Anurag N Malani

Wayne State University, Detroit, Michigan, United States

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Publications (28)231.7 Total impact

  • April C Pettit, Anurag N Malani
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    ABSTRACT: In September 2012, an unprecedented outbreak of fungal infections due to preservative-free, injectable methylprednisolone acetate (MPA) was identified. Exserohilum rostratum was quickly identified as the predominant organism involved in disease cases. Prior to this outbreak, little was known about the pathogenesis, treatment, and prognosis of infections due to this unusual brown-black mold. Almost 2 years after the onset of this outbreak, numerous epidemiologic and basic science studies have provided some guidance in understanding the epidemiology, clinical findings, diagnosis, and treatment of patients exposed to the contaminated medication. Additionally, this outbreak has directly led to the passage of legislation supporting increased regulation in the industry of pharmaceutical compounding. Many unanswered questions, particularly surrounding the long-term prognosis and outcomes for affected patients remain. However, it is clear that a strong relationship between clinicians caring for patients and public health as well as a rapid, effective public health response was critical in preventing additional cases of disease.
    Current Infectious Disease Reports 01/2015; 17(1):441. DOI:10.1007/s11908-014-0441-x
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    ABSTRACT: Background: The prompt diagnosis and treatment of fungal meningitis is critical, but culture is insensitive. (1,3)-beta-D-glucan (BDG) is FDA-cleared for serologic diagnosis of invasive fungal disease. (Fungitell assay, Associates of Cape Cod Incorporated). However, BDG is not cleared for testing cerebrospinal fluid (CSF) and the appropriate cutoff is unknown. We aim to validate the accuracy of CSF BDG for the diagnosis of fungal meningitis among patients exposed to contaminated methylprednisolone acetate (MPA). Methods: A case-control study was conducted at St. Joseph Mercy Hospital and Vanderbilt University from November, 2013 February, 2014. Patients were included if they received a contaminated MPA injection. Cases were classified as probable or confirmed meningitis according to Centers for Disease Control and Prevention guidelines. Controls were defined as persons exposed but not diagnosed with disease. CSF BDG testing was performed according to the package insert for serum and validated using Clinical Laboratory Standards Institute procedures (MiraVista Diagnostics). Results: Of 233 patients, 45 had meningitis (28 confirmed), 53 had spinal/paraspinal infection (19 confirmed), and 135 did not develop disease. The figure depicts CSF BDG results from those with confirmed meningitis, probable meningitis, and controls. Using the manufacturer's cutoff (BDG ≥ 80 pg/mL), the sensitivity and specificity were 96% (95% CI 80-100%) and 93% (95% CI 87-97%) for confirmed meningitis and 84% (95% CI 70-93%) and 93% (95% CI 87-97%) for probable meningitis. The Receiver Operating Characteristic analysis identified the optimal cutoff for confirmed meningitis to be ≥ 500 pg/mL (sensitivity 93% [95% CI 76-99%], specificity 100% [95% CI 97-100%]); for probable meningitis to be 66 pg/mL (sensitivity 91% [95% CI 79-98%],specificity 92% [95% CI 87-96%]). Conclusion: Our results suggest that CSF BDG is both a highly sensitive and specific test for diagnosis of fungal meningitis associated with contaminated MPA injections. Further study is needed on the diagnostic utility of CSF BDG for other types of fungal meningitis.
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
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    ABSTRACT: Background. Voriconazole is a triazole antifungal medication used for prophylaxis or to treat invasive fungal infections. Inflammation of the periosteum resulting in skeletal pain, known as periostitis, is a reported side effect of long-term voriconazole therapy. The trifluorinated molecular structure of voriconazole suggests a possible link between excess fluoride and periostitis, as elevated blood fluoride has been reported among patients with periostitis who received voriconazole. Methods. Two hundred sixty-four patients from Michigan were impacted by the multistate outbreak of fungal infections as a result of contaminated methylprednisolone injections. A retrospective study was conducted among 195 patients who received voriconazole therapy at St Joseph Mercy Hospital during this outbreak. Twenty-eight patients who received both bone scan and plasma fluoride measurements for skeletal pain were included in the statistical analyses. Increased tracer uptake on bone scan was considered positive for periostitis. The primary outcome measure was the correlation between plasma fluoride and bone scan results. Results. Blood fluoride (P < .001), alkaline phosphatase (P = .020), daily voriconazole dose (P < .001), and cumulative voriconazole dose (P = .027) were significantly elevated in patients who had periostitis compared with those who did not. Discontinuation or dose reduction of voriconazole resulted in improvement of pain in 89% of patients. Conclusions. High plasma fluoride levels coupled with skeletal pain among patients who are on long-term voriconazole therapy is highly suggestive of periostitis. Initial measurement of fluoride may be considered when bone scan is not readily available. Early detection should be sought, as discontinuation of voriconazole is effective at reversing the disease.
    Clinical Infectious Diseases 07/2014; 59(9). DOI:10.1093/cid/ciu513 · 9.42 Impact Factor
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    ABSTRACT: BACKGROUND: Fungal infection from a contaminated injection is rare (~4/10,000 injections) and can result in permanent joint damage if untreated. Infection associated with the 2012 nationwide fungal meningitis outbreak caused by contaminated methylprednisolone acetate (CMPA) injections continue to be reported. Michigan has reported 25/33 of U.S.-reported peripheral joint infections (PJIs). We describe the epidemiologic and clinical characteristics of affected Michigan patients. METHODS: A probable case was defined as osteomyelitis or worsening inflammatory arthritis of a peripheral joint after CMPA injection after May 21, 2012. Confirmed cases also had a fungal pathogen detected through direct microscopy, culture, or polymerase chain reaction of synovial fluid, or histopathology of joint tissue. Cases were identified through active surveillance or patients self-reporting symptoms; clinical information was obtained through medical record review. All patients had magnetic resonance imaging (MRI). RESULTS: Among the 22 probable and 3 confirmed cases, all presented with joint pain; however, 15 (60%) were among patients with symptoms unchanged from before their infection. Twenty-three patients had ≥1 underlying chronic condition, including renal insufficiency, diabetes, cardiovascular disease, and immunosuppression. Twenty-four had surgical treatment for infection, including incision and drainage, arthroscopic debridement, clavicle resection, and hip arthroplasty. Median joint aspirate white blood cell count at diagnosis was 717 cells/µL (range: 9–24,000). Median days from last injection to first MRI joint infection evidence was 70 (range: 22–171). Patients had received a median of 1 (range: 1–3) CMPA injection. CONCLUSIONS: Approximately half of Michigan PJIs occurred among patients without new symptoms who later required surgical treatment. A higher index of suspicion should be maintained for patients who received PJIs in the absence of a gold standard for case identification.
    2014 Council of State and Territorial Epidemiologists Annual Conference; 06/2014
  • American Journal of Infection Control 06/2014; 42(6):S158-S159. DOI:10.1016/j.ajic.2014.03.337 · 2.33 Impact Factor
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    ABSTRACT: 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.
    Clinical Infectious Diseases 05/2014; 59(5). DOI:10.1093/cid/ciu275 · 9.42 Impact Factor
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    ABSTRACT: Background. Carbapenem-resistant Enterobacteriaceae (CRE) are clinically challenging, threaten patient safety, and represent an emerging public health issue. CRE reporting is not mandated in Michigan. Methods. The Michigan Department of Community Health-led CRE Surveillance and Prevention Initiative enrolled 21 facilities (17 acute care and 4 long-term acute care facilities) across the state. Baseline data collection began September 1, 2012, and ended February 28, 2013 (duration, 6 months). Enrolled facilities voluntarily reported cases of Klebsiella pneumoniae and Escherichia coli according to the surveillance algorithm. Patient demographic characteristics, laboratory testing, microbiology, clinical, and antimicrobial information were captured via standardized data collection forms. Facilities reported admissions and patient-days each month. Results. One-hundred two cases over 957,220 patient-days were reported, resulting in a crude incidence rate of 1.07 cases per 10,000 patient-days. Eighty-nine case patients had test results positive for K. pneumoniae, whereas 13 had results positive for E. coli. CRE case patients had a mean age of 63 years, and 51% were male. Urine cultures (61%) were the most frequently reported specimen source. Thirty-five percent of cases were hospital onset; sixty-five percent were community onset (CO), although 75% of CO case patients reported healthcare exposure within the previous 90 days. Cardiovascular disease, renal failure, and diabetes mellitus were the most frequently reported comorbid conditions. Common ris k factors included surgery within the previous 90 days, recent infection or colonization with a multidrug-resistant organism, and recent exposures to antimicrobials, especially third- or fourth-generation cephalosporins. Conclusions. CRE are found throughout Michigan healthcare facilities. Implementing a regional, coordinated surveillance and prevention initiative may prevent CRE from becoming hyperendemic in Michigan.
    Infection Control and Hospital Epidemiology 04/2014; 35(4):342-9. DOI:10.1086/675611 · 4.02 Impact Factor
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    ABSTRACT: Background: Tigecycline is one of few remaining therapeutic options for extensively drug resistant (XDR) Gram-negative bacilli (GNB). Minimal inhibitory concentrations (MICs) of tigecycline to Acinetobacter baumannii have been reported to be elevated when determined by E-test compared to broth microdilution (BMD). Study aims were to compare the susceptibility of GNBs to tigecycline by four different testing methods.Methods: GNBs were collected from six different healthcare systems (25 hospitals) in Southeast Michigan from 01/2010 - 09/2011. Tigecycline MICs among A. baumannii, carbapenem-resistant enterobacteriaceae (CRE), extended-spectrum β-lactamase producing enterobacteriaceae (ESBL) and susceptible enterobacteriaceae isolates were determined by E-test, BMD, Vitek-2, and MicroScan. Non-susceptibility was categorized as tigecycline MIC≥4 μg/mL for both A. baumannii and enterobacteriaceae.Results: The study included 4,427 isolates: 2,065 ESBLs, 1,105 A. baumannii, 888 susceptible enterobacteriaceae, and 369 CREs. Tigecycline resistance among A. baumannii isolates was significantly more common as determined by E-test compared to BMD (OR=10.3, p<0.001), MicroScan (OR=12.4, p<0.001), or Vitek-2 (OR=9.4, p<0.001). These differences were not evident with the other pathogens.Conclusion: Tigecycline MICs varied greatly according to in-vitro testing methods among A. baumannii isolates. E-test should probably not be used by laboratories for tigecycline MIC testing of A. baumannii, since MICs are significantly elevated compared to three other methods.
    Journal of clinical microbiology 03/2014; 52(5). DOI:10.1128/JCM.00001-14 · 4.23 Impact Factor
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    ABSTRACT: Urine cultures are frequently obtained for hospitalized patients. We reviewed documented indications for culture and compared these with professional society guidelines. Lack of documentation and important clinical scenarios (before orthopedic procedures and when the patient has altered mental status without a urinary catheter) are highlighted as areas of use outside of current guidelines.
    Infection Control and Hospital Epidemiology 11/2013; 34(11):1204-1207. DOI:10.1086/673449 · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND Since September 18, 2012, public health officials have been investigating a large outbreak of fungal meningitis and other infections in patients who received epidural, paraspinal, or joint injections with contaminated lots of methylprednisolone acetate. Little is known about infections caused by Exserohilum rostratum, the predominant outbreak-associated pathogen. We describe the early clinical course of outbreak-associated infections. METHODS We reviewed medical records for outbreak cases reported to the Centers for Disease Control and Prevention before November 19, 2012, from the six states with the most reported cases (Florida, Indiana, Michigan, New Jersey, Tennessee, and Virginia). Polymerase-chain-reaction assays and immunohistochemical testing were performed on clinical isolates and tissue specimens for pathogen identification. RESULTS Of 328 patients without peripheral-joint infection who were included in this investigation, 265 (81%) had central nervous system (CNS) infection and 63 (19%) had non-CNS infections only. Laboratory evidence of E. rostratum was found in 96 of 268 patients (36%) for whom samples were available. Among patients with CNS infections, strokes were associated with an increased severity of abnormalities in cerebrospinal fluid (P<0.001). Non-CNS infections were more frequent later in the course of the outbreak (median interval from last injection to diagnosis, 39 days for epidural abscess and 21 days for stroke; P<0.001), and such infections developed in patients with and in those without meningitis. CONCLUSIONS The initial clinical findings from this outbreak suggest that fungal infections caused by epidural and paraspinal injection of a contaminated glucocorticoid product can result in a broad spectrum of clinical disease, reflecting possible variations in the pathogenic mechanism and in host and exposure risk factors. (Funded by the Centers for Disease Control and Prevention.)
    New England Journal of Medicine 10/2013; 369:1610. DOI:10.1056/NEJMoa1304879 · 54.42 Impact Factor
  • Anurag N Malani, Bonita Singal, Carol A Kauffman
    JAMA The Journal of the American Medical Association 10/2013; 310(16):1735-6. DOI:10.1001/jama.2013.277458 · 29.98 Impact Factor
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    ABSTRACT: Injection of contaminated methylprednisolone has resulted in an unprecedented nationwide outbreak of Exserohilum rostratum fungal infections, manifested initially as meningitis and/or basilar stroke. Insidious onset of spinal or paraspinal infection at the injection site has been increasingly reported and is occurring months after receipt of injection with the contaminated drug. The clinical findings are often subtle and similar to those that led the patient to undergo the methylprednisolone injection. To determine if patients who had not presented for medical care but who had received contaminated methylprednisolone developed spinal or paraspinal infection at the injection site using contrast-enhanced magnetic resonance imaging (MRI) screening. There were 172 patients who had received an injection of contaminated methylprednisolone from a highly contaminated lot (No. 06292012@26) at a pain facility but had not presented for medical care related to adverse effects after the injection. Screening MRI was performed between November 9, 2012, and April 30, 2013. MAIN OUTCOMES AND MEASURES: Number of persons identified with previously undiagnosed spinal or paraspinal infection. Of the 172 patients screened, MRI was abnormal in 36 (21%), showing epidural or paraspinal abscess or phlegmon, arachnoiditis, spinal osteomyelitis or diskitis, or moderate to severe epidural, paraspinal, or intradural enhancement. Of the 115 patients asked about new or worsening back or neck pain, lower extremity weakness, or radiculopathy symptoms, 35 (30%) had at least 1 symptom. Thirty-five of the 36 patients with abnormal MRIs met the Centers for Disease Control and Prevention (CDC) case definition for probable (17 patients) or confirmed (18 patients) fungal spinal or paraspinal infection. All 35 patients were treated with antifungal agents (voriconazole, with or without liposomal amphotericin B), and 24 required surgical debridement. At the time of surgery, 17 of 24 patients (71%), including 5 patients who denied having symptoms, had laboratory evidence of fungal infection. Among patients who underwent screening MRI to look for infection at the site of injection of contaminated methylprednisolone, 21% had an abnormal MRI, and all but one met CDC criteria for probable or confirmed fungal spinal or paraspinal infection. Screening MRI led to identification of patients who had minimal or no symptoms of spinal or paraspinal infection and allowed early initiation of medical and surgical treatment.
    JAMA The Journal of the American Medical Association 06/2013; 309(23):2465-72. DOI:10.1001/jama.2013.6293 · 29.98 Impact Factor
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    ABSTRACT: (See the commentary by Gilligan, on pages 22-23 .) Objective. To determine relative rates of blood culture contamination for 3 skin antisepsis interventions-10% povidone iodine aqueous solution (PI), 2% iodine tincture (IT), and 2% chlorhexidine gluconate in 70% isopropyl alcohol (CHG)-when used by dedicated phlebotomy teams to obtain peripheral blood cultures. Design. Randomized crossover trial with hospital floor as the unit of randomization. Setting. Teaching hospital with 885 beds. Patients. All adult patients undergoing peripheral blood culture collection on 3 medical-surgical floors from May 2009 through September 2009. Intervention. Each antisepsis intervention was used for 5 months on each study floor, with random crossover after a 1-month washout period. Phlebotomy teams collected all peripheral blood cultures. Each positive blood culture was adjudicated by physicians blinded to the intervention and scored as a true positive or contaminated blood culture. The primary outcome was the rate of blood culture contamination for each antisepsis agent. Results. In total, 12,904 peripheral blood culture sets were evaluated, of which 735 (5.7%) were positive. There were 98 contaminated cultures, representing 13.3% of all positive cultures. The overall blood culture contamination rate for the study population was 0.76%. Intent-to-treat rates of contaminated blood cultures were not significantly different among the 3 antiseptics ([Formula: see text]), yielding 0.58% with PI (95% confidence interval [CI], 0.38%-0.86%), 0.76% with IT (95% CI, 0.52%-1.07%), and 0.93% with CHG (95% CI, 0.67%-1.27%). Conclusion. Choice of antiseptic agent does not impact contamination rates when blood cultures are obtained by a phlebotomy team and should, therefore, be based on costs or preference. Trial registration. ClinicalTrials.gov identifier: NCT01216761 .
    Infection Control and Hospital Epidemiology 01/2013; 34(1):15-21. DOI:10.1086/668777 · 4.02 Impact Factor
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    ABSTRACT: BACKGROUND: Data from community antimicrobial stewardship programs (ASPs) are limited. We describe clinical and economic outcomes from the first year of our hospital's ASP. METHODS: The ASP team comprised 2 infectious disease physicians and 3 intensive care unit pharmacists. The team prospectively audited the new starts and weekly use of 8 target antimicrobials: aztreonam, caspofungin, daptomycin, ertapenem, linezolid, meropenem, tigecycline, and voriconazole. Using administrative data, outcomes from the first year of the program, including death within 30 days of hospitalization, readmission within 30 days of discharge, and development of Clostridium difficile infection (CDI), were compared with outcomes from a similar period before institution of the program. RESULTS: A total of 510 antimicrobial orders were reviewed, of which 323 (63%) were appropriate, 94 (18%) prompted deescalation, 61 (12%) were denied, and 27 (5%) led to formal consultation with an infectious disease physician. On multivariate analysis, implementation of the ASP was associated with an approximate 50% reduction in the odds of developing CDI (odds ratio, 0.46; 95% confidence interval, 0.25-0.82). The ASP was not associated with decreased mortality at 30 days after discharge or readmission rate. The antimicrobial cost per patient-day decreased by 13.3%, from $10.16 to $8.81. The antimicrobial budget decreased by 15.2%, resulting in a total savings of $228,911. There was a 25.4% decrease in defined daily doses of the target antimicrobials. CONCLUSIONS: Implementation of the ASP was associated with significant reductions in CDI rate, antimicrobial use, and pharmacy costs.
    American journal of infection control 05/2012; 41(2). DOI:10.1016/j.ajic.2012.02.021 · 3.01 Impact Factor
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    ABSTRACT: Long-term acute care (LTAC) facilities admit patients with complex, advanced disease states. Study aims were to determine the burden posed on hospitals associated with LTAC exposure and analyze the differences between "present on admission" (POA) multidrug-resistant (MDR), gram-negative organisms (GNO) and POA MDR gram-positive organisms (GPO). A multicenter retrospective study was conducted in 13 hospitals from southeast Michigan, from September 1, 2008, to August 31, 2009. Cultures obtained in the first 72 hours of hospitalization (ie, POA) of MDR-GPO and MDR-GNO were reviewed. LTAC exposures in the previous 6 months and direct admission from a LTAC were recorded. Overall, 5,297 patients with 7,147 MDR POA cultures were analyzed: 2,619 (36.6%) were MDR-GNO, and 4,528 (63.4%) were MDR-GPO. LTAC exposure in the past 6 months was present in 251 (5.2%) infectious episodes and was significantly more common among POA MDR-GNO than MDR-GPO (158 [8.6%] and 94 [3.1%], respectively, odds ratio, 2.87; P < .001). Recent LTAC exposure was strongly associated with both carbapenem-resistant Enterobacteriaceae (CRE) (31.6% of all CRE cases, P < .001) and Acinetobacter baumannii (14.9% of all A baumannii cases, P < .001). Nearly 10% of MDR-GNO POA had recent LTAC exposure. Hospital efforts to control the spread of MDR-GNO should focus on collaborations and communications with referring LTACs and interventions targeted towards patients with recent LTAC exposure.
    American journal of infection control 01/2012; 40(8):760-5. DOI:10.1016/j.ajic.2011.09.011 · 3.01 Impact Factor
  • Rajasekhar Jagarlamudi, Anurag N. Malani
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    ABSTRACT: Two siblings presented with fever and gastrointestinal symptoms, including abdominal pain. Imaging studies of the liver and spleen revealed hypoechoic lesions. Liver biopsy demonstrated granulomatous lesions DNA polymerase chain reaction positive for Bartonella henselae. Bartonella immunoglobulin M and immunoglobulin G antibody testing were positive. Both patients responded to antibiotics active against Bartonella henselae.
    Infectious Disease in Clinical Practice 01/2012; 20(4):278-279. DOI:10.1097/IPC.0b013e3182424151
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    ABSTRACT: 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.
    Mycoses 11/2011; 54(6):531-7. DOI:10.1111/j.1439-0507.2010.01941.x · 1.81 Impact Factor
  • Anurag N. Malani
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    Emerging Infectious Diseases 08/2009; 15(8):1328-30. DOI:10.3201/eid1508.081635 · 7.33 Impact Factor
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    Anurag N Malani, David M Aronoff
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    ABSTRACT: 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.
    Clinical Medicine &amp Research 10/2008; 6(2):83-5. DOI:10.3121/cmr.2008.806

Publication Stats

386 Citations
231.70 Total Impact Points

Institutions

  • 2014
    • Wayne State University
      Detroit, Michigan, United States
    • St Joseph Mercy Oakland
      Pontiac, Michigan, United States
  • 2012–2014
    • Saint Joseph Mercy Health System
      Canton, Michigan, United States
  • 2007–2008
    • University of Michigan
      • Division of Infectious Diseases
      Ann Arbor, Michigan, United States