Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk.

Choice of Intravenous Crystalloid Fluid and Mortality in Critically Ill Adult Patients.

OBJECTIVES: Intravenous balanced crystalloid fluid therapy may improve mortality and other outcomes in critically ill adult patients, but data are conflicting. We conducted a meta-analysis and literature review to evaluate the impact of intravenous balanced crystalloid, as compared with normal saline, fluid therapy on outcomes in critically ill adult patients. METHODS: We searched PubMed, Scopus, MEDLINE, and the Cochrane Register of Clinical Trials for relevant studies. Randomized controlled trials comparing the effects of balanced intravenous crystalloids with normal saline on intensive care unit (ICU) or hospital mortality were included. Pooled risk ratios (RRs) were calculated using a fixed effects model. Heterogeneity was calculated using the I2 statistic. The risk of bias was assessed using the Cochrane tool. RESULTS: Seven randomized controlled trials with 20,171 patients (10,179 participants received balanced crystalloids and 9992 participants received normal saline) were included. For hospital mortality, the pooled RR (95% confidence interval [CI]) was 0.92 (0.85-1.00). For ICU mortality, the pooled RR (95% CI) was 0.91 (0.82-1.00). For major adverse kidney events at 30 days, pooled RR (95% CI) was 0.95 (0.88-1.01). For stage ≥2 acute kidney injury, the pooled RR (95% CI) was 0.94 (0.86-1.02). For receipt of new renal replacement therapy, the pooled RR (95% CI) was 0.91 (0.77-1.07). None of these findings reached statistical significance. CONCLUSIONS: Intravenous balanced crystalloid use, compared with normal saline, does not result in a statistically significant reduction in hospital or ICU mortality, major adverse kidney events at 30 days, stage ≥2 acute kidney injury, or receipt of new renal replacement therapy in critically ill adult patients.

Possible Transfusion-Transmitted Babesia divergens-like/MO-1 Infection in an Arkansas Patient.

A patient with asplenia and multiple red blood cell transfusions acquired babesiosis infection with Babesia divergens-like/MO-1 organisms and not Babesia microti, the common United States species. He had no known tick exposure. This is believed to be the first transfusion-transmitted case and the fifth documented case of B. divergens-like/MO-1 infection.

The endemic mimic: blastomycosis an illness often misdiagnosed.

One of the endemic fungi, Blastomyces dermatitidis, can cause epidemics of infection with multiple persons involved in a point source outbreak but more commonly causes sporadic cases of infection within the areas of endemicity. Blastomycosis can present as an acute pneumonia which is often misdiagnosed as acute pneumococcal pneumonia or the infection may present as a chronic pneumonia along with weight loss, night sweats, hemoptysis, and a lung mass suggesting tuberculosis or carcinoma of the lung. Extrapulmonary infection with B. dermatitidis is protean with many different manifestations. Most commonly, skin or subcutaneous lesions are found with either a verrucous or warty appearance or in an ulcerative form. Cases have been misidentified as keratoacanthoma, pyoderma gangrenosum, carcinoma, or as Weber-Christian panniculitis if there are nodular subcutaneous lesions. Essentially any site or organ can have lesions of disseminated blastomycosis. In our series, cases of laryngeal carcinoma, adrenal insufficiency, thyroid nodules, granulomatous hypercalcemia, abnormal mammograms thought to represent breast carcinoma, otitis media with cranial extension, immune thrombocytopenic purpura, and hemolytic anemia of unknown cause have been misdiagnosed and blastomycosis subsequently identified as the cause. This infection causes manifestations which mimic many other more commonly diagnosed conditions and must always be considered by clinicians practicing in the endemic region.

Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era.

BACKGROUND: Central nervous system (CNS) involvement with Blastomyces dermatitidis is an uncommon and potentially fatal complication of blastomycosis. METHODS: We retrospectively reviewed 22 patients with CNS blastomycosis at our institutions from 1990 through 2008 (13 proven, 5 probable, and 4 possible cases). RESULTS: Magnetic resonance imaging was used in most patients, alone or in addition to computed tomography. CNS blastomycosis manifested as epidural abscess (1 of 22), meningitis (7 of 22), intracranial mass lesions (10 of 22), and concomitant intracranial mass lesions and meningitis (4 of 22). All patients received amphotericin B deoxycholate or a lipid formulation of amphotericin B as part of their treatment regimens. Most patients received amphotericin B followed by a prolonged course of oral azole therapy (voriconazole, fluconazole, or itraconazole). Four (18%) of 22 patients died during follow-up. CONCLUSIONS: On the basis of these data, we recommend initial treatment with a lipid formulation of amphotericin B followed by a prolonged course of oral azole therapy, preferably voriconazole.

A clinical review of Lyme disease in Arkansas.

Lyme disease is the most common tick-borne disease in the northern hemisphere. Since it was first described more than 30 years ago, Lyme disease has generated a great deal of controversy. Lyme disease is not endemic in Arkansas, and testing for Borrelia burgdorferi can lead to clinical confusion, unnecessary treatment and excess cost. This article will present a brief review of Lyme disease, with an emphasis on what is known regarding Lyme disease in Arkansas.

Serendipitous Treatment of Tularemia in Pregnancy.

We present a young pregnant woman who developed ulceroglandular tularaemia following a bite wound from a kitten. She grew Francisella tularensis from the ulcer. While awaiting bacterial culture results and serology for Bartonella, she was treated with azithromycin, with resolution of fever and axillary tenderness. Treatment recommendations for tularemia are either gentamicin or doxycycline, both of which can be perilous to the fetus. A Centers for Disease Control and Prevention report on the macrolide susceptibility of North American isolates of this organism has been underappreciated. The unanticipated result from this patient may give another potential option for treatment of tularemia in pregnancy.

Clinical practice guidelines for the management of blastomycosis: 2008 update by the Infectious Diseases Society of America.

Evidence-based guidelines for the management of patients with blastomycosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous management guidelines published in the April 2000 issue of Clinical Infectious Diseases. The guidelines are intended for use by health care providers who care for patients who have blastomycosis. Since 2000, several new antifungal agents have become available, and blastomycosis has been noted more frequently among immunosuppressed patients. New information, based on publications between 2000 and 2006, is incorporated in this guideline document, and recommendations for treating children with blastomycosis have been noted.

Community-onset methicillin-resistant Staphylococcus aureus skin and soft-tissue infections: impact of antimicrobial therapy on outcome.

BACKGROUND: Conflicting data exist on the role of antimicrobial therapy for the treatment of uncomplicated community-onset methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTIs). METHODS: We performed a retrospective cohort study of 492 adult patients with 531 independent episodes of community-onset MRSA SSTIs, which consisted of abscesses, furuncles/carbuncles, and cellulitis, at 2 tertiary care medical centers. The purpose of the study was to determine the impact of active antimicrobial therapy (i.e., the use of an agent to which the organism is susceptible) and other potential risk factors on the outcome for patients with uncomplicated community-onset MRSA SSTIs. Treatment failure was the primary outcome of interest and was defined as worsening signs of infection associated with microbiological and/or therapeutic indicators of an unsuccessful outcome. Bivariate analyses and logistic regression analyses were preformed to determine predictors of treatment failure. RESULTS: An incision and drainage procedure was performed for the majority of patients. Treatment failure occurred in 45 (8%) of 531 episodes of community-onset MRSA SSTI. Therapy was successful for 296 (95%) of 312 patients who received an active antibiotic, compared with 190 (87%) of 219 of those who did not (P=.001 in bivariate analysis). Use of an inactive antimicrobial agent was an independent predictor of treatment failure on logistic regression analysis (adjusted odds ratio, 2.80; 95% confidence interval, 1.26-6.22; P=.01). CONCLUSIONS: Our findings suggest that certain patients with SSTIs that are likely caused by MRSA would benefit from treatment with an antimicrobial agent with activity against this organism.

Intermediate care to intensive care triage: A quality improvement project to reduce mortality.

PURPOSE: Medical patients whose care needs exceed what is feasible on a general ward, but who do not clearly require critical care, may be admitted to an intermediate care unit (IMCU). Some IMCU patients deteriorate and require medical intensive care unit (MICU) admission. In 2012, staff in the Johns Hopkins IMCU expressed concern that patient acuity and the threshold for MICU admission were too high. Further, shared triage decision-making between residents and supervising physicians did not consistently occur. METHODS: To improve our triage process, we used a 4Es quality improvement framework (engage, educate, execute, evaluate) to (1) educate residents and fellows regarding principles of triage and (2) facilitate real-time communication between MICU residents conducting triage and supervising physicians. RESULTS: Among patients transferred from the IMCU to the MICU during baseline (n=83;July-December 2012) and intervention phases (n=94;July-December 2013), unadjusted mortality decreased from 34% to 21% (p=0.06). After adjusting for severity of illness, admitting diagnosis, and bed availability, the odds of death were lower during the intervention vs. baseline phase (OR 0.33; 95%CI 0.11-0.98). CONCLUSIONS: Using a structured quality improvement process targeting triage education and increased resident/supervisor communication, we demonstrated reduced mortality among patients transferred from the IMCU to the MICU.

Outcomes of Emergency Medical Patients Admitted to an Intermediate Care Unit With Detailed Admission Guidelines.

BACKGROUND: An important, but not well characterized, population receiving intermediate care is that of medical patients admitted directly from the emergency department. OBJECTIVE: To characterize emergency medical patients and their outcomes when admitted to an intermediate care unit with clearly defined admission guidelines. METHODS: Demographic data, admitting diagnoses, illness severity, comorbid conditions, lengths of stay, and hospital mortality were characterized for all emergency medical patients admitted directly to an intermediate care unit from July through December 2012. RESULTS: A total of 317 unique patients were admitted (mean age, 54 [SD, 16] years). Most patients were admitted with respiratory (26.5%) or cardiac (17.0%) syndromes. The mean (SD) Acute Physiology and Chronic Health Evaluation score version II, Simplified Acute Physiology Score version II, and Charlson Comorbidity Index were 15.6 (6.5), 20.7 (11.8), and 2.7 (2.3), respectively. Severity of illness and length of stay were significantly different for patients who required intensive care within 24 hours of admission (n = 16) or later (n = 25), patients who continued with inter mediate care for more than 24 hours (n = 247), and patients who were downgraded or discharged in less than 24 hours (n = 29). Overall hospital mortality was 4.4% (14 deaths). CONCLUSIONS: Emergency medical patients with moderate severity of illness and comorbidity can be admitted to an intermediate level of care with relatively infrequent transfer to intensive care and relatively low mortality.

Use of long-acting tetracyclines for methicillin-resistant Staphylococcus aureus infections: case series and review of the literature.

BACKGROUND: Few data exist on the efficacy of the long-acting tetracyclines doxycycline and minocycline against methicillin-resistant Staphylococcus aureus (MRSA) infection. METHODS: The medical records of 24 patients with serious tetracycline-susceptible MRSA infections who were treated with doxycycline or minocycline were reviewed. A review of the literature on the use of these antibiotics for treatment of both methicillin-susceptible and methicillin-resistant S. aureus infection was also performed. RESULTS: Complicated skin and skin-structure infections were most common (67%). Clinical cure was achieved in 20 (83%) of 24 patients in our case series. Both drugs were well-tolerated. The review of the literature on a total of 85 patients with S. aureus infection revealed similar results. CONCLUSIONS: Long-acting tetracyclines may be a reasonable treatment alternative for patients with certain types of MRSA infection.

A randomized and blinded multicenter trial of high-dose fluconazole plus placebo versus fluconazole plus amphotericin B as therapy for candidemia and its consequences in nonneutropenic subjects.

A randomized, blinded, multicenter trial was conducted to compare fluconazole (800 mg per day) plus placebo with fluconazole plus amphotericin B (AmB) deoxycholate (0.7 mg/kg per day, with the placebo/AmB component given only for the first 5-6 days) as therapy for candidemia due to species other than Candida krusei in adults without neutropenia. A total of 219 patients met criteria for a modified intent-to-treat analysis. The groups were similar except that those who were treated with fluconazole plus placebo had a higher mean (+/- standard error) Acute Physiology and Chronic Health Evaluation II score (16.8+/-0.6 vs. 15.0+/-0.7; P=.039). Success rates on study day 30 by Kaplan-Meier time-to-failure analysis were 57% for fluconazole plus placebo and 69% for fluconazole plus AmB (P=.08). Overall success rates were 56% (60 of 107 patients) and 69% (77 of 112 patients; P=.043), respectively; the bloodstream infection failed to clear in 17% and 6% of subjects, respectively (P=.02). In nonneutropenic subjects, the combination of fluconazole plus AmB was not antagonistic compared with fluconazole alone, and the combination trended toward improved success and more-rapid clearance from the bloodstream.

Use of DNA fingerprinting in decision making for considering closure of neonatal intensive care units because of Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: Bloodstream infections with Pseudomonas aeruginosa have been well-described in neonatal intensive care units (NICU) and have resulted in the temporary closure of some nurseries to new admissions. Nosocomial transmission of these infections has been verified by fingerprint analysis of the isolates. We utilized molecular fingerprinting to identify the source of bloodstream infections in an NICU and used this information to apply infection control measures that allowed the nursery to stay open and continue to accept referrals. METHODS: In June 1998 three premature infants transferred to our hospital (Hospital A) from Hospitals B and C had bloodstream infections with P. aeruginosa. Subsequently one additional neonate transferred from Hospital B was colonized with P. aeruginosa. Random amplification of polymorphic deoxyribonucleic acid (RAPD) was performed on the four isolates. All transfers from Hospital B were cultured, and surveillance programs were instituted in Hospitals A and B. Targeted infection control measures for all transfers were implemented. RESULTS: The four isolates were the same clone by RAPD. Investigation of the environment in Hospital A did not identify any source of the organism. Surveillance cultures on 49 neonates at Hospital A revealed only one patient colonized at an endotracheal tube. This patient was also a transfer from Hospital B. Results from Hospital B identified 4 of 40 (10%) neonates colonized. All isolates were clones identical with the bloodstream isolates from the neonates with bloodstream infections. Infection control measures for all babies transferred from Hospital B resulted in no new cases of P. aeruginosa bacteremia during the next 5 years. CONCLUSIONS: The use of molecular fingerprinting of isolates of P. aeruginosa allowed for a prompt and directed infection control plan to be implemented in Hospitals A and B. It also allowed the NICU in Hospital A to continue to accept referrals from other hospitals and to implement a targeted infection control plan for patients transferred from Hospital B.

Blastomycosis.

Blastomycosis is an endemic mycoses in the central United States caused by a dimorphic fungus, Blastomyces dermatitidis, that exists in nature in mycelial phase and converts to yeast phase at body temperature. The organism may produce epidemics of infection following a point source of infection or sporadic endemic infection. Blastomycosis can be a subclinical illness with subsequent protection against progressive infection afforded by cellular immune mechanisms, but it may present with progressive disease with either pulmonary or extrapulmonary disease or both. Itraconazole has been shown to be the drug of choice for both infections, except in cases of life-threatening infection when amphotericin B should be used.

Blastomyces dermatitidis antigen detection by quantitative enzyme immunoassay.

The second-generation MVista Blastomyces antigen enzyme immunoassay was not quantitative; therefore, specimens obtained previously were tested in the same assay as new specimens to assess the change in antigen levels. Furthermore, the sensitivity in serum had not been fully evaluated. The purpose of this study was to evaluate a quantitative Blastomyces antigen assay and detection of antigen in serum. Calibrators containing known concentrations of Blastomyces galactomannan were used to quantify antigen in urine and serum from patients with proven blastomycosis and from controls. Paired current and previously obtained urine specimens were tested to determine if quantification eliminated the need for concurrent testing to assess change in antigen. Pretreatment of serum with EDTA at 104°C was evaluated to determine if dissociation of immune complexes improved detection of antigenemia. Antigenuria was detected in 89.9% of patients with culture- or histopathology-proven blastomycosis. Specificity was 99.0% in patients with nonfungal infections and healthy subjects, but cross-reactions occurred in 95.6% of patients with histoplasmosis. Change in antigen level categorized as increase, no change, or decrease based on antigen units determined in the same assay agreed closely with the category of change in ng/ml determined from different assays. Pretreatment increased the sensitivity of detection of antigenemia from 35.7% to 57.1%. Quantification eliminated the need for concurrent testing of current and previously obtained specimens for assessment of changes in antigen concentration. Pretreatment increased the sensitivity for detection of antigenemia. Differentiation of histoplasmosis and blastomycosis is not possible by antigen detection.

Detection of Blastomyces dermatitidis antigen in patients with newly diagnosed blastomycosis.

Blastomycosis is a serious and potentially fatal infection, and diagnosis can be difficult at times. We evaluated the diagnostic utility of a commercially available assay for detection of Blastomyces dermatitidis antigen, recently modified to permit quantitation, in subjects with newly diagnosed blastomycosis. Twenty-three of 27 (85.1%) subjects had detectable B. dermatitidis antigenuria. In 2 of these 23, positive results were obtained after concentration of the urine specimen. Nine of 11 (81.8%) subjects had detectable B. dermatitidis antigen in serum, including 3 subjects with negative results before treatment of serum with ethylenediaminetetraacetic acid (EDTA) and positive results after EDTA treatment. B. dermatitidis antigen was not detected in specimens from 50 control subjects but was detected in 15 patients with histoplasmosis. B. dermatitidis antigen was detected in most of the patients with blastomycosis and can be a useful tool for timely diagnosis.