Search Results (34)

AmpC β-lactamases are class C enzymes that hydrolyze penicillins, cephalosporins, and monobactams. The WHO recently classified third-generation cephalosporin-resistant and carbapenem-resistant Enterobacterales as critical pathogens. We conducted a systematic review and meta-analysis to evaluate AmpC prevalence in hospital isolates across South America. We searched PubMed/MEDLINE, SciELO, and Google Scholar. We included 69 observational studies that phenotypically or genotypically identified AmpC producers. A random-effects generalized linear mixed model with logit transformation estimated pooled prevalence; heterogeneity and moderators were explored through subgroup analyses and meta-regression. Seventy studies, including 48,801 isolates, were eligible. AmpC β-lactamases were detected in 11.7% of isolates (95% CI 11.4–12.0), with extreme heterogeneity (I² ≈ 97%). Enterobacter species showed the highest prevalence (~46%), whereas Escherichia spp. had the lowest (~4.5%) prevalence of AmpC positivity within each genus. Meta-regression indicated that studies focusing on a single genus reported higher prevalence and that including pediatric patients was associated with a lower prevalence of AmpC-positive microorganisms among isolates. Quality of evidence was rated low due to inconsistency, moderate risk of bias, and indirectness of data. AmpC producers are entrenched in South American hospitals, and species-aware surveillance and harmonized detection are critical to guide empiric therapy and antimicrobial stewardship. Full article

This systematic review assessed the global epidemiology of metallo-β-lactamase (MBL)-producing Acinetobacter clinical isolates and the associated antimicrobial resistance. A total of 475 relevant articles from the Cochrane Library, Google Scholar, PubMed, Scopus, and Web of Science were identified and screened as potentially eligible articles. Data from 85 articles were extracted for the analysis. Most reports on MBL-producing Acinetobacter clinical isolates originated from Asia [68/85 (80%) studies] and Africa [14/85 (16.5%) studies]. There were also scarce reports from Europe and America. The bla_VIM (in 31 studies), bla_IMP (in 29 studies), and bla_NDM (in 21 studies) genes were the most commonly identified genes. In 22 out of 28 (78.6%) studies with comparable data, the proportions of MBL-producing pathogens detected using phenotypic methods were numerically higher than those using genotypic methods. MBL-producing Acinetobacter isolates showed high resistance (up to 100%) to several antibiotic classes, including carbapenems, cephalosporins, fluoroquinolones, and monobactams. However, they showed low resistance to colistin [ranging from 0% (in six studies) to 14.3% (in one study)] and to tigecycline [0% (in three studies)]. No risk of bias assessment was conducted. The findings emphasize the global spread of MBL-producing Acinetobacter and the need for enhanced antimicrobial stewardship, infection control measures, and surveillance. Full article

Pseudomonas aeruginosa is a significant threat to public health as an aggressive, opportunistic pathogen. The use of β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems remains a front-line treatment against P. aeruginosa. However, the widespread use of β-lactams has led to the emergence of β-lactam-resistant isolates that significantly increase the economic burden and risk of mortality in patients. With the declining productivity of the antibiotic discovery pipeline, research has investigated synergistic agents to revive the use of β-lactam antibiotics against β-lactam-resistant P. aeruginosa. In this review, we summarize the mechanism of β-lactam antibiotics and provide an overview of major mechanisms associated with β-lactam resistance in P. aeruginosa. We then describe the background and use of three promising classes of agents that have shown extensive beneficial effects with β-lactam antibiotics against P. aeruginosa, namely β-lactamase inhibitors, bacteriophages, and antimicrobial peptides. The current understanding of the mechanisms of these synergistic agents is discussed. Lastly, we provide an overview of the current barriers impeding antibiotic development, and offer a glimpse into recent advances of artificial intelligence-based discovery that may serve as a new foundation for antimicrobial discovery and treatment. Full article

This review examines the latest progress of β-lactam antibiotics, focusing on penems. Penems are distinguished by their unique structural characteristics and remarkable antibacterial activity. The structural characteristics of the class that differentiate it from carbapenems or monobactams are addressed. Notable representatives such as sulopenem and faropenem are discussed. Faropenem’s stability and efficacy against resistant bacterial strains emphasize the therapeutic potential of penems. The review highlights sulopenem’s recent FDA approval, marking a key point in treating uncomplicated urinary tract infections caused by specific bacteria in adult women with minimal or no other options for oral antibiotic treatment. The review covers sulopenem’s structural considerations, physicochemical properties, mechanisms of action, antibacterial activity, and clinical pharmacology. The development of penem derivatives is also addressed, emphasizing their potential in combating resistant bacterial infections. Despite having few approved representatives, penems show promising prospects for future design and may significantly contribute to the fight against bacterial resistance. The review also highlights the challenges and future possibilities in penem research, including the need for improved oral bioavailability and the potential for combination therapies with β-lactamase inhibitors. Overall, penems are valuable antibacterial agents in the antimicrobial arsenal, offering hope in the ongoing battle against multidrug-resistant pathogens. Full article

The occurrence of esophagitis and ingluvitis caused by Salmonella Typhimurium in passerines seized from illegal wildlife trafficking is described. This illegal activity causes stress and leads to lowered immunity in the birds. Additionally, inadequate hygiene conditions predispose the birds to diseases such as salmonellosis. Few studies report the occurrence of Salmonella-induced lesions in the esophagus and crop of passerines; therefore, this study aimed to describe the disease in birds of the genus Sporophila, as well as to investigate the presence of the bacterium in the environment and determine the antimicrobial resistance profile of the isolated bacteria. Three birds of the genus Sporophila were necropsied. In the esophagus and crop, yellowish plaques corresponding to necrosis with bacterial aggregates were observed. Salmonella spp. was isolated from these lesions, with genus confirmation via MALDI-TOF mass spectrometry. Environmental samples were collected from the enclosures and cages where the animals were quarantined, and the same bacterium was isolated. In two birds, the serotype S. Typhimurium was identified. Antibiograms performed on the strains from the birds and the environment revealed resistance to antibiotics in the classes of penicillins, sulfonamides, aminoglycosides, monobactams, tetracyclines, and first and third-generation cephalosporins. To the authors’ knowledge, this is the first report of this agent causing death in Sporophila due to esophagitis and ingluvitis. It is also the first report of salmonellosis in three species of passerines in Brazil. The study underscores the importance of understanding the pathogens circulating in wild animals, especially within the context of One Health. Full article

Patients hospitalized in ICUs with severe COVID-19 are at risk for developing hospital-acquired infections, especially infections caused by Pseudomonas aeruginosa. We aimed to describe the evolution of P. aeruginosa infections in ICUs at CHRU-Nancy (France) in patients with severe COVID-19 during the three initial waves of COVID-19. The second aims were to analyze P. aeruginosa resistance and to describe the antibiotic treatments. We conducted a retrospective cohort study among adult patients who were hospitalized for acute respiratory distress syndrome due to COVID-19 and who developed a hospital-acquired infection caused by P. aeruginosa during their ICU stay. Among the 51 patients included, most were male (90%) with comorbidities (77%), and the first identification of P. aeruginosa infection occurred after a median ICU stay of 11 days. Several patients acquired infections with MDR (27%) and XDR (8%) P. aeruginosa strains. The agents that strains most commonly exhibited resistance to were penicillin + β-lactamase inhibitors (59%), cephalosporins (42%), monobactams (32%), and carbapenems (27%). Probabilistic antibiotic treatment was prescribed for 49 patients (96%) and was subsequently adapted for 51% of patients after antibiogram and for 33% of patients after noncompliant antibiotic plasma concentration. Hospital-acquired infection is a common and life-threatening complication in critically ill patients. Efforts to minimize the occurrence and improve the treatment of such infections, including infections caused by resistant strains, must be pursued. Full article

Since the discovery of penicillin, β-lactam antibiotics have commonly been used to treat bacterial infections. Unfortunately, at the same time, pathogens can develop resistance to β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems by producing β-lactamases. Therefore, a combination of β-lactam antibiotics with β-lactamase inhibitors has been a promising approach to controlling β-lactam-resistant bacteria. The discovery of novel β-lactamase inhibitors (BLIs) is essential for effectively treating antibiotic-resistant bacterial infections. Therefore, this review discusses the development of innovative inhibitors meant to enhance the activity of β-lactam antibiotics. Specifically, this review describes the classification and characteristics of different classes of β-lactamases and the synergistic mechanisms of β-lactams and BLIs. In addition, we introduce potential sources of compounds for use as novel BLIs. This provides insights into overcoming current challenges in β-lactamase-producing bacteria and designing effective treatment options in combination with BLIs. Full article

Medicinal plants with multiple targets of action have become one of the most promising solutions in the fight against multidrug-resistant (MDR) bacterial infections. Tanacetum vulgare (Tansy) is one of the medicinal plants with antibacterial qualities that deserve to be studied. Thus, this research takes a closer look at tansy extract’s composition and antibacterial properties, aiming to highlight its potential against clinically relevant bacterial strains. In this respect, the antibacterial test was performed against several drug-resistant pathogenic strains, and we correlated them with the main isolated compounds, demonstrating the therapeutic properties of the extract. The essential oil was extracted via hydrodistillation, and its composition was characterized via gas chromatography. The main isolated compounds known for their antibacterial effects were α-Thujone, β-Thujone, Eucalyptol, Sabinene, Chrysanthenon, Camphor, Linalool oxide acetate, cis-Carveol, trans-Carveyl acetate, and Germacrene. The evaluation of the antibacterial activity was carried out using the Kirby–Bauer and binary microdilution methods on Gram-positive and Gram-negative MDR strains belonging to the ESKAPE group (i.e., Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.). Tansy essential oil showed MIC values ranging from 62.5 to 500 μg/mL against the tested strains. Synergistic activity with different classes of antibiotics (penicillins, cephalosporins, carbapenems, monobactams, aminoglycosides, and quinolones) has also been noted. The obtained results demonstrate that tansy essential oil represents a promising lead for developing new antimicrobials active against MDR alone or in combination with antibiotics. Full article

Several studies have reported an increased frequency of colonization and/or infection with antibiotic-resistant bacteria (ARB) during the COVID-19 pandemic. Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) are a group of bacteria with intrinsic resistance to multiple antibiotics, including penicillins, cephalosporins, and monobactams. These pathogens are easy to spread and can cause difficult-to-treat infections. Here, we summarize the available evidence on the impact of the COVID-19 pandemic on infections caused by ESBL-PE. Using specific criteria and keywords, we searched PubMed, MEDLINE, and EMBASE for articles published up to 30 March 2023 on potential changes in the epidemiology of ESBL-E since the beginning of the COVID-19 pandemic. We identified eight studies that documented the impact of COVID-19 on ESBL-E. Five studies were focused on assessing the frequency of ESBL-PE in patient-derived specimens, and three studies investigated the epidemiological aspects of ESBL-PE infections in the context of the COVID-19 pandemic. Some of the studies that were focused on patient specimens reported a decrease in ESBL-PE positivity during the pandemic, whereas the three studies that involved patient data (1829 patients in total) reported a higher incidence of ESBL-PE infections in patients hospitalized for COVID-19 compared with those with other conditions. There are limited data on the real impact of the COVID-19 pandemic on the epidemiology of ESBL-PE infections; however, patient-derived data suggest that the pandemic has exacerbated the spread of these pathogens. Full article

In response to pathogen infection, some plants increase production of secondary metabolites, which not only enhance plant defense but also induce fungicide resistance, especially multidrug resistance (MDR) in the pathogen through preadaptation. To investigate the cause of MDR in Botrytis cinerea, grapes ‘Victoria’ (susceptible to B. cinerea) and ‘Shine Muscat’ (resistant to B. cinerea) were inoculated into seedling leaves with B. cinerea, followed by extraction of metabolites from the leaves on days 3, 6, and 9 after inoculation. The extract was analyzed using gas chromatography/quadrupole time-of-flight mass (GC/QTOF) combined with solid-phase microextraction (SPME) for volatile and nonvolatile metabolomic components. Nonvolatile metabolites γ-aminobutyric acid (GABA), resveratrol, piceid, and some carbohydrates or amino acids, coupled with volatile metabolites β-ocimene, α-farnesene, caryophyllene, germacrene D, β-copaene, and alkanes, accumulated at a higher level in grape leaves infected with B. cinerea compared to in noninoculated leaves. Among the established metabolic pathways, seven had greater impacts, including aminoacyl-tRNA biosynthesis, galactose metabolism, valine, leucine, and isoleucine biosynthesis. Furthermore, isoquinoline alkaloid biosynthesis; phenylpropanoid biosynthesis; monobactam biosynthesis; tropane, piperidine, and pyridine alkaloid biosynthesis; phenylalanine metabolism; and glucosinolate biosynthesis were related to antifungal activities. Based on liquid chromatography/quadrupole time-of-flight mass (LC/QTOF) detection and bioassay, B. cinerea infection induced production of plant secondary metabolites (PSMs) including eugenol, flavanone, reserpine, resveratrol, and salicylic acid, which all have inhibitory activity against B. cinerea. These compounds also promoted overexpression of ATP-binding cassette (ABC) transporter genes, which are involved in induction of MDR in B. cinerea. Full article

The aim of this work was to study the microbiological safety and quality of marketed fresh turkey meat, with special emphasis on methicillin-resistant S. aureus, ESBL-producing E. coli, and K. pneumoniae. A total of 51 fresh turkey meat samples were collected at retail level in Spain. Mesophile, Pseudomonas spp., enterococci, Enterobacteriaceae, and staphylococci counts were 5.10 ± 1.36, 3.17 ± 0.87, 2.03 ± 0.58, 3.18 ± 1.00, and 2.52 ± 0.96 log CFU/g, respectively. Neither Campylobacter spp. nor Clostridium perfringens was detected in any sample. ESBL-producing K. pneumoniae and E. coli were detected in 22 (43.14%), and three (5.88%) samples, respectively, all of which were multi-resistant. Resistance to antimicrobials of category A (monobactams, and glycilcyclines) and category B (cephalosporins of third or fourth generation, polymixins, and quinolones), according to the European Medicine Agency classification, was found among the Enterobacteriaceae isolates. S. aureus and methicillin-resistant S. aureus were detected in nine (17.65%) and four samples (7.84%), respectively. Resistance to antimicrobials of category A (mupirocin, linezolid, rifampicin, and vancomycin) and category B (cephalosporins of third- or fourth generation) was found among S. aureus, coagulase-negative staphylococci, and M. caseolyticus isolates. Full article

Antimicrobial resistance (AMR) is a public health risk that needs to be faced from a One Health perspective that includes humans, animals, and environmental health. The food production chain has been identified as a possible route of transmission of AMR bacteria to humans. The most critical phenomenon is related to Critically Important Antimicrobial (CIA) resistance. β-lactams antibiotics (cephalosporin of 3rd, 4th generation, carbapenem, monobactams, and penicillins), quinolones, aminoglycosides, polymyxin, and glycylcyclines were the CIAs chosen in this study. Samples derived from all the stages of the pork food production chain were collected, including pig feces, carcasses, and pork food products (fresh meat, fermented, and seasoned). Escherichia coli were isolated, and AMR and MDR profiles were evaluated. Enterobacterial Repetitive Intragenic Consensus (ERIC-PCR) was used to evaluate phylogenetic similarities. Data showed that 50% of phenotypical AMR observed in the entire pork food chain were related phylogenetically. The contamination of fresh meat, in half of the cases, was not directly related to contamination from feces or carcasses. Despite this, some similarities were found between feces and carcasses. In group analysis, phylogenetic similarities were detected in a 3/36 cluster (8.3%). Nevertheless, further studies are needed to improve consumer risk communication and access to clear and reliable information and health concerns on food labels. Full article

Mycobacterium kansasii (Mkn) causes tuberculosis-like lung infection in both immunocompetent and immunocompromised patients. Current standard therapy against Mkn infection is lengthy and difficult to adhere to. Although β-lactams are the most important class of antibiotics, representing 65% of the global antibiotic market, they have been traditionally dismissed for the treatment of mycobacterial infections, as they were considered inactive against mycobacteria. A renewed interest in β-lactams as antimycobacterial agents has shown their activity against several mycobacterial species, including M. tuberculosis, M. ulcerans or M. abscessus; however, information against Mkn is lacking. In this study, we determined the in vitro activity of several β-lactams against Mkn. A selection of 32 agents including all β-lactam chemical classes (penicillins, cephalosporins, carbapenems and monobactams) with three β-lactamase inhibitors (clavulanate, tazobactam and avibactam) were evaluated against 22 Mkn strains by MIC assays. Penicillins plus clavulanate and first- and third-generation cephalosporins were the most active β-lactams against Mkn. Combinatorial time-kill assays revealed favorable interactions of amoxicillin–clavulanate and cefadroxil with first-line Mkn treatment. Amoxicillin–clavulanate and cefadroxil are oral medications that are readily available, and well tolerated with an excellent safety and pharmacokinetic profile that could constitute a promising alternative option for Mkn therapy. Full article

The emergence and dissemination of Escherichia coli (E. coli) strains that produce extended-spectrum beta-lactamases (ESBLs) represents a major public health threat. The present study was designed to evaluate the prevalence and characteristics of ESBL-producing Escherichia coli isolates from chickens in central China during 2016–2019. A total of 407 E. coli strains isolated from 581 chicken swabs were identified conventionally and analyzed for various cephalosporin susceptibility by disk-diffusion assay. ESBL-producing strains were screened using the double=disk synergy test and ESBL-encoding genes were carried out by PCR/sequencing. A total of 402 E. coli isolates exhibited strong resistance to first- to fourth-generation cephalosporins and monobactam antibiotics, especially cefazolin (60.69%), cefuroxime (54.05%), cefepime (35.14%), ceftriaxone (54.30%), and aztreonam (40.29%). Piperacillin/tazobactam (1.72%) was the most effective drug against the strains, but the resistance rates increased each year. Among the isolates, 262 were identified as ESBL producers and the isolation rates for the ESBL producers increased from 63.37% to 67.35% over the four years. CTX-M (97.33%) was the most prevalent type, followed by TEM (76.72%) and SHV (3.05%). The most common ESBL genotype combination was bla_TEM + bla_CTX-M (74.46%), in which the frequency of carriers increased steadily, followed by bla_CTX-M + bla_SHV (3.05%). In addition, the most predominant specific CTX-M subtypes were CTX-M-55 (48.47%) and CTX-M-1 (17.94%), followed by CTX-M-14 (11.01%), CTX-M-15 (8.02%), CTX-M-9 (6.11%), CTX-M-65 (4.58%), and CTX-M-3 (1.15%). Moreover, a novel multiplex qPCR assay was developed to detect bla_CTX-M, bla_TEM, and bla_SHV, with limits of detection of 2.06 × 10¹ copies/μL, 1.10 × 10¹ copies/μL, and 1.86 × 10¹ copies/μL, respectively, and no cross-reactivity with other ESBL genes and avian pathogens. The assays exhibited 100% sensitivity and specificities of 85%, 100%, and 100% for bla_CTX-M, bla_TEM, and bla_SHV, respectively. In conclusion, our findings indicated that ESBL-producing E.coli strains isolated from chickens in central China were highly resistant to cephalosporins and frequently harbored diversity in ESBL-encoding genes. These isolates can pose a significant public health risk. The novel multiplex qPCR method developed in this study may be a useful tool for molecular epidemiology and surveillance studies of ESBL genes. Full article

Aztreonam is a Gram-negative bacteria-targeting synthetic monobactam antibiotic. Human serum albumin (HSA) plays an important role in the transference of pharmaceuticals, hormones, and fatty acids, along with other compounds, determining their biodistribution and physiological fate. Using several biophysical and in silico approaches, we studied the interaction of aztreonam with HSA under physiological environments in this study. Results confirm the formation of HSA-aztreonam complex where aztreonam showed moderate affinity towards HSA. A static mode of quenching was confirmed from the steady state fluorescence data. FRET findings also showed that there was a significant feasibility of energy transfer between HSA and aztreonam. Site marker displacement experimental conclusion suggested the binding site of aztreonam was the sub-domain IB of HSA. Circular dichroic spectroscopic analysis suggested that aztreonam interaction decreases the α-helical content of HSA. Changes in microenvironment were studied through synchronous fluorescence data. According to molecular docking results, the HSA-aztreonam complex is mostly maintained by non-covalent forces, with a binding energy of 7.7 kcal mol⁻¹. The presence of a hydrogen bond, van der Waal interaction, and pi-anion interaction in the binding process, as well as conformational changes in HSA after binding with aztreonam, are all confirmed by molecular dynamic simulation. Full article