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This overview of reviews (i.e., an umbrella review) is designed to reappraise the validity of systematic reviews (SRs) and meta-analyses related to the performance of Aspergillus PCR tests for the diagnosis of invasive aspergillosis in immunocompromised patients. The methodological quality of the SRs was assessed using the AMSTAR-2 checklist; the quality of the evidence (QOE) within each SR was appraised following the GRADE approach. Eight out of 12 SRs were evaluated for qualitative and quantitative assessment. Five SRs evaluated Aspergillus PCR on bronchoalveolar lavage fluid (BAL) and three on blood specimens. The eight SRs included 167 overlapping reports (59 evaluating PCR in blood specimens, and 108 in BAL), based on 107 individual primary studies (98 trials with a cohort design, and 19 with a case−control design). In BAL specimens, the mean sensitivity and specificity ranged from 0.57 to 0.91, and from 0.92 to 0.97, respectively (QOE: very low to low). In blood specimens (whole blood or serum), the mean sensitivity ranged from 0.57 to 0.84, and the mean specificity from 0.58 to 0.95 (QOE: low to moderate). Across studies, only a low proportion of AMSTAR-2 critical domains were unmet (1.8%), demonstrating a high quality of methodological assessment. Conclusions. Based on the overall methodological assessment of the reviews included, on average we can have high confidence in the quality of results generated by the SRs. [ABSTRACT FROM AUTHOR]

Despite the availability of four different classes of antifungal agents, invasive fungal infections, in particular mould diseases, continue to have a high crude mortality rate in adult haematology patients, especially when diagnosed late. Early diagnosis, resulting in prompt and adequate antifungal intervention, is of great importance when trying to improve the overall outcome of these infections, but depends on the availability of rapid and sensitive diagnostic tools. The medical community has developed and continues to evaluate a continuum of antifungal strategies (starting with prophylaxis followed by empirical therapy and more recently a diagnostic-driven or pre-emptive approach) to better tackle these life-threatening diseases. While the empirical approach seems to have lost some of its popularity, the jury is still out about the pros and cons of universal antifungal prophylaxis in at-risk adult haematology patients compared with an approach that uses radiological and mycological diagnostic methods with good to excellent negative predictive values (also erroneously called pre-emptive), trying to exclude the presence of an invasive fungal disease. Whilst awaiting the results of comparative clinical studies, believers and non-believers around the globe continue to argue about the advantages and shortcomings of both strategies. The debate presented here provides a rationale for both prophylaxis for 'high-risk' haematology patients as well as for a more targeted approach based on the appropriate use of mycological, radiological, immunological (and genetic) methods for the diagnosis of invasive fungal diseases. [ABSTRACT FROM AUTHOR]

There are a variety of challenges faced in the management of invasive fungal diseases (IFD), including high case-fatality rates, high cost of antifungal drugs and development of antifungal resistance. The diagnostic challenges and poor outcomes associated with IFD have resulted in excessive empirical use of antifungals in various hospital settings, exposing many patients without IFD to potential drug toxicities as well as causing spiralling antifungal drug costs. Further complexity arises as different patient groups show marked variation in their risk for IFD, fungal epidemiology, sensitivity and specificity of diagnostic tests and the pharmacokinetics and pharmacodynamics of antifungal drugs. To address these issues and to ensure optimal management of IFD, specialist knowledge and experience from a range of backgrounds is required, which extends beyond the remit of most antibiotic stewardship programmes. The first step in the development of any antifungal stewardship (AFS) programme is to build a multidisciplinary team encompassing the necessary expertise in the management of IFD to develop and implement the AFS programme. The specific roles of the key individuals within the AFS team and the importance of collaboration are discussed in this article. [ABSTRACT FROM AUTHOR]

Summary: Objectives: The aim of this study was to assess the clinical utility of enhanced diagnostics on the management of invasive fungal disease in high risk patients within an integrated care pathway and to audit compliance and efficacy of antifungal prophylaxis. Methods: A cohort of 549 high risk haematology and stem-cell transplant recipients was followed over a 5 year period. The routine standard of care involved the use of antimould prophylaxis and a neutropenic care pathway utilizing twice weekly antigen and PCR testing. Results: Prophylaxis with itraconazole was poorly tolerated and therapeutic levels could not be maintained. Antigen testing and PCR showed good clinical utility in the management of invasive aspergilosis with high sensitivity (98%) and negative predictive value (99.6%) when both tests were used together, allowing a diagnosis IA to be excluded and obviating the need for empirical antifungal agents. When used serially, multiple positive PCR and antigen test results enabled accurate diagnosis of IA with a specificity of 95% and a positive likelihood ratio of 11. Biomarkers preceded clinical signs in 85% of proven and probable invasive disease. Conclusion: The combination of both tests showed optimum clinical utility for the diagnosis and management of IA in this high risk group. [Copyright &y& Elsevier]

Despite improvements in medical technology, the definitive diagnosis of invasive fungal disease (IFD) is limited. The prevalence of disease is relatively low but many cases are undiagnosed. With the diagnosis of proven IFD dependent on histopathology or culture from a sterile site, clinicians have become more reliant on noninvasive nonculture diagnostic techniques. PCR technology has the capacity to overcome classical limitations but has its own drawbacks, resulting from an incomplete knowledge of the various disease processes and subsequent shortage of optimal specimens, leading to a lack of methodological standardization. This review will consider the general principles and limitations of fungal PCR before discussing genus-specific PCR applications. It is by no means a systematic review of the literature but is intended, where possible, to provide the reader with access to assays with proficient clinical performance. [ABSTRACT FROM AUTHOR]

Background. Invasive aspergillosis (IA) is associated with high mortality. Successful outcome with treatment is linked to early diagnosis. The utility of classic diagnostic methods, however, is limited. Methods. To aid in the diagnosis of IA, we retrospectively assessed our diagnostic service, using real-time polymerase chain reaction (PCR) and galactomannan sandwich enzyme-linked immunosorbent assay (ELISA). Results. A total of 203 patients at risk of invasive fungal infection were screened by PCR, and 116 of the patients were also tested by ELISA. The patient group comprised 176 patients with hematological malignancy and 28 control patients with evidence of invasive candidal infection. Consensus European Organisation for Research and Treatment of Cancer and Mycoses Study Group criteria were used to classify fungal infection, which, by definition, excluded the PCR result. The PCR method was sensitive (up to 92.3% sensitivity) and specific (up to 94.6% specificity) and had good agreement with the galactomannan ELISA (76.7%) and high-resolution computed tomography scan results. Conclusions. A negative PCR result can be used to rule out IA and to limit the need for empirical antifungal therapy', thus, it has a role in diagnosing IA infections, especially in combination with antigen testing. PCR-positive cases classified as "false positives" regularly reflect the limitations of classic microbiological procedures or restricted use of consensus clinical methods employed to classify infection. [ABSTRACT FROM AUTHOR]

It is suspected that childhood urinary tract infection (UTI) remains under-diagnosed in primary care, and is consequently the cause of subsequent morbidity from renal scarring, hypertension and eventual renal failure. Practice-based education and service developments were undertaken to try to improve the detection of childhood UTI.A controlled before-and-after intervention study was conducted. The educational and service developments promoted awareness of and greater testing for UTI among children less than two years of age presenting with febrile illness or other potentially relevant symptoms or signs. Appropriate diagnostic equipment was provided.More urine samples were sent by the intervention practices but without a concomitant increase in detection of UTIs. This may indicate that current practice is approaching near maximal detection of UTI in young children. [ABSTRACT FROM AUTHOR]