John Dyer

Cryptococcal Immune Reconstitution Inflammatory Syndrome following Alemtuzumab Therapy

Alemtuzumab is a lymphocyte ablative agent that may cause susceptibility to severe opportunistic infections similar to those seen in AIDS. Pathogen-specific immune reconstitution syndromes can complicate antiretroviral therapy and immune recovery in HIV-infected patients. We present the first reported case of immune reconstitution syndrome associated with T lymphocyte recovery after alemtuzumab therapy.

Continuous Infusions of Meropenem in Ambulatory Care: Clinical Efficacy, Safety and Stability

Objectives Concerns regarding the clinical impact of meropenem instability in continuous infusion (CI) devices may contribute to inconsistent uptake of this method of administration across outpatient parenteral antimicrobial therapy (OPAT) services. Methods We retrospectively reviewed the clinical efficacy and safety of CIs of meropenem in two Australian tertiary hospitals and assessed its stability under simulated OPAT conditions including in elastomeric infusion devices containing 1% (2.4 g) or 2% (4.8 g) concentrations at either ‘room temperature’ or ‘cooled’ conditions. Infusate aliquots were assayed at different time-points over 24 hours. Results Forty-one (82%) of 50 patients had clinical improvement or were cured. Adverse patient outcomes including hemato-, hepato- and nephrotoxicity were infrequent. Cooled infusers with 1% meropenem had a mean 24-hour recovery of 90.3%. Recoveries of 1% and 2% meropenem at room temperature and 2% under cooled conditions were 88%, 83% and 87%, respectively. Patients receiving 1% meropenem are likely to receive >95% of the maximum deliverable dose (MDD) over a 24-hour period whilst patients receiving 2% meropenem should receive 93% and 87% of the MDD under cooled and room temperature conditions, respectively. Conclusions Meropenem infusers are likely to deliver ∼95% MDD and maintain effective plasma concentrations throughout the dosing period. These data reflect our local favourable clinical experience with meropenem CIs.

Not only ‘Flinders Island’ spotted fever

Aim: To demonstrate that Flinders Island spotted fever (FISF), a spotted fever group rickettsial infection caused by Rickettsia honei, is found not only on Flinders Island (Bass Strait), Tasmania, but elsewhere in south‐east Australia. Methods: Cases of FISF were identified by rickettsial serology, culture and the detection of rickettsial DNA via PCR. Isolates and PCR products were sequenced to identify the aetiological agent as R. honei. Results: Three new cases of FISF were detected outside of Flinders Island. One on Schouten Island, south of the Freycinet Peninsula, Tasmania, and two in south‐eastern South Australia (McLaren Vale and Goolwa). Conclusions: These cases show that FISF extends beyond Flinders Island and most likely has the same distribution across south‐east Australia as its vector, the reptile tick Aponomma hydrosauri. FISF should be considered as a differential diagnosis in patients from south‐eastern Australia presenting with fever, headache and rash following a tick bite.

The conservative management of renal trauma: a literature review and practical clinical guideline from Australia and New Zealand.

To review the literature and make practical recommendations regarding the conservative management of renal trauma.

Endemic (Murine) Typhus in Returned Travelers from Asia, a Case Series: Clues to Early Diagnosis and Comparison with Dengue

Two cases of endemic typhus are described in detail with a clinical summary of eight cases in returned travelers. Compared with a similar cohort of patients with dengue, typhus cases had higher CRP and less neutropenia. These findings may guide empirical therapy and improve use of definitive diagnostic tests. A report of the GeoSentinel Network identified rickettsial infection in 280 (1.5%) of around 14,000 febrile travelers.1 Only 10 individuals were considered to have endemic (murine) typhus caused by flea-borne infection with Rickettsia typhi. In a Swedish cohort of febrile returned travelers, 1% of 1,049 patients with routine testing and 4% of 383 patients with additional serological investigation were diagnosed with typhus group (R. prowazekii or R. typhi) rickettsiosis.2 Thirty-two cases of endemic typhus were identified in a retrospective analysis of all samples sent to the World Health Organization (WHO) Collaborative Center for Rickettsial Diseases and Other Arthropod-Borne Bacterial Diseases, Marseille, France, over a 3-year period.3 Of these cases, 13 individuals had traveled to Africa, and 12 individuals had traveled to Southeast Asia. There have been sporadic case reports of endemic typhus in tourists returning from Southeast Asia, including seven cases acquired in Indonesia,4–7 one case acquired in Thailand, and one case acquired in Vietnam.8,9 Conclusions from these reports are that endemic typhus remains a rare but probably underdiagnosed cause of febrile illness in returned travelers, severe presentations do occur,7and Southeast Asia is the main source. Indonesia is the most popular holiday destination for Western Australians, accounting for 259,737 (42% of total) annual short-term overseas departures according to the Australian Bureau of Statistics (2011). Since 2009, we have diagnosed endemic typhus in eight returned travelers. Here, we present two illustrative cases and a clinical summary of the series. Because it is a rare condition presenting as a non-specific febrile illness and most commonly diagnosed serologically, definitive diagnosis is often retrospective, requiring early treatment with doxycycline to provide adequate empiric cover. Because dengue fever was the most common working diagnosis in our series of patients, we compared initial laboratory parameters of endemic typhus patients with those parameters of a similar cohort of dengue patients to identify features that may help clinicians differentiate between these two infections.

Limited role for outpatient parenteral antibiotic therapy for community-acquired pneumonia

Background and objective:  This study examined the potential utility of outpatient parenteral antibiotic therapy (OPAT) as a means of reducing the excessive number of patients hospitalized with low‐risk community‐acquired pneumonia (CAP).

Validation and application of a dried blood spot assay for biofilm-active antibiotics commonly used for treatment of prosthetic implant infections

ABSTRACT Dried blood spot (DBS) antibiotic assays can facilitate pharmacokinetic (PK)/pharmacodynamic (PD) studies in situations where venous blood sampling is logistically difficult. We sought to develop, validate, and apply a DBS assay for rifampin (RIF), fusidic acid (FUS), and ciprofloxacin (CIP). These antibiotics are considered active against organisms in biofilms and are therefore commonly used for the treatment of infections associated with prosthetic implants. A liquid chromatography-mass spectroscopy DBS assay was developed and validated, including red cell partitioning and thermal stability for each drug and the rifampin metabolite desacetyl rifampin (Des-RIF). Plasma and DBS concentrations in 10 healthy adults were compared, and the concentration-time profiles were incorporated into population PK models. The limits of quantification for RIF, Des-RIF, CIP, and FUS in DBS were 15 μg/liter, 14 μg/liter, 25 μg/liter, and 153 μg/liter, respectively. Adjusting for hematocrit, red cell partitioning, and relative recovery, DBS-predicted plasma concentrations were comparable to measured plasma concentrations for each antibiotic (r > 0.95; P < 0.0001), and Bland-Altman plots showed no significant bias. The final population PK estimates of clearance, volume of distribution, and time above threshold MICs for measured and DBS-predicted plasma concentrations were comparable. These drugs were stable in DBSs for at least 10 days at room temperature and 1 month at 4°C. The present DBS antibiotic assays are robust and can be used as surrogates for plasma concentrations to provide valid PK and PK/PD data in a variety of clinical situations, including therapeutic drug monitoring or studies of implant infections.

Seroepidemiological Study of Outdoor Recreationists' Exposure to Spotted Fever Group Rickettsia in Western Australia

Bushland activity has previously been linked to rickettsial exposure in eastern and central regions of Australia, whereas little is known about the risks in Western Australia. The isolation of Rickettsia gravesii sp. nov. from Amblyomma triguttatum ticks and anecdotal reports of low-grade illness among bush recreationists raised the possibility of rickettsial transmission in the State. This study investigated rickettsial seroprevalence and potential risk of exposure to the spotted fever group rickettsiae in rogainers. Our results showed that rogainers active in the bush had a significantly higher risk of seropositivity (immunofluorescence total antibody titer ≥ 128) for the spotted fever group Rickettsia (odds ratio [OR] = 14.02, 95% confidence interval [CI] = 1.38-142.07) compared with a reference population, the overall seroprevalence in the rogainer group being 23.1%.

Prevalence, risk factors and sequelae of Staphylococcus aureus carriage in diabetes: the Fremantle Diabetes Study Phase II

AIMS To determine the prevalence and associates of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage in community-based diabetes, and their relationship to hospitalization with S. aureus infection. METHODS A cross-sectional subset of 660 Fremantle Diabetes Study Phase II patients (mean±SD age 65.1±11.5years, 53.1% males) had nasal/axillary swabs as part of biennial review. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured in 358 patients. Those with positive swabs were invited back for a repeat swab. Hospitalizations with S. aureus infections were ascertained from validated data linkage. Multiple logistic regression was used to identify associates of carriage, and Cox proportional hazards modelling was used to determine predictors of subsequent hospitalization. RESULTS 258 patients (39.1%) were positive for S. aureus and eight (3.1%) carried MRSA. S. aureus carriage was independently associated with being married/in a de facto relationship and inversely with older age and being born overseas (P≤0.043). Repeat swabs in 137 patients (53.1% of those with an initially positive swab) grew S. aureus in 113 (82.5%). Five of eight MRSA-positive patients were re-swabbed, and four were MRSA-positive. Independent predictors of hospitalization with staphylococcal infection after the initial swab were S. aureus carriage (hazard ratio (95% CI) 5.42 (1.49-19.79)), prior hospitalization with S. aureus (4.84 (1.19-19.63)) and Aboriginality (7.20 (1.91-27.17) (P≤0.027). Serum 25(OH)D was not associated with S. aureus carriage or subsequent hospitalization. CONCLUSIONS S. aureus and MRSA carriage in our patients was consistent with previous general population studies. There were no diabetes-specific risk factors. Persistent colonization may underlie the increased risk of hospitalization with S. aureus.

Optimizing adherence to advice from antimicrobial stewardship audit and feedback rounds

We examined adherence to antimicrobial stewardship prospective audit and feedback rounds in a rehabilitation service compared with the remainder of the acute hospital, and explored the reasons for this. Between October 2014 and December 2015, we retrospectively assessed the rate of non-adherence to advice from antimicrobial stewardship prospective audit and feedback rounds between the rehabilitation service and the acute hospital, along with the source of the patient referral. Compared with the rehabilitation service, acute hospital medical staff were almost twice as likely to not adhere to advice provided on antimicrobial stewardship prospective audit and feedback rounds (13.8% vs. 7.6%, p < 0.0001, relative risk 1.8 [95% confidence interval 1.3, 2.5]). In the rehabilitation service, referrals were more likely to come from medical staff (61.9% vs. 16.3%, p < 0.0001). These findings may be explained by regular, direct engagement of the antimicrobial stewardship team with the rehabilitation service clinical team, a model potentially applicable to other settings.