Search

Multidrug-resistant (MDR) Staphylococcus aureus represents a major global health issue resulting in a wide range of debilitating infections and fatalities. The slow progression of new antibiotics, limited choices for treatment, and scarcity of new drug approvals create immense obstacles in new drug line development. S. aureus poses a significant public health risk, due to the emergence of methicillin-resistant (MRSA) and vancomycin-resistant strains (VRSA), necessitating novel antibiotics for effective control management. Current studies are delving into the terpenes' potential as an antimicrobial agent, indicating positive prospects as promising substitutes or complementary to conventional antibiotics. Concurrent reactions of terpenes with conventional antibiotics create synergistic effects that significantly enhance antibiotic efficacy. Accumulated evidence has shown that while efflux pump (e.g., NorA, TetK, and MepA) is revealed as an essential defense of S. aureus against antibiotics, terpene and its derivative act as its potent inhibitor, suggesting the promising potential of terpenes in combating those infectious pathogens. Furthermore, pronounced cell membrane disruptive activity and antibiofilm properties by terpenes have been exerted, signifying their significance as promising prevention against microbial pathogenesis and antimicrobial resistance. This review provides an overview of the potential of terpenes and their derivatives in combating S. aureus infections, highlighting their potential mechanisms of action (MOA), synergistic effects with conventional antibiotics, and challenges in clinical translation. The unique properties of terpenes offer an opportunity for their use in developing an exceptional defense strategy against antibiotic-resistant S. aureus. [ABSTRACT FROM AUTHOR]

BackgroundAntimicrobial resistance (AMR) is one of the biggest threats to global public health systems. This study aimed to assess the knowledge, attitudes and practice about AMR, antimicrobial stewardship programs (ASPs) and multidrug-resistant (MDR) bacteria.MethodsA web-based questionnaire survey was conducted among the residents of Isfahan University of Medical Sciences from May to November 2023. Data analysis was done using SPSS version 24.0 software.ResultsOverall, 400 out of 450 medical residents responded to the questionnaire, giving a response rate of 88.9%. The participants’ ages ranged from 26 to 54 years, and the majority were female (227/400 56.8%). Average scores for knowledge, attitudes, and practices were 53.70 ± 15.88, 36.97 ± 5.89 and 24.69 ± 4.24, respectively. In terms of knowledge, only 26.8% had heard the term “ASPs” and knew what it was. Most incorrect answers appeared to the treatment of infection caused by MDR bacteria including ESBL-producing Escherichia coli (27.8%) and carbapenem-resistant Klebsiella pneumoniae (30.8%), as well as the atypical bacteria (45.5%). Approximately, 50 and 71.7% said they had received no specific training in the fields of microbiological sampling methods and the appropriate time to prescribe antibiotics, respectively. Surprisingly, regarding practice, 81.8% of the respondents stated that antibiotics are used to treat flu or the common cold.ConclusionResidents considered their training on important issues including ASPs, MDR bacteria and the spectrum of antibiotics insufficient. This result highlights the need for targeted training interventions about antibiotic prescription in the curriculum at the university with more emphasis on ASPs to limit the development of resistance.

Copyright of Saudi Medical Journal is the property of Saudi Medical Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The rapid emergence of multidrug-resistant (MDR) bacteria in recent times has prompted the search for new and more potent antibiotics. Bacteriophages (commonly known as phages) are viruses that target and infect their bacterial hosts. As such, they are also a potential alternative to antibiotics. These phages can be broadly categorized into monovalent (with a narrow host range spectrum and specific to a single bacterial genus) and polyvalent (with a broad host range and specific to more than two genera). However, there is still much ambiguity in the use of these terms, with researchers often describing their phages differently. There is considerable research on the use of both narrow- and broad-host range phages in the treatment of infections and diseases caused by MDR bacteria, including tuberculosis, cystic fibrosis, and carbapenem-resistant Enterobacterales (CRE) infectious diseases. From this, it is clear that the host range of these phages plays a vital role in determining the effectiveness of any phage therapy, and this factor is usually analyzed based on the advantages and limitations of different host ranges. There have also been efforts to expand phage host ranges via phage cocktail development, phage engineering and combination therapies, in line with current technological advancements. This literature review aims to provide a more in-depth understanding of the role of phage host ranges in the effectiveness of treating MDR-bacterial diseases, by exploring the following: phage biology, the importance of phages in MDR bacteria diseases treatment, the importance of phage host range and its advantages and limitations, current findings and recent developments, and finally, possible future directions for wide host range phages. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant (MDR) bacteria and the spread of antimicrobial resistance among various bacteria are major threats to the global community. Due to the increased failure of classical antibiotic treatments against MDR bacterial infections, probiotics and their antimicrobial compounds have been suggested as promising alternatives to deal with MDR bacteria. Various strains of lactic acid bacteria have been reported to produce antagonistic molecules against pathogens. A new strain of Ligilactobacillus animalis, L. animalis SWLA-1, isolated from the feces of healthy dogs, shows strong antimicrobial activity against not only common pathogens but also MDR bacteria. In this study, we compared the antimicrobial activity of L. animalis SWLA-1 with that of other lactobacilli and antibiotics using an agar spot assay. Additionally, a novel spot inhibition index was developed and validated to quantitively evaluate the inhibitory activities of lactobacilli and antibiotics. A competitive coculture assay of L. animalis SWLA-1 with MDR bacteria further demonstrated its antibacterial activity. Furthermore, we evaluated the antimicrobial activity of the cell-free supernatant (CFS) of L. animalis SWLA-1 and its stability under various conditions in vitro. We found that L. animalis SWLA-1 and its CFS are potential alternatives to classic antimicrobial agents. [ABSTRACT FROM AUTHOR]

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new β-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) have received increasing attention as potential alternatives for future antibiotics because of the rise of multidrug-resistant (MDR) bacteria. AMPs are small cationic peptides with broad-spectrum antibiotic activities and different action mechanisms to those of traditional antibiotics. Despite the desirable advantages of developing peptide-based antimicrobial agents, the clinical applications of AMPs are still limited because of their enzymatic degradation, toxicity, and selectivity. In this review, structural modifications, such as amino acid substitution, stapling, cyclization of peptides, and hybrid AMPs with conventional antibiotics or other peptides, will be presented. Additionally, nanodelivery systems using metals or lipids to deliver AMPs will be discussed based on the structural properties and action mechanisms of AMPs. [ABSTRACT FROM AUTHOR]

Due to the increasing application of antibiotics not only in healthcare settings but also in conventional agriculture and farming, multidrug-resistant (MDR) bacterial pathogens are rising worldwide. Given the increasing prevalence of infections caused by MDR bacteria such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species (ESKAPE pathogen complex), it is pivotal to explore novel alternative or adjunct treatment options such as phytochemicals with antibiotic properties. Vanillin and vanillin acid represent biologically active ingredients in vanilla that has been known for long for its health-beneficial including antimicrobial effects besides its role as flavoring agent. Therefore, we performed a literature search from the past 10 years summarizing the knowledge regarding the effects of vanilla constituents against bacterial including MDR pathogens. Our survey revealed that vanillin and vanillic acid exerted potent effects directed against distinct Gram-positive and Gram-negative bacteria by inhibiting growth, viability, biofilm formation, quorum sensing and virulence. Remarkably, when combining vanillin or vanillic acid with defined synthetic antibiotics pronounced synergistic effects directed against distinct pathogenic including ESCAPE strains could be observed. In conclusion, vanilla ingredients constitute promising alternative or adjunct options in the combat of infections caused by MDR bacterial pathogens. [ABSTRACT FROM AUTHOR]

• Effective polymyxin B dosing in patients with pneumonia caused by multidrug-resistant (MDR) gram-negative bacteria is highly challenging. • Epithelial lining fluid (ELF) concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentration of pathogens isolated from the patients. • Therapeutic drug monitoring (TDM) results manifested high ELF antibiotic concentrations in patients who received intravenous and inhaled PMB. • Steady-state concentrations of PMB were more than 2 mg/L in most patients. • Clinical cure was achieved in 57.14% of patients, and a favourable microbiological response in 71.43%. • The incidence of side effects with PMB was low. The incidence of pneumonia caused by multidrug-resistant gram-negative bacteria (MDR GNB) is increasing, which imposes significant burden on public health. Inhalation combined with intravenous polymyxins has emerged as a viable treatment option. However, pharmacokinetic studies focusing on intravenous and inhaled polymyxin B (PMB) are limited. This study included seven patients with MDR GNB-induced pneumonia who were treated with intravenous plus inhaled PMB from March 1 to November 30, 2022, in the intensive care unit of the First Affiliated Hospital of Zhejiang University School of Medicine. Clinical outcomes and therapeutic drug monitoring data of PMB in both plasma and epithelial lining fluid (ELF) were retrospectively reviewed. Median PMB concentrations in the ELF were 7.83 (0.72–66.5), 116.72 (17.37–571.26), 41.1 (3.69–133.78) and 33.82 (0.83–126.68) mg/L at 0, 2, 6 and 12 h, respectively, and were much higher than those detected in the serum. ELF concentrations of PMB at 0, 2, 6 and 12 h were higher than the minimum inhibitory concentrations of pathogens isolated from the patients. Steady-state concentrations of PMB in the plasma were >2 mg/L in most patients. Of the patients, 57.14% were cured and 71.43% showed a favourable microbiological response. The incidence of side effects with PMB was low. Inhaled plus intravenous PMB can achieve high ELF concentrations and favourable clinical outcomes without an increased adverse effect profile. This treatment approach appears promising for the treatment of patients with pneumonia caused by MDR-GNB. [ABSTRACT FROM AUTHOR]

The widespread misuse of antibiotics leads to a rapid development of multi-drug resistant (MDR) bacterial pathogens all over the globe, resulting in serious difficulties when treating infectious diseases. Possible solutions are not limited to the development of novel synthetic antibiotics but extend to application of plant-derived products either alone or in combination with common antibiotics. The aim of this actual review was to survey the literature from the past 10 years regarding the antibacterial effects of distinct Artemisia species including Artemisia absinthiae constituting an integral component of the Absinthe drink. We further explored the synergistic antibacterial effects of the Artemisia plant products with established antibiotics. The survey portrays the Artemisia derived compounds as potent antibacterial agents that can even restore the efficacy of antibiotics against MDR bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA) and MDR Escherichia coli. This, in turn, is presumably triggered in part by the interaction of the Artemisia ingredients with the efflux pumps of MDR bacteria. In conclusion, biologically active molecules in Artemisia plants enhance the antibiotic susceptibility of resistant bacteria, which provide promising future therapeutic strategies to combat MDR bacterial pathogens. [ABSTRACT FROM AUTHOR]

Shigellosis is an enteric infectious disease in which antibiotic treatment is effective, shortening the duration of symptoms and reducing the excretion of the pathogen into the environment. Shigella spp., the etiologic agent, are considered emerging pathogens with a high public health impact due to the increase and global spread of multidrug-resistant (MDR) strains. Since Shigella resistance phenotype varies worldwide, we present an overview of the resistance phenotypes and associated genetic determinants present in 349 Chilean S. sonnei strains isolated during the periods 1995–1997, 2002–2004, 2008–2009, and 2010–2013. We detected a great variability in antibiotic susceptibility patterns, finding 300 (86%) MDR strains. Mobile genetic elements (MGE), such as plasmids, integrons, and genomic islands, have been associated with the MDR phenotypes. The Shigella resistance locus pathogenicity island (SRL PAI), which encodes for ampicillin, streptomycin, chloramphenicol, and tetracycline resistance genes, was detected by PCR in 100% of the strains isolated in 2008–2009 but was less frequent in isolates from other periods. The presence or absence of SRL PAI was also differentiated by pulsed-field gel electrophoresis. An atypical class 1 integron which harbors the bla OXA–1 -aadA1-IS1 organization was detected as part of SRL PAI. The dfrA14 gene conferring trimethoprim resistance was present in 98.8% of the 2008–2009 isolates, distinguishing them from the SRL-positive strains isolated before that. Thus, it seems an SRL- dfrA14 S. sonnei clone spread during the 2008–2009 period and declined thereafter. Besides these, SRL-negative strains harboring class 2 integrons with or without resistance to nalidixic acid were detected from 2011 onward, suggesting the circulation of another clone. Whole-genome sequencing of selected strains confirmed the results obtained by PCR and phenotypic analysis. It is highlighted that 70.8% of the MDR strains harbored one or more of the MGE evaluated, while 15.2% lacked both SRL PAI and integrons. These results underscore the temporal dynamics of antimicrobial resistance in S. sonnei strains circulating in Chile, mainly determined by the spread of MGE conferring MDR phenotypes. Since shigellosis is endemic in Chile, constant surveillance of antimicrobial resistance phenotypes and their genetic basis is a priority to contribute to public health policies. [ABSTRACT FROM AUTHOR]

Among various novel antimicrobial therapies, sonodynamic therapy (SDT) exhibits its advantages for the treatment of bacterial infections due to its high penetration depth and low side effects. In this study, a new nanosonosensitizer (HFH@ZIF-8) that loads sonosensitizer hematoporphyrin monomethyl ether (HMME) into zeolitic imidazolate framework-8 (ZIF-8), was constructed for killing multidrug-resistant (MDR) bacteria and treatment of in vivo infection diseases by SDT. In particular, the developed HFH@ZIF-8 exhibited enhanced water-solubility, good biocompatibility, and improved disease-targeting capability for delivering and releasing HMME and ablating the infected lesion. More importantly, the presence of oxygen-carrying hemoglobin for HFH@ZIF-8 can offer sufficient oxygen consumption by SDT, augmenting the efficacy of SDT by improving ROS generating efficiency against deep tissue multidrug-resistant bacterial infection. Therefore, this study paves a new avenue for treating infection disease, particularly for antibiotic resistant bacterial infection.

Shigellosis is an enteric infectious disease in which antibiotic treatment is effective, shortening the duration of symptoms and reducing the excretion of the pathogen into the environment. Shigella spp., the etiologic agent, are considered emerging pathogens with a high public health impact due to the increase and global spread of multidrug-resistant (MDR) strains. Since Shigella resistance phenotype varies worldwide, we present an overview of the resistance phenotypes and associated genetic determinants present in 349 Chilean S. sonnei strains isolated during the periods 1995–1997, 2002–2004, 2008–2009, and 2010–2013. We detected a great variability in antibiotic susceptibility patterns, finding 300 (86%) MDR strains. Mobile genetic elements (MGE), such as plasmids, integrons, and genomic islands, have been associated with the MDR phenotypes. The Shigella resistance locus pathogenicity island (SRL PAI), which encodes for ampicillin, streptomycin, chloramphenicol, and tetracycline resistance genes, was detected by PCR in 100% of the strains isolated in 2008–2009 but was less frequent in isolates from other periods. The presence or absence of SRL PAI was also differentiated by pulsed-field gel electrophoresis. An atypical class 1 integron which harbors the blaOXA–1-aadA1-IS1 organization was detected as part of SRL PAI. The dfrA14 gene conferring trimethoprim resistance was present in 98.8% of the 2008–2009 isolates, distinguishing them from the SRL-positive strains isolated before that. Thus, it seems an SRL-dfrA14 S. sonnei clone spread during the 2008–2009 period and declined thereafter. Besides these, SRL-negative strains harboring class 2 integrons with or without resistance to nalidixic acid were detected from 2011 onward, suggesting the circulation of another clone. Whole-genome sequencing of selected strains confirmed the results obtained by PCR and phenotypic analysis. It is highlighted that 70.8% of the MDR strains harbored one or more of the MGE evaluated, while 15.2% lacked both SRL PAI and integrons. These results underscore the temporal dynamics of antimicrobial resistance in S. sonnei strains circulating in Chile, mainly determined by the spread of MGE conferring MDR phenotypes. Since shigellosis is endemic in Chile, constant surveillance of antimicrobial resistance phenotypes and their genetic basis is a priority to contribute to public health policies.

The emergence of multidrug-resistant (MDR) bacteria and the spread of antimicrobial resistance among various bacteria are major threats to the global community. Due to the increased failure of classical antibiotic treatments against MDR bacterial infections, probiotics and their antimicrobial compounds have been suggested as promising alternatives to deal with MDR bacteria. Various strains of lactic acid bacteria have been reported to produce antagonistic molecules against pathogens. A new strain of Ligilactobacillus animalis, L. animalis SWLA-1, isolated from the feces of healthy dogs, shows strong antimicrobial activity against not only common pathogens but also MDR bacteria. In this study, we compared the antimicrobial activity of L. animalis SWLA-1 with that of other lactobacilli and antibiotics using an agar spot assay. Additionally, a novel spot inhibition index was developed and validated to quantitively evaluate the inhibitory activities of lactobacilli and antibiotics. A competitive coculture assay of L. animalis SWLA-1 with MDR bacteria further demonstrated its antibacterial activity. Furthermore, we evaluated the antimicrobial activity of the cell-free supernatant (CFS) of L. animalis SWLA-1 and its stability under various conditions in vitro. We found that L. animalis SWLA-1 and its CFS are potential alternatives to classic antimicrobial agents.

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new β-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance.

Antimicrobial peptides (AMPs) have received increasing attention as potential alternatives for future antibiotics because of the rise of multidrug-resistant (MDR) bacteria. AMPs are small cationic peptides with broad-spectrum antibiotic activities and different action mechanisms to those of traditional antibiotics. Despite the desirable advantages of developing peptide-based antimicrobial agents, the clinical applications of AMPs are still limited because of their enzymatic degradation, toxicity, and selectivity. In this review, structural modifications, such as amino acid substitution, stapling, cyclization of peptides, and hybrid AMPs with conventional antibiotics or other peptides, will be presented. Additionally, nanodelivery systems using metals or lipids to deliver AMPs will be discussed based on the structural properties and action mechanisms of AMPs.

Introduction: Recent studies described the threat of emerging multidrug-resistant (MDR) bacteria in intensive care unit (ICU) patients, but few data are available for necrotizing skin and soft tissue infections (NSTI). In a cohort of ICU patients admitted for NSTI, we describe the dynamic changes of microbial population during repeated surgeries.Materials and Methods: This retrospective study compiled consecutive cases admitted for the management of severe NSTI. Clinical characteristics, NSTI features, morbidity and mortality data were collected. The microbiological characteristics of surgical samples obtained during initial surgery were compared with those obtained during the first reoperation, including persistence of initial pathogens and/or emergence of microorganisms. Risk factors for emergence of microorganisms and MDR bacteria were assessed by univariable and multivariable analyses.Results: Among 100 patients {63% male, 58 years old [interquartile ratio (IQR) 50–68]} admitted for NSTI, 54 underwent reoperation with a median [IQR] delay of 3 (1–7) days. Decreased proportions of susceptible strains and emergence of Gram-negative bacteria, including Pseudomonas aeruginosa, staphylococci and enterococci strains, were reported based on the cultures of surgical specimen collected on reoperation. On reoperation, 22 (27%) of the isolated strains were MDR (p < 0.0001 vs. MDR bacteria cultured from the first samples). Broad-spectrum antibiotic therapy as first-line therapy was significantly associated with a decreased emergence of microorganisms. Adequate antibiotic therapy from the initial surgery did not modify the frequency of emergence of microorganisms (p = 0.79) and MDR bacteria (p = 1.0) or the 1-year survival rate.Conclusion: The emergence of microorganisms, including MDR bacteria, is frequently noted in NSTI without affecting mortality.

A global cross-sectional survey was performed to gather data on the current treatment of infections caused by multidrug-resistant (MDR) bacteria among hematological patients admitted to ICUs worldwide. The survey was performed in April 2019 using an electronic platform (SurveyMonkey®) being distributed among 83 physicians and completed by 48 (57.8%) responders. ESBL Enterobacteriaceae, carbapenem-resistant K. pneumoniae and carbapenem-resistant P. aeruginosa were the main concerns. Previous MDR infection (34% of responders), MDR colonization (20%) and previous antibiotic exposure within the last 3 months (20.5%) were considered the most relevant risk factors of bloodstream infection (BSI) due to MDR bacteria. In 48.8% of the ICUs, there was no antimicrobial stewardship (AMS) team focused on hematological patients. Updates on local epidemiology of MDR pathogens were provided in 98% of the centers, using phone or verbal communications (56.1% and 53.7%, respectively). In presence of febrile neutropenia, initial therapy consisted of anti-Gram-negative plus anti-Gram-positive antibiotics for 41% of participants. Antibiotic de-escalation and/or discontinuation of therapy were considered as a promising strategy for the prevention of MDR development (32.4%). Factors associated with antibiotic de-escalation were clinical improvement (43.6%) and neutrophil count recovery (12.8%). Infectious Disease consultation and AMS interventions were not determining factors for de-escalation decisions (more than 50% of responders). Infection control and educational programs were valued as necessary measures for implementation by ICU practitioners. These findings should guide future efforts on collaborative team working, improving compliance with adequate treatment protocols, implementing antimicrobial stewardship programs in critically ill hematological patients, and educational activities. [ABSTRACT FROM AUTHOR]

Nosocomial bacterial infections are associated with high morbidity and mortality, posing a huge burden to healthcare systems worldwide. The ongoing COVID-19 pandemic, with the raised hospitalization of patients and the increased use of antimicrobial agents, boosted the emergence of difficult-to-treat multidrug-resistant (MDR) bacteria in hospital settings. Therefore, current available antibiotic treatments often have limited or no efficacy against nosocomial bacterial infections, and novel therapeutic approaches need to be considered. In this review, we analyze current antibacterial alternatives under investigation, focusing on metal-based complexes, antimicrobial peptides, and antisense antimicrobial therapeutics. The association of new compounds with older, commercially available antibiotics and the repurposing of existing drugs are also revised in this work.

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported.

A questionnaire-based cross-sectional study was conducted to gather information on current microbiological practices for active surveillance of carriage of multidrug-resistant (MDR) bacteria in hospitals from 14 health departments of the Autonomous Community of Valencia (ACV), Spain, which together provided medical attention to 3,271,077 inhabitants in 2017, approximately 70% of the population of the ACV. The survey consisted of 35 questions on MDR bacteria screening policies, surveillance approach chosen (universal vs. targeted), and microbiological methods and processes in use for routine detection and reporting of colonization by MDR bacteria, including the anatomical sites scheduled to be sampled for each MDR bacterial species, and the methodology employed (culture-based, molecular-based, or both). Our study revealed striking differences across centers, likely attributable to the lack of consensus on optimal protocols for sampling, body sites for screening, and microbiological testing, thus underscoring the need for consensus guidelines on these issues. [ABSTRACT FROM AUTHOR]

Introduction: The octapeptins are a family of cyclic lipopeptides first reported in the 1970s then largely ignored. At the time, their reported antibiotic activity against polymyxin-resistant bacteria was a curiosity. Today, the advent of widespread drug resistance in Gram-negative bacteria has prompted their 'rediscovery.' The paucity of new antibiotics in the clinical pipeline is coupled with a global spread of increasing antibiotic resistance, particularly to meropenem and polymyxins B and E (colistin). Areas covered: We review the original discovery of octapeptins, their recent first chemical syntheses, and their mode of action, then discuss their potential as a new class of antibiotics to treat extensively drug-resistant (XDR) Gram-negative infections, with direct comparisons to the closely related polymyxins. Expert commentary: Cyclic lipopeptides in clinical use (polymyxin antibiotics) have significant dose-limiting nephrotoxicity inherent to their chemotype. This toxicity has prevented improved polymyxin analogs from progressing to the clinic, and tainted the perception of lipopeptide antibiotics in general. We argue that the octapeptins are fundamentally different from the polymyxins, with a disparate mode of action, spectra of action against MDR and XDR bacteria and a superior preclinical safety profile. They represent early-stage candidates that can help prime the antibiotic discovery pipeline. [ABSTRACT FROM AUTHOR]

The synergistic action of colistin, with two antibiotics active in Gram-positive bacteria but unable to kill gram negatives (linezolid and rifampicin), was investigated, since triple combinations are emerging as a tool to overtake multidrug resistance. Checkerboard determinations demonstrated that, when combined with colistin, the combination of linezolid and rifampicin turns active in multidrug-resistant Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Thus, the presence of sublethal concentrations of colistin resulted in a strongly synergistic interaction between these two drugs. Moreover, the minimum inhibitory concentrations of linezolid−rifampicin combinations in the presence of colistin were lower than the maximal concentrations of these antimicrobials ain blood. These findings suggest the use of this triple combination as an effective treatment of multidrug-resistant (MDR) bacterial infections.

Death in cancer patients can be caused by the progression of tumors, their malignity, or other associated conditions such as sepsis, which is a multiphasic host response to a pathogen that can be significantly amplified by endogenous factors. Its incidence is continuously rising, which reflects the increasing number of sick patients at a higher risk of infection, especially those that are elderly, pediatric, or immunosuppressed. Sepsis appears to be directly associated with oncological treatment and fatal septic shock. Patients with a cancer diagnosis face a much higher risk of infections after being immunosuppressed by chemotherapy, radiotherapy, or anti-inflammatory therapy, especially caused by non-pathogenic, Gram-negative, and multidrug-resistant pathogens. There is a notorious difference between the incidence and mortality rates related to sepsis in pediatric oncologic patients between developed and developing countries: they are much higher in developing countries, where investment for diagnosis and treatment resources, infrastructure, medical specialists, cancer-related control programs, and post-therapeutic care is insufficient. This situation not only limits but also reduces the life expectancy of treated pediatric oncologic patients, and demands higher costs from the healthcare systems. Therefore, efforts must aim to limit the progression of sepsis conditions, applying the most recommended therapeutic regimens as soon as the initial risk factors are clinically evident—or even before they are, as when taking advantage of machine learning prediction systems to analyze data.

Background: The incidence of multidrug-resistant Gram-negative bacteria (MDR-GNB) pneumonia has increased in the last decade. If antibiotics are given only through intravenous, the antibiotic concentrations in lung tissue will be insufficient. Recently, nebulized antibiotics have shown effectiveness as an adjunctive therapy with intravenous antibiotics for resistant strains. Therefore, the goal of this study was to assess the efficacy and safety of adjunctive nebulized colistin sulfate in combination with intravenous antibiotics in patients with MDR-GNB pneumonia., Methods: A total of 203 patients who were infected with MDR-GNB pneumonia were selected. Based on whether patients received nebulized colistin sulfate, patients were divided into 2 groups: the NCIA group (nebulized colistin sulfate in combination with intravenous antibiotics) and the IA group (intravenous antibiotics without nebulized colistin sulfate). After propensity score matching (PSM) analysis, we compared the efficacy in terms of favorable clinical outcomes, the bacteria detection rate, days of hospital stay, days of intensive care unit (ICU) stay, days of mechanical ventilation (MV), antipyretic time, days of antibiotic therapy, and 28-day all-cause mortality. Safety was also compared between groups., Results: A total of 116 patients met the criteria for evaluation, with 46 patients in the NCIA group and 70 patients in the IA group. After PSM, 31 patients were selected from each group. There were significant differences in favorable clinical outcomes on days 7 (67.7% vs. 32.3%, P=0.005) and 14 (71% vs. 41.9%, P=0.045) and the bacteria detection rate on days 7, 14, and the last day. There were also significant differences in days of hospital stay (17 vs. 23 days, P=0.01), antipyretic time (0.5 vs. 7.5 days, P=0.037), and days of antibiotic therapy (14 vs. 23 days, P=0.002). However, there were no significant differences in days of ICU stay, days of MV, and 28-day all-cause mortality. For nephrotoxicity, the NCIA group did not increase the risk of acute kidney injury (16.1% vs. 9.7%, P=0.707), only one patient (3.2%) in the NCIA group developed airway hyperresponsiveness (P=1.000)., Conclusions: For MDR-GNB pneumonia, nebulized colistin sulfate as an adjuvant supportive treatment for intravenous antibiotics maybe can improve clinical efficacy and has high safety.

Background: The number of lung transplantation procedures is rapidly increasing worldwide. Little is known about the effect of perioperative respiratory microbial colonization on pneumonia during lung transplantation. We evaluated the microbiome composition and incidence of early pneumonia in patients undergoing lung transplantation. We investigated factors related to post-transplant pneumonia (PTP) after lung transplantation., Methods: A retrospective analysis of patients subjected to lung transplantation between May 2013 and December 2019 was performed. Perioperative microbial colonization, and its relationship with early pneumonia, were examined in specimens from bronchial washing, bronchoalveolar lavage, and sputum aspiration before and after surgery. One-year mortality, as the primary outcome, was analyzed using the Kaplan-Meier curve model., Results: Among 76 patients who underwent lung transplantation, 34 donors (44.7%) and 28 recipients (36.8%) showed positive respiratory cultures with respect to preoperative respiratory colonization. A separate analysis of donors and recipients showed that 42 donors and 48 recipients were in respiratory non-colonized state, and 28 (53.8%) donors and 36 (69.2%) recipients survived 1 year after lung transplantation. Acinectobacter baumannii was the most common respiratory multidrug-resistant (MDR) pathogen. PTP was significantly lower in the survivor group (38.5% vs. 70.8%, P=0.009). Out of the recipients with preoperative respiratory colonization, 57.1% survived 1 year after lung transplantation. Patients with PTP had significantly higher 1-year mortality than those without PTP (P=0.009). Preoperative respiratory colonization of the recipients (P=0.010) and PTP patients (P=0.005) was associated with high 1-year mortality rate. Perioperative respiratory colonization of donors was not associated with the incidence of PTP and 1-year survival., Conclusions: Perioperative colonization of recipients was a powerful predictive factor for PTP, which was associated with 1-year mortality in patients subjected to lung transplantation. Our results suggest that donor acceptance criteria may change to better address potential shortages in organ donation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1724/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Nosocomial bacterial infections are associated with high morbidity and mortality, posing a huge burden to healthcare systems worldwide. The ongoing COVID-19 pandemic, with the raised hospitalization of patients and the increased use of antimicrobial agents, boosted the emergence of difficult-to-treat multidrug-resistant (MDR) bacteria in hospital settings. Therefore, current available antibiotic treatments often have limited or no efficacy against nosocomial bacterial infections, and novel therapeutic approaches need to be considered. In this review, we analyze current antibacterial alternatives under investigation, focusing on metal-based complexes, antimicrobial peptides, and antisense antimicrobial therapeutics. The association of new compounds with older, commercially available antibiotics and the repurposing of existing drugs are also revised in this work. [ABSTRACT FROM AUTHOR]

This work reports a detailed characterization of the antimicrobial profile of two trimethoprim-like molecules (compounds 1a and 1b) identified in previous studies. Both molecules displayed remarkable antimicrobial activity, particularly when combined with sulfamethoxazole. In disk diffusion assays on Petri dishes, compounds 1a and 1b showed synergistic effects with colistin. Specifically, in combinations with low concentrations of colistin, very large increases in the activities of compounds 1a and 1b were determined, as demonstrated by alterations in the kinetics of bacterial growth despite only slight changes in the fractional inhibitory concentration index. The effect of colistin may be to increase the rate of antibiotic entry while reducing efflux pump activity. Compounds 1a and 1b were susceptible to extrusion by efflux pumps, whereas the inhibitor phenylalanine arginyl β-naphthylamide (PAβN) exerted effects similar to those of colistin. The interactions between the target enzyme (dihydrofolate reductase), the coenzyme nicotinamide adenine dinucleotide phosphate (NADPH), and the studied molecules were explored using enzymology tools and computational chemistry. A model based on docking results is reported. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) possess great potential for combating drug-resistant bacteria. Thanatin is a pathogen-inducible single-disulfide-bond-containing β-hairpin AMP which was first isolated from the insect Podisus maculiventris. The 21-residue-long thanatin displays broad-spectrum activity against both Gram-negative and Gram-positive bacteria as well as against various species of fungi. Remarkably, thanatin was found to be highly potent in inhibiting the growth of bacteria and fungi at considerably low concentrations. Although thanatin was isolated around 25 years ago, only recently has there been a pronounced interest in understanding its mode of action and activity against drug-resistant bacteria. In this review, multiple modes of action of thanatin in killing bacteria and in vivo activity, therapeutic potential are discussed. This promising AMP requires further research for the development of novel molecules for the treatment of infections caused by drug resistant pathogens. [ABSTRACT FROM AUTHOR]

The increasing prevalence of drug-resistant bacterial strains is causing illness and death in an unprecedented number of people around the globe. Currently implemented small-molecule antibiotics are both increasingly less efficacious and perpetuating the evolution of resistance. Here, we propose a new treatment for drug-resistant bacterial infection in the form of indium phosphide quantum dots (InP QDs), semiconductor nanoparticles that are activated by light to produce superoxide. We show that the superoxide generated by InP QDs is able to effectively kill drug-resistant bacteria in vivo to reduce subcutaneous abscess infection in mice without being toxic to the animal. Our InP QDs are activated by near-infrared wavelengths with high transmission through skin and tissues and are composed of biocompatible materials. Body weight and organ tissue histology show that the QDs are nontoxic at a macroscale. Inflammation and oxidative stress markers in serum demonstrate that the InP QD treatment did not result in measurable effects on mouse health at concentrations that reduce drug-resistant bacterial viability in subcutaneous abscesses. The InP QD treatment decreased bacterial viability by over 3 orders of magnitude in subcutaneous abscesses formed in mice. These InP QDs thus provide a promising alternative to traditional small-molecule antibiotics, with the potential to be applied to a wide variety of infection types, including wound, respiratory, and urinary tract infections.

Background: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting., Methods: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017., Results: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%)., Conclusions: In this pilot study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe., Background: Outpatient parenteral antibiotic therapy (OPAT) was not used in Belgium before 2013, except for patients with cystic fibrosis. Thus, we have performed a pilot study to evaluate clinical characteristics and outcomes of patient receiving OPAT in a Belgian setting., Methods: The study was a prospective observational single-center study of patients receiving OPAT between 1 September 2013 and 31 December, 2017., Results: We included 218 OPATs. The median age was 58 years and 71% were men. At the end of the treatment, 92% of the patients on OPAT were cured. Risk factors for treatment failure were obesity, diabetes and diabetic foot infections, longer duration of hospitalization before OPAT, and duration of OPAT >16 days. An average of 24 days of hospitalization per patient discharge was saved, which amounted to 5205 days saved during the project. During the OPAT and 30 days thereafter, 71 (32.6%) of patients were readmitted, but only 26 (12%) readmissions were directly related to OPAT. Risk factors for readmissions were diabetes and diabetic foot infections, endovascular infections, longer duration of hospitalization before OPAT, duration of OPAT >30 days, and history of hospitalizations in the year before OPAT. There were 2.3 intravenous catheter-related events per 1000 days of catheter use. Patients' level of satisfaction was high (99.5%)., Conclusions: In our study, OPAT is found to be efficacious in saving hospitalization's days, with a low rate of readmissions and complications and a high patients' level of satisfaction. We therefore conclude that OPAT is feasible and safe.

The synergistic action of colistin, with two antibiotics active in Gram-positive bacteria but unable to kill gram negatives (linezolid and rifampicin), was investigated, since triple combinations are emerging as a tool to overtake multidrug resistance. Checkerboard determinations demonstrated that, when combined with colistin, the combination of linezolid and rifampicin turns active in multidrug-resistant Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. Thus, the presence of sublethal concentrations of colistin resulted in a strongly synergistic interaction between these two drugs. Moreover, the minimum inhibitory concentrations of linezolid–rifampicin combinations in the presence of colistin were lower than the maximal concentrations of these antimicrobials ain blood. These findings suggest the use of this triple combination as an effective treatment of multidrug-resistant (MDR) bacterial infections. [ABSTRACT FROM AUTHOR]