinophilia; and a lupuslike syndrome. Side effects that are better known and recognized include photosensitization, skin exanthema with pruritus, and pseudotumor cerebri.

Topics: Acne Vulgaris; Adult; Drug Eruptions; Drug Hypersensitivity; Eosinophilia; Female; Fever; Humans; Liver; Lymphatic Diseases; Minocycline; Neutropenia