Voriconazole therapeutic drug monitoring improves the efficacy and safety of therapy in severely ill patients with invasive mycoses.

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Higher oral than intravenous VRC doses, followed by individualized adjustments based on measured plasma concentrations, improve achievement of the therapeutic target that maximizes the probability of therapeutic response and minimizes the probability of neurotoxicity. These findings challenge dose recommendations for VRC.

Viral respiratory infections are the most frequent cause of hospital admission for infants and young children during winter. However, the mechanisms of illness that are associated with viral lower-respiratory-tract infection (LRI) are unclear. A widely accepted hypothesis attributes the pathogenesis of viral LRI in infants to the induction of innate inflammatory responses. This theory is supported by studies showing that Toll-like receptor 4 is activated by respiratory syncytial virus (RSV), leading to production of inflammatory cytokines. We prospectively examined previously naive infants in Buenos Aires, Argentina, who had either upper- or lower-respiratory-tract symptoms. Infection with human metapneumovirus (hMPV) was second only to RSV in frequency. Both viruses were associated with rhinorrhea, cough, and wheezing; however, hMPV elicited significantly lower levels of respiratory inflammatory cytokines than did RSV. Symptoms in infants infected with influenza virus were different from those in infants infected with RSV, but cytokine responses were similar. These findings suggest that hMPV and RSV either cause disease via different mechanisms or share a common mechanism that is distinct from innate immune activation.

High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at >22 mg/liter (P ‫؍‬ 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.Cefepime, an extended-spectrum cephalosporin, is recommended for the empirical therapy of febrile neutropenia (11). The time during which the antibiotic plasma concentration is higher than the MIC for the causative pathogen is crucial for efficacy under this life-threatening condition (16). High-dose cefepime therapy (6 g/day for a glomerular filtration rate [GFR] of Ͼ50 ml/min) is recommended to achieve coverage of the most frequent bacterial pathogens in febrile neutropenia, including Pseudomonas aeruginosa (9, 26). Despite success rates of up to 60 to 80%, similar to those of other broadspectrum beta-lactams, cefepime therapy has recently been found to be associated with higher mortality rates (29). These findings indirectly suggest that the excess mortality might be due to toxicity. In vitro and in vivo studies have attributed the proconvulsive effect of cephalosporins to the drug-induced suppression of inhibitory neurotransmission via a concen...

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The present 3-year clinical study shows that an extrasinus approach can be utilized when placing zygomatic implants in patients with pronounced buccal concavities in the posterior maxilla. Moreover, the technique results in an emergence of the zygomatic fixture close to the top of the crest, which is beneficial from a cleaning and patient-comfort point of view.