Balto and Togo during the cold winter of Alaska (1925): the two canine heroes in the fight against diphtheria.

In recent years, diphtheria has re-emerged in areas with inadequate vaccination coverage, and Europe has not been spared with several cases among migrants. Diphtheria is a potentially fatal infection caused mainly by toxigenic strains of Corynebacterium diphtheriae. Due to the high mortality rate, especially among young children, the fight against diphtheria is considered one of the first conquests of immunization. In the history of medicine, there is a unique case of an unconventional response to a diphtheria outbreak in which sled dogs were used to overcome the supply difficulties of diphtheria antitoxin. The mass media followed the medical response to the outbreak and raised audience awareness of public health issues. The facts of Nome, Alaska, in 1925 can serve as a catalyst to rethink conventional responses to diphtheria outbreaks in low-income countries today and promote mass media awareness of public health importance.

Human Campylobacter spp. infections in Italy.

PURPOSE: Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017-2021. METHODS: Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). RESULTS: In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. CONCLUSION: Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity.

Clostridioides difficile infection: history, epidemiology, risk factors, prevention, clinical manifestations, treatment, and future options.

SUMMARYClostridioides difficile infection (CDI) is one of the major issues in nosocomial infections. This bacterium is constantly evolving and poses complex challenges for clinicians, often encountered in real-life scenarios. In the face of CDI, we are increasingly equipped with new therapeutic strategies, such as monoclonal antibodies and live biotherapeutic products, which need to be thoroughly understood to fully harness their benefits. Moreover, interesting options are currently under study for the future, including bacteriophages, vaccines, and antibiotic inhibitors. Surveillance and prevention strategies continue to play a pivotal role in limiting the spread of the infection. In this review, we aim to provide the reader with a comprehensive overview of epidemiological aspects, predisposing factors, clinical manifestations, diagnostic tools, and current and future prophylactic and therapeutic options for C. difficile infection.

Lamivudine, Doravirine, and Cabotegravir Downregulate the Expression of Human Endogenous Retroviruses (HERVs), Inhibit Cell Growth, and Reduce Invasive Capability in Melanoma Cell Lines.

This study explores the impact of antiretroviral administration on the expression of human endogenous retroviruses (HERVs), cell growth, and invasive capability of human melanoma cell lines in culture. We investigated three antiretrovirals-lamivudine, doravirine, and cabotegravir-in A375, FO-1, and SK-Mel-28, BRAF-mutated, and in MeWo, P53-mutated, melanoma cell lines. The findings indicate a general capability of these drugs to downregulate the expression of HERV-K Pol and Env genes and hinder cell viability, mobility, and colony formation capacity of melanoma cells. The antiretroviral drugs also demonstrate selectivity against malignant cells, sparing normal human epithelial melanocytes. The study reveals that the integrase inhibitor cabotegravir is particularly effective in inhibiting cell growth and invasion across different cell lines in comparison with lamivudine and doravirine, which are inhibitors of the viral reverse transcriptase enzyme. The investigation further delves into the molecular mechanisms underlying the observed effects, highlighting the potential induction of ferroptosis, apoptosis, and alterations in cell cycle regulatory proteins. Our findings showed cytostatic effects principally revealed in A375, and SK-Mel-28 cell lines through a downregulation of retinoblastoma protein phosphorylation and/or cyclin D1 expression. Signs of ferroptosis were detected in both A375 cells and FO-1 cells by a decrease in glutathione peroxidase 4 and ferritin expression, as well as by an increase in transferrin protein levels. Apoptosis was also detected in FO-1 and SK-Mel-28, but only with cabotegravir treatment. Moreover, we explored the expression and activity of the stimulator of interferon genes (STING) protein and its correlation with programmed death-ligand 1 (PD-L1) expression. Both the STING activity and PD-L1 expression were decreased, suggesting that the antiretroviral treatments may counteract the detrimental effects of PD-L1 expression activation through the STING/interferon pathway triggered by HERV-K. Finally, this study underscores the potential therapeutic significance of cabotegravir in melanoma treatment. The findings also raise the prospect of using antiretroviral drugs to downregulate PD-L1 expression, potentially enhancing the therapeutic responses of immune checkpoint inhibitors.

Antimicrobial Resistance of Genital Mycoplasma and Ureaplasma: A Multicentre Study Over a 5-Year Period in Italy (2017-2021).

Updated data on genital Mollicutes prevalence and antimicrobial susceptibility can help provide guidance for antibiotic stewardship and set up effective strategies for infection control policies. In this multicentre study, we assessed the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma species (U. parvum/U. urealyticum), analyzing data from 21,210 subjects who provided urogenital samples for Mollicutes detection by culture over a 5-year period (2017-2021) in two high-density urban areas in the North of Italy (i.e., Bologna and Lecco). Overall prevalence of Mollicutes infection was 22.3%, with women showing a significantly higher detection rate than men (p < 0.00001). The prevalence decreased with age (highest prevalence <30 years) and over the years considered. Ureaplasma strains were much more frequently detected (62.3%) compared to MH (8.3%) and to mixed infections (29.4%). Ureaplasma species showed high levels of ciprofloxacin resistance (39.5%), whereas MH strains were nonsusceptible to azithromycin and roxithromycin in about 60% of cases. Over time, a significant decrease of resistance to azithromycin and doxycycline was detected (p < 0.0001 and 0.0004, respectively), in parallel with an important increase of ciprofloxacin-resistance levels (p < 0.0001). Overall, our results revealed that minocycline and josamycin can be first-line drugs for Mollicutes empirical treatment.

Vancomycin-resistant enterococcus bloodstream infection successfully managed with oritavancin and fosfomycin as sequential treatment.

Bloodstream infections caused by vancomycin-resistant enterococci are increasingly reported and a consensus therapy does not exist. Oritavancin has shown good antimicrobial activity against VRE, but its use is mainly limited to skin, soft tissue, and/or bone infections. Fosfomycin is increasingly used for enterococcal infections (including bloodstream infections and endocarditis) as a partner drug given its anti-biofilm and synergistic properties. Recently in vitro and in vivo synergism between oritavancin and fosfomycin against VRE isolates has been demonstrated. Herein we report the case of a hematologic patient with a VRE bloodstream infection successfully treated with oritavancin and fosfomycin as sequential treatment.

The current state of knowledge on dracunculiasis: a narrative review of a rare neglected disease.

Dracunculiasis (Guinea Worm Disease) is a chronic disease that is primarily found in the arid and poor areas of our planet where water supply systems consist of open wells. This parasitic disease is transmitted to humans not only through the consumption of water contaminated with crustaceans harbouring larvae of Dracunculus medinensis, but also through the ingestion of paratenic (frogs) or transport hosts (fish). The natural progression of the disease is caused by adult worms invading connective tissues, leading to blistering and ulceration of the extremities, approximately one year after infection. In 1986, the Guinea Worm Eradication Program (GWEP) was launched and since then, the incidence of the disease has been reduced by over 99%. Indeed, the most recent global report from 2022 shows only 13 cases of human dracunculiasis worldwide, the lowest annual incidence ever reported. The new found knowledge of potential animal reservoirs and the recent discovery of possible edible paratenic hosts could pose challenges to the future eradication of this debilitating disease. Therefore, attempts to eradicate this parasitosis should not be postponed. Intensive research is needed in this neglected area of medicine, now that the goal is within reach.

Enterococcal meningitis associated with Strongyloides infection: a case report and literature review.

Strongyloides stercoralis is an intestinal nematode endemic throughout tropical and subtropical areas, with a life cycle consisting of free-living and parasitic components. Unlike other soil-transmitted nematodes, it is capable of self-infection, which can cause chronic disease that lasts for decades, or cause overwhelming hyperinfection in people taking corticosteroids or other immunosuppressive drugs or who have impaired Th2 cell-mediated immunity, particularly those infected with human T-lymphotropic virus 1. During hyperinfection, a large numbers of larvae have access to the bloodstream, lungs, central nervous system, and other organs. Bacteremia and polymicrobial meningitis can occur due to disruption of the intestinal mucosa and the presence of bacteria on the surface of foreign larvae. Enterococcal meningitis for instance may occur concurrently with strongyloidiasis as a consequence of haematogenous dissemination. We present a clinical case of a 45-year-old, man from Bangladesh, in which co-infection occurred. The patient was not immunocompromized and had no apparent risk factors, which represents the unusual aspect of this case report. A literature review on enterococcal meningitis and Strongyloides coinfection in adult patients was performed encountering 21 cases. Cases have been reviewed and discussed. Clinicians may suspect S. stercoralis co-infection when identifying an enterococcal meningitis in adult patients coming from endemic areas.

Intravenous Fosfomycin for Systemic Multidrug-Resistant Pseudomonas aeruginosa Infections.

Human Pseudomonas infections have high morbidity and mortality rates. Pseudomonas bacteria can cause sepsis or septic shock; they produce biofilm and commonly exhibit a multidrug-resistant phenotype. The choice of antimicrobial therapy in many cases is challenging, and deep knowledge of clinical, microbiological, and pharmacological issues is required. Intravenous fosfomycin is being repurposed in a combination given its favorable pharmacokinetic/pharmacodynamic properties (a small molecule with favorable kinetic both in bloodstream infection and in deep-seated infections), antibiofilm activity, and its interesting synergistic effects with other antimicrobials. Recent literature on epidemiological, microbiological, pharmacological, and clinical data on intravenous fosfomycin therapy against Pseudomonas is herein reviewed and discussed.

New Antimicrobials for Gram-Positive Sustained Infections: A Comprehensive Guide for Clinicians.

Antibiotic resistance is a public health problem with increasingly alarming data being reported. Gram-positive bacteria are among the protagonists of severe nosocomial and community infections. The objective of this review is to conduct an extensive examination of emerging treatments for Gram-positive infections including ceftobiprole, ceftaroline, dalbavancin, oritavancin, omadacycline, tedizolid, and delafloxacin. From a methodological standpoint, a comprehensive analysis on clinical trials, molecular structure, mechanism of action, microbiological targeting, clinical use, pharmacokinetic/pharmacodynamic features, and potential for therapeutic drug monitoring will be addressed. Each antibiotic paragraph is divided into specialized microbiological, clinical, and pharmacological sections, including detailed and appropriate tables. A better understanding of the latest promising advances in the field of therapeutic options could lead to the development of a better approach in managing antimicrobial therapy for multidrug-resistant Gram-positive pathogens, which increasingly needs to be better stratified and targeted.

Endemic Systemic Mycoses in Italy: A Systematic Review of Literature and a Practical Update.

Endemic systemic mycoses such as blastomycosis, coccidioidomycosis, histoplasmosis, talaromycosis, paracoccidioidomycosis are emerging as an important cause of morbidity and mortality worldwide. We conducted a systematic review on endemic systemic mycoses reported in Italy from 1914 to nowadays. We found out: 105 cases of histoplasmosis, 15 of paracoccidioidomycosis, 10 of coccidioidomycosis, 10 of blastomycosis and 3 of talaromycosis. Most cases have been reported in returning travelers and expatriates or immigrants. Thirtytwo patients did not have a story of traveling to an endemic area. Fortysix subjects had HIV/AIDS. Immunosuppression was the major risk factor for getting these infections and for severe outcomes. We provided an overview on microbiological characteristics and clinical management principles of systemic endemic mycoses with a focus on the cases reported in Italy.

Dracunculiasis over the centuries: the history of a parasite unfamiliar to the West.

Dracunculiasis (Guinea Worm Disease) is a terrible disease limited, even historically, to the arid and poor areas of our planet and which in the West has always been seen as an exotic disease and therefore has never taken root in the collective imagination. This parasitosis is transmitted to humans by drinking water contaminated with crustacean harboring larvae of Dracunculus medinensis, a nematode. The natural history of the disease is caused by adult worms invading connective tissues and causing blistering, ulceration and edema. Well known in Ancient Egypt where the disease was endemic in its southern area, was known in Europe mainly from the reports of medical writers starting from the Roman imperial period but without direct knowledge. In Middle age the descriptions of this disease that physicians and surgeons could read on medical books, at the end, were attributed to veterinary parasitic disease. In Modern age only during the colonialist era dracunculiasis was perceived as a problem, however sporadic. In 1986 Guinea Worm Eradication Program (GWEP) was launch without success. Thus, the disappearance of this parasitosis should still be postponed but not abandoned.

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

Diverticular Disease and Rifaximin: An Evidence-Based Review.

There have been considerable advances in the treatment of diverticular disease in recent years. Antibiotics are frequently used to treat symptoms and prevent complications. Rifaximin, a non-absorbable antibiotic, is a common therapeutic choice for symptomatic diverticular disease in various countries, including Italy. Because of its low systemic absorption and high concentration in stools, it is an excellent medicine for targeting the gastrointestinal tract, where it has a beneficial effect in addition to its antibacterial properties. Current evidence shows that cyclical rifaximin usage in conjunction with a high-fiber diet is safe and effective for treating symptomatic uncomplicated diverticular disease, while the cost-effectiveness of long-term treatment is unknown. The use of rifaximin to prevent recurrent diverticulitis is promising, but further studies are needed to confirm its therapeutic benefit. Unfortunately, there is no available evidence on the efficacy of rifaximin treatment for acute uncomplicated diverticulitis.

Pylephlebitis: A Systematic Review on Etiology, Diagnosis, and Treatment of Infective Portal Vein Thrombosis.

Pylephlebitis, defined as infective thrombophlebitis of the portal vein, is a rare condition with an incidence of 0.37-2.7 cases per 100,000 person-years, which can virtually complicate any intra-abdominal or pelvic infections that develop within areas drained by the portal venous circulation. The current systematic review aimed to investigate the etiology behind pylephlebitis in terms of pathogens involved and causative infective processes, and to report the most common symptoms at clinical presentation. We included 220 individuals derived from published cases between 1971 and 2022. Of these, 155 (70.5%) were male with a median age of 50 years. There were 27 (12.3%) patients under 18 years of age, 6 (2.7%) individuals younger than one year, and the youngest reported case was only 20 days old. The most frequently reported symptoms on admission were fever (75.5%) and abdominal pain (66.4%), with diverticulitis (26.5%) and acute appendicitis (22%) being the two most common causes. Pylephlebitis was caused by a single pathogen in 94 (42.8%) cases and polymicrobial in 60 (27.2%) cases. However, the responsible pathogen was not identified or not reported in 30% of the included patients. The most frequently isolated bacteria were Escherichia coli (25%), Bacteroides spp. (17%), and Streptococcus spp. (15%). The treatment of pylephlebitis consists initially of broad-spectrum antibiotics that should be tailored upon bacterial identification and continued for at least four to six weeks after symptom presentation. There is no recommendation for prescribing anticoagulants to all patients with pylephlebitis. However, they should be administered in patients with thrombosis progression on repeat imaging or persistent fever despite proper antibiotic therapy to increase the rates of thrombus resolution or decrease the overall mortality, which is approximately 14%.

New polyimidazole ligands against subclass B1 metallo-ß-lactamases: Kinetic, microbiological, docking analysis.

Beta-lactam antibiotics are one of the most commonly used drug classes in managing bacterial infections. However, their use is threatened by the alarming phenomenon of antimicrobial resistance, which represents a worldwide health concern. Given the continuous spread of metallo-ß-lactamases (MBLs) producing pathogens, the need to discover broad-spectrum ß-lactamase inhibitors is increasingly growing. A series of zinc chelators have been synthesized and investigated for their ability to hamper the Zn-ion network of interactions in the active site of MBLs. We assessed the inhibitory activity of new polyimidazole ligands N,N'-bis((imidazol-4-yl)methyl)-ethylenediamine, N,N,N'-tris((imidazol-4-yl)methyl)-ethylenediamine, N,N,N,N'-tetra((imidazol-4-yl-methyl)-ethylenediamine toward three different subclasses B1 MBLs: VIM-1, NDM-1 and IMP-1 by in vitro assays. The activity of known zinc chelators such as 1,4,7,10,13-Pentaazacyclopentadecane, 1,4,8,11-Tetraazacyclotetradecane and 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid was also assessed. Moreover, a molecular docking study was carried to gain insight into the interaction mode of the most active ligands.

Time to reconsider moxifloxacin anti-anaerobic activity?

Large data on moxifloxacin activity on anaerobes are old. Moxifloxacin is often used for empiric therapy therefore the knowledge of current epidemiologic data is fundamental. We analyzed 69 anaerobic strains, from a recent multicenter Italian study, for moxifloxacin susceptibility. Using EUCAST criteria 81% of Bacteroides spp. and 48% of anaerobes other than Bacteroides were resistant to moxifloxacin. Using CLSI criteria moxifloxacin resistance rates decrease to 35% for all anaerobes, and to 41% for Bacteroides spp. We reported an alarming increase in moxifloxacin resistance among anaerobes in Italy.

A combined role for low vitamin D and low albumin circulating levels as strong predictors of worse outcome in COVID-19 patients.

PURPOSE: We aimed to assess the combined role of vitamin D and albumin serum levels as predictors of COVID-19 disease progression. METHODS: We conducted a prospective observational study on adult patients hospitalized for SARS-CoV-2 pneumonia (March-September 2020). Vitamin D and albumin serum levels were measured on admission. These variables were categorized in albumin < 3.5 or ≥ 3.5 g/dL and vitamin D < 30 ng/mL or ≥ 30 ng/mL. We excluded patients with known bone diseases, renal failure, hypercalcemia and/or treated with antiepileptic drugs and steroids, and patients who received previous vitamin D supplementation. A composite outcome including any ventilatory support, PaO2/FiO2 ratio, and 60-day mortality was defined. RESULTS: Sixty-nine patients were enrolled, of whom 50% received non-invasive (NIV) or invasive mechanical ventilation (IMV), 10% died, whereas 89% and 66% presented low albumin and low vitamin D serum levels, respectively. No correlation between vitamin D and albumin levels was found. In multivariable logistic regression analyses adjusted for sex and age-corrected comorbidities, patients having albumin < 3.5 g/dL and vitamin D < 30 ng/mL showed a significant increased risk for all study outcomes, namely NIV/IMV (OR 3.815; 95% CI 1.122-12.966; p = 0.032), NIV/IMV or death (OR 3.173; 95% CI 1.002-10.043; p = 0.049) and PaO2/FIO2 ≤ 100 (OR 3.410; 95% CI 1.138-10.219; p = 0.029). CONCLUSION: The measurement of both vitamin D and serum albumin levels on COVID-19 patients' admission, and their combined evaluation, provides a simple prognostic tool that could be employed to guide prompt clinical decisions.