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The authors present the case of a 34-year-old male patient who underwent therapeutic plasma exchange (TPE) for amyopathic dermatomyositis. Immunosuppression resulted in Aspergillus lentuluspulmonary infection,requiring treatment with super bioavailable-itraconazole. Therapeutic itraconazole concentrations were attained after 2 weeks of treatment after dose adjustments. Interestingly, a substantial reduction in plasma itraconazole concentration was observed during TPE, which was attributed to an insufficient delay between the dosing of itraconazole and TPE initiation. Furthermore, there was an increase in plasma concentration post-TPE, which presumably reflects the redistribution of itraconazole from peripheral compartments back into plasma. This was confirmed by sampling of the TPE plasmapheresate, which revealed that changes in plasma concentration overestimated itraconazole clearance. These findings highlight that the pharmacokinetics of itraconazole are altered during TPE, which should be considered when timing drug administration and obtaining plasma concentrations.

Individualization of vancomycin dosing based on therapeutic drug monitoring (TDM) data is known to improve patient outcomes compared with fixed or empirical dosing strategies. There is increasing evidence to support area-under-the-curve (AUC24)–guided TDM to inform vancomycin dosing decisions for patients receiving therapy for more than 48 hours. It is acknowledged that there may be institutional barriers to the implementation of AUC24-guided dosing, and additional effort is required to enable the transition from trough-based to AUC24-based strategies. Adequate documentation of sampling, correct storage and transport, accurate laboratory analysis, and pertinent data reporting are required to ensure appropriate interpretation of TDM data to guide vancomycin dosing recommendations. Ultimately, TDM data in the clinical context of the patient and their response to treatment should guide vancomycin therapy. Endorsed by the International Association of Therapeutic Drug Monitoring and Clinical Toxicology, the IATDMCT Anti-Infectives Committee, provides recommendations with respect to best clinical practice for vancomycin TDM.

Fluconazole has been associated with higher mortality compared with the echinocandins in patients treated for invasive candida infections. Underexposure from current fluconazole dosing regimens may contribute to these worse outcomes, so alternative dosing strategies require study.

A case of tenofovir-induced Fanconi syndrome in a patient receiving antiretroviral therapy for HIV infection, with resolution of the related electrolyte abnormalities upon switch from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate, is reported. Tenofovir alafenamide fumarate, a novel prodrug of tenofovir containing significantly lower doses of tenofovir than tenofovir disoproxil fumarate, has been associated with a favourable renal profile compared to tenofovir disoproxil fumarate. Generally, the rare complication of tenofovir disoproxil fumarate–induced Fanconi syndrome is managed by cessation of tenofovir. There are limited reports of the impact of a switch strategy from tenofovir disoproxil fumarate to tenofovir alafenamide fumarate, which may be necessary in patients unable to discontinue tenofovir.

ABSTRACTColonization with Candidaspecies is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candidacolonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR] = 2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of =2 sites and heavy colonization of =1 site were significant independent risk factors for IC (RR = 2.25 and RR = 3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC.

To assess the efficacy and tolerance of fluconazole (150 mg oral dose, once a week) in the prevention of recurrent oropharyngeal candidiasis in patients with moderate to severe human immunodeficiency virus (HIV) infection. A randomised, double‐blind, placebo‐controlled trial. Eighty‐four patients with moderate to severe HIV infection who had successfully completed two to four weeks treatment with fluconazole for oropharyngeal candidiasis were randomly allocated to receive either placebo or fluconazole. Pre‐treatment clinical and laboratory characteristics were similar in the two groups. Success was classified as absence throughout the course of treatment of clinical evidence of oropharyngeal candidiasis, and failure as recurrence or relapse of symptomatic oropharyngeal candidiasis. Of 73 evaluable patients the median time to relapse was ≥ 168 days in the fluconazole group and 37 days in the placebo group (P<0.0001). One patient in the placebo group and 18 patients in the fluconazole group completed six months’ treatment without clinical relapse (P<0.001). Fluconazole was well tolerated and prevented clinical relapse of oropharyngeal candidiasis In 71% of patients who completed three months of treatment (95% confidence interval [CI], 55–86) and 58% (95% CI, 41–75) who completed six months of treatment.

Apply the science, use a team approach, help patients to promote their own health, ensure access to support and accept a public health role. These are the practical lessons of our experience in HIV medicine.

To determine whether microsporidian infections occur in Australian patients infected with human immunodeficiency virus (HIV), to assess the incidence, and to discuss microscopic detection methods. 180 consecutive HIV‐infected patients (109 with chronic diarrhoea and 71 with other indications) underwent upper gastrointestinal tract endoscopy and pinch biopsies of the second part of the duodenum. The biopsies were handled by a protocol: four levels, with haematoxylin and eosin stain (H&E) at each level, periodic acid Schiff reagent after diastase (DiPAS) and auramine stain at the second level, and Warthin–Starry (WS) stain and cytomegalovirus early antigen immunoperoxidase study at the third level. Electron microscopy was carried out on samples from the first 95 patients, and thereafter from selected patients. The patients came from the HIV Medicine Unit of a teaching hospital and from the practice of a gastroenterologist. Diagnosis of microsporidia was to be based on the H&E stain, with electron microscopy as the definitive test because the microsporidia are often difficult to see with H&E. Empirically, the WS stain was found to stain the microorganisms and it replaced electron microscopy during the study as the screening diagnostic test. Microsporidia were present in 36 of the 109 patients with diarrhoea (33%) and one of 71 patients without diarrhoea. The WS stain in all cases showed developing spores in the enterocytes and in four case's in macrophages as well. The H&E stain showed non‐specific duodenitis and was not diagnostic in some cases. Electron microscopy on samples from the first 95 consecutive patients showed 100% concordance with the WS stain. In 33 cases, electron microscopy showed the multinucleated Plasmodia and the spores of Enterocytozoon bieneusl and in the four cases confirmed the spores in macrophages and showed a new Encephalltozoon‐like species with a septate parasitophorous vacuole. Other causes of duodenal infection were cytomegalovirus (11 cases), mycobacteria (8), Cryptosporidia (8) and Giardia lambiia (5). E. bieneusi was the commonest microorganism found in our series of 180 consecutive patients. The actual prevalence of the two microsporidia species within the HIV‐positive population and general community awaits further study. The WS stain provides a sensitive diagnostic test for the presence of E. bieneusi and the new Encephalitozoon‐like species, avoiding the cost and potential sampling error of electron microscopy. The detailed ultrastructure and taxonomy of the new species requires further study.

A 54‐year‐old man, with a history of alcohol abuse and previous skull fractures, developed a low‐grade meningitis. The causative organism was Pasteurella ureae, an uncommon cause of bacterial infection, which has not been reported previously in Australia. The patient recovered after therapy with penicillin. A review of the cases of serious infection with this organism suggests that liver disease and skull trauma are common predisposing factors. Problems with the identification of P. ureaemay be encountered unless its particular biochemical properties are recognized.

Disseminated microsporidiosis due to the newly described species Septata intestinalis in nine patients infected with human immunodeficiency virus is described. All patients were male homosexuals; the mean age was 41 years (range, 35–58 years). They were all severely immunocompromised, with a mean CD4 lymphocyte count of 15/mm3 (range, 0–32/mm3). Infection by S. intestinalis was seen in duodenal biopsy specimens from all patients, and dissemination was demonstrated by the presence of microsporidial spores in urine (9 of 9 patients), sinonasal secretions and/or nasal mucosal biopsy specimens (6 of 6), and sputum (6 of 6). Seven patients were treated with albendazole (400 mg twice daily), resulting in significant dissipation or complete resolution of diarrhea for six patients and abatement of symptoms for the six patients with chronic rhinosinusitis. There was a parallel parasitological response, with clearance of S. intestinalis infection from almost all sites.