Genomic surveillance of Escherichia coli and Klebsiella spp. in hospital sink drains and patients.

Escherichia coli and Klebsiella spp. are important human pathogens that cause a wide spectrum of clinical disease. In healthcare settings, sinks and other wastewater sites have been shown to be reservoirs of antimicrobial-resistant E. coli and Klebsiella spp., particularly in the context of outbreaks of resistant strains amongst patients. Without focusing exclusively on resistance markers or a clinical outbreak, we demonstrate that many hospital sink drains are abundantly and persistently colonized with diverse populations of E. coli, Klebsiella pneumoniae and Klebsiella oxytoca, including both antimicrobial-resistant and susceptible strains. Using whole-genome sequencing of 439 isolates, we show that environmental bacterial populations are largely structured by ward and sink, with only a handful of lineages, such as E. coli ST635, being widely distributed, suggesting different prevailing ecologies, which may vary as a result of different inputs and selection pressures. Whole-genome sequencing of 46 contemporaneous patient isolates identified one (2 %; 95 % CI 0.05-11 %) E. coli urine infection-associated isolate with high similarity to a prior sink isolate, suggesting that sinks may contribute to up to 10 % of infections caused by these organisms in patients on the ward over the same timeframe. Using metagenomics from 20 sink-timepoints, we show that sinks also harbour many clinically relevant antimicrobial resistance genes including blaCTX-M, blaSHV and mcr, and may act as niches for the exchange and amplification of these genes. Our study reinforces the potential role of sinks in contributing to Enterobacterales infection and antimicrobial resistance in hospital patients, something that could be amenable to intervention. This article contains data hosted by Microreact.

Enhanced recovery for esophagectomy: a systematic review and evidence-based guidelines.

OBJECTIVE: This article aims to provide the first systematic review of enhanced recovery after surgery (ERAS) programs for esophagectomy and generate guidelines. BACKGROUND: ERAS programs use multimodal approaches to reduce complications and accelerate recovery. Although ERAS is well established in colorectal surgery, experience after esophagectomy has been minimal. However, esophagectomy remains an extremely high-risk operation, commonly performed in patients with significant comorbidities. Consequently, ERAS may have a significant role to play in improving outcomes. No guidelines or reviews have been published in esophagectomy. METHODS: We undertook a systematic review of the PubMed, EMBASE, and the Cochrane databases in July 2012. The literature was searched for descriptions of ERAS in esophagectomy. Components of successful ERAS programs were determined, and when not directly available for esophagectomy, extrapolation from related evidence was made. Graded recommendations for each component were then generated. RESULTS: Six retrospective studies have assessed ERAS for esophagectomy, demonstrating favorable morbidity, mortality, and length of stay. Methodological quality is, however, low. Overall, there is little direct evidence for components of ERAS, with much derived from nonesophageal thoracoabdominal surgery. CONCLUSIONS: ERAS in principle seems logical and safe for esophagectomy. However, the underlying evidence is poor and lacking. Despite this, a number of recommendations for practice and research can be made.

Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilator-associated pneumonia: a retrospective observational study.

BACKGROUND: Despite consensus criteria, diagnosing acute lung injury, or its more severe form acute respiratory distress syndrome (ALI/ARDS) remains challenging. Adding objective measures, such as plasma levels of biological markers could facilitate recognition of ALI/ARDS. This study was designed to assess and compare the diagnostic accuracy of biological markers for ALI/ARDS with ventilator-associated pneumonia (VAP). METHODS: We performed serial measurements of Clara cell protein (CC16), soluble receptor for advanced glycation end products (sRAGE), surfactant protein D (SP-D) and Krebs von den Lungen (KL-6) in plasma of patients with VAP and mechanically ventilated control patients without VAP. ALI/ARDS was diagnosed using the criteria of the North-American European consensus conference. RESULTS: Thirty-seven patients were enrolled - 22 patients with VAP and 15 control patients. Ten patients with pneumonia met the ALI/ARDS consensus criteria. Control patients never met these criteria. Plasma CC16 had a good diagnostic capacity for ALI/ARDS as shown by the receiver operating characteristic curve with an area under the curve of 0.91 (95% confidence interval (CI) 0.79 - 1.00; p < 0.001). Identification of ALI/ARDS patients by sudden increases in plasma CC16 of 30% or more yielded a sensitivity of 90% and a specificity of 92%. Of note, levels of CC16 increased 2 days before ALI/ARDS diagnosis. A cut-off level of 50 ng/ml SP-D yielded a specificity of 100% while the sensitivity was 70%. The area under the curve for SP-D was 0.80 (95% CI 0.58 - 1.00; p = 0.02). The diagnostic accuracies of KL-6 and sRAGE were low. CONCLUSION: Plasma CC16 seems a potential biological marker for ALI/ARDS in patients with VAP. Plasma levels of sRAGE, SP-D and KL-6 have limited discriminative power for diagnosing ALI/ARDS in VAP.

Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during development of ventilator-associated pneumonia.

OBJECTIVE: To determine the diagnostic role of soluble triggering receptor expressed on myeloid cells (sTREM)-1 in non-directed bronchial lavage fluid in ventilator-associated pneumonia (VAP). DESIGN: Non-directed bronchial lavage fluid and plasma were collected on alternate days in critically ill mechanically ventilated patients from the start of ventilatory support until complete weaning from the ventilator. Soluble TREM-1 levels were measured by an enzyme-linked immunosorbent assay. SETTING: A general adult medical and surgical university hospital intensive care unit. PATIENTS: Nine patients who developed VAP and 19 patients who did not develop VAP (controls). RESULTS: Plasma levels of sTREM-1 did not change significantly in either patient group. While in controls concentrations of sTREM-1 in non-directed bronchial lavage fluid did not change significantly over time, in patients who developed VAP levels of sTREM-1 in non-directed bronchial lavage fluid increased towards the diagnosis of VAP. A cut-off value for non-directed bronchial lavage fluid sTREM-1 levels of 200 pg/ml on the day of VAP had a diagnostic sensitivity of 75% and a specificity of 84%. Sensitivity increased when taking into account all sTREM-1 levels higher than 200 pg/ml from the 6-day period before the day of diagnosis that were preceded by an increase of at least 100 pg/ml (sensitivity 88%, specificity 84%). CONCLUSIONS: Soluble TREM-1 is a potential biomarker of VAP.

Compartmentalisation of cytokines and cytokine inhibitors in ventilator-associated pneumonia.

OBJECTIVE: To examine whether cytokine concentrations change in the pulmonary compartment during the development of ventilator-associated pneumonia (VAP). DESIGN: Non-directed bronchial lavage (NBL) was performed every 48 h in critically ill mechanically ventilated patients. Serial measurements of the cytokines tumor necrosis factor (TNF) alpha, interleukin (IL)-1alpha, IL-1beta, IL-6, and IL-10 and the cytokine inhibitors soluble TNFalpha receptor type I (sTNFalphaRI), IL-1 receptor antagonist (IL-1Ra) and soluble IL-1 receptor II (sIL-1RII) were performed on the NBL fluid and matching plasma samples by ELISA. SETTING: An adult medical and surgical university hospital intensive care unit. PATIENTS: Nine patients who developed VAP and nineteen patients who did not develop VAP served as controls. INTERVENTIONS: None. RESULTS: Plasma concentrations of the measured cytokines and cytokine inhibitors did not change significantly in any patients. In control patients, NBL fluid concentrations of sIL-1RII decreased significantly over time (P=0.01). In patients who developed VAP, NBL fluid concentrations of TNFalpha, sTNFalphaRI, IL-1alpha, and IL-1beta increased significantly (P=0.002, P=0.03, P=0.04 and P=0.02, respectively). Furthermore, NBL fluid/plasma concentration ratios for TNFalpha, sTNFalphaRI, IL-1alpha, IL-1Ra and IL-6 increased significantly as VAP developed (P=0.001, P=0.001, P=0.04, P=0.03, and P=0.04, respectively). CONCLUSION: Our results suggest that the production of important cytokines and cytokine inhibitors is compartmentalised within the lung in critically ill mechanically ventilated patients who develop VAP.