Antibiotics-Basel最新文献

Background/Objectives: While new methods for measuring antimicrobial susceptibility have been associated with improved patient outcomes, they should also be validated using standard protocols for error rates and other test metrics. The objective of this study was to validate a novel susceptibility assay for complicated and recurrent urinary tract infections (UTIs): pooled antibiotic susceptibility testing (P-AST). This assay was compared to broth microdilution (BMD) and disk diffusion (DD), following Clinical and Laboratory Standards Institute (CLSI) guidelines for assessment of error rates and agreement. Methods: This study analyzed consecutive fresh clinical urine specimens submitted for UTI diagnostic testing. Upon receipt, the urine samples were subjected in parallel to standard urine culture and multiplex polymerase chain reaction (M-PCR) for microbial identification and quantification. Specimens with the same monomicrobial non-fastidious bacteria detected by both M-PCR and standard urine culture (SUC) underwent standard antibiotic susceptibility testing (AST) and P-AST antibiotic susceptibility testing. Analysis was also undertaken to assess the presence of heteroresistance for specimens with P-AST-resistant and BMD/DD consensus-susceptible results. Results: The performance measures without correction for heteroresistance showed essential agreement (EA%) of ≥90%, very major errors (VMEs) of <1.5%, and major errors (MEs) of <3.0% for P-AST, all meeting the threshold guidelines established by CLSI for AST. The categorical agreement (CA%) also met acceptable criteria (>88%), as the majority of the errors were minor (mEs) with essential agreement. The very major and major error rates for P-AST decreased to <1.0% when heteroresistance was accounted for. Conclusions: The P-AST assay methodology is validated within acceptable parameters when compared to broth microdilution and disk diffusion using CLSI criteria.

Background: The COVID-19 pandemic has intensified concerns over bacterial infections and antimicrobial resistance, particularly in Romania. This systematic review explores bacterial infection patterns and resistance during the pandemic to address critical gaps in knowledge. Methods: A systematic review, following PRISMA guidelines, was conducted using databases such as PubMed and Scopus, focusing on studies of bacterial infections from 2020 to 2022. Articles on bacterial infections in Romanian patients during the pandemic were analyzed for demographic data, bacterial trends, and resistance profiles. Results: A total of 87 studies were included, detailing over 20,000 cases of bacterial infections. The review found that Gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae, were the most frequently identified pathogens, alongside Gram-positive Staphylococcus aureus and Enterococcus spp. Multidrug resistance (MDR) was noted in 24% of the reported strains, with common resistance to carbapenems and cephalosporins. Conclusions: The pandemic has amplified the complexity of managing bacterial infections, particularly in critically ill patients. The rise in MDR bacteria underscores the need for stringent antimicrobial stewardship and infection control measures. Continuous monitoring of bacterial trends and resistance profiles will be essential to improve treatment strategies in post-pandemic healthcare settings.

Background: In hospital- and community-acquired central nervous system infections, resistant Gram-positive bacteria are an increasing therapeutic challenge. The present approach does not attempt to identify rapidly bactericidal therapies for susceptible pathogens but aims to improve methods to find antibiotic regimens for multi-resistant pathogens that are effective in vivo in spite of reduced in vitro susceptibility in culture media. Methods: Antibiotic susceptibility was tested in cerebrospinal fluid (CSF) and Mueller-Hinton broth (Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis) or brain-heart infusion (Streptococcus pneumoniae). Results: Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were either lower in CSF than in broth or equal in CSF and broth. The difference between MICs in CSF and broth was prominent with gentamicin, levofloxacin, linezolid (staphylococci), and vancomycin (staphylococci and pneumococcus), whereas it was absent with ampicillin (E. faecalis), penicillin G (S. pneumoniae), linezolid (enterococcus and pneumococcus), and vancomycin (enterococcus). In no case was the MIC or MBC higher in CSF than in broth. Conclusions: Several antibiotics possess an antibacterial effect in CSF at lower concentrations than the MICs determined in broth, i.e., MICs in broth underestimate in situ susceptibility in CSF.

Background: Serum C-reactive protein (CRP) levels vary depending on radiological and bacteriological findings at the time of tuberculosis (TB) diagnosis. However, the utility of this biomarker in monitoring response to anti-TB treatment and identifying patients at risk of treatment failure is not well established. Objectives: This study evaluated the impact of patients' baseline characteristics and anti-TB drug plasma exposure on the early reduction in serum CRP levels and its relationship with treatment response. Methods: We enrolled 42 patients with drug-susceptible pulmonary TB, who received a standard six-month regimen. The plasma concentrations of four anti-TB drugs were analysed using LC-MS/MS. Clinically relevant data, including serum CRP levels before and 10-12 days after treatment initiation (CRP_10-12d), were obtained from electronic medical records and patient questionnaires. Results: In 10-12 days, the median serum CRP level decreased from 21.9 to 6.4 mg/L. Lower body mass index, positive sputum-smear microscopy results, and lung cavitations at diagnosis were related to higher biomarker levels at both time points; smoking had a more pronounced effect on serum CRP_10-12d levels. Variability in anti-TB drug plasma exposure did not significantly affect the reduction in serum CRP levels. The serum CRP_10-12d levels, or fold change from the baseline, did not predict the time to sputum culture conversion. Conclusions: Disease severity and patient characteristics may influence the pattern of early CRP reduction, while anti-TB drug plasma exposure had no significant effect at this stage. These early changes in serum CRP levels were not a predictor of response to anti-TB therapy.

Background/Objectives: The high recurrence rate of bacterial vaginosis (BV) after antibiotic treatment is at least partially attributed to resistant bacteria. The CAPRISA 083 (CAP083) study investigated the influence of metronidazole (MTZ) treatment on the vaginal microbiome in 56 South African women diagnosed with BV. To explore the etiology of recurrent BV in this cohort, we retrospectively analyzed vaginal swabs collected in CAP083 before and after MTZ treatment. Methods: We isolated over 1200 bacterial strains, including Gardnerella, Lactobacillus, Prevotella, and Fannyhessa, and determined the minimum inhibitory concentration (MIC) of MTZ and the resistance status according to CLSI and EUCAST guidelines. Results: At baseline, 64% (CLSI) of Gardnerella isolates were resistant to MTZ, rising to 80% after MTZ treatment by the 12-week visit. Lactobacillus species consistently exhibited resistance of 100%, while Fannyhessea vaginae maintained resistance rates of 78-91% across visits. Prevotella strains varied, showing two susceptible isolates at baseline and one resistant isolate at the 6-week visit. Susceptible and resistant Gardnerella isolates were often isolated from the same swab, and 70% (CLSI) of participants had at least one resistant Gardnerella strain already at baseline. Sensitive Gardnerella isolates were not a predictor of an MTZ-mediated reduction in Gardnerella abundance. Conclusions: Our data indicate that the 23% cure rate in CAP083 was associated with a combination of a high share of MTZ-resistant bacteria at baseline, a potentially insufficient MTZ dose regimen, and a constantly high average abundance of Gardnerella. Future research should explore novel therapeutic strategies to enhance treatment efficacy and combat antibiotic resistance.

The indole nucleus stands out as a pharmacophore, among other aromatic heterocyclic compounds with remarkable therapeutic properties, such as benzimidazole, pyridine, quinoline, benzothiazole, and others. Moreover, a series of recent studies refer to strategies for the synthesis of bisindole derivatives, with various medicinal properties, such as antimicrobial, antiviral, anticancer, anti-Alzheimer, anti-inflammatory, antioxidant, antidiabetic, etc. Also, a series of natural bisindole compounds are mentioned in the literature for their various biological properties and as a starting point in the synthesis of other related bisindoles. Drawing from these data, we have proposed in this review to provide an overview of the synthesis techniques and medicinal qualities of the bisindolic compounds that have been mentioned in recent literature from 2010 to 2024 as well as their numerous uses in the chemistry of materials, nanomaterials, dyes, polymers, and corrosion inhibitors.

Multidrug-resistant (MDR) bacteria, especially Escherichia coli, are a major contributor to healthcare-associated infections globally, posing significant treatment challenges. This study explores the efficacy of (-)-epigallocatechin gallate (EGCG), a natural constituent of green tea, in combination with ampicillin (AMP) to restore the effectiveness of AMP against 40 isolated MDR E. coli strains. Antimicrobial activity assays were conducted to determine the minimum inhibitory concentrations (MIC) of EGCG using the standard microdilution technique. Checkerboard assays were employed to assess the potential synergistic effects of EGCG combined with AMP. The pharmacodynamic effects of the combination were evaluated through time-kill assays. Outer membrane disruption was analyzed by measuring DNA and protein leakage and with assessments using N-phenyl-1-naphthylamine (NPN) and rhodamine 123 (Rh123) fluorescence dyes. Biofilm eradication studies involved biofilm formation assays and preformed biofilm biomass and viability assays. Scanning electron microscopy (SEM) was used to examine changes in cellular morphology. The results indicated that EGCG demonstrated activity against all isolates, with MICs ranging from 0.5 to 2 mg/mL, while AMP exhibited MIC values between 1.25 and 50 mg/mL. Importantly, the EGCG-AMP combination showed enhanced efficacy compared to either treatment alone, as indicated by a fractional inhibitory concentration index between 0.009 and 0.018. The most pronounced synergy was observed in 13 drug-resistant strains, where the MIC for EGCG dropped to 8 µg/mL (from 1 mg/mL alone) and that for AMP to 50 µg/mL (from 50 mg/mL alone), achieving a 125-fold and 1000-fold reduction, respectively. Time-kill assays revealed that the bactericidal effect of the EGCG-AMP combination occurred within 2 h. The mechanism of EGCG action includes the disruption of membrane permeability and biofilm eradication in a dose-dependent manner. SEM confirmed that the combination treatment consistently outperformed the individual treatments. This study underscores the potential of restoring AMP efficacy in combination with EGCG as a promising strategy for treating MDR E. coli infections.

In the face of rising the threat of resistant pathogens, antimicrobial peptides (AMPs) offer a viable alternative to the current challenge due to their broad-spectrum activity. This study focuses on enhancing the efficacy of temporin-SHa derived NST-2 peptide (1), which is known for its antimicrobial and anticancer activities. We synthesized new analogs of 1 using three strategies, i.e., retro analog preparation, lysine addition/substitution, and levofloxacin conjugation. Analogs were tested in terms of their antibacterial, antifungal, and anticancer activities. Analog 2, corresponding to retro analog of NST-2, was found to be more active but also more hemolytic, reducing its selectivity index and therapeutic potential. The addition of lysine (in analog 3) and lysine substitution (in analog 7) reduced the hemolytic effect resulting in safer peptides. Conjugation with levofloxacin on the lysine side chain (in analogs 4 and 5) decreased the hemolytic effect but unfortunately also the antimicrobial and anticancer activities of the analogs. Oppositely, conjugation with levofloxacin at the N-terminus of the peptide via the β-alanine linker (in analogs 6 and 8) increased their antimicrobial and anticancer activity but also their hemolytic effect, resulting in less safe/selective analogs. In conclusion, lysine addition/substitution and levofloxacin conjugation, at least at the N-terminal position through the β-alanine linker, were found to enhance the therapeutic potential of retro analogs of NST-2 whereas other modifications decreased the activity or increased the toxicity of the peptides.

The neonatal intensive care unit (NICU) population, especially low birth weight and critically ill neonates, is at risk of invasive Candida infections, which are associated with high mortality rates and unfavorable long-term outcomes. The timely initiation of an appropriate antifungal treatment has been demonstrated to enhance the prognosis. Factors that should be considered in the choice of an antifungal agent include the causative Candida strain, the presence and location of deep tissue infection, any previous use of antifungal prophylaxis, and the presence of implanted devices. Amphotericin B and fluconazole, the first-line drugs for neonatal candidiasis, are not always suitable due to several limitations in terms of efficacy and adverse effects. Therefore, alternative antifungals have been studied and used in neonates when conventional antifungals are ineffective or contraindicated. This narrative review aims to provide an overview of the current literature regarding the use of echinocandins in the neonatal population. The three echinocandins, micafungin, caspofungin, and anidulafungin, share characteristics that make them useful for the treatment of neonatal candidiasis, including activity against a wide range of Candida strains and Candida biofilms and a favorable safety profile.

Vancomycin-variable enterococci (VVE), though genetically containing van genes, are phenotypically sensitive to vancomycin. If VVE is undetected or does not grow on the vancomycin-resistant enterococci (VRE) selection medium, or both, it can acquire resistance upon exposure to vancomycin. This characteristic is clinically important for the treatment and prevention of VRE. This study aims to analyze the prevalence and characteristics of VVE in Korea through the Global Antibiotic Resistance Surveillance System (Kor-GLASS) and emphasize the importance of VVE. A total of 3342 enterococcal bloodstream isolates were collected through the Kor-GLASS between 2017 and 2022. Antibiotic susceptibility testing, van gene detection, and multilocus sequence typing were conducted with all the isolates. The trends in the domestic prevalence of VVE were analyzed and compared with global prevalence data. Among the isolates, 197 (5.9%), including 124 Enterococcus faecium and 73 E. faecalis, were identified as VVE. While the VRE incidence has declined in Korea since 2020, the VVE incidence is significantly rising. In Korea, only the vanA gene has been detected in both VRE and VVE, and no other van gene variants have been identified. Most of these isolates belong to CC17 (91.3%), with ST17, ST817, and ST80 as the predominant types. We have shown that continuous surveillance is essential in Korea due to the persistently high prevalence of VRE and the potential evolution of VVE into VRE. Consequently, it is critical to evaluate Enterococcus species isolated from domestic clinical settings for their phenotypic vancomycin resistance and the molecular detection of van genes, irrespective of the strain.