Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increase in the incidence of infections due to beta-lactam-resistant coagulase-negative staphylococci has resulted in expanded use of vancomycin for such infections. Despite this, coagulase-negative staphylococci have remained susceptible to vancomycin in recent years. This report describes a strain of Staphylococcus haemolyticus with increased resistance to vancomycin (MIC, 8.0 to 16 micrograms/ml). S. haemolyticus was initially isolated from a patient with acute leukemia and neutropenia in surveillance throat and stool cultures. The microdilution vancomycin MICs for these isolates were 1.0 to 2.0 micrograms/ml. Subsequent S. haemolyticus isolates from the bloodstream and tracheal aspirate occurred in the setting of prolonged empirical vancomycin therapy. MICs for these isolates were 8.0 to 16 micrograms/ml. Further vancomycin resistance (MIC, 32 micrograms/ml) could be selected for in vitro in all four isolates. Restriction endonuclease analysis of plasmid DNA indicated that the isolates were very closely related and likely to be of the same strain. We conclude that colonization with a vancomycin-susceptible strain of S. haemolyticus was subsequently linked to a nosocomial bloodstream infection with an apparently identical strain with intermediate levels of vancomycin resistance. Prolonged empirical vancomycin therapy was temporally associated with this episode.
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PMID:Vancomycin resistance in Staphylococcus haemolyticus causing colonization and bloodstream infection. 222 88

In an open study, 42 venous Port-A-Cath systems (PAC) were implanted in 40 patients with AML (12), ALL/AUL (11), NHL with bone marrow infiltration (8), Hodgkin's lymphoma (3), solid tumors (5) and severe aplastic anemia (1). Mean duration of system use was 212 days. The cumulated duration of use of all systems was 8.883 days. 1,627 blood samples were taken from the PAC. Blood sampling was possible on 8,696 of 8,883 days of cumulated access (98%). A total of 522 blood transfusions were administrated. Fifty-two episodes of neutropenia (granulocyte counts less than 0.5 x 10(9)/l) with a mean duration of 17 days were observed in the group of the 23 patients with acute leukemias. A total of 25 complications were registered. The incidence was 2.8/1,000 days of access. Twelve complications were regarded as severe. Venous thrombosis was observed in 3 cases. In addition, there were 2 disruptions of the catheter, 1 disconnection, 1 looping and 4 local infections. The rate of systemic infection could not be accurately estimated because the catheter was always left in place and antibiotic treatment was started immediately in case of fever with or without bacteriemia. The overall rate of catheter-related complications in patients with acute leukemia was not higher than in patients with solid tumors.
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PMID:Use of a fully implantable drug delivery system in the treatment of acute leukemias and disseminated lymphomas. 224 62

We evaluated the courses of 115 consecutive cases of pediatric acute leukemia treated with induction chemotherapy. Seventy-two patients developed fever associated with neutropenia; 15 developed systemic fungal infections. We reviewed multiple demographic and treatment characteristics of these patients in an attempt to identify potential risk factors for the development of invasive fungal disease (IFD). Risk factors identified in a univariate analysis included duration of neutropenia after first fever (P less than .0001), diagnosis of acute nonlymphocytic leukemia (ANLL) (P = .003), onset of fever and neutropenia within 5 days of starting induction chemotherapy (P = .009), and multiple (greater than one) surveillance culture sites positive for fungal organisms (P = .02). In a multiple logistic regression analysis, duration of neutropenia (P less than .001) remained a significant risk factor. The study group of patients had a significantly higher risk of fungal infections than a matched group of leukemia patients developing fever with neutropenia due to postremission consolidation chemotherapy (P = .003). In the first 48 patients, 14 (29%) developed IFD. In the subsequent patients (n = 24), intravenous miconazole (5 mg/kg every 8 hours) was begun at the time of the first fever. One of the 24 patients (4%) given miconazole developed IFD. The use of miconazole was a negative risk factor for the development of IFD in univariate (P = .01) and multivariate (P = .05) analysis. We conclude that pediatric leukemia patients who develop fever associated with neutropenia during induction chemotherapy are at high risk for developing IFD. The role of intravenous miconazole at the time of the first fever in this group deserves further study.
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PMID:Invasive fungal disease in pediatric acute leukemia patients with fever and neutropenia during induction chemotherapy: a multivariate analysis of risk factors. 229 71

Aminoglycoside pharmacokinetic parameters were studied prospectively in 27 patients with an underlying hematologic malignancy and fever associated with neutropenia and in 18 control patients. Pharmacokinetic parameters and dosages were determined by linear regression analysis of a one-compartment model by the method of Sawchuk et al. (R. J. Sawchuk, D. E. Zaske, R. J. Cippolle, W. A. Wargin, and R. G. Strate, Clin. Pharmacol. Ther. 21:362-369, 1976). Significant differences between the study and control groups were found for aminoglycoside volume of distribution (0.40 +/- 0.1 versus 0.27 +/- 0.05 liter/kg [mean +/- standard deviation], respectively; P less than 0.0001), clearance (116.6 +/- 48.9 versus 68.6 +/- 26.7 ml/min, respectively; P less than 0.0001), half-life (2.27 +/- 0.66 versus 3.5 +/- 1.8 h, respectively; P less than 0.0001), and elimination rate constant (0.33 +/- 0.11 versus 0.24 +/- 0.09 h-1, respectively; P less than 0.001). The percentage of bone marrow blast cells (at the time of diagnosis) in patients with acute leukemia significantly correlated with increased aminoglycoside clearance (R2 = 36.98%; P = 0.0001). Patients with stage IV lymphomas (Hodgkins disease and non-Hodgkins lymphoma) had a significantly increased clearance compared with patients with lower stages of lymphomas (105.1 +/- 18.5 versus 84.1 +/- 14.9 ml/min; P = 0.014). Fever, leukocyte count, or chemotherapy, among other clinical and laboratory parameters that were studied, had no significant correlation or effect on aminoglycoside disposition. The average dose of amikacin required to maintain peak concentrations in serum above 20 micrograms/ml in patients with a hematologic malignancy was 27.5 +/- 8.43 mg/kg per day. Pharmacokinetic parameters and dosages for the control patients were comparable to general literature standards. we conclude that the dosages recommended by the manufacturers or those derived from nomograms underestimate the aminoglycoside volume of distribution and clearance in patients with a hematologic malignancy and result in suboptimal peak aminoglycoside concentrations in serum. We recommend that in febrile neutropenic patients with an underlying hematologic malignancy, amikacin be initiated at 7.5 to 10 mg/kg per dose every 8 h (2 to 2.5 mg/kg per dose every 8 h for gentamicin) and adjusted within 24 h based on individual pharmacokinetic analysis.
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PMID:Increased aminoglycoside dosage requirements in hematologic malignancy. 236 Aug 11

The authors report two cases of splenic and hepatosplenic candidiasis occurring during a protracted neutropenia induced by chemotherapy for acute leukemia (lymphoblastic and myeloblastic respectively). Fungal infection was revealed by persistent or recurrent fever after correction of neutropenia. Diagnosis was suggested by findings at abdominal ultrasonography. It was confirmed by histological analysis which, in the first case, required open liver biopsy. In both cases, lack of improvement of splenic lesions despite treatment with Amphotericin B followed by fluconazole led to splenectomy. Both patients received postoperative anti fungal therapy with Ampho B and at one year's follow up, the patient who had the hepatosplenic candidiasis seems to have recovered.
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PMID:[Visceral candidiasis in 2 children treated for acute leukemia]. 236 69

In order to better understand the patho-physiologic role of granulocyte colony-stimulating factor (G-CSF), we estimated its serum levels in healthy persons and patients with various disorders, using a newly developed enzyme immunoassay (Motojima et al). In 49 of 56 normal healthy persons (88%), the levels were beneath the sensitivity of the assay (less than 30 pg/mL), while in the remaining seven healthy persons, the levels ranged from 33 to 163 pg/mL. On the other hand, nine of 11 patients (82%) with idiopathic aplastic anemia (AA), one patient with Fanconi's anemia, six of 12 patients (50%) with myelodysplastic syndrome (MDS), five of 12 patients (42%) with acute leukemia without any blast cells in the blood (M4: one, M5: one, L1: one, and L2: two), six of 18 patients (33%) with chronic myeloid leukemia (CML), one of two patients with chronic lymphoid leukemia (CLL), two of four patients with lung cancer, one patient with cyclic neutropenia, two of seven patients with malignant lymphoma, and four patients with acute infection had G-CSF levels ranging from 46 pg/mL to greater than 2,000 pg/mL. Interestingly, a reverse correlation between blood neutrophil count and serum G-CSF level was clearly demonstrated for aplastic anemia (r = -.8169, P less than .01). Moreover, it was found that the G-CSF level rose during the neutropenic phase of cyclic neutropenia and after chemotherapy or bone marrow transplantation (BMT) in three patients with leukemia; also high G-CSF levels were positively correlated to blood neutrophil counts in some cases of infectious disorders and lung cancer. The cellular sources and the mechanisms for production and secretion of circulating G-CSF were not investigated in this study, but the data presented here strongly indicate that G-CSF plays an important role as a circulating neutrophilopoietin.
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PMID:Serum granulocyte colony-stimulating factor levels in healthy volunteers and patients with various disorders as estimated by enzyme immunoassay. 246 34

A phase I/II study of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in 24 leukemia patients was conducted at our institute. Recombinant human G-CSF (50-200 micrograms/m2/day) was administered i.v. In seven allogeneic bone marrow transplantation (BMT) recipients, treatment with rhG-CSF was started 5 days after BMT. Neutrophils began to increase within 3 days after the start of rhG-CSF administration in five of seven patients. The mean duration necessary for recovery of neutrophils to greater than 500/microliters was 11.3 days after BMT with rhG-CSF; 26.8 days is the figure for recovery without rhG-CSF from Japanese historical data. In seven out of eight patients who received rhG-CSF administration after the first remission-induction chemotherapy, the neutrophil counts increased from less than 300/microliters to greater than 4000/microliters within 10 days. Blasts did not increase in all patients including four acute nonlymphocytic leukemia (ANLL) patients. Severe infections such as septicemia and pneumonia, which were unable to be controlled by antibiotics only, were successfully treated with rhG-CSF and antibiotics. rhG-CSF either stimulated or inhibited myeloid leukemic cells in some refractory cases. Mild bone pain occurred in one patient while receiving rhG-CSF i.v. rhG-CSF seems to have the ability to shorten the period of neutropenia, prevent infections after allogeneic BMT and remission-induction chemotherapy for acute leukemia, and support therapy for infections.
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PMID:Clinical effects of recombinant human granulocyte colony-stimulating factor in leukemia patients: a phase I/II study. 247 58

We analyzed infections complicating 140 episodes of severe neutropenia in 86 patients. The underlying diagnosis was acute leukemia in 64, lymphoma in 12 and isolated cases of bone marrow aplasia, agranulocytosis, dysmyelopoiesis and solid tumors. No fever developed in 35 (25%) episodes. No cause for the fever was identified in 40% of the remaining episodes. Clinical evidence of an infection was present in 20%, with positive bacteriologic findings in 27%. Respiratory infection (16%), pneumonia (11%) and sepsis (10%) were the most common infectious processes. Infectious agents isolated were gram negative bacilli (72%), gram positive cocci (19%) and fungi (9%). The association of amikacin and carbenicillin or cephalosporins proved to be superior to gentamycin-penicillin (p less than 0.01). 16 patients died for an overall mortality of 11%. Pneumonia and infection by K pneumoniae or C albicans were associated to a poorer prognosis.
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PMID:[Infection in severe neutropenia: analysis of 140 episodes]. 251 58

Ninety-nine consecutive patients who received cytotoxic therapy for acute leukemia were retrospectively studied to determine the pattern of infection at the Tata Memorial Hospital, Bombay, India. In all, 224 infective episodes occurred in these patients. Bacterial infection was the commonest type, accounting for 152 (67.9%) of 224 infective episodes, followed by fungal and viral infections (15.6% and 14.3%, respectively). Gram-negative organisms (Pseudomonas and Klebsiella) were the commonest bacterial organisms isolated, constituting 38 (76%) of 50 positive cultures; infection with Staphylococcus was rare (10%). Infective hepatitis, malaria, and systemic tuberculosis were responsible for fever with neutropenia in 20, 4, and 2 patients, respectively. Three hundred fifty-two patients with lymphoproliferative malignancies were also retrospectively studied to determine the pattern of infection. Only 53 infective episodes were recorded. In these patients, in contrast to those with acute leukemia, viral infection (33 [62.3%] of 53) and pulmonary tuberculosis (18 [34%] of 53) were frequently seen. It is interesting that 50% of our patients with hairy cell leukemia also had tuberculosis. Bacterial infection was conspicuous by its absence. Knowledge of the prevailing pattern of infection permits the development of investigative and therapeutic approaches of optimal efficacy.
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PMID:Pattern of infection in hematologic malignancies: an Indian experience. 260 80

Two cases of hepatosplenic candidiasis (HSC) are reported occurring after protracted episodes of neutropenia, induced by chemotherapy for acute leukemia in one case and drug hypersensitivity in the other. The disease presented with persistent or recurrent fever after correction of the neutropenia and with splenomegaly. The alkaline phosphatases were elevated. The diagnosis was strongly suggested by abdominal ultrasonography, CT scan and MRI, which showed multiple hepatosplenic defects. It was confirmed by serologic tests for candidiasis, the presence, in 1 case, of circulating candida antigens, and the rapid response to amphotericin B. The diagnosis of HSC should be considered in patients with persistent fever after an episode of neutropenia. Ideally, histologic confirmation is desirable, but this is often obtainable only by open liver biopsy, an aggressive procedure in such patients. Failing this, our 2 cases stress the diagnostic value of noninvasive imaging techniques, serological testing (in particular the discovery of circulating candida antigens) and the response to amphotericin B.
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PMID:Hepatosplenic candidiasis: an overlooked cause of prolonged fever during recovery from an episode of neutropenia. 264 20


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