Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

INTRODUCTION: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. METHODS: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. RESULTS: In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum ß-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). CONCLUSIONS: After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.

Tigecycline use in the outpatient parenteral antibiotic therapy setting.

In the context of globally increasing antimicrobial resistance, tigecycline appears to be a useful therapeutic option. The need for prolonged courses for complex infections has prompted consideration of its use via outpatient parenteral antibiotic therapy (OPAT) programmes, although clinical outcomes when used in this setting remain unknown. We retrospectively reviewed the patient characteristics and outcomes of 11 patients who received tigecycline, most commonly delivered as 100 mg once daily, via OPAT at three tertiary Australian hospitals. Rates of co-morbidity and prior antibiotic use were high. Patients had a wide range of infections including bone and/or joint (n = 5), intra-abdominal (n = 3), lower respiratory tract (n = 2) and parapharyngeal abscess (n = 1). Mycobacterial species (n = 5) were the most frequent pathogen, and multi-resistant organisms were common (n = 4). The median OPAT duration was 14 days (IQR 6-30). Nausea was encountered in 45 % of cases. At completion of OPAT, 1 patient (9 %) was cured, 2 (18 %) had improved and 8 (73 %) failed therapy. Failure occurred due to either progression or non-response of infection (n = 4), re-admission (n = 3), premature cessation of tigecycline due to nausea (n = 3) or death (n = 1). Whilst OPAT delivery of tigecycline is a therapeutic option, when used as second-line therapy for complex, often multi-resistant infections in patients with multiple comorbidities, high rates of clinical failure, readmissions and adverse effects, especially nausea, should be anticipated.

A comparison of paediatric and adult infectious diseases consultations in Australia and New Zealand.

The objective of this paper is to describe paediatric infectious diseases consultations across Australia and New Zealand. We surveyed infectious diseases physicians at 51 hospitals over a period of 2 weeks in 2012. Compared with adult consults, paediatric consults were more frequently received from general paediatricians/physicians and intensive care, yet less frequently from surgeons and emergency. Respiratory, skin/soft tissue and bone/joint infections were the most frequent consultations in children. These data demonstrate the breadth of formal infectious diseases consults in children. Differences between paediatric and infectious diseases consultations need to be considered when planning both paediatric and adult physician training and future curriculum development.

What do infectious diseases physicians do? A 2-week snapshot of inpatient consultative activities across Australia, New Zealand and Singapore.

The practice of an infectious diseases (ID) physician is evolving. A contemporary understanding of the frequency and variety of patients and syndromes seen by ID services has implications for training, service development and setting research priorities. We performed a 2-week prospective survey of formal ID physician activities related to direct inpatient care, encompassing 53 hospitals throughout Australia, New Zealand and Singapore, and documented 1722 inpatient interactions. Infections involving the skin and soft tissue, respiratory tract and bone/joints together accounted for 49% of all consultations. Suspected/confirmed pathogens were primarily bacterial (60%), rather than viral (6%), fungal (4%), mycobacterial (2%) or parasitic (1%). Staphylococcus aureus was implicated in 409 (24%) episodes, approximately four times more frequently than the next most common pathogen. The frequency of healthcare-related infections (35%), immunosuppression (21%), diabetes mellitus (19%), prosthesis-related infections (13%), multiresistant pathogens (13%) and non-infectious diagnoses (9%) was high, although consultation characteristics varied between geographical settings and hospital types. Our study highlights the diversity of inpatient-related ID activities and should direct future teaching and research. ID physicians' ability to offer beneficial consultative advice requires broad understanding of, and ability to interact with, a wide range of referring specialities.

Point-prevalence study of inappropriate antibiotic use at a tertiary Australian hospital.

A point-prevalence study at a tertiary Australian hospital found 199 of 462 inpatients (43%) to be receiving antibiotic therapy. Forty-seven per cent of antibiotic use was discordant with guidelines or microbiological results and hence considered inappropriate. Risk factors for inappropriate antibiotic prescribing included bone/joint infections, the absence of infection, creatinine level >120 µmol/L, carbapenem or macrolide use and being under the care of the aged care/rehabilitation team. In the setting of finite antimicrobial stewardship resources, identification of local determinants for inappropriate antibiotic use may enable more targeted interventions.

Induced encystment improves resistance to preservation and storage of Acanthamoeba castellanii.

Several conditions that allow the preservation, storage and rapid, efficient recovery of viable Acanthamoeba castellanii organisms were investigated. The viability of trophozoites (as determined by time to confluence) significantly declined over a period of 12 months when stored at -70 degrees C using dimethyl sulfoxide (DMSO; 5 or 10%) as cryopreservant. As A. castellanii are naturally capable of encystment, studies were undertaken to determine whether induced encystment might improve the viability of organisms under a number of storage conditions. A. castellanii cysts stored in the presence of Mg2+ at 4 degrees C remained viable over the study period, although time to confluence was increased from approximately 8 days to approximately 24 days over the 12-month period. Storage of cysts at -70 degrees C with DMSO (5 or 10%) or 40% glycerol, but not 80% glycerol as cryopreservants increased their viability over the 12-month study period compared with those stored at room temperature. Continued presence of Mg2+ in medium during storage had no adverse effects and generally improved recovery of viable organisms. The present study demonstrates that A. castellanii can be stored as a non-multiplicative form inexpensively, without a need for cryopreservation, for at least 12 months, but viability is increased by storage at -70 degrees C.