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Invasive aspergillosis (IA) is an acute infection affecting patients who are immunocompromised, as a result of receiving chemotherapy for malignancy, or immunosuppressant agents for transplantation or autoimmune disease. Whilst criteria exist to define the probability of infection for clinical trials, there is little evidence in the literature or clinical guidelines on when to change antifungal treatment in patients who are receiving prophylaxis or treatment for IA. To try and address this significant gap, an advisory board of experts was convened to develop criteria for the management of IA for use in designing clinical trials, which could also be used in clinical practice. For primary treatment failure, a change in antifungal therapy should be made: (i) when mycological susceptibility testing identifies an organism from a confirmed site of infection, which is resistant to the antifungal given for primary therapy, or a resistance mutation is identified by molecular testing; (ii) at, or after, 8 days of primary antifungal treatment if there is increasing serum galactomannan, or galactomannan positivity in serum, or bronchoalveolar lavage fluid when the antigen was previously undetectable, or there is sudden clinical deterioration, or a new clearly distinct site of infection is detected; and (iii) at, or after, 15 days of primary antifungal treatment if the patient is clinically stable but with ≥2 serum galactomannan measurements persistently elevated compared with baseline or increasing, or if the original lesions on CT or other imaging, show progression by >25% in size in the context of no apparent change in immune status. [ABSTRACT FROM AUTHOR]

Objectives: To prevent invasive fungal disease (IFD) in adult patients undergoing remission-induction chemotherapy for newly diagnosed acute lymphoblastic leukaemia (ALL).Patients and methods: In a double-blind multicentre Phase 3 study, patients received prophylactic liposomal amphotericin B (L-AMB) at 5 mg/kg intravenously or placebo twice weekly in a 2:1 random allocation during remission-induction treatment. The primary endpoint was the development of proven or probable IFD. Secondary endpoints included those focused on the safety and tolerability of prophylactic L-AMB.Results: Three hundred and fifty-five patients from 86 centres in Europe and South America received at least one dose of L-AMB ( n =  237) or placebo ( n =  118). Rates of proven and probable IFD assessed independently were 7.9% (18/228) in the L-AMB group and 11.7% (13/111) in the placebo group ( P  =   0.24). Rates of possible IFD were 4.8% (11/228) in the L-AMB and 5.4% (6/111) in the placebo group ( P  =   0.82). The remission-induction phase was a median of 22 days for both groups. Overall mortality was similar between the groups: 7.2% (17/237) for L-AMB and 6.8% (8/118) for placebo ( P  =   1.00). Hypokalaemia and creatinine increase were significantly more frequent with L-AMB.Conclusions: The IFD rate among adult patients undergoing remission-induction chemotherapy for newly diagnosed ALL was 11.7% in the placebo group, and was not significantly different in patients receiving L-AMB, suggesting that the L-AMB regimen studied is not effective as prophylaxis against IFD. The IFD rate appears higher than previously reported, warranting further investigation. Tolerability of L-AMB was what might be expected. Further studies are needed to determine the optimal antifungal strategy during remission-induction chemotherapy of ALL. [ABSTRACT FROM AUTHOR]

Many countries have observed an increase in the incidence of invasive fungal infections (IFIs) over the past two decades with emergence of new risk factors and isolation of new fungal pathogens. Early diagnosis and appropriate antifungal treatment remain the cornerstones of successful outcomes. However, due to non-specific clinical presentations and limited availability of rapid diagnostic tests, in more than half of cases antifungal treatment is inappropriate. As a result, the emergence of antifungal resistance both in yeasts and mycelial fungi is becoming increasingly common. The Delhi Chapter of the Indian Association of Medical Microbiologists (IAMM-DC) organized a 1 day workshop in collaboration with BSAC on 10 December 2015 in New Delhi to design a road map towards the development of a robust antifungal stewardship programme in the context of conditions in India. The workshop aimed at developing a road map for optimizing better outcomes in patients with IFIs while minimizing unintended consequences of antifungal use, ultimately leading to reduced healthcare costs and prevention development of resistance to antifungals. The workshop was a conclave of all stakeholders, eminent experts from India and the UK, including clinical microbiologists, critical care specialists and infectious disease physicians. Various issues in managing IFIs were discussed, including epidemiology, diagnostic and therapeutic algorithms in different healthcare settings. At the end of the deliberations, a consensus opinion and key messages were formulated, outlining a step-by-step approach to tackling the growing incidence of IFIs and antifungal resistance, particularly in the Indian scenario. [ABSTRACT FROM AUTHOR]

Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%-60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors. [ABSTRACT FROM AUTHOR]

The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen. [ABSTRACT FROM AUTHOR]

The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II: ). Real-time PCR is recommended for the routine diagnosis of PCP ( A-II: ). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value ( A-II: ). Non-invasive specimens can be suitable alternatives ( B-II: ), acknowledging that PCP cannot be ruled out in case of a negative PCR result ( A-II: ). Detecting β-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP ( A-II: ). A negative serum β-d-glucan result can exclude PCP in a patient at risk ( A-II: ), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks ( A-II: ). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended ( B-II: ) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies. [ABSTRACT FROM AUTHOR]

The article offers the author's insight on his tasks as editor-in-chief of the journal, providing information on the developments and accomplishments of the "Journal of Antimicrobial Chemotherapy" (JAC) in 2015. Topics include the rate of article submissions, the rejection rate of submissions, and the changes in the editorial team and structure of the journal.

Background: Voriconazole is used to manage invasive fungal diseases in recipients of an allogeneic haematopoietic stem cell transplant (HSCT) after myeloablative treatment. Little is known about the pharmacokinetics (PK) of voriconazole in this population, who also receive cyclosporine A. [ABSTRACT FROM PUBLISHER]

Selective decontamination of the digestive tract (SDD) is an established form of infection prevention which relies upon local antibiotic action to afford suppression of potential pathogens while preserving ‘colonization resistance’ (CR). However, CR has never been shown conclusively to play a decisive role in either achieving or maintaining effective prophylaxis in patients and by employing absorbable antimicrobials or parenteral antibiotics, prophylaxis is actually achieved by both local and systemic action. The role of prophylaxis in neutropenic patients is also far from clear since morbidity and mortality remain the same whether or not prophylactic antibacterials are given and most patients still require empirical therapy for fever. In addition, the Gram-positive cocci, rather than Gram-negative bacilli presently predominate as pathogens. There is also an increasing trend towards including fungal and viral infection as targets for prophylaxis. Moreover, current anti-infective strategies are more akin to ‘pre-emptive therapy’ (PET) since the antimicrobials are available systemically and given at optimum therapeutic doses and there is little to distinguish treatment given to prevent colonization from progressing to infection from that used to arrest incipient infection or effect a cure of established infection. In contrast, SDD as originally conceived may well prove cost-effective for the prevention of infection in intensive care although neither the optimum regimen nor the patient group who would gain most benefit have been defined. None the less, by affording protection against Gram-negative sepsis, both SDD and PET would reduce the pressure on the clinicians to treat empirically and shift the emphasis once more on appropriate investigations which would involve the microbiologist more directly and immediately in patient care. Any savings from lowering the drug usage could then be diverted to improving diagnosis and providing the regular monitoring that is essential to the success of both PET and SDD. [ABSTRACT FROM PUBLISHER]

Teicoplanin at a dose of 400 mg per day was added to the initial empirical therapy of 65 of 202 febrile granulocytopenic episodes. Of 53 cases evaluable for outcome 23 (43%) responded. Responders and nonresponders were comparable in terms of time of starting teicoplanin treatment, duration of therapy and of granulocytopenia, number of granulocytopenic days after therapy was stopped and peak and trough concentrations of the drug. Teicoplanin was given most often because of persistent fever or initial Gram-positive bacteraemia and only one-third of these cases responded. However, when teicoplanin was given because of proven or presumed Gram-positive infection 67% of cases were treated successfully. Patients with skin and soft tissue infections achieved a 78% response rate. The development of a lung infiltrate was the most common reason for failure to respond, although in most instances the aetiology was not determined. Serum concentrations of teicoplanin were predictable; peak and trough concentrations on the fourth day were 30.4 ± 5.0 mg/l and 9.8 ± 1.7 mg/l, respectively. Concentrations achieved in individual patients did not correspond to outcome. Hearing loss of 20 dB at 800 Hz was noted in one of 15 cases and transient liver or kidney disturbances attributable to the drug were observed in 4% of cases. Teicoplanin therapy was safe but only effective when used to treat infective episodes with a high probability of being due to Gram-positive bacteria. [ABSTRACT FROM PUBLISHER]

The article discusses the 40th anniversary of the "Journal of Antimicrobial Chemotherapy," which will be celebrated with a series of articles, the Garrold Lecture and a special Supplement.

Mucormycosis can be devastating and, as yet, there are no ideal therapies available. Observations that iron chelation may be a useful adjunct to antifungal treatment encouraged Spellberg et al. (J Antimicrob Chemother 2012; 715–22) to undertake a trial of deferasirox combined with liposomal amphotericin B (AmBisome®) as short-term therapy for mucormycosis. The results were disappointing as patients treated with deferasirox had a higher mortality rate at 90 days, leading the authors to conclude that the data did not support a role for initial, adjunctive deferasirox therapy for mucormycosis. We review the issues arising from this study to help decide whether the evidence that now exists supports further studies or represents the end of this line of enquiry. [ABSTRACT FROM PUBLISHER]

An introduction is presented in which the editor discusses various reports within the issue on topics including the high prevalence of azole resistance, cases of invasive aspergillosis defined by the detection of galactomannan, aspect of antimicrobial chemotherapy.

The article focuses on invasive fungal disease (IFD). It relates the growing incidence of IFD in patients undergoing intensive chemotherapy for haematological malignancies. It outlines the various approaches to manage IFD in patients undergoing chemotherapy or conditioning therapy for haematological stem cell transplant (HSCT). An overview of a meeting that explored IFD diagnosis and treatment is presented.

Timing of treatment for invasive fungal disease (IFD) is critical for making appropriate clinical decisions. Historically, many centres have treated at-risk patients prior to disease detection to try to prevent fungal colonization or in response to antibiotic-resistant fever. Many studies have indicated that a diagnostic-driven approach, using radiological tests and biomarkers to guide treatment decisions, may be a more clinically relevant and cost-effective approach. The Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) defined host clinical and mycological criteria for proven, probable and possible classes of IFD, to aid diagnosis. However, some patients at risk of IFD do not meet EORTC/MSG criteria and have been termed Groups B (patients with persistent unexplained febrile neutropenia) and C (patients with non-definitive signs of IFD) in a study by Maertens et al. (Haematologica 2012; 97: 325–7). Consequently, we considered the most appropriate triggers (clinical or radiological signs or biomarkers) for treatment of all patient groups, especially the unclassified B and C groups, based on our clinical experience. For Group C patients, additional diagnostic testing is recommended before a decision to treat, including repeat galactomannan tests, radiological scans and analysis of bronchoalveolar lavage fluid. Triggers for stopping antifungal treatment were considered to include resolution of all clinical signs and symptoms. For Group B patients, it was concluded that better definition of risk factors predisposing patients to fungal infection and the use of more sensitive diagnostic tests are required to aid treatment decisions and improve clinical outcomes. [ABSTRACT FROM PUBLISHER]

A preface for the "Journal of Antimicrobial Chemotherapy" is presented.

An introduction to the journal is presented wherein the authors discuss the increasing number of patients undergoing treatment of haematological malignancies and haemotopoietic stem cell transplantation (HSCT), the development of an integrated care pathway in Cardiff, Wales, and a meeting of experts convened in Amsterdam, Netherlands on June 11-12, 2010.