Use of microbiology tests in the era of increasing AMR rates- a multicentre hospital cohort study

Background: Effective use of microbiology test results may positively influence patient outcomes and limit the use of broad-spectrum antibiotics. However, studies indicate that their potential is not fully utilized. We investigated microbiology test ordering practices and the use of test results for antibiotic decision-making in hospitals. Methods: A multicentre cohort study was conducted during five months in 2014 in Medical departments across three hospitals in Western Norway. Patients treated with antibiotics for sepsis, urinary tract infections, skin and soft tissue infections, lower respiratory tract infections or acute exacerbations of chronic obstructive pulmonary disease were included in the analysis. Primary outcome measures were degree of microbiology test ordering, compliance with microbiology testing recommendations in the national antibiotic guideline and proportion of microbiology test results used to inform antibiotic treatment. Data was obtained from electronic- and paper medical records and charts and laboratory information systems. Results: Of the 1731 patient admissions during the study period, mean compliance with microbiology testing recommendations in the antibiotic guideline was 89%, ranging from 81% in patients with acute exacerbations of chronic obstructive pulmonary disease to 95% in patients with sepsis. Substantial additional testing was performed beyond the recommendations with 298/606 (49%) of patients with lower respiratory tract infections having urine cultures and 42/194 (22%) of patients with urinary tract infections having respiratory tests. Microbiology test results from one of the hospitals showed that 18% (120/672) of patient admissions had applicable test results, but only half of them were used for therapy guidance, i.e. in total, 9% (63/672) of patient admissions had test results informing prescription of antibiotic therapy. Conclusions: This study showed that despite a large number of microbiology test orders, only a limited number of tests informed antibiotic treatment. To ensure that microbiology tests are used optimally, there is a need to review the utility of existing microbiology tests, test ordering practices and use of test results through a more targeted and overarching approach

emm gene diversity, superantigen gene profiles and presence of SlaA among clinical isolates of group A, C and G streptococci from western Norway

In order to investigate molecular characteristics of beta-hemolytic streptococcal isolates from western Norway, we analysed the entire emm gene sequences, obtained superantigen gene profiles and determined the prevalence of the gene encoding streptococcal phospholipase A2 (SlaA) of 165 non-invasive and 34 contemporary invasive group A, C and G streptococci (GAS, GCS and GGS). Among the 25 GAS and 26 GCS/GGS emm subtypes identified, only emm3.1 was significantly associated with invasive disease. M protein size variation within GAS and GCS/GGS emm types was frequently identified. Two non-invasive and one invasive GGS possessed emm genes that translated to truncated M proteins as a result of frameshift mutations. Results suggestive of recombinations between emm or emm-like gene segments were found in isolates of emm4 and stG485 types. One non-invasive GGS possessed speC, speG, speH, speI and smeZ, and another non-invasive GGS harboured SlaA. speA and SlaA were over-represented among invasive GAS, probably because they were associated with emm3. speGdys was identified in 83% of invasive and 63% of non-invasive GCS/GGS and correlated with certain emm subtypes. Our results indicate the invasive potential of isolates belonging to emm3, and show substantial emm gene diversity and possible lateral gene transfers in our streptococcal population

MicroRNA-146a and AMD3100, two ways to control CXCR4 expression in acute myeloid leukemias

CXCR4 is a negative prognostic marker in acute myeloid leukemias (AMLs). Therefore, it is necessary to develop novel ways to inhibit CXCR4 expression in leukemia. AMD3100 is an inhibitor of CXCR4 currently used to mobilize cancer cells. CXCR4 is a target of microRNA (miR)-146a that may represent a new tool to inhibit CXCR4 expression. We then investigated CXCR4 regulation by miR-146a in primary AMLs and found an inverse correlation between miR-146a and CXCR4 protein expression levels in all AML subtypes. As the lowest miR-146a expression levels were observed in M5 AML, we analyzed the control of CXCR4 expression by miR-146a in normal and leukemic monocytic cells and showed that the regulatory miR-146a/CXCR4 pathway operates during monocytopoiesis, but is deregulated in AMLs. AMD3100 treatment and miR-146a overexpression were used to inhibit CXCR4 in leukemic cells. AMD3100 treatment induces the decrease of CXCR4 protein expression, associated with miR-146a increase, and increases sensitivity of leukemic blast cells to cytotoxic drugs, this effect being further enhanced by miR-146a overexpression. Altogether our data indicate that miR-146a and AMD3100, acting through different mechanism, downmodulate CXCR4 protein levels, impair leukemic cell proliferation and then may be used in combination with anti-leukemia drugs, for development of new therapeutic strategies