Pulmonary Cryptococcosis in the Immunocompetent Patient-Many Questions, Some Answers.

Background. There are no prospective data regarding the management of pulmonary cryptococcosis in the immunocompetent patient. Clinical guidelines recommend oral fluconazole for patients with mild to moderate symptoms and amphotericin B plus flucytosine followed by fluconazole for severe disease. It is unclear whether patients who have histological evidence of Cryptococcus neoformans but negative cultures will even respond to drug treatment. We evaluated and managed a patient whose presentation and course raised important questions regarding the significance of negative cultures, antifungal choices, duration of therapy, and resolution of clinical, serologic, and radiographic findings. Methods. In addition to our experience, to answer these questions we reviewed available case reports and case series regarding immunocompetent patients with pulmonary cryptococcosis for the last 55 years using the following definitions: Definite - Clinical and/or radiographic findings of pulmonary infection and respiratory tract isolation of C. neoformans without other suspected etiologies; Probable - Clinical and radiographic findings of pulmonary infection, histopathologic evidence of C. neoformans, and negative fungal cultures with or without a positive cryptococcal polysaccharide antigen. Results. Pulmonary cryptococcosis resolves in most patients with or without specific antifungal therapy. Clinical, radiographic, and serologic resolution is slow and may take years. Conclusions. Persistently positive antigen titers are most common in untreated patients and may remain strongly positive despite complete or partial resolution of disease. Respiratory fungal cultures are often negative and may indicate nonviable organisms.

Permanent resident.

The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to-day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff.

Recreational vehicle water tanks as a possible source for legionella infections.

We investigated recreational vehicle (RV) water reservoirs in response to a case of pneumonia in which Legionella pneumophila was cultured both from the patient and a RV reservoir in which he travelled. Water samples processed and cultured at the CDC according to standard protocol were positive for Legionella spp. in 4/17 (24%) faucets, 1/11 (9%) water tanks from 4/20 (20%) RVs from three different campsites. Legionella spp. that were isolated included L. pneumophila (serogroups 1 and 6), L. anisa, L. feeleii, and L. quateriensis. Environmental controls from the potable water of the three campsites were culture-negative. A survey of maintenance practices by the RV users at the campsites revealed that chlorine disinfection of the water tanks was rarely performed. To prevent the possibility of Legionella infections, RV owners should implement regular chlorine disinfection of their water tanks and follow the recommended maintenance guidelines according to their owner's manuals.

Evaluation of salvage techniques for infected baclofen pumps in pediatric patients with cerebral palsy.

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.

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.

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 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.

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 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.

Unsuspected polymicrobial brain abscess arising from an intra-abdominal source in a patient with hereditary hemorrhagic telangiectasia.

The unusual and unprecedented occurrence of a patient with hereditary hemorrhagic telangiectasia (HHT) and a polymicrobial abscess with three different organisms, including fungi, is reported. The patient was a 48-year-old woman with human immunodeficiency virus (HIV) infection and HHT who was brought to the hospital after a motor vehicle accident with altered mental status. Computed tomography did not reveal evidence of acute brain injury but showed a left frontal brain abscess. The patient underwent neurosurgical drainage of the abscess. On culture the abscess yielded methicillin-resistant Staphylococcus aureus, Streptococcus intermedius, and Candida guilliermondii.

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.

Brain abscess caused by Streptomyces infection following penetration trauma: case report and results of susceptibility analysis of 92 isolates of Streptomyces species submitted to the CDC from 2000 to 2004.

The case of a patient who presented with a brain abscess caused by Streptomyces infection following penetrating cerebral trauma with a soil-contaminated object generated an interest in optimizing antimicrobial therapy. Collaboration with the Centers for Disease Control and Prevention led to the analysis of susceptibility data for Streptomyces isolates that suggested that amikacin (100% susceptibility for 92 isolates tested) and linezolid, an oxazolidinone (100% susceptibility for 41 isolates tested), offer reliable activity against all isolates.

The Aspergillus fumigatus cell wall is organized in domains that are remodelled during polarity establishment.

Aspergillus fumigatus is a life-threatening and increasingly frequent pathogen of the immunocompromised. Like other filamentous fungi A. fumigatus grows in a highly polar manner, adding new cell wall to the apical region of hyphae. mAbs were raised against isolated A. fumigatus cell walls. Fifteen antibodies bound reproducibly to isolated cell walls in ELISAs and to the walls of intact cells in immunofluorescence experiments. Surprisingly, individual mAbs showed distinct patterns of localization. Six antibodies labelled exclusively conidial or basal regions, seven labelled apical regions and a single antibody labelled both basal and apical regions of hyphae. Ten antibodies did not label the walls adjacent to septa. In double labelling experiments with representative mAbs there was little or no overlap between epitopes recognized. These labelling patterns suggest that the wall is made up of basal and apical domains that differ in composition or organization and that the wall region flanking septa differs from other regions of the lateral wall. In time-course experiments of early A. fumigatus growth, mAb16C4 failed to label isotropically expanding cells and labelled emerging germ tubes and branches. The same mAb failed to label the Aspergillus nidulans swoC mutant, which is defective in polarity establishment. However, mAb16C4 did label the A. nidulans swoA mutant, which completes polarity establishment, but is defective in polarity maintenance. Thus, mAb16C4 appears to recognize a cell wall change that occurs during polarity establishment. In immunogold labelling and transmission electron microscopy (TEM) experiments, conidia, basal regions and apical regions of thin-sectioned cells labelled with mAb16C4. That only apical regions labelled in intact cells (immunofluorescence) while conidial, basal and apical regions labelled in thin-sectioned cells (TEM) suggests that the 16C4 epitope is present along the whole hypha, but is masked everywhere except the tip until polarity establishment. That is to say, some remodelling of the wall during polarity establishment exposes the 16C4 epitope. The 16C4 epitope was partially purified from A. fumigatus total protein by passage through hydrophobic interaction and anion-exchange columns. The resulting single ELISA-positive fraction showed relatively few bands by SDS-PAGE and silver staining and a strong band by Western blotting with the16C4 mAb. Sequencing of the fraction yielded a predicted peptide with a 6-amino acid exact match to a region of the Cat1 protein previously identified as an immunodominant A. fumigatus catalase that localizes to the cell wall and is secreted to the medium. Experiments are under way to determine if mAb16C4 recognizes Cat1 or another protein that co-purifies with Cat1.

Congenital pancreatic cysts in children.

The authors report a case of an 11-year-old girl with a solitary, congenital pancreatic cyst and review the literature. Such cysts are very rare and typically are diagnosed in childhood. As a neonate, this patient's paternal half brother also had undergone resection of a congenital pancreatic cyst. The authors believe this is the first documented familial incidence of a congenital pancreatic cyst.