María Guembe
@iisgm.com
Clinical Microbiology and Infectious Diseases Department, Gregorio Marañón Hospital
Fundación para la Investigación Biomédica del Hospital Gregorio Marañón
RESEARCH, TEACHING, or OTHER INTERESTS
Microbiology (medical), Orthopedics and Sports Medicine, Microbiology, Infectious Diseases
Scopus Publications
Scopus Publications
Marta Díaz-Navarro, Ana Crespo, Patricia Muñoz, and María Guembe
Elsevier BV
Marta Díaz-Navarro, Antonio Benjumea, Andrés Visedo, Patricia Muñoz, Javier Vaquero, Francisco Chana, and María Guembe
MDPI AG
As we previously demonstrated that tranexamic acid (TXA), an antifibrinolytic, showed an antibacterial effect alone and in combination with vancomycin and gentamicin, we now wanted to analyze its own efficacy using new, different fluorescent staining reagents that target different components of the biofilm matrix and compare which one quantifies biofilm reduction better. A 108 cfu/mL suspension of the Staphylococcus aureus (ATCC29213) strain was placed into the wells of a 24-multiwell plate covered with glass slides coated with 10% poly-L-lysine under agitation for 24 h at 37 °C. After 3 washes with PBS, wells were treated with either TXA 10 mg/mL or sterile water and incubated for 24 h at 37 °C. After three washes with PBS, the density area of the following biofilm components was calculated using confocal laser scanning microscopy: extracellular proteins (Sypro Ruby), α-extracellular polysaccharides (ConA-Alexa fluor 633), α or β-extracellular polysaccharides (GS-II-Alexa fluor 488), bacterial DNA (PI), and eDNA (TOTO®-1). We observed a statistically significant reduction in the occupied area by all components of the S. aureus biofilm (p < 0.001) after TXA 10 mg/mL treatment, compared to the positive control. All biofilm components’ reduction percentages reached ≥90.0%. We demonstrated that TXA reduced both bacteria and extracellular matrix components of S. aureus biofilm by using five different stain reagents, with all being equally valid for quantification.
Marta Díaz-Navarro, Emilia Cercenado, Andrés Visedo, Mercedes Marín, Marina Machado, Álvaro Irigoyen-von-Sierakowski, Belén Loeches, Juana Cacho-Calvo, Julio García-Rodríguez, Enea G. Di Domenico,et al.
MDPI AG
Objectives: Cefideroccol (FDC) is a siderophore cephalosporin with potent antibacterial activity against a wide range of Gram-negative multidrug-resistant (MDR) microorganisms. We investigated the anti-biofilm capacity of FDC against clinical strains. Methods: This multicenter study was conducted on 28 selected strains of MDR Gram-negative bacilli isolated from clinical samples of Pseudomonas aeruginosa (n = 5), Acinetobacter baumannii (n = 11), and Klebsiella pneumoniae (n = 12). We first determined the minimum inhibitory concentration (MIC) of each strain using the microdilution method. We also defined the minimum biofilm inhibitory concentration (MBIC) as a ≥50% reduction in tetrazolium salt (XTT) (as recommended in the 2017 Spanish Microbiology Protocols [SEIMC] for the microbiological diagnosis of infections related to the formation of biofilms). We also analyzed the reduction in the following biofilm variables after an 8 mg/mL FDC treatment: the CFU count, the cell viability, the biomass, the metabolic activity, and extracellular α or β polysaccharides. Results: The MIC50 and MBIC50 of FDC were 0.5 mg/L and 64 mg/L, respectively. We observed a mean (SD) fold increase in the susceptibility to FDC between planktonic and sessile cells for P. aeruginosa, A. baumannii, and K. pneumoniae of 9.60 (0.55), 6.27 (2.28), and 6.25 (2.80), respectively. When 8 mg/mL of FDC was tested, we observed that the best median (IQR) percentage reductions were obtained for cell viability and the extracellular matrix (73.1 [12.4–86.5] and 79.5 [37.3–95.5], respectively), particularly for P. aeruginosa. The lowest percentage reduction rates were those obtained for biomass. Conclusions: We demonstrated that the susceptibility to FDC was significantly reduced when strains were in a biofilm state. The best percentage reduction rates for all biofilm-defining variables were observed for P. aeruginosa. Our results need to be validated using a larger collection of clinical samples.
Ma Jesús Pérez-Granda, Andrés Visedo, Martín Olivares, Álvaro García-Cañal, Marta Díaz-Navarro, Raquel Carrillo, Teresa Vicente, Patricia Muñoz, María Guembe, and José Ma Lasso
American Society for Microbiology
ABSTRACT Screening and decolonization programs have proven effective in reducing the frequency of Staphylococcus aureus infections, mainly in orthopedic and cardiac procedures. Despite being classified as clean, breast surgery is associated with infection. Using culture and polymerase chain reaction (PCR) assay, we aimed to assess the frequency of nasal carriage of S. aureus in patients undergoing breast surgery. We conducted a prospective observational 10-month study at a large tertiary teaching hospital, including patients undergoing breast reconstruction surgery who met the eligibility criteria and signed the informed consent document. Nasal swabs were collected before surgery from patients with no signs of S. aureus infection and tested using both culture and the Xpert MRSA/SA SSTI PCR assay. The outcomes were nasal colonization by S. aureus , colonization rates at the time of surgery, infection, and length of hospital stay. We included 100 patients, 27% of whom were colonized. Of these, 20 patients were positive by culture and 27 by PCR. The median (IQR) age was 56.0 (49.0–63.7) years. A total of 6 patients had infection, and the median (IQR) number of days until onset of infection was 191 (186.25–197.00). Carriage of S. aureus before surgery was microbiologically confirmed in two patients. We demonstrated that 27% of patients undergoing breast surgery were nasal carriers of S. aureus , with PCR assay being the best diagnostic strategy. Future studies are needed to address the efficacy of bacterial decolonization of the nose and nipples to reduce the frequency of infection and complications. IMPORTANCE We showed that almost 30% of women undergoing breast surgery are nasal carriers of S. aureus , and PCR molecular technique was the best diagnostic tool. However, future studies are needed to implement decolonization of nasal and nipple to reduce infection and complications.
Marta Díaz-Navarro, David Samitier, Félix García-Moreno, María Sanjurjo, Patricia Muñoz, Beatriz Torroba, and María Guembe
MDPI AG
Background/Objectives: Vancomycin (V) is widely used for catheter lock therapy. However, its ad hoc preparation in pharmacy departments involves discarding most of an intravenous vial and contributes to high workload. We aimed to assess the V concentration and minimum inhibitory biofilm concentration (MIBC) of a frozen V lock solution. Methods: Two V-2 mg/mL solutions were tested: (1) V + heparin 100 IU/mL and (2) V + citrate 2%. Solutions were frozen at −20 °C, followed by 48 h refrigeration, and analyses were performed at baseline and after 2, 4, 8, and 12 weeks (experiment 1). In addition, after the 12-week freezing period, solution 1 was also preserved for 1 and 2 weeks at both 4 °C and room temperature (experiment 2). V concentration was assessed by HPLC-DAD at 205 nm and validated with forced degradation tests. A <10% variation indicated significant change. MBIC was determined by XTT staining of 24 h biofilms exposed to decreasing concentrations of each solution. Microorganisms tested included methicillin-susceptible and -resistant Staphylococcus aureus (MSSA, MRSA), Staphylococcus epidermidis ATCC35984 (SE), and a highly biofilm-forming clinical S. epidermidis strain (SEclin). MIBC was defined as ≥50% reduction in metabolic activity. Results: In experiment 1, while V concentration remained stable over time, MIBC values varied, notably increasing from 8 weeks for all strains. Moreover, in experiment 2, significant reductions in both V concentration and MIBC were detected in the 2-week period. Conclusions: V lock solution appears to be able to be 12-weeks frozen followed by up to 1 week at refrigeration or room temperature. This facilitates the optimization of vial preparation in hospital pharmacy laboratories.
Álvaro Irigoyen-von-Sierakowski, Marta Díaz-Navarro, Andrés Visedo, María Jesús Pérez-Granda, Pablo Martín-Rabadán, Patricia Muñoz, and María Guembe
American Society for Microbiology
ABSTRACT The differential time to positivity (DTTP) technique is the recommended conservative procedure to diagnose catheter-related bloodstream infection (C-RBSI). However, its reliability and accuracy remain under debate. Therefore, we aimed to compare the DTTP technique feasibility to detect C-RBSI compared to the catheter culture (CC) method. We conducted a 9-month retrospective study including bacteremic episodes in which both DTTP blood cultures (BC) and CC were obtained. We analyzed the diagnostic validity of the DTTP technique for detecting C-RBSI compared to the gold standard (C-RBSI with CC), along with patient clinical data. We included 37 episodes of C-RBSI where both DTTP BC and CC were obtained. C-RBSI was confirmed by both techniques in only 13 episodes (35.1%), whereas in 11 (29.7%) and 13 (35.1%), only DTTP BC or DTTP BC with CC (with a difference between catheter lumen and peripheral BC growth of <2 hours) was positive, respectively. Therefore, the validity values of the DTTP technique for predicting C-RBSI were as follows: sensitivity, 50.0%; specificity, 71.8%; positive predictive value, 54.2%; and negative predictive value, 68.3%. The distribution of microorganisms was similar among the three groups. All patients in whom colonization was not demonstrated by CC ( n = 11) had been receiving antibiotics before catheter withdrawal. DTTP is a conservative technique that might help to diagnose C-RBSI mostly in situations where catheter removal cannot be achieved. However, it should be interpreted with caution and never be used to rule out C-RBSI. CC before starting antimicrobial therapy remains the most reliable method to diagnose and confirm an episode of C-RBSI. IMPORTANCE We try to clarify the reliability of the differential time to positivity technique to predict C-RBSI. It may be interpreted with caution and considering clinical signs, as some C-RBSI can be misdiagnosed.
María Guembe, Rama Hafian, Marta Díaz-Navarro, Andrés Visedo, Flavio De Maio, Fulvia Pimpinelli, Ilaria Cavallo, Mauro Truglio, Francesca Sivori, and Enea Gino Di Domenico
American Society for Microbiology
ABSTRACT Klebsiella pneumoniae is a significant healthcare-associated pathogen, notable for its diverse virulence and antibiotic resistance profiles. This study aimed to characterize the genotypic and phenotypic diversity of K. pneumoniae isolates and evaluate their virulence using the Galleria mellonella model. Biomass production, metabolic activity, capsule formation, and siderophore production were assessed in 27 K . pneumoniae isolates from hospital-associated infections. Lethality curves were generated using the G. mellonella model, with survival monitored hourly from 16 to 48 hours. The most common sequence types (ST) identified were the high-risk clones ST307 ( N = 10), ST512 ( N = 8), ST101 ( N = 7), and ST661 ( N = 2). These STs were associated with distinct K-locus, including KL102, KL107, KL17, and KL39. Most isolates belonged to the O2afg locus ( N = 18), with the K. pneumoniae carbapenemase genotype detected in 96.3% of strains. None of the isolates were classified as hypervirulent. Phenotypically, ST661 exhibited the highest biomass production despite showing similar metabolic activity to other STs. A positive correlation was observed between biomass and siderophore production, while capsule production was inversely correlated with biomass. In the G. mellonella model, ST661 demonstrated the highest virulence, resulting in 100% mortality by 48 hours, compared to survival rates of 21.4% for ST101, 38.0% for ST307, and 31.2% for ST512. These findings underscore the pathogenic potential of ST661 isolates with enhanced biofilm production. The G. mellonella model may serve as an effective in vivo system for evaluating the virulence of emerging K. pneumoniae lineages. IMPORTANCE We demonstrate that the Galleria mellonella model is a useful tool to analyze the virulence of carbapenem-resistant Klebsiella pneumoniae strains. Our findings highlight the pathogenicity of carbapenem-resistant K pneumoniae isolates, particularly the role of the ST661 that, despite being a rare lineage, harbors the blaVIM gene and is associated with high biofilm production and the highest mortality rates.
Marta Díaz-Navarro, Emilia Cercenado, Ariadna Monte, Andrés Visedo, Carmen Rodríguez, Ma Jesús Pérez-Granda, Patricia Muñoz, and María Guembe
Elsevier BV
Mario González-Arjona, Gorka Sobrino, Lorena Cussó, María Guembe, Daniel Calle, Francisco Díaz Crespo, Emilio Bouza, Patricia Muñoz, Manuel Desco, and Beatriz Salinas
American Chemical Society (ACS)
Infective endocarditis (IE) represents a significant concern among hospital-acquired infections, frequently caused by the Gram-positive bacterium Staphylococcus aureus. Nuclear imaging is emerging as a noninvasive and precise diagnostic tool. However, the gold standard radiotracer [18F]-FDG cannot distinguish between infection and inflammation, resulting in false positives. Based on the presence of collagen-binding proteins in the cell wall of S. aureus, we propose the radiolabeling of collagen for its evaluation in IE animal models by single-photon emission computed tomography (SPECT) imaging. We radiolabeled rat tail collagen I using DTPA chelator and [99mTc]NaTcO4. Selectivity was evaluated in vitro using 3 Gram-positive bacteria, 1 Gram-negative bacteria and 1 yeast. In vivo SPECT/computed tomography (CT) imaging was conducted on 8 SD rat models of IE and 8 sterile sham model as controls. Ex vivo biodistribution and autoradiography were performed following imaging. Diagnosis of IE was confirmed through microbiological studies and H&E histopathology. [99mTc]-DTPA-Collagen was synthesized successfully with a yield of 42.86 ± 6.35%, a purity of 95.84 ± 1.85% and a stability higher than 90% after 50 h postincubation. In vitro uptake demonstrated the selectivity for Gram-positive bacteria (63.85 ± 15.15%). Ex vivo analysis confirmed hepato-splenic excretion. In vivo SPECT/CT imaging revealed highly localized uptake within the aortic valve with a sensitivity of 62.5% and specificity of 87.5%. We successfully synthesized and characterized a new SPECT radiotracer based on [99mTc]Tc-radiolabeled collagen. In vitro studies demonstrated the selectivity of the radiotracer for Gram-positive bacteria. In vivo SPECT/CT-based assessment in an IE model confirmed the potential of this approach to detect active IE.
Francesco Palma, Marta Díaz-Navarro, Andrés Visedo, Pablo Sanz-Ruíz, Giorgio Brandi, Giuditta Fiorella Schiavano, and María Guembe
Frontiers Media SA
Francesco Palma, Marta Díaz-Navarro, Andrés Visedo, Pablo Sanz-Ruíz, Giorgio Brandi, Giuditta Fiorella Schiavano, and María Guembe
Frontiers Media SA
IntroductionBiofilm-related Multidrug Resistance (MDR) is a major problem in healthcare-associated infections (HAI). Hospital surface decontamination is essential to ensure the safety of patients and to eliminate the dissemination of MDR pathogens. New eco-friendly decontamination technologies, such as UV-C irradiation, are only gaining popularity now, but their use against the biofilm of common microorganisms causing HAI has not been properly assessed. We aimed to assess the efficacy of UV-C irradiation (254 nm) in a 2-phase study by assessing its anti-biofilm effect against sessile cells from microorganisms of hospital interest.MethodsThe following strains were tested: methicillin-susceptible Staphylococcus aureus (MSSA) (ATCC 29213), methicillin-resistant Staphylococcus aureus (MRSA) (ATCC 43300), Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 15442, and Candida albicans (ATCC 14053), and a clinical strain of methicillin-resistant Staphylococcus epidermidis. First, the tested strains' UV-susceptibility was evaluated through irradiation tests on plates using different UV doses, considering both planktonic and 24 h-biofilm states. Second, the anti-biofilm effect of UV-C was evaluated on stainless steel discs contaminated with a 24 h-biofilm of each strain.ResultsWith a UV dose of 946.7 mJ/cm2, the UV-C irradiation on MSSA ATCC 29213, MRSA ATCC 43300, and MRSE biofilm showed a log10 reduction of 4.34 ± 0.70, 4.70 ± 0.60, and 4.85 ± 0.98, respectively, while C. albicans ATCC 14053 showed higher UV-resistance in 24 h-biofilm state, being the log10 reduction of 3.17 ± 0.08. Against Gram negative bacteria biofilm, a UV dose of 467.8 mJ/cm2 was enough to achieve a microbial titer &lt;1 CFU/mL. Regarding the 24 h-biofilm on discs, a log10 reduction &gt;3 logs was achieved with all microorganisms applying a UV dose of 946.7 mJ/cm2.ConclusionThe application of UV-C irradiation could be a valid additional approach in the management of biofilm HAI.
Marta Díaz-Navarro, Álvaro Irigoyen, María Palomo, Pilar Escribano, Jesús Guinea, Almudena Burillo, Alicia Galar, Patricia Muñoz, and María Guembe
Elsevier BV
Marta Díaz-Navarro, Álvaro Irigoyen-von-Sierakowski, Imani Delcán, Ariadna Monte, María Palomo, Pilar Escribano, Jesús Guinea, Almudena Burillo, Alicia Galar, Patricia Muñoz,et al.
Frontiers Media SA
BackgroundDespite the pathogenesis of vulvovaginal candidiasis (VVC) is multifactorial, this study aimed to assess whether phenotypic characteristics, such as biofilm production and quality, along with clinical symptoms, are associated with recurrent VVC (RVVC).MethodsOver 1 year (Oct 2021–Oct 2022), we prospectively included 271 patients ≥18 years who attended our institution, had Candida spp. isolated in vaginal swabs, and provided informed consent. Patients were followed for 1 year. Candida spp. isolates were tested by the following techniques: crystal violet (CV) for biomass quantification, XTT for metabolic activity quantification, and microscopy for biofilm area quantification. Clinical and microbiological data were also collected.ResultsOverall, 55 (20.3%) patients experienced at least one recurrence, with 19 (7.0%) meeting the criteria for RVVC (≥3 episodes/year), with 65 episodes in total. Demographic and clinical characteristics were similar in both study groups. Most isolates were C. albicans (90.0%). Median (interquartile, [IQR]) absorbance values for CV and XTT in 18/19 RVVC and 238/252 non-RVVC isolates were as follows: CV, 1.850 (1.578–2.156) vs. 1.426 (1.081–1.823), p = 0.005; XTT, 0.184 (0.116–0.293) vs. 0.228 (0.147–0.331), p = 0.253. Median (IQR) biofilm occupation area percentage in 16/19 RVVC and 16/252 non-RVVC isolates was, respectively: 13.15 (8.54–16.9) and 10.73 (5.88–17.73), p = 0.710.ConclusionRVVC was associated to high biomass production. Additionally, RVVC clinical isolates exhibited a tendency toward lower metabolic activity, which may contribute to treatment failure.
Miguel Márquez-Gómez, Marta Díaz-Navarro, Andrés Visedo, Lourdes Prats-Peinado, Patricia Muñoz, Javier Vaquero, María Guembe, and Pablo Sanz-Ruíz
MDPI AG
Background: Chemical debridement is a fundamental step during the surgical treatment of both acute and chronic periprosthetic joint infection (PJI). However, there is no consensus on the optimal solution, nor is there sufficient evidence on the optimal irrigation time and combination of solutions. In an in vitro study, our group recently demonstrated that sequential combination debridement (SCD) with 3% acetic acid (AA) followed by 10% povidone iodine (PI) and 5 mM hydrogen peroxide (H2O2) was the best strategy for reducing bacterial load. The present study aimed to validate these findings in an in vivo model. Results: The median (IQR) log CFU/mL was lower in the group of mice treated with SCD (2.85 [0.00–3.72]) than in the Bactisure™ group (4.02 [3.41–4.72], p = 0.02). While this reduction was also greater than in the PI group (3.99 [1.11–4.33]), the difference did not reach statistical significance (p = 0.19). Cell viability assays showed no differences between treatments. S. aureus bacteremia was detected in 10% of mice treated with SCD, compared to 30% in the PI group and 10% in the Bactisure™ group. The difference was not statistically significant (p = 0.36). Conclusion: Our findings confirm that SCD significantly reduced bacterial load in an in vivo S. aureus PJI model, showing superior anti-biofilm activity compared to Bactisure™ and comparable performance to PI alone. These results highlight SCD’s potential to serve as a standardized chemical debridement protocol, combining enhanced efficacy with clinical applicability. Methods: We tested SCD with 3% AA for 3 min, 10% PI for 3 min, and H2O2 for 3 min in a 7-day Staphylococcus aureus (ATCC29213)-based murine femur PJI model and compared the results with single treatments of 10% PI for 3 min or Bactisure™ solution for 3 min. A sterile steel implant with local administration of saline solution for 3 min was used as a non-infected control. After completing irrigation procedures, under anesthesia, mice were euthanized, and implants were analyzed for CFU/mL counts and cell viability rates. Blood cultures were obtained pre-euthanasia to detect bacteremia.
Antonio Benjumea-Carrasco, María Guembe, Marta Díaz-Navarro, Patricia Muñoz, Javier Vaquero-Martin, and Francisco Chana-Rodriguez
Elsevier BV
Marta Díaz-Navarro, Rama Hafian, María Jesús Pérez-Granda, Emilia Cercenado, Patricia Muñoz, and María Guembe
Elsevier BV
Patricia Muñoz, María Guembe, María Jesús Pérez-Granda, José Luís del Pozo, Luis Eduardo López-Cortés, Mauro Pittiruti, María Cruz Martín-Delgado, and Emilio Bouza
Sociedad Espanola de Quimioterapia
Catheter-related infections (CRI) are a serious healthcare problem due to their potential to cause serious complications, including bacteraemia or infective endocarditis, and to increase patient morbidity and mortality. In addition, these in fections significantly prolong hospital stay and cost. Preventing CRI is crucial and is considered a criterion for quality and safety in healthcare. For these reasons, the Spanish Society of Cardiovascular Infections (SEICAV) has considered it pertinent to review this topic, with experts in different areas including clinical microbiologists, infectious disease specialists, surgeons and nurses. The data were presented at a session held at the Ramón Areces Foundation, which was organised in the form of specific questions grouped into three round tables. The first panel analysed the scale of the problem including epidemiological, clinical and diagnostic aspects; the second panel addressed advances in the treatment of CRI; and the third panel reviewed developments in the prevention of CRI. The recorded session is available on the Areces Foundation website and we believe it maybe of interest not only to health professionals, but also to any non-expert citizen interested in the subject.
María Jesús Pérez-Granda, Francisca Guzmán Blanco, Sonia Aguado Díaz, Rosario Jiménez Bautista, Julia Orense Velilla, Juana Rodríguez Calero, María Luisa Valls, Antonio Vicente Arellano, Pilar García Santos, Patricia Munoz,et al.
Elsevier BV
María Jesús Pérez-Granda, Almudena Burillo, Julia Serrano-Lobo, Pablo Martín-Rabadán, Patricia Muñoz, Emilio Bouza, and María Guembe
Elsevier BV
Álvaro Irigoyen-von-Sierakowski, Marta Díaz-Navarro, Andrés Visedo, Mª Jesús Pérez-Granda, Pablo Martín-Rabadán, Patricia Muñoz, and María Guembe
MDPI AG
Background. Escherichia coli commonly causes catheter-related bloodstream infection (C-RBSI) in specific populations. The differential time to positivity (DTTP) technique is the recommended conservative procedure for diagnosing C-RBSIs. Methods. We conducted a retrospective study of episodes in which E. coli was isolated from catheter lumens obtained using the DTTP technique. Microbiological and clinical data were obtained based on the DTTP technique as either catheter colonization, C-RBSI, or non-C-RBSI. Results. A total of 89 catheter blood cultures were included, classified as follows: catheter colonization, 33.7%; C-RBSI, 9.0%; and non-C-RBSI, 57.3%. Only 15.7% of the catheters were withdrawn, with no positive catheter-tip cultures. We found no statistically significant differences in catheter type, antibiotic treatment, or clinical outcome among the groups, except for the frequency of catheter lock therapy or in the frequency of successful treatment. Mortality was associated with C-RBSI in only one patient. Conclusion. E. coli bacteremia diagnosed by the DTTP technique was classified as non-catheter-related in most patients. As the majority of the catheters were retained, E. coli bacteremia could not be microbiologically confirmed as catheter-related by the catheter-tip culture. Future studies are needed to assess the profitability of the DTTP technique for diagnosing E. coli C-RBSIs.
Enea Gino Di Domenico, Alessandra Oliva, and María Guembe
MDPI AG
In this Special Issue, titled “Biofilm-Related Infections in Healthcare”, we have reported considerable progress in understanding the physiology and pathology of biofilms [...]
M. Pérez-Granda, Álvaro Irigoyen-von-Sierakowski, Neera Toledo, Eva Rodríguez, María Luisa Cruz, Giovanna Hernanz, José Antonio Serra, M. Kestler, Patricia Muñoz and M. Guembe
María Guembe, Nils P. Hailer, and Pablo Sanz-Ruíz
Frontiers Media SA
Antonio Benjumea, Marta Díaz-Navarro, Rama Hafian, Emilia Cercenado, Mar Sánchez-Somolinos, Javier Vaquero, Francisco Chana, Patricia Muñoz, and María Guembe
Frontiers Media SA
Antonio Benjumea, Marta Díaz-Navarro, Ángela Sai Gago-Campos, Andrés Visedo, Rama Hafian, Emilia Cercenado, Mar Sánchez-Somolinos, Patricia Muñoz, Javier Vaquero, Francisco Chana,et al.
Frontiers Media SA
BackgroundSeveral studies have shown that tranexamic acid (TXA), an antifibrinolytic, reduces postoperative infection rates. Recent in vitro research showed that TXA alone and in combination with vancomycin and gentamicin had a synergistic effect against some staphylococcal strains. In the present study, this synergistic effect was validated in samples from patients with staphylococcal periprosthetic infection (PPI) and in an in vivo model.MethodsWe tested 19 clinical strains (5 Staphylococcus aureus and 14 coagulase-negative staphylococci [CoNS]) against 10 mg/ml TXA alone and in combination with serial dilutions of vancomycin and gentamicin. The standardized microtiter plate method was used. The minimal inhibitory concentration (MIC) were calculated using standard visualization of well turbidity. We also used an S. aureus (ATCC29213) murine subcranial PPI model to compare the synergistic effect of TXA and gentamicin with that of TXA or gentamicin alone after 4 days of monitoring. The mice were euthanized, and disks were removed for analysis of cfu/ml counts and cell viability rate. Biofilm structure of both in vitro and in vivo samples was also analyzed using scanning electron microscopy (SEM).ResultsWhen TXA was combined with vancomycin or gentamicin, the MIC decreased in 30% of the strains studied. According to species, the MIC50 for vancomycin and gentamicin alone and in combination with TXA against S. aureus strains was the same. This was also the case for CoNS with vancomycin and its corresponding combination, whereas with gentamicin and TXA, a reduction in MIC50 was observed (2 dilutions). In addition, in the in vivo model, the mean (SD) log cfu/ml and cell viability rate obtained from the implant was lower in the group of mice treated with TXA and gentamicin than in those treated only with TXA or gentamicin. SEM images also corroborated our findings in strains in which the MIC was reduced, as well as the in the mice implants, with the area occupied by biofilm being greater in samples treated only with gentamicin or TXA than in those treated with TXA+gentamicin.ConclusionWe confirm that combining TXA with vancomycin or gentamicin exerts a synergistic effect. However, this only occurs in selected strains.