Antibiotics-Basel最新文献

Introduction: Despite the rising global awareness and improvement of socioeconomic and living standards, the prevalence of diabetic osteomyelitis (DOM) and its complications has been increasing rapidly. This study aims to investigate the long-term prognosis of DOM of the foot treated using antibiotic-impregnated cement spacer (ACS) and the contributing risk factors for reoperation.

Methods and materials: We retrospectively reviewed the data of 55 diabetic patients with Meggitt-Wagner Grade IIB wounds diagnosed with osteomyelitis of the foot, treated in our institution with excessive debridement, excision of the infected tissue, and implantation of antibiotic-impregnated cement spacer fixed with a Kirschner wire. Descriptive statistics, including patient demographics, were analyzed. Statistical analysis was performed using point-biserial correlation and a Chi-square test with Cramer's V effect-size estimation to determine the relationship between reoperation and various parameters.

Results: 55 patients (36 (65.45%) males and 19 (34.55%) females) with a median age of 64 (39-84) years were thoroughly analyzed throughout a median follow-up of 884 days (2-4671 days). Of the entire cohort, 29 (52.72%) patients achieved primary successful infection eradication without any further intervention, and 8 (14.54%) patients were successfully treated using a secondary procedure. More than half of the reoperated patients underwent the secondary intervention within less than a month after the primary ACS. When assessing correlation, age (r = 0.28, p = 0.04), gender (r = 0.31, p = 0.02), Staphylococcus aureus (r = -0.10, p = 0.04), and the use of gentamicin-only antibiotic cement spacer (r = 0.34, p = 0.01) demonstrated statistically significant correlation to reoperation. 89.18% of the patients who achieved infection eradication did not undergo cement removal.

Conclusions: ACS has shown excellent results in eradicating bone infection with up to 7.23 years of follow-up, acting as a structural stabilizer, preventing soft tissue contractures, and delivering highly concentrated local antibiotic treatment both to soft tissue and bone. Regardless, specific factors should be thoroughly evaluated prior to surgery, as advancing age, gender, and the use of gentamicin-only antibiotics appear to be positively associated with a higher likelihood of reoperation. Conversely, infections caused by cultured Staphylococcus aureus seem to be inversely related to reoperation.

Periprosthetic joint infections (PJIs) are a dangerous complication of joint replacement surgeries which have become much more common in recent years (mostly hip and knee replacement surgeries). Such a condition can lead to many health issues and often requires reoperation. Staphylococci is a bacterial group most common in terms of the pathogens causing PJIs. S. aureus and coagulase-negative staphylococci are found in around two-thirds of PJI cases. Recently, the numbers of staphylococci that cause such infections and that are methicillin-resistant are increasing. This trend leads to difficulties in the treatment and prevention of such infections. That is why MRSA and MRSE groups require extraordinary attention when dealing with PJIs in order to successfully treat them. Controlling carriage, using optimal prosthetic materials, and implementing perioperative antimicrobial prophylaxis are crucial strategies in infection prevention and are as essential as quick diagnosis and effective targeted treatment. The comprehensive professional procedures presented in this review show how to deal with such cases.

Bile salts possess innate antibacterial properties and can cause significant damage to bacteria. To survive in the mammalian gut, Klebsiella pneumoniae has developed mechanisms to tolerate bile salts; however, the specific mechanisms remain unclear. Transposon library screening revealed that the efflux pump AcrAB is involved in bile salt resistance. acrA and acrB mutants exhibited high sensitivity not only to bile salts but also to SDS and various antibiotics, with a switch-loop, comprising residues G615, F616, A617, and G618, proving to be crucial in this process. A colonization defect of acrA and acrB mutants was demonstrated to be located in the mouse small intestine, where the bile salt concentration is higher compared to the large intestine. Additionally, both acrA and acrB mutants displayed reduced virulence in the Galleria mellonella model. In conclusion, our results suggest that the Resistance-Nodulation-Cell Division efflux pump serves as a critical determinant in the pathogenesis of K. pneumoniae through various aspects.

Background: Antimicrobial resistance (AMR) has been identified as one of the top ten public health threats facing humanity. Aim: The purpose of this study was to assess the effect of an antimicrobial stewardship educational intervention on family caregivers' knowledge and practices in primary healthcare settings in Egypt. Methods: A quasi-experimental, one-group pretest-posttest design involving a sample of 300 family caregivers attending family health centers. The data were collected using questionnaires that assessed caregiver knowledge and self-reported practices regarding AMR before and after the intervention (primary outcomes). The intervention combined tailored knowledge and practice components that carefully evaluated participants' knowledge regarding AMR, health risk, antibiotic usage, and prevention of infection. Furthermore, their practice of using antibiotics, including previous antibiotic exposure, their antibiotic use during the past year, reasons for taking antibiotics, ways of obtaining antibiotics, and reasons for discontinuing of antibiotic therapy were also recorded. Results: The pre-intervention assessment revealed poor knowledge and practice regarding antibiotic use. Post-intervention, mean knowledge scores increased significantly from 18.36 to 23.28 (t = 19.5, p < 0.0001), while mean practice scores improved from 9.83 to 12.37 (t = 6.4, p < 0.0001). Conclusions: The intervention successfully improved caregivers' knowledge and practices regarding AMR. However, there are some limitations that could affect the generalization, and the impact of the results such as the relatively small sample size recruited from a single center, lack of a control group, reliance on self-reported data, and lack of long-term follow-up. Future studies should aim to address these constraints in order to assess the intervention's effectiveness.

Background: Infant meningitis, particularly caused by Escherichia coli, remains a life-threatening condition, especially in premature and low-weight infants. Infections of the central nervous system can be fatal, necessitating prompt diagnosis and appropriate treatment. Acute infections caused by various pathogens, including E. coli, often present with similar clinical symptoms. The rapid identification of pathogens and their antimicrobial resistance mechanisms is critical for timely and effective treatment. We report the case of an 8-month-old patient who presented with fever, diarrhea, and convulsive seizures and was subsequently diagnosed with meningitis. Despite initial empirical treatment with ceftriaxone, the patient's condition worsened.

Methods: At Bambino Gesù Children's Hospital, molecular diagnostic tools, including the FilmArray Meningitis/Encephalitis and Blood Culture Identification panels, were employed.

Results: Although the Meningitis panel did not detect any pathogens due to the lack of the specific bacterial target, the off-label use of the Blood Culture Identification panel identified a non-K1 Escherichia coli strain carrying the CTX-M resistance gene, an extended-spectrum beta-lactamase (ESBL). Despite the rapid diagnostic approach and adjustment of antibiotic therapy, the patient succumbed to the infection due to the strain's high virulence and multidrug resistance. Whole-genome sequencing further characterized the strain, revealing that it belonged to the ST131 group, a highly resistant and virulent strain associated with sepsis.

Conclusions: This case highlights the importance of integrating advanced molecular diagnostics, such as whole-genome sequencing, with traditional methods to improve pathogen detection, especially in cases of emerging resistant strains that are not covered by standard diagnostic panels. It also emphasizes the need for the continuous adaptation of diagnostic tools to include non-K1 E. coli strains for more comprehensive and timely meningitis diagnosis.

Background: Osteomyelitis is one of the most frequent infections of the diabetic foot, accounting for 20-70% of foot infections. The treatment of osteomyelitis continues to be debated, and the possibility of performing conservative surgery associated with targeted antibiotic treatment allows for reductions in the amount of bone removed, the resolution of osteomyelitis, and a reduction in the changes in the biomechanics of the foot. The objective of this study was to evaluate the outcomes of osteomyelitis treatment with a combination of antibiotic and surgical procedures based on a histopathological analysis of the infected bone and margins. Materials and Methods: We analyzed 25 diabetic patients with osteomyelitis. We treated each patient with empiric antibiotic treatment, surgical removal of the infected bone, and targeted antibiotic treatment. During the surgical procedure, we collected infected bone samples and margins for microbiological and histopathological analyses. Results: All the patients had type 2 diabetes, with a mean age of 71 ± 10 years. Antibiotic therapy was administered orally for an average duration of 21 ± 9 days, aimed at improving the microbiological outcome. Histological examinations of the resected infected bone revealed the presence of osteomyelitis in 23 (92%) patients. The healthy margin sample, surgically assessed as non-infected, was confirmed negative in 80% of cases. At a follow-up of 18 ± 7 months, we achieved complete healing in twenty patients (80%), with an average healing time of 70 ± 41 days. No recurrence of osteomyelitis was observed. Conclusions: The data from this study demonstrate that the combination of targeted antibiotic therapy and conservative surgical treatment is effective in resolving osteomyelitis without recurrence with a very long follow-up. Histological analyses allowed us to confirm the actual presence of osteomyelitis and demonstrate that clinical differentiation during surgery is effective in identifying a healthy margin.

The COVID-19 pandemic has exacerbated the global antimicrobial resistance (AMR) crisis. Consequently, it is more urgent than ever to prioritize AMR containment and support countries in improving the detection, characterization, and rapid response to emerging AMR threats. We conducted a prospective, multicenter study to assess the prevalence of carbapenemase-producing Enterobacterales in infectious processes in Argentina during the post-COVID-19 pandemic period and explore therapeutic alternatives for their treatment (RECAPT-AR study).

Methods: A total of 182 hospitals participated by submitting Enterobacterales clinical isolates to the National Reference Laboratory (NRL) during the first three weeks of November 2021. Inclusion criteria were defined as an ertapenem MIC ≥ 0.5 mg/L, a zone diameter ≤ 22 mm. Carbapenemase genes and those coding for major extended-spectrum β-lactamases were molecularly characterized using multiplex PCR at the NRL. Antibiotic susceptibility testing followed international standards (CLSI and EUCAST).

Results: The NRL analyzed 821 Enterobacterales isolates. Metallo-β-lactamase (MBL, 42.0%) and KPC (39.8%) accounted for 81.8% of carbapenemases, followed by OXA-163 (7.4%), a variant of OXA-48 with additional activity against extended-spectrum cephalosporins, and enzyme combinations (8.3%). These combinations included NDM plus KPC (3.4%), OXA-163 plus KPC (2.4%), and OXA-163 plus NDM (2.1%). Klebsiella pneumoniae was the main species recovered, representing 76% of the isolates. According to the carbapenemase classes or combinations, tigecycline exhibited a susceptibility range of 33-83%, fosfomycin 59-81%, colistin 27-78%, and amikacin 17-81%. Ceftazidime-avibactam (CZA) and imipenem-relebactam (IMR) showed 92% and 98% susceptibility against serine carbapenemases, respectively. Meanwhile, aztreonam-avibactam (AZA) exhibited 96-98% susceptibility against all carbapenemase classes.

Conclusions: A new epidemiological landscape has emerged, characterized by the equivalent circulation of NDM and KPC. K. pneumoniae remains the primary species responsible for their dissemination. The co-production of carbapenemase combinations, particularly KPC plus NDM, was confirmed, mainly in K. pneumoniae. High activity was observed for AZA against MBLs and for CZA and IMR against KPC and OXA-163 carbapenemases.

CRISPR/Cas systems have emerged as valuable tools to approach the problem of antimicrobial resistance by either sensitizing or lysing resistant bacteria or by aiding in antibiotic development, with successful applications across diverse organisms, including bacteria and fungi. CRISPR/Cas systems can target plasmids or the bacterial chromosome of AMR-bacteria, and it is especially necessary to have an efficient entry into the target cells, which can be achieved through nanoparticles or bacteriophages. Regarding antibiotic development and production, though the use of CRISPR/Cas in this field is still modest, there is an untapped reservoir of bacterial and fungal natural products, with over 95% yet to be characterized. In Streptomyces, a key antibiotic-producing bacterial genus, CRISPR/Cas has been successfully used to activate silent biosynthetic gene clusters, leading to the discovery of new antibiotics. CRISPR/Cas is also applicable to non-model bacteria and different species of fungi, making it a versatile tool for natural products discovery. Moreover, CRISPR/Cas-based studies offer insights into metabolic regulation and biosynthetic pathways in both bacteria and fungi, highlighting its utility in understanding genetic regulation and improving industrial strains. In this work, we review ongoing innovations on ways to treat antimicrobial resistances and on antibiotic discovery using CRISPR/Cas platforms, highlighting the role of bacteria and fungi in these processes.

Background/objectives: Antibiotic-resistant bacteria pose a significant global public health threat that demands serious attention. The proliferation of antimicrobial resistance (AMR) is primarily attributed to the overuse of antibiotics in humans, livestock, and the agro-industry. However, it is worth noting that antibiotic-resistant genes (ARGs) can be found in all ecosystems, even in environments where antibiotics have never been utilized. African great apes (AGAs) are our closest living relatives and are known to be susceptible to many of the same pathogens (and other microorganisms) as humans. AGAs could therefore serve as sentinels for human-induced AMR spread into the environment. They can potentially also serve as reservoirs for AMR. AGAs inhabit a range of environments from remote areas with little anthropogenic impact, over habitats that are co-used by AGAs and humans, to captive settings with close human-animal contacts like zoos and sanctuaries. This provides opportunities to study AMR in relation to human interaction. This review examines the literature on AMR in AGAs, identifying knowledge gaps.

Results: Of the 16 articles reviewed, 13 focused on wild AGAs in habitats with different degrees of human presence, 2 compared wild and captive apes, and 1 study tested captive apes alone. Ten studies included humans working with or living close to AGA habitats. Despite different methodologies, all studies detected AMR in AGAs. Resistance to beta-lactams was the most common (36%), followed by resistance to aminoglycosides (22%), tetracyclines (15%), fluoroquinolones (10%), sulphonamides (5%), trimethoprim (5%), macrolide (3%), phenicoles (2%) and fosfomycin (1%).

Conclusions: While several studies suggest a correlation between increased human contact and higher AMR in AGAs, resistance was also found in relatively pristine habitats. While AGAs clearly encounter bacteria resistant to diverse antibiotics, significant gaps remain in understanding the underlying processes. Comparative studies using standardized methods across different sites would enhance our understanding of the origin and distribution of AMR in AGAs.