Update 2016-2018 of the Nationwide Danish Fungaemia Surveillance Study:Epidemiologic Changes in a 15-Year Perspective

As part of a national surveillance programme initiated in 2004, fungal blood isolates from 2016–2018 underwent species identification and EUCAST susceptibility testing. The epidemiology was described and compared to data from previous years. In 2016–2018, 1454 unique isolates were included. The fungaemia rate was 8.13/100,000 inhabitants compared to 8.64, 9.03, and 8.38 in 2004–2007, 2008–2011, and 2012–2015, respectively. Half of the cases (52.8%) involved patients 60–79 years old and the incidence was highest in males ≥70 years old. Candida albicans accounted for 42.1% of all isolates and Candida glabrata for 32.1%. C. albicans was more frequent in males (p = 0.03) and C. glabrata in females (p = 0.03). During the four periods, the proportion of C. albicans decreased (p < 0.001), and C. glabrata increased (p < 0.001). Consequently, fluconazole susceptibility gradually decreased from 68.5% to 59.0% (p < 0.001). Acquired fluconazole resistance was found in 4.6% Candida isolates in 2016–2018. Acquired echinocandin resistance increased during the four periods 0.0%, 0.6%, 1.7% to 1.5% (p < 0.0001). Sixteen echinocandin-resistant isolates from 2016–2018 harboured well-known FKS resistance-mutations and one echinocandin-resistant C. albicans had an FKS mutation outside the hotspot (P1354P/S) of unknown importance. In C. glabrata specifically, echinocandin resistance was detected in 12/460 (2.6%) in 2016–2018 whereas multidrug-class resistance was rare (1/460 isolates (0.2%)). Since the increase in incidence during 2004–2011, the incidence has stabilised. In contrast, the species distribution has changed gradually over the 15 years, with increased C. glabrata at the expense of C. albicans. The consequent decreased fluconazole susceptibility and the emergence of acquired echinocandin resistance complicates the management of fungaemia and calls for antifungal drug development

Targeted AntiBiotics for Chronic pulmonary diseases (TARGET ABC):can targeted antibiotic therapy improve the prognosis of Pseudomonas aeruginosa-infected patients with chronic pulmonary obstructive disease, non-cystic fibrosis bronchiectasis, and asthma? A multicenter, randomized, controlled, open-label trial

BACKGROUND: Pseudomonas aeruginosa infection is seen in chronic pulmonary disease and is associated with exacerbations and poor long-term prognosis. However, evidence-based guidelines for the management and treatment of P. aeruginosa infection in chronic, non-cystic fibrosis (CF) pulmonary disease are lacking. The aim of this study is to investigate whether targeted antibiotic treatment against P. aeruginosa can reduce exacerbations and mortality in patients with chronic obstructive pulmonary disease (COPD), non-CF bronchiectasis, and asthma. METHODS: This study is an ongoing multicenter, randomized, controlled, open-label trial. A total of 150 patients with COPD, non-CF bronchiectasis or asthma, and P. aeruginosa-positive lower respiratory tract samples will be randomly assigned with a 1:1 ratio to either no antibiotic treatment or anti-pseudomonal antibiotic treatment with intravenous beta-lactam and oral ciprofloxacin for 14 days. The primary outcome, analyzed with two co-primary endpoints, is (i) time to prednisolone and/or antibiotic requiring exacerbation or death, in the primary or secondary health sector, within days 20–365 from study allocation and (ii) days alive and without exacerbation within days 20–365 from the study allocation. DISCUSSION: This trial will determine whether targeted antibiotics can benefit future patients with chronic, non-CF pulmonary disease and P. aeruginosa infection in terms of reduced morbidity and mortality, thus optimizing therapeutic approaches in this large group of chronic patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262142. Registered on August 25, 2017. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06720-z

Composition of the Vaginal Microbiota in Women of Reproductive Age - Sensitive and Specific Molecular Diagnosis of Bacterial Vaginosis Is Possible?

Background and Objective: Bacterial vaginosis (BV) is the most common vaginal disorder, characterized by depletion of the normal lactobacillus-dominant microbiota and overgrowth of commensal anaerobic bacteria. This study aimed to investigate the composition of the vaginal microbiota in women of reproductive age (healthy women and women with BV), with the view of developing molecular criteria for BV diagnosis. Materials and Methods: Vaginal samples from 163 women (79 control, 73 BV and 11 intermediate (Lactobacillary grade II flora) cases) were analyzed using 454 pyrosequencing of the hypervariable regions V3-V4 of the 16S rRNA gene and 16 quantitative bacterial species/genus-specific real-time PCR assays. Sensitivities and specificities of potential BV markers were computed using the Amsel criteria as reference standard for BV. The use of quantitative thresholds for prediction of BV, determined for both relative abundance measured with 454 pyrosequencing and bacterial load measured with qPCR, was evaluated. Results: Relative to the healthy women, the BV patients had in their vaginal microbiota significantly higher prevalence, loads and relative abundances of the majority of BV associated bacteria. However, only Gardnerella vaginalis, Atopobium vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 detected at or above optimal thresholds were highly predictable for BV, with the best diagnostic accuracy shown for A. vaginae. The depletion of Lactobacillus species combined with the presence of either G. vaginalis or A. vaginae at diagnostic levels was a highly accurate BV predictor. Conclusions: Quantitative determination of the presence of G. vaginalis, A. vaginae, Eggerthella, Prevotella, BVAB2 and Megasphaera type 1 as well as the depletion of Lactobacillus was highly accurate for BV diagnosis. Measurements of abundance of normal and BV microbiota relative to total bacteria in vaginal fluid may provide more accurate BV diagnosis, and be used for test-of-cure, rather than qualitative detection or absolute counts of BV related microorganisms

Prevalence of vaginal bacterial species/genera by real-time PCR.

<p>The qualitative detection rates of 16 bacteria by species/genus-specific PCR assays in healthy control women (n = 79), intermediate cases (n = 11) and BV patients (n = 73) are presented. <i>L. iners</i> was the most frequently detected bacterium in the healthy control women (86%), followed by <i>G. vaginalis</i> (78%), <i>A. vaginae</i> (63%), <i>Prevotella</i> (62%), and <i>F. magna</i> (58%). In the intermediate subjects, the most common species/genera were <i>G. vaginalis</i> (100%), <i>L. iners</i> (91%), <i>A. vaginae</i> (91%), <i>Prevotella</i> (82%) and <i>L. amnionii</i> (82%). <i>G. vaginalis</i> and <i>A. vaginae</i> were both found in 100% of the subjects with BV. Other highly prevalent bacteria in the BV patients were <i>Prevotella</i> (96%), <i>Megasphaera</i> type 1 (96%), <i>L. iners</i> (93%), <i>Eggerthella</i> (93%), BVAB2 (90%), <i>L. amnionii</i> (88%) and <i>S. sanguinegens</i> (81%).</p

Relative abundances of bacterial species/genera by 454 pyrosequencing.

<p>The figure presents the average relative abundances of 16 bacterial species/genera by 454 pyrosequencing in the vaginal samples from healthy control women (n = 79), intermediate cases (n = 11) and BV patients (n = 73). The healthy control women had vaginal microbiota dominated by <i>Lactobacillus</i> species, accounting for nearly 90% of all sequences, with <i>L. crispatus</i> and <i>L. iners</i> highly prevailing over other lactobacilli. In the intermediate cases, <i>L. iners</i> and <i>G. vaginalis</i> were dominating over other species, accounting together for nearly 75% of all sequences. The BV patients possessed a diverse array of bacteria, with the most abundant species being <i>G. vaginalis</i>, <i>Prevotella</i>, <i>Megasphaera</i> type 1, <i>A. vaginae</i>, <i>L. amnionii</i>, <i>L. iners</i>, BVAB1, BVAB2, <i>S. sanguinegens</i> and <i>Eggerthella</i>.</p