Association of TLR8 Variants in Sex-Based Clinical Differences in Patients with COVID-19.

The host immune response might confer differential vulnerability to SARS-CoV-2 infection. The Toll-like receptor 8 (TLR8), could participated for severe COVID-19 outcomes. To investigated the relationship of TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G with COVID-19 outcomes and with biochemical parameters. A cross-sectional study of 830 laboratory-confirmed COVID-19 patients was performed, and classified into mild, severe, critical, and deceased outcomes. The TLR8 rs3764879-C/G, rs3764880-A/G, and rs3761624-A/G polymorphisms were genotyped. A logistic regression analysis was performed to determinate the association with COVID-19. A stratified analysis was by alleles was done with clinical and metabolic markets. In all outcomes, men presented the highest ferritin levels compared to women (P < 0.001). LDH levels were significantly different between sex in mild (P = 0.003), severe (P < 0.001) and deceased (P = 0.01) COVID-19 outcomes. The GGG haplotype showed an Odds Ratio of 1.55 (Interval Confidence 95% 1.05-2.32; P = 0.03) in men. Among patients with severe outcome, we observed that the carriers of the GGG haplotype had lower Ferritin, C-reactive protein and LDH levels than the CAA carriers (P < 0.01). After further stratified by sex, these associations were also seen in the male patients, except for D-dimer. Interestingly, among men patients, we could observe associations between TLR8 haplotypes and Ferritin (P < 0.001), D-dimer (P = 0.04), C-reactive protein, and Lactate dehydrogenase in mild (P = 0.04) group. Our results suggest that even though TLR8 haplotypes show a significant association with COVID-19 outcomes, they are associated with clinical markers in COVID-19 severity.

Overview of Staphylococcus epidermidis cell wall-anchored proteins: potential targets to inhibit biofilm formation.

Currently, the treatment of infections by Staphylococcus epidermidis (S. epidermidis) represents a challenge because some strains have multidrug-resistance to antimicrobial products (antibiotic and biocides) and can produce biofilms. These biofilms protect bacterial cells from both antimicrobials and the host immune response. Therefore, it is crucial to encourage research on the development of new treatments. One method is immunotherapy, targeting components of S. epidermidis, such as S. epidermidis surface (Ses) proteins. Ses is expressed constitutively in most strains, and they participate in biofilm formation. This review is an update on Ses, regarding their structure, biological function, their relationship with S. epidermidis biofilm formation, and its possible role as therapeutic targets to develop immunotherapeutic treatments to prevent infections by S. epidermidis.

Leuconostoc mesenteroides periprosthetic knee infection, an unusual fastidious Gram-positive bacteria: a case report.

BACKGROUND: Periprosthetic joint infections are mainly caused by Gram-positive cocci. Leuconostoc mesenteroides is a rare microorganism mainly causing bloodstream infections. At times, it might be confused with another type of cocci and give rise to misdiagnosed infections. Molecular diagnosis and biofilm production comprise important techniques to guide antibiotic treatment. CASE PRESENTATION: A 68-year-old Hispanic female with a previous history of bilateral knee arthroplasty presented with acute right-knee inflammation and gait impairment. Blood tests showed inflammatory response and knee x-ray revealed no prosthesis loosening. Irrigation and debridement was performed. Gram-positive cocci were obtained from cultures, and then biochemical and molecular identification revealed L. mesenteroides. Susceptibility and biofilm production were performed. The patient was treated with IntraVenous (IV) Ceftriaxone for ten days and was then switched to Amoxicillin-Clavulanate for 3 months with clinical and laboratory success. CONCLUSIONS: Microbiology diagnosis of fastidious microorganisms is mandatory to treat periprosthetic joint infections adequately. L. mesenteroides may infect non-immunocompromised persons; however, treatment guidelines are lacking.

In vitro microbicidal, anti-biofilm and cytotoxic effects of different commercial antiseptics.

Topical antiseptics are widely used for wound treatment, with the goal of disrupting biofilm capacity. We analysed the effectiveness of a variety of antiseptics to inhibit various stages of biofilm formation and to remove biofilms in vitro as well as the agents' cytotoxic effects on fibroblasts. We found that the chlorine-releasing agents exhibited immediate anti-biofilm effects in the short term, with lesser cytotoxicity than agents prepared from more stable compounds, such as biguanide or modified diallyl disulfide-oxide, which, conversely, have better long-term effectiveness. Among the examined organisms, Gram-positive bacteria and Candida albicans were the most sensitive to the antiseptics, whereas Pseudomonas aeruginosa and Acinetobacter baumannii were relatively resistant to them. Formulations whose mechanisms of action involve the release of chemically active chlorine were more effective when administered in solution than the gel form, likely because of the stability of the active ingredients during or after preparation of the formula. Interestingly, hypochlorous acid and some superoxidation solutions were effective in preventing biofilm formation within a short time period and showed virtually no toxicity. Our study indicates that most antiseptics remain effective long enough to prevent biofilm formation; thus, even brief application of an antiseptic agent during initial wound treatment can lead to better wound management outcomes.

Implication of myddosome complex genetic variants in outcome severity of COVID-19 patients.

BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.

Antiseptic Effects and Biosafety of a Controlled-Flow Electrolyzed Acid Solution Involve Electrochemical Properties, Rather than Free Radical Presence.

Electrolyzed acid solutions produced by different methods have antiseptic properties due to the presence of chlorine and reactive oxygen species. Our aim was to determine whether a controlled-flow electrolyzed acid solution (CFEAS) has the ability to improve wound healing due to its antiseptic and antibiofilm properties. First, we demonstrated in vitro that Gram-negative and Gram-positive bacteria were susceptible to CFEAS, and the effect was partially sustained for 24 h, evidencing antibiofilm activity (p < 0.05, CFEAS-treated vs. controls). The partial cytotoxicity of CFEAS was mainly observed in macrophages after 6 h of treatment; meanwhile, fibroblasts resisted short-lived free radicals (p < 0.05, CFEAS treated vs. controls), perhaps through redox-regulating mechanisms. In addition, we observed that a single 24 h CFEAS treatment of subacute and chronic human wounds diminished the CFU/g of tissue by ten times (p < 0.05, before vs. after) and removed the biofilm that was adhered to the wound, as we observed via histology from transversal sections of biopsies obtained before and after CFEAS treatment. In conclusion, the electrolyzed acid solution, produced by a novel method that involves a controlled flow, preserves the antiseptic and antibiofilm properties observed in other, similar formulas, with the advantage of being safe for eukaryotic cells; meanwhile, the antibiofilm activity is sustained for 24 h, both in vitro and in vivo.

Staphylococcus epidermidis Controls Opportunistic Pathogens in the Nose, Could It Help to Regulate SARS-CoV-2 (COVID-19) Infection?

Staphylococcus epidermidis is more abundant in the anterior nares than internal parts of the nose, but its relative abundance changes along with age; it is more abundant in adolescents than in children and adults. Various studies have shown that S. epidermidis is the guardian of the nasal cavity because it prevents the colonization and infection of respiratory pathogens (bacteria and viruses) through the secretion of antimicrobial molecules and inhibitors of biofilm formation, occupying the space of the membrane mucosa and through the stimulation of the host's innate and adaptive immunity. There is a strong relationship between the low number of S. epidermidis in the nasal cavity and the increased risk of serious respiratory infections. The direct application of S. epidermidis into the nasal cavity could be an effective therapeutic strategy to prevent respiratory infections and to restore nasal cavity homeostasis. This review shows the mechanisms that S. epidermidis uses to eliminate respiratory pathogens from the nasal cavity, also S. epidermidis is proposed to be used as a probiotic to prevent the development of COVID-19 because S. epidermidis induces the production of interferon type I and III and decreases the expression of the entry receptors of SARS-CoV-2 (ACE2 and TMPRSS2) in the nasal epithelial cells.

Dialkyl Carbamoyl Chloride-Coated Dressing Prevents Macrophage and Fibroblast Stimulation via Control of Bacterial Growth: An In Vitro Assay.

In this work, we evaluated the direct effect of a dialkyl carbamoyl chloride (DACC)-coated dressing on Staphylococcus aureus adhesion and growth in vitro, as well as the indirect effect of the dressing on fibroblast and macrophage activity. S. aureus cultures were treated with the dressing or gauze in Müller-Hinton medium or serum-supplemented Dulbecco's modified Eagle medium. Bacterial growth and attachment were assessed through colony-forming units (CFU) and residual biomass analyses. Fibroblast and macrophage co-cultures were stimulated with filtered supernatants from the bacterial cultures treated with the DACC-coated dressing, following which tumor necrosis factor (TNF)-α/transforming growth factor (TGF)-ß1 expression and gelatinolytic activity were assessed by enzyme-linked immunosorbent assays (ELISA) and zymography, respectively. The DACC-coated dressing bound 1.8−6.1% of all of the bacteria in the culture. Dressing-treated cultures presented biofilm formation in the dressing (enabling mechanical removal), with limited formation outside of it (p < 0.001). Filtered supernatants of bacterial cultures treated with the DACC-coated dressing did not over-stimulate TNF-α or TGF-ß1 expression (p < 0.001) or increase gelatinolytic activity in eukaryotic cells, suggesting that bacterial cell integrity was maintained. Based on the above data, wound caregivers should consider the use of hydrophobic dressings as a first option for the management of acute or chronic wounds.

The rs8176740 T/A and rs512770 T/C Genetic Variants of the ABO Gene Increased the Risk of COVID-19, as well as the Plasma Concentration Platelets.

We conducted a case-control study in order to evaluate whether ABO gene polymorphisms were associated with a high risk of developing COVID-19 in a cohort of patients. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495828 T/G, rs8176746 A/C, rs8176740 T/A, and rs512770 T/C) were determined using TaqMan genotyping assays in a group of 415 COVID-19 patients and 288 healthy controls. The distribution of rs651007 T/C, rs579459 T/C, rs495828 T/G, and rs8176746 A/C polymorphisms was similar in patients and healthy controls. Nonetheless, under co-dominant (OR = 1.89, pCCo-dominant = 6 × 10-6), recessive (OR = 1.98, pCRecessive = 1 × 10-4), and additive (OR = 1.36, pCAdditive = 3 × 10-3) models, the TT genotype of the rs8176740 T/A polymorphism increased the risk of developing COVID-19. In the same way, under co-dominant, recessive, and additive models, the TT genotype of the rs512770 T/C polymorphism was associated with a high risk of developing COVID-19 (OR = 1.87, pCCo-dominant = 2 × 10-3; OR = 1.87, pCRecessive = 5 × 10-4; and OR = 1.35, pCAdditive = 4 × 10-3, respectively). On the other hand, the GTC and GAT haplotypes were associated with a high risk of COVID-19 (OR = 5.45, pC = 1 × 10-6 and OR = 6.33, pC = 1 × 10-6, respectively). In addition, the rs8176740 TT genotype was associated with high-platelet plasma concentrations in patients with COVID-19. Our data suggested that the ABO rs512770 T/C and rs8176740 T/A polymorphisms increased the risk of developing COVID-19 and the plasma concentration of platelets.

Metabolic Reprogramming in SARS-CoV-2 Infection Impacts the Outcome of COVID-19 Patients.

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.

ACE and ACE2 Gene Variants Are Associated With Severe Outcomes of COVID-19 in Men.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes.

Genotypic and phenotypic changes of Staphylococcus epidermidis during relapse episodes in prosthetic joint infections.

Staphylococcus epidermidis is a coagulase-negative bacterium capable of causing recurrent relapses in prosthetic joint infection (PJI). The aim of this study was to determine if Staphylococcus epidermidis isolates from patients with recurrent relapses of prosthetic joint infection (PJI) changed genotypically (pulsed-field gel electrophoresis (PFGE) pattern analysis and genes involved in biofilm formation) and phenotypically (antimicrobial resistance, biofilm formation) during the different episodes. Four patients with PJI recurrent relapses were evaluated clinically and microbiologically. Genotypic and phenotypic characteristics of 31 S. epidermidis isolates were determined. In all cases, PJI was treated with antimicrobial therapy and resection of the prosthesis without reimplantation. Months later, all patients had a relapse episode and treated with rifampin plus vancomycin and surgical debridement. Changes in the antibiotics resistance profile in isolates from patients 1 and 2 were observed in the two episodes. Patient 1 had four clones A, B, C, and D that were distributed differentially in the two episodes. Similarly, patients 2 and 3 had two clones and subclones (E-E1 and F-F1, respectively), and patient 4 had only the clone G in both episodes. The clone F formed small-colony variants (SCVs). High level of biofilm formation was found in all clones, except for clones D and G. Clones/subclones showed a genotypic variation in icaA, sdrF, bap, sesI, and embp genes. The principal coordinate analysis showed that all clones/subclones were different. These results showed that the initial infective clone of S. epidermidis from PJI, changed genotypically and phenotypically after a second relapse as a response to the treatment.

Correction to: Genotypic and phenotypic changes of Staphylococcus epidermidis during relapse episodes in prosthetic joint infections.

In the original publication of the article, the authorship was published incorrectly.

Microbiology and Infection Profile of Electric Burned Patients in a Referral Burn Hospital in Mexico City.

Electrical burn injuries are one of the most severe forms of trauma. This study aims to investigate the infection complications in electrical burn patients in a referral hospital in Mexico City. A longitudinal retrospective study was conducted, involving electrical burn patients admitted from April 2011 to December 2016. Demographic and clinical data including type of electric burns, infection complications, and mortality was sought. Data were collected at admission and daily until discharge. Number and type of infections and microorganism isolations were sought. Risk factors for death were analyzed. A total of 111 patients were included, of which 96.4% were males, mean age of 31.6±16.22, most injuries were high voltage associated. The total body surface area average was 27.8% ± 19.63. The overall infection rate was 72.9 cases per 100 patients. Mortality was observed in 4 (3.6%) patients. About 59.1% (443/749) had growth for Gram-negative bacteria. Multidrug-resistant Pseudomonas aeruginosa was the most frequent microorganism isolated. Fungi were present in 4.9% of cases. Electrical burn injuries occurred in young males in our study. Infection was frequent, most of them caused by Gram-negative rods with an important rate of antimicrobial resistance; however, an important microbial diversity was present.

Prevalence and virulence factors of coagulase negative Staphylococcus causative of prosthetic joint infections in an orthopedic hospital of Mexico.

Objective: To determine the prevalence and virulence factors of coagulase-negative Staphylococci (CNS) in prosthetic joint infections (PJI). Method: CNS were isolated of 66 hip and knee PJI from Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, México City. Antimicrobial susceptibility and biofilm formation in CNS were determined; icaADBC, aap, bap and embp genes were determined by PCR. Results: Staphylococcus and Staphylococcus hominis were the most prevalent with 82 y 80% respectively. Staphylococcus lugdunensis, Staphylococcus haemolyticus, Staphylococcus capitis, Staphylococcus caprae, Staphylococcus sciuri and Staphylococcus lentus were less frequent. The majority of isolates were resistant to ß-lactam antibiotics, fluoroquinolone, and erythromycin. 41% of CNS were biofilm former and 59% were non-biofilm former (p = 0.0551). Biofilm former Staphylococcus epidermidis showed a high presence of icaADBC, aap and embp operons compared to the non-biofilm former isolates (p < 0.05). In contrast, non-S. epidermidis CNS had only the aap gen. Conclusion: S. haemolyticus, S. sciuri and S. lentus are new isolates of PJI not previously reported with virulence factors similar to CNS isolates.

Objetivo: Estudiar la prevalencia y los factores de virulencia de Staphylococcus coagulasa negativos (SCN) de infecciones de prótesis articular (IPA). Método: Los SCN se aislaron de 66 pacientes con IPA de cadera y rodilla procedentes del Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, de Ciudad de México. Se determinaron la sensibilidad antimicrobiana y la producción de biopelículas de los SCN. Los genes icaADBC, aap, bap y embp fueron detectados por reacción en cadena de la polimerasa en SCN. Resultados: La IPA de cadera fue el 80%. Se aislaron en alta proporción S. epidermidis (82%) y S. hominis (80%), y en baja frecuencia S. lugdunensis, S. haemolyticus, S. capitis, S. caprae, S. sciuri y S. lentus. La mayoría de los aislamientos fueron resistentes a los betalactámicos, las fluoroquinolonas y la eritromicina. La producción de biopelículas se determinó en el 41% de los SCN y el 59% fueron no productores de biopelículas (p = 0.0551). S. epidermidis productores de biopelículas tuvieron mayor presencia del operón icaADBC, aap y embp que los aislamientos no productores de biopelícula (p < 0.05). Los SCN no S. epidermidis presentaron únicamente el gen aap. Conclusiones: S. haemolyticus, S. sciuri y S. lentus son aislamientos nuevos de IPA no reportados que poseen factores de virulencia, igual que las otras especies de SCN aisladas.

Modifications in Vaginal Microbiota and Their Influence on Drug Release: Challenges and Opportunities.

Vaginal drug delivery represents an attractive alternative to achieve local and systemic effects due to the high contact surface exposed, the mucoadhesion of the epithelium, and the high innervation that facilitates the absorption of drugs into the bloodstream. However, despite the confinement of the vaginal cavity, it is an organ with a highly variable microenvironment. Mechanical alterations such as coitus, or chemical changes such as pH and viscosity, modify the release of drugs. In addition, changes in vaginal microbiota can influence the entire vaginal microenvironment, thus determining the disposition of drugs in the vaginal cavity and decreasing their therapeutic efficacy. Therefore, the influence of microorganisms on vaginal homeostasis can change the pre-established scenario for the application of drugs. This review aims to provide an explanation of normal vaginal microbiota, the factors that modify it, its involvement in the administration of drugs, and new proposals for the design of novel pharmaceutical dosage forms. Finally, challenges and opportunities directed toward the conception of new effective formulations are discussed.

sesA, sesB, sesC, sesD, sesE, sesG, sesH, and embp genes are genetic markers that differentiate commensal isolates of Staphylococcus epidermidis from isolates that cause prosthetic joint infection.

OBJECTIVES: Staphylococcus epidermidis can cause prosthetic joint infections. Strategies to differentiate between healthy skin and prosthetic joint infections isolates are relatively ineffective, which makes necessary to search for new differential biomarkers. Staphylococcus epidermidis has eleven surface proteins, denoted as Ses proteins. In this work, ses genes are used as biomarkers to differentiate between prosthetic joint infections and healthy skin isolates. METHODS: All prosthetic joint infections (n = 51) and healthy skin (n = 51) isolates were genotyped by pulsed-field gel electrophoresis. icaA, embp, sesA-I, and sdrF genes were determined by PCR. The phenotypic data included biofilm production and antibiotic resistance. RESULTS: 10 pulsed-field gel electrophoresis profiles were identified: four profiles were exclusive of prosthetic joint infections isolates, three profiles presented a higher proportion in prosthetic joint infections isolates and three profiles presented a higher proportion in healthy skin isolates. sesA, sesB, sesC, sesD, sesE, sesG, and sesH genes were more prevalent in healthy skin isolates than in prosthetic joint infections isolates (p < .05). Prosthetic joint infections isolates were more resistant to oxacillin (78%), ciprofloxacin (60%), levofloxacin (60%), and moxifloxacin (57%). The principal coordinate analysis and a discriminant analysis found that prosthetic joint infections isolates had as discriminant biomarker the biofilm formation, the icaA gene, oxacillin, ciprofloxacin, levofloxacin, moxifloxacin, and gentamicin resistance. In contrast, the healthy skin isolates had as discriminant biomarkers the embp, sesA, sesB, sesC, sesD, sesE, sesG, and sesH genes. CONCLUSIONS: These data suggest that ses genes can be considered biomarkers to differentiate between S. epidermidis commensal and prosthetic joint infections clinical.

Non-biofilm-forming commensal Staphylococcus epidermidis isolates produce biofilm in the presence of trypsin.

Epidemiological studies comparing clinical and commensal Staphylococcus epidermidis isolates suggest that biofilm formation is a discriminant biomarker. A study showed that four non-biofilm-forming clinical S. epidermidis isolates could form an induced biofilm by trypsin treatment, suggesting that S. epidermidis can form biofilms in a protease-independent way and in a trypsin-induced way. In this study, the trypsin capacity to induce biofilm formation was evaluated in non-biofilm-forming S. epidermidis isolates (n = 133) in order to support this mechanism and to establish the importance of total biofilms (meaning the sum of protease-independent biofilm and trypsin-induced biofilm). Staphylococcus epidermidis isolates from ocular infections (OI; n = 24), prosthetic joint infections (PJI; n = 64), and healthy skin (HS-1; n = 100) were screened for protease-independent biofilm formation according to Christensen's method. The result was that there are significant differences (p < .0001) between clinical (43.2%) and commensal (17%) protease-independent biofilm producers. Meanwhile, non-biofilm-forming isolates were treated with trypsin, and biofilm formation was evaluated by the same method. The number of commensal trypsin-induced biofilm producers significantly increased from 17% to 79%. In contrast, clinical isolates increased from 43.2% to 72.7%. The comparison between clinical and commensal total biofilm yielded no significant differences (p = .392). A similar result was found when different isolation sources were compared (OI vs. HS-1 and PJI vs. HS-1). The genotype icaA- /aap+ was associated with the trypsin-induced biofilm phenotype; however, no correlation was observed between aap mRNA expression and the level of trypsin-induced biofilm phenotype. Studying another group of commensal S. epidermidis non-biofilm-forming isolates (HS-2; n = 139) from different body sites, it was found that 70 isolates (60.3%) formed trypsin-induced biofilms. In conclusion, trypsin is capable of inducing biofilm production in non-biofilm-forming commensal S. epidermidis isolates with the icaA- /aap+ genotype, and there is no significant difference in total biofilms when comparing clinical and commensal isolates, suggesting that total biofilms are not a discriminant biomarker.