Anti-infective management of infected skin ulcers.

Infected skin ulcers represent a frequent and intricate clinical challenge, necessitating prompt and comprehensive multidisciplinary interventions to avert complications. Anti-infective therapy constitutes a cornerstone in the therapeutic paradigm. This manuscript delineates our approach to anti-infective management of infected ulcers, encompassing insights into clinical classifications, diagnostic features, exampless of early clinical decision-making in anti-infective treatment, comprehensive evaluation of infectious diseases encompassing host clinical considerations and potential interventions, determination of antibiotic therapy duration, methodologies for assessing clinical response, identification of potential causes for lack of clinical response, as well as strategies for outpatient parenteral antibiotic therapy and a diagnostic and therapeutic algorithm.

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.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

When surgical option is not provided: a successful multidisciplinary approach to a refractory case of sternal osteomyelitis following coronary surgery.

PURPOSE: Sternal osteomyelitis is a major complication of cardiac operations performed through median sternotomy. The surgical treatment, which involves the debridement and removal of whole infected and necrotic tissue is the standard of care, although it is sometimes unachievable. This may occur, for instance, when the infectious-inflammatory process invades the anterior mediastinum and tenaciously incorporates one or more of vital anatomical structures. METHODS AND RESULTS: An inoperable case of postoperative sternal osteomyelitis that involved the right ventricle and the right coronary artery, and that was successfully treated using a nonsurgical multidisciplinary approach, is reported here. CONCLUSION: For highly selected patients with sternal osteomyelitis for whom surgery is a too risky option, an approach including the contribution of various specialists might be a viable way out.

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.

Identification of IncA Plasmid, Harboring blaVIM-1 Gene, in S. enterica Goldcoast ST358 and C. freundii ST62 Isolated in a Hospitalized Patient.

In the present study, we analyzed the genome of two S. enterica strains TS1 and TS2 from stool and blood cultures, respectively, and one strain of C. freundii TS3, isolated from a single hospitalized patient with acute myeloid leukemia. The S. enterica Goldcoast ST358 (O:8 (C2-C3) serogroup), sequenced by the MiSeq Illumina system, showed the presence of ß-lactamase genes (blaVIM-1, blaSHV-12 and blaOXA-10), aadA1, ant(2″)-Ia, aac(6')-Iaa, aac(6')-Ib3, aac(6')-Ib-cr, qnrVC6, parC(T57S), and several incompatibility plasmids. A wide variety of insertion sequences (ISs) and transposon elements were identified. In C. freundii TS3, these were the blaVIM-1, blaCMY-150, and blaSHV-12, aadA1, aac(6')-Ib3, aac(6')-Ib-cr, mph(A), sul1, dfrA14, ARR-2, qnrVC6, and qnrB38. IncA plasmid isolated from E.coli/K12 transconjugant and C. freundii exhibited a sequence identity >99.9%. The transfer of IncA plasmid was evaluated by conjugation experiments.

A urokinase-associated outbreak of Ralstonia mannitolilytica bloodstream infections in haemodialysis patients in north-eastern Italy, January to April 2023.

An outbreak of Ralstonia mannitolilytica bloodstream infections occurred in four hospitals in north-eastern Italy, involving 20 haemodialysis patients with tunnelled central vascular catheter access. We identified as the outbreak source a batch of urokinase vials imported from India contaminated with R. mannitolilytica. Whole genome sequences of the clinical and urokinase strains were highly related, and only urokinase-treated patients were reported with R. mannitolilytica infections (attack rate = 34%; 95% confidence interval: 22.1-47.4). Discontinuation of the contaminated urokinase terminated the outbreak.

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.

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.

Molnupiravir, Nirmatrelvir/Ritonavir, or Sotrovimab for High-Risk COVID-19 Patients Infected by the Omicron Variant: Hospitalization, Mortality, and Time until Negative Swab Test in Real Life.

Background. Several drugs which are easy to administer in outpatient settings have been authorized and endorsed for high-risk COVID-19 patients with mild-moderate disease to prevent hospital admission and death, complementing COVID-19 vaccines. However, the evidence on the efficacy of COVID-19 antivirals during the Omicron wave is scanty or conflicting. Methods. This retrospective controlled study investigated the efficacy of Molnupiravir or Nirmatrelvir/Ritonavir (Paxlovid®) or Sotrovimab against standard of care (controls) on three different endpoints among 386 high-risk COVID-19 outpatients: hospital admission at 30 days; death at 30 days; and time between COVID-19 diagnosis and first negative swab test result. Multivariable logistic regression was employed to investigate the determinants of hospitalization due to COVID-19-associated pneumonia, whereas time to first negative swab test result was investigated by means of multinomial logistic analysis as well as Cox regression analysis. Results. Only 11 patients (overall rate of 2.8%) developed severe COVID-19-associated pneumonia requiring admission to hospital: 8 controls (7.2%); 2 patients on Nirmatrelvir/Ritonavir (2.0%); and 1 on Sotrovimab (1.8%). No patient on Molnupiravir was institutionalized. Compared to controls, hospitalization was less likely for patients on Nirmatrelvir/Ritonavir (aOR = 0.16; 95% CI: 0.03; 0.89) or Molnupiravir (omitted estimate); drug efficacy was 84% for Nirmatrelvir/Ritonavir against 100% for Molnupiravir. Only two patients died of COVID-19 (rate of 0.5%), both were controls, one (a woman aged 96 years) was unvaccinated and the other (a woman aged 72 years) had adequate vaccination status. At Cox regression analysis, the negativization rate was significantly higher in patients treated with both antivirals-Nirmatrelvir/Ritonavir (aHR = 1.68; 95% CI: 1.25; 2.26) or Molnupiravir (aHR = 1.45; 95% CI: 1.08; 1.94). However, COVID-19 vaccination with three (aHR = 2.03; 95% CI: 1.51; 2.73) or four (aHR = 2.48; 95% CI: 1.32; 4.68) doses had a slightly stronger effect size on viral clearance. In contrast, the negativization rate reduced significantly in patients who were immune-depressed (aHR = 0.70; 95% CI: 0.52; 0.93) or those with a Charlson index ≥5 (aHR = 0.63; 0.41; 0.95) or those who had started the respective treatment course 3+ days after COVID-19 diagnosis (aOR = 0.56; 95% CI: 0.38; 0.82). Likewise, at internal analysis (excluding patients on standard of care), patients on Molnupiravir (aHR = 1.74; 95% CI: 1.21; 2.50) or Nirmatrelvir/Ritonavir (aHR = 1.96; 95% CI: 1.32; 2.93) were more likely to turn negative earlier than those on Sotrovimab (reference category). Nonetheless, three (aHR = 1.91; 95% CI: 1.33; 2.74) or four (aHR = 2.20; 95% CI: 1.06; 4.59) doses of COVID-19 vaccine were again associated with a faster negativization rate. Again, the negativization rate was significantly lower if treatment started 3+ days after COVID-19 diagnosis (aHR = 0.54; 95% CI: 0.32; 0.92). Conclusions. Molnupiravir, Nirmatrelvir/Ritonavir, and Sotrovimab were all effective in preventing hospital admission and/or mortality attributable to COVID-19. However, hospitalizations also decreased with higher number of doses of COVID-19 vaccines. Although they are effective against severe disease and mortality, the prescription of COVID-19 antivirals should be carefully scrutinized by double opinion, not only to contain health care costs but also to reduce the risk of generating resistant SARS-CoV-2 strains. Only 64.7% of patients were in fact immunized with 3+ doses of COVID-19 vaccines in the present study. High-risk patients should prioritize COVID-19 vaccination, which is a more cost-effective approach than antivirals against severe SARS-CoV-2 pneumonia. Likewise, although both antivirals, especially Nirmatrelvir/Ritonavir, were more likely than standard of care and Sotrovimab to reduce viral shedding time (VST) in high-risk SARS-CoV-2 patients, vaccination had an independent and stronger effect on viral clearance. However, the effect of antivirals or COVID-19 vaccination on VST should be considered a secondary benefit. Indeed, recommending Nirmatrelvir/Ritonavir in order to control VST in high-risk COVID-19 patients is rather questionable since other cheap, large spectrum and harmless nasal disinfectants such as hypertonic saline solutions are available on the market with proven efficacy in containing VST.

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.

Ventilatory associated barotrauma in COVID-19 patients: A multicenter observational case control study (COVI-MIX-study).

BACKGROUND: The risk of barotrauma associated with different types of ventilatory support is unclear in COVID-19 patients. The primary aim of this study was to evaluate the effect of the different respiratory support strategies on barotrauma occurrence; we also sought to determine the frequency of barotrauma and the clinical characteristics of the patients who experienced this complication. METHODS: This multicentre retrospective case-control study from 1 March 2020 to 28 February 2021 included COVID-19 patients who experienced barotrauma during hospital stay. They were matched with controls in a 1:1 ratio for the same admission period in the same ward of treatment. Univariable and multivariable logistic regression (OR) were performed to explore which factors were associated with barotrauma and in-hospital death. RESULTS: We included 200 cases and 200 controls. Invasive mechanical ventilation was used in 39.3% of patients in the barotrauma group, and in 20.1% of controls (p<0.001). Receiving non-invasive ventilation (C-PAP/PSV) instead of conventional oxygen therapy (COT) increased the risk of barotrauma (OR 5.04, 95% CI 2.30 - 11.08, p<0.001), similarly for invasive mechanical ventilation (OR 6.24, 95% CI 2.86-13.60, p<0.001). High Flow Nasal Oxygen (HFNO), compared with COT, did not significantly increase the risk of barotrauma. Barotrauma frequency occurred in 1.00% [95% CI 0.88-1.16] of patients; these were older (p=0.022) and more frequently immunosuppressed (p=0.013). Barotrauma was shown to be an independent risk for death (OR 5.32, 95% CI 2.82-10.03, p<0.001). CONCLUSIONS: C-PAP/PSV compared with COT or HFNO increased the risk of barotrauma; otherwise HFNO did not. Barotrauma was recorded in 1.00% of patients, affecting mainly patients with more severe COVID-19 disease. Barotrauma was independently associated with mortality. TRIAL REGISTRATION: this case-control study was prospectively registered in clinicaltrial.gov as NCT04897152 (on 21 May 2021).

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.

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.

Case report: Long-lasting SARS-CoV-2 infection with post-COVID-19 condition in two patients with chronic lymphocytic leukemia: The emerging therapeutic role of casirivimab/imdevimab.

Post-coronavirus disease 2019 (post-COVID-19) condition, previously referred to as long COVID, includes a post-acute syndrome defined by the presence of non-specific symptoms occurring usually 3 months from the onset of the acute phase and lasting at least 2 months. Patients with chronic lymphocytic leukemia (CLL) represent a high-risk population for COVID-19. Moreover, the response to SARS-CoV-2 vaccination is often absent or inadequate. The introduction of monoclonal antibodies (mAbs) in the treatment landscape of COVID-19 allowed to reduce hospitalization and mortality in mild-moderate SARS-CoV-2 infection, but limited data are available in hematological patients. We here report the effective use of casirivimab/imdevimab (CI) in the treatment of two CLL patients with persistent infection and post-COVID-19 condition. Full genome sequencing of viral RNA from nasopharyngeal swabs was performed at the time of COVID-19 diagnosis and before the administration of CI. Both patients experienced persistent SARS-CoV-2 infection with no seroconversion for 8 and 7 months, respectively, associated with COVID symptoms. In both cases after the infusion of CI, we observed a rapid negativization of the nasal swabs, the resolution of post-COVID-19 condition, and the development of both the IgG against the trimeric spike protein and the receptor-binding domain (RBD) of the spike protein. The analysis of the viral genome in the period elapsed from the time of COVID-19 diagnosis and the administration of mAbs showed the development of new mutations, especially in the S gene. The genome variations observed during the time suggest a role of persistent SARS-CoV-2 infection as a possible source for the development of viral variants. The effects observed in these two patients appeared strongly related to passive immunity conferred by CI treatment permitting SARS-CoV-2 clearance and resolution of post-COVID-19 condition. On these grounds, passive anti-SARS-CoV-2 antibody treatment may represent as a possible therapeutic option in some patients with persistent SARS-CoV-2 infection.

In Vitro and In Vivo Studies of Oritavancin and Fosfomycin Synergism against Vancomycin-Resistant Enterococcus faecium.

Therapeutic options for infections caused by vancomycin-resistant enterococci are currently suboptimal. Combination regimens where fosfomycin is used alongside existing treatments are emerging given the proven synergistic potential and PK/PD properties. In the studies presented here, we tested five vanA and five vanB clinical isolates of Enterococcus faecium using a combination of oritavancin + fosfomycin both in vitro (checkerboard, time killing) and in vivo (Galleria mellonella). The combination of oritavancin and fosfomycin increased drug susceptibility, showing a synergistic effect in 80% of isolates and an additive effect in the remaining isolates. The combination restored fosfomycin susceptibility in 85% of fosfomycin-resistant isolates. Time killing on four selected isolates demonstrated that the combination of oritavancin and fosfomycin provided a CFU/mL reduction > 2 log10 compared with the most effective drug alone and prevented the bacterial regrowth seen after 8−24 h at sub-inhibitory drug concentrations. In addition, the combination was also tested in a biofilm assay with two isolates, and a strong synergistic effect was observed in one isolate and an additive effect in the other. Finally, we demonstrated in vivo (Galleria mellonella) a higher survival rate of the larvae treated with the combination therapy compared to monotherapy (fosfomycin or oritavancin alone). Our study provides preclinical evidence to support trials combining oritavancin and fosfomycin for VRE BSI in humans, even when biofilm is involved.

DM management in HIV patients: the adoption of population health management to transform the chronic management of HIV.

BACKGROUND: The success of antiretroviral therapies has made human immunodeficiency virus (HIV) a chronic disease, changing the care scenario dramatically. This study aimed to measure adherence to diabetes mellitus standards of care provided for people living with HIV (PLWH). Diabetes represents a paradigmatic case for tackling chronic care management in this target group. METHODS: This retrospective observational study was performed on administrative health data retrieved from 2014 to 2016, with a validated algorithm to identify patients with HIV using: (i) hospital discharge records (ICD9-CM codes); (ii) drug dispensing records (with ATC codes); and (iii) disease-specific exemptions from co-payments for healthcare services. HIV-related treatments, comorbidities and health service utilization were measured, as was adherence to clinical guidelines-recommended standards of care for diabetes. RESULTS: A population of 738 cases were identified in two Local Health Authorities in Italy, representing a prevalence of 0.14% of the general population, in line with the expected prevalence. Thirty-one cases of HIV patients diagnosed with diabetes were identified, a prevalence ratio of 4.2% compared to the 8% in the overall population. Adherence to diabetes standards of care tested within the same population was low, with the exception of those tests commonly administered for standard HIV follow-up care. CONCLUSIONS: The use of administrative data, combined with a Population Health Management approach represents a powerful tool for evaluating system capacity to manage HIV comorbidities. Study findings prove that it is time to design new care models for PLWH, affected by one or more chronic conditions, both to prevent their onset and to manage their comorbidities.