The EC-COMPASS: Long-term, multi-centre surveillance of Enterobacter cloacae complex - a clinical perspective.

BACKGROUND: Enterobacter cloacae complex (ECCO) comprises closely related Enterobacterales, causing a variety of infections ranging from mild urinary tract infections to severe bloodstream infections. ECCO has emerged as a significant cause of healthcare-associated infections, particularly in neonatal and adult intensive care. AIM: The Enterobacter Cloacae COMplex PASsive Surveillance (EC-COMPASS) aims to provide a detailed multi-centre overview of ECCO epidemiology and resistance patterns detected in routine microbiological diagnostics in four German tertiary-care hospitals. METHODS: In a sentinel cluster of four German tertiary-care hospitals, all culture-positive ECCO results between 1st January 2020 and 31st December 2022, were analysed based on Hybase® laboratory data. FINDINGS: Analysis of 31,193 ECCO datasets from 14,311 patients revealed a higher incidence in male patients (P<0.05), although no significant differences were observed in ECCO infection phenotypes. The most common sources of ECCO were swabs (42.7%), urine (17.5%), respiratory secretions (16.1%), blood cultures (8.9%) and tissue samples (5.6%). The annual bacteraemia rate remained steady at approximately 33 cases per hospital. Invasive ECCO infections were predominantly found in oncology and intensive care units. Incidences of nosocomial outbreaks were infrequent and limited in scope. Notably, resistance to carbapenems was consistently low. CONCLUSION: EC-COMPASS offers a profound clinical perspective on ECCO infections in German tertiary-healthcare settings, highlighting elderly men in oncology and intensive care units as especially vulnerable to ECCO infections. Early detection strategies targeting at-risk patients could improve ECCO infection management.

Myeloid PTEN deficiency impairs tumor-immune surveillance via immune-checkpoint inhibition.

Tumor-host interaction is determined by constant immune surveillance, characterized by tumor infiltration of myeloid and lymphoid cells. A malfunctioning or diverted immune response promotes tumor growth and metastasis. Recent advances had been made, by treating of certain tumor types, such as melanoma, with T-cell checkpoint inhibitors. This highlights the importance of understanding the molecular mechanisms underlying the crosstalk between tumors and their environment, in particular myeloid and lymphoid cells. Our aim was to study the contribution of the myeloid PI3K/PTEN-signaling pathway in the regulation of tumor-immune surveillance in murine models of cancer. We made use of conditional PTEN-deficient mice, which exhibit sustained activation of the PI3K-signaling axis in a variety of myeloid cell subsets such as macrophages and dendritic cells (DCs). In colitis-associated colon cancer (CAC), mice deficient in myeloid PTEN showed a markedly higher tumor burden and decreased survival. We attributed this observation to the increased presence of immune-modulatory conventional CD8α(+) DCs in the spleen, whereas other relevant myeloid cell subsets were largely unaffected. Notably, we detected enhanced surface expression of PD-L1 and PD-L2 on these DCs. As a consequence, tumoricidal T-cell responses were hampered or redirected. Taken together, our findings indicated an unanticipated role for the PI3K/PTEN-signaling axis in the functional regulation of splenic antigen-presenting cells (APCs). Our data pointed at potential, indirect, tumoricidal effects of subclass-specific PI3K inhibitors, which are currently under clinical investigation for treatment of tumors, via myeloid cell activation.

[Correlation between microbial growth in conjunctival swabs of corneal donors and contamination of organ culture media]. / Korrelation zwischen mikrobiellem Wachstum in Bindehautabstrichen von Hornhautspendern und Kontamination des Organkulturmediums.

PURPOSE: The aim of the study was to determine the rate of contamination in conjunctival swabs from corneal donors by microbiological investigations and to correlate this with microbial contamination of the culture medium. PATIENTS AND METHODS: Contamination of conjunctival swabs and culture media was analyzed retrospectively for the years 2009, 2010 and 2011 at the LIONS corneal bank of Saar-Lor-Lux Trier/Westpfalz at the Saarland University Medical Center. The total annual number of conjunctival swabs was 316 in 2009, 341 in 2010 and 381 in 2011. Conjunctival swabs were taken prior to 1.25% povidone-iodine application. After disinfection donor corneas were harvested by in situ corneoscleral disc excision in all cases. The correlation between positive conjunctival swabs and microbial contamination of the culture medium was analyzed. RESULTS: In every year examined the contamination rate of the culture medium was significantly higher in cases of contaminated conjunctival swabs (p < 0.05 in 2009, p < 0.001 in 2010 and p = 0.004 in 2011). Of the conjunctival swabs 38.3% (2009), 53.7% (2010) and 55.6% (2011), respectively exhibited microbial growth. The principal microorganisms detected in the conjunctival swabs were coagulase negative staphylococci, gram negative rods and Staphylococcus aureus. Extending the exposure time to povidone-iodine prior to removal of the corneoscleral disc from 3 min in the year 2009 to 5 min since the year 2010 resulted in a highly statistically significant (p < 0.001) reduction in contamination frequency of the medium from 10.8% (2009) to 7.0% (2010) and 4.5% (2011) was observed. In 2009, 2010 and 2011 the culture medium was contaminated in 16.5%, 11.5% and 7.6% of the donated corneas with positive conjunctival swabs and in 7.2%, 1.9% and 0.6% in donated corneas with negative conjunctival swabs, respectively. CONCLUSIONS: A positive correlation was found between contamination of the culture medium and microbial colonization of the conjunctival swabs, Nevertheless, microbial colonization of the conjunctiva was high and contamination of the culture medium was relatively low. For the microbial contamination rate of the donated corneas in the medium, conjunctival disinfection time with iodine solution before explantation of the corneoscleral disc and the addition of antibiotics to the culture medium seem to play a protective role.

[Current data and trends on the development of antibiotic resistance of Clostridium difficile]. / Aktuelle Daten und Trends zur Antibiotikaresistenzentwicklung von Clostridium difficile.

Clostridium difficile is the most common pathogen causing antibiotic-associated diarrhea. Antibiotic therapy also favors the development and the epidemic spreading of multiresistant strains. In this present retrospective study clinical isolates from the University of Saarland Medical Center and of other German isolate referring hospitals were characterized by genotyping and antibiotic resistance testing. The most prevalent strains were ribotypes 001 (18%), 014 (16%) and 027 (15%). Sensitivity to metronidazole and vancomycin was demonstrated for 99.7 % of the clinical isolates independent of the genotype. Of the isolates 96 % were rifampicin susceptible; however, significantly more cases of rifampicin resistance were found among 027 strains (12 %). Of the isolates 58% were clarithromycin sensitive and 57% moxifloxacin sensitive. In contrast to the various sporadic genotypes the majority of epidemic strains were macrolide or fluoroquinolone resistant (001, 027 and 078); however, discrimination between epidemic strains by antibiotic resistance profiles could not be discerned. A combination of consistent adherence to hygiene management guidelines and to a prudent and rational use of antimicrobials (antibiotic stewardship) may help to reduce the total number of C. difficile infections (CDI) and also the selection of multiresistant strains. On the other hand in the collection of isolates the sensitivity towards the standard oral antibiotic agents used for C. difficile treatment appears to be unimpaired by the global changes of C. difficile resistant profiles.