Healthcare-associated infections: New challenges looking for answers

Nosocomial transmission of multiresistant bacteria is a growing healthcare issue. In addition, new pathogens and pathogenic mechanisms, associated with therapies based on the use of live microorganisms, can be of importance in the near future. The current issue of CKJ illustrates healthcare-associated infections that go beyond common bacteria. First, the therapeutic use of live BCG mycobacteria is not without risks in the chronic kidney disease patients. Familiarity with these complications will allow their rapid recognition and optimized management. Second, strict adherence to universal precautions and healthcare guidelines is still mandatory in order to avoid undesirable risks such as transmission of hepatitis B virus

Disminución del nivel de conciencia, fiebre y disnea en una paciente infectada con el virus de la inmunodeficiencia humana

Monthly newsletter providing updates of interest to the Boston University School of Medicine community

SARS-CoV-2 mutant spectra at different depth levels reveal an overwhelming abundance of low frequency mutations

Populations of RNA viruses are composed of complex and dynamic mixtures of variant genomes that are termed mutant spectra or mutant clouds. This applies also to SARS-CoV-2, and mutations that are detected at low frequency in an infected individual can be dominant (represented in the consensus sequence) in subsequent variants of interest or variants of concern. Here we briefly review the main conclusions of our work on mutant spectrum characterization of hepatitis C virus (HCV) and SARS-CoV-2 at the nucleotide and amino acid levels and address the following two new questions derived from previous results: (i) how is the SARS-CoV-2 mutant and deletion spectrum composition in diagnostic samples, when examined at progressively lower cut-off mutant frequency values in ultra-deep sequencing; (ii) how the frequency distribution of minority amino acid substitutions in SARS-CoV-2 compares with that of HCV sampled also from infected patients. The main conclusions are the following: (i) the number of different mutations found at low frequency in SARS-CoV-2 mutant spectra increases dramatically (50-to 100-fold) as the cut-off frequency for mutation detection is lowered from 0.5% to 0.1%, and (ii) that, contrary to HCV, SARS-CoV-2 mutant spectra exhibit a deficit of intermediate frequency amino acid substitutions. The possible origin and implications of mutant spectrum differences among RNA viruses are discussedThis work was supported by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181), and co-financed by European Development Regional Fund ‘A way to achieve Europe’. The work was also supported by grants CSIC-COV19-014 from Consejo Superior de Investigaciones Científicas (CSIC), project 525/C/2021 from Fundació La Marató de TV3, PID2020-113888RB-I00 from Ministerio de Ciencia e Innovación, BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 and PI21/00139 from Instituto de Salud Carlos III, and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P., M.C., and P.M. are supported by the Miguel Servet programme of the Instituto de Salud Carlos III (CPII19/00001, CPII17/00006, and CP16/00116, respectively) cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo) cofinanced by Fondo Social Europeo (FSE). R.L.-V. is supported by predoctoral contract PEJD-2019-PRE/BMD-16414 from Comunidad de Madrid. C.G.-C. is supported by predoctoral contract PRE2018-083422 from MCIU. P.S. is supported by postdoctoral contract “Margarita Salas” CA1/RSUE/2021 from MCIU. B.S. was supported by a predoctoral research fellowship (Doctorados Industriales, DI-17-09134) from Spanish MINEC

Sonication of intramedullary nails: Clinically-related infection and contamination

Background and Aim: Sonication is currently considered the best procedure for microbiological diagnosis of implant-related osteoarticular infection, but studies in nail-related infections are lacking. The study aim was to evaluate implant sonication after intramedullary nail explantation, and relate it to microbiological cultures and clinical outcome. Patients and Methods: A study was performed in two University Hospitals from the same city. Thirty-one patients with implanted nails were prospectively included, whether with clinical infection (8 cases) or without (23 cases). Retrieved nails underwent sonication according a previously published protocol. The clinical and microbiological outcome patient was related to the presence of microorganisms in the retrieved implant. Results: Positive results appeared in 15/31 patients (9 with polymicrobial infections) almost doubling those clinically infected cases. The most commonly isolated organisms were Staphylococcus epidermidis (19.2 %) and Staphylococcus aureus (15.4 %). A significant relationship was found between the presence of positive cultures and previous local superficial infection (p=0.019). The presence of usual pathogens was significantly related to clinical infection (p=0.005) or local superficial infection (p=0.032). All patients with positive cultures showed pain diminution or absence of pain after nail removal (15/15), but this only occurred in 8 (out of 16) patients with negative cultures. Conclusions: In patients with previously diagnosed infection or local superficial infection, study of the hardware is mandatory. In cases where pain or patient discomfort is observed, nail sonication can help diagnose the implant colonization with potential pathogens that might require specific treatment to improve the final outcomePart of this work was funded by grants from the Comunidad de Madrid (S2009/MAT-1472) and from the CONSOLIDER-INGENIO Program (FUNCOAT-CSD2008- 00023). DMM was funded by a grant from the Fundación Conchita Rábago de Jiménez Día

Biofilm development by clinical strains of non-pigmented rapidly growing mycobacteria

AbstractThe relationship between clinical significance of non-pigmented, rapidly growing mycobacteria (NPRGM), in vitro biofilm development and sliding motility was evaluated in this study. One hundred and sixty-eight clinical strains of NPRGM were included. Forty-one of these were clinically significant isolates. Biofilm was formed by 123 strains. Seventy-six biofilm-positive and 25 biofilm-negative strains showed sliding motility. There was a relationship between clinical significance and biofilm development (p <0.000 001), sliding motility (p 0.0037) and species (p <0.000 001). No relationship was found between motility and biofilm development. The ability to develop biofilm is a characteristic that can have importance in the development of infections caused by NPRGM

Cranberry-derived phenolic metabolites and urinary tract infections

Resumen del póster presentado a la 7th International Conference on Polyphenols and Health, celebrada en Tours (Francia) del 27 al 30 de octubre de 2015.The beneficial effects of cranbeny products against urinary tract infections (UTIs) have been attributed, at least partly, to their A-type proanthocyanidin (PAC) content. A-type PACs have shown uropathogenic Escherichia coli (UPEC)-anti-adhesive activity, although they are unlikely to appear in urine at relevant concentrations as they are poorly absorbed. One leading hypothesis is that PAC-derived metabolites present in urine would operate in the phase of UPEC adyherence to uroepithelial cells, preventing bacterial colonization. In addition to this, and as it is becoming evident that the intestine is a reservoir for uropathogenic bacteria, other hypothesis is that. A-type proanthocyanidins specifically decrease the transient intestinal colonisation b UPEC, consequently reducing the risk of UTI incidence. In any case, gut microbiota (and its inter-individual variability) seems to be an important factor to be considered. In this communication, we summarize our results from different approaches aimed to look into the mechanisms that are behind the protedive action of cranberry polyphenols against ITUs: 1)in vitro fermentations of cranbeny polyphenols with colonic microbiota, that were performed to access the microbial-derived metabolic profile of cranbeny polyphenols as well as their effect on gut microbiota survival, 2) an in vivo trial with model mouse intraurethral-inoculated wilh UPEC, that evaluated the effectiveness of cranbeny supplementation in bacterial infection as well as its impact on faecal phenolic metabolism and faecal microbiota, 3) testing the UPEC-antiadhesive capacity of cranbeny phenolic compounds and their metabolites in bladder epithelial cell culíures, and 4) ex vivo studies of UPEC-antiadhesive capacity of mice mines collected after cranbeny supplementation.Ministry of Economy and Competitiveness (MiNECO) (Projects AGL-2010-17499 and AGL2012-40172-C02-01) and the Comunidad Autónoma de Madrid (Project ALIBIRD S2013/ABI-2728), Spain.Peer Reviewe

Comparative effects of A- and B-type proanthocyanidins in the prevention of urinary tract infection in mice

Resumen del póster presentado a la VI International Conference on Polyphenols and Health celebrada en Buenos Aires (Argentina) del 16 al 19 de octubre de 2013.Consumption of cranberry (Vaccinium macrocarpum) is widely recommended forprophylaxis against urinary tract infections (UTI) in women. Among cranberry components, A-type proanthocyanins would be implicated in these preventive effects against UTI. However, proanthocyanidins are poorly absorbed in the small intestine, but subjected to extensive biotransformation in the colon, although studies are almost restricted to B-type proanthocyanidins. Therefore, the hypothesis of this study is that urinary metabolome from of A-type and B-type proanthocyanidins-mainly derived from their colonic catabolism-differ,and only metabolites from the A-type procyanidins have protective effects against UTI. To test this hypothesis, JAXc3H/OuJ female mice previously fed with specific diet (control, 1% cranberry extract and 1% grape seed extract) for 2 weeks, were inoculated with the uropathogenic E. coli (ATCC 53503™) to provoke infection, and maintained 2 weeks more before being sacrificed. Urine samples were collected at different times and subjected to E.coli counting, leukocytary esterase and nitrites analyses, and mieloperoxidase task. Samples of kidney and bladder tissues were also collected for E. coli counting and histopathologic analysis. Additionally, the capacity of the urine samples to inhibit bacterial adherence was tested in the T24 bladder cell line (ATCC HTB4 ™).Peer reviewe

Antibody response in patients admitted to the hospital with suspected SARS-CoV-2 infection: results from a multicenter study across Spain

Aim: To evaluate the serological response against SARS-CoV-2 in a multicenter study representative of the Spanish COVID pandemic. Methods: IgG and IgM + IgA responses were measured on 1466 samples from 1236 Spanish COVID-19 patients admitted to the hospital, two commercial ELISA kits (Vircell SL, Spain) based on the detection of antibodies against the viral spike protein and nucleoprotein, were used. Results: Approximately half of the patients presented antibodies (56.8% were IgM + IgA positive and 43.0% were IgG positive) as soon as 2 days after the first positive PCR result. Serological test positivity increased with time from the PCR test, and 10 days after the first PCR result, 91.5% and 88.0% of the patients presented IgM + IgA and IgG antibodies, respectively. Conclusion: The high values of sensitivity attained in the present study from a relatively early period of time after hospitalization support the use of the evaluated serological assays as supplementary diagnostic tests for the clinical management of COVID-19

Vaccine breakthrough infections with SARS-CoV-2 Alpha mirror mutations in Delta Plus, Iota, and Omicron

Replication of SARS-CoV-2 in the human population is defined by distributions of mutants that are present at different frequencies within the infected host and can be detected by ultra-deep sequencing techniques. In this study, we examined the SARS-CoV-2 mutant spectra of amplicons from the spike-coding (S-coding) region of 5 nasopharyngeal isolates derived from patients with vaccine breakthrough. Interestingly, all patients became infected with the Alpha variant, but amino acid substitutions that correspond to the Delta Plus, Iota, and Omicron variants were present in the mutant spectra of the resident virus. Deep sequencing analysis of SARS-CoV-2 from patients with vaccine breakthrough revealed a rich reservoir of mutant types and may also identify tolerated substitutions that can be represented in epidemiologically dominant variants.This work was supported by the Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (COVID-19 Research Call COV20/00181) and co-financed by the European Development Regional Fund “A way to achieve Europe.” The work was also supported by grants CSIC-COV19-014 from the CSIC, project 525/C/2021 from the Fundació La Marató de TV3; PID2020-113888RB-I00 from the Ministerio de Ciencia e Innovación; BFU2017-91384-EXP from the Ministerio de Ciencia, Innovación y Universidades (MCIU);PI18/00210 and PI21/00139 from the Instituto de Salud Carlos III; and S2018/BAA-4370 (PLATESA2) from the Comunidad de Madrid/ FEDER. This research work was also funded by the European Commission – NextGenerationEU (regulation EU 2020/2094), through the CSIC’s Global Health Platform (PTI Salud Global). CP and PM are supported by the Miguel Servet programme of the Instituto de Salud Carlos III (CPII19/00001 and CP16/00116, respectively), cofinanced by the European Regional Development Fund (ERDF). CIBERehd is funded by the Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). BMG is supported by predoctoral contract PFIS FI19/00119 from the Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo), cofinanced by the Fondo Social Europeo (FSE). CGC is supported by predoctoral contract PRE2018- 083422 from the MCIU. BS was supported by a predoctoral research fellowship (Doctorados Industriales, DI-17-09134) from the Spanish Ministry of Economy and Competitiveness (MINECO).Peer reviewe