Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures.

Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls' microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.

Assessment of Bacterial Colonization of Intracranial Pressure Transducers: A Prospective Study.

OBJECTIVES: Cerebral infections related to the presence of an intraparenchymal intracranial pressure transducer (ICPT) are rare. We assessed the incidence of ICPT-related infections and colonization using culture, molecular biology, and electron microscopy. METHODS: All consecutive patients in a neurosurgical intensive care unit who had an ICPT inserted between March 2017 and February 2018 were prospectively included. Presence of colonization on the ICPTs was assessed after removal using culture, scanning electron microscopy (SEM), and next-generation sequencing (NGS). RESULTS: Fifty-three ICPTs (53 patients), indwelling for a median of 4 (range 3-7) days, were studied. Median patient follow-up was 3 months. SEM, microbial culture, and NGS were performed for 91%, 79%, and 72% of ICPTs, respectively; 28 ICPTs (53%) were assessed using all three techniques. No patient developed ICPT-related infection. Microbial cultures were positive for two of the ICPTs (5%); colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was observed on 35/48 (73%) of ICPTs. A median of 10 (8-12) operational taxonomic units were identified for each ICPT, most being of environmental origin. There was no association between biofilm maturity and antimicrobial treatment or duration of ICPT insertion. Antimicrobial treatment was associated with decreased alpha and beta-diversity (p = 0.01). CONCLUSIONS: We observed no ICPT-related cerebral infections although colonization was identified on all ICPTs using NGS and SEM. Mature biofilm was the main bacterial lifestyle on the ICPTs.

Clinical, biological, and microbiological pattern associated with ventriculostomy-related infection: a retrospective longitudinal study.

BACKGROUND: Our aim was to describe the pattern of ventriculostomy-related infection (VRI) development using a dynamic approach. STUDY DESIGN: Retrospective longitudinal study. METHODS: We analyzed the files of 449 neurosurgical patients who underwent placement of external ventricular drain (EVD). During the study period, CSF sampling was performed on a daily base setting. VRI was defined as a positive CSF culture resulting in antibiotic treatment. For VRI patients, we arbitrary defined day 0 (D0) as the day antibiotic treatment was started. In these patients, we compared dynamic changes in clinical and biological parameters at four pre-determined time points: (D-4, D-3, D-2, D-1) with those of D0. For all CSF-positive cultures, we compared CSF biochemical markers' evolution pattern between VRI patients and the others, considered as a control cohort. RESULTS: Thirty-two suffered from VRI. Peripheral white blood cell count did not differ between D-4-D0. Median body temperature, CSF cell count, median Glasgow Coma Scale, CSF protein, and glucose concentrations were significantly different between D-4, D-3, D-2, and D0. At D0, 100 % of CSF samples yielded organisms in culture. The physician caring for the patient decided to treat VRI based upon positive CSF culture in only 28 % (9/32) of cases. In the control cohort, CSF markers' profile trends to normalize, while it worsens in the VRI patients. CONCLUSIONS: We showed that clinical symptoms and biological abnormalities of VRI evolved over time. Our data suggest that VRI decision to treat relies upon a bundle of evidence, including dynamic changes in CSF laboratory exams combined with microbiological analysis.

Natural history of ventriculostomy-related infection under appropriate treatment and risk factors of poor outcome: a retrospective study.

OBJECTIVEThe authors aimed to describe the natural history of ventriculostomy-related infections (VRIs) under appropriate treatment and to assess risk factors for poor outcome.METHODSAll patients older than 18 years in whom an external ventricular drain (EVD) had been implanted and who had developed a VRI requiring treatment were included in this retrospective study. D0 was defined as the first day of antibiotic administration. Clinical and biological parameters were compared each day beginning with D1 and ending with D10 to those of D0. The authors defined D0 in a control group as the day a CSF culture came back positive, without any sign of infection. The authors then searched for poor prognostic factors in the VRI group.RESULTSAmong 567 patients requiring an EVD between January 2007 and October 2017, 39 developed a VRI. Most were monomicrobial infections, and 47 microbes were responsible (45% were gram-positive cocci). Clinical parameters differed significantly from the control group during the first 2 days and then returned to baseline. The CSF parameters differed significantly from the control group for a longer period, returning to baseline after 5 days. CSF sterilization occurred in a median time of 2 days. An intrathecal route or EVD exchange was not associated with a poor outcome. No clinical or biological parameter between D3 and D5 was linked to outcome.CONCLUSIONSClinical status improved faster than CSF parameters (before and after D5, respectively). Some CSF parameters remained abnormal until D10. Body temperature and microbiological cultures normalized faster than other parameters.

Is First-Line Vancomycin Still the Best Option to Treat Staphylococcus Health Care-Associated Meningitis?

BACKGROUND: Cerebrospinal fluid (CSF) penetration of vancomycin through the blood-brain barrier is poor but important inflammation improved it. Hence, vancomycin is recommended for the treatment of community meningitis. However, what about mild inflammatory health care-associated meningitis? The aim of this study was to evaluate the impact of vancomycin diffusion on CSF in Staphylococcus epidermidis health care-associated meningitis. CASE DESCRIPTION: This was a retrospective study of all consecutive patients with S. epidermidis CSF shunt-associated infection, which was treated by continuous intravenous vancomycin after standard of care (60 mg/kg/d after a loading dose of 15 mg/kg). Patient outcome, CSF protein level, and vancomycin concentration in CSF and serum were assessed. We report 6 consecutives cases. Clinical and biologic manifestations were of mild intensity. Meningeal permeability was moderately altered with low CSF protein levels. Despite appropriate vancomycin dosage resulting in high serum concentrations, CSF remained below the S. epidermidis minimal inhibitory concentration. CONCLUSIONS: We propose to reassess vancomycin use as first-line therapy when meningeal inflammation is mild-to-moderate in favor of antibiotics, which have a better CSF penetration.

The multistep road to ventilator-associated lung abscess: A retrospective study of S.aureus ventilator-associated pneumonia.

OBJECT: We observed some cases of lung abscess (LA) in ICU patients suffering S.aureus ventilator-associated pneumonia (S.aureus-VAP). We aimed to assess which of the host and/or bacteria-related features are associated with LA. METHODS: We conducted a retrospective study from January 2009 to July 2013 in a trauma surgical ICU within a teaching hospital. All adult patients presenting with S.aureus-VAP were included. We compared two groups of patients according to the formation or not of LA concomitantly to S.aureus-VAP. RESULTS: Seventy-nine S.aureus-VAP patients, predominantly males (85%) of rather young age (mean [SD]: 35yr [21-64]) with severe trauma (initial Simplified Acute Score II = 42 [32-52]) related-ICU admission, were included. Among them, 10 (14%) developed LA. Patient's characteristics significantly associated with LA development were: a younger age (p = 0.003), road traffic accidents admission (p = 0.017), head injury (p = 0.002), lower Glasgow Coma Scale (p = 0.009), blunt chest trauma (p = 0.01) pneumothorax (p = 0.01) and lung contusions (p = 0.002). No microbiological factors were significantly associated with LA formation. Abscesses were mostly bilateral, ≥5 cm of diameter and with a posterior location. CONCLUSIONS: Our results do not favor a specific virulence of S.aureus, but rather highlight the role of multiple insults to the lung, promoting LA formation. Despite a similar severity score, patients with LA had more serious trauma, combining severe both chest and head insults.

Psoas abscess and chronic Q fever: a contiguous or hematogenous complication? A case report and literature review.

Few cases of psoas abscesses (PA) during chronic Q fever have been reported, and the route of transmission remains unknown. Here, we report a new case and have performed a systematic literature review to determinate the spreading route of this complication. Medline, EMBASE and Web of Science were searched. Local spreading was supported by endocarditis exclusion, evidence of vascular infection and absence of distantly infected sites. Among 275 retrieved references, 179 were initially rejected, and 85 additional references were rejected after full-text review. A total of 11 studies, reporting 13 cases, were included. Additionally, we reported one new case. A total of 14/14 cases reached Q fever vascular infection diagnostic criteria, and 7/14 provided adequate evidence supporting a causal relationship between Q fever vascular infection and PA. All patients presented aorta defects. In conclusion, Q fever PA results from the spreading of a local infection and occurs specifically in patients presenting a vascular graft or an abdominal aortic aneurysm.

From the Skin to the Brain: Pathophysiology of Colonization and Infection of External Ventricular Drain, a Prospective Observational Study.

Ventriculostomy-related infection (VRI) is a serious complication of external ventricular drain (EVD) but its natural history is poorly studied. We prospectively tracked the bacteria pathways from skin towards ventricles to identify the infectious process resulting in ventriculostomy-related colonization (VRC), and VRI. We systematically sampled cerebrospinal fluid (CSF) on a daily basis and collected swabs from both the skin and stopcock every 3.0 days for microbiological analysis including in 101 neurosurgical patient. Risk factors for positive event defined as either VRC or VRI were recorded and related to our microbiological findings. A total of 1261 CSF samples, 473 skin swabs, and 450 stopcock swabs were collected. Skin site was more frequently colonized than stopcock (70 (60%) vs 34 (29%), p = 0.023), and earlier (14 ±1.4 vs 24 ±1.5 days, p<0.0001). Sixty-one (52%) and 32 (27%) skin and stopcock sites were colonized with commensal bacteria, 1 (1%) and 1 (1%) with pathogens, 8 (7%) and 1 (1%) with combined pathogens and commensal bacteria, respectively. Sixteen positive events were diagnosed; a cutaneous origin was identified in 69% of cases. The presence of a pathogen at skin site (6/16 vs 4/85, OR: 11.8, [2.5-56.8], p = 0.002) and CSF leakage (7/16 vs 6/85, OR 10 [2.4-41.2], p = 0.001)) were the two independent significant risk factors statistically linked to positive events occurrence. Our results suggest that VRC and VRI mainly results from an extra-luminal progression of pathogens initially colonizing the skin site where CSF leaks.