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BACKGROUND: There was a reported increase in the antimicrobial consumption in hospitals during the COVID-19 pandemic, accompanied by an increase in infections due to multidrug-resistant (MDR) bacteria. METHODS: This retrospective time series study from intensive care units in Buenos Aires examined changes in antibiotic consumption (defined daily doses/1000 patients/day), the incidence of Gram-negative bacilli (GNB) and the mechanism of resistance. Antibiotics were categorised into group 1 (agents against MDR GNB) and group 2 (agents against non-MDR infections). Bacteriological samples included respiratory samples and blood cultures. Periods were divided into pre-pandemic (July 2019 to March 2020) and pandemic (April 2020 to March 2022). Correlation coefficients (r) were analysed and the Mann-Whitney test was performed to compare both periods. RESULTS: During the study period, GNB incidence, group 1 antibiotic consumption and resistance mechanisms increased, whereas antibiotics decreased in group 2. A significant positive correlation was seen between the consumption of antibiotics in group 1 and the incidence of GNB (r = 0.63; P < 0.001) and resistance (r = 0.52; P = 0.002). Significant differences were found between pre-pandemic and pandemic periods regarding the medians of group 1 consumption (520 [408-570] vs. 753 [495-851] DDD/1000 patients/day; P = 0.029), incidence of GNB (12 [10-13] vs. 43 [25-52.5] cases/month; P < 0.001) and resistance mechanisms (5 [4-8] vs. 17 [10-25] cases/month; P < 0.001), extended-spectrum beta lactamases (2 [1-2] vs. 6 [3-8] cases/month; P < 0.001) and metallo-beta-lactamases (0 [0-0] vs. 6 [1.75-8.5] cases/month; P < 0.001). CONCLUSION: During the COVID-19 pandemic, the rise in GNB incidence and the amount of resistance mechanisms significantly correlated with the increase in consumption of agents against MDR strains.

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BACKGROUND: Bacterial infections are increasingly difficult to combat, which makes them a threat to public health on a global level. Staphylococcus aureus is considered one of the main causes of infections in hospitals, as it has a variety of virulence factors, as well as is able to produce bacterial biofilms, which, consequently, bring numerous damages to public health as a result of increased resistance to conventional antibiotics and a longer hospital stay. Therefore, the use of compounds extracted from medicinal plants is a potential pharmaceutically acceptable target, as they do not have toxicity and the potential to disrupt biofilms produced by Staphylococcus aureus already evidenced, thus revealing their relevance to our study. OBJECTIVE: The objective of this work was to perform a critical analysis of a patent with natural extracts against bacterial biofilms found in the United States Patent and Trademark Office (USPTO) database, to map the possible bioactive compounds that may serve as potential future antimicrobial drugs. METHODS: A technological survey was carried out to verify existing patents using natural extracts with anti-biofilm potential. For this, it was searched with the keywords: Botanical extracts AND biofilms; which were performed in the United States Patent and Trademark Office (USPTO) database. Thus, the selected patent used a non-aqueous extract partitioned and vacuum-contracted, subsequently lyophilized for assays with antimicrobial potential. Because of this, a patent was analyzed regarding its chemistry, and biological activity, followed by a critical analysis of the technology proposed in the invention. RESULTS: When using the keywords Botanical extracts AND biofilms in the USPTO, it was possible to find twenty-two inventions; however, only four patents in the USPTO were in agreement with the proposal of the natural extract having antimicrobial activity and an anti-biofilm potential, of which two belonged to the same applicant with similar proposals. The key point of this invention was to enable the compounds of the Castanea sativa plant and its methods of obtaining the extract to present a significant antimicrobial action associated or not with antibiotics, promoting the development of new therapies against bacterial infections capable of disrupting biofilms. The invention developed a methodology for extracting Castanea sativa, in which pentacyclic triterpene compounds were found mostly in its leaves. Whereas for the extraction, the crude methanol extracts called extracts 224 from the ground leaves were made by maceration, filtered, combined, concentrated under pressure in rotary evaporators, and lyophilized. After that, they were resuspended in water and partitioned in succession with hexane, ethyl acetate, and butanol. The most active refined partition was the 224C extract with the solvent ethyl acetate, which was subjected to further fractionation using silica column chromatography. Resulting in the most refined extract, which was 224C-F2, capable of acting directly on the quorum sensing of bacteria, mainly Staphylococcus aureus, blocking the translation of RNAIII, including a series of exotoxins. Regarding the antimicrobial capacity against Staphylococcus aureus, it presented Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of 1.56 µg/mL-1 and > 100 µg/mL -1, respectively. CONCLUSION: Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact of bacterial biofilms, which causes damage to industries in general and to health. From this, the invention analyzed has a promising proposal with antimicrobial potential focusing on the great impact of bacterial biofilms. Therefore, natural extracts with antibiofilmic potential can help to minimize the economic losses caused to health due to these multidrug-resistant microorganisms with different virulence mechanisms.

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The rise of antibiotic-resistant bacteria calls for innovative approaches to combat multidrug-resistant strains. Here, the potential of the standard histological stain, Giemsa, to act as a photosensitizer (PS) for antimicrobial photodynamic inactivation (aPDI) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) strains is reported. Bioassays were performed using various Giemsa concentrations (ranging from 0.0 to 20.0 µM) under 625 nm illumination at a light dose of 30 J cm-2. Remarkably, Giemsa completely inhibited the growth of MSSA and MRSA bacterial colonies for concentrations at 10 µM and higher but exhibited no inhibitory effect without light exposure. Partition coefficient analysis revealed Giemsa's affinity for membranes. Furthermore, we quantified the production of reactive oxygen species (ROS) and singlet oxygen (1O2) to elucidate the aPDI mechanisms underlying bacterial inactivation mediated by Giemsa. These findings highlight Giemsa stain's potential as a PS in aPDI for targeting multidrug-resistant bacteria.

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In intensive care units (ICUs), infection rates range from 18 to 54%, which is five to ten times higher than those observed in other hospital units, with a mortality rate of 9% to 60%. In recent decades, the susceptibility pattern has changed and Gram-Negative Bacteria (GNB) have become a threat due to their high frequency of multidrug resistance associated with a scarcity of therapeutic options. However, the drugs Ceftolozane/Tazobactam (C/T) and Ceftazidime/Avibactam (C/A) are demonstrating good clinical and microbiological response in the treatment of severe nosocomial infections. Therefore, this study aims to evaluate the clinical outcome of patients with severe infections caused by Multidrug-Resistant (MDR) GNB treated with C/T and C/A. Our study evaluates a total of 131 patients who received treatment with C/T and C/A due to infections caused by MDR GNB within the period from 2018 to 2021. The main infections were urinary tract (46,6%) and respiratory (26,7%) infections. Pseudomonas aeruginosa was the prevailing agent in the sample evaluation (34.3%), followed by Klebsiella pneumoniae (30,1%). About 54,9% of patients showed a favorable response, with culture negativation in 66,4% of the samples, with no discrepancy in negativations when comparing ages: 67,7% in young and 66% in elderly patients. Among the patients, 62,6% received monotherapy with C/T and C/A with a better response observed with monotherapy compared to combination therapy (58,6% vs 41,4%). The overall mortality rate was 45%, with MDR GNB infections responsible for 33,9% of these deaths, and the others (66,1%) due to factors such as oncological, hematological, and degenerative neurological diseases. In regards to hematological aspect, 35,1% of patients showed changes, with 28,2% of them presenting anemia, 4,5% thrombocytopenia, and 2,5% thrombocytosis. Concerning the use of invasive devices, higher mortality was observed in patients on mechanical ventilation (52%). In this manner, it was possible to observe that therapy with C/T and C/A yielded a favorable clinical outcome in patients with severe infections caused by MDR GNB in the study. These drugs also demonstrated good tolerability regardless of age or the presence of preexisting comorbidities and were deemed safe when assessing adverse effects. Our data also demonstrate the importance of determining the mechanism of resistance to carbapenems so that these drugs can be used more effectively and rationally.

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BACKGROUND: The aim of this study is to evaluate the outcome of patients with cavitary chronic osteomyelitis undergoing adjuvant treatment with bioactive glass (BAG) S53P4 and identify the independent risk factors (RFs) for recurrence in 6- and 12-month patient follow-up. METHODS: A retrospective, multicentre observational study conducted in tertiary specialised hospitals among patients undergoing the surgical treatment of chronic cavitary osteomyelitis using BAG-S53P4 in a granule and/or putty formulation to assess the clinical outcome and RFs for failure in 6- and 12-month patient follow-up. RESULTS: Of the 92 and 78 patients with 6-month and 12-month follow-ups, infection was eradicated in 85.9% and 87.2%, respectively. In the 6-month follow-up, BAG-S53P4 in the granule formulation presented a greater risk of recurrence compared to the bioactive glass putty formulation or combined granules and putty (prevalence ratio (PR) = 3.04; confidence interval 95% [CI95%]: 1.13-10.52) and neoplasia (PR = 5.26; CI95%: 1.17-15.52). In the 12-month follow-up cohort of 78 patients, smoking (PR = 4.0; 95% CI: 1.03-15.52) and nonfermenting GNB infection (PR = 3.87; CI95%: 1.09-13.73) presented a greater risk of recurrence. CONCLUSIONS: BAG-S53P4 is a viable option for bone-void filling and the treatment of chronic cavitary osteomyelitis. Formulations of BAG with putty or in combination with granules showed better results.

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Antimicrobial resistance has become a growing public health concern in recent decades, demanding a search for new effective treatments. Therefore, this study aimed to elucidate the phytochemical composition and evaluate the antibacterial activity of the essential oil obtained from the fruits of Piper tuberculatum Jacq. (EOPT) against strains carrying different mechanisms of antibiotic resistance. Phytochemical analysis was performed using gas chromatography-mass spectrometry (GC/MS). The antibacterial activity of EOPT and its ability to inhibit antibiotic resistance was evaluated through the broth microdilution method. The GC-MS analysis identified 99.59% of the constituents, with ß-pinene (31.51%), α-pinene (28.38%), and ß-cis-ocimene (20.22%) being identified as major constituents. The minimum inhibitory concentration (MIC) of EOPT was determined to assess its antibacterial activity against multidrug-resistant strains of Staphylococcus aureus (IS-58, 1199B, K2068, and K4100). The compound showed a MIC of ≥ 1024 µg/mL, suggesting a lack of intrinsic antibacterial activity. However, when the EOPT was associated with antibiotics and EtBr, a significant decrease in antibiotic resistance was observed, indicating the modulation of efflux pump activity. This evidence was corroborated with the observation of increased fluorescent light emission by the bacterial strains, indicating the involvement of the NorA and MepA efflux pumps. Additionally, the significant potentiation of ampicillin activity against the S. aureus strain K4414 suggests the ß-lactamase inhibitory activity of EOPT. These results suggest that the essential oil from P. tuberculatum fruits has antibiotic-enhancing properties, with a mechanism involving the inhibition of efflux pumps and ß-lactamase in MDR S. aureus strains. These findings provide new perspectives on the potential use of EOPT against antibiotic resistance and highlight the importance of Piper species as sources of bioactive compounds with promising therapeutic activities against MDR bacteria. Nevertheless, further preclinical (in vivo) studies remain necessary to confirm these in vitro-observed results.

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The present study centers on the synthesis of ultra-small silver nanoparticles (AgNPs) with antibacterial properties using citrus peel residues (orange, lemon, and grapefruit) as reducing and stabilizing agents, and on assessing their antibacterial activity against multidrug-resistant clinical Staphylococcus aureus. The synthesized AgNPs were analyzed by various techniques, including UV-Vis spectroscopy, SAED, TEM, XRD, FTIR, and Raman. The results demonstrate the formation of ultra-small, monodisperse, quasi-spherical AgNPs with an average particle size of 2.42 nm for AgNPs produced with mixed extracts. XRD analysis indicated that the AgNPs have a crystal size of 9.71 to 16.23 nm. The AgNPs exhibited potent inhibitory activity against resistant S. aureus, with a minimum inhibitory concentration (MIC) of 15.625 to 62.50 ppm. The findings suggest that the ultra-small nanometer size of the AgNPs could be attributed to the synthesis method that employs ambient conditions and the presence of polyphenolic compounds from citrus peel. Consequently, AgNPs obtained through sustainable green synthesis hold significant potential in combating clinical multi-resistant bacterial strains that are challenging to treat and eradicate. This approach also contributes to the revaluation of citrus residues in the region, which is an ongoing environmental issue today.

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The pathogenic microorganisms linked to fresh fruits and juices sold out in retail low-cost markets raise safety concerns as they may carry multidrug-resistant (MDR) genes. To evaluate the microbiological quality and safety of highly consumed fruits and derivatives in Imbabura Province, Ecuador, ready-to-eat strawberries (5 independent batches; n = 300 samples), and gooseberries (5 separate batches; n = 500 samples), purchased from a local fruit farm grower and low-cost retail market, along with 20 different natural fruit- and vegetables-based juices (3 independent batches; n = 60 samples) purchased from food courts located within the low-cost markets were analyzed. Bacteriological analysis showed that the microbial quality was lower as several indicators (n = 984) consisting of total coliforms (TCOL), total aerobes (AEROB), Enterobacter spp. (ENT), Shigella spp., (SHIGA), yeasts (YE), and molds (M) were detected. Staphylococcus spp. (STAPHY) was found in both fruits regardless of origin, while Escherichia coli (EC) isolates were found in strawberries but not gooseberries. Salmonella spp. (SALM) were detected in juices only. Antibiotic susceptibility testing showed multidrug resistance of several isolates. The hemolytic pattern revealed that 88.89% of EC and 61.11% of ENT isolates were beta-hemolytic. All STAPHY isolates were beta-hemolytic while SALM and SHIGA were alpha-hemolytic. Plasmid curing assay of MDR isolates (ENT, EC, SALM, and STAPHY) showed that the antibiotic resistance (AR) was highly indicative of being plasmid-borne. These results raise concerns about the consumption of MDR bacteria. However, good agricultural and industrial practices, behavioral change communication, and awareness-raising programs are necessary for all stakeholders along the food production and consumption supply chain.

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Recent studies have shown that the peptide [des-Cys11,Lys12,Lys13-(p-BthTX-I)2K] (p-Bth) is a p-BthTX-I analog that shows enhanced antimicrobial activity, stability and hemolytic activity, and is easy to obtain compared to the wild-type sequence. This molecule also inhibits SARS-CoV-2 viral infection in Vero cells, acting on SARS-CoV-2 PLpro enzymatic activity. Thus, the present study aimed to assess the effects of structural modifications to p-Bth, such as dimerization, dendrimerization and chirality, on the antibacterial activity and inhibitory properties of PLpro. The results showed that the dimerization or dendrimerization of p-Bth was essential for antibacterial activity, as the monomeric structure led to a total loss of, or significant reduction in, bacterial activities. The dimers and tetramers obtained using branched lysine proved to be prominent compounds with antibacterial activity against Gram-positive and Gram-negative bacteria. In addition, hemolysis rates were below 10% at the corresponding concentrations. Conversely, the inhibitory activity of the PLpro of SARS-CoV-2 was similar in the monomeric, dimeric and tetrameric forms of p-Bth. Our findings indicate the importance of the dimerization and dendrimerization of this important class of antimicrobial peptides, which shows great potential for antimicrobial and antiviral drug-discovery campaigns.

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Background: In intensive care units (ICUs), infections by multidrug-resistant (MDR) microorganisms should be monitored to prevent healthcare-associated infections (HAIs). Methods: From 2018 to 2020, we investigated all medical records of patients admitted to the ICU of a public university hospital. All patients colonized/infected by MDR microorganisms and submitted to active surveillance cultures (ASCs) were included. Results and discussion: Male patients prevailed, and 9.5% were positive for MDR bacteria. In-hospital deaths were statistically significant (p < 0.05) for older patients, patients with orotracheal tube use during previous and current hospitalization, and patients with high blood pressure, cardiac and pulmonary diseases, and chronic kidney disease. Carbapenem resistant Enterobacteriaceae was the most frequently resistance profile, followed by extended-spectrum beta-lactamase. The diagnosis or evolution of HAIs was statistically significant (p < 0.0001) for patients treated with meropenem and vancomycin, and in-hospital deaths occurred in 29.5% of patients using polypeptides while the use of macrolides reduced the odds for mortality. The BRADEN Scale demonstrated that 50% of the patients were at high risk of dying. Conclusion: Patients hospitalized in the ICU, colonized or infected by MDR bacteria, using invasive medical devices, and with underlying medical conditions presented increased mortality rates. The prescription of meropenem and vancomycin should be carefully monitored once patients using these antimicrobials already have or develop an HAI.

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Klebsiella pneumoniae is a multidrug-resistant opportunistic human pathogen related to various infections. As such, synthetic peptides have emerged as potential alternative molecules. Mo-CBP3-PepI has presented great activity against K. pneumoniae by presenting an MIC50 at a very low concentration (31.25 µg mL-1). Here, fluorescence microscopy and proteomic analysis revealed the alteration in cell membrane permeability, ROS overproduction, and protein profile of K. pneumoniae cells treated with Mo-CBP3-PepI. Mo-CBP3-PepI led to ROS overaccumulation and membrane pore formation in K. pneumoniae cells. Furthermore, the proteomic analysis highlighted changes in essential metabolic pathways. For example, after treatment of K. pneumoniae cells with Mo-CBP3-PepI, a reduction in the abundance of protein related to DNA and protein metabolism, cytoskeleton and cell wall organization, redox metabolism, regulation factors, ribosomal proteins, and resistance to antibiotics was seen. The reduction in proteins involved in vital processes for cell life, such as DNA repair, cell wall turnover, and protein turnover, results in the accumulation of ROS, driving the cell to death. Our findings indicated that Mo-CBP3-PepI might have mechanisms of action against K. pneumoniae cells, mitigating the development of resistance and thus being a potent molecule to be employed in producing new drugs against K. pneumoniae infections.

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Introducción: La presencia de enterobacterias multirresistentes en los hospitales es cada vez más frecuente. Objetivos: Describir la variación de la susceptibilidad a los antimicrobianos en aislados de Klebsiella pneumoniae y Escherichia coli e identificar la frecuencia de aislados multirresistentes. Métodos: Estudio descriptivo retrospectivo realizado entre el 1 de enero de 2018 y 31 de diciembre de 2021. Se estudió la susceptibilidad a los antimicrobianos por el método de difusión de discos Bauer-Kirby a 220 aislados (111 de K. pneumoniae y 109 de E. coli) obtenidos de muestras clínicas (sangre, lesiones de piel, catéteres vasculares, secreciones traqueobronquiales y de herida quirúrgica) de pacientes hospitalizados en el Hospital Clínico-Quirúrgico Docente Aleida Fernández Chardiet, provincia Mayabeque, Cuba. Resultados: Durante los 4 años de estudio, en los aislados de K. pneumoniae la resistencia mostró tendencia a crecer en el tiempo para todos los antimicrobianos probados, excepto para amoxicilina/ácido clavulánico con tendencia a decrecer de -3,34. La diferencia porcentual de la resistencia del año 2021 con respecto al 2018 fue mayor para meropenem, cloranfenicol y amikacina (108,3 %, 70,2 % y 70,2 %, respectivamente). Aun así, los datos mostraron significación estadística para los antibióticos cefepima, aztreonam y meropenem (p ≤ 0,05). En cuanto a los aislados de E. coli, la resistencia mostró tendencia a decrecer en ocho de los antimicrobianos investigados, pero el cloranfenicol y amikacina evidenciaron una tendencia al incremento de 3,65 y 4,83, respectivamente. La diferencia porcentual entre los años extremos del estudio en nueve antimicrobianos mostró valores inferiores al 50,0 %. Los datos evidenciaron significación estadística (p ≤ 0,05) para cefotaxima y ampicilina/sulbactam. Conclusiones: Hubo variación en la susceptibilidad a los antimicrobianos en los aislados de K. pneumoniae y E. coli durante los 4 años del estudio. Además, se observó una alta prevalencia de aislados multirresistentes.

Introduction: The presence of multidrug resistant enterobacteria in hospitals is increasingly frequent. Objectives: To describe the variation of the antimicrobial susceptibility pattern of Klebsiella pneumoniae and Escherichia coli isolates obtained from clinical samples of patients who were hospitalized and to identify the frequency of multidrug resistant isolates. Methods: A retrospective and descriptive study was performed between January 1, 2018 and December 31, 2021. The antimicrobial susceptibility was analyzed using the Bauer- Kirby disc diffusion method of 220 isolates (111 K. pneumoniae and 109 E. coli) obtained from clinical samples (blood, skin lesions, vascular catheters and tracheobronchial and surgical wound secretions) of patients hospitalized at the Hospital teaching surgical - clinic Aleida Fernández Chardiet, located in the province of Mayabeque, Cuba. Results: In the K. pneumoniae isolates during the four years of the study, resistance showed a tendency to increase over time, for all antibiotic tested, except for amoxicillin / ácid clavulánic, which showed a tendency to decrease from 3.34. The percentage difference of the resistance between the year 2021 in relation to 2018 were greater for meropenem, chloramphenicol and amikacin (108.3%, 70,2% y 70.2% respectively). Even so, the data provided evidence that showed statistical significance for the antibiotics cefepime, aztreonam y meropenem (p ≤ 0,05). Regarding the E. coli isolates, resistance showed a tendency to decrease over the course of the four years of the study in eight of the investigated antibiotics. chloramphenicol and amikacin showed an increasing trend of 3.65 y 4.83 respectively. The percentage difference between the extreme years of the study in nine antimicrobials showed values lower than 50.0%. The data provide elements to suggest the presence of statistical significance (p ≤ 0.05) for cefotaxim y ampicilin/sulbactam. Finally, 83.87% of K. pneumoniae isolates and 80.73% of E. coli isolates were multidrug resistant. Conclusions: There was variation in the susceptibility to antibiotic in the K. pneumoniae and E. coli isolates during the four years of the study. In addition, a high prevalence of multiresistant isolates was observed.

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The prevalence of multidrug-resistant (MDR) bacteria and the limited efficacy of current available antibiotics cause every year approximately 700 000 deaths per year. This study aimed to evaluate the anti-inflammatory effect and antibacterial potential of the ibuprofen derivative Methyl 2-(-4-isobutylphenyl)propanoate (MET-IBU). The molecular structure of MET-IBU was confirmed by Nuclear Magnetic Resonance (NMR) and, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) spectroscopy. Our in vivo study using adult zebrafish model demonstrated that the ibuprofen derivative MET-IBU also possesses anti-inflammatory effect, and in vitro antibacterial activity assays showed that in the association of ampicillin, norfloxacin, and gentamicin with MET-IBU occurred reduction in the minimum inhibitory concentration (MIC) for MDR bacterial strains of Escherichia coli 06 and Staphylococcus aureus 10, indicating a potentiating in the growth inhibition of these pathogenic bacteria. Regarding the strain of Staphylococcus aureus K2068 (overexpressing mepA gene), a potentiation of ethidium bromide was found in the association with MET-IBU, indicating the action of this compound on the efflux pump mechanism present in this strains. This result corroborates the molecular docking study that indicated a high affinity of the MET-IBU with the MepA efflux pump. It was also noticed an antibiotic potentiating activity in the association MET-IBU with norfloxacin against strains of Staphylococcus aureus 1199B (overexpressing norA gene) when compared to the norfloxacin control. This enhanced antibiotic effect of MET-IBU is associated with a second resistance mechanism, which is due to the modification in the topoisomerase enzyme. These results bring attention to the ibuprofen derivative MET-IBU as possible candidate for the development of new options for the treatment of bacterial infections with protective anti-inflammatory action.

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This article seeks to characterize the bacterial profile of pediatric hospital wastewater samples collected at the outlet of a wastewater treatment plant, and to estimate their relative susceptibility to antimicrobial agents. A total of 64 strains were isolated in the wastewater samples, of which 49 were identified as belonging to different families: Enterobacteriaceae (e.g. Escherichia coli, Klebsiella sp., Citrobacter sp.) comprised 57.2% of the identified bacteria, non-Enterobacteriaceae (e.g. Aeromonas sp., Pseudomonas sp.) comprised 30.6%, and Streptococcaceae (e.g. Enterococcus sp.) comprised 12.2%. The tests of the susceptibility of the bacteria to the antimicrobial agents used in the hospital showed that 100% of the bacterial species found discharged in the hospital wastewater treatment system were resistant to one or more of the antimicrobial agents according to the criteria of the U.S. Clinical Laboratory Standards Institute/National Committee for Clinical Laboratory Standards. The antimicrobial agent tests showed that meropenem, norfloxacin, ciprofloxacin, levofloxacin, and cefepime were the most effective antimicrobials against bacteria of the Enterobacteriaceae family. For bacteria of the non-Enterobacteriaceae family, norfloxacin, ciprofloxacin, levofloxacin, and cefepime presented the most effective antimicrobial action, whereas for bacteria of the Streptococcaceae family, ampicillin, vancomycin, and gentamicin were the most effective antimicrobials. Hospital wastewater treatment plants could be considered as places of selection pressure for bacterial resistance because of the presence of antibiotic-resistant bacteria coming from sewers or created at the treatment plant.

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Since the discovery of antibiotics, humanity has been able to cope with the battle against bacterial infections. However, the inappropriate use of antibiotics, the lack of innovation in therapeutic agents, and other factors have allowed the emergence of new bacterial strains resistant to multiple antibiotic treatments, causing a crisis in the health sector. Furthermore, the World Health Organization has listed a series of pathogens (ESKAPE group) that have acquired new and varied resistance to different antibiotics families. Therefore, the scientific community has prioritized designing and developing novel treatments to combat these ESKAPE pathogens and other emergent multidrug-resistant bacteria. One of the solutions is the use of combinatorial therapies. Combinatorial therapies seek to enhance the effects of individual treatments at lower doses, bringing the advantage of being, in most cases, much less harmful to patients. Among the new developments in combinatorial therapies, nanomaterials have gained significant interest. Some of the most promising nanotherapeutics include polymers, inorganic nanoparticles, and antimicrobial peptides due to their bactericidal and nanocarrier properties. Therefore, this review focuses on discussing the state-of-the-art of the most significant advances and concludes with a perspective on the future developments of nanotherapeutic combinatorial treatments that target bacterial infections.

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Bacteriophages offer an alternative for the treatment of multidrug-resistant bacterial diseases as their mechanism of action differs from that of antibiotics. However, their application in the clinical field is limited to specific cases of patients with few or no other alternative therapies. This systematic review assesses the effectiveness and safety of phage therapy against multidrug-resistant bacteria through the evaluation of studies published over the past decade. To that end, a bibliographic search was carried out in the PubMed, Science Direct, and Google Scholar databases. Of the 1500 studies found, 27 met the inclusion criteria, with a total of 165 treated patients. Treatment effectiveness, defined as the reduction in or elimination of the bacterial load, was 85%. Except for two patients who died from causes unrelated to phage therapy, no serious adverse events were reported. This shows that phage therapy could be an alternative treatment for patients with infections associated with multidrug-resistant bacteria. However, owing to the phage specificity required for the treatment of various bacterial strains, this therapy must be personalized in terms of bacteriophage type, route of administration, and dosage.

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Cancer and bacterial infections are among the leading causes of death worldwide. Plant-derived bioactive compounds constitute promising alternatives for development of new therapeutics. This study aimed at evaluating the biological activity of Withaferin A using 6 tumor cell lines: A549 (lung cancer), U87MG (glioblastoma), SH-SY5Y (neuroblastoma), B16-F10 (mouse melanoma), HeLa (uterine colon cancer) and K562 (chronic myeloid leukemia). In addition, 17 other standard bacterial strains and several multidrug resistant bacteria (MDR) clinical isolates were examined. Cell viability was assessed using the following assays: MTT, neutral red, and dsDNA PicoGreen®. Further, oxidative stress was measured by quantification of reactive oxygen species (ROS) production. The activity against bacteria was determined by the minimum inhibitory concentration (MIC), minimum bacterial concentration (CBM) and antibiofilm activity in the production of strains. Withaferin A was effective, as evidenced by its cytotoxic activity in tumor cell lines, enhanced ROS production in tumor cells and bactericidal and antibiofilm activity. Data demonstrated that Withaferin A may be therapeutically considered as an antitumor and antibacterial agent.

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INTRODUCTION AND OBJECTIVES: Bacterial infections are associated with a dismal prognosis in patients with liver cirrhosis. Data on their prevalence and the associated pathogen spectra in Germany are scarce. This study aimed to evaluate the impact of bacterial infections on mortality in hospitalized patients with liver cirrhosis and to analyze the prevalence of multidrug-resistant (MDR) bacteria in a German tertiary care center. PATIENTS AND METHODS: Consecutive, non-electively hospitalized patients with liver cirrhosis were enrolled in this study between 03/2019-06/2021. All patients underwent clinical, laboratory and microbiological testing to detect potential bacterial infections. Patients were followed for 30 days regarding the composite endpoint of death or liver transplantation (mortality). RESULTS: In total, 239 patients were recruited (median MELD 18). Bacterial infection was detected in 81 patients (33.9%) at study inclusion. A total of 70 patients (29.3%) developed a hospital-acquired infection. When comparing community-acquired and hospital-acquired infections, the pathogen pattern shifted from a gram-negative to a more gram-positive spectrum and showed an increase of Staphylococcus spp.. MDR bacteria were detected in seven infected patients (5.8%). 34 patients reached the composite endpoint during 30-days follow-up. In multivariable logistic regression analysis, the presence of infection during hospitalization remained independently associated with higher mortality (OR 2.522, 95% CI 1.044 - 6.091, p = 0.040). CONCLUSIONS: This study demonstrates that bacterial infections are common in hospitalized patients with liver cirrhosis in Germany and are a major determinant of short-term mortality. Our data highlight the importance of regional differences in MDR bacteria and may guide physicians' decision-making regarding calculated antibiotic treatment.

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The prevalence of Carbapenem-resistant Enterobacteriaceae (CRE) has increased dramatically in recent years and has become a global public health issue. Since carbapenems are considered the last drugs of choice, infections caused by these pathogens are difficult to treat and carry a high risk of mortality. Several antibiotic combination regimens have been utilized for the management of CRE infections or to eradicate colonization in CRE carriers with variable clinical responses. In addition, recent studies have explored the use of fecal microbiota transplantation (FMT) to eradicate CRE infections. Here, we conducted a systematic review of publications in which FMT was used to eliminate CRE colonization in infected individuals. We searched the PubMed, Cochrane, and Medline databases up to November 30, 2021. Ten studies (209 patients) met the inclusion criteria for this review with three articles describing retrospective cohorts (n = 53 patients) and seven reporting prospective data (n = 156 patients), including one randomized open-label clinical trial. All studies were published between 2017 and 2021 with eight studies from Europe and two from South Korea. There were substantial variations in terms of outcome measurements and study endpoint among these studies. Among the 112 FMT recipients with confirmed CRE colonization, CRE decolonization was reported in 55/90 cases at one month after FMT and at the end of the study follow-up (6-12 months), decolonization was documented in 74/94 (78.7%) patients. The predominant CRE strains reported were Klebsiella pneumoniae and Escherichia coli and the most frequently documented carbapenemases were KPC, OXA-48, and NDM. In general, FMT was well tolerated, with no severe complications reported even in immunosuppressed patients and in those with multiple underlying conditions. In conclusion, FMT appears to be safe and effective in eradicating CRE colonization, however, more studies, especially randomized trials, are needed to validate the safety and clinical utility of FMT for CRE eradication.

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RESUMO

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

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