Antifungal pipeline: Is there light at the end of the tunnel?

The misuse and overuse of classic antifungals have accelerated the development of resistance mechanisms, diminishing the efficacy of established therapeutic pathways and necessitating a shift towards alternative targets. Despite this pressing need for new treatments, the antifungal drug pipeline has been largely stagnant for the past three decades, primarily due to the high risks and costs associated with antifungal drug development, compounded by uncertain market returns. Extensive research durations, special patient populations and rigorous regulatory demands pose significant barriers to bringing novel antifungal agents to market. In response, the "push-pull" incentive model has emerged as a vital strategy to invigorate the pipeline and encourage innovation. This editorial critically examines the current clinical landscape and spotlights emerging antifungal agents, such as Fosmanogepix, Ibrexafungerp, and Olorofim, while also unraveling the multifaceted challenges faced in new antifungal drug development. The generation of novel antifungals offers a beacon of hope in the battle against antimicrobial resistance, but it is premature to declare them as definitive solutions. Their future role hinges on thorough clinical validation, cost-effectiveness assessments, and continuous post-marketing surveillance. Only through strategic implementation and integration with market strategies we can transform the landscape of antifungal development, addressing both the resistance crisis and the treatment challenges.

Not surprising: a rebound in antibacterial consumption in Europe, with Cyprus and Greece on the podium.

Recent European-wide data place Cyprus and Greece in the highest positions of total antimicrobial consumption. While this level of consumption might be partly attributed to the high rates of infections due to MDR bacteria in these countries, several other reasons should be sought to help apply local measures, to decrease inappropriate and excess antimicrobial use. The present viewpoint aims to provide a roadmap for interventions, by briefly discussing the various factors that underlie antimicrobial use and prescribing practices in Greece and Cyprus.

Brucella Spondylitis: Current Knowledge and Recent Advances.

The most prevalent zoonotic disease is brucellosis, which poses a significant threat for worldwide public health. Particularly in endemic areas, spinal involvement is a major source of morbidity and mortality and can complicate the course of the disease. The diagnosis of Brucella spondylitis is challenging and should be suspected in the appropriate epidemiological and clinical context, in correlation with microbiological and radiological findings. Treatment depends largely on the affected parts of the body. Available treatment options include antibiotic administration for an adequate period of time and, when appropriate, surgical intervention. In this article, we examined the most recent data on the pathophysiology, clinical manifestation, diagnosis, and management of spinal brucellosis in adults.

Endophthalmitis caused by Enterococcus casseliflavus: a systematic review of literature.

Introduction: Enterococcus casseliflavus is a rare pathogen in human infections, despite being widely distributed in natural environments. This systematic review aims to evaluate the evidence related to endophthalmitis caused by E. casseliflavus. Methods: A thorough search of PubMed, PubMed Central, and Scopus databases was conducted, covering the period up to October 2022. Results: A total of 53 records were identified, with 8 studies reporting a total of 21 cases meeting the inclusion criteria. Among these studies, 7 described isolated case reports, while 1 study described 14 cases. The overall quality of the reports was good, as all articles were determined to have low risk of bias. Vancomycin susceptibility was reported in only one case of isolated case reports, while the remaining cases were all vancomycin resistant. With regard to management, in most cases intravenous ampicillin and linezolid were administered, while only one study reported administration of vancomycin. Conclusions: Ophthalmologists should be aware of the potential for E. casseliflavus to cause endophthalmitis infections and the challenges associated with its intrinsic resistance to vancomycin.

In vitro study on the transmission of multidrug-resistant bacteria from textiles to pig skin.

BACKGROUND: The survival of microorganisms on textiles and specifically on healthcare professionals' (HCP) attire has been demonstrated in several studies. The ability of microorganisms to adhere and remain on textiles for up to hours or days raises questions as to their possible role in transmission from textile to skin via HCP to patients. AIM: To evaluate the presence, survival and transmission of different multidrug-resistant bacteria (MDRB) from HCP attire onto skin. METHODS: Three MDRB [methicillin-resistant Staphylococcus aureus (MRSA); vancomycin-resistant Enterococcus faecium (VRE); carbapenem-resistant Klebsiella pneumoniae, CRKP)] were inoculated on textiles from scrubs (60% cotton-40% polyester) and white coat (100% cotton) at concentrations of 108 colony-forming units (CFU), 105 CFU, and 103 CFU per mL. The inoculation of swatches was divided in time intervals of 1 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, and 6 h. At the end of each period, textiles were imprinted onto pig skins and each skin square was inverted onto three different selective chromogenic media. Growth from the pig skin squares was recorded for the 3 MDRB at the three above concentrations, for the whole length of the 6-h experiment. RESULTS: MRSA was recovered from pig skins at all concentrations for the whole duration of the 6-h study. VRE was recovered from the concentration of 108 CFU/mL for 6 h and from 105 CFU/mL for up to 3 h, while showing no growth at 103 CFU/mL. CRKP was recovered from 108 CFU/mL for 6 h, up to 30 min from 105 CFU/mL and for 1 min from the concentration of 103 CFU/mL. CONCLUSION: Evidence from the current study shows that MRSA can persist on textiles and transmit to skin for 6 h even at low concentrations. The fact that all MDRB can be sustained and transferred to skin even at lower concentrations, supports that textiles are implicated as vectors of bacterial spread.