Cefiderocol use for the treatment of infections by carbapenem-resistant Gram-negative bacteria: an Italian multicentre real-life experience.

BACKGROUND: Cefiderocol is a novel siderophore cephalosporin with promising activity against most carbapenem-resistant Gram-negative bacteria (CRGNB). However, extensive postmarketing experiences are lacking. This study aimed to analyse the early experience on cefiderocol postmarketing use at three tertiary care hospitals in Italy. METHODS: We retrospectively included patients with infections caused by CRGNB treated with cefiderocol at three Italian tertiary care hospitals from 1 March 2021 to 30 June 2022. A multivariate Cox model was used to identify predictors of 30 day mortality. A propensity score (PS) analysis with inverse probability weighting (IPW) was also performed to compare the treatment effect of cefiderocol monotherapy (CM) versus combination regimens (CCRs). RESULTS: The cohort included 142 patients (72% male, median age 67 years, with 89 cases of Acinetobacter baumannii infection, 22 cases of Klebsiella pneumoniae, 27 cases of Pseudomonas aeruginosa and 4 of other pathogens). The 30 day all-cause mortality was 37% (52/142). We found no association between bacterial species and mortality. In multivariate analysis, a Charlson Comorbidity Index >3 was an independent predictor of mortality (HR 5.02, 95% CI 2.37-10.66, P < 0.001). In contrast, polymicrobial infection (HR 0.41, 95% CI 0.21-0.82, P < 0.05) was associated with lower mortality. There was no significant difference in mortality between patients receiving CM (n = 70) and those receiving a CCR (n = 72) (33% versus 40%, respectively), even when adjusted for IPW-PS (HR 1.11, 95% CI 0.63-1.96, P = 0.71). CONCLUSIONS: Real-life data confirm that cefiderocol is a promising option against carbapenem-resistant Gram-negative infections, even as monotherapy.

The prognostic role of IL-10 in non-severe COVID-19 with chemosensory dysfunction.

OBJECTIVES: Olfactory and gustatory dysfunction (OD/GD) are now recognized as typical symptoms of COVID-19 infection. However, their pathogenesis remains unclear and no clear prognostic factors have been identified. We have analyzed a cohort of mild/moderate hospitalized patients to identify possible clinical or immunological predictors of recovery from OD/GD. METHODS: Clinical and biological parameters were reviewed along with associated comorbidities. Chemosensory Complaint Score was administered on admission and 30 days after the first negative swab. Unpaired Wilcoxon and chi-squared tests were used to compare the variables in the patients who recovered versus those who did not. RESULTS: From a cohort of 119 hospitalized patients, 43 (36%) reported OD/GD on admission. 60.6% had a full recovery from OD and 69.2% from GD. Only the concentration of IL-10 on admission emerged as significantly associated with recovery of taste (p = 0.041) while allergic respiratory disease was more prevalent in the group who did not recover from OD (p = 0.049) and GD (p = 0.007). CONCLUSION: These findings suggest that COVID-19 associated OD/GD is an inflammatory-mediated condition and that clinical and immunological parameters could predict the evolution of these symptoms.

Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic, Florence, Italy, February to March 2020.

We analysed the first 84 coronavirus disease (COVID-19) patients hospitalised in an infectious and tropical disease unit in Florence, Italy, over 30 days after the start of the COVID-19 outbreak in Italy. A 12% reduction in the rate of intensive care unit transfer was observed after the implementation of intensity care measures in the regular ward such as increasing the nurse/patient ratio, presence of critical care physicians and using high flow nasal cannulae oxygenation.

People with HIV pioneers of injectable cabotegravir and rilpivirine long acting in Italy: who are they?

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations.

Efficacy and safety of pentamidine isethionate for tegumentary and visceral human leishmaniasis: a systematic review.

RATIONALE FOR REVIEW: We performed a systematic review of the literature to investigate the efficacy and safety of pentamidine isethionate for the treatment of human tegumentary and visceral leishmaniasis. KEY FINDINGS: A total of 616 papers were evaluated, and 88 studies reporting data on 3108 cases of leishmaniasis (2082 patients with tegumentary leishmaniasis and 1026 with visceral leishmaniasis) were finally included. The majority of available studies were on New World cutaneous leishmaniasis and visceral leishmaniasis caused by Leishmania donovani. At the same time, few data are available for Old World cutaneous leishmaniasis, mucosal leishmaniasis, and visceral leishmaniasis caused by L. infantum. Pooled cure rate for tegumentary leishmaniasis was 78.8% (CI 95%, 76.9-80.6%) and 92.7% (CI 95%, 88.3-97.1%) according to controlled randomized trial and observational studies and case report and case series respectively. Pooled cure rate for visceral leishmaniasis was 84.8% (CI 95%, 82.6-87.1%) and 90.7% (CI 95%, 84.1-97.3%) according to controlled randomized trial and observational studies and case report and case series, respectively. Comparable cure rate was observed in recurrent and refractory cases of visceral leishmaniasis. Concerning the safety profile, among about 2000 treated subjects with some available information, the most relevant side effects were six cases of arrhythmia (including four cases of fatal ventricular fibrillation), 20 cases of irreversible diabetes, 26 cases of muscular aseptic abscess following intramuscular administration. CONCLUSIONS/RECOMMENDATIONS: Pentamidine isethionate is associated with a similar cure rate of the first-line anti-leishmanial drugs. Severe and irreversible adverse effect appear to be rare. The drug may still have a role in the treatment of any form of human leishmaniasis when the first-line option has failed or in patients who cannot tolerate other drugs also in the setting of travel medicine. In difficult cases, the drug can also be considered as a component of a combination treatment regimen.

Use of the FebriDx point-of-care test for the exclusion of SARS-CoV-2 diagnosis in a population with acute respiratory infection during the second (COVID-19) wave in Italy.

OBJECTIVE: Evaluate the real-world accuracy of Myxovirus resistance protein A (MxA) detected by the rapid, point-of-care FebriDx test during the second-wave pandemic in Italy in patients with acute respiratory infection (ARI) and a clinical suspicion of COVID-19. DESIGN AND METHODS: Prospective, observational, diagnostic accuracy study whereby hospitalized patients with ARI were consecutively enrolled in a single tertiary care center in Italy from August 1, 2020 to January 31, 2021. RESULTS: COVID-19 was diagnosed in 136/200 (68.0%) patients and Non-COVID-19 was diagnosed in 64/200 (32.0%) patients. COVID-19 patients were younger and had a lower Charlson comorbidity index compared to Non-COVID-19 patients (p < 0.001). Concordance between FebriDx, MxA and rt-PCR for SARS-CoV-2 (gold standard) was good (k 0.93, 95% CI 0.87-0.99). Overall sensitivity and specificity were 97.8% [95% CI 93.7-99.5] and 95.3% [95% CI 86.9%-99.0%], respectively. FebriDx demonstrated a negative predictive value of 95.3% (95% CI 86.9-99.0) for an observed disease prevalence of 68%. CONCLUSIONS: FebriDx MxA showed high diagnostic accuracy to identify COVID-19 and could be considered as a real-time triage tool to streamline the management of suspected COVID-19 patients. FebriDx also detected bacterial etiology in Non-COVID-19 patients suggesting good performance to distinguish bacterial from viral respiratory infection.

Refractory mucocutaneous leishmaniasis resolved with combination treatment based on intravenous pentamidine, oral azole, aerosolized liposomal amphotericin B, and intralesional meglumine antimoniate.

INTRODUCTION: Mucocutaneous leishmaniasis (MCL) is a complication of tegumentary leishmaniasis, causing potentially life-threatening lesions in the ear, nose, and throat (ENT) region, and most commonly due to Leishmania (Viannia) braziliensis. We report a case of relapsing MCL in an Italian traveler returning from Argentina. CASE DESCRIPTION: A 65-year-old Italian male patient with chronic kidney disease, arterial hypertension, prostatic hypertrophy, and type-2 diabetes mellitus was referred for severe relapsing MCL acquired in Argentina. ENT examination showed severe diffuse pharyngolaryngeal edema and erythema, partially obstructing the airways. A nasopharyngeal biopsy revealed a lymphoplasmacytic inflammation and presence of Leishmania amastigotes, subsequently identified as L. (V.) braziliensis by hsp70 PCR-RFLP analysis and sequencing. Despite receiving four courses of liposomal amphotericine B (L-AmB) and two courses of miltefosine over a 2-year period, the patient presented recurrence of symptoms a few months after the end of each course. After the patient was referred to us, a combined treatment was started with intravenous pentamidine 4 mg/kg on alternate days for 10 doses, followed by one dose per week for an additional seven doses, intralesional meglumine antimoniate on the nasal lesion once per week for six doses, oral azoles for three months, and aerosolized L-AmB on alternate days for three months. The treatment led to regression of mucosal lesions and respiratory symptoms. Renal function temporarily worsened, and the addition of insulin was required to maintain glycemic compensation after pentamidine discontinuation. CONCLUSIONS: This case highlights the difficulties in managing a life-threatening refractory case of MCL in an Italian traveler with multiple comorbidities. Even though parenteral antimonial derivatives are traditionally considered the treatment of choice for MCL, they are relatively contraindicated in cases of chronic kidney disease.The required dose adjustment in cases of impaired renal function is unknown, therefore the use of alternative drugs is recommended. This case was resolved with combination treatment, including aerosolized L-AmB, which had never been used before for MCL.