Invasive aspergillosis occurs in a wide range of clinical scenarios, is protean in its manifestations, and is still associated with an unacceptably high mortality rate. Early diagnosis is critical to ...a favourable outcome, but is difficult to achieve with current methods. Deep tissue diagnostic specimens are often difficult to obtain from critically ill patients. Newer antifungal agents exhibit differential mould activity, thus increasing the importance of establishing a specific diagnosis of invasive aspergillosis. For these reasons, a range of alternate diagnostic strategies have been investigated. Most investigative efforts have focused on molecular and serological diagnostic techniques. The detection of metabolites produced by Aspergillus spp and a range of aspergillus-specific antibodies represent additional, but relatively underused, diagnostic avenues. The detection of galactomannan has been incorporated into diagnostic criteria for invasive aspergillosis, reflecting an increased understanding of the performance, utility, and limitations of this technique. Measurement of (1,3)-β-D glucan in blood may be useful as a preliminary screening tool for invasive aspergillosis, despite the fact that this antigen can be detected in a number of other fungi. There have been extensive efforts directed toward the detection of Aspergillus spp DNA, but a lack of technical standardisation and relatively poor understanding of DNA release and kinetics continues to hamper the broad applicability of this technique. This review considers the application, utility, and limitations of the currently available and investigational diagnostic modalities for invasive aspergillosis.
Aspergillus spp. produce a wide range of invasive and sapropytic syndromes which may involve any tissue. Within a given tissue or organ the pathology and pathogenesis varies enormously, ranging from ...angioinvasive disease to non-invasive saprophytic disease. The individual invasive and saprophytic syndromes in which a causative role can be attributed to Aspergillus spp. are detailed specifically with reference to the underlying pathology and pathogenesis, the clinical setting and features, and the manner in which a diagnosis can be established.
Candida infections are common and often fatal in infants and neonates. Anidulafungin has excellent activity against Candida species, but the pharmacokinetics (PK) and safety of the drug in infants ...and neonates are unknown. The object of our study was to determine the PK and safety of anidulafungin in infants and neonates at risk for invasive candidiasis. Intravenous anidulafungin (1.5 mg/kg/day maintenance dose) was administered to 15 infants and neonates over 3 to 5 days. Plasma samples were collected after the first dose and again after the third to fifth doses. The pharmacokinetic parameters of the drug were determined by noncompartmental analysis. Safety was assessed using National Cancer Institute common toxicity criteria. The study showed that drug exposure levels were similar between neonates and infants; the median areas under the concentration–time curve (range) was 75 (30–109) µg·h/ml and 98 (55–278) µg·h/ml (P = 0.12) for neonates and infants, respectively. No drug‐related serious adverse events were observed. The study results indicate that neonates and infants receiving 1.5 mg/kg/day have anidulafungin exposure levels similar to those in children receiving similar weight‐based dosing and in adult patients receiving 100 mg/day.
Clinical Pharmacology & Therapeutics (2011) 89 5, 702–707. doi:10.1038/clpt.2011.26
This review examines both early and late wound complications following laparotomy closure, with particular emphasis on technical aspects that reduce hernia formation. Abdominal fascial closure is an ...area of considerable variation within the field of general surgery. The formation of hernias following abdominal wall incisions continues to be a challenging problem. Ventral hernia repairs are among the most common surgeries performed by general surgeons, and despite many technical advances in the field, incisional hernia rates remain high. Much attention and research has been directed to the surgical management of hernias. Less focus has been placed on prevention of hernia formation despite its obvious importance. This review examines the effects of factors such as the type of incision, suture type and size, closure method, patient risk factors, and the use of prophylactic mesh. Keywords: incisional, abdominal, hernia, prevention, wound closure techniques
Invasive aspergillosis is an increasingly common disease. While there have been significant advances in the past decade, significant challenges remain in terms of diagnosis and therapy. Some of the ...recent advances are outlined and future opportunities to improve the unacceptable mortality that is currently associated with this infection are considered.
The strategy of combining antifungal drugs in a treatment regimen may improve the outcome of invasive candidiasis. Using a well-validated pharmacodynamic murine model of invasive candidiasis, we ...defined the effect of the combination of amphotericin B deoxycholate (AmB) and 5-fluorocytosine (5FC) by use of the Greco model of drug interaction. The combination was additive, meaning that the experimental effect did not deviate in a statistically significant manner from the null reference model (or additive surface) of the combined effect. From a clinical perspective, the addition of 5FC to a regimen of AmB may enable the near-maximum effect to be reached in circumstances in which the administration of a given dose of AmB alone produces a submaximum effect but an increase in the dose is not possible, because of dose-related toxicity. Our methods provide a way in which some of the complex issues surrounding antifungal combination treatment can be addressed
Empyema, a pyogenic or suppurative infection of the pleural space, continues to cause significant morbidity and mortality in patients with pneumonia. The advent of video-assisted thoracoscopy has ...placed the treatment algorithm of empyema in flux. We retrospectively reviewed all patients who underwent surgical treatment for parapneumonic empyema from January 1, 1999, through December 31, 2003. Data collected included demographic information, preoperative CT scanning/ thoracostomy tube placement, morbidity/mortality, days from admission to surgery, and postoperative length of stay. We compared patients undergoing video-assisted thoracoscopy to those requiring conversion to open thoracotomy and those who had initial open thoracotomy. Morbidity and mortality rates were similar among all groups. Conversion rate to open thoracotomy was 21 per cent. We found patients operated on within 11 days of admission had a shorter postoperative length of stay with similar morbidity and mortality. Our data supports early aggressive surgery treatment for parapneumonic empyema.
This case describes a 61-year-old apparently immunocompetent female with invasive pulmonary aspergillosis (IPA) and eosinophilia who demonstrated spontaneous clinical and radiological recovery. The ...patient had a history of asthma and had been corticosteroid dependent until 2 months prior to her presentation. This report explores the role of PCR in confirming the diagnosis of invasive aspergillosis in circumstances where only histological data are available and highlights the fact that invasive infections with
Aspergillus spp. can occur without profound immunological deficiency. The case also documents the resolution of IPA without specific therapy.
PDF
