In situ gels have been developed as an innovative strategy to prolong corneal residence time and enhance drug absorption compared to traditional eye drops. Our study aimed to formulate an ophthalmic in situ gel with a combination of two thermosensitive poloxamers, P407 and P188, in an optimal ratio not only to increase the time of action but also to increase the solubility of selected antibiotics for the treatment of ophthalmic infections. Two BSC II class substances, Azithromycin and Ofloxacin, with different mechanisms of action, have been incorporated into the in situ gel system after determining their solubility. The antibiotics-loaded in situ gel formulation was evaluated for its clarity, pH, rheological properties, and gel characteristics of gelling time, temperature, and capacity. The formulation demonstrated satisfactory clarity, appropriate pH, effective gelation properties in simulated tear fluid, and suitable rheological characteristics. In addition, APIs release insight has been studied through a dissolution test, and the effectivity against sensitive and resistant bacterial strains has been proved through the antimicrobial study. Therefore, our in situ gel system based on thermosensitive poloxamers, with two hydrophobic antibiotics, AZM and OFX, can be considered a valuable approach for ophthalmic drug delivery with an enhancement of the antibiotics bioavailability through increasing the contact time with the ocular surface and enhancing patient compliance.

Multidrug resistance due to the production of extended-spectrum beta-lactamases (ESBLs) is a major problem in human as well as in veterinary medicine. These strains appear in animal and human microbiomes and can be the source of infection both in animal and in human healthcare, in accordance with the One Health theorem. In this study we examined the prevalence of ESBL-producing bacteria in food-producing animals. We collected 100 porcine and 114 poultry samples to examine the prevalence of ESBL producers. Isolates were identified using the MALDI-TOF system and their antibiotic susceptibility was tested using the disk diffusion method. ESBL gene families and phylogroups were detected by polymerase chain reactions. The prevalence of ESBL producers was relatively high in both sample groups: 72 (72.0%) porcine and 39 (34.2%) poultry isolates were ESBL producers. Escherichia coli isolates were chosen for further investigations. The most common ESBL gene was CTX-M-1 (79.3%). Most of the isolates belong to the commensal E. coli phylogroups. The porcine isolates could be divided into three phylogroups, while the distribution of the poultry isolates was more varied. In summary, ESBL-producing bacteria are prevalent in the faecal samples of the examined food-producing animals, with a dominance of the CTX-M-1 group enzymes and commensal E. coli phylogroups.

Candida auris is a multidrug-resistant fungus against which in some clinical situations amphotericin B (AMB) remains the alternative or first line drug. We compared daily 1 mg/kg of AMB efficacy in a neutropenic murine bloodstream infection model against 10 isolates representing four C. auris clades (South Asian n = 2; East Asian n = 2; South African n = 2; South American n = 4; two of which were of environmental origin). Five days of AMB treatment significantly increased the survival rates in mice infected with isolates of the East Asian clade, and 1 isolate each from the South African and South American clades (originated from bloodstream), but not in mice infected with the South Asian and 2 environmental isolates from the South American clades. AMB treatment decreased the fungal burden in mice infected with the 2 isolates each from East Asian and South African, and 1 out of 2 bloodstream isolates from South American clades in the hearts (p < 0.01), kidneys (p < 0.01) and brain (p < 0.05). AMB treatment, regardless of clades, significantly decreased colony forming units in the urine at day 3. However, histopathological examination in AMB-treated mice revealed large aggregates of yeast cells in the kidneys and hearts, and focal lesions in the cerebra and cerebelli, regardless of precise C. auris clade. Our clade-specific data confirm that the efficacy of AMB against C. auris is weak, explaining the therapeutic failures in clinical situations. Our results draw attention to the necessity to maximize the killing at the start of treatment to avoid later complications in the heart and central nervous system.

Candida auris is a potential multidrug-resistant pathogen able to cause biofilm-associated outbreaks, where frequently indwelling devices are the source of infections. The number of effective therapies is limited; thus, new, even-combination-based strategies are needed. Therefore, the in vitro efficacy of caspofungin with posaconazole against FKS wild-type and mutant Candida auris isolates was determined. The interactions were assessed utilizing the fractional inhibitory concentration indices (FICIs), the Bliss model, and a LIVE/DEAD assay. Planktonic minimum inhibitory concentrations (pMICs) for the caspofungin–posaconazole combination showed a 4- to 256-fold and a 2- to 512-fold decrease compared to caspofungin and posaconazole alone, respectively. Sessile minimum inhibitory concentrations (sMICs) for caspofungin and posaconazole in combination showed an 8- to 128-fold and a 4- to 512-fold decrease, respectively. The combination showed synergy, especially against biofilms (FICIs were 0.033–0.375 and 0.091–0.5, and Bliss cumulative synergy volumes were 6.96 and 32.39 for echinocandin-susceptible and -resistant isolates, respectively). The caspofungin-exposed (4 mg/L) C. auris biofilms exhibited increased cell death in the presence of posaconazole (0.03 mg/L) compared to untreated, caspofungin-exposed and posaconazole-treated biofilms. Despite the favorable effect of caspofungin with posaconazole, in vivo studies are needed to confirm the therapeutic potential of this combination in C. auris-associated infections.

Trichophyton indotineae is associated with difficult-to-treat, often extensive dermatophytosis and resistance to the commonly used antifungal agents. Successful therapy often necessitates higher than usual doses of systemic therapy for prolonged periods. The spread of this species has gained much attention lately, as several European and other Western hemisphere countries have recently reported their first respective cases or increasing numbers of them. Until recently, this species was not described in Hungary. Here, we report a case caused by this species in a patient with a travel history to an endemic region. The isolate was identified preliminarily by MALDI-TOF mass spectrometry and confirmed by DNA sequencing; furthermore, it was subject to phenotypic antifungal susceptibility testing by broth microdilution to fluconazole, voriconazole, posaconazole, itraconazole, and terbinafine. According to the susceptibility results, the isolate was wild type to all tested agents, including terbinafine which was in line with the sequencing data, and with the uncommon excellent therapeutic response to topical allylamine treatment. This case also further confirms the applicability of the MSI-2 database for the rapid identification of T. indotineae in routine clinical microbiology laboratories as a cost-effective and simple method.

Increasing prevalence of A. baumannii was found in the faecal samples of inpatients without infection caused by A. baumannii (0.15%; 55/7806). The aim of the study was to determine whether there is a relationship between the clinical strains and the increased faecal occurrence. Characteristics of faecal and clinical isolates were compared between 2017 and 2019, and the direction of causality was assessed by Granger causality tests. In the case of the antibiotic resistance, faecal carriage of carbapenem-resistant Acinetobacter baumannii (CRAb) was Granger-caused by prevalence of CRAb in inpatients (F = 15.84, p < 0.001), but inpatient prevalence was not Granger-caused by CRAb faecal carriage (F = 0.03, p = 0.855). Whole genomes of 16 faecal isolates were sequenced by Illumina MiSeq; cgMLST types were determined. In faecal isolates, the occurrence of carbapenem resistance was lower than among the clinical isolates from the same period; only bla_OXA-72 harbouring ST636 and ST492 were detected, and the bla_OXA-23 harbouring ST2 and ST49 strains previously dominant in clinical isolates were absent. Carriage of bla_OXA-72 was linked to pMAL-1-like and pA105-2-like plasmids in ST636 and ST492 isolates, respectively, both in clinical and faecal isolates. The new ST636 and ST492 strains may colonise the gut microbiota of the patients, which thus may play a role as a reservoir.