Exploring treatment and antifungal resistance in an outbreak of tinea caused by Microsporum audouinii.

BACKGROUND: Microsporum audouinii has resurged recently. Infections with the dermatophyte are difficult to treat, which raises the question if we treat M. audouinii infections with the most effective antifungal (AF) agent. OBJECTIVES: The aims of this study was to investigate an outbreak of tinea capitis (TC) in Denmark, address the challenges in outbreak management and to conduct two reviews regarding previous outbreaks and minimal inhibitory concentration (MIC). METHODS: We used Wood's light, culture, direct microscopy, and PCR for screening and antifungal susceptibility testing (AFST) for treatment optimization. We performed two reviews to explore M. audouinii outbreaks and MIC values using broth microdilution method. RESULTS: Of 73 screened individuals, 10 had confirmed M. audouinii infections. Clinical resistance to griseofulvin was observed in 4 (66%) cases. While previous outbreaks showed high griseofulvin efficacy, our study favoured terbinafine, fluconazole and itraconazole in our hard-to-treat cases. AFST guided the choice of AF. Through the literature search, we identified five M. audouinii outbreaks, where differences in management included the use of Wood's light and prophylactic topical AF therapy. Terbinafine MIC values from the literature ranged from 0.002 to 0.125 mg/L. CONCLUSION: Use of Wood's light and preventive measurements were important for limiting infection. The literature lacked MIC data for griseofulvin against M. audouinii, but indicated sensitivity for terbinafine. The clinical efficacy for M. audouinii treatment was contradictory favouring both terbinafine and griseofulvin. AFST could have a key role in the treatment of difficult cases, but lack of standardisation of AFST and MIC breakpoints limits its usefulness.

JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms.

BACKGROUND: Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady-state hematopoiesis. METHODS: We analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next-generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre-MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub-diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub-diagnoses and MPN mutation. RESULTS: MPN patients had a higher observed richness (median, 245 [range, 49-659]) compared with HCs (191.5 [range, 111-300; p = .003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p < .001). The microbiota of CALR-positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F-positive patients, only minor differences in the gut microbiota were observed between MPN sub-diagnoses, illustrating the importance of this mutation. CONCLUSION: The gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis.

BACKGROUND: Linezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci. OBJECTIVES: Because rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated. PATIENTS AND METHODS: Pharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination. RESULTS: We demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively. CONCLUSIONS: A substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.

Pronounced gut microbiota signatures in patients with JAK2V617F-positive essential thrombocythemia.

Essential thrombocythemia (ET) is part of the Philadelphia chromosome-negative myeloproliferative neoplasms. It is characterized by an increased risk of thromboembolic events and also to a certain degree hypermetabolic symptoms. The gut microbiota is an important initiator of hematopoiesis and regulation of the immune system, but in patients with ET, where inflammation is a hallmark of the disease, it is vastly unexplored. In this study, we compared the gut microbiota via amplicon-based 16S rRNA gene sequencing of the V3-V4 region in 54 patients with ET according to mutation status Janus-kinase 2 (JAK2V617F)-positive vs JAK2V617F-negative patients with ET, and in 42 healthy controls (HCs). Gut microbiota richness was higher in patients with ET (median-observed richness, 283.5; range, 75-535) compared with HCs (median-observed richness, 191.5; range, 111-300; P < 0.001). Patients with ET had a different overall bacterial composition (beta diversity) than HCs (analysis of similarities [ANOSIM]; R = 0.063, P = 0.004). Patients with ET had a significantly lower relative abundance of taxa within the Firmicutes phylum compared with HCs (51% vs 59%, P = 0.03), and within that phylum, patients with ET also had a lower relative abundance of the genus Faecalibacterium (8% vs 15%, P < 0.001), an important immunoregulative bacterium. The microbiota signatures were more pronounced in patients harboring the JAK2V617F mutation, and highly similar to patients with polycythemia vera as previously described. These findings suggest that patients with ET may have an altered immune regulation; however, whether this dysregulation is induced in part by, or is itself inducing, an altered gut microbiota remains to be investigated. IMPORTANCE Essential thrombocythemia (ET) is a cancer characterized by thrombocyte overproduction. Inflammation has been shown to be vital in both the initiation and progression of other myeloproliferative neoplasms, and it is well known that the gut microbiota is important in the regulation of our immune system. However, the gut microbiota of patients with ET remains uninvestigated. In this study, we characterized the gut microbiota of patients with ET compared with healthy controls and thereby provide new insights into the field. We show that the gut microbiota of patients with ET differs significantly from that of healthy controls and the patients with ET have a lower relative abundance of important immunoregulative bacteria. Furthermore, we demonstrate that patients with JAK2V617F-positive ET have pronounced gut microbiota signatures compared with JAK2V617F-negative patients. Thereby confirming the importance of the underlying mutation, the immune response as well as the composition of the microbiota.

Predicting ß-lactam susceptibility from the genome of Streptococcus pneumoniae and other mitis group streptococci.

Introduction: For Streptococcus pneumoniae, ß-lactam susceptibility can be predicted from the amino acid sequence of the penicillin-binding proteins PBP1a, PBP2b, and PBP2x. The combination of PBP-subtypes provides a PBP-profile, which correlates to a phenotypic minimal inhibitory concentration (MIC). The non-S. pneumoniae Mitis-group streptococci (MGS) have similar PBPs and exchange pbp-alleles with S. pneumoniae. We studied whether a simple BLAST analysis could be used to predict phenotypic susceptibility in Danish S. pneumoniae isolates and in internationally collected MGS. Method: Isolates with available WGS and phenotypic susceptibility data were included. For each isolate, the best matching PBP-profile was identified by BLAST analysis. The corresponding MICs for penicillin and ceftriaxone was retrieved. Category agreement (CA), minor-, major-, and very major discrepancy was calculated. Genotypic-phenotypic accuracy was examined with Deming regression. Results: Among 88 S. pneumoniae isolates, 55 isolates had a recognized PBP-profile, and CA was 100% for penicillin and 98.2% for ceftriaxone. In 33 S. pneumoniae isolates with a new PBP-profile, CA was 90.9% (penicillin) and 93.8% (ceftriaxone) using the nearest recognized PBP-profile. Applying the S. pneumoniae database to non-S. pneumoniae MGS revealed that none had a recognized PBP-profile. For Streptococcus pseudopneumoniae, CA was 100% for penicillin and ceftriaxone in 19 susceptible isolates. In 33 Streptococcus mitis isolates, CA was 75.8% (penicillin) and 86.2% (ceftriaxone) and in 25 Streptococcus oralis isolates CA was 8% (penicillin) and 100% (ceftriaxone). Conclusion: Using a simple BLAST analysis, genotypic susceptibility prediction was accurate in Danish S. pneumoniae isolates, particularly in isolates with recognized PBP-profiles. Susceptibility was poorly predicted in other MGS using the current database.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

The gut microbiota in patients with polycythemia vera is distinct from that of healthy controls and varies by treatment.

Chronic inflammation is believed to play an important role in the development and disease progression of polycythemia vera (PV). Because an association between gut microbiota, hematopoiesis, and inflammation is well established, we hypothesized that patients with PV have a gut microbiota distinct from healthy control participants (HCs). Recombinant interferon alfa 2 (IFN-α2)-treatment of patients with PV is reportedly disease modifying in terms of normalization of elevated blood cell counts in concert with a reduction in the JAK2V617F allelic burden. Therefore, we hypothesized that patients treated with IFN-α2 might have a composition of the gut microbiota toward normalization. Herein, via amplicon-based next-generation sequencing of the V3 to V4 regions of the 16S ribosomal RNA gene, we report on an abnormal gut microbiota in 102 patients with PV compared with 42 HCs. Patients with PV had a lower alpha diversity and a lower relative abundance of several taxa belonging to Firmicutes (45%) compared with HCs (59%, P <.001). Furthermore, we report the composition of the gut microbiota to differ between the treatment groups (IFN-α2, hydroxyurea, no treatment, and combination therapy with IFN-α2 and ruxolitinib) and the HCs. These observations are highly interesting considering the potential pathogenetic importance of an altered gut microbiota for development of other diseases, including chronic inflammatory diseases. Our observations call for further gut microbiota studies to decipher potential causal associations between treatment and the gut microbiota in PV and related neoplasms.

Prevalence and Mortality of Infective Endocarditis in Community-Acquired and Healthcare-Associated Staphylococcus aureus Bacteremia: A Danish Nationwide Registry-Based Cohort Study.

Background: Staphylococcus aureus bacteremia (SAB) can be community-acquired or healthcare-associated, and prior small studies have suggested that this mode of acquisition impacts the subsequent prevalence of infective endocarditis (IE) and patient outcomes. Methods: First-time SAB was identified from 2010 to 2018 using Danish nationwide registries and categorized into community-acquired (no healthcare contact within 30 days) or healthcare-associated (SAB >48 hours of hospital admission, hospitalization within 30 days, or outpatient hemodialysis). Prevalence of IE (defined from hospital codes) was compared between groups using multivariable adjusted logistic regression analysis. One-year mortality of S aureus IE (SAIE) was compared between groups using multivariable adjusted Cox proportional hazard analysis. Results: We identified 5549 patients with community-acquired SAB and 7491 with healthcare-associated SAB. The prevalence of IE was 12.1% for community-acquired and 6.6% for healthcare-associated SAB. Community-acquired SAB was associated with a higher odds of IE as compared with healthcare-associated SAB (odds ratio, 2.12 [95% confidence interval {CI}, 1.86-2.41]). No difference in mortality was observed with 0-40 days of follow-up for community-acquired SAIE as compared with healthcare-associated SAIE (HR, 1.07 [95% CI, .83-1.37]), while with 41-365 days of follow-up, community-acquired SAIE was associated with a lower mortality (HR, 0.71 [95% CI, .53-.95]). Conclusions: Community-acquired SAB was associated with twice the odds for IE, as compared with healthcare-associated SAB. We identified no significant difference in short-term mortality between community-acquired and healthcare-associated SAIE. Beyond 40 days of survival, community-acquired SAIE was associated with a lower mortality.

Temporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: A Nationwide Study.

Background Monitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in-hospital and long-term mortality, according to microbiological cause in patients with IE from 2010 to 2017. Methods and Results Linking Danish nationwide registries, we identified all patients with first-time IE. In-hospital and long-term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase-negative staphylococci (6.2%), and "other microbiological causes" (5.3%). Blood culture-negative IE was registered in 18.9%. The proportion of blood culture-negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in-hospital and long-term mortality (median follow-up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in-hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74-4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11-1.97]), coagulase-negative staphylococci IE (OR, 1.79 [95% CI, 1.21-2.65]), "other microbiological cause" (OR, 1.47 [95% CI, 0.95-2.27]), and blood culture-negative IE (OR, 1.99 [95% CI, 1.52-2.61]); and the following causes were associated with higher mortality following discharge (median follow-up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19-1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11-1.54]), coagulase-negative staphylococci IE (HR, 1.07 [95% CI, 0.85-1.36]), "other microbiological cause" (HR, 1.45 [95% CI, 1.13-1.85]), and blood culture-negative IE (HR, 1.05 [95% CI, 0.89-1.25]). Conclusions This nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in-hospital mortality.

Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis.

OBJECTIVE: To assess the prevalence and severity of anaemia in patients with left-sided infective endocarditis (IE) and association with mortality. METHODS: In the Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis trial, 400 patients with IE were randomised to conventional or partial oral antibiotic treatment after stabilisation of infection, showing non-inferiority. Haemoglobin (Hgb) levels were measured at randomisation. Primary outcomes were all-cause mortality after 6 months and 3 years. Patients who underwent valve surgery were excluded due to competing reasons for anaemia. RESULTS: Out of 400 patients with IE, 248 (mean age 70.6 years (SD 11.1), 62 women (25.0%)) were medically managed; 37 (14.9%) patients had no anaemia, 139 (56.1%) had mild anaemia (Hgb <8.1 mmol/L in men and Hgb <7.5 mmol/L in women and Hgb ≥6.2 mmol/L) and 72 (29.0%) had moderate to severe anaemia (Hgb <6.2 mmol/L). Mortality rates in patients with no anaemia, mild anaemia and moderate to severe anaemia were 2.7%, 3.6% and 15.3% at 6-month follow-up and 13.5%, 20.1% and 34.7% at 3-year follow-up, respectively. Moderate to severe anaemia was associated with higher mortality after 6 months (HR 4.81, 95% CI 1.78 to 13.0, p=0.002) and after 3 years (HR 2.14, 95% CI 1.27 to 3.60, p=0.004) and remained significant after multivariable adjustment. CONCLUSION: Moderate to severe anaemia was present in 29% of patients with medically treated IE after stabilisation of infection and was independently associated with higher mortality within the following 3 years. Further investigations are warranted to determine whether intensified treatment of anaemia in patients with IE might improve outcome.

Identification of Streptococcus pseudopneumoniae and other mitis group streptococci using matrix assisted laser desorption/ionization - time of flight mass spectrometry.

This study evaluated the ability of the MALDI-ToF MS from Bruker Daltonics to identify clinical Mitis-Group-Streptococcus isolates with a focus on Streptococcus pseudopneumoniae. The results were analyzed using the standard log(score) and the previously published list(score). Importantly, using the log(score) no misidentifications occurred and 27 of 29 (93%) S. pneumoniae and 27 of 30 (90%) S. oralis strains were identified, but only 1 of 31 (3%) S. pseudopneumoniae and 1 of 13 (8%) S. mitis strains were identified. However, our results show that 30 of 31 S. pseudopneumoniae strains had a S. pseudopneumoniae Main Spectral Profiles within the 3 best matches. Using the list(score) all S. oralis and S. pneumoniae strains were identified correctly, but list(score) misidentified 10 S. pseudopneumoniae and 5 S. mitis. We propose to use the log(score) for identification of S. pneumoniae, S. pseudopneumoniae, S. mitis and S. oralis, but for some strains additional testing may be needed.

Extensive microbiological respiratory tract specimen characterization in critically ill COVID-19 patients.

Microbial co-infections may contribute to the pulmonary deterioration in COVID-19 patients needing intensive care treatment. The present study portrays the extent of co-infections in COVID-19 ICU patients. Conventional culture, molecular detections for atypical aetiologies, QiaStat-Dx® respiratory panel V2 detecting 21 respiratory pathogens and ribosomal DNA genes 16S/18S amplicon-based microbiome analyses were performed on respiratory samples from 34 COVID-19 patients admitted to the ICU. Potential pathogens were detected in seven patients (21%) by culturing, in four patients (12%) by microbiome analysis and in one patient (3%) by respiratory panel. Among 20 patients receiving antibiotics prior to ICU admission, fungi (3 Candida albicans, 1 C. tropicalis, 1 C. dubliniensis) were cultured in 5 (15%) endotracheal aspirates. Among 14 patients who were antibiotic-naive at ICU admission, two patients (6%) had bacterial respiratory pathogens (Staphylococcus aureus, Streptococcus pseudopneumoniae) cultured in their endotracheal aspirates. Microbiome analysis recognized four potential respiratory pathogens (3 Haemophilus influenza, 1 Fusobacterium necrophorum) isolated in samples from four other patients (12%). QiaStat-Dx® respiratory panel V2 detected adenovirus in one patient (3%). The prevalence of pulmonary microbial co-infections is modest among COVID-19 patients upon admission to ICU. Microbiome analysis complements conventional microbial diagnostics in characterization of respiratory co-infections.

Streptococcus pseudopneumoniae: Use of Whole-Genome Sequences To Validate Species Identification Methods.

A correct identification of Streptococcus pseudopneumoniae is a prerequisite for investigating the clinical impact of the bacterium. The identification has traditionally relied on phenotypic methods. However, these phenotypic traits have been shown to be unreliable, with some S. pseudopneumoniae strains giving conflicting results. Therefore, sequence-based identification methods have increasingly been used for identification of S. pseudopneumoniae In this study, we used 64 S. pseudopneumoniae strains, 59 S. pneumoniae strains, 22 S. mitis strains, 24 S. oralis strains, 6 S. infantis strains, and 1 S. peroris strain to test the capability of three single genes (rpoB, gyrB, and recA), two multilocus sequence analysis (MLSA) schemes, the single nucleotide polymorphism (SNP)-based phylogeny tool CSI phylogeny, a k-mer-based identification method (KmerFinder), average nucleotide identity (ANI) using fastANI, and core genome analysis to identify S. pseudopneumoniae Core genome analysis and CSI phylogeny were able to cluster all strains into distinct clusters related to their respective species. It was not possible to identify all S. pseudopneumoniae strains correctly using only one of the single genes. The MLSA schemes were unable to identify some of the S. pseudopneumoniae strains, which could be misidentified. KmerFinder identified all S. pseudopneumoniae strains but misidentified one S. mitis strain as S. pseudopneumoniae, and fastANI differentiated between S. pseudopneumoniae and S. pneumoniae using an ANI cutoff of 96%.

Reconstruction and Validation of a Genome-Scale Metabolic Model of Streptococcus oralis (iCJ415), a Human Commensal and Opportunistic Pathogen.

The mitis group of streptococci (MGS) is a member of the healthy human microbiome in the oral cavity and upper respiratory tract. Troublingly, some MGS are able to escape this niche and cause infective endocarditis, a severe and devastating disease. Genome-scale models have been shown to be valuable in investigating metabolism of bacteria. Here we present the first genome-scale model, iCJ415, for Streptococcus oralis SK141. We validated the model using gene essentiality and amino acid auxotrophy data from closely related species. iCJ415 has 71-76% accuracy in predicting gene essentiality and 85% accuracy in predicting amino acid auxotrophy. Further, the phenotype of S. oralis was tested using the Biolog Phenotype microarrays, giving iCJ415 a 82% accuracy in predicting carbon sources. iCJ415 can be used to explore the metabolic differences within the MGS, and to explore the complicated metabolic interactions between different species in the human oral cavity.

Similar genomic patterns of clinical infective endocarditis and oral isolates of Streptococcus sanguinis and Streptococcus gordonii.

Streptococcus gordonii and Streptococcus sanguinis belong to the Mitis group streptococci, which mostly are commensals in the human oral cavity. Though they are oral commensals, they can escape their niche and cause infective endocarditis, a severe infection with high mortality. Several virulence factors important for the development of infective endocarditis have been described in these two species. However, the background for how the commensal bacteria, in some cases, become pathogenic is still not known. To gain a greater understanding of the mechanisms of the pathogenic potential, we performed a comparative analysis of 38 blood culture strains, S. sanguinis (n = 20) and S. gordonii (n = 18) from patients with verified infective endocarditis, along with 21 publicly available oral isolates from healthy individuals, S. sanguinis (n = 12) and S. gordonii (n = 9). Using whole genome sequencing data of the 59 streptococci genomes, functional profiles were constructed, using protein domain predictions based on the translated genes. These functional profiles were used for clustering, phylogenetics and machine learning. A clear separation could be made between the two species. No clear differences between oral isolates and clinical infective endocarditis isolates were found in any of the 675 translated core-genes. Additionally, random forest-based machine learning and clustering of the pan-genome data as well as amino acid variations in the core-genome could not separate the clinical and oral isolates. A total of 151 different virulence genes was identified in the 59 genomes. Among these homologs of genes important for adhesion and evasion of the immune system were found in all of the strains. Based on the functional profiles and virulence gene content of the genomes, we believe that all analysed strains had the ability to become pathogenic.

Bacteremia and urogenital infection with Actinomyces urogenitalis following prolonged urinary retention.

A case of bacteremia with the fastidious bacteria Actinomyces urogenitalis following lengthy urinary retention is reported in a sixty-year-old man. In 2013, the first case of bacteremia due to A. urogenitalis was presented, secondary to a tubo-ovarian abscess following transvaginal oocyte retrieval. To the best of our knowledge, this is the first male bacteremic episode involving A. urogenitalis related to a urinary tract focus. The patient had no prior urogenital medical history. Extensive susceptibility testing was done on isolates from urinary and blood cultures. The organism exhibited fluoroquinolone resistance but was susceptible to most other antibiotics used in the treatment of urinary infections. Due to its unusual growth requirements infections with A. urogenitalis are most likely an underdiagnosed entity.

In silico assessment of virulence factors in strains of Streptococcus oralis and Streptococcus mitis isolated from patients with Infective Endocarditis.

Purpose. Streptococcus oralis and Streptococcus mitis belong to the Mitis group, which are mostly commensals in the human oral cavity. Even though S. oralis and S. mitis are oral commensals, they can be opportunistic pathogens causing infective endocarditis. A recent taxonomic re-evaluation of the Mitis group has embedded the species Streptococcus tigurinus and Streptococcus dentisani into the species S. oralis as subspecies. In this study, the distribution of virulence factors that contribute to bacterial immune evasion, colonization and adhesion was assessed in clinical strains of S. oralis (subsp. oralis, subsp. tigurinus and subsp. dentisani) and S. mitis. Methodology. Forty clinical S. oralis (subsp. oralis, subsp. dentisani and subsp. tigurinus) and S. mitis genomes were annotated with the pipeline PanFunPro and aligned against the VFDB database for assessment of virulence factors.Results/Key findings. Three homologues of pavA, psaA and lmb, encoding adhesion proteins, were present in all strains. Seven homologues of nanA, nanB, ply, lytA, lytB, lytC and iga, of importance regarding survival in blood and modulation of the human immune system, were variously present in the genomes. Few S. oralis subspecies specific differences were observed. iga homologues were identified in S. oralis subsp. oralis, whereas lytA homologues were identified in S. oralis subsp. oralis and subsp. tigurinus. Conclusion. Differences in the presence of virulence factors among the three S. oralis subspecies were observed. The virulence gene profiles of the 40 S. mitis and S. oralis (subsp. oralis, subsp. dentisani and subsp. tigurinus) contribute with important new knowledge regarding these species and new subspecies.

Genomic characterization, phylogenetic analysis, and identification of virulence factors in Aerococcus sanguinicola and Aerococcus urinae strains isolated from infection episodes.

Aerococcus sanguinicola and Aerococcus urinae are emerging pathogens in clinical settings mostly being causative agents of urinary tract infections (UTIs), urogenic sepsis and more seldomly complicated infective endocarditis (IE). Limited knowledge exists concerning the pathogenicity of these two species. Eight clinical A. sanguinicola (isolated from 2009 to 2015) and 40 clinical A. urinae (isolated from 1984 to 2015) strains from episodes of UTIs, bacteremia, and IE were whole-genome sequenced (WGS) to analyze genomic diversity and characterization of virulence genes involved in the bacterial pathogenicity. A. sanguinicola genome sizes were 2.06-2.12 Mb with 47.4-47.6% GC-contents, and 1783-1905 genes were predicted whereof 1170 were core-genes. In case of A. urinae strains, the genome sizes were 1.93-2.44 Mb with 41.6-42.6% GC-contents, and 1708-2256 genes of which 907 were core-genes. Marked differences were observed within A. urinae strains with respect to the average genome sizes, number and sequence identity of core-genes, proteome conservations, phylogenetic analysis, and putative capsular polysaccharide (CPS) loci sequences. Strains of A. sanguinicola showed high degree of homology. Phylogenetic analyses showed the 40 A. urinae strains formed two clusters according to two time periods: 1984-2004 strains and 2010-2015 strains. Genes that were homologs to virulence genes associated with bacterial adhesion and antiphagocytosis were identified by aligning A. sanguinicola and A. urinae pan- and core-genes against Virulence Factors of Bacterial Pathogens (VFDB). Bacterial adherence associated gene homologs were present in genomes of A. sanguinicola (htpB, fbpA, lmb, and ilpA) and A. urinae (htpB, lap, lmb, fbp54, and ilpA). Fifteen and 11-16 CPS gene homologs were identified in genomes of A. sanguinicola and A. urinae strains, respectively. Analysis of these genes identified one type of putative CPS locus within all A. sanguinicola strains. In A. urinae genomes, five different CPS loci types were identified with variations in CPS locus sizes, genetic content, and structural organization. In conclusion, this is the first study dealing with WGS and comparative genomics of clinical A. sanguinicola and A. urinae strains from episodes of UTIs, bacteremia, and IE. Gene homologs associated with antiphagocytosis and bacterial adherence were identified and genetic variability was observed within A. urinae genomes. These findings contribute with important knowledge and basis for future molecular and experimental pathogenicity study of UTIs, bacteremia, and IE causing A. sanguinicola and A. urinae strains.

2017 European guideline for the management of chancroid.

Chancroid is a sexually acquired infection caused by Haemophilus ducreyi. The infection is characterized by one or more genital ulcers, which are soft and painful, and regional lymphadenitis, which may develop into buboes. The infection may easily be misidentified due to its rare occurrence in Europe and difficulties in detecting the causative pathogen. H. ducreyi is difficult to culture. Nucleic acid amplification tests can demonstrate the bacterium in suspected cases. Antibiotics are usually effective in curing chancroid.

Complete Genome Sequences of Aerococcus christensenii CCUG 28831T, Aerococcus sanguinicola CCUG 43001T, Aerococcus urinae CCUG 36881T, Aerococcus urinaeequi CCUG 28094T, Aerococcus urinaehominis CCUG 42038 BT, and Aerococcus viridans CCUG 4311T.

Strains belonging to the genus Aerococcus are causative agents of human and animal infections, including urogenital infections, bacteremia/septicemia, and infective endocarditis. This study reports the first fully closed and complete genome sequences of six type strains belonging to the genus Aerococcus using a combination of Illumina HiSeq and PacBio sequencing technologies.