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.

Four-dimensional ultrasound current source density imaging of a dipole field.

Ultrasound current source density imaging (UCSDI) potentially transforms conventional electrical mapping of excitable organs, such as the brain and heart. For this study, we demonstrate volume imaging of a time-varying current field by scanning a focused ultrasound beam and detecting the acoustoelectric (AE) interaction signal. A pair of electrodes produced an alternating current distribution in a special imaging chamber filled with a 0.9% NaCl solution. A pulsed 1 MHz ultrasound beam was scanned near the source and sink, while the AE signal was detected on remote recording electrodes, resulting in time-lapsed volume movies of the alternating current distribution.

An anatomical study of the myelination of human laryngeal nerves.

OBJECTIVE: To determine the differences in myelination between the human recurrent laryngeal nerve and superior laryngeal nerve. METHODS: Fifteen confirmed laryngeal nerve specimens were harvested from five cadavers. Cross-sections were examined under a photomicroscope and morphometric analysis performed. RESULTS: There was a significantly greater number of myelinated fibres than unmyelinated fibres, in both the recurrent laryngeal nerve (p = 0.018) and the superior laryngeal nerve (p = 0.012). There was a significantly greater number of myelinated fibres in the superior laryngeal nerve, compared with the recurrent laryngeal nerve (p = 0.028). However, there was no significant difference in the number of unmyelinated fibres, comparing the two nerves (p = 0.116). CONCLUSION: These findings support those of previous studies, and provide further evidence against the historical plexus theory of laryngeal nerve morphology. The differences in the degree of myelination, both within and between the human laryngeal nerves, may have clinical consequence regarding recovery of function following nerve injury.

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.

Peripheral intravenous cannulation: safe insertion and removal technique.

The aim of this article is to reinforce good practice in insertion and removal techniques for peripheral intravenous cannulation. The article is intended as a practical guide. It is important that staff receive adequate education and training to undertake this skill competently, and also that they maintain competence in practice.

The safe removal of central venous catheters.

Many nurses working in general wards and departments are caring for patients with central venous catheters and are increasingly responsible for their removal. This article outlines the basis of good practice and the possible complications, focusing on air embolism.

Prevention of infection in peripheral intravenous devices.

This article focuses on peripheral intravenous cannulation devices as one source of infection. Using the chain of infection, each aspect is explored to help reduce or prevent infection.

Sudden unexpected death in infancy: place and time of death.

In recent years, many babies who die of Sudden Unexpected Death in Infancy (SUDI) in Northern Ireland are found dead in bed--i.e. co-sleeping--with an adult. In order to assess its frequency autopsy reports between April 1996 and August 2001 were reviewed and linked to temporal factors. The day and month of death, and the place where the baby was found were compared to a reference population of infant deaths between one week of age and the second birthday. Although the rate of SUDI was lower than the UK average, 43 cases of SUDI were identified, and two additional deaths with virtually identical autopsy findings that were attributed to asphyxia caused by suffocation due to overlaying. Thirty-two of the 45 (71%) were less than four months of age. In 30 of the 45 cases (67%) the history stated that the baby was bed sharing with others; 19 died sleeping in an adult bed, and 11 on a sofa or armchair. In 16 of the 30 (53%) there were at least two other people sharing the sleeping surface, and in one case, three. SUDI was twice as frequent at weekends (found dead Saturday-Monday mornings) compared to weekdays (p<0.02), and significantly more common compared to reference deaths (p<0.002). Co-sleeping deaths were also more frequent at weekends. Almost half of all SUDI (49%) occurred in the summer months--more than twice the frequency of reference deaths. While sharing a place of sleep per se may not increase the risk of death, our findings may be linked to factors such as habitual smoking, consumption of alcohol or illicit drugs as reported in case-control studies. In advising parents on safer childcare practices, health professionals must be knowledgeable of current research and when, for example, giving advice on co-sleeping this needs to be person-specific cognisant of the risks within a household. New and better means of targeting such information needs to be researched if those with higher risk life-styles are to be positively influenced.

Venepuncture: best practice.

Venepuncture is the introduction of a needle into a vein to obtain a blood sample for haematological, biochemical or bacteriological analysis. It is the most common invasive procedure undertaken in hospital. This article provides guidance on the theory and practice of venepuncture.

An investigation of erectile dysfunction in Gwent, Wales.

OBJECTIVE: To quantify incidence of erectile dysfunction (ED) and the associated risk factors in men attending community clinics in a large population in Wales, UK. SUBJECTS AND METHODS: Of 4060 men who were invited to attend 11 community clinics, primarily to check for prostate disease, 2025 (aged 55-70 years) attended. Of these, 2002 men answered a questionnaire about personal details, medical, family and sexual history, and detailed alcohol and smoking habits. All had their serum prostate-specific antigen (PSA) analysed and those referred for investigation of prostatic disease underwent serum testosterone analysis. RESULTS: Complete ED was reported by 265 men (13.2%), and was closely related to age (r = 0.19, P < 0.001) and medication (r = 0.2, P < 0.001). ED occurred in 6.9% of men aged 55-60 years, 12.5% aged 61-65 and 22.2% of those aged 66-70. Patients taking diabetic medication had the highest relative risk for ED and 11.3% of men with ED were taking nitrates. The numbers of years of smoking had the third closest correlation with impotence (r = 0.16, P < 0.001). A low serum testosterone level was a poor predictor of ED and increasing serum PSA levels did not influence the distribution of ED. CONCLUSION: About 13% of these men aged 55-70 years had complete ED; if this value is extrapolated to the whole of the UK, this equates to almost half a million men being unable to achieve any erections. The estimate would be much greater if those with milder forms of ED are included.

Compartmental responses to acute osmotic stress in Leishmania major result in rapid loss of Na+ and Cl-.

The elemental composition of the cytoplasm, electron dense vacuoles, and heterochromatin and euchromatin regions of the nucleus of Leishmania major promastigotes was measured by electron probe X-ray microanalysis under iso-osmotic conditions (305 mOsM) and shortly after a sudden increase (to 615 mOsM) or decrease (to 153 mOsM) in the osmolality of the buffer in which they were suspended. In response to acute hypotonicity a complete loss of Na from the electron dense vacuoles and an approximately threefold decrease in the Na concentrations in the cytoplasm and the nuclear regions occurred, together with an approximately threefold decrease in Cl content in each compartment and a smaller (approx. 1.2-fold) decrease in K content. Thus, in addition to the rapid change in shape and release of amino acids known to occur in response to acute hypo-osmotic stress, a major efflux of Na and Cl, and, to a lesser extent, of K, also occurs. In response to acute hypertonicity Na in the acidocalcisomes did not change but Na content of the cytoplasm decreased by 33%. A small increase in the S content of the cytoplasm and the electron dense vacuolar compartments occurred. No changes were detectable in Ca or Zn content in any of the compartments examined in response to hypotonicity or hypertonicity.

Syringe pumps and start-up time: ensuring safe practice.

The start-up time is the delay between starting an infusion pump and the delivery of fluid at the set flow rate. Mechanical slack in syringe pumps can lead to start-up delays of an hour or more at low-flow rates. During this period no medication is delivered to the patient. The causes of the start-up time delay, its implications and methods of minimising the delay are explained.

Dexamethasone induced cardiac hypertrophy in newborn rats is accompanied by changes in myosin heavy chain phenotype and gene transcription.

Cardiac hypertrophy has been observed in newborn infants treated with dexamethasone (DEX). This study was undertaken to examine whether DEX-induced hypertrophy in newborn rats is associated with redistribution of cardiac myosin heavy chain (MHC) isoforms and, if so, the effects involve transcriptional regulation. Newborn rats were injected with either DEX (1 mg/kg/day; s.c.) or equivalent volume normal saline for 1, 3, 5, 7 or 9 days. Hypertrophy was quantified by heart dry/wet wt ratios, heart/body wt ratios, and total protein content of the myocardium. Changes in the expression of cardiac MHC mRNA were characterized by northern blot and slot blot analyses, using isoform specific probes for alpha- and beta-MHC genes. DEX effect on alpha-MHC gene transcription was analyzed by transiently transfecting various alpha-MHC promoter/CAT reporter constructs into primary cultures of cardiac myocytes derived from one day old rat pups. DEX administration into newborn rats produced significant cardiac hypertrophy ranging from 23% at day 1 to 59% at 9 days. The hypertrophy was accompanied by immediate increase (83%) in steady state level of the alpha-MHC mRNA within one day and a maximum increase (148%) at 7 days of treatment. The steady state level of beta-MHC mRNA declined by 25% at day 1 and a maximum decrease of 54% at day 7 of DEX treatment. The changes in MHC mRNA were also reflected in their protein levels as determined by V1 and V3 isozyme analysis. DEX treatment of primary cultures of cardiomyocytes following transfection with alpha-MHC promoter/CAT reporter constructs resulted in increased CAT expression in a dose dependent manner. The minimum alpha-MHC gene sequences responding to DEX treatment were located between the -200 to -74-bp region of the gene, resulting in 2-fold and 6-fold activation of CAT reporter after 0.05 and 0.1 mM doses of DEX, respectively. Our data indicate that DEX induced cardiac hypertrophy in newborn rats is accompanied by increased expression of alpha-MHC and decreased expression of beta-MHC. The alpha-MHC effects are mediated in part through transcriptional mechanisms.