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BackgroundThere is limited evidence from antimicrobial stewardship programmes in less-resourced settings. This study aimed to improve the quality of antibacterial prescriptions by mitigating overuse and promoting the use of narrow-spectrum agents in intensive care units (ICUs) in a middle-income country.MethodsWe established a quality improvement collaborative (QIC) model involving nine Argentine ICUs over 11 months with a 16-week baseline period (BP) and a 32-week implementation period (IP). Our intervention package included audits and feedback on antibacterial use, facility-specific treatment guidelines, antibacterial timeouts, pharmacy-based interventions and education. The intervention was delivered in two learning sessions with three action periods along with coaching support and basic quality improvement training.ResultsWe included 912 patients, 357 in BP and 555 in IP. The latter had higher APACHE II (17 (95% CI: 12 to 21) vs 15 (95% CI: 11 to 20), p=0.036), SOFA scores (6 (95% CI: 4 to 9) vs 5 (95% CI: 3 to 8), p=0.006), renal failure (41.6% vs 33.1%, p=0.009), sepsis (36.1% vs 31.6%, p<0.001) and septic shock (40.0% vs 33.8%, p<0.001). The days of antibacterial therapy (DOT) were similar between the groups (change in the slope from BP to IP 28.1 (95% CI: −17.4 to 73.5), p=0.2405). There were no differences in the antibacterial defined daily dose (DDD) between the groups (change in the slope from BP to IP 43.9, (95% CI: −12.3 to 100.0), p=0.1413).The rate of antibacterial de-escalation based on microbiological culture was higher during the IP (62.0% vs 45.3%, p<0.001).The infection prevention control (IPC) assessment framework was increased in eight ICUs.ConclusionImplementing an antimicrobial stewardship program in ICUs in a middle-income country via a QIC demonstrated success in improving antibacterial de-escalation based on microbiological culture results, but not on DOT or DDD. In addition, eight out of nine ICUs improved their IPC Assessment Framework Score.

BackgroundThere are only a few studies on handoff quality and adverse events (AEs) rigorously evaluating handoff improvement programmes’ effectiveness. None of them have been conducted in low and middle-income countries. We aimed to evaluate the effect of a handoff programme implementation in reducing AE frequency in paediatric intensive care units (PICUs).MethodsFacility-based, cluster-randomised, stepped-wedge trial in six Argentine PICUs in five hospitals, with >20 admissions per month. The study was conducted from July 2018 to May 2019, and all units at least were involved for 3 months in the control period and 4 months in the intervention period. The intervention comprised a Spanish version of the I-PASS handoff bundle consisting of a written and verbal handoff using mnemonics, an introductory workshop with teamwork training, an advertising campaign, simulation exercises, observation and standardised feedback of handoffs. Medical records (MR) were reviewed using trigger tool methodology to identify AEs (primary outcome). Handoff compliance and duration were evaluated by direct observation.ResultsWe reviewed 1465 MRs: 767 in the control period and 698 in the intervention period. We did not observe differences in the rates of preventable AE per 1000 days of hospitalisation (control 60.4 (37.5–97.4) vs intervention 60.4 (33.2–109.9), p=0.99, risk ratio: 1.0 (0.74–1.34)), and no changes in the categories or AE types. We evaluated 841 handoffs: 396 in the control period and 445 in the intervention period. Compliance with all items in the verbal and written handoffs was significantly higher in the intervention group. We observed no difference in the handoff time in both periods (control 35.7 min (29.6–41.8) vs intervention 34.7 min (26.5–42.1); difference 1.43 min (95% CI −2.63 to 5.49, p=0.49)). The providers’ perception of improved communication did not change.ConclusionsAfter the implementation of the I-PASS bundle, compliance with handoff items improved. Nevertheless, no differences were observed in the AEs’ frequency or the perception of enhanced communication.Trial registration number NCT03924570

Background: During the COVID-19 pandemic, the emergence of multidrug-resistant (MDR) pathogens, driven by heightened antibiotic usage and device-associated infections, has posed significant challenges to healthcare. This study reports an outbreak of Proteus mirabilis producing NDM-5 and CTX-M-15 β-lactamases in a hospital in Buenos Aires, Argentina, from October 2020 to April 2021. To our knowledge, this represents the first documented outbreak of NDM-5-producing P. mirabilis in the country. Methods: A total of 82 isolates were recovered from 40 patients, with 41.5% from blood cultures and 18.3% from respiratory and urinary samples, among others. Antimicrobial susceptibility testing, PCR-based methods, and MALDI-TOF MS cluster analysis were conducted. Whole genome sequencing (WGS) was performed to characterize the MLST, resistome and plasmid content. Biofilm formation assays and in vitro rifampicin susceptibility tests were also conducted. Result: Most isolates exhibited resistance to carbapenems, cephalosporins, aminoglycosides, and fluoroquinolones, while retaining susceptibility to aztreonam. Genetic analysis confirmed the co-presence of the blaNDM-5 and blaCTX-M-15 genes. Clonal relationships was supported by PCR-based typing and MALDI-TOF MS cluster analysis. WGS revealed a resistome comprising 25 resistance genes, including rmtB and both β-lactamases, as well as the presence of an incomplete IncQ1 replicon associated with multiple resistance determinants. MLST classified this clone as belonging to ST135. Despite the biofilm-forming capacity observed across strains, rifampicin demonstrated potential for disrupting established biofilms at concentrations ≥32 µg/mL in vitro. The MDR profile of the outbreak strain significantly limited therapeutic options. Conclusions: This study highlights the growing threat of NDM-producing P. mirabilis in Argentina. The absence of surveillance cultures from the index case limits insights into the outbreak’s origin. These findings underscore the importance of integrating genomic surveillance into infection control protocols to mitigate the spread of MDR pathogens.

BackgroundPrimary care has been essential in ensuring the continuity of health services for patients with COVID-19 and other conditions. We aimed to increase the adoption of evidence-based interventions to identify clinical deterioration in adult patients with confirmed or suspected respiratory COVID-19 at the primary care level.MethodsWe implemented specific interventions in nine Primary Healthcare Centres (PHCC) through a quality improvement collaborative (QIC) with an interrupted time-series design. Interventions included triage for acute respiratory symptoms, the National Early Warning Score 2 (NEWS2) scale, portable oximeters for selected patients and the provincial telehealth system. Additional components involved leadership commitment, teamwork tools, reminders, audits, feedback and direct observation. A mixed-method evaluation was conducted, with two learning sessions and three action periods to test and implement selected change ideas.ResultsSix PHHCs completed the study. Over 48 weeks, data from 877 patients were gathered, 356 in the baseline period (BP) and 477 in the implementation period (IP). Eight hundred and sixty-two medical consultations were reported, 367 for BP and 495 for IP. More COVID-19-confirmed diagnoses were observed in the IP group (1.9% vs 15%, p<0.001).The bundle was implemented in 0% and 28.4% of patients in the BP and IP groups, respectively. On evaluating the individual components of the bundle, we discovered enhancements in the utilisation of triage, application of NEWS2 and utilisation of oximeters when appropriate. A decrease in the number of follow-up calls was observed at the end of the implementation.Patients rated the quality of care as positive in 66% of the cases in the BP and 76% in the IP group (p=0.023).ConclusionWe successfully implemented a triage algorithm based on the NEWS2 score to identify respiratory deterioration in adult patients in primary care through a QIC. This intervention was perceived as an improvement in the quality of care by the patients.

Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.

Worldwide, bacterial resistance is one of the most severe public health problems. Currently, the failure of antibiotics to counteract superbugs highlights the need to search for new molecules with antimicrobial potential to combat them. The objective of this research was to evaluate the antimicrobial activity of Bacillus amyloliquefaciens BS4 against Gram-negative bacteria. Thirty yeasts and thirty-two Bacillus isolates were tested following the agar well-diffusion method. Four Bacillus sp. strains (BS3, BS4, BS17, and BS21) showed antagonistic activity against E. coli ATCC 25922 using bacterial culture (BC) and the cell-free supernatant (CFS), where the BS4 strain stood out, showing inhibitory values of 20.50 ± 0.70 mm and 19.67 ± 0.58 mm for BC and CFS, respectively. The Bacillus sp. BS4 strain can produce antioxidant, non-hemolytic, and antimicrobial metabolites that exhibit activity against several microorganisms such as Salmonella enterica, Klebsiella pneumoniae, Shigella flexneri, Enterobacter aerogenes, Proteus vulgaris, Yersinia enterocolitica, Serratia marcescens, Aeromonas sp., Pseudomonas aeruginosa, Candida albicans, and Candida tropicalis. According to the characterization of the supernatant, the metabolites could be proteinaceous. The production of these metabolites is influenced by carbon and nitrogen sources. The most suitable medium to produce antimicrobial metabolites was TSB broth. The one-factor-at-a-time method was used to standardize parameters such as pH, agitation, temperature, carbon source, nitrogen source, and salts, resulting in the best conditions of pH 7, 150 rpm, 28 °C, starch (2.5 g/L), tryptone (20 g/L), and magnesium sulfate (0.2 g/L), respectively. Moreover, the co-culture was an excellent strategy to improve antimicrobial activity, achieving maximum antimicrobial activity with an inhibition zone of 21.85 ± 1.03 mm. These findings position the Bacillus amyloliquefaciens BS4 strain as a promising candidate for producing bioactive molecules with potential applications in human health.

This chapter examines migratory relations between the European Union (EU) and Africa from the perspective of the Mediterranean Sea, understood as a maritime bridge. Migration historically has been based around paths built through the maritime environment, although these are unregulated, and little mapped, and rarely studied in the theoretical-conceptual currents applied to migration. Based on the processes of migration and securitisation taking place at sea, the chapter discusses the particularities of migration through the maritime environment. It discusses migration relations between the EU and Africa, as well as the forms adopted by the EU to regulate flows from a strategic and a humanitarian perspective. The European continent has historically received African migrants on its Mediterranean borders, which is why we suggest the Mediterranean Sea as a maritime bridge between the EU and Africa.

Background: Plant-derived compounds are sometimes used as substitutes for pharmaceuticals. Mauritia flexuosa is a palm tree that is widely distributed in South America, especially in the Amazon region. The San Martín region of Peru, in which this species of the Arecaceae family is found, has great biological diversity and there is economic potential in the utilization of natural resources in the region. Methods: In this study, the antibacterial effect of the hydroalcoholic extract of Mauritia flexuosa leaves was evaluated for gram-positive bacteria Staphylococcus aureus ATCC 25923 and Bacillus subtilis ATCC 6633 and gram-negative Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and Salmonella enterica subsp. enterica ser. Typhi ATCC 11011. Mauritia flexuosa leaves were used to prepare concentrations of 10, 20, 40 and 60mg/ml. Phytochemical analysis was performed to identify secondary metabolites in the plants. For the experiment, 10 Mueller-Hinton agar plates were prepared and 1ml of bacterial inoculum, standardized to 0.5 McFarland, was added to each plate. The hydroalcoholic extract was added via the diffusion method, making five holes of 5mm each (four with extract concentrations and one with distilled water as a control group), and the plates were incubated for 24 hours at 36°C. The inhibition halo was measured in mm using a digital vernier caliper. Results: For gram-negative bacteria, an antibacterial effect was demonstrated for Pseudomonas aeruginosa only, at an extract concentration of 60mg/ml, with an inhibition halo of 14.8 mm. For gram-positive bacteria Baccillus subtilis and Staphylococcus aureus, an antibacterial effect was demonstrated at an extract concentration of 60mg/ml, with inhibition halos of 13.2mm and 15.4mm in diameter, respectively. Conclusion: It can be concluded that the hydroalcoholic extract of Mauritia flexuosa does not inhibit bacterial growth for gram-negative bacteria Salmonella Typhi and Escherichia coli.

This paper seeks to analyse the marketing concept implementation within both the internal (internal market orientation) and external environment (external market orientation) and assess some of its effects in the context of Portuguese local public sector. More specifically, the paper aims to study the impact of internal marketing implementation on external market orientation. Additionally, it examines the effect of external market orientation on employee's job-related attitudes (job satisfaction and organisational commitment) and organisational performance. A structural equation modelling methodology was employed to analyze the data collected from a sample of Municipality executive board members. This study reports the first known empirical evidence on the market orientation-performance relationship hypothesis in the Portuguese local public sector. Overall, the findings showed that internal marketing implementation has an important effect in fostering market-oriented behaviors of local public organisations. Also, the effect of external market orientation on job-related attitudes and on organisational performance was supported. However, the study findings did not support that increased levels of job satisfaction and organisational commitment enhances organisational performance. [PUBLICATION ABSTRACT]

Imaging of endogenous protein complexes in their native membranes can reveal protein-protein interactions that are lost upon detergent solubilization. To investigate interactions in the mycobacterial oxidative phosphorylation machinery, we prepared inverted membrane vesicles from Mycobacterium smegmatis and enriched for vesicles containing complexes of interest by affinity chromatography. Electron cryomicroscopy (cryo-EM) of these vesicles revealed that malate-quinone oxidoreductase (Mqo), an enzyme from the Krebs cycle, physically associates with the electron transport chain Complex III2IV2 (CIII2CIV2) supercomplex. Analysis of the Mqo:CIII2CIV2 interaction shows that CIII2CIV2 is necessary for malate-driven, but not NADH- driven, electron transport chain activity and oxygen consumption. Further, the association of Mqo with CIII2CIV2 enables electron transfer from malate to CIII2CIV2 with millisecond kinetics. Together, these findings indicate a connection between the Krebs cycle and respiration that directs electrons along a single branch of the mycobacterial electron transport chain.