Penicillium marneffei infection in a lung transplant recipient.

Penicillium marneffei is a thermally dimorphic fungus that can cause severe opportunistic infections in endemic regions of Southeast Asia, particularly in individuals infected with human immunodeficiency virus-1, but has rarely been reported in solid organ transplant recipients. Herein, we report the first case, to our knowledge, of P. marneffei infection in a lung transplant recipient, occurring in a 41-year-old woman 28 months post lung transplantation, after recent travel to Vietnam. We have reviewed the literature to derive some management principles for this rare infection in this clinical context. The number of P. marneffei infections in transplant recipients may increase, as a result of increasing rates of transplantation and travel to endemic areas.

Consensus guidelines for the use of empiric and diagnostic-driven antifungal treatment strategies in haematological malignancy, 2014.

Invasive fungal disease (IFD) causes significant morbidity and mortality in patients undergoing allogeneic haemopoietic stem cell transplantation or chemotherapy for haematological malignancy. Much of these adverse outcomes are due to the limited ability of traditional diagnostic tests (i.e. culture and histology) to make an early and accurate diagnosis. As persistent or recurrent fevers of unknown origin (PFUO) in neutropenic patients despite broad-spectrum antibiotics have been associated with the development of IFD, most centres have traditionally administered empiric antifungal therapy (EAFT) to patients with PFUO. However, use of an EAFT strategy has not been shown to have an overall survival benefit and is associated with excessive antifungal therapy use. As a result, the focus has shifted to developing more sensitive and specific diagnostic tests for early and more targeted antifungal treatment. These tests, including the galactomannan enzyme-linked immunosorbent assay and Aspergillus polymerase chain reaction (PCR), have enabled the development of diagnostic-driven antifungal treatment (DDAT) strategies, which have been shown to be safe and feasible, reducing antifungal usage. In addition, the development of effective antifungal prophylactic strategies has changed the landscape in terms of the incidence and types of IFD that clinicians have encountered. In this review, we examine the current role of EAFT and provide up-to-date data on the newer diagnostic tests and algorithms available for use in EAFT and DDAT strategies, within the context of patient risk and type of antifungal prophylaxis used.

Consensus guidelines for antifungal prophylaxis in haematological malignancy and haemopoietic stem cell transplantation, 2014.

There is a strong argument for the use of antifungal prophylaxis in high-risk patients given the significant mortality associated with invasive fungal disease, the late identification of these infections, and the availability of safe and well-tolerated prophylactic medications. Clinical decisions about which patients should receive prophylaxis and choice of antifungal agent should be guided by risk stratification, knowledge of local fungal epidemiology, the efficacy and tolerability profile of available agents, and estimates such as number needed to treat and number needed to harm. There have been substantial changes in practice since the 2008 guidelines were published. These include the availability of new medications and/or formulations, and a focus on refining and simplifying patient risk stratification. Used in context, these guidelines aim to assist clinicians in providing optimal preventive care to this vulnerable patient demographic.

Antifungal prophylaxis in adult stem cell transplantation and haematological malignancy.

Antifungal prophylaxis can be recommended in patients undergoing induction chemotherapy for acute myeloid leukemia and treatment for grade 2 or greater or chronic extensive graft versus host disease. The evidence for prophylaxis is less clear in other clinical settings although certain groups such as patients with prolonged neutropenia after stem cell transplants using bone marrow or cord blood sources and with impaired cell mediated immunity secondary to treatments such as Alemtuzumab are at high risk. The decision to use prophylaxis and which agent to use will be influenced by effectiveness, number needed to treat and the likelihood of toxicity and drug interactions. The availability of rapid diagnostic tests for fungal infection and institutional epidemiology will also influence the need for and choice of prophylaxis. Whilst prophylaxis can be beneficial, it may impede the ability to make a rapid diagnosis of fungal infection by reducing the yield of diagnostic tests and change the epidemiology of fungal infection. As non-culture based diagnostic tests are refined and become more available there may be a shift from prophylaxis to early diagnosis and treatment.

Mucormycosis in Australia: contemporary epidemiology and outcomes.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p <0.001). Disseminated infection was common (39.2%). Apophysomyces spp. and Saksenaea spp. caused infection in immuno-competent hosts, most frequently associated with trauma and affected sites other than lung and sinuses. The 180-day mortality was 56.7%. The strongest predictors of mortality were rheumatological/autoimmune disorder (OR = 24.0, p 0.038 95% CI 1.2-481.4), haematological malignancy (OR = 7.7, p 0.001, 95% CI 2.3-25.2) and admission to intensive care unit (OR = 4.2, p 0.02, 95% CI 1.3-13.8). Most deaths occurred within one month. Thereafter we observed divergence in survival between the haematological and non-haematological populations (p 0.006). The mortality of mucormycosis remains particularly high in the immuno-compromised host. Underlying rheumatological/autoimmune disorders are a previously under-appreciated risk for infection and poor outcome.

Invasive infections due to filamentous fungi other than Aspergillus: epidemiology and determinants of mortality.

The epidemiology of invasive fungal disease (IFD) due to filamentous fungi other than Aspergillus may be changing. We analysed clinical, microbiological and outcome data in Australian patients to determine the predisposing factors and identify determinants of mortality. Proven and probable non-Aspergillus mould infections (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria) from 2004 to 2012 were evaluated in a multicentre study. Variables associated with infection and mortality were determined. Of 162 episodes of non-Aspergillus IFD, 145 (89.5%) were proven infections and 17 (10.5%) were probable infections. The pathogens included 29 fungal species/species complexes; mucormycetes (45.7%) and Scedosporium species (33.3%) were most common. The commonest comorbidities were haematological malignancies (HMs) (46.3%) diabetes mellitus (23.5%), and chronic pulmonary disease (16%); antecedent trauma was present in 21% of cases. Twenty-five (15.4%) patients had no immunocompromised status or comorbidity, and were more likely to have acquired infection following major trauma (p <0.01); 61 (37.7%) of cases affected patients without HMs or transplantation. Antifungal therapy was administered to 93.2% of patients (median 68 days, interquartile range 19-275), and adjunctive surgery was performed in 58.6%. The all-cause 90-day mortality was 44.4%; HMs and intensive-care admission were the strongest predictors of death (both p <0.001). Survival varied by fungal group, with the risk of death being significantly lower in patients with dematiaceous mould infections than in patients with other non-Aspergillus mould infections. Non-Aspergillus IFD affected diverse patient groups, including non-immunocompromised hosts and those outside traditional risk groups; therefore, definitions of IFD in these patients are required. Given the high mortality, increased recognition of infections and accurate identification of the causative agent are required.

Methicillin-resistant Staphylococcus aureus bacteraemia in Western Australian teaching hospitals, 1997-1999: risk factors, outcomes and implications for management.

The aim of this study was to document the evolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia at teaching hospitals in Perth, Western Australia (WA), and determine the risk factors and outcomes of the disease. We performed a retrospective case series analysis of all laboratory-confirmed episodes of S. aureus bacteraemia at Perth teaching hospitals between 1 July 1997 and 30 June 1999 by linking laboratory data with hospitalization data from the state's Hospital Morbidity Data System. Episodes of S. aureus bacteraemia were stratified according to methicillin susceptibility and the relationship between methicillin resistance and key factors or outcomes was determined. Almost 11% of episodes of S. aureus bacteraemia (55/509) were caused by MRSA. On age-adjusted multivariate analysis, Aboriginality (RR 6.71, 95% CI 3.20-14.10, P<0.001), geriatric unit admission (RR 5.74, 95% CI 2.01-16.37, P=0.001), female sex (RR 1.88, 95% CI 1.03-3.42, P=0.04) and healthcare-associated disease (RR 1.93, 95% CI 1.01-3.70, P=0.05) were independently associated with MRSA bacteraemia. Outcomes among those with MRSA bacteraemia included death in 15 patients and re-admission for an MRSA-related complication in five. Empirical use of vancomycin needs consideration in at-risk patients in whom Gram-positive bacteraemia is suspected clinically, with prompt review of therapy once antibiotic susceptibility results are known. The rates of re-admission after discharge for MRSA bacteraemia could be used as a clinical indicator to monitor the quality of care in hospitals.

Emergence of multi-resistant Pseudomonas aeruginosa in a Western Australian hospital.

Multi-resistant Pseudomonas aeruginosa (MRPa) has been isolated from patients in a Western Australian teaching hospital with increasing frequency since first encountered in 2006. Between 2006 and 2008 the number of patients with MRPa increased from three to nine per annum, and their location shifted from intensive care to a high dependency unit. A novel water-saving device (aerator) in a staff hand basin was identified as a likely disseminator, with MRPa being isolated from biofilm in the basin's plumbing. The disposal of patient waste, surplus intravenous antibiotic infusions and solid items via hand basins were possible contributory factors. Genotyping of MRPa from patients in other hospitals showed distinct genotypic lineages. The third seasonal cluster persisted for longer, indicating adaption to environment. More effective environmental control of P. aeruginosa is urgently needed.

Ophthalmic manifestation of Candida: case report and review of the literature.

Candidemia in the pediatric burn population poses a management dilemma due to the paucity of good clinical data to guide treatment decisions. Whilst candidemia is less common than bacteremia in pediatric burns patients, it is associated with significant morbidity and mortality. We report a case of candidemia in an infant with 40% burns with ophthalmic complications secondary to nappy rash. We review the investigation and management of ocular candidemia.

Population-based surveillance for scedosporiosis in Australia: epidemiology, disease manifestations and emergence of Scedosporium aurantiacum infection.

Australia-wide population-based surveillance for scedosporiosis identified 180 cases, with 118 (65.6%) cases of colonization and 62 (34.4%) cases of infection. Predisposing factors for isolation of Scedosporium spp. included chronic lung disease in 37.8% and malignancy in 21.7% of cases. Predictors of invasive disease (n=62) included haematological stem cell transplantation (n=7), leukaemia (n=16) and diabetes mellitus (n=8). Of 183 phenotypically-speciated isolates, 75 (41%) were Scedosporium prolificans (risk factors: haematologic cancer (n=17), neutropaenia (n=14)) and 108 (59%) had Scedosporium apiospermum/Pseudallescheria boydii phenotype [risk factor: diabetes (n=15)]. Scedosporium prolificans (p 0.01) and leukaemia (p 0.03) independently predicted death. Epidemiological and antifungal susceptibility profiles of Scedosporium aurantiacum (prevalence>or=15.8%) and S. apiospermum were similar. No patient with S. aurantiacum infection (n=6) died. This is the first description of clinical features associated with S. aurantiacum.

Normal limits of knee angle in white children--genu varum and genu valgum.

Knee angle and intermalleolar (IM) or intercondylar (IC) distance were measured in 196 white children aged 6 months to 11 years to establish normal limits of tibiofemoral angle. Children were maximally bowlegged at age 6 months and progressed toward approximately neutral knee angles (0 degree) by age 18 months. Greatest mean knock knee of 8 degrees was observed at age 4 years, followed by a gradual decrease to a mean of < 6 degrees at 11 years. Normal children aged 2-11 years had knock knee up to 12 degrees and intermalleolar distance up to 8 cm; the existence of bowlegs after age 2 years was abnormal.

Emerging resistance in Enterococcus spp.

Enterococcus spp. are becoming increasingly important nosocomial pathogens. They are intrinsically resistant to most antibiotics, and effective therapy depends primarily on the penicillins, vancomycin and the aminoglycosides. Under antibiotic selection pressure they have developed high level resistance to these agents, and the first vancomycin-resistant enterococcal infection in Australia was described recently. The vancomycin-resistance genes are of particular concern because of their potential to transfer to other gram-positive organisms. The prevention and control of resistant enterococci is a major challenge that is best met by a combination of active infection control measures and restriction of broad-spectrum antibiotic use.

Local anesthetic distribution in a spinal model: a possible mechanism of neurologic injury after continuous spinal anesthesia.

BACKGROUND AND OBJECTIVES: Cauda equina syndrome has been reported recently in patients receiving continuous spinal anesthesia using newly developed microcatheters (28 gauge). Failure of microcatheters to allow adequate mixing of local anesthetic was studied as a possible mechanism of the neurologic injury reported with these catheters. METHODS: A spinal canal model was developed and the distribution of hyperbaric lidocaine was measured after injection through catheters typically used for continuous spinal anesthesia (i.e., 20, 28, and 32 gauge). RESULTS: Lidocaine distribution was less uniform and lidocaine concentration and osmolarity in the dependent portions of the model were significantly higher after injection through microcatheters compared to the 20-gauge catheter. CONCLUSIONS: Dependent drug concentrations were greater than those reported in the literature, capable of producing permanent neurologic injury. Directing the catheter tip in the nondependent direction and injecting lidocaine rapidly or through catheters with multiple end holes improved mixing and decreased dependent drug concentration.

Delay in appropriate therapy of Legionella pneumonia associated with increased mortality.

The prognostic significance of delayed therapy in Legionnaires' disease is poorly defined. Thirty-nine consecutive serologically confirmed cases of Legionnaires' disease were reviewed to examine whether an association exists between delayed therapy and prognosis. Clinical and laboratory factors predictive of mortality were also sought. Thirty-one cases (79%) were classified as having severe pneumonia at diagnosis. Thirty-six patients (92%) had community-acquired infection, and three patients (8%) had nosocomial disease. Ten patients died, resulting in a crude mortality rate of 26%. At the first assessment, variables noted for pneumonia associated with death were low diastolic blood pressure (p < 0.02), low serum albumin concentration (p < 0.04), and increased number of days from onset of pneumonia to hospitalisation (prodrome) (p < 0.02). However, multiple logistic regression analysis revealed that the prodrome was the only variable noted at diagnosis that achieved significance (p = 0.024). Mortality also correlated with both delay in the initiation of erythromycin therapy following admission (p < 0.001) and the total delay in starting erythromycin therapy (p < 0.001). It is therefore recommended that erythromycin be included early in the empiric therapy of severe community-acquired pneumonia.