Impact of supplementary air filtration on aerosols and particulate matter in a UK hospital ward: a case study.

BACKGROUND: Aerosol spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a major problem in hospitals, leading to an increase in supplementary high-efficiency particulate air filtration aimed at reducing nosocomial transmission. This article reports a natural experiment that occurred when an air cleaning unit (ACU) on a medicine for older people ward was switched off accidentally while being commissioned. AIM: To assess aerosol transport within the ward and determine whether the ACU reduced airborne particulate matter (PM) levels. METHODS: An ACU was placed in a ward comprising two six-bedded bays plus three single-bed isolation rooms which had previously experienced several outbreaks of coronavirus disease 2019. During commissioning, real-time measurements of key indoor air quality parameters (PM1-10, CO2, temperature and humidity) were collected from multiple sensors over 2 days. During this period, the ACU was switched off accidentally for approximately 7 h, allowing the impact of the intervention on PM to be assessed. FINDINGS: The ACU reduced the PM counts considerably (e.g. PM1 65.5-78.2%) throughout the ward (P<0.001 all sizes), with positive correlation found for all PM fractions and CO2 (r=0.343-0.817; all P<0.001). PM counts rose/fell simultaneously when the ACU was off, with correlation of PM signals from multiple locations (e.g. r=0.343-0.868; all P<0.001) for particulates <1 µm). CONCLUSION: Aerosols migrated rapidly between the various ward subcompartments, suggesting that social distancing alone cannot prevent nosocomial transmission of SARS-CoV-2 as this fails to mitigate longer-range (>2 m) transmission. The ACU reduced PM levels considerably throughout the ward space, indicating its potential as an effective intervention to reduce the risk posed by infectious airborne particles.

Viral infections in critical care: a narrative review.

Viral infections form a substantial part of the intensive care workload, even before the recent and ongoing COVID-19 pandemic. The growing availability of molecular diagnostics for viral infections has led to increased recognition of these pathogens. This additional information, however, provides new challenges for interpretation and management. As the SARS-CoV-2 pandemic has amply demonstrated, the emergence and global spread of novel viruses are likely to provide continued challenges for critical care physicians into the future. This article will provide an overview of viral infections relevant to the critical care physician, discussing the diagnosis and management of respiratory viral infections, blood borne and enteric viruses. We will also discuss herpesviridae complications, commonly seen due to reactivation of latent infections. Further, we explore some rarer and emerging viruses, including recognition of viral haemorrhagic fevers, and briefly discuss post-viral syndromes which may present to the intensive care unit. Finally, we will discuss infection control and its importance in preventing nosocomial viral transmission.

Low-pathogenicity Mycoplasma spp. alter human monocyte and macrophage function and are highly prevalent among patients with ventilator-acquired pneumonia.

BACKGROUND: Ventilator-acquired pneumonia (VAP) remains a significant problem within intensive care units (ICUs). There is a growing recognition of the impact of critical-illness-induced immunoparesis on the pathogenesis of VAP, but the mechanisms remain incompletely understood. We hypothesised that, because of limitations in their routine detection, Mycoplasmataceae are more prevalent among patients with VAP than previously recognised, and that these organisms potentially impair immune cell function. METHODS AND SETTING: 159 patients were recruited from 12 UK ICUs. All patients had suspected VAP and underwent bronchoscopy and bronchoalveolar lavage (BAL). VAP was defined as growth of organisms at >10(4) colony forming units per ml of BAL fluid on conventional culture. Samples were tested for Mycoplasmataceae (Mycoplasma and Ureaplasma spp.) by PCR, and positive samples underwent sequencing for speciation. 36 healthy donors underwent BAL for comparison. Additionally, healthy donor monocytes and macrophages were exposed to Mycoplasma salivarium and their ability to respond to lipopolysaccharide and undertake phagocytosis was assessed. RESULTS: Mycoplasmataceae were found in 49% (95% CI 33% to 65%) of patients with VAP, compared with 14% (95% CI 9% to 25%) of patients without VAP. Patients with sterile BAL fluid had a similar prevalence to healthy donor BAL fluid (10% (95% CI 4% to 20%) vs 8% (95% CI 2% to 22%)). The most common organism identified was M. salivarium. Blood monocytes from healthy volunteers incubated with M. salivarium displayed an impaired TNF-α response to lipopolysaccharide (p=0.0003), as did monocyte-derived macrophages (MDMs) (p=0.024). MDM exposed to M. salivarium demonstrated impaired phagocytosis (p=0.005). DISCUSSION AND CONCLUSIONS: This study demonstrates a high prevalence of Mycoplasmataceae among patients with VAP, with a markedly lower prevalence among patients with suspected VAP in whom subsequent cultures refuted the diagnosis. The most common organism found, M. salivarium, is able to alter the functions of key immune cells. Mycoplasmataceae may contribute to VAP pathogenesis.

Development of two real-time multiplex PCR assays for the detection and quantification of eight key bacterial pathogens in lower respiratory tract infections.

The frequent lack of a positive and timely microbiological diagnosis in patients with lower respiratory tract infection (LRTI) is an important obstacle to antimicrobial stewardship. Patients are typically prescribed broad-spectrum empirical antibiotics while microbiology results are awaited, but, because these are often slow, negative, or inconclusive, de-escalation to narrow-spectrum agents rarely occurs in clinical practice. The aim of this study was to develop and evaluate two multiplex real-time PCR assays for the sensitive detection and accurate quantification of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. We found that all eight bacterial targets could be reliably quantified from sputum specimens down to a concentration of 100 CFUs/reaction (8333 CFUs/mL). Furthermore, all 249 positive control isolates were correctly detected with our assay, demonstrating effectiveness on both reference strains and local clinical isolates. The specificity was 98% on a panel of nearly 100 negative control isolates. Bacterial load was quantified accurately when three bacterial targets were present in mixtures of varying concentrations, mimicking likely clinical scenarios in LRTI. Concordance with culture was 100% for culture-positive sputum specimens, and 90% for bronchoalveolar lavage fluid specimens, and additional culture-negative bacterial infections were detected and quantified. In conclusion, a quantitative molecular test for eight key bacterial causes of LRTI has the potential to provide a more sensitive decision-making tool, closer to the time-point of patient admission than current standard methods. This should facilitate de-escalation from broad-spectrum to narrow-spectrum antibiotics, substantially improving patient management and supporting efforts to curtail inappropriate antibiotic use.

Combined dysfunctions of immune cells predict nosocomial infection in critically ill patients.

BACKGROUND: Nosocomial infection occurs commonly in intensive care units (ICUs). Although critical illness is associated with immune activation, the prevalence of nosocomial infections suggests concomitant immune suppression. This study examined the temporal occurrence of immune dysfunction across three immune cell types, and their relationship with the development of nosocomial infection. METHODS: A prospective observational cohort study was undertaken in a teaching hospital general ICU. Critically ill patients were recruited and underwent serial examination of immune status, namely percentage regulatory T-cells (Tregs), monocyte deactivation (by expression) and neutrophil dysfunction (by CD88 expression). The occurrence of nosocomial infection was determined using pre-defined, objective criteria. RESULTS: Ninety-six patients were recruited, of whom 95 had data available for analysis. Relative to healthy controls, percentage Tregs were elevated 6-10 days after admission, while monocyte HLA-DR and neutrophil CD88 showed broader depression across time points measured. Thirty-three patients (35%) developed nosocomial infection, and patients developing nosocomial infection showed significantly greater immune dysfunction by the measures used. Tregs and neutrophil dysfunction remained significantly predictive of infection in a Cox hazards model correcting for time effects and clinical confounders {hazard ratio (HR) 2.4 [95% confidence interval (CI) 1.1-5.4] and 6.9 (95% CI 1.6-30), respectively, P=0.001}. Cumulative immune dysfunction resulted in a progressive risk of infection, rising from no cases in patients with no dysfunction to 75% of patients with dysfunction of all three cell types (P=0.0004). CONCLUSIONS: Dysfunctions of T-cells, monocytes, and neutrophils predict acquisition of nosocomial infection, and combine additively to stratify risk of nosocomial infection in the critically ill.

Pulmonary and systemic effects of mononuclear leukapheresis.

BACKGROUND AND OBJECTIVES: There is increasing evidence that monocytes play a key role in the pathogenesis of acute lung inflammation. Mononuclear cell (MNC) leukapheresis can be used to remove large numbers of monocytes from circulating blood; however, the detailed characteristics of monocyte subpopulations removed by MNC leukapheresis, and the biological effects on the lung, remain incompletely defined. MATERIAL AND METHODS: Six healthy male volunteers underwent MNC leukapheresis of four total blood volumes. Blood was collected at 0, 2, 4, 6, 8 and 24 h; bronchoscopy with bronchoalveolar lavage (BAL) was performed at 8-9 h. Multiparameter flow cytometry was used to identify subpopulations of monocytes in blood and monocyte-like cells in BAL fluid. RESULTS: A median of 5·57×10(9) monocytes were retrieved. Blood monocyte counts indicated that the circulating blood monocyte pool was actively replenished during leukapheresis and subsequently contained a greater proportion of classical (CD14(++) CD16(-)) monocytes. A particular subpopulation of monocyte-like cells, reminiscent of classical monocytes, was also prominent in BAL fluid after leukapheresis. CONCLUSION: Mononuclear cell leukapheresis was safe. The greater proportion of classical monocytes present in blood after MNC leukapheresis may be clinically significant. MNC leukapheresis also appears to affect the proportion of monocyte-like cells in the lung; however, we found no evidence that leukapheresis has a clinically important pro-inflammatory effect in the human lung.

Pain in medical inpatients: an under-recognised problem?

Pain is a common feature of a range of illnesses. Although it is perceived as a significant problem for surgical patients and those with terminal malignancy, there is a paucity of evidence regarding the prevalence of pain in general medical patients. This study set out to determine pain prevalence and the contribution of chronic pain in a teaching hospital medical unit. All wards on the medical unit were visited on three consecutive days and all eligible patients were asked to complete a questionnaire indicating occurrence and severity of pain. Their analgesic prescriptions were also reviewed. A total of 156 patients took part, representing 85% of all inpatients. Chronic pain prior to admission was a common finding, being reported by 57 (37%) of patients and was associated with the occurrence of pain and severe pain (pain score >6) while an inpatient. Overall, 53% of patients experienced pain, 38% had severe pain and 18% had less than 50% analgesic efficacy. Prescription of non-recommended analgesics was common, and was strongly associated with the occurrence of pain (odds ratio 12, 95% confidence interval 4-38). Large numbers of patients had contraindications to commonly prescribed medications. Dissatisfaction was closely linked to poor response to prescribed analgesics, non-recommended prescription and severe pain. Pain is common among medical patients. Chronic pain is a major problem and complicates the issue of analgesic prescription. There is considerable scope for improvement in the management of pain among medical patients. However, pain control for these patients is likely to be more complex than for surgical patients.