Antibiotics-Basel最新文献

Background/Objectives: The widespread use of antibiotics, which wastewater treatment plants (WWTPs) cannot fully remove, in human and veterinary medicine leads to their release into wastewater, resulting in the contamination of aquatic environments. Bivalves can accumulate these antibiotics, posing a risk to shellfish consumers, including potential antimicrobial resistance. This study aimed to assess how three cooking methods-marinating, steaming, and grilling-affect the concentration of 33 different antibiotics in bivalves fortified at the level of maximum residue limit (MRL) and twice the MRL (2MRL). Results: The data show the percentage of antibiotic remaining after cooking: 100% indicates stability or no reduction; values above 100% show an increase in concentration, and values below 100% reflect a decrease in antibiotic concentration. In general, all culinary procedures removed part of the added antibiotics. However, the most effective method was marinating (47%), followed by steaming (60%) and finally grilling (92%). It was also found that, overall, the fortification level, MRL or 2MRL, did not impact antibiotic removal in each cooking method. Moreover, different antibiotics' classes presented diverse removals when cooked, ranging between 0% for penicillins and 73% for sulphonamides. Furthermore, the results showed a great diversity of responses to cooking within some antibiotic classes. Methods: After cooking, the analysis was based on solid-liquid extraction followed by liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-ToF-MS). Conclusions: The ongoing monitoring of antibiotic levels is essential, and further research is needed to understand how cooking affects these substances and their metabolites. This will help assess the real risk to consumers and guide risk-mitigation measures.

The prevalence of resistance in Gram-positive bacterial infections is rapidly rising, presenting a pressing global challenge for both healthcare systems and economies. The WHO categorizes these bacteria into critical, high, and medium priority groups based on the urgency for developing new antibiotics. While the first priority pathogen list was issued in 2017, the 2024 list remains largely unchanged. Despite six years having passed, the progress that has been made in developing novel treatment approaches remains insufficient, allowing antimicrobial resistance to persist and worsen on a global scale. Various strategies have been implemented to address this growing threat by targeting specific resistance mechanisms. This review evaluates antimicrobial resistance (AMR) in Gram-positive bacteria, highlighting its critical impact on global health due to the rise of multidrug-resistant pathogens. It focuses on the unique cell wall structure of Gram-positive bacteria, which influences their identification and susceptibility to antibiotics. The review explores the mechanisms of AMR, including enzymatic inactivation, modification of drug targets, limiting drug uptake, and increased drug efflux. It also examines the resistance strategies employed by high-priority Gram-positive pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium, as identified in the WHO's 2024 priority list.

Background: Whole genome sequencing of clinical bacterial isolates holds promise in predicting their susceptibility to antibiotic therapy, based on a detailed understanding of the phenotypic manifestation of genotypic variation. The aac(6') aminoglycoside acetyltransferase gene family is the most abundant aminoglycoside resistance determinant encountered in clinical practice. A variety of AAC(6') isozymes have been described, suggesting a phenotypic distinction between subtype I, conferring resistance to amikacin (AMK), and subtype II, conferring resistance to gentamicin (GEN) instead. However, the epidemiology and thus clinical relevance of the various and diverse isozymes and their phenotypic distinction demand systematic and contemporary re-assessment to reliably predict bacterial susceptibility to aminoglycoside antibiotics.

Methods: We analyzed the resistance gene annotations of 657,603 clinical bacterial isolates to assess the prevalence and diversity of aac(6') genes. Seventeen unique aac(6') amino acid sequences were cloned and expressed under defined promoter control in otherwise isogenic E. coli cells for phenotypic analysis with twenty distinct aminoglycoside antibiotics. A panel of clinical isolates was analyzed for the genotype-phenotype correlation of aac(6').

Results: An aac(6') resistance gene annotation was found in 139,236 (21.2%) of the clinical isolates analyzed. AMK resistance-conferring aac(6')-I genes dominated in Enterobacterales (28.5%). In Pseudomonas aeruginosa and Acinetobacter baumannii, a gene conferring the aac(6')-II phenotype but annotated as aac(6')-Ib₄ was the most prevalent. None of the aac(6') genes were annotated as subtype III, but gene aac(6')-Ii identified in Gram-positive isolates displayed a subtype III phenotype. Genes that were annotated as aac(6')-Ib₁₁ in Enterobacterales conferred resistance to both AMK and GEN, which we propose constitutes a novel subtype IV when applying established nomenclature. A phenotypic assessment facilitated structural re-assessment of the substrate promiscuity of AAC(6') enzymes.

Conclusions: Our study provides the most comprehensive analysis of clinically relevant aac(6') gene sequence variations to date, providing new insights into a differentiated substrate promiscuity across the genotypic spectrum of this gene family, thus translating into a critical contribution towards the development of amino acid sequence-based in silico antimicrobial susceptibility testing (AST).

Background: Plant-derived phytochemicals are crucial in fighting bacterial infections and in cancer therapy. Objective: This study investigates the phytochemical composition of the ethanolic extract obtained from Caralluma indica (C. indica) seeds and assesses its antimicrobial, anticancer, and antioxidant activities. Results: GC-MS analysis found 30 phytochemicals in C. indica seeds, including 5 bioactive compounds that have been shown to have antioxidant, antimicrobial, and cytotoxicity properties, through in silico evaluation. Phytochemical screening of C. indica identified and measured the phenolic compounds, providing insight into its bioactive potential and therapeutic properties. C. indica exhibited robust antioxidant capacity (DPPH, ABTS, nitric oxide, and H₂O₂ radical scavenging) alongside potent antimicrobial activity against oral pathogen and cytotoxicity activity on a human oral squamous carcinoma cell line (OECM-1) (EC₅₀ of 169.35 µg/mL) and yeast cell Saccharomyces cerevisiae (215.82 µg/mL), with a selective index of 1.27. The subminimum % MBC/MFC of C. indica significantly reduced biofilm formation against oral pathogens (p < 0.05). Molecular docking studies showed a strong correlation (r = 0.862) between antifungal and anticancer targets, suggesting that the antimicrobial agents in C. indica contribute to cancer prevention mechanisms. Conclusions: These findings propose C. indica seeds as promising candidates for combating oral pathogens, inhibiting biofilm formation, and reducing the risk of oral cancer progression.

Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) can cause cases of community-acquired pneumonia, hospital-acquired pneumonia, and ventilator-associated pneumonia, and nasal colonization with this pathogen increases the risk of infection. Due to its high negative predictive value, multiple studies support using the MRSA nasal polymerase chain reaction (PCR) test to discontinue antimicrobials that target MRSA in the setting of a negative test result. The purpose of this project was to assess the utility of a protocol to allow pharmacists the ability to order MRSA nasal PCR screenings in hospitalized patients with pneumonia. Results: The pre-protocol group included a random sample of 100 patients, and the post-protocol group included 625 patients. Vancomycin DOTs when pharmacists ordered PCRs were significantly lower compared to the pre-protocol group (p < 0.5; 95% CI, 0.46-2.24). The average length of stay and readmission rates at 30 days were significantly lower in the post-protocol group compared to the pre-protocol group (p < 0.05 and p = 0.02, respectively), but there was no significant difference in mortality (p = 0.33). Methods: A protocol was implemented at our institution that allowed pharmacists to order an MRSA nasal PCR test in patients with pneumonia. This retrospective chart review compared a cohort of patients who received vancomycin from before implementation of the protocol to patients who received vancomycin after the protocol's implementation. The primary endpoint was vancomycin days of therapy (DOTs) between the pre-protocol group and the post-protocol group. Other endpoints assessed included the length of hospitalization, readmission rates, and mortality. Conclusions: Pharmacists ordering MRSA nasal PCR tests significantly reduced vancomycin DOTs, average length of stay, and 30-day readmission rates, contributing to positive outcomes in patients with pneumonia.

Background: Infections caused by S. aureus strains encoding Panton-Valentine leukocidin (PVL-SA) have become increasingly relevant in community settings and can cause severe conditions in pediatric populations. We present the pediatric case of an invasive disease caused by PVL-SA and provide a literature review of severe manifestations caused by these strains in children. Methods: A PubMed search (February 2024) found studies that included relevant clinical outcomes, diagnostics, and treatments, excluding cases of asymptomatic infection or in adult populations. A logistical multivariate analysis was used to find predictors of the need for intensive care. Results: A 10-year-old boy came to the attention of our Pediatric Infectious Diseases Unit with fever, chest pain, and tachypnea. A rapid worsening of his clinical conditions was observed, with the development of necrotizing pneumonia, osteomyelitis, deep vein thrombosis (DVT), and multiple abscesses. Blood cultures confirmed the presence of PVL-producing methicillin-resistant S. aureus (MRSA). The initial treatment included linezolid and ceftaroline and was later adjusted to clindamycin, daptomycin, and fosfomycin, with clinical improvement. Discussion: Our review collected 36 articles, including 156 pediatric cases of severe PVL-SA infection. Bacteremia was present in 49% of cases, lung infection in 47%, and osteomyelitis in 37%. The presence of pulmonary localization was predictive of the need for intensive care, O.R. 25.35 (7.46-86.09; p < 0.001). Anti-toxin molecules were used in about half the cases where information on treatment was reported. Our report highlights the capacity of PVL-SA to cause life-threatening complications in children, while also discussing the full range of its clinical spectrum and the most effective therapeutic approaches.

Background: The global spread of antimicrobial resistance (AMR) represents one of the most significant challenges of our generation. It is crucial to continuously monitor AMR, not only by investigating clinical, pathogenic strains but also by monitoring commensal bacterial strains, as they can serve as natural reservoirs of resistance. Infections caused by Enterococcus species are increasingly recognized as emerging threats to both animal and public health. Among economically important livestock, poultry as a major source of animal protein for humans is a frequent carrier of enterococci, and also of sporadically detected clinical disease. Methods: This study aimed to determine the antimicrobial susceptibility profile of Enterococcus strains (n = 499) isolated from chicken farms in Hungary. The minimum inhibitory concentration (MIC) was determined for 15 antibiotics, including 10 with established clinical breakpoints. Results: The strains exhibited good sensitivity to amoxicillin, one of the first-line treatments for Enterococcus infections in veterinary medicine, with only 20.8% showing resistance. However, we observed an alarming 27.9% resistance rate to vancomycin, which is reserved to treat infections caused by multidrug-resistant strains in humans. A comparison of our findings with Hungarian hospital records revealed that the resistance patterns of poultry-derived Enterococcus faecalis strains were very similar to those of human isolates, particularly regarding penicillins and aminoglycosides. Conclusions: Overall, the increasing rates of AMR reinforce the importance of conducting periodic studies to establish long-term trends. For multidrug-resistant strains, next-generation sequencing is recommended to elucidate the genetic basis of resistance.

Objectives: Aminoglycosides are one of the first classes of natural antibiotics which have not lost relevance due to their broad spectrum of action against Gram-positive, Gram-negative bacteria and mycobacteria. The high growth rate of antimicrobial resistance (AMR) together with the severe side effects of aminoglycosides increase the importance of developing improved semisynthetic derivatives. Methods: In this work, we proposed a synthetic route to new tobramycin derivatives modified at the 6″-position with aminoalkylamine or guanidinoalkylamine residues. Results: The antibacterial activity of the new compounds against reference strains of microorganisms was comparable to the parental tobramycin. In striking contrast to tobramycin (resistance index, >256), its 6″-modified derivatives were significantly more potent against resistant clinical isolates of P. aeruginosa strains (resistance index = 4-16) and they demonstrated a promising AMR circumvention in E. coli strains associated with mutations in the fusA gene encoding elongation factor G. All the obtained tobramycin derivatives exhibited reduced cytotoxicity for the eukaryotic HEK293T cells compared to the tobramycin and thereby they potentially may have improved therapeutic index. The proposed modification of the 6″-position of tobramycin does not change the mechanism of aminoglycoside's antibacterial activity: new compounds induced translation errors which resulted in the inhibition of protein synthesis in bacterial cells. Conclusions: Taken together, we can suggest that further modifications of the 6″-position of tobramycin may be beneficial for circumvention of AMR to aminoglycosides or used for conjugation with other molecules of interest.

Introduction: Antimicrobial resistance poses a significant global health threat, partly due to the overprescription of antibiotics. Understanding prescribers' behaviors and identifying knowledge gaps and misconceptions are essential for addressing antibiotic misuse and inappropriate use. Methods: Through online questionnaires, this study surveyed key stakeholders in outpatient antibiotic use in Germany (DE) and Poland (PL), including patients, physicians, and pharmacists. Results: Despite generally good knowledge about antibiotics, discrepancies exist between physicians' perceptions and patients' actual expectations regarding antibiotic prescriptions. Physicians often misjudge patients' attitudes toward antibiotics, with many patients having a neutral stance. This study found a strong physician interest in non-antibiotic treatments and patient willingness to engage with information about antibiotics. Conclusions: Improved communication between healthcare providers and patients was identified as a potential measure for enhancing antimicrobial stewardship, with education on effective alternative treatments, such as symptomatic therapies, as a likely strategy to reduce antibiotic reliance.

Purpose: Our aim was to investigate risk factors, clinical characteristics, and antibiotic susceptibility patterns of cornea-isolated Streptococcus species collected at a tertiary hospital in China over 18 years. Methods: This retrospective study reviewed data from 350 patients diagnosed with Streptococcal keratitis at Beijing Tongren Hospital between January 2006 and December 2023, including demographics, risk factors, clinical signs, in vivo confocal microscopy (IVCM) imaging, and antibiotic susceptibility testing. Results: The predominant type was Streptococcus pneumoniae (n = 108, 29.8%), followed by Streptococcus mitis (n = 90, 24.9%) and Streptococcus oralis (n = 85, 23.5%). Main risk factors included previous ocular surface disease (24.6%), ocular surgery (21.4%), and trauma (16.3%). Significant differences in clinical characteristics were observed among S. pneumoniae, S. oralis, and S. mitis regarding infiltration location (p = 0.038) and size (p = 0.037), as well as hypopyon presence (p = 0.006). IVCM revealed deeper inflammatory cell distribution and structural disruption as the disease progressed. Resistance rates of aminoglycosides, β-lactams, and fluoroquinolones have increased, with significant differences among species for amikacin (p = 0.010), gentamicin (p = 0.007), and others. Poor outcomes correlated with disease duration over one month, central corneal ulcers, dense infiltrations, hypopyon, and scar tissue presence on IVCM. Conclusions:Streptococcal keratitis is a complex ocular infection with multiple risk factors. S. pneumoniae, S. mitis, and S. oralis are the primary causative agents, exhibiting varying clinical features and antibiotic resistance patterns. Key factors associated with poor outcomes include long disease duration, central corneal ulcers, and severe infiltration.