Cervicovaginal microbiota and metabolome predict preterm birth risk in an ethnically diverse cohort.

The syndrome of spontaneous preterm birth (sPTB) presents a challenge to mechanistic understanding, effective risk stratification, and clinical management. Individual associations between sPTB, self-reported ethnic ancestry, vaginal microbiota, metabolome, and innate immune response are known but not fully understood, and knowledge has yet to impact clinical practice. Here, we used multi-data type integration and composite statistical models to gain insight into sPTB risk by exploring the cervicovaginal environment of an ethnically heterogenous pregnant population (n = 346 women; n = 60 sPTB < 37 weeks' gestation, including n = 27 sPTB < 34 weeks). Analysis of cervicovaginal samples (10-15+6 weeks) identified potentially novel interactions between risk of sPTB and microbiota, metabolite, and maternal host defense molecules. Statistical modeling identified a composite of metabolites (leucine, tyrosine, aspartate, lactate, betaine, acetate, and Ca2+) associated with risk of sPTB < 37 weeks (AUC 0.752). A combination of glucose, aspartate, Ca2+, Lactobacillus crispatus, and L. acidophilus relative abundance identified risk of early sPTB < 34 weeks (AUC 0.758), improved by stratification by ethnicity (AUC 0.835). Increased relative abundance of L. acidophilus appeared protective against sPTB < 34 weeks. By using cervicovaginal fluid samples, we demonstrate the potential of multi-data type integration for developing composite models toward understanding the contribution of the vaginal environment to risk of sPTB.

Antibiotic use and clinical outcomes in the acute setting under management by an infectious diseases acute physician versus other clinical teams: a cohort study.

OBJECTIVES: To assess the magnitude of difference in antibiotic use between clinical teams in the acute setting and assess evidence for any adverse consequences to patient safety or healthcare delivery. DESIGN: Prospective cohort study (1 week) and analysis of linked electronic health records (3 years). SETTING: UK tertiary care centre. PARTICIPANTS: All patients admitted sequentially to the acute medical service under an infectious diseases acute physician (IDP) and other medical teams during 1 week in 2013 (n=297), and 3 years 2012-2014 (n=47 585). PRIMARY OUTCOME MEASURE: Antibiotic use in days of therapy (DOT): raw group metrics and regression analysis adjusted for case mix. SECONDARY OUTCOME MEASURES: 30-day all-cause mortality, treatment failure and length of stay. RESULTS: Antibiotic use was 173 vs 282 DOT/100 admissions in the IDP versus non-IDP group. Using case mix-adjusted zero-inflated Poisson regression, IDP patients were significantly less likely to receive an antibiotic (adjusted OR=0.25 (95% CI 0.07 to 0.84), p=0.03) and received shorter courses (adjusted rate ratio (RR)=0.71 (95% CI 0.54 to 0.93), p=0.01). Clinically stable IDP patients of uncertain diagnosis were more likely to have antibiotics held (87% vs 55%; p=0.02). There was no significant difference in treatment failure or mortality (adjusted p>0.5; also in the 3-year data set), but IDP patients were more likely to be admitted overnight (adjusted OR=3.53 (95% CI 1.24 to 10.03), p=0.03) and have longer length of stay (adjusted RR=1.19 (95% CI 1.05 to 1.36), p=0.007). CONCLUSIONS: The IDP-led group used 30% less antibiotic therapy with no adverse clinical outcome, suggesting antibiotic use can be reduced safely in the acute setting. This may be achieved in part by holding antibiotics and admitting the patient for observation rather than prescribing, which has implications for costs and hospital occupancy. More information is needed to indicate whether any such longer admission will increase or decrease risk of antibiotic-resistant infections.

Breath metabolite response to major upper gastrointestinal surgery.

BACKGROUND: Esophagectomy and gastrectomy are associated with profound metabolic changes and significant postoperative morbidity. The aim of this prospective clinical study was to determine whether breath analysis can offer novel insight into the surgical metabolic response and identify biomarkers of postoperative complications, including lung injury. METHODS: Breath samples were collected preoperatively and at 24, 48, 72, 96 and 168 h after esophagectomy (n = 25) and gastrectomy (n = 15). Targeted analysis of four prominent breath metabolites was performed by selected ion flow-tube mass spectrometry. Patients with nonsurgical lung injury (community-acquired pneumonia) were recruited as positive controls. RESULTS: Perioperative starvation and subsequent reintroduction of nutritional input were associated with significant changes in breath acetone levels. Breath acetone levels fell after esophagectomy (P = 0.008) and were significantly lower than in gastrectomy patients at postoperative time points 48 (P < 0.001) and 72 h (P < 0.001). In contrast, concentrations of isoprene increased significantly after esophagectomy (P = 0.014). Pneumonia was the most frequently observed postoperative complication (esophagectomy 36% and gastrectomy 7%). The concentration of hydrogen cyanide was significantly lower in the breath of patients who developed pneumonia, 72 h after surgery (P = 0.008). Exhaled hydrogen cyanide (P = 0.001) and isoprene (P = 0.014) were also reduced in patients with community-acquired pneumonia compared with healthy controls. CONCLUSIONS: Selected ion flow-tube mass spectrometry can be used as a totally noninvasive resource to monitor multiple aspects of metabolic alterations in the postoperative period. Exhaled concentrations of several prominent metabolites are significantly altered after major upper gastrointestinal surgery and in response to pneumonia.

On-line, real time monitoring of exhaled trace gases by SIFT-MS in the perioperative setting: a feasibility study.

A study is described of the first on line, real time analyses of the exhaled breath of five anaesthetized patients during the complete perioperative periods of laparoscopic surgery. These breath analyses were achieved using a selected ion flow tube, SIFT-MS, instrument, located in the operating theatre at an acceptable distance from the operating table, and coupled to the endotracheal tube in the ventilation circuit via a 5 metre long capillary tube. Thus, inhalation/exhalation breathing cycles, set to be at a frequency of 10 per minute, were sampled continuously for water vapour, the metabolites acetone and isoprene and the propofol used to induce anaesthesia for each operating period that ranged from 20 min (shortest) to 80 min (longest). Whilst there was some loss of water vapour along the long sampling line, the concentrations of the other trace compounds were not diminished. The breath acetone was essentially at a constant level for each patient, but increased somewhat over the longest operating period due to the onset of lipolysis. Most interesting is the clear increase of breath isoprene following abdomen inflation with carbon dioxide. The vapour of the intravenously injected propofol was detected in the exhaled breath and remained essentially constant during the perioperative period. These analyses were performed totally non-invasively and the data were immediately and constantly available to the anaesthetist and surgeon. Exploitation of this development could influence decision making and potentially improve patient safety within the perioperative setting.