Antibiotic prophylaxis before dental procedures to prevent infective endocarditis: a systematic review.

PURPOSE: Infective endocarditis (IE) is a severe bacterial infection. As a measure of prevention, the administration of antibiotic prophylaxis (AP) prior to dental procedures was recommended in the past. However, between 2007 and 2009, guidelines for IE prophylaxis changed all around the word, limiting or supporting the complete cessation of AP. It remains unclear whether AP is effective or not against IE. METHODS: We conducted a systematic review whether the administration of AP in adults before any dental procedure, compared to the non-administration of such drugs, has an effect on the risk of developing IE. We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via OVID, and EMBASE. Two different authors filtered articles independently and data extraction was performed based on a pre-defined protocol. RESULTS: The only cohort study meeting our criteria included patients at high-risk of IE. Analysis of the extracted data showed a non-significant decrease in the risk of IE when high-risk patients take AP prior to invasive dental procedures (RR 0.39, p-value 0.11). We did not find other studies including patients at low or moderate risk of IE. Qualitative evaluation of the excluded articles reveals diversity of results and suggests that most of the state-of-the-art articles are underpowered. CONCLUSIONS: Evidence to support or discourage the use of AP prior to dental procedures as a prevention for IE is very low. New high-quality studies are needed, even though such studies would require big settings and might not be immediately feasible.

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19.

BACKGROUND: Whereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear. OBJECTIVES: Our aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases. METHODS: Using immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2-specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109). RESULTS: SARS-CoV-2-specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2-specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2-specific serum antibody titers showed SARS-CoV-2-specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2-specific IgA titers in nasal fluids were inversely correlated with age. CONCLUSIONS: Systemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2-specific antibodies but may stimulate mucosal SARS-CoV-2-specific IgA secretion.

Polyester Vascular Graft Material and Risk for Intracavitary Thoracic Vascular Graft Infection1.

Prosthetic vascular graft infections of the thoracic aorta are rare but can be fatal. Our comparison of collagen- and gelatin-coated grafts showed that collagen-coated grafts were associated with increased biofilm formation and bacterial adherence in vitro and with higher rates of perioperative vascular graft infections in vivo.

Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord.

BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in HIV/HCV co-infected patients in a large European cohort collaboration, including data from different European countries. METHODS: HIV/HCV co-infected patients were included if they were aged ≥16 years, received pegIFN alfa-2a or 2b and RBV combination treatment and were enrolled in the COHERE cohort collaboration. Logistic regression was used to evaluate the impact of abacavir on achieving a sustained virologic response (SVR) to HCV treatment. RESULTS: In total 1309 HIV/HCV co-infected patients who had received HCV therapy were included, of whom 490 (37 %) had achieved an SVR. No statistically significant difference was seen for patients using ABC-containing regimens compared to patients using an emtricitabine + tenofovir (FTC + TDF)-containing backbone, which was the most frequently used backbone. In the multivariate analyses, patients using a protease inhibitor (PI)-boosted regimen were less likely to achieve an SVR compared to patients using a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen (OR: 0.61, 95 % CI: 0.41-0.91). The backbone combinations zidovudine&lamivudine (AZT + 3TC) and stavudine&lamivudine (d4t + 3TC) were associated with lower SRV rates (0.45 (0.24-0.82) and 0.46 (0.22-0.96), respectively). CONCLUSION: The results of this large European cohort study validate that SVR rates are generally not affected by ABC. Use of d4T or AZT as part of the HIV treatment regimen was associated with a lower likelihood of achieving an SVR.

Oropharyngeal group A streptococcal colonization disrupts latent Epstein-Barr virus infection.

Epstein-Barr virus (EBV) infects >90% of the human population within the first 2 decades of life and establishes reversible latent infection in B cells. The stimuli that lead to switching from latent to lytic EBV infection in vivo are still elusive. Group A streptococci (GAS) are a common cause of bacterial pharyngotonsillitis in children and adolescents and colonize the tonsils and pharynx of up to 20% of healthy children. Thus, concomitant presence of EBV and GAS in the same individual is frequent. Here, we show that EBV carriers who are colonized with GAS shed EBV particles in higher numbers in their saliva, compared with EBV carriers not colonized with GAS. Messenger RNA levels of the master lytic regulatory EBV gene BZLF1 were more frequently detected in tonsils from EBV carriers colonized with GAS than from EBV carriers not colonized. Heat-killed GAS, potentially mimicking GAS colonization, elicited lytic EBV in latently infected lymphoblastoid cell lines (LCLs) partially via Toll-like receptor 2 triggering, as did purified GAS peptidoglycan. Thus, colonization by GAS might benefit EBV by increasing the EBV load in saliva and thereby enhancing the likelihood of EBV spread to other hosts.

Eligibility for and outcome of hepatitis C treatment of HIV-coinfected individuals in clinical practice: the Swiss HIV cohort study.

BACKGROUND: Morbidity and mortality of individuals co-infected with HIV and hepatitis C virus (HCV) is often determined by the course of their HCV infection. Only a selected proportion of those in need of HCV treatment are studied in randomized controlled trials (RCTs). We analysed the prevalence of HCV infection in a large cohort, the number of individuals requiring treatment, the eligibility for HCV treatment, and the outcome of the combination therapy with pegylated interferon-a and ribavirin in routine practice. METHODS: We analysed prescription patterns of HCV treatment and treatment outcomes among participants from the Swiss HIV Cohort Study with detectable hepatitis C viraemia (between January 2001 and October 2004). Efficacy was measured by the number of patients with undetectable HCV RNA at the end of therapy (EOTR) and at 6 months after treatment termination (SVR). Intention-to-continue-treatment principles were used. RESULTS: A total of 2150 of 7048 (30.5%) participants were coinfected with HCV; HCV RNA was detected in 60%, and not assessed in 26% of HCV-antibody-positive individuals. One hundred and sixty (12.5%) of HCV-RNA-positive patients started treatment. In patients infected with HCV genotypes 1/4 or 2/3, EOTR was achieved in 43.3% and 81.2% of patients, respectively, and SVR rates were 28.4% and 51.8%, respectively. More than 50% of the HCV-treated patients would have been excluded from two large published RCTs due to demographic, clinical and laboratory criteria. CONCLUSIONS: Despite clinical and psychosocial obstacles encountered in clinical practice, HCV treatment in HIV-coinfected individuals is feasible with results similar to those obtained in RCTs.

Protein adsorption steers blood contact activation on engineered cobalt chromium alloy oxide layers.

Biomaterials upon implantation are immediately covered by blood proteins which direct the subsequent blood activation. These early events determine the following cascade of biological reactions and consequently the long-term success of implants. The ability to modulate surface properties of biomaterials is therefore of considerable clinical significance. Goal of this study was an in-depth understanding of the biological response to cobalt chromium stent alloys with engineered surface oxide layers, which showed altered body reactions in vivo. We analyzed in vitro the biological events following initial blood contact on engineered cobalt chromium surfaces featuring said oxide layers. Surface-specific blood reactions were confirmed by scanning electron microscopy and the adsorbed protein layers were characterized by mass spectrometry. This powerful proteomics tool allowed the identification and quantification of over hundred surface-adhering proteins. Proteins associated with the coagulation cascade, platelet adhesion and neutrophil function correlated with the various blood surface activations observed. Furthermore, results of pre-coated surfaces with defined fibrinogen-albumin mixtures suggest that neutrophil adhesion was controlled by fibrinogen orientation and conformation rather than quantity. This study highlights the importance of controlling the biological response in the complex protein-implant surface interactions and the potential of the surface modifications to improve the clinical performance of medical implants. STATEMENT OF SIGNIFICANCE: The blood contact activation of CoCr alloys is determined by their surface oxide layer properties. Modifications of the oxide layer affected the total amount of adsorbed proteins and the composition of the adsorbed protein layer. Additionally fibrinogen coatings mediated the surface-dependent neutrophil adhesion in a concentration-independent manner, indicating the influence of conformation and/or orientation of the adsorbed protein. Despite the complexity of protein-implant interactions, this study highlights the importance of understanding and controlling mechanisms of protein adhesion in order to improve and steer the performance of medical implants. It shows that modification of the surface oxide layer is a very attractive strategy to directly functionalize metallic implant surfaces and optimize their blood interaction for the desired orthopedic or cardiovascular applications.

Quantitative detection of Porphyromonas gingivalis fimA genotypes in dental plaque.

We developed quantitative fimA genotype assays and applied them in a pilot study investigating the fimbrial genotype distribution of Porphyromonas gingivalis in European subjects with or without chronic periodontitis. P. gingivalis was found in 71% and 9% of the samples from patients and healthy subjects, respectively. Enumeration of total P. gingivalis cell numbers by polymerase chain reaction and immunofluorescence showed excellent correspondence (r = 0.964). 73% of positive samples contained multiple fimA genotypes, but generally one genotype predominated by one to three orders of magnitude. Genotype II predominated in 60% of the samples. Genotype IV occurred with similar prevalence (73%) as genotype II but predominated in only 20% of the samples. Genotypes I, III and V were of much lower prevalence and cell densities of the latter two remained sparse. Our results suggest marked differences among the fimA genotypes' ability to colonize host sites with high cell numbers.

Porphyromonas gingivalis regulates TREM-1 in human polymorphonuclear neutrophils via its gingipains.

The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, with the capacity to amplify pro-inflammatory cytokine production and regulate apoptosis. Polymorphonuclear neutrophils (PMNs) are the first line of defence against infection, and a major source of TREM-1. Porphyromonas gingivalis is a Gram-negative anaerobe highly implicated in the inflammatory processes governing periodontal disease, which is characterized by the destruction of the tooth-supporting tissues. It expresses a number of virulence factors, including the cysteine proteinases (or gingipains). The aim of this in vitro study was to investigate the effect of P. gingivalis on TREM-1 expression and production by primary human PMNs, and to evaluate the role of its gingipains in this process. After 4 h of challenge, P. gingivalis enhanced TREM-1 expression as identified by quantitative real-time PCR. This was followed by an increase in soluble (s)TREM-1 secretion over a period of 18 h, as determined by ELISA. At this time-point, the P. gingivalis-challenged PMNs exhibited diminished TREM-1 cell-membrane staining, as identified by flow cytometry and confocal laser scanning microscopy. Furthermore engagement of TREM-1, by means of anti-TREM-1 antibodies, enhanced the capacity of P. gingivalis to stimulate interleukin (IL)-8 production. Conversely, antagonism of TREM-1 using a synthetic peptide resulted in reduction of IL-8 secretion. Using isogenic P. gingivalis mutant strains, we identified the Arg-gingipain to be responsible for shedding of sTREM-1 from the PMN surface, whereas the Lys-gingipain had the capacity to degrade TREM-1. In conclusion, the differential regulation of TREM-1 by the P. gingivalis gingipains may present a novel mechanism by which P. gingivalis manipulates the host innate immune response helping to establish chronic periodontal inflammation.