John F. Fisher

Clinical Practice Guidelines for the Management of Candidiasis: 2009 Update by the Infectious Diseases Society of America

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.

Infection due to the fungus Acremonium (cephalosporium).

Human infections due to fungi belonging to the genus Acremonium occur uncommonly, but unlike infections due to other filamentous fungi, usually affect immunocompetent individuals. Mycetoma, which usually develops following trauma, is the most common infection caused by Acremonium spp. Other sites of infection include the eye (generally following abrogation of ocular defenses), colonizing disease of the lung and gastrointestinal tract, as well as locally invasive infections such as osteomyelitis, sinusitis, arthritis, and peritonitis. Pneumonia and disseminated infections including meningitis, endocarditis, and cerebritis rarely have been reported. Optimal treatment of acremonium infections is not well defined both because infections due to these organisms are rare, and because many reports antedate effective antifungal therapy. In addition, susceptibility testing of filamentous fungi is poorly standardized, and in vitro sensitivity may not correlate with clinical response. Based on anecdotal reports, treatment of most invasive acremonium infections requires a combination of surgical intervention, when possible, and a regimen of amphotericin B. Some azoles also display inhibitory activity. Until more details are available regarding susceptibility of these organisms to antifungal agents, amphotericin B is recommended as initial therapy with the addition of either ketoconazole or fluconazole in infections of a life-threatening nature.

Candida Urinary Tract Infections—Treatment

In many instances a report from the clinical laboratory indicating candiduria represents colonization or procurement contamination of the specimen and not invasive candidiasis. Even if infection of the urinary tract by Candida species can be confirmed, antifungal therapy is not always warranted. Further investigation may reveal predisposing factors, which if corrected or treated, result in the resolution of the infection. For those with symptomatic urinary tract infections (UTIs), the choice of antifungal agent will depend upon the clinical status of the patient, the site of infection, and the pharmacokinetics and pharmacodynamics of the agent. Because of its safety, achievement of high concentrations in the urine, and availability in both an oral and intravenous formulation, fluconazole is preferred for the treatment of Candida UTIs. Flucytosine is concentrated in urine and has broad activity against Candida spp, but its use requires caution because of toxicity. Low-dose amphotericin B may be useful for Candida UTIs in selected patients. The role of echinocandins and azoles that do not achieve measurable concentrations in the urine is not clear. Small case series note some success, but failures have also occurred. Irrigation of the bladder with antifungal agents has limited utility. However, with fungus balls, irrigation of the renal pelvis through a nephrostomy tube can be useful in combination with systemic antifungal agents.

Candida Urinary Tract Infections—Epidemiology

Candiduria is rarely present in healthy individuals. In contrast, it is a common finding in hospitalized patients, especially those in intensive care units (ICUs) who often have multiple predisposing factors, including diabetes mellitus, indwelling urinary catheters, and exposure to antimicrobials. Candiduria occurs much less commonly in the community setting. In a majority of episodes in adult patients in critical care facilities candiduria represents colonization, and antifungal therapy is not required. However, the presence of yeast in the urine can be a sign of a disseminated infection. In the critically ill newborn, candiduria often reflects disseminated candidiasis and is accompanied by obstructing fungus ball formation in the urinary tract. In ICU patients, although candiduria is a marker for increased mortality, it is only rarely attributable to Candida urinary tract infection.

Candida Urinary Tract Infections—Diagnosis

The finding of candiduria in a patient with or without symptoms should be neither dismissed nor hastily treated, but requires a careful evaluation, which should proceed in a logical fashion. Symptoms of Candida pyelonephritis, cystitis, prostatitis, or epididymo-orchitis are little different from those of the same infections produced by other pathogens. Candiduria occurring in critically ill patients should initially be regarded as a marker for the possibility of invasive candidiasis. The first step in evaluation is to verify funguria by repeating the urinalysis and urine culture. Pyuria is a nonspecific finding; the morphology of the offending yeast may allow separation of Candida glabrata from other species. Candida casts in the urine are indicative of renal candidiasis but are rarely seen. With respect to culture, colony counts have not proved to be diagnostically useful. In symptomatic or critically ill patients with candiduria, ultrasonography of the kidneys and collecting systems is the preferred initial study. However, computed tomography (CT) is better able to discern pyelonephritis or perinephric abscess. The role of magnetic resonance imaging and renal scintigraphy is ill defined, and prudent physicians should consult with colleagues in the departments of radiology and urology to determine the optimal studies in candiduric patients who require in-depth evaluation.

Candida urinary tract infection: pathogenesis.

Candida species are unusual causes of urinary tract infection (UTI) in healthy individuals, but common in the hospital setting or among patients with predisposing diseases and structural abnormalities of the kidney and collecting system. The urinary tract may be invaded in either an antegrade fashion from the bloodstream or retrograde via the urethra and bladder. Candida species employ a repertoire of virulence factors, including phenotypic switching, dimorphism, galvano - and thigmotropism, and hydrolytic enzymes, to colonize and then invade the urinary tract. Antegrade infection occurs primarily among patients predisposed to candidemia. The process of adherence to and invasion of the glomerulus, renal blood vessels, and renal tubules by Candida species was elegantly described in early histopathologic studies. Armed with modern molecular biologic techniques, the various virulence factors involved in bloodborne infection of the kidney are gradually being elucidated. Disturbances of urine flow, whether congenital or acquired, instrumentation of the urinary tract, diabetes mellitus, antimicrobial therapy, and immunosuppression underlie most instances of retrograde Candida UTI. In addition, bacterial UTIs caused by Enterobacteriaceae may facilitate the initial step in the process. Ascending infections generally do not result in candidemia in the absence of obstruction.

Therapeutic Failures with Miconazole

A retrospective review of therapeutic failures of miconazole in three patients is presented. Miconazole, a new imidazole derivative, is a broad-spectrum antifungal agent purportedly effective topically, orally, and parenterally against a number of species of fungi. Three patients with the following culturally proven deep fungal infections were treated with miconazole: (i) destructive arthritis (Sporothrix schenckii), (ii) meningoencephalitis (Cryptococcus neoformans), and (iii) disseminated aspergillosis (Aspergillus fumigatus). All the organisms were susceptible in vitro to 1.56 μg or less of miconazole per ml using a broth dilution technique. In each patient, miconazole administered intravenously in dosages of 30 mg/kg per day failed to control or eradicate infection. Miconazole serum levels ranged from <0.5 to 4.35 μg/ml as determined by radial diffusion bioassay. Cerebrospinal fluid levels were virtually undetectable. In one patient (C. neoformans), miconazole was given intraventricularly in doses of 15 mg without response. Therapeutic failures were attributed to suboptimal body fluid levels of miconazole. The reason(s) for such low levels of activity was not clear, but may have been poor penetrance into tissues, in vitro inactivation, and/or unusually rapid excretion. Untoward reactions from miconazole included fever, chills, nausea, vomiting, and phlebitis. Images

Candida Urinary Tract Infections—Epidemiology, Pathogenesis, Diagnosis, and Treatment: Executive Summary

The frequency of infection of the urinary tract due to Candida species is increasing in parallel with the rapid advances of medical progress, and these infections are now among the most common problems facing physicians. Despite this fact, much remains to be learned regarding the pathogenesis, diagnosis, and management of bloodborne (antegrade) kidney infections and ascending (retrograde) invasion of the urinary collecting system. The following is a summary of the in-depth analysis of available information from the literature provided in this journal supplement.

Evaluation of salvage techniques for infected baclofen pumps in pediatric patients with cerebral palsy: Clinical article

OBJECT Intrathecal baclofen therapy has been used successfully for intractable spasticity in children with cerebral palsy. Infections are rare, but they are potentially life threatening if complicated by bacteremia or meningitis. Treatment without removal of the system is desirable if it can be done safely and effectively. METHODS The Authors reviewed the records of 207 patients ranging from 3 to 18 years of age with cerebral palsy who underwent placement or revision of a baclofen pump. They identified 38 patients with suspected or documented infectious complications. Initial attempts were made to eradicate infection with the devices in situ in all patients. Methods and effectiveness of pump salvage were evaluated. RESULTS Of the 38 patients identified, 13 (34.2%) had documented infections; 11 had deep wound/pocket empyemas and 2 had meningitis. Eight patients with deep wound infections received intravenous antibiotics alone. All required pump explantation. The remaining 3 patients underwent a washout procedure as well; the infection was cured in 1 patient. Both patients with meningitis received intravenous and intrathecal antibiotics, and both required device explantation. In addition, 25 patients (65.8%) had excessive or increasing wound erythema. No objective criteria to document a superficial infection were present. The wounds were considered suspicious and were managed with serial examinations and oral antibiotics. The erythema resolved in 24 of the 25 patients. CONCLUSIONS In general, observation, wound care, and oral antibiotics are sufficient for wounds that are suspicious for superficial infection. For deep-seated infection, antibiotic therapy alone is generally insufficient and explantation is required. Washout procedures can be considered, but failures are common.

Guías de práctica clínica para el manejo de la candidiasis: actualización del 2009, de la Infectious Diseases Society of America

Las guias para el manejo de pacientes con candidiasis invasiva y candidiasis mucosa fueron elaboradas por un panel de expertos de la Infectious Diseases Society of America (Sociedad de Enfermedades Infecciosas de los Estados Unidos). Estas guias actualizadas sustituyen las guias anteriores, publicadas en la edicion del 15 de enero de 2004 deClinical Infectious Diseases, y estan disenadas para ser usadas por profesionales de atencion medica que atiendan pacientes que padezcan o que corran riesgo de contraer estas infecciones. Desde 2004 se han puesto a disposicion varios agentes antifungicos nuevos, y se han publicado varios estudios nuevos relacionados con el tratamiento de la candidemia, de otras formas de candidiasis invasiva y de enfermedad de la mucosa, incluidas las candidiasis orofaringea y esofagica. Tambien existen estudios recientes sobre la prevencion de la candidiasis invasiva en recien nacidos y adultos en alto riesgo y en el tratamiento empirico de supuesta candidiasis invasiva en adultos. Esta informacion nueva se incorpora a este documento revisado.