Relationship between Motor Corticospinal System, Endogenous Pain Modulation Mechanisms and Clinical Symptoms in Patients with Knee Osteoarthritis: New Perspectives on an Old Disease.

Knee osteoarthritis (OA) is a painful condition characterized by joint and bone changes. A growing number of studies suggest that these changes only partially explain the pain experienced by individuals with OA. The purpose of the current study was to evaluate if corticospinal and bulbospinal projection measurements were interrelated in patients with knee OA, and to explore the relationship between these neurophysiological measures and temporal summation (excitatory mechanisms of pain) on one hand, and clinical symptoms on the other. Twenty-eight (28) patients with knee OA were recruited. Corticospinal projections were measured using transcranial magnetic stimulation, while bulbospinal projections were evaluated with a conditioned pain modulation (CPM) protocol using a counter-irritation paradigm. Validated questionnaires were used to document clinical and psychological manifestations. All participants suffered from moderate to severe pain. There was a positive association between corticospinal excitability and the effectiveness of the CPM (rs = 0.67, p = 0.01, n = 13). There was also a positive relationship between pain intensity and corticospinal excitability (rs = 0.45, p = 0.03, n = 23), and between pain intensity and temporal summation (rs = 0.58, p = 0.01, n = 18). The results of this study highlight some of the central nervous system changes that could be involved in knee OA and underline the importance of interindividual variability to better understand and explain the semiology and pathophysiology of knee OA.

The influence of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation in healthy participants: A cross sectional study.

OBJECTIVES: Several studies suggest that acute pain decreases corticomotor excitability. However, the variability between patients remains important and unexplained. The aim of this study was to unveil potential sources of variation by looking at the effect of kinesiophobia and pain catastrophizing on pain-induced corticomotor modulation. METHODS: Corticomotor excitability was assessed with the slopes of recruitment curves measured from the first dorsal interosseous elicited by transcranial magnetic stimulation before and during pain induced by capsaicin application on the forearm. Participants completed the Tampa Scale for Kinesiophobia (TSK) and the Pain Catastrophizing Scale (PCS). RESULTS: Twenty-four persons participated in the study. There was a moderate and positive correlation between individual changes in the slope of the recruitment curves and TSK questionnaire scores (rs=0.47; p = 0.02). During the painful condition, unlike those with higher TSK scores, participants with lower TSK scores demonstrated recruitment curves with reduced slopes compared to baseline. There was a difference between changes in the slopes of recruitment curves between individuals with "highest" vs. "lowest" kinesiophobia scores (p = 0.01). No relationship was observed between changes in the slopes of the recruitment curves and PCS scores (p = 0.20). DISCUSSION: The results suggest that kinesiophobia may affect neuromotor processes and influence the corticomotor pain response. CONCLUSIONS: Higher kinesiophobia scores during experimental induced pain were associated with smaller decreases in the slopes of recruitment curves. These findings suggest that there is less inhibition of corticospinal excitability in participants with greater TKS scores.

Training muscle activation patterns of the lower paretic extremity using directional exertion improves mobility in persons with hemiparesis: a pilot study.

BACKGROUND: Controlled static exertion performed in the sagittal plane on a transducer attached to the foot requires coordinated moments of force of the lower extremity. Some exertions and plantarflexion recruit muscular activation patterns similar to synergies previously identified during gait. It is currently unknown if persons with hemiparesis following stroke demonstrate similar muscular patterns, and if force feedback training utilizing static exertion results in improved mobility in this population. METHODS: Electromyographic (EMG) activity of eight muscles of the lower limb were recorded using surface electrodes in healthy participants (n = 10) and in persons with hemiparesis (n = 8) during an exertion exercise (task) performed in eight directions in the sagittal plane of the foot and a plantarflexion exercise performed at 20 and 40% maximum voluntary effort (MVE). Muscle activation patterns identified during these exertion exercises were compared between groups and to synergies reported in the literature during healthy gait using cosine similarities (CS). Functional mobility was assessed in four participants with hemiparesis using GAITRite® and the Timed Up and Go (TUG) test at each session before, during and after static force feedback training. Tau statistics were used to evaluate the effect on mobility before and after training. Measures of MVE and the accuracy of directional exertion were compared before and after training using ANOVAs. Spearman Rho correlations were also calculated between changes in these parameters and changes in mobility before and after the training. RESULTS: Muscle activation patterns during directional exertion and plantarflexion were similar for both groups of participants (CS varying from 0.845 to 0.977). Muscular patterns for some of the directional and plantarflexion were also similar to synergies recruited during gait (CS varying from 0.847 to 0.951). Directional exertion training in hemiparetic subjects resulted in improvement in MVE (p < 0.040) and task performance accuracy (p < 0.001). Hemiparetic subjects also demonstrated significant improvements in gait velocity (p < 0.032) and in the TUG test (p < 0.022) following training. Improvements in certain directional efforts were correlated with changes in gait velocity (p = 0.001). CONCLUSION: Static force feedback training following stroke improves strength and coordination of the lower extremity while recruiting synergies reported during gait and is associated with improved mobility.

Invasive infections with Purpureocillium lilacinum: clinical characteristics and outcome of 101 cases from FungiScope® and the literature.

OBJECTIVES: To provide a basis for clinical management decisions in Purpureocillium lilacinum infection. METHODS: Unpublished cases of invasive P. lilacinum infection from the FungiScope® registry and all cases reported in the literature were analysed. RESULTS: We identified 101 cases with invasive P. lilacinum infection. Main predisposing factors were haematological and oncological diseases in 31 cases (30.7%), steroid treatment in 27 cases (26.7%), solid organ transplant in 26 cases (25.7%), and diabetes mellitus in 19 cases (18.8%). The most prevalent infection sites were skin (n = 37/101, 36.6%) and lungs (n = 26/101, 25.7%). Dissemination occurred in 22 cases (21.8%). Pain and fever were the most frequent symptoms (n = 40/101, 39.6% and n = 34/101, 33.7%, respectively). Diagnosis was established by culture in 98 cases (97.0%). P. lilacinum caused breakthrough infection in 10 patients (9.9%). Clinical isolates were frequently resistant to amphotericin B, whereas posaconazole and voriconazole showed good in vitro activity. Susceptibility to echinocandins varied considerably. Systemic antifungal treatment was administered in 90 patients (89.1%). Frequently employed antifungals were voriconazole in 51 (56.7%) and itraconazole in 26 patients (28.9%). Amphotericin B treatment was significantly associated with high mortality rates (n = 13/33, 39.4%, P = <0.001). Overall mortality was 21.8% (n = 22/101) and death was attributed to P. lilacinum infection in 45.5% (n = 10/22). CONCLUSIONS: P. lilacinum mainly presents as soft-tissue, pulmonary or disseminated infection in immunocompromised patients. Owing to intrinsic resistance, accurate species identification and susceptibility testing are vital. Outcome is better in patients treated with triazoles compared with amphotericin B formulations.

Pain interference may be an important link between pain severity, impairment, and self-reported disability in participants with wrist/hand pain.

STUDY DESIGN: Cross-sectional. INTRODUCTION: Pain severity, sensory and motor impairment, and psychological (distress and anxiety) and social factors have previously been related to self-reported disability in persons with wrist and hand pain. PURPOSE OF THE STUDY: The purpose of this study to determine the relative contribution of pain severity, measures of impairment (sensory and motor function), psychosocial factors, and pain interference on self-reported disability experienced by persons with heterogeneous orthopedic injuries and conditions of the wrist and hand. METHODS: Measures of disability and pain severity as well as measures of sensory (pressure pain thresholds, joint position sense), motor (grip strength, Purdue pegboard), and cognitive performance (Stroop test) and psychosocial variables related to pain and participation (West Haven-Yale Multidimensional Pain Inventory) were administered to 60 participants with wrist and hand pain. Pearson product correlations controlled for age and sex, and multiple linear regression was performed to determine the relationship between measures of impairment, pain severity, psychosocial variables, and pain interference with self-reported disability assessed with the Disability of Arm, Shoulder and Hand (DASH) questionnaire. RESULTS: The best-fitting regression model with DASH scores entered as the dependent variable (F4,50 = 28.8, P < .01) included MPI Pain Interference (ß = -0.54), Life Control (ß = -0.16), Purdue pegboard scores (ß = -0.32), and Stroop test times (ß = 0.21). Pain Interference had the strongest correlation with self-reported disability (adjusted R2 = 0.67, P < .01). CONCLUSION: Pain interference appears to be an important factor explaining the link between impairment, pain severity, and self-reported disability. Addressing pain interference may be important to improve outcomes in this population.

Bilateral sensory and motor as well as cognitive differences between persons with and without musculoskeletal disorders of the wrist and hand.

BACKGROUND: Sensory and motor disturbances are characteristic of musculoskeletal injuries and conditions. Rehabilitation interventions aimed at remediating these disturbances are traditionally exclusively targeted to the affected area. However, there is some evidence of bilateral changes in sensory and motor function associated with unilateral injuries and conditions suggesting central changes. Deficits on specific cognitive tasks have also been documented in persons with chronic pain. PURPOSE: The purpose of the present study was to determine if participants with unilateral pain arising from heterogeneous wrist/hand injuries and conditions demonstrate bilateral changes in sensory and motor functions as well as cognitive deficits. DESIGN/METHODS: Sensory (Pressure Pain Thresholds, Two Point Orientation Discrimination), Motor (grip strength and Purdue Pegboard), and Cognitive function (Stroop test and mental rotation task) were measured in 30 participants with wrist/hand pain and 30 healthy control participants in an observational cross-sectional study. RESULTS: Participants with unilateral wrist/hand pain demonstrated differences in cognitive function measured with the Stroop test (p = 0.03). They also demonstrated bilateral sensorimotor differences in pressure pain thresholds (p = 0.03), grip strength (p = 0.00) and Purdue pegboard test (p = 0.03) results compared to healthy control participants. CONCLUSION: Cognitive as well as bilateral alterations in sensory and motor function in participants with musculoskeletal injuries and conditions suggest central changes are involved in their pathophysiology. These findings in persons with heterogeneous injuries/conditions suggest that these changes are not specific to an injury/condition. Bilateral sensorimotor changes have important implications with regards to the pathophysiology of musculoskeletal disorders of the wrist/hand, for rehabilitative interventions and research.

Left Right Judgement Task and Sensory, Motor, and Cognitive Assessment in Participants with Wrist/Hand Pain.

The Left Right Judgement Task (LRJT) involves determining if an image of the body part is of the left or right side. The LRJT has been utilized as part of rehabilitation treatment programs for persons with pain associated with musculoskeletal injuries and conditions. Although studies often attribute changes and improvement in LRJT performance to an altered body schema, imaging studies suggest that the LRJT implicates other cortical regions. We hypothesized that cognitive factors would be related to LRJT performance of hands and feet and that sensory, motor, and pain related factors would be related to LRJT in the affected hand of participants with wrist/hand pain. In an observational cross-sectional study, sixty-one participants with wrist/hand pain participated in a study assessing motor imagery ability, cognitive (Stroop test), sensory (Two-Point Orientation Discrimination, pressure pain thresholds), motor (grip strength, Purdue Pegboard Test), and pain related measures (West Haven Yale Multidimensional Pain Inventory) as well as disability (Disability of the Arm, Shoulder and Hand). Multiple linear regression found Stroop test time and motor imagery ability to be related to LRJT performance. Tactile acuity, motor performance, participation in general activities, and the taking of pain medications were predictors of LRJT accuracy in the affected hand. Participants who took pain medications performed poorly in both LRJT accuracy (p=0.001) and reaction time of the affected hand (p=0.009). These participants had poorer cognitive (p=0.013) and motor function (p=0.002), and higher pain severity scores (p=0.010). The results suggest that the LRJT is a complex mental task that involves cognitive, sensory, motor, and behavioural processes. Differences between persons with and without pain and improvement in LRJT performance may be attributed to any of these factors and should be considered in rehabilitation research and practice utilizing this task.

Pain-related psychological issues in hand therapy.

STUDY DESIGN: Literature review. INTRODUCTION: Pain is a subjective experience that results from the modulation of nociception conveyed to the brain via the nervous system. Perception of pain takes place when potential or actual noxious stimuli are appraised as threats of injury. This appraisal is influenced by one's cognitions and emotions based on her/his pain-related experiences, which are processed in the forebrain and limbic areas of the brain. Unarguably, patients' psychological factors such as cognitions (eg, pain catastrophizing), emotions (eg, depression), and pain-related behaviors (eg, avoidance) can influence perceived pain intensity, disability, and treatment outcomes. Therefore, hand therapists should address the patient pain experience using a biopsychosocial approach. However, in hand therapy, a biomedical perspective predominates in pain management by focusing solely on tissue healing. PURPOSE OF THE STUDY: This review aims to raise awareness among hand therapists of the impact of pain-related psychological factors. METHODS AND RESULTS: This literature review allowed to describe (1) how the neurophysiological mechanisms of pain can be influenced by various psychological factors, (2) several evidence-based interventions that can be integrated into hand therapy to address these psychological issues, and (3) some approaches of psychotherapy for patients with maladaptive pain experiences. DISCUSSION AND CONCLUSION: Restoration of sensory and motor functions as well as alleviating pain is at the core of hand therapy. Numerous psychological factors including patients' beliefs, cognitions, and emotions alter their pain experience and may impact on their outcomes. Decoding the biopsychosocial components of the patients' pain is thus essential for hand therapists.

Laterality recognition of images, motor performance, and aspects related to pain in participants with and without wrist/hand disorders: An observational cross-sectional study.

OBJECTIVE: Musculoskeletal disorders are associated with altered sensory, proprioceptive and cognitive processes. Sensory processes affect the internal cortical representation of the body in space, the body schema, which in turn influences motor control. The purpose of this study was to determine if participants with wrist/hand disorders had impaired performance on a task associated with the body schema, the Left/Right Judgement Task (LRJT) and secondly how LRJT performance, motor performance, disability, pain and related aspects are associated. METHODS: Fifteen healthy control participants and 15 participants with hand/wrist pain were asked to determine the laterality of images of hands. Measures of motor performance (Purdue Pegboard test), self-reported disability (Australian Canadian Hand Index), and pain related aspects (pain intensity, symptom duration, pain interference and affective distress) were recorded. RESULTS: Participants with wrist/hand pain scored lower on all segments of the Purdue Pegboard test. There were differences in LRJT performance between groups for both Accuracy (p = 0.03) and Reaction Time (RT) (p < 0.01). There was no correlation between RT and Accuracy with pain intensity, pain duration, and disability. Both motor performance (r = 0.58-0.64) and LRJT performance Accuracy (r = 0.59) and RT (r = -0.56) were correlated with affective distress. A significant correlation was observed between RT and motor performance in healthy control participants (r = -0.56, p = 0.03) but not in participants with wrist/hand pain (r = -0.26, p = 0.44). CONCLUSIONS: LRJT and motor performance was correlated with affective distress in participants with wrist/hand pain suggestive of complex interactions between cognitive-affective processes and sensorimotor integration.

pH-Dependant Antifungal Activity of Valproic Acid against the Human Fungal Pathogen Candida albicans.

Current antifungal drugs suffer from limitations including toxicity, the emergence of resistance and decreased efficacy at low pH that are typical of human vaginal surfaces. Here, we have shown that the antipsychotic drug valproic acid (VPA) exhibited a strong antifungal activity against both sensitive and resistant Candida albicans in pH condition similar to that encountered in vagina. VPA exerted a strong anti-biofilm activity and attenuated damage of vaginal epithelial cells caused by C. albicans. We also showed that VPA synergizes with the allylamine antifungal, Terbinafine. We undertook a chemogenetic screen to delineate biological processes that underlies VPA-sensitivity in C. albicans and found that vacuole-related genes were required to tolerate VPA. Confocal fluorescence live-cell imaging revealed that VPA alters vacuole integrity and support a model where alteration of vacuoles contributes to the antifungal activity. Taken together, this study suggests that VPA could be used as an effective antifungal against vulvovaginal candidiasis.

The relationship of corticospinal excitability with pain, motor performance and disability in subjects with chronic wrist/hand pain.

There is a growing body of evidence of changes in corticospinal excitability associated with musculoskeletal disorders, however there is a lack of knowledge of how these changes relate to measures of pain, motor performance and disability. An exploratory study was performed utilizing Transcranial Magnetic Stimulation to investigate differences in corticospinal excitability in the Abductor Pollicis Brevis (APB) between 15 pain-free subjects and 15 subjects with chronic wrist/hand pain and to determine how corticospinal excitability was associated with measures of pain (visual analog scale, AUSCAN™), hand motor performance (isometric and key pinch strength, Purdue Pegboard Test), disability (AUSCAN™), and spinal motoneuronal excitability. Input-output curves demonstrated increased corticospinal excitability of the APB in the affected hand of subjects with chronic pain (p<0.01). Changes in corticospinal excitability were significantly correlated with pain intensity (r=0.77), disability (r=0.58), and negatively correlated with motoneuronal excitability (r=-0.57). Corticospinal excitability in subjects with heterogeneous injuries of the wrist/hand was associated with disability and pain.

Use of phylogenetical analysis to predict susceptibility of pathogenic Candida spp. to antifungal drugs.

Successful treatment of a Candida infection relies on 1) an accurate identification of the pathogenic fungus and 2) on its susceptibility to antifungal drugs. In the present study we investigated the level of correlation between phylogenetical evolution and susceptibility of pathogenic Candida spp. to antifungal drugs. For this, we compared a phylogenetic tree, assembled with the concatenated sequences (2475-bp) of the ATP2, TEF1, and TUF1 genes from 20 representative Candida species, with published minimal inhibitory concentrations (MIC) of the four principal antifungal drug classes commonly used in the treatment of candidiasis: polyenes, triazoles, nucleoside analogues, and echinocandins. The phylogenetic tree revealed three distinct phylogenetic clusters among Candida species. Species within a given phylogenetic cluster have generally similar susceptibility profiles to antifungal drugs and species within Clusters II and III were less sensitive to antifungal drugs than Cluster I species. These results showed that phylogenetical relationship between clusters and susceptibility to several antifungal drugs could be used to guide therapy when only species identification is available prior to information pertaining to its resistance profile. An extended study comprising a large panel of clinical samples should be conducted to confirm the efficiency of this approach in the treatment of candidiasis.

Addressing Neuroplastic Changes in Distributed Areas of the Nervous System Associated With Chronic Musculoskeletal Disorders.

Present interventions utilized in musculoskeletal rehabilitation are guided, in large part, by a biomedical model where peripheral structural injury is believed to be the sole driver of the disorder. There are, however, neurophysiological changes across different areas of the peripheral and central nervous systems, including peripheral receptors, dorsal horn of the spinal cord, brain stem, sensorimotor cortical areas, and the mesolimbic and prefrontal areas associated with chronic musculoskeletal disorders, including chronic low back pain, osteoarthritis, and tendon injuries. These neurophysiological changes appear not only to be a consequence of peripheral structural injury but also to play a part in the pathophysiology of chronic musculoskeletal disorders. Neurophysiological changes are consistent with a biopsychosocial formulation reflecting the underlying mechanisms associated with sensory and motor findings, psychological traits, and perceptual changes associated with chronic musculoskeletal conditions. These changes, therefore, have important implications in the clinical manifestation, pathophysiology, and treatment of chronic musculoskeletal disorders. Musculoskeletal rehabilitation professionals have at their disposal tools to address these neuroplastic changes, including top-down cognitive-based interventions (eg, education, cognitive-behavioral therapy, mindfulness meditation, motor imagery) and bottom-up physical interventions (eg, motor learning, peripheral sensory stimulation, manual therapy) that induce neuroplastic changes across distributed areas of the nervous system and affect outcomes in patients with chronic musculoskeletal disorders. Furthermore, novel approaches such as the use of transcranial direct current stimulation and repetitive transcranial magnetic stimulation may be utilized to help renormalize neurological function. Comprehensive treatment addressing peripheral structural injury as well as neurophysiological changes occurring across distributed areas of the nervous system may help to improve outcomes in patients with chronic musculoskeletal disorders.

Is neuroplasticity in the central nervous system the missing link to our understanding of chronic musculoskeletal disorders?

BACKGROUND: Musculoskeletal rehabilitative care and research have traditionally been guided by a structural pathology paradigm and directed their resources towards the structural, functional, and biological abnormalities located locally within the musculoskeletal system to understand and treat Musculoskeletal Disorders (MSD). However the structural pathology model does not adequately explain many of the clinical and experimental findings in subjects with chronic MSD and, more importantly, treatment guided by this paradigm fails to effectively treat many of these conditions. DISCUSSION: Increasing evidence reveals structural and functional changes within the Central Nervous System (CNS) of people with chronic MSD that appear to play a prominent role in the pathophysiology of these disorders. These neuroplastic changes are reflective of adaptive neurophysiological processes occurring as the result of altered afferent stimuli including nociceptive and neuropathic transmission to spinal, subcortical and cortical areas with MSD that are initially beneficial but may persist in a chronic state, may be part and parcel in the pathophysiology of the condition and the development and maintenance of chronic signs and symptoms. Neuroplastic changes within different areas of the CNS may help to explain the transition from acute to chronic conditions, sensory-motor findings, perceptual disturbances, why some individuals continue to experience pain when no structural cause can be discerned, and why some fail to respond to conservative interventions in subjects with chronic MSD. We argue that a change in paradigm is necessary that integrates CNS changes associated with chronic MSD and that these findings are highly relevant for the design and implementation of rehabilitative interventions for this population. Recent findings suggest that a change in model and approach is required in the rehabilitation of chronic MSD that integrate the findings of neuroplastic changes across the CNS and are targeted by rehabilitative interventions. Effects of current interventions may be mediated through peripheral and central changes but may not specifically address all underlying neuroplastic changes in the CNS potentially associated with chronic MSD. Novel approaches to address these neuroplastic changes show promise and require further investigation to improve efficacy of currents approaches.

Primary Larynx Cryptococcus neoformans Infection: A Distinctive Clinical Entity.

Cryptococcus neoformans can directly infect the vocal cords. Endoscopic findings were undistinctive from most infiltrative diseases. Tissue biopsy was essential for the diagnosis. Inhaled corticosteroids can predispose to the infection, and fluconazole 400 mg daily for at least 6 weeks appeared to be minimal to achieve a permanent cure.

Performance of MycAssay Aspergillus DNA real-time PCR assay compared with the galactomannan detection assay for the diagnosis of invasive aspergillosis from serum samples.

Invasive aspergillosis (IA) is a major problem in the immunocompromised population, and its diagnosis is difficult due to the low sensitivity of available tests. Detection of Aspergillus nucleic acid by polymerase chain reaction (PCR) in serum samples is a promising diagnostic tool; however, use of multiple "in-house" methods precludes standardization. The first commercial PCR assay, MycAssay Aspergillus (Myconostica, Ltd), became available recently, and its performance in the diagnosis of IA was evaluated and compared with the galactomannan (GM) assay. Serum samples obtained from patients with hematological cancer were tested retrospectively with MycAssay Aspergillus PCR. Per-episode and per-test analyses were undertaken with 146 sera from 35 hematological patients. Sixteen patients had proven or probable IA and 19 had possible or no IA. In per-episode analysis, MycAssay Aspergillus had a sensitivity of 43.8% (95% confidence interval [CI], 19.8%-70.1%) and a specificity of 63.2% (95% CI, 38.4%-83.7%) for IA diagnosis. In per-test analyses, MycAssay Aspergillus had a lower specificity than the GM assay (83.3% vs. 93.1%, P = 0.04). The addition of PCR to routine clinical practice would have permitted the diagnosis of one additional probable IA in our cohort. Use of PCR instead of GM assay would have delayed the diagnosis in two cases. Aspergillus DNA detection by PCR with serum specimens using MycAssay showed a lower specificity than the GM assay and was associated with a low sensitivity for IA diagnosis. More studies are needed to determine the exact role of MycAssay in IA diagnosis in patients with hematological malignancy.

Epidemiology and antifungal susceptibility of bloodstream Candida isolates in Quebec: Report on 453 cases between 2003 and 2005.

BACKGROUND: Between May 2003 and April 2005, a population-based surveillance of Candida bloodstream infections was conducted in Quebec. A total of 453 episodes of candidemia (464 yeast isolates) from 54 participating hospitals were studied. RESULTS: The annual incidence rate was three per 100,000 population. Global hospital mortality was 38%. The most common predisposing factors were the presence of an intravascular catheter (80%), use of antibacterial therapy (67%), stay in an intensive care unit (49%), use of parenteral nutrition (32%) and intra-abdominal surgery (31%). Fluconazole alone or in association with other antifungals was used for treatment in over 80% of cases. Candida albicans comprised 62% of isolates, followed by Candida glabrata (17%), Candida parapsilosis (9%), Candida tropicalis (5%), Candida lusitaniae (3%) and Candida krusei (3%). Of the 288 C albicans isolates, seven (2%) were resistant to flucytosine, one to fluconazole and none to itraconazole or voriconazole. Of the 75 non-C albicans species isolates with reduced susceptibility to fluconazole (minimum inhibitory concentration [MIC] 16 mug/mL or greater), none were susceptible to itraconazole (MIC 0.12 mg/L or lower), whereas 71 (95%) were susceptible to voriconazole (MIC 1 mug/mL or lower). However, only five of 12 (42%) fluconazole-resistant isolates were susceptible to voriconazole. Posaconazole, ravuconazole and caspofungin displayed a broad spectrum of activity against these isolates, with MICs of 1 mg/L or lower in 56%, 92% and 100% of isolates, respectively. Overall, a correlation (r(2)>0.87) was observed among increasing fluconazole MICs and the geometric mean MICs of itraconazole, voriconazole, posaconazole and ravuconazole. CONCLUSIONS: These surveillance results when compared with those of the 1993 to 1995 survey confirm little variation in the distribution of species causing invasive Candida infection over a 10-year period in Quebec, as well as the continuous excellent overall in vitro activity of fluconazole.

Emergence of disseminated candidiasis caused by Candida krusei during treatment with caspofungin: case report and review of literature.

Current data indicate that caspofungin has in vitro activity against virtually all Candida species. However, we report herein a case of disseminated candidiasis due to Candida krusei which emerged during caspofungin treatment. Lung and brain secondary sites were then successfully treated using a combination of amphotericin B plus flucytosine, amphotericin B lipid complex, and voriconazole, sequentially. Among the total of four well documented cases of refractory invasive candidiasis during caspofungin therapy, the common risk factors appear to involve prior abdominal surgery, persistent foreign body, and anatomical sites where drug concentrations may be sub-optimal for Candida species with increased MICs. Caspofungin failure should be suspected in patients with persistent or emergent signs and symptoms of deep-seated invasive candidiasis.

Antifungal activity of flocculosin, a novel glycolipid isolated from Pseudozyma flocculosa.

Flocculosin, a glycolipid isolated from the yeast-like fungus Pseudozyma flocculosa, was investigated for in vitro antifungal activity. The compound displayed antifungal properties against several pathogenic yeasts. Synergistic activity was observed between flocculosin and amphotericin B, and no significant cytotoxicity was demonstrated when tested against human cell lines.