Synthesis and Antibacterial Activity of Mono- and Bi-Cationic Pyridinium 1,2,4-Oxadiazoles and Triazoles.

One of the main causes of mortality in humans continues to be infectious diseases. Scientists are searching for new alternatives due to the fast increase in resistance of some harmful bacteria to the frontline antibiotics. To effectively treat pathogenic infections, it is crucial to design antibiotics that can prevent the development of pathogenic resistance. For this purpose, a set of 39 quaternary pyridinium and bis-pyridinium salts with different lengths of side alkyl or fluorinated chains, heterocyclic spacers, and counter ions were tested on diverse reference bacterial ATCC (American Type Culture Collection) strains, such as S. aureus and E. coli. Subsequently, 6 out of the 39 pyridinium salts showing relevant MIC (Minimum Inhibitory Concentration) values were tested on clinically isolated, resistant strains of S. aureus, S. epidermids, S. haemolyticus, K. pneumoniae, A. baumannii, and P. aeruginosa. Additional tests have been performed to assess if the minimum concentration detected through MIC assay may limit the growth of biofilms.

Genotyping and Antifungal Susceptibility of Dipodascus capitatus Isolated in a Neonatal Intensive Care Unit of a Sicilian Hospital.

In August 2015, Dipodascus capitatus was isolated from two patients admitted to the neonatal intensive care unit. Nosocomial acquisition of the fungus was suspected and epidemiological studies were undertaken. The patients were simultaneously hospitalized, and the comparison of the two isolates by two independent molecular typing methods have confirmed clonal dissemination of a single strain of D. capitatus. Antimicrobial susceptibility testing was useful for identifying the appropriated antifungal therapy in micafungin. To our knowledge these are the first described cases of neonatal D. capitatus infection and also the first report of successful treatment by micafungin.

Biofilm production in Staphylococcus epidermidis strains, isolated from the skin of hospitalized patients: genetic and phenotypic characteristics.

A major virulence factor of Staphylococcus epidermidis is its ability to form biofilms, permitting it to adhere to a surface and, in turn, to form a mucoid layer on polymer surfaces. Multiple factors have been found to influence bacterial attachment. Currently, this bacterium is commonly associated with hospital infections as a consequence of its ability to colonize, albeit accidentally, medical devices. This study investigated the genetic and phenotypic formation of biofilm in 105 S. epidermidis strains isolated from the skin of hospitalized patients. Fifty-eight of these patients were positive for the mecA gene (MRSE) and 47 were found to be negative (MSSE). Genetic characterizations were performed for the detection of the mecA, icaADBC, atlE, aap, bhp, IS256 and agr groups by PCR. Biofilm production was examined by culturing the strains in TBS medium and TBS with 0.5 and 1% respectively of glucose, and a semiquantitative assay on tissue culture plates was used. Although a molecular analysis estimate of detailed biofilm formation is costly in terms of time and complexity, a semiquantitative assay can be proposed as a rapid and cheap diagnostic method for initial screening to discover virulent strains. We confirmed a close correlation between genetic and phenotypic characteristics, highlighting the fact that, when S. epidermidis isolates were cultured in TSB with 1% of glucose, an increase in biofilm production was observed, as confirmed by positivity for the ica locus by molecular analysis.

Is Oral Microflora Related to Development of Malfunction in Patients Using Voice Prosthesis?

Background: this prospective study investigated the correlation between the oral bacterial microflora and the microflora found in voice prostheses (VPs) among 20 patients who had undergone laryngectomy. The aim was to explore the associations between the microflora's presence and the malfunction of VPs, along with the association between the predominant microorganism and the longevity of VPs. Methods: the research process included gathering medical histories, conducting ENT examinations, replacing VPs, and performing check-ups every four months for a period of 15.5 months. Additionally, microbiological examinations, blood tests, and voice change surveys were conducted. Results: a correlation between the microflora isolated from VPs and that from oral rinses was demonstrated in a large percentage of patients who experienced a loss of prosthetic functional efficiency. The correlation analysis between the type of microorganism and the lifespan of VPs showed a non-significant Pearson correlation coefficient (r = 0.043, p = 0.678). Conclusions: there is no significant linear correlation between the predominant microorganism and the average lifespan of VPs.

Cephalosporin resistant Escherichia coli from cancer patients in Cairo, Egypt.

Cephalosporin-resistant Escherichia coli has been increasingly reported worldwide. In this study, 32 cephalosporin resistant E. coli isolates identified from cancer patients in Cairo, Egypt in 2009-2010 were analyzed. Twenty-three were of phylogenetic group D, seven A and one each B1 and B2. By rep-PCR 15 phylogroup D isolates were grouped in four clusters, one with sequence type (ST) 405 and three ST68. Seventeen isolates showed single patterns. blaCTX-M-15 and aac(6')-Ib-cr were the most common resistance determinants. blaOXA-48 and blaVIM were also detected. Multidrug resistant E. coli seriously affects healthcare, especially in immunocompromised hosts, such as cancer patients.

Panton-Valentine leukocidin positive sequence type 80 methicillin-resistant Staphylococcus aureus carrying a staphylococcal cassette chromosome mec type IVc is dominant in neonates and children in an Algiers hospital.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major antimicrobial drug-resistant pathogen causing serious infections. It was first detected in healthcare settings, but in recent years it has also become disseminated in the community. Children and young adults are most susceptible to infection by community-acquired (CA) MRSA strains. In this study 25 MRSA isolates implicated in infections of neonates and children admitted to an Algiers hospital during an 18 month period were characterized by molecular methods including staphylococcal cassette chromosome (SCC) mec typing, PCR amplification of pvl genes, pulsed field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Fifteen out of 25 isolates were from hospital-acquired infections. Twenty-four isolates carried SCCmec type IVc and belonged to the sequence type (ST) 80, one isolate carried SCCmec type II and was ST 39. Twenty-two out of 24 ST80-MRSA-IVc isolates carried pvl genes. Our results suggest that the Panton-Valentine leukocidin positive ST80- MRSA-IVc is the dominant MRSA clone causing disease in neonates and children in Algiers.

An Uncommon Case of Syphilis With Simultaneous, Different Lesions: Moth-Eaten Alopecia, Syphilitic Keratoderma, and Psoriasiform Syphilis.

Syphilis is a re-emerging disease, and an increasing number of cases are being reported in Italy and worldwide. In this report, we present a case of a male patient with secondary syphilis characterized by the heterogenicity of the lesions: hyperkeratosis, psoriasiform-like lesions, papules, macules, and patchy alopecia on the scalp. The patient had applied several topical antimicrobials and steroid medicaments and taken oral acyclovir, which yielded no relief, for a previous wrong diagnosis. At the time of his presentation to our clinic, syphilis was suspected and confirmed by serology. The administration of a single intramuscular dose of penicillin led to a full recovery in three weeks. Screening for HIV and other sexually transmitted infections returned negative. Clinicians should maintain a high index of suspicion for syphilis when encountering sexually active patients with atypical skin manifestations.

Arginine-Rich Peptidomimetic Ampicillin/Gentamicin Conjugate To Tackle Nosocomial Biofilms: A Promising Strategy To Repurpose First-Line Antibiotics.

Combined therapy with penicillins and aminoglycosides has been proved beneficial to address many persistent bacterial infections with possible synergistic effects. However, the different pharmacokinetic profiles of these two antibiotic classes may not guarantee a concerted spatio-temporal delivery at the site of action, decreasing the efficacy of this combination and promoting resistance. Herein, we propose a multifunctional antibiotic-polymer conjugate, designed to colocalize ampicillin and gentamicin to tackle persistent biofilm infections. The two antibacterial molecules were grafted along with the amino acid l-arginine to a biocompatible polymer backbone with peptidomimetic hydrophilic structure, obtaining the antimicrobial poly(argilylaspartamide-co-aspartic) acid-ampicillin, gentamicin (PAA-AG) conjugate. The PAA-AG conjugate displayed excellent biocompatibility on human cell lines if compared with free drugs, potentially enlarging their therapeutic window and safety, and suitable mucoadhesive characteristics which may help local treatments of mucosal infections. Studies on planktonic cultures of clinical and reference strains of S. aureus, P. aeruginosa, and E. coli revealed that PAA-AG holds a broad-spectrum antibacterial efficacy, revealing high potency in inhibiting the growth of the tested strains. More interestingly, PAA-AG exhibited excellent antibiofilm activity on both Gram+ and Gram- communities, showing inhibition of their formation at subMIC concentrations as well as inducing the regression of mature biofilms. Given the high biocompatibility and broad antibiofilm efficacy, combined with the opportunity for synchronous co-delivery, the PAA-AG conjugate could be a valuable tool to increase the success of ampicillin/gentamicin-based antibiotic multitherapy.

Hemophagocytic lymphohistiocytosis secondary to histoplasmosis: A case report in a patient with AIDS and recent SARS-CoV-2 infection and minireview.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Serological status for TORCH in women of childbearing age: a decade-long surveillance (2012-2022) in Italy.

Introduction. Serological screening and seroprevalence data for TORCH infections represent a key instrument to estimate immunity and vaccination levels and exposure rates to prevent and treat TORCH congenital infections.Hypothesis. Serology allows us to identify women susceptible to primary infection.Aim. Assess the prevalence of women at risk of primary infections by TORCH pathogens in Palermo, Sicily, Italy, in the decade 2012-2022.Methodology. A retrospective study was performed to evaluate the serological status (IgG and/or IgM) of 2359 women of childbearing age (WCBA), ranging from 16 to 46 years, attending the AOUP 'P. Giaccone' University Hospital of Palermo.Results. The results showed an overall prevalence of anti-TORCH IgG of 90.5 % for herpesvirus (HSV), 81.2 % for rubella virus (RV), 72.1 % for cytomegalovirus (CMV), 20.9 % for Toxoplasma gondii (TOX) and 4.8 % for Treponema pallidum (TP). IgM positivity was 16.9 % for HSV2, 10.3 % for TOX, 4 % for CMV and, 2 % for RV. A recent/active infection by TP was confirmed in 28.3 % of the seropositive women. Our results indicate that only a small percentage of WCBA were subjected to a comprehensive TORCH serological screening, while most WCBA were only tested for a single pathogen. In addition, no significant differences were found in terms of the overall TORCH IgG seroprevalence among different age groups (P>0.05).Conclusion. Identifying WCBA at risk of exposure during pregnancy allows us to prevent and reduce possible congenital infections, providing detailed guidelines and instructions. The results of this study showed that in Italy the risk of acquiring a primary infection by a TORCH agent is still high, therefore effective prevention strategies, including serological screening, should be implemented.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

Polyclonal non multiresistant methicillin resistant Staphylococcus aureus isolates from clinical cases of infection occurring in Palermo, Italy, during a one-year surveillance period.

BACKGROUND: The evolving epidemiology of methicillin resistant Staphylococcus aureus (MRSA) is characterized by the emergence of infections caused by non multiresistant MRSA carrying staphylococcal chromosomal cassette (SCC)mec IV or V in the healthcare settings. A molecular epidemiological analysis of non multiresistant MRSA isolates from four acute general hospitals was performed in Palermo, Italy, during a one year period. METHODS: For the purpose of the study, MRSA isolates were defined as non multiresistant when they were susceptible to at least three classes of non ß-lactam antibiotics. Seventy-five isolates were submitted to antimicrobial susceptibility testing, multilocus sequence typing (MLST) and polymerase chain reaction (PCR) for SCCmec, accessory gene regulator (agr) groups, arginine catabolic mobile element (ACME) and Panton Valentine leukocidin (PVL) toxin genes. For epidemiological typing, Multiple-Locus Variable-Number Tandem Repeat Fingerprinting (MLVF) was performed on all isolates and pulsed field gel electrophoresis (PFGE) on ST8 isolates. RESULTS: Non multiresistant MRSA isolates were isolated from all hospitals. Resistances to ciprofloxacin, macrolides and tetracycline were the most prevalent. MLST attributed 46 isolates with ST22, 13 with ST8, eight with ST1, three with ST50 and three with ST398. SCCmec type IV was found in all isolates. PVL was detected in one ST22 isolate. All isolates tested negative for the ACME element. MLVF identified 31 different patterns, some subtype clusters ranging in size between two and 22 isolates. The closely related PFGE patterns of the ST8 isolates differed from USA300. CONCLUSIONS: A polyclonal circulation of non multiresistant MRSA along with blurring of boundaries between healthcare associated (HA)-MRSA and community associated (CA)-MRSA appear to be occurring in our epidemiological setting. A better understanding of spread of MRSA with the support of molecular typing can provide invaluable information in the epidemiological, microbiological and clinical fields.

Colonization of pressure ulcers by multidrug-resistant microorganisms in patients receiving home care.

Colonization and/or infection with multidrug-resistant microorganisms (MDRO) of pressure ulcers in patients receiving care at home have seldom been investigated. The objective of this study was to assess the prevalence of MDRO colonization in pressure ulcers of patients receiving home care in Palermo, Italy. Vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), and multidrug-resistant Gram-negative bacilli (MDRGN) were isolated, identified, and characterized from pressure ulcers and selected home environment surfaces. Thirty-two patients were enrolled, of whom 12 were under antimicrobial therapy. Five patients had been admitted to hospital in the preceding year. Nineteen patients tested positive for 1 or more MDROs. In particular, 1 patient was colonized by a vanA-containing strain of VRE, 5 by MRSA, and 17 by MDRGN of different species. Our findings suggest that pressure ulcers in home care patients could play a role in bringing MDROs into the community setting.

Ciprofloxacin releasing gellan gum/polydopamine based hydrogels with near infrared activated photothermal properties.

In this work, with the aim to obtain a wound dressing hydrogel, an amine derivative of gellan gum was crosslinked in the presence of 4arm-polyethylenglycole-vinylsulfone. Through this easy and reproducible chemical procedure, a hydrogel with advanced elastic properties and hydrolytic resistance under physiological conditions was obtained. The incorporation of different quantities of polydopamine in the gelling solutions allows to obtain different hydrogels with marked photothermal properties when irradiated with a laser in the near infrared at 810 nm. The organic nanoparticles, reacting with the amino groups of the polysaccharide derivative, contribute to increase the storage moduli of the hydrogels. Ciprofloxacin was loaded into the hydrogel with higher amount of polydopamine and drug delivery experiments were performed to investigate the effect of irradiation on the antibiotic release profile. Antimicrobial studies, evaluated against S. aureus and P. aeruginosa, revealed that generated hyperthermia exerts a direct inhibition on the pathogens growth and, in the case of S. aureus, adjuvates the ciprofloxacin antimicrobial effect.

Socio-Demographic Characteristics and Sexual Behavioral Factors of Patients with Sexually Transmitted Infections Attending a Hospital in Southern Italy.

Sexually transmitted infections (STIs) are a serious global health problem. In Italy, data describing the vulnerability to STIs of specific sexual minorities and the influence of sociodemographic and behavioral determinants are limited, as most infections are not subject to mandatory notification. This retrospective study describes the sociodemographic profile and main sexual behaviors of patients attending a hospital in Palermo (Sicily, Italy) from January 2018 to March 2019 as predictors of STI risk. Patients were divided in subgroups: men-who-have-sex-with-men (MSM), men-who-have-sex-with-women (MSW), bisexual men and females. Data were obtained through an anonymous questionnaire. Patients were tested for chlamydia, syphilis, Mycoplasma genitalium infection, genital herpes and HPV infection. A total of 294 subjects with STIs (male/female ratio about 2:1) were screened. Of the total sample, 79.6% of patients were Italian. MSM accounted for 34.3%, MSW for 29.6%, bisexual men for 5.8% and females for 30.3%. A total of 44.5% of patients had a high education level, 42.5% reported irregular use of condoms, 20.7% reported having had 5-10 partners in the six months prior to the visit and 32.9% were HIV-positive. HPV infection and syphilis were the most prevalent STIs. Conclusions: The most common profile of patients attending our clinic was that of an adult, Italian man with a high level of education, poor use of condoms and a high number of partners. MSM had the highest sex-behavior-related risk for STIs. In addition, our results suggest that all STD teams need to implement counselling topics and recommendations to share with patients, as well as tips on how to approach sexual health education/counselling, thereby promoting patient-centered approaches and educational programs.

A self-sterilizing fluorescent nanocomposite as versatile material with broad-spectrum antibiofilm features.

Hematogenous spread of infections from colonized central intravenous catheters or central lines is a long-recognized problem with infection rates of 2 and 6.8 per 1000 days, respectively. Besides, removal of severe microbial colonization of implanted biomaterials is still a challenge and usually requires invasive operations. Hence, on demand self-sterilizing materials are required to avoid explant of colonized biomaterials and improve patient compliance. Moreover, photoluminescence is needed to make trackable biomaterials, which can be easily monitored upon implanting them in the body. Here, we propose the incorporation of near infrared (NIR) sensitive red-emitting carbon nanodot (CDs) into a polymeric matrix to give rise to innovative biomaterials with self-tracking and photothermal antimicrobial abilities. We obtain a material which can be processed to obtain medical devices using different techniques, among which, for instance, electrospinning. Herein, a proof-of-concept preparation of electrospun scaffolds is reported as it is highly desired in biomedical applications. Beside to confer imaging properties to the scaffold, that would allow an easy control over the in vivo positioning of implanted biomaterials as well as its degradation state and grade of integration with the surrounding native tissues, thanks to the capability to convert NIR light into local heat CDs can be exploited to exert broad-spectrum antimicrobial effect toward several pathogens. The rise in temperature can be easily modulated by controlling the irradiation time to achieve both an in vitro self-sterilization of the device and eventually in vivo destabilization of the microbial colonization. This innovative biomaterial could successfully inhibit biofilm formation and might be used as a powerful tool to treat antibiotic-resistant nature of biofilm-related infections in implanted medical devices.

Candida parapsilosis Infection: A Multilocus Microsatellite Genotyping-Based Survey Demonstrating an Outbreak in Hospitalized Patients.

Microsatellite analysis identifies specific genotypes and the genetic relationship between strains. Our objective was to analyze the genotypes of C. parapsilosis strains isolated on different wards of a Tertiary-Referral University Center. We evaluated 70 C. parapsilosis strains in total, isolated from samples of patients admitted to five different wards over two years (January 2015-December 2016). Eight microsatellite markers were selected, and two multiplex PCR assays were set up for microsatellite analysis. The 70 strains, examined at eight microsatellite loci, showed 46 different multilocus genotypes profiles. A total of 74 alleles were detected, with an average of 9.25 alleles per locus. The most variable loci were CP6 and CP4, with 20 and 15 alleles, respectively. Four clusters were detected in four out of five wards. A significant cluster that involved 16 patients in the General Surgery department was also found in two patients who had been transferred to the General Medicine ward. Two multiplex PCRs allowed us to minimize costs, define genotypes and study the isolates' genetic diversity with extreme accuracy, demonstrating the high discriminative power of the microsatellite markers. Molecular epidemiology constitutes an appropriate tool for evaluating horizontal transmission of C. parapsilosis in different clinical settings. Microsatellite genotyping and the utilization of Bruvo's genetic distance are suitable for detecting and appraising nosocomial fungal infections.

Cluster of Legionnaires' Disease in an Italian Prison.

BACKGROUND: Legionella pneumophila (Lp) is the most common etiologic agent causing Legionnaires' Disease (LD). Water systems offer the best growth conditions for Lp and support its spread by producing aerosols. From 2015 to 2017, the Regional Reference Laboratory of Clinical and Environmental Surveillance of Legionellosis of Palermo monitored the presence of Lp in nine prisons in Western Sicily. During this investigation, we compared Lp isolates from environmental samples in a prison located in Palermo with isolates from two prisoners in the same prison. METHODS: We collected 93 water samples from nine Sicilian prisons and the bronchoalveolar lavages (BALs) of two prisoners considered cases of LD. These samples were processed following the procedures described in the Italian Guidelines for the Prevention and Control of Legionellosis of 2015. Then, genotyping was performed on 19 Lp colonies (17 from water samples and 2 from clinical samples) using the Sequence-Based Typing (SBT) method, according to European Study Group for Legionella Infections (ESGLI) protocols. RESULTS: Lp serogroup (sg) 6 was the most prevalent serogroup isolated from the prisons analyzed (40%), followed by Lp sg 1 (16%). Most of all, in four penitentiary institutions, we detected a high concentration of Lp >104 Colony Forming Unit/Liter (CFU/L). The environmental molecular investigation found the following Sequence Types (STs) in Lp sg 6: ST 93, ST 292, ST 461, ST 728, ST 1317 and ST 1362, while most of the isolates in sg 1 belonged to ST 1. We also found a new ST that has since been assigned the number 2451 in the ESGLI-SBT database. From the several Lp sg 1 colonies isolated from the two BALs, we identified ST 2451. CONCLUSIONS: In this article, we described the results obtained from environmental and epidemiological investigations of Lp isolated from prisons in Western Sicily. Furthermore, we reported the first cluster of Legionnaires' in an Italian prison and the molecular typing of Lp sg 1 from one prison's water system and two BALs, identified the source of the contamination, and discovered a new ST.

Role of environmental and genetic factor interaction in age-related disease development: the gastric cancer paradigm.

The association of Helicobacter pylori (Hp) infection with gastric cancer is well known and might be considered a paradigmatic example of the role that interaction among environmental factors and individual background might play in inducing age-associated disease. To evaluate the role of interaction of Hp infection with genetic background, gastric cancer and chronic gastritis patients as well as random selected controls were typed for five inflammation-related polymorphisms of IL-1 and IL-10 cytokine genes. No association among IL-10 or IL-1 variants with an increased risk of gastric cancer was found, whereas an Hp-independent association of IL-1beta -511T positive genotypes to an increased risk of chronic gastritis was found (Hp-/511T+ OR 1.89, 95% CI: 1.01-3.54; Hp+/-511T+ OR 1.83, 95% CI: 1.05-3.19). Stratification of gastric cancer group according to Hp infection does not allow finding a statistically significant association of Hp+ to the higher histological grading (G3) of gastric cancer (OR 1.54, 95% CI: 0.46-5.11). Our findings seem to confirm that cytokine genetic variants might contribute to determining the background for inflammaging in which H. pylori infection might facilitate cancer development.