Treatment of invasive fungal infections in cancer patients--recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive Candida infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection.     

Treatment options of invasive fungal infections in adults

A panel of infectious disease specialists, clinical microbiologists and hospital epidemiologists of the five Swiss university hospitals reviewed the current literature on the treatment of invasive fungal infections in adults and formulated guidelines for the management of patients in Switzerland. For empirical therapy of Candida bloodstream infection, fluconazole is the drug of choice in non-neutropenic patients with no severe sepsis or septic shock or recent exposure to azoles. Amphotericin B deoxycholate or caspofungin would be the treatment option for patients with previous azole exposure. In neutropenic patients, empirical therapy with amphotericin B deoxycholate is considered first choice. In patients with severe sepsis and septic shock, caspofungin is the drug of first choice. For therapy of microbiologically-documented Candida infection, fluconazole is the drug of choice for infections due to C. albicans, C. tropicalis or C. parapsilosis. When infections are caused by C. glabrata or by C. krusei, caspofungin or amphotericin B deoxycholate are first line therapies. Treatment guidelines for invasive aspergillosis (IA) were stratified into primary therapy, salvage therapy and combination therapy in critically ill patients. Voriconazole is recommended for primary (ie upfront) therapy. Caspofungin, voriconazole (if not used for primary therapy) or liposomal amphotericin B are recommended for salvage therapy for refractory disease. Combination therapy with caspofungin plus voriconazole or liposomal amphotericin B should be considered in critically ill patients. Amphotericin B deoxycholate is recommended as initial therapy for the empirical therapy in patients with neutropenia and persistent fever with close monitoring of adverse events.     

Summary of the Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients.

This article contains highlights of "Guidelines for Preventing Opportunistic Infections among Hematopoietic Stem Cell Transplant Recipients: Recommendations of the CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation," which was published in the Morbidity and Mortality Weekly Report. There are sections on the prevention of bacterial, viral, fungal, protozoal, and helminth infections and on hospital infection control, strategies for safe living following transplantation, immunizations, and hematopoietic stem cell safety. The guidelines are evidence-based, and prevention strategies are rated by both the strength of the recommendation and the quality of evidence that supports it. Recommendations are given for preventing cytomegalovirus disease with prophylactic or preemptive gancyclovir, herpes simplex virus disease with prophylactic acyclovir, candidiasis with fluconazole, and Pneumocystis carinii pneumonia with trimethoprim-sulfamethoxazole. Hopefully, following the recommendations made in the guidelines will reduce morbidity and mortality from opportunistic infections in hematopoietic stem cell transplant recipients.     

Associations antifongiques dans les infections fongiques invasives

Invasive fungal infections (candidiasis, aspergillosis and cryptococcosis) are major complications in immunocompromised patients and account for high morbidity and mortality. Guidelines on first-line therapy of invasive fungal infections are based on randomised clinical trials or experts’ guidelines and include essentially single antifungal therapies, except for cryptococcosis. However, the severe prognosis of these infections raises the interest of antifungal associations, in first line or second-line therapy, and many experimental data have been published on this issue. In humans, amphotericin B plus flucytosine combination therapy in cryptococcal meningitis has been largely validated, especially in HIV-infected patients. Also, a few studies demonstrated that the combination of fluconazole plus amphotericin B in candidiasis is not antagonistic and that caspofungin plus polyene or caspofungin plus azole combinations may be beneficial in invasive aspergillosis. Randomised studies are necessary to confirm these data. A study assessing anidulafungin plus voriconazole association in aspergillosis is oncoming.     

Management of candidemia and invasive candidiasis

Candida species is the fourth most common cause of bloodstream infection and is the leading cause of invasive fungal infection among hospitalized patients. Acute disseminated candidiasis remains a life-threatening disease that now occurs mainly in intensive care units hospitalized patients. Delay in treatment of Candida bloodstream infections could be minimized by the development of more rapid and sensitive diagnostic techniques for the identification of Candida bloodstream infections. Current guidelines for the management of invasive candidiasis recommend fluconazole or an echinocandin as the primary therapeutic option. The optimal choice of the antifungal agent should depend on local epidemiology, prior antifungal therapy and patient's characteristics.     

Practice guidelines for the treatment of candidiasis. Infectious Diseases Society of America.

Infections due to Candida species are the most common of the fungal infections. Candida species produce a broad range of infections, ranging from nonlife-threatening mucocutaneous illnesses to invasive process that may involve virtually any organ. Such a broad range of infections requires an equally broad range of diagnostic and therapeutic strategies. This document summarizes current knowledge about treatment of multiple forms of candidiasis and is the guideline of the Infectious Diseases Society of America (IDSA) for the treatment of candidiasis. Throughout this document, treatment recommendations are scored according to the standard scoring scheme used in other IDSA guidelines to illustrate the strength of the underlying data. The document covers 4 major topical areas. The role of the microbiology laboratory. To a greater extent than for other fungi, treatment of candidiasis can now be guided by in vitro susceptibility testing. The guidelines review the available information supporting current testing procedures and interpretive breakpoints and place these data into clinical context. Susceptibility testing is most helpful in dealing with infection due to non-albicans species of Candida. In this setting, especially if the patient has been treated previously with an azole antifungal agent, the possibility of microbiological resistance must be considered. Treatment of invasive candidiasis. In addition to acute hematogenous candidiasis, the guidelines review strategies for treatment of 15 other forms of invasive candidiasis. Extensive data from randomized trials are really available only for therapy of acute hematogenous candidiasis in the nonneutropenic adult. Choice of therapy for other forms of candidiasis is based on case series and anecdotal reports. In general, both amphotericin B and the azoles have a role to play in treatment. Choice of therapy is guided by weighing the greater activity of amphotericin B for some non-albicans species (e.g., Candida krusei) against the lesser toxicity and ease of administration of the azole antifungal agents. Flucytosine has activity against many isolates of Candida but is not often used. Treatment of mucocutaneous candidiasis. Therapy for mucosal infections is dominated by the azole antifungal agents. These drugs may be used topically or systemically and have been proven safe and efficacious. A significant problem with mucosal disease is the propensity for a small proportion of patients to suffer repeated relapses. In some situations, the explanation for such a relapse is obvious (e.g., relapsing oropharyngeal candidiasis in an individual with advanced and uncontrolled HIV infection), but in other patients the cause is cryptic (e.g., relapsing vaginitis in a healthy woman). Rational strategies for these situations are discussed in the guidelines and must consider the possibility of induction of resistance over time. Prevention of invasive candidiasis. Prophylactic strategies are useful if the risk of a target disease is sharply elevated in a readily identified group of patients. Selected patient groups undergoing therapy that produces prolonged neutropenia (e.g., some bone-marrow transplant recipients) or who receive a solid-organ transplant (e.g., some liver transplant recipients) have a sufficient risk of invasive candidiasis to warrant prophylaxis.     

Randomized trial of fluconazole versus low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic stem cell transplantation

Over the past decade, invasive fungal infections have become an increasingly important problem in patients undergoing hematopoietic stem cell transplantation (HSCT). The optimal approach for prophylactic antifungal therapy has yet to be determined. To resolve this issue, we performed a prospective randomized study to compare the efficacy of fluconazole (FL) versus low-dose amphotericin B (AmB) in preventing fungal infections during the first 100 days after HSCT. Patients undergoing allogenic or autologous HSCT were randomized to receive fluconazole 200 mg/day PO or amphotericin B 0.2 mg/kg/day IV beginning 1 day prior to commencement of conditioning regimen and continuing until engraftment, drug-associated toxicity was suspected, or systemic fungal infection was suspected or proven. High-dose amphotericin B (0.5-1.0 mg/kg/day) was started for patients with suspected or proven fungal infections. From January 1993 to December 1998, a total of 186 patients were enrolled into the trial, with 100 receiving FL and 86 receiving AmB. Eighty (43%) patients were removed from prophylaxis for persistent fever despite broad-spectrum antibacterial therapy or suspected fungal infections (FL 46 vs. AmB 34, P > 0.05). The incidence of proven fungal infections (FL 12% vs. AmB 12.8%), suspected fungal infections (FL 4% vs. AmB 2.3%), superficial fungal infections (FL 1% vs. AmB 4.6%) did not show any significant difference. The survival at 100 days post transplant was similar between the 2 groups (FL 78% vs. AmB 70%, P = 0.254). Death attributable to fungal infections was similar in both groups (6% vs. 7%, P > 0.05). We conclude that fluconazole is as effective as low-dose amphotericin B in prophylaxis against fungal infections in patients undergoing hematopoietic cell transplantation.     

Primary prophylaxis of invasive fungal infections in patients with haematologic malignancies. 2014 update of the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

Invasive fungal infections cause substantial morbidity and mortality in immunocompromised patients, particularly in those with haematological malignancies and recipients of allogeneic haematopoietic stem cell transplantation. Difficulties in diagnosing invasive fungal infections and subsequent delays in treatment initiation lead to unfavourable outcomes and emphasise the importance of prophylaxis. Since the recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology in 2009, results of 14 additional clinical studies have been published comprising 2,899 patients and initiating this update. Key recommendations for adult patients are as follows: Posaconazole remains the drug of choice during remission-induction chemotherapy in acute myeloid leukaemia, myelodysplastic syndrome and allogeneic haematopoietic stem cell transplantation with graft versus host disease (AI). In the pre-engraftment period of allogeneic transplantation, several antifungals are appropriate and can be recommended with equal strength: voriconazole (BI), micafungin (BI), fluconazole (BI) and posaconazole (BII). There is poor evidence regarding antifungal prophylaxis in the post-engraftment period of allogeneic haematopoietic stem cell transplantation if no steroids for treatment of graft versus host disease are required. Aerosolised liposomal amphotericin B inhalation in conjunction with fluconazole can be used in patients with prolonged neutropenia (BII).     

New developments in the diagnosis and management of invasive fungal infections

Invasive fungal infections in cancer patients are on the increase. Candidemia is now the fourth leading cause of bloodstream infections in many intensive care units (ICUs). Although a number of risk factors have been identified, antifungal therapy should not be started in non-neutropenic patients until a diagnosis of invasive candidiasis or candidemia is made or presumed in order to avoid the development of resistance. Even a single positive blood culture should be treated, and requires removal of intravascular lines. Fluconazole is the first line agent for treatment candidemia other than that caused by Candida glabrata or C. krusei. High-resolution CT scan pictures showing a halo sign or crescent air sign are helpful for establishing the diagnosis of invasive aspergillosis. Sandwich ELISA can be used to detect circulating galactomannan in serial serum samples. Polymerase chain reaction (PCR) of blood samples may also be used. There are only a few randomized studies of newly developed antifungal drugs compared to conventional amphotericin B (AmB). So far, both AmB colloidal dispersion and AmB lipid complex have failed to show more favorable efficacy or lesser toxicity rates, except for nephrotoxicity. Liposomal AmB, used during febrile neutropenia, did have a significantly lower toxicity rate. In neutropenic patients with invasive fungal infections liposomal AmB proved to be better than conventional AmB in terms of clinical efficacy, mortality and nephrotoxicity rates. The use of tests to achieve an earlier diagnosis combined with more potent treatment formulations such as liposomal AmB may be significant steps towards successful management of invasive fungal infections.     

Practice guidelines for the management of patients with blastomycosis. Infectious Diseases Society of America.

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 nonlife-threatening non-CNS blastomycosis.     

Successful Treatment of Chronic Disseminated Candidiasis with Caspofungin and Itraconazole in a Patient with Progressive Acute Leukemia and Prolonged Neutropenia

Severe fungal infections remain a significant cause of morbidity and mortality in neutropenic patients undergoing dose-intensive chemotherapy for malignant diseases. Chronic disseminated candidiasis (CDC) is a life-threatening complication in neutropenic patients because of the lack of responsive hematopoietic precursor cells. Resolution of Candida organ lesions after hematopoietic reconstitution may take months. Here, we report the case of a 19-year-old neutropenic woman with relapsed acute myelogenous leukemia and candidiasis of liver, spleen, and kidneys. Antifungal treatment was initiated using fluconazole and caspofungin but was changed to itraconazole and caspofungin. Despite elevated C-reactive protein (CRP) levels and detectable Candida organ lesions, antileukemic therapy was restarted with interleukin 2 at the same time as antimicrobial treatment. Eight weeks after the start of interleukin therapy, CRP levels and organ lesions were decreased significantly irrespective of continuing neutropenia. This case report describes the successful treatment of CDC during neutropenia using combination antifungal therapy and suggests controlled studies to establish optimal therapeutic strategies.     

Micafungin compared with caspofungin for the treatment of febrile episodes in neutropenic patients with hematological malignancies: A retrospective study

BACKGROUND:Invasive fungal infections are associated with morbidity and mortality in neutropenia secondary to hematological malignancies. Empirical antifungal agents are used to reduce their consequences. Caspofungin is the only echinocandin approved for this indication. Micafungin was compared with caspofungin for the treatment of patients with hematological malignancies and prolonged neutropenia.METHODS:A retrospective cohort study was conducted involving patients who had hematological malignancies with profound neutropenia for a minimum of 10 days, and received empirical micafungin or caspofungin for a minimum of five days, between April 2005 and November 2009. Successful outcome was based on a composite end point: survival for a minimum of seven days following antifungal cessation, successful treatment of baseline fungal infection, absence of adverse events and absence of breakthrough fungal infection. Fungal infections were defined according to revised definitions of invasive fungal disease from the 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) criteria, with modification of the diagnostic imaging criteria.RESULTS:Micafungin had similar overall success to caspofungin (60.4% [29 of 48] versus 57.3% [47 of 82], respectively; P=0.729). Survival was higher in the micafungin group compared with the caspofungin group (100% [48 of 48] versus 89% [73 of 82]; P=0.02). No baseline invasive fungal infections were identified in the micafungin group, compared with three proven infections treated successfully with caspofungin (3.7%; P=0.18). Three proven breakthrough infections were observed in the micafungin group (three of 48 [27.3%]) compared with none in the caspofungin group (zero of 82; P=0.02).CONCLUSION:Micafungin has similar efficacy to caspofungin as empirical antifungal therapy in febrile neutropenic patients with hematological malignancies. Verification of these results in a prospective trial is warranted.     

Caspofungin for invasive candidiasis at a tertiary care medical center

Background

Caspofungin is emerging as first-line therapy for invasive candidiasis. Data on the use of caspofungin for treatment for invasive candidiasis are limited to clinical trials and case reports. We report a single-center experience with 104 consecutive courses of caspofungin for the treatment of invasive candidiasis to evaluate a real-world performance of this drug.

Methods

A retrospective chart review of patients receiving caspofungin at a tertiary care medical center was performed. Patient information and microbiologic data were abstracted from patient charts and electronic medical records.

Results

Of 241 patients receiving caspofungin for all indications, 122 (51%) had proven invasive candidiasis. There were 104 treatment courses for candidiasis in 99 patients available for review. Bloodstream (66%) and abdominal infections (25%) were the most common sites of infection. Most infections were non-albicans (80/104, 77%; including patients infected with more than one species). Clinical cure rates at the end of therapy were 83% (57/69) for bloodstream infections and 84% (22/26) for abdominal infections. Caspofungin did not clear candidiasis in 14 episodes (microbiologic cure rate 75%, 42/56).

Conclusions

The clinical use of caspofungin has been successful in the treatment of invasive candidiasis, even in patients with prior antifungal exposure. In this unselected review, caspofungin performed similarly as in clinical trials, and clinicians should consider caspofungin as first-line therapy for invasive candidiasis, particularly non-albicans species.     

Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients

The incidence of invasive fungal infection (IFIs) in hematopoietic stem cell transplantation (HSCT) recipients ranges from 10 to 25% with an overall case fatality rate of up to 70-90%. Candida and Aspergillus genera remain the two most common pathogens. Although fluconazole prophylaxis in this population has been moderately effective in reducing mortality due to invasive candidiasis, this agent does not have activity against invasive aspergillosis (IA) and other mould. Several new agents such as voriconazole and caspofungin have enhanced potency and broad-spectrum antifungal activity and show promising results against yeasts and filamentous fungi when given as therapy and as chemoprophylaxis. Further, new diagnostic tools to detect circulating fungal antigens in biological fluids and PCR-based methods to detect species or genus-specific DNA or RNA have been developed. Incorporating these techniques along with clinical criteria appear to improve the accuracy of preclinical diagnosis of IFIs. Such approaches may alter the current treatment strategy from prophylaxis to pre-emptive therapy, thereby potentially decreasing cost and toxicity in high-risk patients.     

Therapy of invasive fungal infections.

During the past decades, the incidence and severity of invasive fungal infections has been increasing. These events have lead to the development of new antifungal agents, and amphotericin B no longer is the standard therapy for a variety of invasive mycoses. Fluconazole has become the drug of choice for treatment of C. albicans infections in non-neutropenic as well as neutropenic patients. For treatment of cryptococcal meningitis, amphotericin B with flucytosine, followed by fluconazole consolidation therapy is used. For therapy of invasive aspergillosis, the lipid formulations of amphotericin B may be associated with reduced toxicity and allow for larger doses, although the efficacy of each of the formulations still has to be established in randomized trials. Finally, treatment modalities aimed at improving host defense mechanisms, including adjunctive therapy with rG-CSF for disseminated candidiasis and rG-CSF-elicited granulocyte transfusions, are under way.     

Changing face of health-care associated fungal infections

PURPOSE OF REVIEW: The purpose of this review was to evaluate recent publications on the epidemiology, diagnosis and management of invasive fungal infections. RECENT FINDINGS: Epidemiological surveys have highlighted significant differences between Europe and the United States regarding the incidence and etiology of Candida bloodstream infections. Today, invasive aspergillosis is occurring in a much broader patient population than the classical immunocompromised hosts and includes mechanically ventilated intensive care unit patients and patients receiving corticosteroids for treatment of chronic lung diseases. Diagnosis is often delayed in these patients and prognosis is dismal. Measurement of galactomannan, mannan and antimannan antibodies, and beta-(1-3)-D-glucan may help to speed up diagnosis. The epidemiology of invasive mold infections is changing. The frequency of non-fumigatus Aspergillus species is increasing, uncommon hyalo-or phaeo-hyphomycoses are emerging and breakthrough mold infections intrinsically resistant to azoles have been reported. Clinical trials have shown that new azoles and echinocandins are as efficacious as amphotericin B or fluconazole for the treatment of eosophageal or invasive candidiasis, for prophylaxis of invasive fungal infections in transplant patients, or for empirical antifungal therapy in patients with persistent fever and neutropenia. SUMMARY: Recent data suggest that the epidemiology of invasive fungal infections may be changing with the emergence of uncommon molds and the occurrence of invasive aspergillosis in 'nonclassical' immunocompromised hosts. New diagnostic tools and improved antifungal agents are available to facilitate early diagnosis and offer new treatment options.     

Amphotericin B combined with itraconazole or fluconazole for treatment of histoplasmosis

To investigate the efficacy of combined treatment with fluconazole (Flu) and amphotericin B (AmB) for Histoplasma capsulatum meningitis, MICs were determined for 10 clinical isolates, following National Committee for Clinical Laboratory Standards guidelines. Weak synergy was observed for 6 of the 10 isolates. For the in vivo models, mice either were sham treated or were given Flu (75 mg/kg/day), AmB (2 mg/kg every other day), itraconazole (Itra; 75 mg/kg/day), AmB+Flu, or AmB+Itra. Following infection with 5x105 yeasts, Flu antagonized AmB's reduction of fungal burden without reducing its effect on survival. When in vivo antagonism was reproduced following infection with 1x104 yeasts, a higher fungal burden was observed in the lungs. Itra had no effect on AmB's activity and was more effective than Flu for clearance of fungal burden. These findings caution against use of AmB+Flu for treatment of histoplasmosis, but studies of the effect of treatment on the fungal burden in the brain are needed to assess combination therapy for meningitis.     

Empirical antifungal therapy in patients with neutropenia and persistent or recurrent fever of unknown origin

Persistent or recurrent fever of unexplained origin (PFUO) in neutropenic patients receiving antibiotic therapy is commonly treated with empirical antifungal therapy (EAFT). EAFT was established as an adequate management of PFUO around 20 years ago with conventional amphotericin B deoxycholate (c-AmB), despite its high rate of infusional and systemic toxicities. In recent years, EAFT trials for PFUO have used less toxic agents, such as the lipid formulations of AmB, the new azoles, and the echinocandin, caspofungin. In clinical trials, the lipid formulations of AmB [especially liposomal AmB (L-AmB)] provided similar efficacy with lower toxicity but at a much higher cost. Although rarely used in clinical practice, fluconazole is equivalent to c-AmB, provided patients at high risk of Aspergillus infections are excluded. Intravenous itraconazole was shown to be equivalent to c-AmB, with a lower toxicity. Voriconazole did not meet non-inferiority criteria when compared with L-AmB. Caspofungin was shown to be non-inferior to L-AmB and more effective in treating baseline invasive fungal infections. To date, alternatives to AmB have shown less toxicity, but improved efficacy is less clear. This is probably because of the weakness of the indication and to the consequent difficulty in establishing objective and reproducible endpoints for comparisons. The new challenge for physicians in this field is probably presumptive antifungal therapy, an approach based on patient risk-group stratification for developing invasive candidiasis or aspergillosis and/or the use of new diagnostic techniques to identify patients at a very early stage of infection.     

Prolonged fluconazole prophylaxis is associated with persistent protection against candidiasis-related death in allogeneic marrow transplant recipients: long-term follow-up of a randomized, placebo-controlled trial

Two randomized, placebo-controlled trials previously showed that fluconazole (400 mg/d) administered prophylactically decreases the incidence of candidiasis in blood and marrow transplant (BMT) recipients. However, there exists conflicting data regarding the optimal duration of fluconazole administration, specifically whether prophylaxis through acute graft-versus-host disease (GVHD) results in improved survival in allograft recipients. Reported here are the results of long-term follow-up and a detailed analysis of invasive candidiasis and candidiasis-related death in 300 patients who received fluconazole (400 mg/d) or placebo for 75 days after BMT at the Fred Hutchinson Cancer Research Center. Patients in both treatment arms were compared for survival, causes of death, and the incidence of invasive fungal infections early (less than 110 days) and late (more than 110 days) after BMT. After 8 years of follow-up, survival is significantly better in fluconazole recipients compared with placebo recipients (68 of 152 vs 41 of 148, P =.0001). The overall incidence of invasive candidiasis was increased in patients who received placebo compared with fluconazole (30 of 148 vs 4 of 152, P <.001). More patients who received placebo died with candidiasis early (13 of 148 vs 1 of 152, P =.001) and late (8 of 96 vs 1 of 121, P =.0068) after BMT. The incidence of severe GVHD involving the gut was higher in patients who did not receive fluconazole (20 of 143 vs 8 of 145, P =.02), and fewer patients who received fluconazole died with this complication. Thus, administration of fluconazole (400 mg/d) for 75 days after BMT appears to be associated with decreased gut GVHD, a persistent protection against disseminated candidal infections and candidiasis-related death, resulting in an overall survival benefit in allogeneic BMT recipients.     

Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA).

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America (IDSA) through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of two specific types of urinary tract infections (UTIs): uncomplicated, acute, symptomatic bacterial cystitis and acute pyelonephritis in women. The guideline does not contain recommendations for asymptomatic bacteriuria, complicated UTIs, Foley catheter-associated infections, UTIs in men or children, or prostatitis. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent women. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members represented experts in adult infectious diseases and urology. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendation and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council, the sponsor and supporter of the guideline. The American Urologic Association and the European Society of Clinical Microbiology and Infectious Diseases have endorsed it. An executive summary and tables highlight the major recommendations. Performance measures are described to aid in monitoring compliance with the guideline. The guideline will be listed on the IDSA home page at http://www.idsociety.org It will be evaluated for updating in 2 years.