Dermatophytes are the most common cause of fungal infections worldwide, affecting millions of people annually. The emergence of resistance among dermatophytes along with the availability of ...antifungal susceptibility procedures suitable for testing antifungal agents against this group of fungi make the combinatorial approach particularly interesting to be investigated. Therefore, we reviewed the scientific literature concerning the antifungal combinations against dermatophytes. A literature search on the subject performed in PubMed yielded 68 publications: 37 articles referring to in vitro studies and 31 articles referring to case reports or clinical studies. In vitro studies involved over 400 clinical isolates of dermatophytes (69% Trichophyton spp., 29% Microsporum spp., and 2% Epidermophyton floccosum). Combinations included two antifungal agents or an antifungal agent plus another chemical compound including plant extracts or essential oils, calcineurin inhibitors, peptides, disinfectant agents, and others. In general, drug combinations yielded variable results spanning from synergism to indifference. Antagonism was rarely seen. In over 700 patients with documented dermatophyte infections, an antifungal combination approach could be evaluated. The most frequent combination included a systemic antifungal agent administered orally (i.e., terbinafine, griseofulvin, or azole—mainly itraconazole) plus a topical medication (i.e., azole, terbinafine, ciclopirox, amorolfine) for several weeks. Clinical results indicate that association of antifungal agents is effective, and it might be useful to accelerate the clinical and microbiological healing of a superficial infection. Antifungal combinations in dermatophytes have gained considerable scientific interest over the years and, in consideration of the interesting results available so far, it is desirable to continue the research in this field.
Candida spp. is the major causative agent of fungal infections in hospitalized patients and the fourth most common cause of nosocomial bloodstream infection (BSI). The availability of standardized ...methods for testing the in vitro activity of antifungals along with the expanding of antifungal armamentarium, the rising of drug-resistance and the persistence of a high mortality rate in systemic candidiasis have led to an increased interest in combination therapy. Therefore, we aimed to review the scientific literature concerning the antifungal combinations against Candida. A literature search performed in PubMed yielded 92 studies published from 2000 to 2021: 29 articles referring to in vitro studies, six articles referring to either in vitro and in vivo (i.e., animal models) studies and 57 clinical articles. Pre-clinical studies involved 735 isolates of Candida species and 12 unique types of antifungal combination approaches including azoles plus echinocandins (19%), polyenes plus echinocandins (16%), polyenes plus azoles (13%), polyenes plus 5-flucytosine (5-FC, 13%), azoles plus 5-FC (11%) and other types of combinations (28%). Results varied greatly, often being species-, drug- and methodology-dependent. Some combinatorial regimens exerted a synergistic effect against difficult-to-treat Candida species (i.e., azoles plus echinocandins; polyenes plus 5-FC) or they were more effective than monotherapy in prevent or reducing biofilm formation and in speeding the clearance of infected tissues (i.e., polyenes plus echinocandins). In 283 patients with documented Candida infections (>90% systemic candidiasis/BSI), an antifungal combination approach could be evaluated. Combinations included: azoles plus echinocandins (36%), 5-FC-combination therapies (24%), polyenes plus azoles (18%), polyenes plus echinocandins (16%) and other types of combination therapy (6%). Case reports describing combination therapies yielded favorable response in most cases, including difficult-to-treat fungal infections (i.e., endocarditis, osteoarticular infections, CNS infections) or difficult-to-treat fungal pathogens. The only randomized trial comparing amphotericin-B deoxycholate (AMB) plus FLU vs. AMB alone for treatment of BSI in nonneutropenic patients showed that the combination trended toward improved success and more-rapid clearance from the bloodstream. In summary, antifungal combinations against Candida have produced great interest in the past two decades. To establish whether this approach can become a reliable treatment option, additional in vitro and clinical data are warranted.
Skin and chronic wound infections are an increasing and urgent health problem worldwide. Their management is difficult and the development of antibiotic resistance by both planktonic and ...biofilm-associated bacteria necessitates the use of alternative treatments. The purpose of this study was to compare the antimicrobial activity of four honeys from different floral and geographical origins:
honey (Cuba) and three
honeys Manuka honey (New Zealand),
honey (Cuba), and African honey (Kenya). The physicochemical parameters were within the ranges reported for these honeys and
honey stood out due to its acidic character. An agar incorporation technique was used to determine the minimum active dilution of each honey against 52 clinical isolates (34 Gram-positive, 17 Gram-negative, and 1
). The antibiofilm activity of honeys was tested by assessing their ability to inhibit biofilm formation and to disrupt preformed biofilms. Overall,
honey had the highest antimicrobial and antibiofilm activity, although a marked disruption in preformed biofilms was shared by all tested honeys. Structural changes induced by
honey on
and
cells were observed by transmission electron microscopy suggesting that this honey has a potent antimicrobial action and may be an excellent candidate for the development of topical preparations for the treatment of infected wounds.
E35048, a bloodstream isolate from Italy, was the first strain where the oxazolidinone resistance gene
was detected outside China. The strain was also positive for the oxazolidinone resistance gene
. ...WGS analysis revealed that the two genes were linked (23.1 kb apart), being co-carried by a 41,816-bp plasmid that was named pE35048-oc. This plasmid also carried the macrolide resistance gene
(B) and a backbone related to that of the well-known
plasmid pRE25 (identity 96%, coverage 65%). The
gene context was original,
being part of a composite transposon, named Tn
, which was integrated into the gene encoding for the ζ toxin protein (
of pRE25). The
gene was flanked by two IS
insertion sequences and the element was inserted into an
(E) gene. Both
and
contexts were excisable. pE35048-oc could not be transferred to enterococcal recipients by conjugation or transformation. A plasmid-cured derivative of
E35048 was obtained following growth at 42°C, and the complete loss of pE35048-oc was confirmed by WGS. pE35048-oc exhibited some similarity but also notable differences from pEF12-0805, a recently described enterococcal plasmid from human
also co-carrying
and
; conversely it was completely unrelated to other
- and
-carrying plasmids from
. The
-
linkage is a matter of concern since it could herald the possibility of a co-spread of the two genes, both involved in resistance to last resort agents such as the oxazolidinones.
One hundred forty-five florfenicol-resistant enterococci, isolated from swine fecal samples collected from 76 pig farms, were investigated for the presence of
,
, and
genes by PCR. Thirty ...florfenicol-resistant
isolates had at least one linezolid resistance gene.
was found to be the most widespread linezolid resistance gene (23/30), while
and
were detected in 6/30 and 7/30 enterococcal isolates, respectively. WGS analysis also showed the presence of the
(D) gene in
(
= 2 isolates) and in
(
= 1 isolate). The linezolid resistance genes hybridized both on chromosome and plasmids ranging from ~25 to ~240 kb. Twelve isolates were able to transfer linezolid resistance genes to enterococci recipient. WGS analysis displayed a great variability of
genetic contexts identical or related to transposons (Tn
and Tn
), plasmids (pE035 and pWo27-9), and chromosomal regions.
environments showed identities with Tn
-like transposon and a region from p12-2300 plasmid;
(D) genetic contexts were related to the corresponding region of the plasmid 4 of
E8014;
was always found on Tn
. Circular forms were obtained only for
- and
-carrying genetic contexts. Clonality analysis revealed the presence of
(ST16, ST27, ST476, and ST585) and
(ST21) clones previously isolated from humans. These results demonstrate a dissemination of linezolid resistance genes in enterococci of swine origin in Central Italy and confirm the spread of linezolid resistance in animal settings.
We conducted a 10 years’ retrospective study in 347 symptomatic individuals to assess the regional distribution of leptospirosis. A total of 173 individuals were diagnosed positive (49.8%): 11.5% ...were found positive to Leptospira by microscopic agglutination test positive, whereas 38.3% were found positive by microscopy analysis. The maximum peak of leptospirosis was reached in 2017 (n = 32). The most common serovars were Icterohaemorrhagiae and Poi.
Candidemia is the most common healthcare associated invasive fungal infection. Over the last few decades, candidemia caused by Candida species other than Candida albicans, particularly the Candida ...parapsilosis complex, has emerged worldwide. The aims of this study were: to analyze the genotypic and phenotypic characteristics of C. parapsilosis strains isolated from blood cultures and the environment in a hospital in southern Italy, to study the possible source of infection and to correlate the isolated strains.
From April to October 2022, cases of candidemia due to C. parapsilosis in patients admitted to a hospital in the Apulia region were investigated. However, 119 environmental samples from the intensive care unit were collected for identification of the likely environmental reservoir of infection. Routine antifungal (amphotericin B, anidulafungin, fluconazole) susceptibility was performed on all isolates. Whole genome sequencing was performed to study the genotypic correlation of the isolates. Biofilm biomass and metabolic activity were also quantified for all isolates.
A total of 43 C. parapsilosis isolates were cultured from the bloodstream of each patient in different departments, and seven surface samples were positive for C. parapsilosis. Most of the isolated yeasts (41/50; 85 %) were resistant to fluconazole and were genetically related to each other, suggesting an ongoing clonal outbreak of this pathogen. The fluconazole-susceptible isolates produced significantly more biofilm than did the resistant isolates. Metabolic activity was also higher for fluconazole-susceptible than resistant isolates.
Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.
Recently, mineral healing clays have gained much attention for wound-dressing applications. Here, we selected halloysite (HAL) clay as a biocompatible, non-toxic material that is useful as a drug ...delivery system to enhance the healing properties of water-soluble terpenoids 1-3 (T1-3). Terpenoids-loaded HAL clay (TH1-3) was prepared and characterized by adsorption equilibrium studies, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier-transform infrared (FTIR) spectroscopy, and release studies. The results reveal that T1-3 were adsorbed at the HAL surface with good efficiency. The prevalent mechanism of drug retention is due to the adsorption via electrostatic interactions between the cationic groups of the T1-3 and the HAL’s external surface. Release studies demonstrated that T3 was released in a higher percentage (>60%) compared to T1-2 (≈50%). Additionally, TH1-3 were assessed for their antimicrobial activity and capability to promote the re-epithelialization of scratched HaCat monolayers, through the time-kill test and the wound-healing assays, respectively. The results reveal that all the tested formulations were able to reduce the microbial growth after 1 h of incubation and that they ensured complete wound closure after 48 h. Furthermore, at the concentration of 1 µg/mL, TH3 exhibited 45% wound closure at 24 h, compared to TH1 (27%) and TH2 (30%), proving to be the best candidate in making the tissue-repair process easier and faster.
Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced ...extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six
and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time-kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM.
and
were not inhibited by any ATM-BLI combination. ATM-BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.
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