Intravenous antibiotics given for 2 weeks do not eradicate persistent Staphylococcus aureus clones in cystic fibrosis patients

AbstractStaphylococcus aureus is the most commonly isolated pathogen in respiratory tract secretions from young patients with cystic fibrosis (CF), and several treatment strategies are used to control the infection. However, it is not known whether intensified treatment with antimicrobial agents causes eradication of S. aureus clones. We retrospectively determined the impact of intravenous (IV) antimicrobial agents on the suppression and eradication of S. aureus clones. One thousand and sixty-one S. aureus isolates cultured from 2526 samples from 130 CF patients during a 2-year study period were subjected to spa typing. Intervals between positive samples and the occurrence of clone replacements were calculated in relation to courses of IV antimicrobial agents. Of 65 patients chronically infected with S. aureus, 37 received 139 courses of IV antimicrobial agents with activity against S. aureus (mean duration, 15 days; range, 6–31 days). Administration of IV antibiotics increased the time to the next sample with growth of S. aureus: the mean interval between two positive samples was 68 days if IV treatment had been administered, in contrast to 49 days if no IV treatment had been administered (p 0.003). When S. aureus recurred in sputum after IV treatment, the isolate belonged to a different clone in 33 of 114 (29%) intervals, in comparison with 68 of 232 (29%) intervals where IV treatment had not been prescribed (OR 0.98, 95% CI 0.60–1.61). In conclusion, we show that 2 weeks of IV antimicrobial treatment can significantly suppress chronic staphylococcal infection in CF, but is not associated with the eradication of persistent bacterial clones

Incidence of HACEK bacteraemia in Denmark:A 6-year population-based study

Objectives: Bacteria with common microbiological and clinical characteristics are often recognized as a particular group. The acronym HACEK stands for five fastidious genera associated with infective endocarditis (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella). Data on the epidemiology of HACEK are sparse. This article reports a 6-year nationwide study of HACEK bacteraemia in Denmark. Methods: Cases of HACEK bacteraemia occurring during the years 2010–2015 were retrieved from the national Danish microbiology database, covering an average surveillance population of 5.6 million per year. Results: A total of 147 cases of HACEK bacteraemia were identified, corresponding to an annual incidence of 0.44 per 100 000 population. The annual incidence for males was 0.56 per 100 000 and for females was 0.31 per 100 000. The median age was 56 years (range 0–97 years), with variation among the genera. One hundred and forty-three isolates were identified to the species level and six to the genus level: Haemophilus spp, n = 55; Aggregatibacter spp, n = 37; Cardiobacterium spp, n = 9; Eikenella corrodens n = 21; and Kingella spp, n = 27. Conclusions: This is the first study on the incidence of HACEK bacteraemia in a large surveillance population and may inspire further studies on the HACEK group. Haemophilus spp other than Haemophilus influenzae accounted for most cases of HACEK bacteraemia in Denmark, with Aggregatibacter spp in second place. Keywords: Epidemiology, Incidence, Age, Sex, Haemophilus, Aggregatibacte

Multispacer sequence typing of Coxiella burnetii DNA from removed prosthetic heart valve material discloses first human case of infective endocarditis caused by MST_18

Introduction: In Denmark, Q fever has previously been considered a rare and imported disease; however, recent testing of antibodies in cattle as well as humans has indicated that the infection is widespread. A 76-year-old Danish man was diagnosed with infective endocarditis and underwent open surgical aortic valve replacement with insertion of a biological valve. Due to paravalvular leakage, destruction of the aortic annulus, and an aortic root abscess, the patient underwent re-operation 3 weeks later, with replacement of the biological valve and insertion of an aortic prosthetic tube. Despite treatment with various broad-spectrum antibiotic regimes, the patient died 3.5 months after initial hospital admission. Methods: The causative agent was probed by PCR amplification of bacterial DNA on the removed prosthetic aortic valve using broad range primers targeting the variable regions V1–V3 of the 16S RNA gene. After identification of Coxiella burnetii, multispacer sequence typing (MST) was performed by PCR amplification of 10 intergenic sequences. Results: BLAST analysis of DNA from prosthetic valve material identified a 16S rRNA gene fragment almost identical to the type strain of C. burnetii (462/463 nt). Molecular typing allocated the strain to MST_18. Conclusions: Molecular methods are increasingly used to characterize isolates and to determine relationships between isolates that cause disease in different contexts and geographical areas. The present case demonstrates that identification and typing of C. burnetii is achievable without access to biosafety level 3 containment and highlights the first molecular characterization of an uncultured strain of C. burnetii causing infective endocarditis. Keywords: Q fever, Coxiella burnetii, Culture-negative infective endocarditis, Multispacer sequence typing, 16S rRN

Motility, Biofilm Formation and Antimicrobial Efflux of Sessile and Planktonic Cells of <i>Achromobacter xylosoxidans</i>

Achromobacter xylosoxidans is an innately multidrug-resistant bacterium capable of forming biofilms in the respiratory tract of cystic fibrosis (CF) patients. During the transition from the planktonic stage to biofilm growth, bacteria undergo a transcriptionally regulated differentiation. An isolate of A. xylosoxidans cultured from the sputum of a CF patient was separated into sessile and planktonic stages in vitro, and the transcriptomes were compared. The selected genes of interest were subsequently inactivated, and flagellar motility was found to be decisive for biofilm formation in vitro. The spectrum of a new resistance-nodulation-cell division (RND)-type multidrug efflux pump (AxyEF-OprN) was characterized by inactivation of the membrane fusion protein. AxyEF-OprN is capable of extruding some fluoroquinolones (levofloxacin and ciprofloxacin), tetracyclines (doxycycline and tigecycline) and carpabenems (ertapenem and imipenem), which are classes of antimicrobials that are widely used for treatment of CF pulmonary infections