Pharmacokinetics and Pharmacodynamics of Cefepime in Adults with Hematological Malignancies and Febrile Neutropenia after Chemotherapy.

Patients with chemotherapy-induced febrile neutropenia (CIFN) may have changes in the pharmacokinetics (PK) compared to patients without malignancies or neutropenia. Those changes in antibiotic PK could lead to negative outcomes for patients if the therapy is not adequately adjusted to this. In this, open-label, non-randomized, prospective, observational, and descriptive study, a PK model of cefepime was developed for patients with hematological neoplasms and post-chemotherapy febrile neutropenia. This study was conducted at a cancer referral center, and study participants were receiving 2 g IV doses of cefepime every 8 h as 30-min infusions. Cefepime PK was well described by a two compartment model with a clearance dependent on a serum creatinine level. Using Monte Carlo simulations, it was shown that continuous infusions of 6g q24h could have a good achievement of PK/PD targets for MIC levels below the resistance cut-off point of Enterobacteriaceae. According to the simulations, it is unnecessary to increase the daily dose of cefepime (above 6 g daily) to increase the probability of target attainment (PTA). Cumulative fraction of response (CFR) using interment dosing was suboptimal for empirical therapy regimens against K. pneumoniae and P. aeruginosa, and continuous infusions could be used in this setting to maximize exposure. Patients with high serum creatinine levels were more likely to achieve predefined PK/PD targets than patients with low levels.

Idiopathic Acquired Hemophilia A, a Rare Cause of Bleeding: A Case Report and Literature Review.

BACKGROUND Acquired hemophilia is a bleeding disorder mediated by an autoimmune process, in which antibodies against clotting factors are developed. This is a rarely suspected complex condition in which the initial manifestations are spontaneous bleeding in the skin, soft tissues, and mucosa in patients with no known history of bleeding disorders. Most of the cases are idiopathic (50%), but it can be associated with autoimmune diseases, malignancy, pregnancy, and medications. The most frequent type is mediated by inhibitors against factor VIII, followed by coagulation factor IX and XI. It is a disease with high morbidity and mortality rates without adequate treatment. Diagnosis is based on the detection of low concentrations of clotting factors and the presence of an inhibitor. CASE REPORT We present 2 cases of patients with spontaneous bleeding in whom the diagnosis of idiopathic acquired hemophilia A was made, an extensive malignancy study was performed that was negative, and the presence of autoimmunity markers (positive antinuclear antibodies (ANA)) was observed, without any another sign of autoimmune disease. They received immunosuppressive therapy with bleeding control and inhibitor eradication. CONCLUSIONS Acquired hemophilia A is a rare but potentially lethal disease, representing a medical challenge from its diagnosis to its treatment. An early recognition and treatment are fundamental because delays are associated with adverse outcomes. Optimal management includes the workup and treatment for an underlying disease, use of "bypass" agents when active bleeding presents, and inhibitor titer eradication through immunosuppressants drugs. With the present cases, we highlight the importance of considering acquired hemophilia A in older patients with similar symptoms, to achieve early diagnosis and treatment.

Paraneoplastic Hypoglycemia in Hepatocarcinoma: Case Report and Literature Review.

Hypoglycemia is a common medical emergency in the context of insulin treatment in diabetic patients and oral hypoglycemic agents such as sulfonylureas. In anecdotal cases, hypoglycemia is associated with non-islet cell tumor-induced hypoglycemia (NICTH). In hepatocellular carcinoma (HCC), it has been reported in 4-27% of patients, and it is associated with poor prognosis. We present a case report of a patient with hypoglycemia associated with HCC secondary to chronic hepatitis B virus infection without response to treatment with glucagon, steroids, octreotide, and embolizations, who required parenteral nutrition at home. Even though hypoglycemia associated with HCC is a recognized entity, there is not sufficient evidence in its treatment and prevention. The article aims to review the literature on prevention and therapeutic options.

Iron status markers are only transiently affected by a football game.

We examined the temporal variation of iron's status markers during a 60 h period following a football game. Thirty-four male football players were randomly assigned to a control group (CG, N = 14, participated only in measurements and training) or an experimental group (EG, N = 20, took part in a football game one week after the completion of the competitive season). All participants trained regularly for two consecutive days after the game. Training and game load was monitored with high time-resolution global positioning system (GPS) devices. Blood samples were collected and muscle damage markers and repeated sprint ability (RSA) were assessed pre-game and at 2 h, 12 h 36 h and 60 h post-game. No changes were noted in CG. Iron concentration decreased (P < 0.05) 2 h post-game and normalised thereafter whereas total iron binding capacity increased (P < 0.05) 12-60 h of recovery (P < 0.05). Erythrocytes, haemoglobin (HGB) concentration, plasma volume, haematocrit, mean cell volume, mean cell HGB, mean cell HGB concentration, red cell width-SD, red cell width-CV, ferritin concentration and transferrin saturation remained unaltered during the intervention period. Creatine kinase activity and muscle soreness increased (P < 0.05) throughout recovery in EG. RSA declined (P < 0.05) until 36 h of recovery and normalised thereafter. Our data demonstrate that iron status markers are only transiently affected by a football game.

Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy.

INTRODUCTION: Patients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center. METHODS: This was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent. RESULTS: We investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm³ (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1-1133 mg/L; minimum concentration, 0.47-37.65 mg/L; volume of distribution, 0.08-0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42-27.25 L/h (mean, 9.93 L/h); half-life (t(1/2)), 0.55-2.65 h (mean, 1.38 h); and area under the curve, 115.12-827.16 mg · h/L. CONCLUSION: Patients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1(/2) and decreased CL.