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Aerosols released from the oral cavity help spread the SARS-CoV-2 virus. The use of a mouthwash formulated with an antiviral agent could reduce the viral load in saliva, helping to lower the spread of the virus. The aim of this study was to assess the efficacy of a mouthwash with 0.07% cetylpyridinium chloride (CPC) to reduce the viral load in the saliva of Coronavirus disease 2019 (COVID-19) patients.In this multi-centre, single-blind, randomized, parallel group clinical trial, 80 COVID-19 patients were enrolled and randomized to two groups, namely test (n = 40) and placebo (n = 40). Saliva samples were collected at baseline and 2 h after rinsing. The samples were analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and an enzyme-linked immunosorbent assay test specific for the nucleocapsid (N) protein of SARS-CoV-2.With RT-qPCR, no significant differences were observed between the placebo group and the test group. However, 2 h after a single rinse, N protein concentration in saliva was significantly higher in the test group, indicating an increase in lysed virus.The use of 0.07% CPC mouthwash induced a significant increase in N protein detection in the saliva of COVID-19 patients. Lysis of the virus in the mouth could help reduce the transmission of SARS-CoV-2. However, more studies are required to prove this.

7 figures, 1 table., [Aims]: Peritonitis is one of the most common causes of sepsis, a serious syndrome characterized by a dysregulated systemic inflammatory response. Recent evidence suggests that Granzyme A (GzmA), a serine protease mainly expressed by NK and T cells, could act as a proinflammatory mediator and could play an important role in the pathogenesis of sepsis. This work aims to analyze the role and the therapeutic potential of GzmA in the pathogenesis of peritoneal sepsis., [Methods]: The level of extracellular GzmA as well as GzmA activity were analyzed in serum from healthy volunteers and patients with confirmed peritonitis and were correlated with the Sequential Organ Failure Assessment (SOFA) score. Peritonitis was induced in C57Bl/6 (WT) and GzmA-/- mice by cecal ligation and puncture (CLP). Mice were treated intraperitoneally with antibiotics alone or in combination serpinb6b, a specific GzmA inhibitor, for 5 days. Mouse survival was monitored during 14 days, levels of some proinflammatory cytokines were measured in serum and bacterial load and diversity was analyzed in blood and spleen at different times., [Results]: Clinically, elevated GzmA was observed in serum from patients with abdominal sepsis suggesting that GzmA plays an important role in this pathology. In the CLP model GzmA deficient mice, or WT mice treated with an extracellular GzmA inhibitor, showed increased survival, which correlated with a reduction in proinflammatory markers in both serum and peritoneal lavage fluid. GzmA deficiency did not influence bacterial load in blood and spleen and GzmA did not affect bacterial replication in macrophages in vitro, indicating that GzmA has no role in bacterial control. Analysis of GzmA in lymphoid cells following CLP showed that it was mainly expressed by NK cells. Mechanistically, we found that extracellular active GzmA acts as a proinflammatory mediator in macrophages by inducing the TLR4-dependent expression of IL-6 and TNFα., [Conclusions]: Our findings implicate GzmA as a key regulator of the inflammatory response during abdominal sepsis and provide solid evidences about its therapeutic potential for the treatment of this severe pathology., This work was supported by grant SAF2017-83120-C2-1-R and SAF2014-54763-C2-2-R from the Ministry of Science, Innovation and Universities and FEDER (Group B29_17R, Aragon Government). MG and LS were supported by a PhD fellowship (FPI) from the Ministry of Science, Innovation and Universities. IUM was supported by a PhD fellowship from Aragon Government, MA was supported by a post-doctoral fellowship “Juan de la Cierva-formación” from the Ministry of Science, Innovation and Universities. JP was supported by ARAID Foundation.

7 figures, 2 tables., Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by Aspergillus fumigatus and other fungi of the Aspergillus genus. Some evidence suggests that GT shows antimicrobial activity against S. aureus in vitro, albeit its efficacy against multidrug-resistant strains such as MRSA or vancomycin-intermediate S. aureus (VISA) strainsis not known. This work aimed to evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a Caenorhabditis elegans infection model., This research was funded by FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón (Group B29_17R), Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación (SAF2017-83120-C2-1-R), ASPANOA, GILEAD (GLD18/00100), Donación Javier Saura Carceller, and Carrera de la Mujer de Monzón. J.P. was supported by Fundacion Aragon I+D (ARAID). P.E. was supported by Fondo Garantıa Empleo Juvenil/INAEM. L.C. and S.R. were granted funding by a DGA predoctoral contract. M.A. was granted funding by a Juan de la Cierva contract of Spanish Ministry of Economy and Competitiveness (FJCI-2017-31629).

ContextIt has been more than 10 years since the human papillomavirus (HPV) vaccination program was initiated in most advanced countries. Thus, it seems necessary to change the uterine cervical cancer screening strategy. Molecular-based tests are considered essential in this scenario.ObjectiveWe aimed to review the distribution of the HPV genotypes after the introduction of the vaccination program with Cervarix® and Gardasil 4® in two autonomous communities in Spain, looking for possible changes in distribution and the occurrence of a herd effect.DesignA cross-sectional study was performed in 45,362 samples that were processed in the Cantabria and Aragon communities during the period from 2002 to 2016. We compared the genotype distribution before and after the vaccination program was initiated.ResultsGenotypes HPV6 and HPV11 have decreased significantly after the introduction of the vaccine. HPV16 has had a decrease, but not a significant one in the statistical analysis. However, HPV31, HPV52, and HPV45 have increased in percentage. A replacement phenomenon with other genotypes not included in the vaccine has been observed in our population.ConclusionsContinued surveillance is needed to provide further indication of any changes over time in the genotypes in circulation. This will be facilitated by monitoring the genotyping results from the new model of cervical screening using primary HPV DNA testing.

Multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) is one of the major causes of hospital-acquired and community infections and pose a challenge to the human health care system. Therefore, it is important to find new drugs that show activity against these bacteria, both in monotherapy and in combination with other antimicrobial drugs. Gliotoxin (GT) is a mycotoxin produced by Aspergillus fumigatus and other fungi of the Aspergillus genus. Some evidence suggests that GT shows antimicrobial activity against S. aureus in vitro, albeit its efficacy against multidrug-resistant strains such as MRSA or vancomycin-intermediate S. aureus (VISA) strainsis not known. This work aimed to evaluate the antibiotic efficacy of GT as monotherapy or in combination with other therapeutics against MRSA in vitro and in vivo using a Caenorhabditis elegans infection model.

a b s t r a c t Introduction: MRSA population dynamics is undergoing significant changes, and for this reason it is important to know which clones are circulating in our nosocomial environment. Materials and methods: A total of 118 MRSA isolates were collected from clinical samples from patients with previous hospital or healthcare contact (named as hospital-onset MRSA (HO-MRSA)) during a one year period. Susceptibility testing was performed by disk diffusion and microdilution. The presence of resistance genes and virulence factors were tested by PCR. All isolates were typed by SCCmec, spa and agr typing. PFGE and MLST were applied to a selection of them. Results: Eighty-three HO-MRSA isolates (70.3%) were resistant to any antibiotic included in the macrolide-lincosamide-streptogramin B group. Among these isolates, the M phenotype was the most frequent (73.5%). One hundred and seven of HO-MRSA isolates (90.7%) showed aminoglycoside resistance. The combination aac(6 � )-Ie-aph(2 �� )-Ia + ant(4 � )-Ia genes was the most frequent (22.4%). Tetracycline resis- tance rates in HO-MRSA isolates were low (3.4%), although a high level of mupirocin resistance was observed (25.4%). Most of the HO-MRSA isolates (approximately 90%) showed SCCmec type IVc and agr type II. Fifteen unrelated pulsotypes were identified. CC5 was the most prevalent (88.1%), followed by CC8 (5.9%), CC22 (2.5%), CC398 (2.5%) and CC1 (0.8%). Conclusion: CC5/ST125/t067 lineage was the most frequent. This lineage was related to aminoglycoside resistance, and to a lesser extent, with macrolide resistance. The presence of international clones as EMRSA-15 (CC22/ST22), European clones as CC5/ST228, community clones related to CC1 or CC8 and livestock associated clones, as CC398, were observed in a low percentage.

Spanish HIV-2 Study Group., [Background] A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir., [Methods] All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded., [Results] From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R., [Conclusions] A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R., This work was supported in part by grants from Fundación Investigación y Educación en SIDA (F-IES); Fondo de Investigación Sanitaria-Fondos FEDER (FIS, PI13/01574; ICI14/0274, CES12/003, FI14/00264, CD14/00243).

A total of 128 isolates associated with catheter-related infections was recovered from 101 intensive care unit patients in a Spanish hospital during March 2008 to August 2009, and 27 of these isolates (from 21 patients) were typed as methicillin- and linezolid-resistant Staphylococcus epidermidis . Thirteen of these 21 patients (62%) had received linezolid during the 3 months preceding S. epidermidis recovery. Two closely related pulsotypes (P1a and P1b) were identified among the 27 studied isolates that belonged to the sequence type ST2 and harboured the mecA gene and the SCC mec III type. The strains recovered from patients 1–4 (pulsotype P1a) showed the nucleotide mutation G2474T inside the amplified fragment of the 23S rRNA region and carried the aac (6′)-Ie- aph (2″)-Ia, ant (4′), and catA genes, whereas the strains from patients 5–21 (pulsotype P1b) showed the mutation G2603T and carried the aac (6′)-Ie- aph (2″)-Ia gene. None of the strains amplified the cfr gene. The ica gene and the IS 256 element were detected in all strains. The emergence of 2 closely related methicillin- and linezolid-resistant S. epidermidis strains with 2 different mutations in the 23S rRNA region (G2474T and G2603T) is reported in this study as a cause of a nosocomial outbreak. The presence of G2474T or G2603T point mutations suggests that there are multiple potential sites within domain V of the 23S rRNA region at which mutations could confer resistance to linezolid in the clinical isolates. To our knowledge, this is the first report in which the G2474T mutation has been detected in domain V of the 23S rRNA gene of clinical S. epidermidis .

The increasing prevalence of carbapenem-resistant Enterobacteriaceae and nonfermenting Gram-negative bacteria is a growing public health threat. The carbapenemase acquisition is one of the most clinically important and reported carbapenem resistance mechanisms, highlighting metallo-beta-lactamases (