Orbital mycoses in an adult subtropical population.

BACKGROUND/OBJECTIVES: To report the spectrum of fungal infections involving the orbit encountered in an Australian subtropical population with respect to presentation, host risk factors, involved pathogens, treatment and outcomes. SUBJECTS/METHODS: A retrospective chart review was performed on all adult patients with orbital mycosis treated by the senior author (TJS) from 1986 to 2017 in a tertiary setting. RESULTS: Thirty cases of fungal infection involving the orbit were included in this case series. Of these, 26 patients had invasive disease and four patients had non-invasive disease. Causative organisms included mucormycosis (16), aspergillus (8) and other fungi (7). Common risk factors included haematological disorders or malignancy, neutropenia, corticosteroid use and diabetes mellitus. Mucormycosis in three immunocompetent patients was caused by Apophysomyces elegans. Orbital apex syndrome was observed in approximately one third of patients at initial ophthalmological assessment. Amphotericin B was used in most cases of mucormycosis, while there was a more varied spectrum of anti-fungal use in other fungal infections. Seven patients with mucormycosis proceeded to orbital exenteration with a survival rate of 43%. No patients with other orbital fungal infections were exenterated. CONCLUSIONS: Orbital mycoses are not only opportunistic but true pathogenic infections. While initial symptoms may be varied, the development of orbital apex syndrome should raise suspicion for this condition, regardless of patient immune status or age. Survival and visual outcomes are often poor with invasive disease. Multidisciplinary team management with early orbital specialist involvement is essential.

Integrating multiple genomic technologies to investigate an outbreak of carbapenemase-producing Enterobacter hormaechei.

Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent threat to human health. Here we report the application of several complementary whole-genome sequencing (WGS) technologies to characterise a hospital outbreak of blaIMP-4 carbapenemase-producing E. hormaechei. Using Illumina sequencing, we determined that all outbreak strains were sequence type 90 (ST90) and near-identical. Comparison to publicly available data linked all outbreak isolates to a 2013 isolate from the same ward, suggesting an environmental source in the hospital. Using Pacific Biosciences sequencing, we resolved the complete context of the blaIMP-4 gene on a large IncHI2 plasmid carried by all IMP-4-producing strains across different hospitals. Shotgun metagenomic sequencing of environmental samples also found evidence of ST90 E. hormaechei and the IncHI2 plasmid within the hospital plumbing. Finally, Oxford Nanopore sequencing rapidly resolved the true relationship of subsequent isolates to the initial outbreak. Overall, our strategic application of three WGS technologies provided an in-depth analysis of the outbreak.

Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis.

A single blind, randomized, placebo-controlled, single-center phase I clinical trial of a CD8(+) T-cell peptide epitope vaccine against infectious mononucleosis was conducted with 14 HLA B*0801-positive, Epstein-Barr virus (EBV)-seronegative adults. The vaccine comprised the HLA B*0801-restricted peptide epitope FLRGRAYGL and tetanus toxoid formulated in a water-in-oil adjuvant, Montanide ISA 720. FLRGRAYGL-specific responses were detected in 8/9 peptide-vaccine recipients and 0/4 placebo vaccine recipients by gamma interferon enzyme-linked immunospot assay and/or limiting-dilution analysis. The same T-cell receptor Vbeta CDR3 sequence that is found in FLRGRAYGL-specific T cells from most EBV-seropositive individuals could also be detected in the peripheral blood of vaccine recipients. The vaccine was well tolerated, with the main side effect being mild to moderate injection site reactions. After a 2- to 12-year follow-up, 1/2 placebo vaccinees who acquired EBV developed infectious mononucleosis, whereas 4/4 vaccinees who acquired EBV after completing peptide vaccination seroconverted asymptomatically. Single-epitope vaccination did not predispose individuals to disease, nor did it significantly influence development of a normal repertoire of EBV-specific CD8(+) T-cell responses following seroconversion.

Central venous Access device SeCurement And Dressing Effectiveness for peripherally inserted central catheters in adult acute hospital patients (CASCADE): a pilot randomised controlled trial.

BACKGROUND: Peripherally inserted central catheters (PICCs) are commonly used for delivering intravenous therapy. PICC failure is unacceptably high (up to 40%) due to mechanical, infectious and thrombotic complications. Poor securement potentiates all complication types. This randomised controlled trial (RCT) aimed to examine the feasibility of a large RCT of four dressing and securement methods to prevent PICC failure. METHODS: This single-centre pilot RCT included 124 admitted medical/surgical/cancer patients aged ≥ 16 years with a PICC. Interventions were: (i) standard polyurethane dressing and sutureless securement device (SPU + SSD, control); (ii) polyurethane with absorbent lattice pad dressing (PAL + Tape); (iii) combination securement-dressing (CSD); and (iv) tissue adhesive (TA + SPU). All groups except TA + SPU had a chlorhexidine-gluconate (CHG) impregnated disc. Feasibility outcomes were recruitment and safety/acceptability of the interventions. The primary outcome was PICC failure, a composite of PICC removal for local infection, catheter-associated bloodstream infection, dislodgement, occlusion, and/or catheter fracture. Secondary outcomes included individual complications, dressing failure and dwell time, PICC dwell time, skin complications/phlebitis indicators, product costs, and patient and staff satisfaction. Qualitative feedback was also collected. RESULTS: PICC failure incidence was: PAL + CHG + Tape (1/5; 20%; 17.4/1000 days), SPU + SSD + CHG (control) (4/39; 10%; 9.0/1000 days), TA + SPU (3/35; 9%; 9.6/1000 days), and CSD + CHG (3/42; 7%; 9.4/1000 days). Recruitment to PAL + CHG + Tape was ceased after five participants due to concerns of PICC dislodgement when removing the dressing. CSD + CHG, TA + SPU (TA applied only at PICC insertion time), and control treatments were acceptable to patients and health professionals. CONCLUSION: A large RCT of CSD + CHG and TA + SPU (but not PAL + CHG + Tape) versus standard care is feasible. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12616000027415 . Registered on 15 January 2016.

Three cases of Q fever osteomyelitis in children and a review of the literature.

Q fever is a common zoonosis worldwide. Awareness of the disease and newer diagnostic modalities have resulted in increasing recognition of unusual manifestations. We report 3 cases of Q fever osteomyelitis in children and review the literature on 11 other reported cases. The cases demonstrate that Coxiella burnetii can cause granulomatous osteomyelitis that presents without systemic symptoms and frequently results in a chronic, relapsing, multifocal clinical course. Optimal selection and duration of antimicrobial therapy and methods of monitoring therapy are currently uncertain.

Hip structural parameters over 96 weeks in HIV-infected adults switching treatment to tenofovir-emtricitabine or abacavir-lamivudine.

BACKGROUND: Therapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV. METHODS: Dual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups. RESULTS: Participants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p = 0.001), lower cross-sectional area (-15.01 mm3, p = 0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p = 0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p = 0.008) and cross-sectional area (p = 0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p = 0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p = 0.025), and higher osteoprotegerin (p = 0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine. CONCLUSION: In this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00192634.

A case of Mycoplasma pneumoniae-associated encephalomyelitis in a 16-year-old female presenting to an adult teaching hospital.

We report a rare cause of encephalitis that is not often described in the adult clinical setting. Our case was a 16-year-old female who presented with a clinical picture of viral encephalitis; however, magnetic resonance imaging showed a demyelinating lesion of the left frontal lobe. In this age group, differential diagnoses of acute demyelination encephalomyelitis and multiple sclerosis were entertained. Further investigations demonstrated positive Mycoplasma pneumoniae serology. As a result, a diagnosis of Mycoplasma pneumoniae-associated encephalitis was made based on a process of exclusion.

Histoplasmosis in Australia: report of 16 cases and literature review.

We describe 16 previously unreported patients with histoplasmosis from Queensland and northern New South Wales, Australia, and review all previous Australian reports, providing 63 cases in total to study (17 cases of acute pulmonary histoplasmosis, 2 cases of chronic pulmonary disease, and 44 cases of systemic disease, including 17 cases of single-organ infection and 27 instances of disseminated disease). All acute pulmonary disease was acquired in Australia, with 52% of systemic disease definitely autochthonous. Most cases of single-organ disease occurred in immunocompetent patients (76%), and were oropharyngeal (53%) in location. Forty-one percent of disseminated disease occurred in patients with human immunodeficiency virus (HIV). Patients with HIV had high rates of systemic symptoms, pancytopenia, fungemia, and hepatosplenomegaly. Oropharyngeal and adrenal involvement as well as systemic symptoms were prominent in immunocompetent patients with disseminated disease, with 6 of 7 cases of adrenal involvement leading to Addison disease. Most systemic disease was diagnosed by culture of Histoplasma capsulatum. Where serology was assessed in cases other than acute pulmonary disease, it was positive in only 32%.Prognosis for patients with single-organ disease was excellent. Disseminated disease was associated with recurrence in 30% and death in 37%. The results of this study confirm several previously known patterns of disease but also provide new insights into this rare but endemic condition in Australia.

Control of an outbreak of carbapenem-resistant Acinetobacter baumannii in Australia after introduction of environmental cleaning with a commercial oxidizing disinfectant.

In the midst of an outbreak, carbapenem-resistant Acinetobacter baumannii was grown from samples of multiple environmental sites in an intensive care unit. A commercial oxidizing disinfectant (potassium peroxomonosulphate 50%, sodium alkyl benzene sulphonate 15%, and sulphamic acid 5%) was introduced throughout the intensive care unit, and its use coincided with cessation of the outbreak.

False impressions from clear cerebrospinal fluid and a normal computed tomography scan: the pressure is still on for a diagnosis.

We report the case of a 33-year-old man presenting with seizures following a 3 week, non-specific febrile illness characterized by progressive confusion. Despite the presence of risk factors, his HIV serology was negative and he had no premorbid suggestion of immunocompromise. We describe the difficulties in making the diagnosis of cryptococcal meningitis in the presence of cerebrospinal fluid analysis with the only abnormality initially being hypoglycorrhachia. This case also highlights the importance of measuring an opening pressure, a procedure which should be routine, but is often neglected in the performance of lumbar punctures. Finally, this case reinforces the maxim that cranial CT cannot be relied upon alone to diagnose intracranial hypertension, which also requires clinical examination, including fundoscopy.

Ethanol lock therapy to treat tunnelled central venous catheter-associated blood stream infections: results from a prospective trial.

In order to assess the efficacy of 70% ethanol locks in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bloodstream infections, a pilot study of 19 patients was performed prospectively using ethanol locks for 5 d in addition to antibiotic therapy to treat tunnelled central venous catheter-associated bacteraemia. 12 patients had mono-microbial infections and 7 had polymicrobial isolates. 17 of 19 patients completed ethanol lock therapy. 15 of 17 patients completing ethanol lock therapy had no recurrence of the original organism and retained their catheter for a median of 36 and an average of 47 d following initiation of ethanol lock therapy. These results demonstrate the safety and potential efficacy of this technique against a broad range of potentially virulent organisms. The intervention was acceptable to both staff and patients with no significant side-effects. These preliminary results from our prospective pilot study suggest that ethanol lock therapy is safe and easily integrated into clinical practice, and may have utility in treating central venous catheter-associated infections, avoiding removal of catheters in patients requiring long-term venous access.

Immune reconstitution inflammatory syndrome producing atypical presentations of cryptococcal meningitis: case report and a review of immune reconstitution-associated cryptococcal infections.

Atypical presentations of cryptococcal infection have been described as manifestations of immune reconstitution in HIV-infected patients following introduction of antiretroviral therapy. We describe a patient presenting with cryptococcal meningitis as an immune reconstitution reaction 10 weeks after initiation of anti-retroviral therapy. Subclinical CSF cryptococcal infection was demonstrated and the serum cryptococcal antigen was negative.

A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant.

A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 microg, 20 microg or 80 microg of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study.

Emerging viral infections in Australia.

Hendra virus infection should be suspected in someone with close association with horses or bats who presents acutely with pneumonia or encephalitis (potentially after a prolonged incubation period). Australian bat lyssavirus infection should be suspected in a patient with a progressive neurological illness and a history of exposure to a bat. Rabies vaccine and immunoglobulin should be strongly considered after a bite, scratch or mucous membrane exposure to a bat. Japanese encephalitis vaccine should be considered for people intending to reside in or visit endemic areas of southern or eastern Asia for more than 30 days.