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PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. METHODS: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. RESULTS: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole. CONCLUSION: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.
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Anfotericina B , Antifúngicos , COVID-19 , Unidades de Terapia Intensiva , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/administração & dosagem , Masculino , Feminino , Anfotericina B/administração & dosagem , Anfotericina B/uso terapêutico , Pessoa de Meia-Idade , Idoso , COVID-19/prevenção & controle , COVID-19/complicações , SARS-CoV-2 , Itália/epidemiologia , Triazóis/administração & dosagem , Triazóis/uso terapêutico , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/prevenção & controle , Estudos de CoortesRESUMO
Patients with viral infections are at higher risk to acquire bacterial and fungal superinfections associated with a worse prognosis. We explored this critical point in the setting of patients with severe COVID-19 disease. The study included 1911 patients admitted to intensive care unit (ICU) during a 2-year study period (March 2020-March 2022). Of them, 713 (37.3%) were infected with SARS-CoV-2 and 1198 were negative (62.7%). Regression analysis was performed to determine risk factors associated with the presence of bacterial and/or fungal superinfections in SARS-CoV-2 patients and to evaluate predictors of ICU mortality. Of the 713 patients with SARS-CoV-2 infection, 473 (66.3%) had respiratory and/or bloodstream bacterial and/or fungal superinfections, while of the 1198 COVID-19-negative patients, only 369 (30%) showed respiratory and/or bloodstream bacterial and/or fungal superinfections (p < 0.0001). Baseline characteristics of COVID-19 patients included a median age of 66 (interquartile range [IQR], 58-73), a predominance of males (72.7%), and the presence of a BMI higher than 24 (median 26; IQR, 24.5-30.4). Seventy-four percent (527, 73.9%) had one or more comorbidities and 135 (18.9%) of them had received previous antibiotic therapy. Furthermore, most of them (473, 66.3%) exhibited severe radiological pictures and needed invasive mechanical ventilation. Multivariate logistic regression analysis showed that 1 unit increment in BMI rises the risk of bacterial and/or fungal superinfections acquisition by 3% and 1-day increment in ICU stays rises the risk of bacterial and/or fungal superinfections acquisition by 11%. Furthermore, 1-day increment in mechanical ventilation rises the risk of bacterial and/or fungal superinfection acquisition by 2.7 times. Furthermore, patients with both bacterial and fungal infections had a significantly higher mortality rate than patients without superinfections (45.8% vs. 26.2%, p < 0.0001). Therefore, bacterial and fungal superinfections are frequent in COVID-19 patients admitted to ICU and their presence is associated with a worse outcome. This is an important consideration for targeted therapies in critically ill SARS-CoV-2 infected patients to improve their clinical course.
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Infecções Bacterianas , COVID-19 , Coinfecção , Micoses , SARS-CoV-2 , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/terapia , COVID-19/complicações , COVID-19/mortalidade , COVID-19/terapia , Unidades de Terapia Intensiva , Micoses/epidemiologia , Micoses/mortalidade , Micoses/terapia , Gravidade do Paciente , Estudos Retrospectivos , Resultado do Tratamento , SARS-CoV-2/fisiologiaRESUMO
BACKGROUND: The SARS-nCoV-2019 epidemic has spread since December 2019, quickly gaining worldwide attention. Symptoms consist of fever, cough and breathing difficulties. An increasing number of studies are focusing on neurological manifestations. In addition to the typical ageusia and anosmia, up to 30% of cases can present headache, nausea and vomiting. More serious neurological manifestations, such as encephalitis, thrombosis and cerebral haemorrhage have been reported. CASE DESCRIPTION: We described the case of a 47-year-old man who tested positive for COVID-19 virus in early March 2020. After two negative nasopharyngeal swabs, 41 days after the diagnosis of COVID-19 infection, he developed intense headache with fever, and he was hospitalized. He had subsequent generalized epileptic seizures and intubation was necessary. Contrast Head MRI was negative for brain abscesses or tumours but detected severe vasogenic oedema of the white matter with 10 mm shift of the midline and compression of the right lateral ventricle. Massive cortisone support therapy was ineffective. We diagnosed brain death on day 43 from the infection diagnosis. DISCUSSION: COVID-19 virus can reach the brain, penetrating into the neuronal cells through the interaction between the spike protein S1 and the host ACE-2 receptor, expressed in the capillary endothelium. We believe that in this infection, the pro-inflammatory state induced by the cytokine storm can cause a cerebral cell-mediated response, with subsequent vasodilatation and brain oedema. CONCLUSION: To our knowledge, this is the first description of a delayed onset cell-mediated encephalitis caused by COVID-19 virus after more than 40 days from the diagnosis.
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COVID-19 , Encefalite , Masculino , Humanos , Pessoa de Meia-Idade , COVID-19/complicações , SARS-CoV-2 , Encefalite/diagnóstico por imagem , Encéfalo , CefaleiaRESUMO
Skull base osteomyelitis (SBO) is a potentially life-threatening inflammation of cranial base bony structures of variable origin. Criteria for diagnosis and treatment are still controversial. Demographics, predisposing factors, symptoms, imaging, and clinical, laboratory, histological, and microbiological data of patients managed for SBO at the University Hospital of Brescia (ASST Spedali Civili) between 2002 and 2017 were retrospectively reviewed. Patients were included in different etiological groups. The topographic distribution of magnetic resonance (MR) abnormalities was recorded on a bi-dimensional model of skull base, on which three different patterns of inflammatory changes (edematous, solid, or necrotic) were reported. In patients with a history of radiotherapy, the spatial distribution of SBO was compared with irradiation fields. The association between variables and etiological groups was verified with appropriate statistical tests. A classification tree analysis was performed with the aim of inferring a clinical-radiological diagnostic algorithm for SBO. The study included 47 patients, divided into 5 etiological groups: otogenic (n = 5), radio-induced (n = 16), fungal (n = 14), immune-mediated (n = 6), and idiopathic (n = 6). At MR, five types of topographical distribution were identified (central symmetric, central asymmetric, orbital apex, sinonasal, maxillary). In patients with a history of radiotherapy, the probability to develop SBO was significantly increased in areas receiving the highest radiation dosage. The analysis of patients allowed for design of a classification tree for the diagnosis of SBO. The integration of clinical and radiologic information is an efficient strategy to categorize SBO and potentially guide its complex management.
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Osteomielite/diagnóstico por imagem , Osteomielite/etiologia , Base do Crânio , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteomielite/patologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
SARS-CoV-2 can attack the central nervous system in the early stages of infection. Headache, anosmia, and dysgeusia are common symptoms. Disturbance of consciousness and seizures can occur as complications in case of severe COVID-19. We described the case of a COVID-19 patient admitted for interstitial pneumonia and seizures. MRI showed newly diagnosed demyelinating lesions. High-dose steroid treatment allowed neurological and respiratory recovery. We speculated a delayed immune response induced by SARS-CoV-2. The virus may lead to a SIRS-like immune disorder or play a role of infective trigger. Prompt invasive treatment should be adopted to avoid hypoxic neurotoxicity and prevent CNS injuries.
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BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.
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Antibacterianos/farmacocinética , Infecção Hospitalar/sangue , Infecção Hospitalar/líquido cefalorraquidiano , Daptomicina/farmacocinética , Meningite/sangue , Meningite/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Infecção Hospitalar/tratamento farmacológico , Daptomicina/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Meningite/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
OBJECTIVE: Use of external ventricular drains and lumbar catheters is associated with a risk of ventriculitis and meningitis ranging from 2% to 24% because of lack of standardized diagnostic criteria. We evaluated the prevalence of ventriculitis or meningitis in 13 Italian ICUs. DESIGN: Multicenter, prospective study. SETTING: Thirteen Italian ICUs. PATIENTS: Two hundred seventy-one patients (mean age, 57 yr) receiving a total number of 311 catheters. Two hundred fifty patients (92.2%) had an external ventricular drain, 17 patients (6.3%) had a lumbar catheter, and four patients (1.5%) had both external ventricular drain and lumbar catheter. INTERVENTIONS: ICUs enrolled at least 10 consecutive adult patients with an external ventricular drain or lumbar catheter in place for more than 24 hours. Confirmed cerebrospinal fluid infection was defined by presence of a positive cerebrospinal fluid culture, a cerebrospinal fluid/blood glucose ratio less than 0.5, a neutrophilic cerebrospinal fluid pleocytosis (> 5 cells/µL), and fever. Abnormal cerebrospinal fluid findings with negative cultures were defined as suspected infection. MEASUREMENTS AND MAIN RESULTS: Median duration of device use was 13 days (interquartile range, 8-19). Fifteen patients (5.5%) had a confirmed ventriculitis or meningitis, and 15 patients (5.5%) had a suspected ventriculitis or meningitis. Cerebrospinal fluid glucose and cerebrospinal fluid/blood glucose ratio were lower in patients with confirmed ventriculitis or meningitis and suspected ventriculitis or meningitis; proteins and lactates were significantly higher in confirmed ventriculitis or meningitis. Gram-negative and Gram-positive bacteria were equally cultured. Risk factors for infection were a concomitant extracranial infection (odds ratio, 2.34; 95% CI, 1.01-5.40; p = 0.05) and placement of catheters outside the operation room (odds ratio, 4.01; 95% CI, 0.98-16.50; p = 0.05). CONCLUSIONS: Ventriculitis or meningitis remains a problem in Italian ICUs, and a strategy for reducing the prevalence is worth planning.
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Ventriculite Cerebral/epidemiologia , Drenagem/efeitos adversos , Drenagem/métodos , Unidades de Terapia Intensiva/estatística & dados numéricos , Meningite/etiologia , Glicemia , Catéteres/efeitos adversos , Líquido Cefalorraquidiano/química , Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosAssuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/líquido cefalorraquidiano , Pneumonia Viral/líquido cefalorraquidiano , Betacoronavirus/patogenicidade , Encefalopatias/virologia , COVID-19 , Sistema Nervoso Central/virologia , Infecções por Coronavirus/diagnóstico , Doenças Desmielinizantes/virologia , Humanos , Trombose Intracraniana/virologia , Pandemias , Pneumonia Viral/diagnóstico , SARS-CoV-2RESUMO
The rise of Vancomycin-resistant enterococci (VRE) strains among cellular therapy recipients raises concerns due to increased morbidity, mortality, and hospitalization costs, particularly impacting transplanted patients with diminished survival expectations. Recent research linking lactose to Enterococcus growth and graft-versus-host disease (GVHD) emphasizes the need for data on reducing lactose in the diets of VRE-carrying patients, especially in cellular therapy contexts like CAR-T or allogeneic hematopoietic stem cell transplantation. Responding to elevated VRE positivity rates in rectal swabs among patients in our BMT Unit, a unique nutritional strategy was implemented, introducing lactose-free milk and strictly enforcing lactose-free diets. This approach resulted in a significant reduction in VRE carriers, with a 16% positivity rate in the Lactose Group versus 3.6% in the Lactose-Free Group, as of June 2023. These results indicate the potential efficacy of this innovative nutritional strategy in high-risk departments, such as BMT Units and Intensive Care Units, with implications for reducing isolation strategies and inappropriate antibiotic use in cases of VRE colonization.
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Enterococos Resistentes à Vancomicina , Humanos , Lactose , Infecções por Bactérias Gram-Positivas/prevenção & controle , Masculino , Feminino , Leite/microbiologia , Transplante de Medula ÓsseaRESUMO
Central nervous system infections are among the most severe infectious conditions in the neonatal period and are still burdened by significant mortality, especially in preterm infants and those with a low birth weight or other comorbidities. In this study, we examined the role of fosfomycin-containing antibiotic regimens in neonates with central nervous system infections. We included six neonates over a period of five years: four with meningitis and two with cerebral abscesses. All patients underwent fosfomycin therapy after failing first-line antibiotic regimens. Of the six neonates, two died; two developed neurological and psychomotor deficits and two recovered uneventfully. None of the neonates experienced adverse reactions to fosfomycin, confirming the safety of the molecule in this population. In conclusion, the deep penetration in the central nervous system, the unique mechanism of action, the synergy with other antibiotic therapies, and the excellent safety profile all make fosfomycin an attractive drug for the treatment of neonatal central nervous system infections.
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Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood-brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.
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Background: Meropenem-vaborbactam is a recent and promising option for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections, including those resistant to ceftazidime-avibactam. Methods: We conducted a retrospective analysis of observational data from 19 Italian hospitals on use and outcomes of patients treated with meropenem-vaborbactam for at least ≥24â hours for KPC-Kp infections. Crude and propensity-weighted multiple Cox regression models were performed to ascertain risk factors independently associated with 30-day mortality. Results: The cohort included 342 adults with bloodstream infections (n = 172) and nonbacteremic infections (n = 170), of which 107 were lower respiratory tract infections, 30 were complicated urinary tract infections, and 33 were infections involving other sites. Most infections (62.3%) were managed with meropenem-vaborbactam monotherapy, or in combination with at least 1 other active drug (usually fosfomycin, tigecycline, or gentamicin) (37.7%). The 30-day mortality rate was 31.6% (108/342). In multiple Cox regression model, 30-day mortality was independently associated with septic shock at infection onset, Charlson comorbidity index ≥ 3, dialysis, concomitant COVID-19, and INCREMENT score ≥ 8. Administration of meropenem-vaborbactam within 48â hours from infection onset was a negative predictor of mortality. All predictors, except administration of meropenem-vaborbactam within 48â hours, remained significant when the multiple Cox regression model was repeated after adjustment for the propensity score for receipt of combination therapy. Conclusions: Despite the limits of a retrospective study, the data derived from this multicenter cohort provide additional evidence on the efficacy of meropenem-vaborbactam in treating severe KPC-Kp infections, even when used as monotherapy.
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Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes. Optimizing antimicrobial prescriptions improves treatment effectiveness, increases patients' safety, and minimizes the risk of opportunistic infections (such as Clostridioides difficile) and antimicrobial resistance selection. The growing emergence of multi-drug resistant organisms has caused an impending crisis with alarming implications, especially regarding Gram-negative bacteria. The Multidisciplinary and Intersociety Italian Council for the Optimization of Antimicrobial Use promoted a consensus conference on the antimicrobial management of IAIs, including emergency medicine specialists, radiologists, surgeons, intensivists, infectious disease specialists, clinical pharmacologists, hospital pharmacists, microbiologists and public health specialists. Relevant clinical questions were constructed by the Organizational Committee in order to investigate the topic. The expert panel produced recommendation statements based on the best scientific evidence from PubMed and EMBASE Library and experts' opinions. The statements were planned and graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence. On November 10, 2023, the experts met in Mestre (Italy) to debate the statements. After the approval of the statements, the expert panel met via email and virtual meetings to prepare and revise the definitive document. This document represents the executive summary of the consensus conference and comprises three sections. The first section focuses on the general principles of diagnosis and treatment of IAIs. The second section provides twenty-three evidence-based recommendations for the antimicrobial therapy of IAIs. The third section presents eight clinical diagnostic-therapeutic pathways for the most common IAIs. The document has been endorsed by the Italian Society of Surgery.
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Infecções Intra-Abdominais , Humanos , Infecções Intra-Abdominais/tratamento farmacológico , Itália , Anti-Infecciosos/uso terapêutico , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections. METHODS: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. RESULTS: A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%). CONCLUSIONS: DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.
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BACKGROUND: Actinomycosis represents a challenging and under-reported complication of vascular surgery. Optimal management of Actinomyces spp. prosthetic vascular graft infection (PVGI) is highly uncertain because of the paucity of reports on this disease. METHODS: We conducted a retrospective case-series of Actinomyces-PVGI that occurred in the last five years in two major university hospitals in northern Italy. We searched for previously published cases in the scientific literature. RESULTS: We report five original cases of Actinomyces spp. prosthetic vascular graft infection following aortic aneurysm repair. Our literature review retrieved eight similar cases. Most patients were immunocompetent males. Most infections were polymicrobial (11/13 cases), with a prevalence of A. odontolyticus involvement (3/13 cases were associated with. Salmonella spp. infection). All cases had a late presentation (≥4 months from graft placement), with 61% associated with an aorto-enteric fistula. All patients received antibiotic therapy, but the duration was highly heterogeneous (from two weeks to life-long antibiotics). The patients without surgical revision experienced septic recurrences (2/13), permanent dysfunction (1/13), or a fatal outcome (2/13), while of the remainder who underwent vascular graft explant, six recovered completely and one developed a periprosthetic abscess. In two cases follow-up was not available. CONCLUSIONS: This case-series aims to raise the diagnostic suspicion and to describe the current management of Actinomyces-PVGIs. We highlight a high heterogeneity in antibiotic duration, choice of the antibiotic regimen, and surgical management. Higher reporting rate is advisable to produce better evidence and optimize management of this rare complication of vascular surgery.
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Objective: We report an outbreak of 14 cases of Q fever among tourists caused by an infected calf and characterized by respiratory transmission and a high attack rate in humans. Materials and methods: Following the identification of an index case of Q fever in September 2021, an epidemiological investigation was conducted in collaboration with local Health and Veterinary authorities and an unknown outbreak was discovered and terminated. Results: The outbreak originated from the delivery by an infected cow, with spread of C. burnetii by air and infection via the respiratory route. The transmission period was calculated, and 25 potentially exposed tourists were identified: 14 were infected (56%) based on serological investigations, four were hospitalized, there were no deaths. All the 22 cows were tested by PCR for C. burnetii: 3 cows (14%) were positive on milk samples and one, the index animal, was also positive on blood. Conclusions: Timely diagnosis in a human patient was pivotal to identify the outbreak since involved animals were asymptomatic. The close collaboration between veterinary and human Public Health services in six different geographical areas of two countries was crucial for the rapid termination of the outbreak.
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Trichosporon spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated Trichosporon ashaii as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that Trichosporon spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as Trichosporon spp.
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Background: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk factors, and early ocular lesions in cases of Gram-negative EBE. Methods: All peer-reviewed articles between January 2002 and August 2022 regarding Gram-negative EBE were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. Results: A total of 115 studies and 591 patients were included, prevalently Asian (98; 81.7%) and male (302; 62.9%). The most common comorbidity was diabetes (231; 55%). The main aetiologies were Klebsiella pneumoniae (510; 66.1%), Pseudomonas aeruginosa (111; 14.4%), and Escherichia coli (60; 7.8%). Liver abscesses (266; 54.5%) were the predominant source of infection. The most frequent ocular lesions were vitreal opacity (134; 49.6%) and hypopyon (95; 35.2%). Ceftriaxone (76; 30.9%), fluoroquinolones (14; 14.4%), and ceftazidime (213; 78.0%) were the most widely used as systemic, topical, and intravitreal anti-Gram-negative agents, respectively. The most reported surgical approaches were vitrectomy (130; 24.1%) and evisceration/exenteration (60; 11.1%). Frequently, visual acuity at discharge was no light perception (301; 55.2%). Conclusions: Gram-negative EBEs are associated with poor outcomes. Our systematic review is mainly based on case reports and case series with significant heterogeneity. The main strength is the large sample spanning over 20 years. Our findings underscore the importance of considering ocular involvement in Gram-negative infections.
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Background: Infectious complications are a significant cause of morbidity and mortality in patients undergoing allogeneic haematopoietic stem cell transplantation (Allo-SCT). The BATMO (Best-Antimicrobial-Therapy-TMO) is an innovative program for infection prevention and management and has been used in our centre since 2019. The specific features of the BATMO protocol regard both prophylaxis during neutropenia (abandonment of fluoroquinolone, posaconazole use in high-risk patients, aerosolized liposomal amphotericin B use until engraftment or a need for antifungal treatment, and letermovir use in CMV-positive recipients from day 0 to day +100) and therapy (empirical antibiotics based on patient clinical history and colonization, new antibiotics used in second-line according to antibiogram with the exception of carbapenemase-producing K pneumoniae for which the use in first-line therapy is chosen). Methods: Data on the infectious complications of 116 transplant patients before BATMO protocol (Cohort A; 2016 - 2018) were compared to those of 84 transplant patients following the introduction of the BATMO protocol (Cohort B; 2019 - 2021). The clinical and transplant characteristics of the 2 Cohorts were comparable, even though patients in Cohort B were at a higher risk of developing bacterial, fungal, and CMV infections, due to a significantly higher proportion of myeloablative regimens and haploidentical donors. Results: No change in the incidence of infections with organ localization was observed between the two Cohorts. A significant reduction in Clostridioides difficile infections by day +100 was observed in Cohort B (47% vs. 15%; p=0.04). At day +30, a higher incidence of Gram-negative bloodstream infections (BSIs) was observed in Cohort B (12% vs. 23%; p=0.05). By day +100 and between days +100 and +180, the incidence of BSIs and of the various etiological agents, the mortality from Gram-negative bacteria, and the incidence of invasive fungal infections were not different in the two Cohorts. The incidence of CMV reactivations by day +100 dropped drastically in patients of Cohort B, following letermovir registration (51% vs. 15%; p=0.00001). Discussion: The results of this study suggest that the BATMO program is safe. In particular, the choice to avoid prophylaxis with fluoroquinolone was associated with an increase in Gram-negative BSIs by day +30, but this did not translate into higher levels of mortality. Moreover, this strategy was associated with a significant reduction of Clostridiodes difficile infections. The efficacy of anti-CMV prophylaxis with letermovir was confirmed by a significant reduction in CMV reactivations. Even though patients in Cohort B were at higher risk of developing fungal infections (more haploidentical transplants with more myeloablative regimens), the extensive use of posaconazole for prophylaxis balanced this risk, and no increase in the incidence of fungal-associated complications was observed.