Clinical relevance of colonization with antimicrobial-resistant bacteria (AMRB) and methicillin susceptible Staphylococcus aureus (MSSA) for mothers during pregnancy.

PURPOSE: The impact of colonization with antimicrobial-resistant bacteria (AMRB) and methicillin-sensitive Staphylococcus aureus (MSSA) of healthy pregnant women is not described in detail in Germany. In this study, we screened for MSSA and AMRB, especially for methicillin-resistant S. aureus (MRSA) as well as extended-spectrum beta-lactamase (ESBL)-producing E. coli. Potential risk factors for colonization with AMRB/MSSA and the potential effects of colonization with these on the obstetric population were investigated. METHODS: From October 2013 until December 2015 pregnant women were screened before birth for colonization with AMRB/MSSA from the mammillae, nose, perianal and vaginal area. Before birth, the expectant mother was administered a standardized interview questionnaire by a trained interviewer. Data from the hospital admission records were also included. RESULTS: Samples from 651 pregnant women were analyzed. Colonization with MSSA was detected in 14.3% (n = 93), AMRB in 3.5% [(n = 23); MRSA: n = 3/ESBL: n = 20]. Significantly more colonization of AMRB/MSSA could be detected in women who had previously given birth compared to women who were nulliparous (p < 0.05). MSSA colonization was significantly associated with self-reported respiratory diseases during pregnancy (p < 0.05), but AMRB/MSSA colonization was not statistically associated with other types of infection. CONCLUSION: Our results demonstrate a low overall rate of colonization with AMRB/MSSA, as well as a low percentage of colonized pregnant women who developed infections. Multiparous women are at higher risk for colonization with MSSA/MRSA or ESBL. Because the prevalence of AMRB/MSSA is low, this study suggests that general screening of pregnant women without risk factors is not recommended.

Evaluation of sampling locations in pregnant women and newborns for the detection of colonisation with antibiotic-resistant bacteria.

Up to now, little has been known about the prevalence and clinical relevance of colonisation of asymptomatic pregnant women with methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) or extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. In this two-centre cross-sectional study, we evaluated the performance and importance of screening at different times and different locations for colonisation in pregnant women and newborns. Between October 2013 and December 2015, four samples were collected from pregnant women, two from newborns at birth and three from 3-day-old newborns. Samples were screened on culturing media and were confirmed with molecular methods. MSSA was used as a surrogate for MRSA, as the two share most microbiologic characteristics and colonisation patterns. Of 763 pregnant women, 14.5% (111) were colonised with MSSA, 0.4% (3) with MRSA and 2.6% (20) with ESBL-producing E. coli. Of 658 newborns, 0.9% (10) were colonised with MSSA at birth and 13.1% (70) at 3 days old, 0.5% (3) were colonised with MRSA and 2.6% (17) with ESBL-producing E. coli. Nasal sampling identified 91.0% of MSSA-colonised pregnant women and 60.0% of newborns. In newborns, nasal and umbilical sampling at 3 days after birth discovered 84.0% of colonised cases. For ESBL-producing E. coli, the perianal region was positive in all colonised pregnant women and in 88.2% of colonised newborns. Combining nasal and perianal swabs is optimal when screening for antibiotic-resistant bacteria in pregnant women. Nasal, perianal and umbilical sample collection from 3-day-old newborns significantly increased the sensitivity compared to screening immediately after birth.

A multidimensional network approach reveals microRNAs as determinants of the mesenchymal colorectal cancer subtype.

Colorectal cancer (CRC) is a heterogeneous disease posing a challenge for accurate classification and treatment of this malignancy. There is no common genetic molecular feature that would allow for the identification of patients at risk for developing recurrences and thus selecting patients who would benefit from more stringent therapies still poses a major clinical challenge. Recently, an international multicenter consortium (CRC Subtyping Consortium) was established aiming at the classification of CRC patients in biologically homogeneous CRC subtypes. Four consensus molecular subtypes (CMSs) were identified, of which the mesenchymal CMS4 presented with worse prognosis signifying the importance of identifying these patients. Despite the large number of samples analyzed and their clear association with unifying biological programs and clinical features, single-driver mutations could not be identified and patients are heterogeneous with regard to currently used clinical markers. We therefore set out to define the regulatory mechanisms underlying the distinct gene expression profiles using a network-based approach involving multiple molecular modalities such as gene expression, methylation levels and microRNA (miR) expression. The miR-200 family presented as the most powerful determinant of CMS4-specific gene expression, tuning the majority of genes differentially expressed in the poor prognosis subtype, including genes associated with the epithelial-mesenchymal transition program. Furthermore, our data show that two epigenetic marks, namely the methylation of the two miR-200 promoter regions, can identify tumors belonging to the mesenchymal subtype and is predictive of disease-free survival in CRC patients. Importantly, epigenetic silencing of the miR-200 family is also detected in epithelial CRC cell lines that belong to the mesenchymal CMS. We thus show that determining regulatory networks is a powerful strategy to define drivers of distinct cancer subtypes, which possess the ability to identify subtype affiliation and to shed light on biological behavior.