Updates in hematopoietic cell transplant and cellular therapies that enhance the risk for opportunistic infections.

BACKGROUND: Infectious disease physicians may be asked to evaluate and manage a variety of infections in immunocompromised hosts undergoing hematopoietic cell transplant (HCT) and cellular therapies. Over the last decade, several advances in cellular therapy have occurred, with implications for the types of infectious complications that may be seen. AIMS: The purpose of this review is to update the infectious disease physician on newer advances in HCT and cellular therapy, including haploidentical transplant, expanding indications for transplant in older individuals and children, and chimeric antigen receptor T-cells. We will review how these advances might influence infectious disease complications following HCT. We will also provide a perspective that infectious disease physicians can use to evaluate the degree of immune suppression in an individual patient to help determine the type of infections that may be encountered.

Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

BACKGROUND: Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease. METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of -1·0% (95% CI -7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0·016), eye disorders (39 [15%] vs 69 [27%]; p=0·002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001). INTERPRETATION: Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.

Combination antifungal therapy for invasive aspergillosis: a randomized trial.

BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. OBJECTIVE: To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479). SETTING: 93 international sites. PATIENTS: 454 patients with HM or HCT and suspected or documented IA were randomly assigned to treatment with voriconazole and anidulafungin or placebo. Primary analysis was done in the modified intention-to-treat population of 277 patients in whom IA was confirmed. MEASUREMENTS: The primary outcome was 6-week mortality; secondary outcomes included 12-week mortality, mortality in major subgroups, and safety measures. RESULTS: Mortality rates at 6 weeks were 19.3% (26 of 135) for combination therapy and 27.5% (39 of 142) for monotherapy (difference, -8.2 percentage points [95% CI, -19.0 to 1.5]; P  = 0.087). Secondary mortality outcomes favored combination therapy. Multivariable regression analysis suggested that maximum galactomannan value, Karnofsky score, and baseline platelet count had prognostic significance. Most patients (218 of 277 [78.7%]) had IA diagnosis established by radiographic findings and maximum galactomannan positivity. In a post hoc analysis of this dominant subgroup, 6-week mortality was lower in combination therapy than monotherapy (15.7% [17 of 108] vs. 27.3% [30 of 110]; difference, -11.5 percentage points [CI, -22.7 to -0.4]; P = 0.037). Safety measures, including hepatotoxicity, were not different. LIMITATIONS: Mortality at 6 weeks was higher than expected, and the difference in mortality was lower than expected, which reduced power to detect a treatment effect. Enrollment was restricted to patients with HM or HCT, which limited generalizability. CONCLUSION: Compared with voriconazole monotherapy, combination therapy with anidulafungin led to higher survival in subgroups of patients with IA. Limitations in power preclude definitive conclusions about superiority. PRIMARY FUNDING SOURCE: Pfizer.

Systematic review and mixed treatment comparison meta-analysis of randomized clinical trials of primary oral antifungal prophylaxis in allogeneic hematopoietic cell transplant recipients.

BACKGROUND: Antifungal prophylaxis is a promising strategy for reducing invasive fungal infections (IFIs) in allogeneic hematopoietic cell transplant (alloHCT) recipients, but the optimum prophylactic agent is unknown. We used mixed treatment comparison (MTC) meta-analysis to compare clinical trials examining the use of oral antifungals for prophylaxis in alloHCT recipients, with the goal of informing medical decision-making. METHODS: Randomized controlled trials (RCTs) of fluconazole, itraconazole, posaconazole, and voriconazole for primary antifungal prophylaxis were identified through a systematic literature review. Outcomes of interest (incidence of IFI/invasive aspergillosis/invasive candidiasis, all-cause mortality, and use of other antifungals) were extracted from eligible RCTs and incorporated into a Bayesian hierarchical random-effects MTC. RESULTS: Five eligible RCTs, randomizing 2147 patients in total, were included. Relative to fluconazole, prophylaxis with itraconazole (odds ratio [OR]: 0.52; interquartile range [IQR]: 0.35-0.76), posaconazole (OR: 0.56; IQR: 0.32-0.99), and voriconazole (OR: 0.46; IQR: 0.28-0.73) reduced incidence of overall proven/probable IFI. Posaconazole (OR: 0.31; IQR: 0.17-0.58) and voriconazole (OR: 0.33; IQR: 0.17-0.58) prophylaxis reduced proven/probable invasive aspergillosis more than itraconazole (OR: 0.68; IQR: 0.42-1.12). All-cause mortality was similar across all mould-active agents. CONCLUSION: As expected, mould-active azoles prevented IFIs, particularly invasive aspergillosis, more effectively than fluconazole in alloHCT recipients. The paucity of comparative efficacy data suggests that other factors such as long-term tolerability, availability of intravenous formulations, local IFI epidemiology, and drug costs may need to form the basis for selection among the mould-active azoles.

Therapeutic drug monitoring for triazoles: A needs assessment review and recommendations from a Canadian perspective.

Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document.

Les infections fongiques invasives sont responsables d'une morbidité et d'une mortalité importantes chez les patients atteints d'une maladie immunodépressive. L'ajout des nouveaux triazoles aux traitements antifongiques a élargi le spectre d'activité et la flexibilité d'administration. Au fil des ans, leur utilisation clinique a suscité des inquiétudes quant au degré d'exposition au médicament selon une posologie approuvée standard, ce qui soulève la nécessité de la pharmacovigilance thérapeutique (PVT). Les présentes lignes directrices portent donc sur la PVT des antifongiques triazolés. Dans le présent document sont exposées une analyse de la raison d'être de la PVT des triazoles, les populations de patients ciblées et les méthodes de laboratoire offertes, de même que des recommandations pratiques fondées sur des données probantes à jour tirées d'une analyse bibliographique approfondie.

Modeling Invasive Aspergillosis Risk for the Application of Prophylaxis Strategies.

The epidemiology of invasive aspergillosis (IA) is evolving. To define the patient groups who will most likely benefit from primary or secondary Aspergillus prophylaxis, particularly those whose medical conditions and IA risk change over time, it is helpful to depict patient populations and their risk periods in a temporal visual model. The Sankey approach provides a dynamic figure to understand the risk of IA for various patient populations. While the figure depicted within this article is static, an internet-based version could provide pop-up highlights of any given flow's origin and destination nodes. A future version could highlight links to publications that support the color-coded incidence rates or other actionable items, such as bundles of applicable pharmacologic or non-pharmacologic interventions. The figure, as part of the upcoming Infectious Diseases Society of America's aspergillosis clinical practice guidelines, can guide decision-making in clinical settings.

Potential consequences of essential drug shortages in Canada: Brain abscess due to Nocardia farcinica associated with dapsone prophylaxis for Pneumocystis jirovecii pneumonia.

In 2012, Canadian pharmacies experienced a shortage of trimethoprim-sulfamethoxazole tablets. Drug shortages may result in unintended clinical consequences such as infection with pathogens against which the alternative medication is ineffective. This is highlighted in the present article, which describes a case of brain abscess due to Nocardia species that developed while receiving dapsone as an alternative for prophylaxis against Pneumocystis jirovecii pneumonia in a highly immune-suppressed patient. Clinicians should be cognizant of these issues when prescribing alternative agents.

En 2012, les pharmacies canadiennes ont subi une pénurie de comprimés de triméthoprim-sulfaméthoxazole. Les pénuries de médicaments peuvent avoir des conséquences non intentionnelles, telles qu'une infection par des pathogènes contre lesquels le médicament de remplacement n'a pas d'effets. C'est ce qu'on souligne dans le présent article, qui décrit un cas d'abcès cérébral attribuable à une espèce de Nocardia qui s'est manifesté pendant l'administration de dapsone en prophylaxie de remplacement contre une pneumonie à Pneumocystis jirovecii chez un patient très immunodéprimé. Les cliniciens devraient connaître ces enjeux lorsqu'ils prescrivent des médicaments de remplacement.

Evaluation of the Impact of the Urgent Cancer Care Clinic on Emergency Department Visits, Primary Care Clinician Visits, and Hospitalizations in Winnipeg, Manitoba.

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015. Rates of ED visits were also stratified by ED location, severity, and cancer type. We found a 6% (95% CI 1.00-1.13, p-value = 0.0389) increase in PCC visits, a 7% (95% CI 0.99-1.15, p-value = 0.0737) increase in hospitalizations, a 4% (95% CI 0.86-1.08, p-value = 0.5053) decrease in the rate of ED visits, and a 3% (95% CI 0.92-1.17, p-value = 0.5778) increase in the rate of ED visits during the UCC clinic hours after the UCC clinic opened. The implementation of the UCC clinic had minimal impact on health care utilization. Future work should examine the impact of the UCC clinic on other aspects of healthcare utilization (e.g., number of tests ordered and time spent waiting in CCMB's main clinics) and patient quality of life and patient and health care provider experience.

Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 Update by the Infectious Diseases Society of America.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia. Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving. What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens. Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

Early treatment of candidemia in adults: a review.

Invasive candidiasis is associated with high mortality, particularly in adults. Retrospective studies show that shorter times to treatment are correlated with a lower risk of death. A number of factors can be used to predict which patients would benefit from antifungal prophylaxis or early (pre-emptive or empirical) therapy. Detection of the fungal cell wall component (1→3)-ß-D-glucan (BDG) shows promise as an early biomarker of invasive fungal infection and may be useful in identifying patients who would benefit from early antifungal treatment. To date, no consistent early treatment strategy has evolved. Proof-of-concept studies are needed to assess the role of pre-emptive and empirical therapy in ICU patients and the relevance of BDG as an early marker of infection.

Hand Hygiene Compliance at a Canadian provincial cancer centre - the complementary roles of nurse auditor-driven and patient auditor-driven audit processes and impact upon practice in ambulatory cancer care.

BACKGROUND: We examined the patterns of hand hygiene compliance (HHC) among health care providers (HCP) as observed by trained nurse and patient auditors over time in an ambulatory care Canadian provincial cancer agency. METHODS: Nurse and volunteer patient auditors completed separate standardized forms documenting hand-cleansing opportunities during clinic visits. HHC rates were compared over time by HCP group and by specialty teams. Observations from 10 calendar quarters were analyzed from April 2015 to September 2019. RESULTS: Nurse audit HHC rates ranged from 84% to 96%, encompassing 7,213 opportunities with no significant time-dependent trends by linear regression (R2 = 2.3E-005, P = .9895). The patient audit HHC rates ranged from 57% to 82%, encompassing 23,402 opportunities, were lower overall compared to the nurse audit (73.6% vs 89.2%, respectively, P < .0001), but displayed an increasing trend (R2 = 0.5374, P = .0159) over the same 10 time periods. The relative risk ratio for the differences decreased over time (R2 = .5101, P = .0203). Patients acknowledged the importance of HHC and the audit process, but were reticent to remind HCP to comply. CONCLUSIONS: The nurse audit measuring HCP HHC before entering and after exiting patient examination rooms showed persistently high compliance over time whereas the patient-driven audit measuring HHC within the examination room increased over time suggesting a training effect upon practice. These measures appeared complementary.

Predictors of Urgent Cancer Care Clinic and Emergency Department Visits for Individuals Diagnosed with Cancer.

In 2013, CancerCare Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs of individuals diagnosed with cancer experiencing acute complications of cancer or its treatment. This retrospective cohort study compared the characteristics of individuals diagnosed with cancer that visited the UCC to those who visited an emergency department (ED) and determined predictors of use. Multivariable logistic mixed models were run to predict an individual's likelihood of visiting the UCC or an ED. Scaled Brier scores were calculated to determine how greatly each predictor impacted UCC or ED use. We found that UCC visits increased up to 4 months after eligibility to visit and then decreased. ED visits were highest immediately after eligibility and then decreased. The median number of hours between triage and discharge was 2 h for UCC visits and 9 h for ED visits. Chemotherapy had the strongest association with UCC visits, whereas ED visits prior to diagnosis had the strongest association with ED visits. Variables related to socioeconomic status were less strongly associated with UCC or ED visits. Future studies would be beneficial to planning service delivery and improving clinical outcomes and patient satisfaction.

Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

Considerations in the approach to invasive fungal infection in patients with haematological malignancies.

Invasive infections because of opportunistic yeasts and moulds have contributed significantly to the morbidity and mortality associated with potentially curative treatment for haematological malignancies. Many risk factors have been identified that permit the clinician to predict the likelihood of these infections. The diagnostic process involves maintaining a high index of suspicion based upon an understanding of the clinical circumstances under which invasive fungal infections occur, of the spectrum of fungal syndromes, and of the advantages and limitations of diagnostic testing strategies now available. Treatment strategies may be categorized as prophylactic, pre-emptive, empiric, or directed based upon the circumstances. The therapeutic options have increased in recent years but are not applicable to all clinical circumstances. These considerations are discussed.

Economic evaluation of voriconazole for the treatment of candidemia in Canadian adults.

BACKGROUND: Candidemia is a common cause of nosocomial bloodstream infection. When selecting therapeutic treatments for candidemia, cost-effectiveness is an important consideration. The present study assessed the cost-effectiveness of voriconazole for the treatment of candidemia. METHODS: A decision-analytical model was used for evaluating the cost-effectiveness of voriconazole compared with a regimen of conventional amphotericin B (CAB) followed by fluconazole (FLU) in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting, based on the Global Candidemia Study. The time frame of the model was 98 days (14 weeks). Model parameters were based primarily on clinical outcome, and resource use data collected from the clinical trial were used. Supplemental data were obtained from an independent panel of 12 Canadian experts for parameters not available from the clinical trial. Unit costs were collected from Canadian sources. The outcome variables selected in the study were the number of patients cured within 98 days, the number of patients surviving at 98 days and the number of patients avoiding toxicity. Incremental costs per outcome were calculated to compare the cost-effectiveness analyses (both probabilistic and one-way sensitivity analyses were performed). RESULTS: The cost-effectiveness analysis demonstrated a difference of $1,121 in the total average cost of treatment with voriconazole ($70,489) versus CAB/FLU ($69,368). While the costs of voriconazole exceeded the costs of CAB/FLU, these costs were almost completely offset by lower hospitalization costs. While patients in both treatment arms experienced cure rates of 41%, both the percentage of patients surviving at day 98 (64.5% versus 58.2%) and the percentage of patients avoiding toxicity (64.5% versus 52.5%) were higher in the voriconazole arm. Accounting for differences in total costs and clinical outcomes, this analysis estimated an incremental cost per patient surviving at day 98 of $17,739, and an incremental cost per patient avoiding toxicity of $9,298. In the case of cost per patient cured, voriconazole had a higher cost ($1,121) than CAB/FLU. The results of the deterministic and probabilistic sensitivity analyses indicated that the model was robust. CONCLUSIONS: Results of the decision-analytical model provided evidence to support the cost-effectiveness of voriconazole relative to a regimen of CAB/FLU in the treatment of non-neutropenic patients diagnosed with candidemia in the Canadian setting.

Fungicidal versus fungistatic therapy of invasive Candida infection in non-neutropenic adults: a meta-analysis.

The purpose of this study was to determine whether fungicidal versus fungistatic pharmacotherapy of invasive candidiasis/candidemia yields superior outcomes. Data sources included MEDLINE (1966-June 2017), EMBASE (1980-June 2017), PubMed (1966-June 2017), Global Health-Ovid (inception to June 2017), LILACS Virtual Health Library (inception to June 2017) and the Cochrane Central Register of Controlled Trials (to 2nd quarter 2017). The ClinicalTrial.gov database, the SCOPUS database, SIGLE (System for Information on Grey Literature) and Google Scholar were also utilised to search for relevant studies. Randomised studies of any pharmacotherapy of invasive candidiasis including candidemia using a fungicidal (amphotericin B or echinocandin compound) versus a fungistatic (triazole) compound in adolescent or adult non-neutropenic patients. Eight studies met the inclusion criteria. Pooled odds ratios demonstrated an advantage of fungicidal therapy with respect to early therapeutic success (OR 1.61, 95% CI 1.27-2.03, p < 0.0001, I2 = 0%) and persistence or recurrence of infection (OR 0.51, 95% CI 0.35-0.74, p = 0.0005, I2 = 0%) but no advantage for late survival (OR 0.97, 95% CI 0.77-1.21, p = 0.77, I2 = 0%). Fungicidal therapy of invasive candidiasis and candidemia is associated with a higher probability of early therapeutic success and decreased probability of persistent or recurrent infection. However, there is no improvement in survival.

Antimicrobial Prophylaxis for Adult Patients With Cancer-Related Immunosuppression: ASCO and IDSA Clinical Practice Guideline Update.

PURPOSE: To provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment. METHODS: ASCO and IDSA convened an update Expert Panel and conducted a systematic review of relevant studies from May 2011 to November 2016. The guideline recommendations were based on the review of evidence by the Expert Panel. RESULTS: Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. RECOMMENDATIONS: Antibacterial and antifungal prophylaxis is recommended for patients who are at high risk of infection, including patients who are expected to have profound, protracted neutropenia, which is defined as < 100 neutrophils/µL for > 7 days or other risk factors. Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir. Pneumocystis jirovecii prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage). Treatment with a nucleoside reverse transcription inhibitor (eg, entecavir or tenofovir) is recommended for patients at high risk of hepatitis B virus reactivation. Recommendations for vaccination and avoidance of prolonged contact with environments that have high concentrations of airborne fungal spores are also provided within the updated guideline. Additional information is available at www.asco.org/supportive-care-guidelines .