Antibiotics-Basel最新文献

The rapid spread of carbapenemase-producing strains has led to increased levels of resistance among Gram-negative bacteria, especially enterobacteria. The current study aimed to collect and genetically characterize the colistin- and carbapenem-resistant isolates, obtained in one of the biggest hospitals (Military Medical Academy) in Sofia, Bulgaria. Clonal relatedness was detected by RAPD and MLST. Carbapenemases, ESBLs, and mgrB were investigated by PCR amplification and sequencing, replicon typing, and 16S rRNA methyltransferases with PCRs. Fourteen colistin- and carbapenem-resistant K. pneumoniae isolates were detected over five months. Six carbapenem-resistant and colistin-susceptible isolates were also included. The current work revealed a complete change in the spectrum of carbapenemases in Bulgaria. bla_NDM-5 was the only NDM variant, and it was always combined with bla_OXA-232. The coexistence of bla_OXA-232 and bla_NDM-5 was observed in 10/14 (72%) of colistin- and carbapenem-resistant K. pneumoniae isolates and three colistin-susceptible isolates. All bla_NDM-5- and bla_OXA-232-positive isolates belonged to the ST6260 (ST101-like) MLST type. They showed great mgrB variability and had a higher mortality rate. In addition, we observed bla_OXA-232 ST14 isolates and KPC-2-producing ST101, ST16, and ST258 isolates. The colistin- and carbapenem-resistant isolates were susceptible only to cefiderocol for bla_NDM-5- and bla_OXA-232-positive isolates and to cefiderocol and ceftazidime/avibactam for bla_OXA-232- or bla_KPC-2-positive isolates. All bla_OXA-232-positive isolates carried rmtB methylase and the colE replicon type. The extremely limited choice of appropriate treatment for patients infected with such isolates and their faster distribution highlight the need for urgent measures to control this situation.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6'-N-acetyltransferase type I enzyme, of which type Ib [AAC(6')-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive for drug development. Mixture-based combinatorial libraries and positional scanning strategy have led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1-R5), inhibits AAC(6')-Ib-mediated inactivation of amikacin. Structure-activity relationship studies have shown that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003, reduced inhibition levels, demonstrating the essential nature not only of the presence of an S-phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions had varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of the compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity.

(1) Background: Antibiotic surveillance data are crucial to map out strategies to promote their optimal use at hospital and community levels. We conducted a comprehensive analysis of longitudinal trends in antibiotic consumption over 7 years at a core "National Antimicrobial Consumption Network" site in North India. (2) Methods: In-patient antibiotic consumption data (2017-2023) were obtained from the hospital's central drug store and organised as follows: defined daily dose per 100 bed-days; antibiotic consumption as per the WHO access, watch and reserve classification; trends in overall and different antibiotic classes' consumption; paediatric formulations of antibiotics; and hospital's annual expenditure on antibiotics. (3) Results: During the 7-year study period, no significant trend could be observed in the overall antibiotic consumption (average annual percent change, AAPC: 9.22; 95% CI: -16.46, 34.9) and cost (AAPC: 13.55; -13.2, 40.3). There was a higher proportion of the consumption of antibiotics in the "reserve" group from 2021 onwards compared to previous years, but the overall trend over 7 years was not significant (AAPC: 319.75; -137.6, 777.1). Antibiotic combinations, classified under the WHO "not recommended" category, comprised a significant proportion of antibiotics consumed. A remarkably increased consumption of azithromycin and doxycycline was recorded during 2020 and 2021, coinciding with the COVID-19 pandemic. (4) Conclusions: Some recommendations to optimise antibiotic use are promoting the use of narrow spectrum "access" group agents; linking antimicrobial resistance and consumption data to formulate effective therapeutic and prophylactic antibiotic use guidelines; and the adoption of restrictive antibiotic policy.

Spondylodiscitis is a severe spinal infection that requires an effective antibiotic treatment. Therefore, we sought to analyse the causative pathogens from intraoperative specimen in patients with spondylodiscitis and a need for surgery. To this end, we performed a retrospective study of all patients with spondylodiscitis and a need for operative treatment admitted to our hospital between January 2020 and December 2022. A total of 114 cases with spondylodiscitis were identified. A total of 120 different pathogens were detected. Overall, 76.7% of those microorganisms were Gram-positive bacteria. The most common causative pathogen was Staphylococcus aureus (n = 32; 26.6%), followed by coagulase-negative staphylococci (n = 28; 23.4%), of which Staphylococcus epidermidis (n = 18; 15%) was the most frequently detected, as well as enterococci (n = 10; 8.4%) and Streptococcus spp. (n = 11; 9.2%). Moreover, 19.1% (n = 22) and 3.4% (n = 4) of all detected isolates were Gram-negative pathogens or fungi, respectively. Overall, 42.8% of all coagulase-negative staphylococci were oxacillin-resistant, while none of them were vancomycin-resistant. In summary, 50% of the pathogens could be identified as staphylococci. The results of our study highlight the important burden of oxacillin-resistant Gram-positive bacteria as an aetiological cause of spondylodiscitis, providing a relevant finding for antimicrobial stewardship programmes.

Antibiotic Resistance Genes (ARGs) are contaminants of emerging concern with marked potential to impact public and environmental health. This review focusses on factors that influence the presence, abundance, and dissemination of ARGs within Wastewater Treatment Plants (WWTPs) and associated effluents. Antibiotic-Resistant Bacteria (ARB) and ARGs have been detected in the influent and the effluent of WWTPs worldwide. Different levels of wastewater treatment (primary, secondary, and tertiary) show different degrees of removal efficiency of ARGs, with further differences being observed when ARGs are captured as intracellular or extracellular forms. Furthermore, routinely used molecular methodologies such as quantitative polymerase chain reaction or whole genome sequencing may also vary in resistome identification and in quantifying ARG removal efficiencies from WWTP effluents. Additionally, we provide an overview of the One Health risk assessment framework, as well as future strategies on how WWTPs can be assessed for environmental and public health impact.

Background: The aim of the study was to characterize the procedure of peripheral intravenous therapy (IT), including the characteristics of vascular access and related complications and qualitative and quantitative analyses of drug consumption.

Materials and methods: A two-year, retrospective, single-center observational study was conducted. The criterion for including a patient in the study was the use of peripheral intravenous catheters (PIVCs) upon admission or during the stay at the internal medicine department (IMD).

Results: The main reasons for hospitalization were exacerbations of chronic diseases for 78% of the patients and acute infections for 22%. IT was used in 83.6% of all the patients. IT was used primarily for antibiotics (5009.9 defined daily doses (DDD)). Further, 22.6% of the PIVCs stopped functioning within 24 h, more frequently in infectious patients. The main reasons for PIVC removal were leakage (n = 880, 26.6%) and occlusion (n = 578, 17.5%). The PIVC locations were mostly suboptimal (n = 2010, 59.5%), and such locations were related to leakage and occlusion (p = 0.017).

Conclusions: In the IMD, most patients require the use of a PIVC, and antibiotics dominate the group of drugs administered intravenously. Up to 1/5 of peripheral intravenous catheters are lost within the first 24 h after their insertion, with most of them placed suboptimally. A properly functioning PIVC appears to be crucial for antimicrobial treatment.

Carbapenem-resistant Pseudomonas aeruginosa infections represent a critical public health concern, highlighting the need for the development of effective antibiotics. Cefiderocol demonstrated potent in vitro activity against Pseudomonas aeruginosa, particularly in strains that are resistant to other drugs. However, concerns regarding the emergence of drug-resistant strains persist. This study, conducted with 109 carbapenem-resistant Pseudomonas aeruginosa strains from the Spanish Hospital (Dr. Balmis, Alicante). The study evaluated susceptibility to cefiderocol in comparison to alternative antibiotics and including their susceptibility to bacterial inoculum, while assessing various testing methods. Our findings revealed high susceptibility to cefiderocol against carbapenem-resistant strains, with only 2 of 109 strains exhibiting resistance. Comparative analysis demonstrated superiority of cefiderocol towards alternative antibiotics. Both the E-test and disk-diffusion methods showed 100% concordance with the microdilution method in classifying strains as susceptible or resistant. However, 4.6% (5/109) of disc zone diameters fell within the technical uncertainty zone, so the E-test technique was found to be more useful in routine clinical practice. Additionally, escalating bacterial inoculum correlated with decreases in vitro activity, so this parameter should be adjusted very carefully in in vivo studies. This study underscores cefiderocol's potential as a therapeutic option for carbapenem-resistant Pseudomonas aeruginosa infections. However, the emergence of drug-resistant strains emphasizes the critical need for a wise use of antibiotics and a continuous monitoring of resistance to antibiotics. Based on our in vitro data, further investigation concerning the impact of bacterial inoculum on drug efficacy is warranted in order to detect resistance mechanisms and optimize treatment strategies, thereby mitigating the risk of resistance.

Bacteriocins is the name given to products of the secondary metabolism of many bacterial genera that must display antimicrobial activity. Although there are several bacteriocins described today, it has not been possible to reach a consensus on the method of classification for these biomolecules. In addition, many of them are not yet authorized for therapeutic use against multi-drug-resistant microorganisms due to possible toxic effects. However, recent research has achieved considerable progress in the understanding, classification, and elucidation of their mechanisms of action against microorganisms, which are of medical and biotechnological interest. Therefore, in more current times, protocols are already being conducted for their optimal use, in the hopes of solving multiple health and food conservation problems. This review aims to synthetize the information available nowadays regarding bacteriocins, and their classification, while also providing an insight into the future possibilities of their usage for both the pharmaceutical, food, and biotechnological industry.

The Arcobacteraceae bacterial family includes species isolated from animals and related food products. Moreover, these species have been found in other ecological niches, including water. Some species, particularly Arcobacter butzleri and Arcobacter cryaerophilus, have been isolated from human clinical cases and linked to gastrointestinal symptoms. The presence of antibiotic-resistant strains is a concern for public health, considering the possible zoonoses and foodborne infections caused by contaminated food containing bacteria resistant to antibiotic treatments. This review aims to highlight the importance of antibiotic resistance in Arcobacter spp. isolates from several sources, including information about antibiotic classes to which this bacterium has shown resistance. Arcobacter spp. demonstrated a wide spectrum of antibiotic resistance, including several antibiotic resistance genes. Antibiotic resistance genomic traits include efflux pumps and mutations in antibiotic target proteins. The literature shows a high proportion of Arcobacter spp. that are multidrug-resistant. However, studies in the literature have primarily focused on the evaluation of antibiotic resistance in A. butzleri and A. cryaerophilus, as these species are frequently isolated from various sources. These aspects underline the necessity of studies focused on several Arcobacter species that could potentially be isolated from several sources.

Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.