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Unilateral spastic Cerebral Palsy (UCP) results from congenital brain injury, and Magnetic Resonance Imaging (MRI) has a role in understanding the etiology and severity of brain insult. In UCP, functional impairment predominantly occurs in the upper limb (UL) of the more affected side, where manual ability and dexterity are typically reduced. Also, mirror movements (MMs), are often present in UCP, with a further possible negative functional impact. This study aims to investigate the relationships among neuroanatomical characteristics of brain injury at MRI, manual functional impairment and MMs, in children with UCP. Thirty-five children with UCP participated in the study (20, M = 15, F, mean age 9.2 ± 3.5 years). Brain lesions at MRI were categorized according to the Magnetic Resonance Classification System (MRICS) and by using a semi-quantitative MRI (sqMRI) scale. Gross manual performance was assessed through Manual Ability Classification System (MACS) and the Box and Block Test (BBT), and MMs by Woods and Teuber scale, for both hands. Non-parametric correlation analyses were run to determine the relationship between neuroanatomical and functional features. Regression models were run to explore the contribution of neuroanatomical features and MMs to UL function. Correlation analyses revealed moderate to strong associations between sqMRI scores contralateral to the more affected side and UL functional impairment on MACS and BBT, with more severe brain injuries significantly correlating with poorer function in the more affected hand. No association emerged between brain lesion severity scores and MMs. MRICS showed no association with MACS or BBT, while a significant correlation emerged between MRICS category and MMs in the more affected hand, with brain lesion category that are suggestive of presumed earlier injury being associated with more severe MMs. Finally, exploratory regression analyses showed that neuroanatomical characteristics of brain injury and MMs contributed to the variability of UL functional impairment. This study contributes to the understanding of the neuroanatomical and neurological correlates of some aspects of manual functional impairment in UCP by using a simple clinical brain MRI assessment.

Background: Acquired Brain Injury (ABI) describes a range of brain injuries occurring after birth, including tumor, traumatic brain injury or stroke. Although MRIs are routinely used for diagnosis, prediction of outcome following brain injury is challenging. Quantitative structural information from brain images may provide an opportunity to predict patient outcomes; however, due to the high prevalence of severe pathology in children with ABI, quantitative approaches must be robust to injury severity. Methods: In this pilot cross-sectional study, automated quantitative measures were extracted from the MRIs of a cohort of children with ABI (n = 30, 8–16 years, follow up MRI taken 1.8–13.4 years after time of injury) as well as 36 typically developing controls with no brain injury (7–17 years) using a pathology-robust technique. Measures of brain volume, lesion volume and cortical morphology were associated with concurrent motor, behavioral, visual and communicative function using Least Absolute Shrinkage and Selection Operator (LASSO) regression. Results: These regression models were validated on a separate test set (n = 8 of the ABI cohort), which revealed significant correlations between measures of brain structure with motor, cognitive, visual and communicative function (r = 0.65–0.85, all p

Carbon monoxide (CO) poisoning during pregnancy is a rare occurrence, associated with high maternal and fetal mortality rates. As CO can cross the placenta, leading to intrauterine hypoxia, CO intoxication can result in neurological sequelae and neurologic complications in fetuses who survive. We report a case of a preterm newborn acutely exposed to CO in-utero and delivered by emergent cesarean section at the 31st week of gestation due to the severe burns suffered by the mother following an indoor boiler explosion. As CO has serious adverse effects both on the mother and fetus, it is important to recognize and treat poisoning in a timely manner. Despite maternal blood CO levels, CO intoxication at critical stage of central nervous system development can lead to hypoxic-ischemic lesions, thus interdisciplinary care and follow up for these patients are mandatory.

IntroductionThe achievement of alimentary competencies is a milestone in the development of preterm neonates. Ten percent of neonates

BackgroundCommunication and cognitive impairments are common impediments to participation and social functioning in children with cerebral palsy (CP). Bilateral language networks underlie the function of some high-level language-related cognitive functions.PurposeTo explore the association between receptive vocabulary and white-matter microstructure in the temporal lobes and the central part of the temporo-temporal bundles in children with CP.Materials and methods37 children with spastic motor type CP (mean age 9.6 years, 25 male) underwent a receptive vocabulary test (Peabody Picture Vocabulary Test, PPVT-IV) and 3T MRI. Mean fractional anisotropy (FA) and mean diffusivity (MD) were calculated for the temporal lobes and the interhemispheric bundles traversing the splenium of the corpus callosum and the anterior commissure. Associations between microstructure and receptive vocabulary function were explored using univariable linear regression.ResultsPPVT-IV scores were significantly associated with mean white matter MD in the left temporal lobe, but not the right temporal lobe. There was no association between PPVT-IV and mean white matter FA in the temporal lobes. PPVT-IV scores were not significantly associated with the laterality of these diffusion tensor metrics. Within the corpus callosum, FA, but not MD of the temporo-temporal bundles was significantly associated with the PPVT-IV scores. Within the anterior commissure no equivalent relationship between diffusion metrics and PPVT-IV was found.ConclusionOur findings add further understanding to the pathophysiological basis underlying receptive vocabulary skills in children with CP that could extend to other patients with early brain damage. This study highlights the importance of interhemispheric connections for receptive vocabulary.

Infants and children with neurological impairment, such as cerebral palsy (CP), often experience abnormal ingestion functions, including oropharyngeal dysphagia and gastroesophageal reflux disease, which led to aspiration-related respiratory complications, morbidity, hospitalization, or death. There is a lack of evidence-based, repeatable, infant-friendly instrumental procedures to assess aspiration-risk in infants with CP or other neurological disorders, with also a lack of clinical assessment measures to support the use of more invasive diagnostic techniques. To this purpose, in the current study we explore the feasibility of lung ultrasound (LUS), to assess lung deaeration possibly related to aspiration during meal, in a cohort of 35 subjects affected by CP or other encephalopathies, and 10 controls in the same age-range. We coupled LUS procedure with meal caregiver administration for each child. Our results support the feasibility of this innovative approach in the clinical setting. Exploratory findings revealed a number of lung abnormalities likely related to abnormal ingestion function in subjects. Subgroup analyses revealed possible differences in LUS abnormalities between CP and other encephalopathies, possibly related to different mechanism of disease or dysfunction. Also, some evidences arose about the possible relationship between such LUS abnormalities and feeding and swallowing abilities in CP or other encephalopathies. LUS showed preliminarily feasibility and effectiveness in detecting meal-related LUS abnormalities in a dynamic manner in the clinical setting. This approach demonstrated usefulness as a potential tool for improving assessment and management in complex care of infants and young children with severe neurological disorders.

Cerebral excitability and systemic metabolic balance are closely interconnected. Energy supply to neurons depends critically on glucose, whose fluctuations can promote immediate hyperexcitability resulting in acute symptomatic seizures. On the other hand, chronic disorders of sugar metabolism (e.g., diabetes mellitus) are often associated with long-term epilepsy. In this paper, we aim to review the existing knowledge on the association between acute and chronic glycaemic imbalances (hyper- and hypoglycaemia) with seizures and epilepsy, especially in the developing brain, focusing on clinical and instrumental features in order to optimize the care of children and adolescents and prevent the development of chronic neurological conditions in young patients.

Childhood apraxia of speech (CAS) is a motor speech disorder often co-occurring with language impairment and complex neurodevelopmental disorders. A cohort of 106 children with CAS associated to other neurodevelopmental disorders underwent a multidimensional investigation of speech and language profiles, chromosome microarray analysis and structural brain magnetic resonance (MR). Our aim was to compare the clinical profiles of children with CAS co-occurring with only language impairment with those who, in addition to language impairment, had other neurodevelopmental disorders. Expressive grammar was impaired in the majority of the sample in the context of similar alterations of speech, typical of the core symptoms of CAS. Moreover, children with complex comorbidities also showed more severe and persistent receptive language deficits. About 25% of the participants harbored copy number variations (CNVs) already described in association to neurodevelopmental disorders. CNVs occurred more frequently in children with complex comorbidities. MR structural/signal alterations were found in a small number of children and were of uncertain pathogenic significance. These results confirm that CAS needs multidimensional diagnostic and clinical management. The high frequency of language impairment has important implications for early care and demands a personalized treatment approach in which speech and language goals are consistently integrated.

Background: 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. Methods: 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. Results: 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. Conclusion: Cross-transmission of the microorganisms is suggested by the phenotypic similarity and genetic correlation between clinical and environmental strains observed in our study.

Obesity is a chronic, complex, and multifactorial disease resulting from the interaction of genetic, environmental, and behavioral factors. It is characterized by excessive fat accumulation in adipose tissue, which damages health and deteriorates the quality of life. Although dietary treatment can significantly improve health, high attrition is a common problem in weight loss interventions with serious consequences for weight loss management and frustration. The strategy used to improve compliance has been combining dietary prescriptions and recommendations for physical activity with cognitive behavioral treatment (CBT) for weight management. This systematic review determined the dropout rate and predictive factors associated with dropout from CBT for adults with overweight and obesity. The data from the 37 articles selected shows an overall dropout rate between 5 and 62%. The predictive factors associated with attrition can be distinguished by demographics (younger age, educational status, unemployed status, and ethnicity) and psychological variables (greater expected 1-year Body Mass Index loss, previous weight loss attempts, perceiving more stress with dieting, weight and shape concerns, body image dissatisfaction, higher stress, anxiety, and depression). Common reasons for dropping out were objective (i.e., long-term sickness, acute illness, and pregnancy), logistical, poor job conditions or job difficulties, low level of organization, dissatisfaction with the initial results, lack of motivation, and lack of adherence. According to the Mixed Methods Appraisal quality analysis, 13.5% of articles were classified as five stars, and none received the lowest quality grade (1 star). The majority of articles were classified as 4 stars (46%). At least 50% of the selected articles exhibited a high risk of bias. The domain characterized by a higher level of bias was that of randomization, with more than 60% of the articles having a high risk of bias. The high risk of bias in these articles can probably depend on the type of study design, which, in most cases, was observational and non-randomized. These findings demonstrate that CBT could be a promising approach for obesity treatment, achieving, in most cases, lower dropout rates than other non-behavioral interventions. However, more studies should be conducted to compare obesity treatment strategies, as there is heterogeneity in the dropout assessment and the population studied. Ultimately, gaining a deeper understanding of the comparative effectiveness of these treatment strategies is of great value to patients, clinicians, and healthcare policymakers.Systematic review registration: PROSPERO 2022 CRD42022369995 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022369995.

Healthy eating habits are the basis for good health status, especially for children and adolescents, when growth and development are still ongoing. Nutrition educational programs are essential to prevent and treat chronic diseases. Nutritional counseling (NC), as a collaborative process between the counselor and the client process, could help to achieve better outcomes. This review aims to collect information about the utilization of NC during childhood and adolescence and to highlight its possible impact on adherence/compliance rates, nutrition knowledge, status and dietary intake. The methods applied in this systematic review followed the instruction of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search in PubMed/Medline, Scopus, Web of Science, LILACS, and Science Direct included observational or randomized studies. RoB 2.0 and Robins-I tools was used for the risk of bias assessment in randomized and non-randomized studies, respectively. The quality of evidence was checked by the Mixed Methods Appraisal Tool system. A total of 21 articles were selected, computing 4,345 individuals. 11 achieved at least 4 stars quality level. The highest risk of bias for randomized studies was related to the randomization process. 42.9% of non-randomized studies had some concerns of bias, mainly because of a lack of control of all confounding factors. Different strategies of NC were used in children and adolescents with positive results for health or diseases. NC strategies can be effectively used in children and adolescents. In general, NC showed benefits in pediatrics age for anthropometric or body composition parameters, dietary intake, nutrition knowledge and physical activity improvement. Performing NC in pediatrics is challenging due to the counseling strategies that must be adapted in their contents to the cognitive ability of each age. More structured research must be done focused on this population. Investments in healthy eating behaviors in pediatrics can lead to better health outcomes in the future population with substantial benefits to society.Systematic review registration[https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42022374177].

Many studies report poor adherence to sports nutrition guidelines, but there is a lack of research on the effectiveness of nutrition education and behavior change interventions in athletes. Some studies among athletes demonstrate that nutrition education (NE), often wrongly confused with nutritional counseling (NC), alone is insufficient to result in behavior change. For this reason, a clear distinction between NC and NE is of paramount importance, both in terms of definition and application. NE is considered a formal process to improve a client’s knowledge about food and physical activity. NC is a supportive process delivered by a qualified professional who guides the client(s) to set priorities, establish goals, and create individualized action plans to facilitate behavior change. NC and NE can be delivered both to individuals and groups. To our knowledge, the efficacy of NC provided to athletes has not been comprehensively reviewed. The aim of this study was to investigate the current evidence on the use and efficacy of nutritional counseling within athletes. A systematic literature review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses method. The search was carried out in: PubMed, Scopus, Web of Science, Science Direct, Cochrane Library between November 2022 and February 2023. Inclusion criteria: recreational and elite athletes; all ages; all genders; NC strategies. The risk of bias was assessed using the RoB 2.0 Cochrane tool. The quality of evidence checking was tested with the Mixed Methods Appraisal Tool system. From 2,438 records identified, 10 studies were included in this review, with athletes representing different levels of competition and type of sports. The most commonly applied behavior change theory was Cognitive Behavioral Theory. NC was delivered mainly by nutrition experts. The duration of the intervention ranged from 3 weeks to 5 years. Regarding the quality of the studies, the majority of articles reached more than 3 stars and lack of adequate randomization was the domain contributing to high risk of bias. NC interventions induced positive changes in nutrition knowledge and dietary intake consequently supporting individual performance. There is evidence of a positive behavioral impact when applying NC to athletes, with positive effects of NC also in athletes with eating disorders. Additional studies of sufficient rigor (i.e., randomized controlled trials) are needed to demonstrate the benefits of NC in athletes.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022374502.

ABSTRACT: Objectives: Ceftolozane/tazobactam (C/T) is a novel cephalosporin and β-lactamase inhibitor combination with great activity against Pseudomonas aeruginosa. To assess P. aeruginosa susceptibility to C/T, a surveillance study was conducted from October 2018 to March 2019 at the University Hospital ‘Ospedali Riuniti’ in Ancona, Italy. Methods: Minimum inhibitory concentrations (MICs) to C/T were determined by Etest strip. Resistant isolates were characterized by phenotypic (broth microdilution antimicrobial susceptibility testing and modified Carbapenem Inactivation Method [mCIM]) and genotypic (Polymerase Chain Reaction [PCR], Pulsed Field Gel Electrophoresis [PFGE], and whole-genome sequencing [WGS]) methods. Clinical variables of patients infected by C/T-resistant P. aeruginosa were collected from medical records. Results: Fifteen of 317 P. aeruginosa collected showed resistance to C/T (4.7%). Ten strains demonstrated carbapenemase activity by mCIM method, and PCR confirmed that eight strains harbored a blaVIM gene while the other two were positive for blaIMP. Additionally, three isolates carried acquired extended spectrum β-lactamase genes (two isolates carried blaPER and one carried blaGES). Eight strains were strictly related by PFGE and WGS analysis confirmed that they belonged to sequence type (ST)111. The other STs found were ST175 (two isolates), ST235 (two isolates), ST70 (one isolate), ST621 (one isolate), and the new ST3354 (one isolate). Most patients had received previous antibiotic therapies, carried invasive devices, and experienced prolonged hospitalization. Conclusion: This study demonstrated the presence of C/T-resistant P. aeruginosa isolates in a regional hospital carrying a number of resistance mechanisms acquired by different high-risk clones.

Currently available data suggest that the union of a balanced diet and an overall healthy lifestyle may determine an amelioration in several clinical parameters and in the quality of life for patients with MS (pwMS). The study objective was to investigate the possible difference in MS severity in a group of Italian patients with MS based on their adherence to Mediterranean Diet (MedDiet). Eating habits were collected through a validated 110-items Food Frequency Questionnaire, the Medi-Lite score was used for adherence to MedDiet evaluation. MS severity was graded according to Herbert’s severity scale, based on the MSSS. 106 patients were classified in 3 groups according to their MedDiet adherence (low/medium/high). Higher adherence was associated with a 6.18 (95% CI: 1.44, 26.59) higher probability of having a mild-to-moderate MS. When studying the single constituents of the Medi-Lite score, none of them was individually associated with MS severity. It remains unclear whether effects of specific dietary components included in the MedDiet may impact the health status at disease onset or can slow down the symptoms due course of disease. Future studies are needed to reproduce our findings and should focus on answering the latter raised question.

Background: several strategies are used to assess adherence to ketogenic dietary therapies (KDTs), the most commonly used being ketonemia or ketonuria, despite their limitations. The purpose of this article is to carry out an exploratory and confirmatory factor analysis on the proposed Keto-check (adherence’s KDT Brazilian questionnaire). Methods: there was a methodological study of a quantitative nature, complementary to the analysis realized previously, with a complimentary sample. The factorial analysis was performed with Factor software for parallel exploratory analysis, replicability, and confirmatory factor analysis. Graphical representation was created according to the number of factors resulting from the analysis. Results: 116 questionnaires were reached by complementary data collection (n = 69 actual data, complementing n = 47 previous data) through online forms. A polychoric correlation matrix suitability analysis resulted in a significant Bartlett statistic (p = 0.0001) and a Kaiser–Meyer–Olkin (KMO) test of 0.56. The parallel factorial analysis resulted in two factors, graphically represented as “efficacy” and “adherence”. A confirmatory factor analysis, considered fair, indicated an RMSEA of 0.063, NNFI resulted in 0.872, CFI in 0.926, and GFI in 0.897. Conclusion: this study confirms the validity of Keto-check through a more detailed analysis. Adherence is the key to improving the effectiveness of KDTs; therefore, improving knowledge about it can lead to a better healthcare approach.

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.

Aspergillosis, which is mainly sustained by Aspergillus fumigatus, includes a broad spectrum of diseases. They are usually severe in patients with co-morbidities. The first-line therapy includes triazoles, for which an increasing incidence of drug resistance has been lately described. As a consequence of this, the need for new and alternative antifungal molecules is absolutely necessary. As peptides represent promising antimicrobial molecules, two lipopeptides (C14-NleRR-NH2, C14-WRR-NH2) were tested to assess the antifungal activity against azole-resistant A. fumigatus. Antifungal activity was evaluated by determination of minimum inhibitory concentrations (MICs), time–kill curves, XTT assay, optical microscopy, and checkerboard combination with isavuconazole. Both lipopeptides showed antifungal activity, with MICs ranging from 8 mg/L to 16 mg/L, and a dose-dependent effect was confirmed by both time–kill curves and XTT assays. Microscopy showed that hyphae growth was hampered at concentrations equal to or higher than MICs. The rising antifungal resistance highlights the usefulness of novel compounds to treat severe fungal infections. Although further studies assessing the activity of lipopeptides are necessary, these molecules could be effective antifungal alternatives that overcome the current resistances.

Results have been implemented with additional data, which have been commented in the following paragraphs [...]

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 Enterobacterales 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. E. meningoseptica and C. indologenes 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.

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.