Antibiotics-Basel最新文献

Mycobacterial infections caused by tuberculous and non-tuberculous strains pose significant treatment challenges, especially among immunocompromised patients. Conventional antibiotic therapies often fail due to bacterial resistance, highlighting the need for alternative therapeutic strategies. Mycobacteriophages are emerging as promising candidates for the treatment of mycobacteria. This review comprehensively explores phage isolation, characterization, and clinical applications. Despite the need for more extensive in vitro and in vivo studies, existing evidence shows their efficacy against both sensitive and antibiotic-resistant mycobacterial strains, even under disease-mimicking conditions, particularly when used in cocktails to minimize resistance development. Mycobacteriophages can be engineered and evolved to overcome limitations associated with lysogeny and narrow host range. Furthermore, they exhibit activity in ex vivo and in vivo infection models, successfully targeting mycobacteria residing within macrophages. Delivery methods such as bacterial and liposomal vectors facilitate their entry into human cells. Considering the potential for phage-treatment-induced bacterial resistance, as described in this review, the combination of mycobacteriophages with antibiotics shows efficacy in countering mycobacterial growth, both in the laboratory setting and in animal models. Interestingly, phage-encoded products can potentiate the activity of relevant antibiotics. Finally, the application of phages in different compassionate cases is reported. The positive outcomes indicate that phage therapy represents a promising solution for the treatment of antibiotic-resistant mycobacteria.

Background: Monitoring antimicrobial use is crucial for understanding current prescribing practices. Such information helps in establishing stewardship programs for effectively using antimicrobials and combating resistance to them. Objectives: This study describes how antimicrobials are prescribed at the Veterinary Teaching Hospital of the University of Pisa and compares how the internal medicine and intensive care units differ in their usage of antimicrobials. Methods: The study involved cats that were presented in the units in 2021 and 2022. Antimicrobial prescriptions were obtained via the hospital's management software (OCIROE). Results: In a population of 1164 non-surgical cats with 397 antimicrobials prescribed, the most prescribed ones were amoxicillin-clavulanic acid in the internal medicine unit and ampicillin in the intensive care unit. Twenty-five percent of all antimicrobials were Highest-Priority Critically Important Antimicrobials or Antimicrobial Advice Ad Hoc Expert Group Category B. The oral route was the main route of administration in the internal medicine unit, while parenteral was the most common route used in the intensive care unit. Most antimicrobials were prescribed to treat pathologic conditions affecting the urinary (39%), gastroenteric (21%), respiratory (13%), and integumentary (12%) systems. A diagnosis, accurate dosage, and the use of species-approved medications were recorded in the antimicrobial prescriptions. However, only 11% of these prescriptions were supported by antimicrobial susceptibility tests. Conclusions: These results suggest room for improvement, particularly in increasing the use of antimicrobial susceptibility testing to ensure more targeted antimicrobial therapy. Given the importance of antimicrobial resistance and the One Health approach, the study also highlights the need to consider the broader impact of antimicrobial use in animals, including the potential contribution to resistance in bacteria that affect both animal and human health.

Background/Objectives: The global emergence of antibiotic-resistant zooanthroponotic Escherichia coli strains, producing extended-spectrum beta-lactamases (ESBL-E) and persisting in the intestines of farm animals, has now led to the development of a pandemic of extra-intestinal infectious diseases in humans. The search for innovative probiotic microorganisms that eliminate ESBL-E from the intestines of humans and animals is relevant. Previously, we received three isolates of bifidobacteria: from milk of a calved cow (BLLT1), feces of a newborn calf (BLLT2) and feces of a three-year-old child who received fresh milk from this calved cow (BLLT3). Our goal was to evaluate the genetic identity of BLLT1, BLLT2, BLLT3 isolates using genomic DNA fingerprinting (GDF), to study the tolerance, adhesion, homeostatic and antibacterial activity of BLLT1 against ESBL-E. Methods: We used a complex of microbiological, molecular biological, and immunological methods, including next generation sequencing (NGS). Results: GDF showed that DNA fragments of BLLT2 and BLLT3 isolates were identical in number and size to DNA fragments of BLLT1. These data show for the first time the possibility of natural horizontal transmission of BLLT1 through with the milk of a calved cow into the intestines of a calf and the intestines of a child. BLLT1 was resistant to gastric and intestinal stresses and exhibited high adhesive activity to calf, pig, chicken, and human enterocytes. This indicates the unique ability of BLLT1 to inhabit the intestines of animals and humans. We are the first to show that BLLT1 has antibacterial activity against ESBL-E strains that persist in humans and animals. BLLT1 produced 145 ± 8 mM of acetic acid, which reduced the pH of the nutrient medium from 6.8 to 5.2. This had an antibacterial effect on ESBL-E. The genome of BLLT1 contains ABC-type carbohydrate transporter gene clusters responsible for the synthesis of acetic acid with its antibacterial activity against ESBL-E. BLLT1 inhibited TLR4 mRNA expression induced by ESBL-E in HT-29 enterocytes, and protected the enterocyte monolayers used in this study as a bio-model of the intestinal barrier. BLLT1 increased intestinal alkaline phosphatase (IAP) as one of the main molecular factors providing intestinal homeostasis. Conclusions: BLLT1 shows promise for the creation of innovative functional nutritional products for humans and feed additives for farm animals that will reduce the spread of ESBL-E strains in the food chain.

Background/Objectives: Urinary tract infection (UTI) is a prevalent microbial infection in medical practise, leading to significant patient morbidity and increased treatment costs, particularly in developing countries. This retrospective study, conducted at a tertiary care hospital in Dhaka, Bangladesh, aims to examine the antimicrobial resistance (AMR) patterns of uropathogens and evaluate whether these patterns are influenced by demographic factors such as gender, age, or patient status. Methods: Standard microbiological techniques were used to identify uropathogens, and AMR patterns were determined using the Kirby-Bauer disc diffusion method. Results: Out of 6549 urine samples, 1001 cultures were positive. The infection was more prevalent in females compared to males. The incidence of UTIs in children aged 0-10 years accounted for 12.59% of the total cases, with this age group also exhibiting the highest rate of polymicrobial infections. Among the bacterial uropathogens, 71.19% of isolates were multidrug resistant (MDR) and 84.27% were resistant to at least one antibiotic. Escherichia coli (n = 544, 73.90% MDR) and Klebsiella species (n = 143, 48.95% MDR) were the most common Gram-negative uropathogens, while Enterococcus species (n = 78, 94.87% MDR) was the predominant Gram-positive isolate in this study. Our results indicate that most uropathogens showed resistance against ceftazidime, followed by cefuroxime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and netilmicin. Moderate levels of resistance were observed against ciprofloxacin, levofloxacin, aztreonam, and cefpodoxime. Conclusions: Amikacin was observed to be effective against Gram-negative uropathogens, whereas cefixime was more active against Gram-positive microorganisms, such as Enterococcus species. Moreover, a principal coordinate analysis (PCoA) depicted no significant influence of gender, patient status, or age on AMR patterns. For the continued usefulness of most antibiotics, periodic analysis of the AMR patterns of uropathogens can help assess the rise of MDR bacteria, and therefore guide the selection of appropriate antibiotic treatment strategies.

Objectives: Overuse of antibiotics in healthcare remains prevalent and requires urgent attention in China, particularly in primary healthcare (PHC) facilities. This study aimed to describe the patterns of antibiotic prescriptions for acute upper respiratory tract infections (URTIs) in PHC facilities in China and to investigate how PHC physicians' knowledge influences their antibiotic prescribing behavior.

Methods: A cross-sectional survey linking physician questionnaire responses and their prescription data was conducted in Shaanxi Province, China. The proportions of URTI visits that received at least one antibiotic, combined antibiotics, and broad-spectrum antibiotics were the main outcomes reflecting antibiotic prescribing behavior. Multivariate mixed-effects logistic regressions were applied to analyze the relationship between PHC physicians' knowledge about antibiotics and their antibiotic prescribing behavior.

Results: A total of 108 physicians filled out the questionnaires between February 2021 and July 2021, and a sample of 11,217 URTI visits attended by these physicians from 1 January 2020 to 31 December 2020 were included in the analysis. The overall mean score of our respondents on the knowledge questions was 5.2 (total score of 10). Over sixty percent (61.2%; IQR 50.2-72.1) of the URTI visits received antibiotics. The percentages of URTI visits prescribed with combined and broad-spectrum antibiotics were 7.8% (IQR 2.3-10.2) and 48.3% (IQR 36.7-58.7), respectively. Third-generation cephalosporins were the most frequently used antibiotics. Physicians with lower antibiotic knowledge scores were more inclined to prescribe antibiotics (p < 0.001), combined antibiotics (p = 0.001), and broad-spectrum antibiotics (p < 0.001).

Conclusions: Physicians' insufficient knowledge was significantly associated with antibiotic overprescribing. Professional training targeting physicians' knowledge of antibiotics is urgently needed to improve the rational use of antibiotics in grassroots healthcare facilities in China.

Escherichia coli is a gram-negative commensal bacterium living in human and animal intestines. Its pathogenic strains lead to high morbidity and mortality, which can adversely affect people by causing urinary tract infections, food poisoning, septic shock, or meningitis. Humans can contract E. coli by eating contaminated food-such as raw or undercooked raw milk, meat products, and fresh produce sold in open markets-as well as by coming into contact with contaminated settings like wastewater, municipal water, soil, and faeces. Some pathogenic strains identified in Nigeria, include Enterohemorrhagic (Verotoxigenic), Enterotoxigenic, Enteropathogenic, Enteroinvasive, and Enteroaggregative E. coli. This causes acute watery or bloody diarrhoea, stomach cramps, and vomiting. Apart from the virulence profile of E. coli, antibiotic resistance mechanisms such as the presence of bla_CTX-M found in humans, animals, and environmental isolates are of great importance and require surveillance and monitoring for emerging threats in resource-limited countries. This review is aimed at understanding the underlying mechanisms of evolution and antibiotic resistance in E. coli in Nigeria and highlights the use of improving One Health approaches to combat the problem of emerging infectious diseases.

Background/Objectives: Intestinal colonization by multidrug-resistant (MDR) bacteria is considered one of the main risk factors for invasive infections in the hematopoietic stem-cell transplant (HSCT) setting, associated with hard-to-eradicate microorganisms. The aim of this study was to assess the rate of intestinal colonization by MDR bacteria and their microbial spectrum in a group of post-HSCT patients to study the genetic determinants of beta-lactam and glycopeptide resistance in the recovered isolates, as well as to determine the epidemiological relation between them. Methods: The intestinal colonization status of 74 patients admitted to the transplantation center of University Hospital "St. Marina"-Varna in the period January 2019 to December 2021 was investigated. Stool samples/rectal swabs were screened for third-generation cephalosporin and/or carbapenem-resistant Gram-negative bacteria, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and Stenotrophomonas maltophilia. Identification and antimicrobial susceptibility testing were performed by Phoenix (BD, Sparks, MD, USA) and MALDI Biotyper sirius (Bruker, Bremen, Germany). Molecular genetic methods (PCR, DNA sequencing) were used to study the mechanisms of beta-lactam and glycopeptide resistance in the collected isolates, as well as the epidemiological relationship between them. Results: A total of 28 patients (37.8%) were detected with intestinal colonization by MDR bacteria. Forty-eight non-duplicate MDR bacteria were isolated from their stool samples. Amongst them, the Gram-negative bacteria prevailed (68.8%), dominated by ESBL-producing Escherichia coli (30.3%), and followed by carbapenem-resistant Pseudomonas sp. (24.2%). The Gram-positive bacteria were represented exclusively by Enterococcus faecium (31.2%). The main beta-lactam resistance mechanisms were associated with CTX-M and VIM production. VanA was detected in all vancomycin-resistant enterococci. A clonal relationship was observed among Enterobacter cloacae complex and among E. faecium isolates. Conclusions: To the best of our knowledge, this is the first Bulgarian study that presents detailed information about the prevalence, resistance genetic determinants, and molecular epidemiology of MDR gut-colonizing bacteria in HSCT patients.

Background/Objective: Intravenous fluid shortages have led to fluid-sparing measures such as intravenous push (IVP) administration of antibiotics. This study aimed to compare the safety and efficacy of IVP and intravenous piggyback (IVPB) ceftriaxone in critically ill patients. Results: Demographics were similar in IVP (n = 201) and IVPB (n = 200) groups. Sequential Organ Failure Assessment (SOFA) score was higher, and sepsis and septic shock were more common in the IVP group. Treatment failure occurred in 37.8% of IVP and 19.5% of IVPB groups (p < 0.001). Hospital mortality was more common with IVP (21.4% vs. 9.5%, p < 0.001). Hospital LOS was longer with IVP while intensive care unit (ICU) LOS was similar between the groups. IVP ceftriaxone (OR 2.33, 95% CI 1.43-3.79) and the SOFA score (OR 1.18, 95% CI 1.1-1.27) were associated with treatment failure. Methods: A single-center, retrospective cohort study included adults admitted to an ICU from 2016 to 2021 who received empiric ceftriaxone for ≥72 h. The primary outcome was treatment failure, defined as a composite of inpatient mortality or escalation of antibiotics. Secondary outcomes included length of stay (LOS) and mortality. Chi-squared and independent-sample t-tests were used. Treatment failure was evaluated using multivariate logistic regression. Conclusions: Compared to IVPB, IVP ceftriaxone was associated with higher treatment failure in critically ill patients. Both safety and efficacy should be considered before implementing novel antibiotic administration strategies in practice based primarily on convenience.

The prevalence of multidrug resistance (MDR) and stagnant drug-development pipelines have led to the rapid rise of hard-to-treat antibiotic-resistant bacterial infections. These infectious diseases are no longer just nosocomial but are also becoming community-acquired. The spread of MDR has reached a crisis level that needs immediate attention. The landmark O'Neill report projects that by 2050, mortality rates associated with MDR bacterial infections will surpass mortality rates associated with individuals afflicted with cancer. Since conventional antimicrobials are no longer very reliable, it is of great importance to investigate different strategies to combat these life-threatening infectious diseases. Here, we provide an overview of recent advances in viable alternative treatment strategies mainly targeting a pathogen's virulence capability rather than viability. Topics include small molecule and immune inhibition of virulence factors, quorum sensing (QS) quenching, inhibition of biofilm development, bacteriophage-mediated therapy, and manipulation of an individual's macroflora to combat MDR bacterial infections.

The global emergence of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae presents a significant public health threat and complicates antibiotic treatment for infections. This study aimed to determine the prevalence of ESBL-producing K. pneumoniae in a clinical setting, analyze their antimicrobial susceptibility profiles, and characterize both phenotypic and genetic determinants. A total of 507 non-duplicate clinical isolates of Enterobacterales were collected between 2019 and 2020, and third-generation cephalosporin resistance was screened by disk diffusion. Identification of K. pneumoniae was confirmed using biochemical tests and PCR with species-specific primers. Antimicrobial susceptibility testing was conducted using disk diffusion, and phenotypic ESBL production was confirmed using the combined disk method. Multiplex PCR detected ESBL genes (bla_TEM, bla_SHV, and bla_CTX-M) and identified bla_CTX-M groups. The genetic relatedness of ESBL-producing strains was assessed using the ERIC-PCR approach. Fitty-four isolates were confirmed as ESBL producers, all classified as multidrug-resistant (MDR). All ESBL-producing K. pneumoniae isolates exhibited resistance to ampicillin and cefotaxime, with high resistance rates for ciprofloxacin (98.2%), azithromycin (94.4%), piperacillin-tazobactam (88.9%), and trimethoprim (83.3%). Genotypic analysis revealed bla_CTX-M was present in 94.4% of isolates, bla_SHV in 87%, and bla_TEM in 55.5%. The bla_CTX-M-1 group was the most prevalent, accounting for 96.1% of isolates. Co-harboring of bla_CTX-M, bla_SHV, and bla_TEM occurred in 42.6% of isolates, with co-carrying of bla_CTX-M, and bla_SHV was observed in 23/54 isolates. The ERIC-PCR analysis revealed 15 distinct types, indicating high genetic diversity. These findings highlight the urgent need for ongoing monitoring to control the spread of ESBL among K. pneumoniae and emphasize the importance of early detection and appropriate antibiotic selection for effectively treating infection caused by these pathogens.