Ticarcillin 3g / Clavulanic acid 200mg powder for solution for infusion vials

​ Introduction: Antibiotic resistance is now one of the most serious threats to global health, food security and development. We have seen an increase in the number of antibiotic-resistant bacteria, especially in hospitals over the last few decades. The objective of this study was to investigate carbapenem-resistant Enterobacteriaceae strains isolated in Senegal. Methodology: In this retrospective study conducted at the Medical Biology Laboratory of the Pasteur Institute of Dakar from January 2017 to December 2019, we describe carbapenem-resistant Enterobacteriaceae (CRE) isolates obtained from 144 patients as part of efforts to monitor and control the emergence of antibiotic-resistant Enterobacteriaceae strains. Data was analyzed using Microsoft Excel 2010 for processing. Results: A total of 144 strains of ertapenem-resistant Enterobacteriaceae were isolated during the study period and number of strains increased considerably from year to year : 26 strains in 2017, 45 in 2018 and 73 in 2019. Most frequently isolated species were E. coli (38%), K. pneumoniae (28.5%) and E. cloacae (25.7%) and majority of samples were urine samples (93% ; n=134). The strains were isolated from patients in the 70-79 and 60-69 age groups, which were most represented with 27.8% and 24.3% respectively. The strains of enterobacteria were all resistant to amoxicillin, amoxicillin-clavulanic acid, ticarcillin, ticarcillin-clavulanic acid, piperacillin, cefalotin, cefuroxime, cefotaxime, ceftazidime and aztreonam, with the exception of the piperacillin-tazobactam and cefoxitin, where 10 strains were sensitive. All strains were resistant to ertapenem, while the rates of resistance to meropenem and imipenem were 91.7% and 68.1% respectively. For fluoroquinolones, almost all strains were resistant to the four compounds tested: nalidixic acid (97.9%), norfloxacin (97.9%), ofloxacin (97.2%) and ciprofloxacin (96.5%). The rate of resistance to tobramycin, gentamicin and amikacin was 79.9%, 54.2% and 18.1% respectively. Amikacin was the most active compound against E. cloacae (86.5%), K. pneumoniae (82.9%), E. coli (78.2%) and C. freundii (75%). Conclusion: This study supports the need to monitor CRE in Senegal and draws attention to the significant increase of ertapenem resistance in Enterobacteriaceae. Future surveillance analysis should include a genetic description of carbapenem resistance to provide new strategies.

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• High carbapenem-resistant P. aeruginosa strains carrying blaGES genes. • Five dominant virulence genotypes profiles with key pathogenicity factors like toxA and plcN/H. • Genetic diversity among isolates, indicating no clonal transmission. The aim of this study was to determine the antimicrobial susceptibility, virulence genotypes, presence of extended spectrum β-lactamase (ESBL) and carbapenemase genes, and clonality of Pseudomonas aeruginosa isolates responsible for lower respiratory tract infections in patients admitted to the National Bone Marrow Transplant Center (NBMTC) of Tunisia. During the 11-year study period, a total of 50 P. aeruginosa isolates were responsible for lower respiratory tract infections. Isolates were studied by determining their serotypes, antimicrobial susceptibility, genes encoding ESBL/carbapenemases and virulence factors, and genetic relatedness by ERIC-PCR. High to moderate resistance rates were observed for ticarcillin, ticarcillin–clavulanic acid, piperacillin–tazobactam, ceftazidime, cefepime, imipenem, meropenem, ciprofloxacin, amikacin, and fosfomycin. One isolate showed an ESBL phenotype encoded by the bla SHV-2a gene. Of 13 isolates resistant to both imipenem and meropenem, the bla GES gene was amplified in nine isolates. Isolates exhibited 19 virulence genotypes, of which five were prevalent: V1 (14 genes; n = 14), V2 (14 genes, n = 6), V3 (all genes, n = 6), V4 (13 genes, n = 5), and V5 (13 genes, n = 5). ERIC-PCR showed high genetic heterogeneity. These findings highlight the high genetic heterogeneity of P. aeruginosa isolates in these neutropenic patients, as well as their remarkable pathogenic power, raising significant concern. El objetivo de este estudio fue evaluar un conjunto de aislados de Pseudomonas aeruginosa responsables de infecciones de las vías respiratorias bajas en pacientes ingresados en el Centro Nacional de Trasplante de Médula Ósea (CNTMO) de Túnez, focalizando en la sensibilidad a los antimicrobianos, los genotipos de virulencia, la presencia de genes de β-lactamasa de espectro extendido (BLEE) y carbapenemasa y la clonalidad. Durante un período de estudio de 11 años, se recuperaron 50 aislados de P. aeruginosa a partir de infecciones respiratorias bajas. Se determinaron los serotipos y el parentesco genético se estableció mediante la técnica ERIC-PCR. Se observaron tasas de resistencia de moderadas a altas frente a ticarcilina, ticarcilina-ácido clavulánico, piperacilina-tazobactam, ceftazidima, cefepima, imipenem, meropenem, ciprofloxacina, amikacina y fosfomicina. Solo un aislado presentó el fenotipo BLEE codificado por el gen bla SHV-2a . Entre las 13 cepas resistentes a imipenem y meropenem, 9 dieron positiva la amplificación del gen bla GES . Los aislados exhibieron 19 genotipos de virulencia, de los cuales 5 fueron predominantes: V1 (14 genes; n = 14), V2 (14 genes; n = 6), V3 (todos los genes; n = 6), V4 (13 genes; n = 5) y V5 (13 genes; n = 5). La ERIC-PCR reveló una elevada heterogeneidad genética. Estos hallazgos evidencian la gran heterogeneidad genética de los aislados de P. aeruginosa en estos pacientes neutropénicos, así como su alto potencial patógeno, lo que constituye un importante motivo de preocupación clínica.

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BACKGROUND: Urinary tract infections (UTIs) are among the most common community-acquired bacterial infections and Enterobacteriaceae are the leading etiological agents. Rising antimicrobial resistance (AMR) within this family poses major challenges for empirical treatment. This study aimed to describe the species distribution and antimicrobial resistance patterns of uropathogenic Enterobacteriaceae isolated from outpatients in Tétouan, Morocco. METHODS: A cross-sectional descriptive study was conducted between April 2022 and December 2023 in three medical laboratories. Enterobacteriaceae isolated from urine cultures with significant bacteriuria were identified using the VITEK®2 system. Antimicrobial susceptibility testing was performed according to EUCAST 2021 guidelines. Extended-spectrum β-lactamase (ESBL) production was assessed using the Modified Double Disc Synergy Test (MDDST). Statistical analyses were performed using SPSS version 26, with significance set at p < 0.05. RESULTS: A total of 422 Enterobacteriaceae isolates were obtained, predominantly from female patients (74.9%). Escherichia coli was the most frequent species (83.4%), followed by Klebsiella pneumoniae (9.2%). High resistance rates were observed for ampicillin (60.9%) and ticarcillin (56.2%), while resistance to imipenem (1.2%) and ertapenem (0.9%) remained low. ESBL production was detected in 20 isolates (4.7%), with E. coli being the predominant ESBL-producing species (16/20; 80.0%), while K. pneumoniae exhibited a higher species-specific prevalence (4/39; 10.3%). Male patients exhibited significantly higher resistance to several β-lactams, while pediatric patients showed higher resistance to cephalosporins and aminoglycosides. CONCLUSION: Uropathogenic Enterobacteriaceae circulating in the community of Tétouan exhibit substantial resistance to commonly prescribed oral antibiotics, although carbapenems remain highly effective. The moderate prevalence of ESBL-producing strains highlights the need for reinforced antimicrobial stewardship and continuous regional surveillance to guide empirical treatment and limit the spread of resistant pathogens.

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Genomics have become crucial in addressing the public health challenges posed by antimicrobial resistance (AMR). In this study, we performed the first whole-genome sequencing (WGS) and genomic analyses of clinical Acinetobacter baumannii ( A. baumannii ) strains isolated at the Sylvanus Olympio University Teaching Hospital in Lomé, Togo. This prospective study, conducted from April 19 to September 02, 2019. Susceptibility profiles were obtained using the Kirby-Bauer disc diffusion method, and the nine studied carbapenem-resistant A. baumannii strains were subjected to next generation sequencing (NGS) using an Illumina platform. All isolates exhibited resistance to imipenem, ticarcillin, clavulanic acid, cefotaxime, and ciprofloxacin, but remained susceptible to colistin, tigecycline, and rifampicin. The study identified five A. baumannii ST1 strains, two ST103 strains, one ST52 strain, and one ST1153 strain. The number of AMR genes per strain ranged from six to 24, whereas the number of virulence genes per strain varied from 32 to 67. Each isolate contained at least one plasmid, with the number of plasmids per isolate ranging from one to four per isolate. The carbapenemase-producing genes bla OXA-23 , bla OXA-58 , bla OXA-68 , bla OXA-69 , bla OXA-70 , bla OXA-91 , and bla NDM-1 were identified, along with bla CTX-M-15 and other antibiotic resistance genes. Additionally, multidrug efflux system genes, including ade CFGHIJKLMNS, abe SJ, and amv A, and a wide array of virulence and biofilm-forming genetic determinants were found in all isolates. Eleven integrons were detected, featuring aac(3)-Ia , sat- 2, and dfr A1 cassettes. Tn 6018 , carrying the mercury resistance gene mer R and czc D (Co/Zn/Cd efflux system), and Tn 2007 , carrying bla OXA-23 , were present in six genomes. Four Ghanaian genomes were most closely related to the A. baumannii ST1 and ST103 strains reported in this study. Furthermore, several multidrug resistance plasmids and one virulence and AMR hybrid plasmid (accession number JBFMWK020002174.1) were identified. This study provides valuable insights into clinical A. baumannii in Togo, underscoring the need for more frequent genomic studies in sub-Saharan countries to effectively monitor and combat AMR in Africa.

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Background/Objectives: Antibiotic-resistant strains have been reported in aquatic ecosystems, with varying prevalence and resistance patterns by region. In Tamaulipas, Mexico, little information has been generated on this topic, making it difficult to estimate their potential risk to environmental and human health. Therefore, the objective of this study was to evaluate the presence and virulence of antibiotic-resistant strains of Pseudomonas aeruginosa in environmental water from Tamaulipas, Mexico. Methods: One hundred water samples were collected from different water bodies in Tamaulipas to identify P. aeruginosa by PCR and MALDI-TOF, virulence gene detection, antimicrobial susceptibility testing, and detection class 1 integrons. Results: In this study, 109 P. aeruginosa strains were isolated. Eight virulence genes were identified in 47.7% to 80.7% of the strains, with the rhlAB gene being the most frequent. The strains showed resistance or intermedia resistance to 10 of the 16 antibiotics tested, in a range of resistance values 0.9–66.2%. In total, 100% (109/109) were susceptible to ceftazidime (CAZ), gentamicin (GM), amikacin (AN), netilmicin (NET), tobramycin (NN) and norfloxacin (NOR), and 65.7% were resistant to ticarcillin/clavulanic acid and 53.5% to ticarcillin; the resistance to the remaining antibiotics was between 19.4% and 0.9%. The class 1 integron was not identified in any of the strains analyzed. Conclusions:P. aeruginosa in environmental waters of Tamaulipas showed potential to cause infections and low rates of resistance to most of the antibiotics tested. However, 20% were resistant to one of the most common treatments, which could pose a risk to public health.

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Abstract This study aimed to examine the motility, biofilm production, endotoxin release, and antibiotic resistance of 81 Ralstonia pickettii isolates collected from different pharmaceutical water systems in Croatia. Swimming and twitching motility were detected in all isolates, while swarming was not observed. Biofilm production was detected in approximately 40 % of the isolates under the tested conditions. Notably, extracellular polymeric substance (EPS) production was a common trait among all isolates. Endotoxin production was detected with the Limulus Amoebocyte Lysate test. Antibiotic susceptibility testing revealed consistent resistance to colistin, as well as significant resistance rates to β-lactam antibiotics, ertapenem, amoxicillin/clavulanic acid, ticarcillin and ampicillin. High susceptibility to first-generation cephalosporins, cephalexin, cefoxitin and chloramphenicol was observed. All isolates were susceptible to tigecycline and tetracycline. The isolates were grouped into three genetically closely related clusters, yet notable phenotypic diversity in biofilm production and antibiotic susceptibility persisted within these groups. The study highlights R. pickettii ’s adaptability in pharmaceutical water systems, marked by its motility, biofilm-forming capabilities, and multidrug resistance. These results emphasise the importance of rigorous monitoring of water systems to reduce transmission risks and prevent the emergence of resistant strains in clinical environments.

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Antibiotic-associated encephalopathy (AAE) is a serious adverse drug reaction that can cause significant neurological complications. This study aimed to identify the antibiotics associated with AAE by mining data from the US Food and Drug Administration Adverse Event Reporting System (FAERS), thereby providing insights into antibiotic-related neurotoxicity risks. Disproportionality analysis was performed using the reporting odds ratio method based on FAERS data from Q1 2004 to Q4 2024. A total of 87 preferred terms potentially related to AAE were identified. Antibiotics classified under Anatomical Therapeutic Chemical codes J01 to J07 and other antimicrobial agents were included. All identified antibiotics were grouped into 3 categories according to their clinical neurotoxic profiles. In total, 13,698 patients with AAE were identified over the 21-year period. The 5 most frequently reported antibiotics were metronidazole (1464 cases), levofloxacin (1447), ciprofloxacin (1290), ertapenem (825), and imipenem/cilastatin (788). The incidence of AAE increased with age. Among the 121 antibiotics analyzed, 52 showed positive reporting odds ratio signals: 28 were classified as type 1, 6 as type 2, and 18 as type 3. Most AAE cases occurred within 10 days of antibiotic exposure, except for several agents, including meropenem/vaborbactam and ticarcillin/clavulanic acid (type 1), and isoniazid, pyrazinamide, rifampicin, and paromomycin (type 3), which exhibited delayed onset. This study represents the first large-scale pharmacovigilance analysis of AAE using FAERS data and identifies 52 antibiotics with significant neurotoxicity signals. Most antibiotics trigger early-onset AAE, and older patients demonstrate greater susceptibility. These findings expand our understanding of AAE and inform safer antibiotic use.

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Background Pseudomonas promysalinigenes is a newly described bacterial species renowned for producing promysalin, a species-selective lipopeptide antibiotic. All previously reported strains of this species are derived from environmental niches such as plant rhizospheres, and no clinical infection cases associated with this bacterium have been documented to date. Thus, the clinical microbiology relevance, genomic features, and adaptive potential of P. promysalinigenes remain largely unexplored, and current reference databases have limited coverage of this rare species. Methods A bacterial strain designated W2469 was isolated from the bile specimen of a patient with acute suppurative cholecystitis and cholecystolithiasis. Conventional phenotypic and molecular identification [matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), VITEK 2 biochemical assay, 16S ribosomal RNA (rRNA), and whole-genome sequencing (WGS)] was performed. Bioinformatics analyses, including average nucleotide identity (ANI), digital DNA–DNA hybridization (dDDH), core genome single-nucleotide polymorphism (cgSNP), pan-genome analysis, and functional annotation against COG, KEGG, CAZy, VFDB, and CARD databases, were conducted to characterize the strain. Results Conventional methods yielded consistent misidentification of the strain, while WGS definitively assigned it to P. promysalinigenes (ANI = 98.8%, dDDH = 91.1% against the type strain RW10S1). The strain exhibited a narrow-spectrum resistance phenotype, with resistance to aztreonam and ticarcillin/clavulanic acid, intermediate susceptibility to meropenem, and susceptibility to most clinically used antibiotics. Genomic annotation identified 25 antimicrobial resistance genes and 139 niche adaptation-related factors, most of which are low-identity homologs (&amp;lt;80%) of canonical reference sequences. Pan-genome analysis identified 571 clinical-specific genes associated with host adaptation, with complete loss of the environmental promysalin biosynthetic gene cluster. Conclusion This study provides the first documentation of P. promysalinigenes as a clinical isolate from human bile, expanding the known ecological niche of this species to the clinical setting. Conventional methods are prone to misidentifying this rare species, and WGS is critical for accurate taxonomic identification. Importantly, the strain exhibits clear adaptive phenotypes despite low sequence identity to known functional elements, highlighting profound knowledge gaps in the genomic diversity and uncharacterized adaptive mechanisms of this rare Pseudomonas species. This work provides a foundational genomic resource for future investigations into this emerging opportunistic pathogen.

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Background/Objectives: The emergence of hypervirulent Pseudomonas aeruginosa strains resistant to β-lactamase inhibitor antibiotics is a critical health problem as they impede the treatment of infections. The objective of this study was to determine the different molecular arrangements of the virulence genotype related to β-lactamase genotype and the resistance phenotype to a combination of β-lactam antibiotics and β-lactamase inhibitors, and the phylogroups in P. aeruginosa strains isolated from patients with healthcare-associated infections and community-acquired infections. Methods: P. aeruginosa, virulence genes, β-lactamase genes and phylogroups were identified using polymerase chain reaction. Resistance to β-lactam antibiotics and β-lactamase inhibitors was determined using the disk diffusion method. The MIC determination of ticarcillin/clavulanic acid and piperacillin/tazobactam was performed using the MIC test strip for antimicrobial susceptibility testing. Results: In total, 124 P. aeruginosa strains from patients with healthcare-associated (67/124) and community-acquired infections (57/124) were analyzed. Most strains from patients with healthcare-associated infections and community-acquired infections harbored genes for proteases (aprA), phospholipases (pIcH and pIcN), elastases (lasA and lasB), rhamnolipids (rhLA), quorum-sensing system (lasI and rhII), and β-lactamase (blaoxa-4, blaoxa-1, and blaGES). In total, 100% (124/124) and 99.1% (123/124) of the strains isolated from patients with healthcare-associated and community-acquired infections were resistant to the β-lactamase inhibitor antibiotics, amoxicillin/clavulanic acid and ampicillin/sulbactam, respectively, while 54% (67/124) of the strains were resistant to piperacillin/tazobactam. Phylogroup 1 (22/124) was detected more frequently among the strains in relation to phylogroup 2 (8/12). Conclusions: We demonstrated different association profiles of virulence genotype related to the β-lactamase genotype, the β-lactamase inhibitor resistome, phylogroups, and clinical origin of the strains. Therefore, medical treatment regimens against infections caused by P. aeruginosa should be improved.

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