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Amphotericin B (AmB) has broad fungicidal activity against many fungi, but the high incidence of adverse events, particularly nephrotoxicity, and the need for intravenous administration restrict its use for many patients. MAT2203, an investigational oral AmB formulation available under a compassionate use program, uses a lipid nanocrystal bilayer structure to deliver AmB with lower toxicity. We present a synopsis of clinical characteristics, treatment course, and outcomes for 5 patients who were treated with MAT2203. Outcomes were positive, with cure of infection noted in 4 patients and improvement in 1 patient who remains on therapy. MAT2203 was well tolerated with only modest gastrointestinal adverse effects. This new oral formulation might provide a safer treatment option for patients requiring extended courses of AmB. [ABSTRACT FROM AUTHOR]

Invasive fungal infections continue to increase as at-risk populations expand. The high associated morbidity and mortality with fungal diseases mandate the continued investigation of novel antifungal agents and diagnostic strategies that include surrogate biomarkers. Biologic markers of disease are useful prognostic indicators during clinical care, and their use in place of traditional survival end points may allow for more rapid conduct of clinical trials requiring fewer participants, decreased trial expense, and limited need for long-term follow-up. A number of fungal biomarkers have been developed and extensively evaluated in prospective clinical trials and small series. We examine the evidence for these surrogate biomarkers in this review and provide recommendations for clinicians and regulatory authorities. [ABSTRACT FROM AUTHOR]

Background Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. Methods To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. Results There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. Conclusions These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk. [ABSTRACT FROM AUTHOR]

Background The largest health care–associated infection outbreak in the United States occurred during 2012–2013. Following injection of contaminated methylprednisolone, 753 patients developed infection with a dematiaceous mold, Exserohilum rostratum. The long-term outcomes of these infections have not been described. Methods This retrospective cohort study of 440 of a total of 753 patients with proven or probable Exserohilum infection evaluated clinical and radiographic findings, antifungal therapy and associated adverse effects, and outcomes at 6 weeks, 3, 6, 9, and 12 months after diagnosis. Patients were grouped into 4 disease categories: meningitis with/without stroke, spinal or paraspinal infections, meningitis/stroke plus spinal/paraspinal infections, and osteoarticular infections. Results Among the 440 patients, 223 (51%) had spinal/paraspinal infection, 82 (19%) meningitis/stroke, 123 (28%) both, and 12 (3%) osteoarticular infection. Of 82 patients with meningitis/stroke, 18 (22%) died; among those surviving, 87% were cured at 12 months. Only 7 (3%) of 223 patients with spinal/paraspinal infection died, but at 12 months, 68% had persistent or worsening pain and only 47% were cured. For the 123 patients with both meningitis/stroke and spinal/paraspinal infection, 10 (8%) died, pain persisted in 72%, and 52% were cured at 12 months. Only 37% of those with osteoarticular infection were cured at 12 months. Adverse events from antifungal therapy were noted at 6 weeks in 71% of patients on voriconazole and 81% on amphotericin B. Conclusions Fungal infections related to contaminated methylprednisolone injections culminated in death in 8% of patients. Persistent pain and disability were seen at 12 months in most patients with spinal/paraspinal infections. [ABSTRACT FROM AUTHOR]

Objectives: A high-dose 12 mg/kg/day (6 mg/kg twice daily) voriconazole regimen was recommended by the CDC to treat patients injected with contaminated methylprednisolone acetate that caused a multi-state fungal outbreak in 2012-13. Therapeutic drug monitoring results of this unique regimen are unknown, as is the most appropriate dosing weight for obese patients. We evaluated voriconazole trough measurements for this dosing scheme, as well as the use of adjusted body weight dosing for obese patients.Methods: Voriconazole trough levels were analysed in obese (BMI ≥35 kg/m 2 ) and non-obese (BMI <35 kg/m 2 ) patients who were given initial therapy with 12 mg/kg/day.Results: Of 138 patients, the first steady-state voriconazole troughs were supratherapeutic (>5 mg/L) in 65 (47%) patients, therapeutic (2-5 mg/L) in 57 (41%) patients and subtherapeutic (<2 mg/L) in 16 (12%) patients. Twenty-three patients had pre-steady-state dose decreases due to supratherapeutic levels, with subsequent first steady-state troughs in the therapeutic ( n  =   17) and subtherapeutic ( n  =   6) categories. Voriconazole doses >11 and >8 mg/kg/day produced mainly first steady-state supratherapeutic troughs in 44 obese and 94 non-obese patients, respectively. An initial 12 mg/kg/day was progressively lowered to a median maintenance dose of 8.5 mg/kg/day in the obese and 8.6 mg/kg/day in the non-obese.Conclusions: A high-dose voriconazole regimen produced initial supratherapeutic troughs that required dose adjustment downward by nearly 30%. Adjusted body weight dosing in obese patients resulted in a similar maintenance dose to total body weight dosing in the non-obese, and appears to be a sensible dosing strategy for these patients. [ABSTRACT FROM AUTHOR]

Background. Infection is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Our object was to better define the epidemiology and outcomes of infections after HCT. Methods. This was a prospective, multicenter cohort study of HCT recipients and conducted from 2006 to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data were prospectively collected for up to 30 months after HCT using a standardized data collection tool. Results. The median age was 53 years, and median follow up was 413 (range, 5-980) days. The most common reason for HCT was hematologic malignancy (87%). The overall crude mortality was 52%. Death was due to underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231 (52%) cases and occurred early posttransplant (median day 48). Gram-negative bloodstream infections were less frequent than Gram-positive, but it was associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile infection developed in 148 patients (33%) at a median of 27 days post-HCT. There were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection, 4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13 (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial infection. This study lacked standardized antifungal and antiviral prophylactic strategies. Conclusions. Infection remains a significant cause of morbidity and mortality after HCT. Bacteremias and C difficile infection are frequent, particularly in the early posttransplant period. The rate of IFI is approximately 10%. Organ involvement with CMV is infrequent, as are serious infections with VZV and herpes simplex virus, likely reflecting improved prevention strategies. [ABSTRACT FROM AUTHOR]

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances. [ABSTRACT FROM AUTHOR]

Isavuconazole is a new extended-spectrum triazole with activity against yeasts, molds, and dimorphic fungi. It is approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. A randomized, double-blind comparison clinical trial for treatment of invasive aspergillosis found that the efficacy of isavuconazole was noninferior to that of voriconazole. An open-label trial that studied primary as well as salvage therapy of invasive mucormycosis showed efficacy with isavuconazole that was similar to that reported for amphotericin B and posaconazole. In patients in these studies, as well as in normal volunteers, isavuconazole was well tolerated, appeared to have few serious adverse effects, and had fewer drug-drug interactions than those noted with voriconazole. As clinical experience increases, the role of this new triazole in the treatment of invasive fungal infections will be better defined. [ABSTRACT FROM AUTHOR]

The Long-Term Persistence Substudy of the Shingles Prevention Study (SPS) assessed zoster vaccine efficacy in a subset of the SPS vaccine recipients followed for up to 11 years postvaccination. Vaccine efficacy was no longer statistically significant beyond 8 years postvaccination.Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination.Methods. Surveillance, case determination, and follow-up were comparable to those in SPS and STPS. Because SPS placebo recipients were offered zoster vaccine before the LTPS began, there were no unvaccinated controls. Instead, SPS and STPS placebo results were used to model reference placebo groups.Results. The LTPS enrolled 6867 SPS vaccine recipients. Compared to SPS, estimated vaccine efficacy in LTPS decreased from 61.1% to 37.3% for the herpes zoster (HZ) burden of illness (BOI), from 66.5% to 35.4% for incidence of postherpetic neuralgia, and from 51.3% to 21.1% for incidence of HZ, and declined for all 3 outcome measures from 7 through 11 years postvaccination. Vaccine efficacy for the HZ BOI was significantly greater than zero through year 10 postvaccination, whereas vaccine efficacy for incidence of HZ was significantly greater than zero only through year 8.Conclusions. Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8. [ABSTRACT FROM PUBLISHER]

Invasive candidiasis is a common infection in the intensive care unit associated with morbidity and mortality. In this multicenter clinical trial, caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis or preemptive therapy.Background. Invasive candidiasis is the third most common bloodstream infection in the intensive care unit (ICU) and is associated with morbidity and mortality. Prophylaxis and preemptive therapy are attractive strategies for this setting.Methods. We conducted a multicenter, randomized, double-blind, placebo-controlled trial of caspofungin as antifungal prophylaxis in 222 adults who were in the ICU for at least 3 days, were ventilated, received antibiotics, had a central line, and had 1 additional risk factor (parenteral nutrition, dialysis, surgery, pancreatitis, systemic steroids, or other immunosuppressants). Subjects’ (1,3)-β-d-glucan levels were monitored twice weekly. The primary endpoint was the incidence of proven or probable invasive candidiasis by EORTC/MSG criteria in patients who did not have disease at baseline. Patients who had invasive candidiasis were allowed to break the blind and receive preemptive therapy with caspofungin. The preemptive approach analysis included patients all patients who received study drug, including those positive at baseline.Results. The incidence of proven/probable invasive candidiasis in the placebo and caspofungin arms was 16.7% (14/84) and 9.8% (10/102), respectively, for prophylaxis (P = .14), and 30.4% (31/102) and 18.8% (22/117), respectively, for the preemptive approach (P = .04); however, this analysis included patients with baseline disease. There were no significant differences in the secondary endpoints of mortality, antifungal use, or length of stay. There were no safety differences.Conclusions. Caspofungin was safe and tended to reduce the incidence of invasive candidiasis when used for prophylaxis, but the difference was not statistically significant. A preemptive therapy approach deserves further study.Clinical Trials Registration. NCT00520234. [ABSTRACT FROM PUBLISHER]

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ).Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS.Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable.Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ. [ABSTRACT FROM AUTHOR]

The article focuses on several updates related to the fungal research from the IDWeek meeting which was held in San Diego, California by the Centers for Disease Control and Prevention (CDC) of the U.S. and the U.S. Food and Drug Administration (FDA). It mentions that the update highlights several issues including the clinical manifestation, treatment and management of asymptomatic patients. It further mentions that interim guidance for treatment of joint infections recommends voriconazole.

The impact of antifungal therapy on economic outcomes in patients with invasive aspergillosis (IA) needs further exploration. The purpose of this study was to describe antifungal therapy and factors associated with hospital length of stay (LOS) in transplant patients with IA. Patients were enrolled from March 2001 to October 2005 and IA cases identified through March 2006 from a sub-group of patients in the Transplant Associated Infection Surveillance Network (TRANSNET). Factors associated with hospital LOS were determined by logistic regression analysis. Of 361 patients, the mean age was 49 years, 60.7% were male, and 63% were hematopoietic stem cell transplantation (HSCT) recipients. Primary monotherapy was used in 233 (64.5%) patients, of which voriconazole (93/233, 39.9%) was most commonly used antifungal. Primary combination therapy was used in 128 (35.4%) of 361 patients, with voriconazole plus caspofungin (81/361, 22.4%) the most frequently employed. Mean duration of therapy was 115 days (HSCT 109.7; solid organ transplant [SOT] 125.3). Mean hospital LOS was 35.3 days (HSCT 38.7; SOT 29.7). Regression analysis identified disseminated IA, neutropenia, malnutrition and length of ICU stay as factors associated with increased hospital LOS. Initial voriconazole use was associated with decreased LOS. Further investigation on impact of antifungal therapy on economic outcomes is needed. [ABSTRACT FROM AUTHOR]

Infections in skilled nursing facilities (SNFs) are common and result in frequent hospital transfers, functional decline, and death. Colonization with multidrug-resistant organisms (MDROs) - including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacilli (R-GNB) - is also increasingly prevalent in SNFs. Antimicrobial resistance among common bacteria can adversely affect clinical outcomes and increase health care costs. Recognizing a need for action, legislators, policy-makers, and consumer groups are advocating for surveillance cultures to identify asymptomatic patients with MDROs, particularly MRSA in hospitals and SNFs. Implementing this policy for all SNF residents may be costly, impractical, and ineffective. Such a policy may result in a large increase in the number of SNF residents placed in isolation precautions with the potential for reduced attention by health care workers, isolation, and functional decline. Detection of colonization and subsequent attempts to eradicate selected MDROs can also lead to more strains with drug resistance. We propose an alternative strategy that uses a focused multicomponent bundle approach that targets residents at a higher risk of colonization and infection with MDROs, specifically those who have an indwelling device. If this strategy is effective, similar strategies can be studied and implemented for other high-risk groups. [ABSTRACT FROM AUTHOR]

Endogenous fungal endophthalmitis, involving only the chorioretinal structures or extending to involve the vitreous (vitritis), is a sight-threatening infection requiring early appropriate therapy. Endophthalmitis is a relatively frequent complication of candidemia and less commonly occurs in patients who have invasive aspergillosis. Because the eye is a protected compartment, penetration of systemically administered antifungal agents is highly variable. In the posterior segment of the eye, amphotericin B (AmB) achieves very poor concentrations, but fluconazole concentrations are high. Among newer antifungal agents, voriconazole shows the most promise, because therapeutic concentrations for most Candida and Aspergillus species are achieved in the vitreous, and its antifungal activity is broad. In contrast, neither posaconazole nor the 3 echinocandins achieve adequate therapeutic concentrations in the vitreous. For sight-threatening macular involvement and vitritis, intravitreal injection of either AmB or voriconazole is helpful to achieve high local antifungal activity as quickly as possible. We review the available evidence regarding the most appropriate use of antifungal agents for endogenous fungal endophthalmitis, with the emphasis on treatment of infections due to Candida species. [ABSTRACT FROM AUTHOR]

Background. Invasive aspergillosis (IA) is an important cause of morbidity and mortality in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The purpose of this study was to evaluate factors associated with mortality in transplant patients with IA. Methods. Transplant patients from 23 US centers were enrolled from March 2001 to October 2005 as part of the Transplant Associated Infection Surveillance Network. IA cases were identified prospectively in this cohort through March 2006, and data were collected. Factors associated with 12-week all-cause mortality were determined by logistic regression analysis and Cox proportional hazards regression. Results. Six-hundred forty-two cases of proven or probable IA were evaluated, of which 317 (49.4%) died by the study endpoint. All-cause mortality was greater in HSCT patients (239 [57.5%] of 415) than in SOT patients (78 [34.4%] of 227; ). Independent poor prognostic factors P< .001 in HSCT patients were neutropenia, renal insufficiency, hepatic insufficiency, early-onset IA, proven IA, and methylprednisolone use. In contrast, white race was associated with decreased risk of death. Among SOT patients, hepatic insufficiency, malnutrition, and central nervous system disease were poor prognostic indicators, whereas prednisone use was associated with decreased risk of death. Among HSCT or SOT patients who received antifungal therapy, use of an amphotericin B preparation as part of initial therapy was associated with increased risk of death. Conclusions. There are multiple variables associated with survival in transplant patients with IA. Understanding these prognostic factors may assist in the development of treatment algorithms and clinical trials. [ABSTRACT FROM AUTHOR]

Background. Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among organ transplant recipients. Multicenter prospective surveillance data to determine disease burden and secular trends are lacking. Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), non- Aspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies. [ABSTRACT FROM AUTHOR]

Background. The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods. The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results. We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versushost disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelvemonth cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matchedrelated allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions. In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design. [ABSTRACT FROM AUTHOR]

Background. The objectives of this study were to evaluate the association between varicella-zoster virus (VZV)— specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine. Methods. In 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-g enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA). Results. Robust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower. Conclusions. Higher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI. [ABSTRACT FROM AUTHOR]

Guidelines for the management of patients with invasive candidiasis and mucosal candidiasis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous guidelines published in the 15 January 2004 issue of Clinical Infectious Diseases and are intended for use by health care providers who care for patients who either have or are at risk of these infections. Since 2004, several new antifungal agents have become available, and several new studies have been published relating to the treatment of candidemia, other forms of invasive candidiasis, and mucosal disease, including oropharyngeal and esophageal candidiasis. There are also recent prospective data on the prevention of invasive candidiasis in high-risk neonates and adults and on the empiric treatment of suspected invasive candidiasis in adults. This new information is incorporated into this revised document. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Evidence-based guidelines for the management of patients with blastomycosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous management guidelines published in the April 2000 issue of Clinical Infectious Diseases. The guidelines are intended for use by health care providers who care for patients who have blastomycosis. Since 2000, several new antifungal agents have become available, and blastomycosis has been noted more frequently among immunosuppressed patients. New information, based on publications between 2000 and 2006, is incorporated in this guideline document, and recommendations for treating children with blastomycosis have been noted. [ABSTRACT FROM AUTHOR]

Background. Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. Methods. After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. Results. The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. Conclusions. These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients. [ABSTRACT FROM AUTHOR]

Background. We sought to characterize the clinical and molecular epidemiologic characteristics of Staphylococcus aureus colonization (especially extranasal colonization) and to determine the extent to which community-associated methicillin-resistant S. aureus (MRSA) has emerged in community nursing homes. Methods. The study enrolled a total of 213 residents, with or without an indwelling device, from 14 nursing homes in southeastern Michigan. Samples were obtained from the nares, oropharynx, groin, perianal area, wounds, and enteral feeding tube site. Standard microbiologic methods were used to identify methicillin-susceptible S. aureus and MRSA. Molecular epidemiologic methods included pulsed-field gel electrophoresis, PCR detection of Panton-Valentine leukocidin, and SCCmec and agr typing. Results. One hundred thirty-one residents (62%) were colonized with S. aureus (MRSA colonization in 86). S. aureus colonization occurred in 80 (76%) of 105 residents with indwelling devices and in 51 (47%) of 108 residents without indwelling devices (P < .001). Of the 86 residents who were colonized with MRSA, nares culture results were positive for only 56 (65%). Residents with devices in place were more likely to be colonized at multiple sites. Eleven different strains of MRSA were identified by pulsed-field gel electrophoresis. Seventy-three residents (85%) were colonized with hospital-associated SCCmec II strains, and 8 (9%) were colonized with community-associated SCCmec IV strains, 2 of which carried Panton-Valentine leukocidin. Conclusions. Extranasal colonization with MRSA is common among nursing home residents—particularly among residents with an indwelling device. We documented the emergence of community-associated SCCmec IV MRSA strains in the community nursing home setting in southeastern Michigan. [ABSTRACT FROM AUTHOR]

Background. Although urinary tract infection (UTI) is the most common hospital-acquired infection in the United States, to our knowledge, no national data exist describing what hospitals in the United States are doing to prevent this patient safety problem. We conducted a national study to examine the current practices used by hospitals to prevent hospital-acquired UTI. Methods. We mailed written surveys to infection control coordinators at a national random sample of non-federal US hospitals with an intensive care unit and ⩾50 hospital beds (n = 600) and to all Veterans Affairs (VA) hospitals (n = 119). The survey asked about practices to prevent hospital-acquired UTI and other device-associated infections. Results. The response rate was 72%. Overall, 56% of hospitals did not have a system for monitoring which patients had urinary catheters placed, and 74% did not monitor catheter duration. Thirty percent of hospitals reported regularly using antimicrobial urinary catheters and portable bladder scanners; 14% used condom catheters, and 9% used catheter reminders. VA hospitals were more likely than non-VA hospitals to use portable bladder scanners (49% vs. 29%; P<.001), condom catheters (46% vs. 12%; P<.001), and suprapubic catheters (22% vs. 9%; P<.001); non-VA hospitals were more likely to use antimicrobial urinary catheters (30% vs. 14%; P = .002). Conclusions. Despite the strong link between urinary catheters and subsequent UTI, we found no strategy that appeared to be widely used to prevent hospital-acquired UTI. The most commonly used practices-bladder ultrasound and antimicrobial catheters-were each used in fewer than one-third of hospitals, and urinary catheter reminders, which have proven benefits, were used in <10% of US hospitals. [ABSTRACT FROM AUTHOR]

Background Guidelines for the management of patients with sporotrichosis were prepared by an Expert Panel of the Infectious Diseases Society of America and replace the guidelines published in 2000. Sporotrichosis is caused by the dimorphic fungus Sporothrix schenckii, which is found throughout the world in decaying vegetation, sphagnum moss, and soil. The usual mode of infection is by cutaneous inoculation of the organism. Pulmonary and disseminated forms of infection, although uncommon, can occur when S. schenckii conidia are inhaled. Infections are most often sporadic and are usually associated with trauma during the course of outdoor work. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos. Outbreaks have been well described and often are traced back to activities that involved contaminated sphagnum moss, hay, or wood. Most cases of sporotrichosis are localized to the skin and subcutaneous tissues. Dissemination to osteoarticular structures and viscera is uncommon and appears to occur more often among patients who have a history of alcohol abuse or immunosuppression, especially patients with AIDS. Spontaneous resolution of sporotrichosis is rare, and treatment is required for most patients. Although sporotrichosis localized to skin and subcutaneous tissues is readily treated, management of osteoarticular, other localized visceral, and disseminated forms of sporotrichosis is difficult. [ABSTRACT FROM AUTHOR]

Evidence-based guidelines for the management of patients with histoplasmosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (din Infect Dis 2000; 30:688-95). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflam- matory disorders have created new questions about the approach to prevention and treatment of histoplasmosis. New information, based on publications from the period 1999-2006, are incorporated into this guideline document. In addition, the panel added recommendations for management of histoplasmosis in children for those aspects that differ from aspects in adults. [ABSTRACT FROM AUTHOR]

Background. Vancomycin-resistant enterococcal (VRE) infections cause significant morbidity and mortality among patients undergoing liver transplantation. We performed a prospective study among patients awaiting transplantation to assess rates, risk factors, and outcomes associated with VRE colonization before and after transplantation. Methods. All adults on the transplantation waiting list from 2000-2003 were eligible. Demographic, historical, and laboratory data, as well as stool samples to be analyzed for VIRE, were collected at enrollment and every 4- 6 months thereafter until transplantation. After transplantation, samples were obtained every 3 days during hospitalization and were analyzed for VRE; outcomes were assessed at 90 days. Results. Overall, 375 patients were enrolled in our study, and 142 received transplants. VIRE colonization occurred in 50 (13%) of 375 patients before transplantation and was independently associated with treatment with antian aerobic antimicrobials, third-generation cephalosporins, proton pump inhibitors, or neomycin; having a recent endoscopic retrograde cholangiopancreatogram or paracentesis procedure; and admission to the liver unit. Of these 50 patients, 22 (44%) received a transplant, and 7 (32%) of 22 developed a VIRE infection after transplantation. An additional 22 patients (18%) who were not colonized before transplantation acquired VRE after transplantation; VIRE infection developed in 5 (23%) of these patients. Patients colonized with VIRE either before or after transplantation had longer stays in the intensive care unit and the hospital. Mortality at 90 days was significantly greater among those who acquired VRE after transplantation (5 [23%] of 22), compared with those who had V"RE colonization before transplantation (2 [9%] of 22). Conclusions. Liver transplantation candidates with VIRE colonization before transplantation experience greater morbidity but not greater mortality, compared with noncolonized candidates. Transplant recipients who acquire VIRE after transplantation have a higher mortality rate than noncolonized recipients. Strategies should be implemented to reduce nosocomial VRE acquisition after transplantation among this vulnerable group. [ABSTRACT FROM AUTHOR]

Background. During the past decade, Candida glabrata has emerged as an important cause of fungemia. We reviewed demographic data, risk factors, treatment, and outcomes associated with C. glabrata fungemia from 1995- 2002 and performed susceptibility testing of isolates. Methods. Data on all episodes of fungemia were prospectively recorded, and the associated isolates were saved. Medical records were reviewed retrospectively. Susceptibility testing was performed for fluconazole, itraconazole, and voriconazole. Results. C. glabrata caused 103 (17%) of 609 fungemic episodes during the 8-year period that we studied. Medical records and isolates were available for 94 episodes that occurred in 91 patients. The patients included 42 men and 49 women. The mean age was 51 years. Thirty-four episodes (36%) occurred in patients >60 years old; only 3 episodes occurred in patients <1 year old. The most common predisposing factors were use of broad-spectrum antibiotics (in 86% of episodes), use of central venous catheters (77%), stay in an intensive care unit (48%), renal failure (46%), and receipt of parenteral nutrition (45%). Of the 94 episodes, 83 were treated with antifungal agents. The overall mortality rate at day 30 was 29%. For the 11 episodes that were not treated, the mortality rate was 64% (7 of 11 episodes). Outcome appeared to be unrelated to whether fluconazole or amphotericin B was administered. In vitro, 60% of isolates were resistant to fluconazole, 83% to itraconazole, and 44% to voriconazole. Susceptibility to these azoles did not change over the 8 years of the study. Conclusion. C. glabrata fungemia was most often seen in older adults and was associated with a mortality rate of 29%. Outcomes appeared to be unrelated to in vitro susceptibility results and to the antifungal agent used. [ABSTRACT FROM AUTHOR]

Candiduria is a common finding. Yeasts can be detected in urine that is contaminated during collection, in patients who have bladder colonization, and in patients who have upper urinary tract infection that developed either from retrograde spread from the bladder or hematogenous spread from a distant source. Most patients with candiduria are asymptomatic. The rate of development of complications is not known but appears to be low; candidemia rarely results from asymptomatic candiduria unless obstruction is present or instrumentation of the urinary tract is done. Unfortunately, there are no established diagnostic tests that reliably distinguish infection from colonization. Guidelines for the treatment of candiduria, based almost entirely on anecdotal reports and expert opinions, rather than controlled clinical trials, have been suggested by the Infectious Diseases Society of America. Until reliable methods to distinguish infection from colonization are developed, further treatment trials are unlikely to provide information to guide the clinician in the treatment of candiduria. [ABSTRACT FROM AUTHOR]

Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P = .017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents who received placebo remained colonized (P < .001). At day 90 after study entry, 61% of the residents in the mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction in infections was seen with mupirocin treatment. [ABSTRACT FROM AUTHOR]

We conducted a prospective, multicenter observational study of adults (n=1447) and children (n=144) with candidemia at tertiary care centers in the United States in parallel with a candidemia treatment trial that included nonneutropenic adults. Candida albicans was the most common bloodstream isolate recovered from adults and children (45% vs. 49%) and was associated with high mortality (47% among adults vs. 29% among children). Three-month survival was better among children than among adults (76% vs. 54%; P<.001). Most children received amphotericin B as initial therapy, whereas most adults received fluconazole. In adults, Candida parapsilosis fungemia was associated with lower mortality than was non-parapsilosis candidemia (24% vs. 46%; P<.001). Mortality was similar among subjects with Candida glabrata or non-glabrata candidemia; mortality was also similar among subjects with C. glabrata candidemia who received fluconazole rather than other antifungal therapy. Subjects in the observational cohort had higher Acute Physiology and Chronic Health Evaluation II scores than did participants in the clinical trial (18.6 vs. 16.1), which suggests that the former subjects are more often excluded from therapeutic trials. [ABSTRACT FROM AUTHOR]

Enterococci are naturally resistant to a wide range of antimicrobial agents. In addition, some enterococci, known as vancomycin-resistant enterococci (VRE) have become resistant to glycopeptide antibiotics. The therapeutic options for VRE infections are therefore very limited. New antimicrobials have been developed that are active against VRE, such as linezolid and quinupristin/dalfopristin. Others, e.g. tigecycline, daptomycin and oritavancin, are in the later stages of development. However, resistance has already been detected to some of these agents. Some success has been enjoyed through the application of older antibiotics against VRE. The lack of therapeutic options has led to the consideration of measures to prevent infection with VRE. In addition to standard infection control procedures such as isolation and hand washing, decolonization of the gastrointestinal tract has been investigated as a method for the prevention of VRE infection in vulnerable patient groups. Several decolonization regimens have been investigated. These include the use of ramoplanin, a new glycolipodepsipeptide antibiotic that has features that particularly suit it for decolonization. Ramoplanin is not absorbed from the gastrointestinal tract, has potent bactericidal activity against Gram-positive organisms and limited side effects. These features and current clinical evidence suggest that ramoplanin may have a role in future gastrointestinal decolonization regimens. [ABSTRACT FROM AUTHOR]

This forum report contains conclusions about 3 different issues relevant to conducting clinical trials in deep mycoses. (1) Trials of diagnostic tests for deep mycoses must define the population appropriate for testing and the clinical question being asked. The unanswered question for the serum Aspergillus galactomannan assay is whether knowledge of results can change use of empirical therapy to treat febrile patients at high risk of invasive aspergillosis. (2) Use of historical controls is suboptimal but offers a pragmatic solution for studying rare mycoses; use of contemporaneous controls, matched for critical variables and evaluated by a blinded data review committee using detailed criteria, appears optimal. (3) Established groups of independent investigators, such as the European Organization for Research on Treatment of Cancer's Invasive Fungal Infections Group and National Institute of Allergy and Infectious Diseases's Bacteriology and Mycology Study Group, provide a pool of experienced investigators, defined operating rules, impartiality, and specialized expertise. Considering the enormous investment required for adequately powered efficacy trials of antifungal agents and the importance of these trials to guide clinical practice, use of collaborative groups outweighs the extra administrative time that is sometimes required. [ABSTRACT FROM AUTHOR]

There is inferential evidence that some patients with prolonged neutropenia and fever not responding to antibacterial agents are at sufficient risk of deep mycoses to warrant empirical therapy, although superiority of an antifungal agent over placebo has not been conclusively demonstrated. Amphotericin B deoxycholate, liposomal amphotericin B, and intravenous itraconazole followed by oral itraconazole solution are licensed in the United States for this indication. Fluconazole and voriconazole have given favorable results in clinical trials of patients with low and high risk of deep mold infections, respectively. Design features that can profoundly influence outcome of empirical trials are (1) inclusion of low-risk patients, (2) failure to blind the study, (3) obscuration of antifungal effects by changing antibacterial antibiotics, (4) failure to balance both arms of the study in terms of patients with prior antifungal prophylaxis or with severe comorbidities, (5) the merging of end points evaluating safety with those of efficacy, and (6) choice of different criteria for resolution of fever. [ABSTRACT FROM AUTHOR]

A recent trial of drugs for invasive aspergillosis was used as a background for discussing critical features in the design of antifungal trials. The study under discussion allowed stopping either drug without classifying the patient as having treatment failure, so the trial should be understood as a comparison of 2 treatment strategies, not just 2 drugs. Although the study was a noninferiority trial, the outcome permitted a claim of superiority. Use of the category of "probable" in addition to "proven" aspergillosis permitted inclusion of patients for whom the diagnosis was less certain but who were still early enough in the disease progression to respond to therapy. Different opinions still exist about some of the criteria for the diagnosis of "probable" aspergillosis. A blinded data review committee was helpful in evaluating efficacy in this unblinded trial but had limited value in assessing toxicity. An understanding of these features of design of antifungal drug trials is important in applying the results to clinical practice. [ABSTRACT FROM AUTHOR]

Eleven patients developed deep sternal wound infections due to Candida albicans after undergoing coronary artery bypass grafting (CABG) and were assessed. Six had sternal osteomyelitis, 1 had osteomyelitis and mediastinitis, and 4 had deep wound infections that probably involved bone. Seven patients experienced onset of infection within 28 days of CABG, but 4 experienced onset 48-150 days after CABG. Infections were characterized by a chronic, indolent course requiring prolonged treatment with an antifungal agent. Delay in initiating antifungal therapy was common. All patients were treated with fluconazole, and 1 also received amphotericin B. Six patients underwent incision and drainage, with or without wire removal, and 3 underwent sternectomy with placement of a muscle flap. Of 10 patients for whom follow-up data were available, 7 were cured after initial therapy (median duration of treatment, 6 months), and 3 experienced a relapse and required a second course of fluconazole. [ABSTRACT FROM AUTHOR]

Focuses on a study which evaluated the safety and efficacy of oral ramoplanin, a nonabsorbed glycolipodepsipeptide, for the suppression of gastrointestinal vancomycin-resistant enterococci (VRE) colonization. Demographic characteristics of patients; Information on antimicrobial susceptibility; Role of ramoplanin against VRE.

We conducted a case study of human immunodeficiency virus (HIV)--negative patients with cryptococcosis at 15 United States medical centers from 1990 through 1996 to understand the demographics, therapeutic approach, and factors associated with poor prognosis in this population. Of 306 patients with cryptococcosis, there were 109 with pulmonary involvement, 157 with central nervous system (CNS) involvement, and 40 with involvement at other sites. Seventy-nine percent had a significant underlying condition. Patients with pulmonary disease were usually treated initially with fluconazole (63%); patients with CNS disease generally received amphotericin B (92%). Fluconazole was administered to approximately two-thirds of patients with CNS disease for consolidation therapy. Therapy was successful for 74% of patients. Significant predictors of mortality in multivariate analysis included age 60 years, hematologic malignancy, and organ failure. Overall mortality was 30%, and mortality attributable to cryptococcosis was 12%. Cryptococcosis continues to be an important infection in HIV-negative patients and is associated with substantial overall and cause-specific mortality. [ABSTRACT FROM AUTHOR]

Invasive fungal infections have become an increasing problem in older adults. Infections with opportunistic fungi have increased because older patients are more likely to be considered for transplantation, receive aggressive regimens of chemotherapy for cancer, and take immunosuppressive drugs for nonmalignant diseases. In addition, healthy older adults are now more likely to travel extensively and to indulge in outdoor activities, which put them at risk for exposure to endemic mycoses. Although many of the clinical manifestations of fungal infections in older and younger adults are similar, there are aspects of histoplasmosis, aspergillosis, and cryptococcosis that are unique to older patients. Treatment of older adults with amphotericin B is difficult because of the intrinsic nephrotoxicity of the drug. Although they are less toxic, azoles must be used carefully for treatment of older adults, who are more likely to experience serious drug-drug interactions than are younger persons. [ABSTRACT FROM AUTHOR]

Presents a study which found that several patients who underwent median sternotomy developed infections with Pseudomonas aeruginosa. Methods; Results; Discussion.

Focuses on the randomized controlled trials of therapy for invasive mycoses. Reasons for the difficulties in implementing comparative trials of antifungal agents; Motivation for undertaking the task of implementing a comparative trial design in the field of infectious disease research; Alternatives to a randomized, controlled trial; Challenge for trials of antifungal agents; Future of trials of antifungal agents.

Executive Summary The recommendations for the treatment of sporotrichosis were derived primarily from multicenter, nonrandomized treatment trials, small retrospective series, and case reports; no randomized, comparative treatment trials have been reported. Most cases of sporotrichosis are non-life-threatening localized infections of the skin and subcutaneous tissues that can be treated with oral antifungal agents. The treatment of choice for fixed cutaneous or lymphocutaneous sporotrichosis is itraconazole for 3-6 months. The preferred treatment for osteoarticular sporotrichosis also is itraconazole, but therapy must be continued for at least 12 months. Pulmonary sporotrichosis responds poorly to treatment. Severe infection requires treatment with amphotericin B; mild to moderate infection can be treated with itraconazole. Meningeal and disseminated forms of sporotrichosis are rare and usually require treatment with amphotericin B. AIDS patients most often have disseminated infection and require life-long suppressive therapy with itraconazole after initial use of amphotericin B. Overview. Sporotrichosis is caused by the dimorphic fungus Sporothrix schenckii, which is found throughout the world in decaying vegetation, sphagnum moss, and soil [1]. The usual mode of infection is by cutaneous inoculation of the organism. Pulmonary and disseminated forms of infection, although uncommon, can occur when S. schenckii conidia are inhaled. Infections are most often sporadic and usually associated with trauma during the course of outdoor work. Infection can also be related to zoonotic spread from infected cats or scratches from digging animals, such as armadillos [2, 3]. Outbreaks have been well-described and often are traced back to activities that involved contaminated sphagnum moss, hay, or... [ABSTRACT FROM AUTHOR]

Executive Summary Objective. The objective of this guideline is to provide recommendations for treating patients with the more common forms of histoplasmosis. Participants and consensus process. A working group of 8 experts in this field was convened to develop this guideline. The working group developed and refined the guideline through a series of conference calls. Outcomes. The goal of treatment is to eradicate the infection when possible, although chronic suppression may be adequate for patients with AIDS and other serious immunosuppressive disorders. Other important outcomes are resolution of clinical abnormalities and prevention of relapse. Evidence. The published literature on the management of histoplasmosis was reviewed. Controlled trials have been conducted that address the treatment of chronic pulmonary and disseminated histoplasmosis, but clinical experience and descriptive studies provide the basis for recommendations for other forms of histoplasmosis. Value. Value was assigned on the basis of the strength of the evidence supporting treatment recommendations, with the highest value assigned to controlled trials, according to conventions established for developing practice guidelines. Benefits and costs. Certain forms of histoplasmosis cause life-threatening illnesses and result in considerable morbidity, whereas other manifestations cause no symptoms or minor self-limited illnesses. The nonprogressive forms of histoplasmosis, however, may reduce functional capacity, affecting work capacity and quality of life for several months. Treatment is clearly beneficial and cost-effective for patients with progressive forms of histoplasmosis, such as chronic pulmonary or disseminated infection. It remains unknown.... [ABSTRACT FROM AUTHOR]

Executive Summary Guidelines for the treatment of blastomycosis are presented; these guidelines are the consensus opinion of an expert panel representing the National Institute of Allergy and Infectious Diseases Mycoses Study Group and the Infectious Diseases Society of America. The clinical spectrum of blastomycosis is varied, including asymptomatic infection, acute or chronic pneumonia, and extrapulmonary disease. Most patients with blastomycosis will require therapy. Spontaneous cures may occur in some immunocompetent individuals with acute pulmonary blastomycosis. Thus, in a case of disease limited to the lungs, cure may have occurred before the diagnosis is made and without treatment; such a patient should be followed up closely for evidence of disease progression or dissemination. In contrast, all patients who are immunocompromised, have progressive pulmonary disease, or have extrapulmonary disease must be treated. Treatment options include amphotericin B, ketoconazole, itraconazole, and fluconazole. Amphotericin B is the treatment of choice for patients who are immunocompromised, have life-threatening or central nervous system (CNS) disease, or for whom azole treatment has failed. In addition, amphotericin B is the only drug approved for treating blastomycosis in pregnant women. The azoles are an equally effective and less toxic alternative to amphotericin B for treating immunocompetent patients with mild to moderate pulmonary or extrapulmonary disease, excluding CNS disease. Although there are no comparative trials, itraconazole appears more efficacious than either ketoconazole or fluconazole. Thus, itraconazole is the initial treatment of choice for non-life-threatening non-CNS blastomycosis. [ABSTRACT FROM AUTHOR]

Discusses the epidemiology, management and outcomes of funguria urinary tract infections through the analysis of a multicenter prospective surveillance study of a large sample of patients. Percentage of patients with underlying illnesses and concommitant nonfungal infections; Percentage who have received antimicrobial agents and who had urinary tract drainage devices; Percentage of those with candida infection.

Presents information on sporotrichosis. Substance present in Sporothrix schenckii that complexes with glycopeptides to form rhamnomannans; Activities associated with sporotrichosis; Modes of transmission of sporotrichosis; Clinical features; Treatment modalities for several forms of sporotrichosis.

Evaluates the effect of itraconazole prophylaxis for fungal infections in a randomized, placebo-controlled, double-blind study of HIV-positive persons. Efficacy of itraconazole antifungal drug in preventing histoplasmosis and cryptococcosis in patients; Factors associated with prophylaxis failure; Laboratory findings.

Distemper virus is very similar antigenically to measles virus, and the disease produced in ferrets by distemper is a systemic illness quite similar to measles infection in humans. Using an attenuated strain of distemper virus, we produced a mild systemic illness in ferrets and were able to study the effects of the viral infection on cell-mediated immunity (CMI), Beginning on day 5 after viral inoculation and continuing to day 30, infected ferrets showed a marked lymphopenia, with a reduction in total numbers of all lymphocyte subpopulations studied. Transformation of circulating lymphocytes to the mitogens phytohaemagglutinin, concanavalin A, and pokeweed mitogen was suppressed on day 5, reached a nadir by days 8 to 11, and returned toward normal by days 23 to 30 after viral inoculation. Production of macrophage migration inhibitory factor by splenic macrophages was diminished during distemper infection. In contrast to marked suppression of these in vitro assays for CMI, delayed hypersensitivity skin test responses were only slightly diminished in animals infected with distemper virus. This model should prove useful in exploring the mechanisms of measles induced immunosuppression. [ABSTRACT FROM AUTHOR]

Several parameters of cell-mediated immunity were assessed in thirty patients with chronic renal failure treated with long-term haemodialysis. Lymphopenia was uncommon, and only two patients showed diminished numbers of thymus-derived peripheral blood lymphocytes. Skin test energy to three antigens was documented in only one patient. No serious infections with intracellular organisms were noted in any oldie patients. Phytohaemagglutinin (PHA) induced DNA synthesis in eleven patients was lower than that shown by normal subjects. This poor responsiveness to PHA was not corrected by haemodialysis, and in only two patients was the response improved by substituting normal human plasma for uraemic plasma in the lymphocyte cultures. Thus with the exception of PHA response, other parameters of cell- mediated immunity were intact in this group chronic stable haemodialysis patients. [ABSTRACT FROM AUTHOR]