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.

Human bile microbiota: A retrospective study focusing on age and gender.

AIMS: The emerging biliary colonization of microorganisms in patients with biliary diseases may be devastating. Recent evidence suggests that age and gender may influence changes in the microbial composition of gut microbiota. To study the relationship between these parameters on bile microbiota, we retrospectively reviewed positive bile cultures following an endoscopic retrograde cholangiopancreatography (ERCP) in a QA-certified academic surgical unit of a single institution. METHODS: 449 positive bile cultures from 172 Italian patients with diseases of the biliopancreatic system hospitalized from 2006 through 2017 were investigated for aerobic, anaerobic, and fungal organisms. The patients were stratified into four age intervals (22-66, 67-74, 75-81, and 82-93 years) and followed up for five years. RESULTS: Gram-positive bacteria (GPB) was negatively associated with age only in multivariate analysis (Rpartial = -0.114, p = 0.017), with younger patients prone to harbor GPB and older patients likely to have Gram-negative bacteria (GNB). There was a definite link with the male gender using both univariate and multivariate analysis (p < 0.001). Enterococcus spp. was the most common strain identified in patients with GPB except for patients aged 67-74 years for male (95.2%) and female (80.9%) patients. Escherichia coli and Klebsiella spp. were most frequent than others in every group analyzed. Analogous results were found for bacteria Non-fermenting Gram-negative bacilli (NFGNB), such as Pseudomonas spp. and Stenotrophomonas spp. apart of the 2nd quartile. CONCLUSIONS: Our study strengthens the bond of age and gender with bile microbiota composition and suggests that further investigations may be required in targeting the aging microbiome. Other studies should also focus on Mediterranean epidemiological characteristics and antibiotic resistance surveillance system strategies.

Investigation and control of a Norovirus outbreak of probable waterborne transmission through a municipal groundwater system.

During March 2011 an outbreak of gastroenteritis occurred in Santo Stefano di Quisquina, Agrigento, Sicily, Italy. Within two weeks 156 cases were identified among the 4,965 people living in the municipality. An epidemiological investigation was conducted to characterize the outbreak and target the control measures. A case was defined as a person developing diarrhea or vomiting during February 27-March 13, 2011. Stool specimens were collected from 12 cases. Norovirus (NoV) genotype GII.4 variant New Orleans 2009 was identified in stool samples from 11 of 12 cases tested (91.7%). Epidemiological investigations suggested a possible association with municipal drinking water consumption. Water samples from the public water system were tested for NoV and a variety of genotypes were detected during the first 3 months of surveillance, including GII.4 strains belonging to different variants from that involved in the gastroenteritis outbreak. Contamination of the well and springs supplying the public water network was eventually thought to be the source of the NoV contamination.

Estimating the burden of hospitalization for pneumococcal pneumonia in a general population aged 50 years or older and implications for vaccination strategies.

Streptococcus pneumoniae is a major cause of human infectious diseases worldwide. Despite this documented evidence, data on pneumococcal disease rates among general populations are scant because of the frequent lack of cultural identification. In this study we propose a model for estimating the burden of pneumococcal pneumonia on hospitalizations. The study was performed by analyzing administrative and clinical data of patients aged 50 years or older, resident in Sicily, and hospitalized, from 2005 to 2012. Demographic information, admission/discharge dates, discharge status, and up to 6 discharge diagnoses coded according to ICD-9 CM were collected for each hospitalized patient. During the 8-year study period, a total of 72,372 hospitalizations with at least one ICD-9 CM diagnosis code suggestive of all-cause pneumonia were recorded. Of these, 1943 (2.7%) hospitalizations had specific ICD-9 CM diagnosis codes for pneumococcal pneumonia. According to the proposed model, 16,541 (22.9%) pneumonia out of all-cause pneumonia was estimated to be attributable to S. pneumoniae. Pneumococcal pneumonia and model-estimated pneumococcal pneumonia had mean hospitalization rates of 13.4 and 113.3/100,000, respectively, with a decreasing temporal trend. The risk of hospitalization for pneumococcal pneumonia was strongly correlated with age (P<0.001). Our model provides data usable to construct suitable decisional models for the decision-makers and could allow to the responsibles of healthcare facilities to assess the budget impact if they hypothesize to offer vaccination for pneumococcal disease to certain cohorts of subjects aged 50 years or older. In our area, the high estimated hospitalization rates among adults aged ≥65 years suggest the need to implement effective preventive strategies (e.g., vaccination) tailored for these groups.

Occult hepatitis B infection in the immigrant population of Sicily, Italy.

In Italy, about 7 % of the resident population is represented by immigrants originating from geographic regions at high endemicity for hepatitis B virus infection. This study aims to assess the prevalence of occult HBV infection (OBI) including the identification of HBV-genotypes in a population of immigrants serologically negative for hepatitis B surface antigen (HBsAg). Between May 2006 and May 2010, 339 immigrants were tested for markers of HBV, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HBV-DNA was tested by using nested-PCR assays on three different genetic region. HBV-DNA was detected in plasma samples of 11/339 (3.2 %) patients. Most of them had no serological markers of HBV infection, 3/58 (5.2 %) were anti-HBc-alone, and 4/13 (30.8 %) were anti-HIV positive. HIV positivity was the only factor independently associated with the higher probability of observing OBI (OR = 16.5, p < 0.001). No HCV co-infected patients were found. Genotype D was detected in 9/11 (81.8 %) OBI cases, while the remaining two (18.2 %) were classified as genotype E. Although OBI was found at lower rate than expected among immigrants from highly endemic countries, anti-HBc alone positivity was confirmed as a sentinel marker of occult HBV infection. Nevertheless, a marked heterogeneity of HBV markers was found among HBV-DNA positive subjects. Our finding evidenced the predominance of HBV-genotype D viral strains among OBI cases, also in those from geographical areas where overt HBV infections are mainly sustained by viral genotypes other than D.

Urban air pollution and emergency room admissions for respiratory symptoms: a case-crossover study in Palermo, Italy.

BACKGROUND: Air pollution from vehicular traffic has been associated with respiratory diseases. In Palermo, the largest metropolitan area in Sicily, urban air pollution is mainly addressed to traffic-related pollution because of lack of industrial settlements, and the presence of a temperate climate that contribute to the limited use of domestic heating plants. This study aimed to investigate the association between traffic-related air pollution and emergency room admissions for acute respiratory symptoms. METHODS: From January 2004 through December 2007, air pollutant concentrations and emergency room visits were collected for a case-crossover study conducted in Palermo, Sicily. Risk estimates of short-term exposures to particulate matter and gaseous ambient pollutants including carbon monoxide, nitrogen dioxide, and sulfur dioxide were calculated by using a conditional logistic regression analysis. RESULTS: Emergency departments provided data on 48,519 visits for respiratory symptoms. Adjusted case-crossover analyses revealed stronger effects in the warm season for the most part of the pollutants considered, with a positive association for PM10 (odds ratio = 1.039, 95% confidence interval: 1.020 - 1.059), SO2 (OR = 1.068, 95% CI: 1.014 - 1.126), nitrogen dioxide (NO2: OR = 1.043, 95% CI: 1.021 - 1.065), and CO (OR = 1.128, 95% CI: 1.074 - 1.184), especially among females (according to an increase of 10 µg/m3 in PM10, NO2, SO2, and 1 mg/m3 in CO exposure). A positive association was observed either in warm or in cold season only for PM10. CONCLUSIONS: Our findings suggest that, in our setting, exposure to ambient levels of air pollution is an important determinant of emergency room (ER) visits for acute respiratory symptoms, particularly during the warm season. ER admittance may be considered a good proxy to evaluate the adverse effects of air pollution on respiratory health.