Evaluating the Use of Neonatal Colonization Screening for Empiric Antibiotic Therapy of Sepsis and Pneumonia.

(1) Background: Since 2013, weekly screening for multidrug-resistant Gram-negative (MDRGN) bacteria has been performed in German neonatal intensive care units (NICU). National guidelines recommend considering these colonization analyses for antibiotic treatment regimens. Our retrospective single center study provides insight into the clinical dichotomy of bacterial colonization and infection rates in neonates. (2) Methods: We analyzed microbiological data of neonates admitted to our tertiary level NICU over nine years. Colonization with MDRGN/Serratia marcescens (SERMA) was compared to microbiological findings in sepsis and pneumonia. (3) Results: We analyzed 917 blood and 1799 tracheal aspirate samples. After applying criteria from the Nosocomial Infection Surveillance for Neonates (NEO-KISS), we included 52 and 55 cases of sepsis and pneumonia, respectively; 19.2% of sepsis patients and 34.5% of pneumonia patients had a prior colonization with MDRGN bacteria or SERMA. In these patients, sepsis was not attributable to MDRGN bacteria yet one SERMA, while in pneumonias, ten MDRGN bacteria and one SERMA were identified. We identified late-onset pneumonia and cesarean section as risk factors for MDRGN/SERMA acquisition. (4) Conclusions: Colonization screening is a useful tool for hygiene surveillance. However, our data suggest that consideration of colonization with MDRGN/SERMA might promote extensive use of last resort antibiotics in neonates.

Diagnostic Utility of Interleukin-6 in Early-Onset Sepsis among Term Newborns: Impact of Maternal Risk Factors and CRP Evaluation.

(1) Background: Interleukin-6 (IL-6) levels act as an early infection marker preceding C-reactive protein (CRP) elevation. This study seeks to analyze IL-6 behavior in suspected early-onset sepsis (EOS) cases among term newborns, comparing it to that of CRP and evaluating IL-6's diagnostic utility. We also aim to assess the impact of maternal risk factors on EOS in term newborns, quantifying their influence for informed decision making. (2) Methods: The retrospective data analysis included 533 term newborns who were admitted to our hospital because of suspected EOS. IL-6, CRP, and the impact of maternal risk factors were analyzed in the context of EOS using binomial test, Chi-squared test, logistic and linear regression. (3) Results: In the cases of EOS, both IL-6 and CRP were elevated. The increase in CRP can be predicted by the initial increase in IL-6 levels. Among the assessed risk factors, intrapartum maternal fever (adjusted odds ratio 18.1; 95% CI (1.7-4.1)) was identified as the only risk factor significantly associated with EOS. (4) Conclusions: Employing IL-6 as an early infection marker enhanced EOS diagnostic precision due to its detectable early rise. However, caution is required, as elevations in IL-6 and CRP levels do not exclusively indicate EOS. Increased CRP levels in healthy newborns with maternal risk factors may be attributed to dynamics of vaginal labor.

Effects of a combined treatment with GPR30 agonist G-1 and herceptin on growth and gene expression of human breast cancer cell lines.

Expression of G-protein-coupled receptor 30 (GPR30) is present in HER2-overexpressing breast cancer. In this study, we examined to what extent GPR30-agonist G-1 would affect the antitumoral action of trastuzumab (Herceptin). Combined treatment with both drugs exerted an additive growth-inhibitory effect on breast cancer cells which was accompanied by a significant decline of cyclin A2 expression both on the protein and the mRNA level. Combined treatment also resulted in expression changes of c-fos, cyclin D1, or p21/WAF-1. The results of our study encourage further attempts to test the relevance of these in vitro data in the clinical setting.

Additive effects of trastuzumab and genistein on human breast cancer cells.

Soy isoflavone genistein, a tyrosine kinase inhibitor and agonist of estrogen receptor-ß (ERß), is known to have antitumoral properties. Given that ERß often is coexpressed with HER2 in breast cancer, both functions of genistein might be able to enhance the antitumoral action of trastuzumab. In this in-vitro study, we tested whether combined treatment with genistein and trastuzumab exerts additive effects on breast cancer cells. HER2-overexpressing breast cancer cell lines were treated with genistein alone and in combination with trastuzumab. The effects of this treatment on proliferation and gene expression were analyzed. Treatment with high-dose genistein (10 µmol/l) significantly increased the growth-inhibitory effect of trastuzumab on HER2-overexpressing, ERα/ß-positive BT-474 breast cancer cells. Combinatory treatment using lower doses of trastuzumab exerted similar effects as a single treatment with standard doses of this drug. In contrast, this effect was absent in ERα-negative SK-BR-3 cells. Similar results were obtained after cotreatment with the ERß agonist, 2,3-bis(4-hydroxyphenyl)propionitrile. The growth-inhibitory effect of both drugs was accompanied by an increased expression of the putative tumor suppressor ERß variant, cx, and their combination further elevated mRNA levels of this receptor. In conclusion, genistein significantly enhanced the antitumoral effect of trastuzumab on BT-474 breast cancer cells in vitro. The relevance of these data particularly for women with HER2-overexpressing and ERα/ß-positive breast cancer has to be verified in animal or clinical studies.