A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship.

Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting. Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification. Results: Overall, 6.4% of ICU admissions (305/4781) received AFT, accounting for 11.41 days of therapy/100 occupied bed days (DOT/100 OBD). The dominant prescribing mode was empirical (41% of consumption), followed by targeted (22%), prophylaxis (18%), pre-emptive (12%) and non-invasive (7%). Echinocandins were the most commonly prescribed drug class (4.59 DOT/100 OBD). In total, 217 patients received AFT for suspected or confirmed IFI; 12%, 10% and 23% were classified as possible, probable or proven IFI, respectively. Hence, in 55%, IFI was unlikely. Proven IFI (n = 50) was mostly invasive candidiasis (92%), of which 48% had been initiated on AFT empirically before yeast identification. Where on-site (1 → 3)-ß-d-glucan (BDG) testing was available (1 day turnaround), in those with suspected but unproven invasive candidiasis, median (IQR) AFT duration was 10 (7-15) days with a positive BDG (≥80 pg/mL) versus 8 (5-9) days with a negative BDG (<80 pg/mL). Post-prescription review occurred in 79% of prescribing episodes (median time to review 1 [0-3] day). Where suspected IFI was not confirmed, 38% episodes were stopped and 4% de-escalated within 5 days. Conclusions: Achieving a better balance between promptly treating IFI patients and avoiding inappropriate antifungal prescribing in the ICU requires timely post-prescription review by specialist multidisciplinary teams and improved, evidence-based-risk prescribing strategies incorporating rapid diagnostics to guide AFT start and stop decisions.

Antibiotic-resistant hypervirulent Klebsiella pneumoniae causing community- acquired liver abscess: an emerging disease.

We report a case of a patient with fatal community-acquired pyogenic liver abscess (CA-PLA) caused by multi drug-resistant, hypervirulent, Klebsiella pneumoniae (mdrhvKP). HvKP causing PLA has been described in East and South East Asia and it is recognized as an emerging infection worldwide. The syndrome is characterized by cryptogenic liver abscess formation without a previous history of hepatobiliary or colonic disease and metastatic spread of infection via the bloodstream to distant sites, including lungs, central nervous system and other organ systems. Diabetes mellitus is a recognized risk factor. Most previously reported cases have involved antibiotic susceptible strains of hvKP although reports of bloodstream infections caused by resistant strains, including carbapenemase producers, are increasing. Our report highlights the need for awareness of this devastating infection in patients presenting with sepsis and liver abscess without underlying hepatobiliary or colonic disease.

Gram negative septicaemia diagnosed on peripheral blood smear appearances.

Buffy coat smears from febrile patients may contain visible bacteria and therefore detect bacteraemia before conventional blood cultures become positive. However, it is unusual to see micro-organisms in an otherwise untreated peripheral blood smear. The case of a febrile neutropenic patient is reported. A Wright's stained peripheral blood smear contained bacterial elements, thus making earlier diagnosis of septicaemia and identification of the causative bacterium possible.

The use of a squid third order spatial gradiometer to measure magnetic fields of the brain.

It appears to be clear from the results that the third order gradiometer is able to detect small biomagnetic signals from the brain which are related to evoked potentials and spontaneous electrical activity. The instrument operates reasonably well within a noisy environment, however further development is necessary to balance the first gradient. We intend to pursue this direction with software systems. Some of the data presented suggest that components of MEG evoked activity may change independently of EEG. One interpretation which may derive from this is that the same current dipoles are probably not responsible for the entire configuration of evoked fields. This interpretation is consistent with EEG evidence which indicates that analogous components in the evoked potential may vary independently as a function of stimulus parameters and information processing. Perhaps a model of magnetic dipoles due to small current loops would be more compatible with the electrophysiological data.

Giant cell arteritis--A cause of pyrexia of unknown origin.

Giant cell arteritis may present atypically with symptoms of malaise, anorexia, weight loss and fever that could lead to diagnostic difficulties. We describe two cases which the prominent initial feature was protracted pyrexia. Clinicians should seriously consider temporal artery biopsy in such cases.

Advanced electronics for the CTF MEG system.

Development of the CTF MEG system has been advanced with the introduction of a computer processing cluster between the data acquisition electronics and the host computer. The advent of fast processors, memory, and network interfaces has made this innovation feasible for large data streams at high sampling rates. We have implemented tasks including anti-alias filter, sample rate decimation, higher gradient balancing, crosstalk correction, and optional filters with a cluster consisting of 4 dual Intel Xeon processors operating on up to 275 channel MEG systems at 12 kHz sample rate. The architecture is expandable with additional processors to implement advanced processing tasks which may include e.g., continuous head localization/motion correction, optional display filters, coherence calculations, or real time synthetic channels (via beamformer). We also describe an electronics configuration upgrade to provide operator console access to the peripheral interface features such as analog signal and trigger I/O. This allows remote location of the acoustically noisy electronics cabinet and fitting of the cabinet with doors for improved EMI shielding. Finally, we present the latest performance results available for the CTF 275 channel MEG system including an unshielded SEF (median nerve electrical stimulation) measurement enhanced by application of an adaptive beamformer technique (SAM) which allows recognition of the nominal 20-ms response in the unaveraged signal.

Psychoneuroimmunology and cancer: historical perspectives and current research.

The belief that cancer might be related to temperament or distress has been emphasized throughout the history of medicine. The field of psychoneuroimmunology has its origins in psychosomatic medicine, and has evolved to the investigations of complex interactions between the psyche and the nervous, immune, and endocrine systems. Such interactions may have implications in both cancer risk and survival.

pIF21, a versatile donor of transposons Tn1, Tn5 and Tn7 for tagging and mobilizing cryptic and non-selectable plasmids.

A plasmid, pIF21, has been constructed that is able to donate transposons Tn1, Tn5 and Tn7. The transposons are located on a temperature-sensitive derivative of the incP1 plasmid pRP1, which is transferable to a wide range of Gram-negative genera.

Biomagnetometers for unshielded and well shielded environments.

The paper describes magnetometers for operation in well shielded and unshielded environments. For unshielded environments, the noise cancellation is accomplished by spatial filtering using higher-order gradiometers which are formed in software. The theory of the software formation of high-order gradiometers has been successfully tested experimentally to the second-order gradient level, using a seven-channel prototype system. An unshielded, open environment system, designed to operate with third-order noise cancellation is presently under construction. It is a whole head system, consisting of a minimum of 64 sensing channels, and is expected to be operational by late 1991. In the opposite extreme, a magnetometer is being developed for operation in a well shielded environment of a whole body superconducting shield. The high temperature superconducting shield will operate in liquid nitrogen, while the magnetometer detection system will operate in liquid helium. The high level of shielding will allow detection of biomagnetic signals using magnetometers. The whole body high temperature superconducting shielded system is presently under development and a half scale working shield already exists. The complete whole body shielded system is expected to be operational in 1994/95.

Psychosocial effects of enhanced external counterpulsation in the angina patient: a second study.

Enhanced external counterpulsation (EECP) is a noninvasive technique that has shown promise in the treatment of ischemic coronary artery disease. Patients undergoing EECP were tested for alterations in psychosocial state associated with treatment. Overall perception of health and quality of life improved with EECP. There was also significant improvement in levels of depression, anxiety, and somatization but no change in levels of anger or hostility. On most measures, change was more significant for subjects who showed objective evidence of resolution of ischemia. Given the known predictive relationship between depression and mortality from cardiac disease, the improvement in depression scores through EECP indicates a finding of potential importance that may warrant further study in future research.

Psychiatric symptoms and medical utilization in primary care patients.

In two studies, the authors evaluated the impact of psychiatric disorders on medical care utilization in a primary care setting. In the first study, 526 consecutive patients in a teaching hospital primary care practice completed the 18-item RAND Mental Health Inventory to identify clinically significant depression and/or anxiety and a questionnaire about the use of psychiatric treatment and psychoactive medications. The medical utilization of those patients defined as depressed and/ or anxious was compared with those defined as not depressed and/or anxious. Patients identified as depressed and/or anxious reported significantly increased medical utilization, but this was not confirmed by the hospital's computerized record system. In the second study, the authors analyzed medical care utilization for the years before and after the first outpatient psychiatry appointment of a sample of 91 patients referred from the same primary care practice to the hospital's outpatient psychiatry clinic over a 1-year period. In both studies there was not a statistically significant difference in medical utilization among those patients receiving psychiatric treatment. The findings demonstrate the difficulties in examining cost offset in a primary care population and raise questions about it as a realistic outcome measure of the effect of psychiatric treatment.