Anurag N. Malani

Candida glabrata Fungemia: Experience in a Tertiary Care Center

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.

Changing epidemiology of rare mould infections: Implications for therapy

There has been an increase in rare mould infections in recent decades. These infections have been reported primarily in severely immunocompromised patients. The emergence of these organisms is multifactorial and can be related to more intense immunosuppression, the prolonged survival of patients who have what were previously fatal diseases, and the selective pressure of broad spectrum antifungal agents used for prophylaxis or therapy. Among these rare mould infections, the Zygomycetes are the most commonly encountered, and in some institutions the increase in these organisms appears to be associated with the use of voriconazole. Aspergillus terreus, a species that is resistant to amphotericin B, and less frequently, A. ustus and A. lentulus, have been noted increasingly as causes of invasive aspergillosis in tertiary care centres in the US. Several species of Scedosporium with innate resistance to many antifungal agents have emerged as major causes of disseminated mould infections that are frequently very difficult to treat. Among patients who have haematological malignancies, are neutropenic or have received a haematopoietic stem cell transplant, infections due to Fusarium species respond poorly to many antifungal agents. Dematiaceous, or brown-black, fungi, most often associated with chronic localised infections, are now increasingly reported as a cause of disseminated infection in immunosuppressed hosts.Concomitant with the increased number of infections with these rare moulds, several new mould-active antifungal agents have been developed. The new expanded spectrum azole, voriconazole, has changed our approach to moulds such as S. apiospermum, Fusarium species and A. terreus that are amphotericin B resistant. Posaconazole, the most recently approved expanded spectrum azole, is the first drug in the azole class to show activity against the Zygomycetes and has proven extremely useful for step-down therapy after initial treatment with amphotericin B. It is not known whether posaconazole is effective as primary therapy for zygomycosis; the use of this agent for that purpose awaits clinical trials with the recently developed intravenous formulation of posaconazole.

Candida urinary tract infections: treatment options

Candiduria is a nonspecific finding that occurs with contamination of a urine sample, colonization of an indwelling catheter and/or the bladder, symptomatic cystitis and invasive upper tract infection. Most patients are colonized and do not require antifungal therapy. Removing predisposing factors, such as indwelling catheters and antibiotics, will clear candiduria in almost 50% of asymptomatic patients. For patients with symptomatic Candida urinary tract infections, a variety of treatment options are available. Fluconazole is the antifungal agent of choice, achieving high urine concentrations with the oral formulation. Rarely, amphotericin B or flucytosine are used. Newer azole agents and echinocandins are not recommended for the treatment of urinary tract infections since they fail to achieve adequate urine concentrations.

Review of Clinical Trials of Skin Antiseptic Agents Used to Reduce Blood Culture Contamination

False-positive blood culture results may lead to prolonged hospitalization, inappropriate antibiotic administration, and increased healthcare costs. We conducted a review of the literature to assess the effect of skin antiseptic agents on the rate of false-positive blood culture results. We found no clear evidence to suggest which antiseptic should be used to prevent false-positive results. Studies suggest, however, a possible benefit from the use of prepackaged skin antiseptic kits and alcohol-containing antiseptics.

Voriconazole-Induced Photosensitivity

Voriconazole is a broad-spectrum triazole antifungal agent indicated for invasive aspergillosis, refractory Candida infections, and other emerging invasive fungal infections. Adverse cutaneous reactions associated with voriconazole therapy occur in fewer than 10% of treated patients and range from mild erythematous eruptions to life-threatening reactions such as the Stevens-Johnson syndrome and toxic epidermal necrolysis. Photosensitivity reactions are an uncommon but characteristic dermatitis in voriconazole recipients, particularly following chronic administration. We report a case of voriconazole-induced phototoxicity in a 50-year-old male with Candida parapsilosis endocarditis that reversed on discontinuation of the drug.

Alopecia and Nail Changes Associated With Voriconazole Therapy

BACKGROUND Voriconazole was 1 of 2 antifungal agents recommended for treatment of fungal infections associated with injection of contaminated methylprednisolone. Alopecia and nail changes are not commonly reported side effects of voriconazole. Having noted increasing hair loss among our patients treated with voriconazole, we sought to determine the prevalence and characteristics of alopecia associated with this agent. METHODS Patients who received voriconazole for at least 1 month for probable or confirmed fungal infection were eligible to complete a survey regarding alopecia and nail changes. For those patients who reported alopecia, additional questions about reversal of hair loss were asked after voriconazole had been stopped for at least 3 months. RESULTS A total of 152 of 175 eligible patients (87%) completed the survey. One hundred twenty-five (82%) reported alopecia. Hair loss on the scalp was noted in 120 (96%), arms and legs in 52 (42%), and eyebrows and eyelashes in 47 each (38%). Nineteen patients (15%) reported wearing a wig or hat because of extensive hair loss. Alopecia developed a mean (standard deviation) of 75 (54) days after initiation of voriconazole. Of 114 patients who were off voriconazole for at least 3 months, hair loss had stopped in 94 (82%) and regrowth had begun in 79 (69%), including those who were changed to either itraconazole or posaconazole. Nail changes or loss occurred in 106 (70%) patients. CONCLUSIONS Alopecia and nail changes were common adverse effects associated with voriconazole therapy during the multistate fungal outbreak.

Is age a risk factor for Candida glabrata colonisation

Studies have reported that Candida glabrata infections are more common in older adults. We sought to determine colonisation rates of C. glabrata in the oral cavity and its relationship with age, comorbid illnesses and hospital or extended care facility stay. Samples were obtained from four sites in the oral cavity and from dentures, when available, from 408 subjects from the community (136), hospital (126) or an extended care facility (146). Overall, 219 (53.7%) subjects were colonised with yeast; the predominant species was Candida albicans. Sixty‐two patients (15.2%) were colonised with C. glabrata. None of the subjects <40 years was colonised with C. glabrata; in those from the community, only nine persons, all of whom were >60 years, were colonised with C. glabrata. By multivariate analysis, increasing age, dentures and use of psychotropic medications were independently associated with C. glabrata colonisation; residing in the community, rather than hospital or extended care, was strongly protective against colonisation. Candida glabrata colonisation is multifactorial; age, and hospitalisation/extended care stay contribute to colonisation. Dentures are strongly associated with colonisation with any yeast and with C. glabrata. Further study is needed to evaluate the relationship of these findings to increasing C. glabrata infections in older adults.

Management of Clostridium difficile Infection : Survey of Practices and Compliance with National Guidelines Among Primary Care Physicians

Guidelines Among Primary Care Physicians • Author(s): Gayle L. Byker, MD; Marie T. Dinh, MD; Naresh T. Gunaratnam, MD; Eileen A. Robinson, MPH; Thomas M. Shehab, MD; Anurag N. Malani, MD Source: Infection Control and Hospital Epidemiology, Vol. 30, No. 4 (April 2009), pp. 397-399 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/596200 . Accessed: 14/05/2014 19:20

Fungal infections associated with contaminated steroid injections

In mid-September 2012, the largest healthcare-associated outbreak in U.S. history began. Before it was over, 751 patients were reported with fungal meningitis, stroke, spinal or paraspinal infection, or peripheral osteoarticular infection, and 64 (8.5%) died. Most patients had undergone epidural injection, and a few osteoarticular injection, of methylprednisolone acetate that had been manufactured at the New England Compounding Center (NECC). The offending pathogen in most cases was Exserohilum rostratum, a brown-black soil organism that previously was a rare cause of human infection. Three lots of methylprednisolone were contaminated with mold at NECC; the mold from unopened bottles of methylprednisolone was identical by whole-genome sequencing to the mold that was isolated from ill patients. Early cases manifested as meningitis, some patients suffered posterior circulation strokes, and later cases were more likely to present with localized infection at the injection site, including epidural abscess or phlegmon, vertebral diskitis or osteomyelitis, and arachnoiditis with intradural involvement of nerve roots. Many patients with spinal or paraspinal infection required surgical intervention. Recommendations for treatment evolved over the first few weeks of the outbreak. Initially, combination therapy with liposomal amphotericin B and voriconazole was recommended for all patients; later, combination therapy was recommended only for those who were most ill, and voriconazole monotherapy was recommended for most patients. Among those patients who continued antifungal therapy for at least 6 months, outcomes for most appeared to be successful, although a few patients remain on therapy.

Laxative Use in the Setting of Positive Testing for Clostridium difficile Infection

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