Long-Term Suppressive Therapeutic-Drug-Monitoring-Guided Dalbavancin Therapy for Cardiovascular Prosthetic Infections.

Dalbavancin represents a promising treatment for cardiovascular prosthetic infections due to its prolonged half-life, bactericidal activity, large spectrum of activity, and excellent biofilm penetration. However, the use of dalbavancin in this setting is limited, and only a few cases have performed therapeutic drug monitoring (TDM) analysis to optimize dosage in suppressive treatments longer than 4 weeks. Our retrospective case series reports the use of dalbavancin in a small cohort of patients with cardiovascular prosthetic infections (cardiac implantable electronic device infections (CEDIs), prosthetic valve endocarditis (PVE), prosthetic vascular graft infections (PVGIs)) treated with dalbavancin as sequential therapy. From May 2019 to May 2023, 14 patients were included: eight cases of PVE (57.1%), seven cases of PVGI (50%), three cases of CEDI (21.4%), and four cases with overlap of infection sites (28.6%). The main pathogen was Staphylococcus aureus (35.7%). Prosthesis replacement was obtained in four patients (28.6%). The median time between symptom onset and the end of treatment was 15 weeks (IQR 7-53), with a median duration of dalbavancin therapy of 8 weeks (IQR 1 to 45 weeks) and 3.5 doses per patient. Among patients managed with TDM-guided strategy, dalbavancin infusion intervals ranged from 4 to 9 weeks. The median length of follow-up was 65 weeks (IQR 23 to 144 weeks). Clinical success was achieved in 10 cases (76.9%); all clinical failures occurred in patients with the implant retained. Among patients monitored by TDM, clinical success was 87.5% vs. 60% in patients treated without TDM. Because of pharmacokinetic individual variability, dalbavancin TDM-guided administration could improve clinical outcomes by individualizing dosing and selecting dosing intervals. This case series seems to suggest a promising role of long-term suppressive dalbavancin treatment for difficult-to-treat cardiovascular prosthesis infection, also with limited surgical indications.

Efficacy of bezlotoxumab in preventing the recurrence of Clostridioides difficile infection: an Italian multicenter cohort study.

OBJECTIVES: Bezlotoxumab (BEZ) is a promising tool for preventing the recurrence of Clostridioides difficile infection (rCDI). The aim of the study was to emulate, in a real-world setting, the MODIFY trials in a cohort of participants with multiple risk factors for rCDI treated with BEZ in addition to the standard of care (SoC) versus SoC alone. METHODS: A multicenter cohort study was conducted including 442 patients with Clostridioides difficile infection from 2018 to 2022, collected from 18 Italian centers. The main outcome was the 30-day occurrence of rCDI. The secondary outcomes were (i) all-cause mortality at 30 days (ii) and the composite outcome (30-day recurrence and/or all-cause death). RESULTS: rCDI at day 30 occurred in 54 (12%): 11 in the BEZ + SoC group and 43 treated with SoC alone (8% vs 14%, odds ratio [OR] = 0.58, 95% confidence interval [CI]: 0.31-1.09, P = 0.09). The difference between BEZ + SoC versus SoC was statistically significant after controlling for confounding factors (adjusted OR = 0.40, 95% CI: 018-0.88, P = 0.02) and even more using the composite outcome (adjusted OR = 0.35, 95% CI: 0.17-0.73, P = 0.005). CONCLUSION: Our study confirms the efficacy of BEZ + SoC for the prevention of rCDI and death in a real-world setting. BEZ should be routinely considered among participants at high risk of rCDI regardless of age, type of Clostridioides difficile infection therapy (vancomycin vs fidaxomicin), and number of risk factors.

Multimodal assessment in polymicrobial infective endocarditis with silent spondylodiscitis and cerebral embolism / Evaluación multimodal en endocarditis infecciosa polimicrobiana con espondilodiscitis silenciosa y embolia cerebral

Abstract Infective endocarditis (IE) is a rare but severe disease, due to an infection of the endocardial surface of the heart. The annual incidence ranging from 3 to 7 per 100 000 person-years, with an overall mortality rates of 25%. Staphylococci and Streptococci accounted for approximately 80% of IE cases. Enterococci are the third leading cause accounted for approximately 5-18% of all cases and are increasingly linked to health-care contact. The increasing number of cardiovascular electronic devices, prosthetic valves implants along with frequent invasive diagnostic or therapeutic procedures performed in elderly, may also contribute to the rise of IE in this population. Blood cultures and echocardiographic findings are the cornerstone of the IE diagnosis, confirmed or rejected according to modified Duke criteria. Other imaging modalities as Cardiac Computed Tomography, Cardiac Magnetic Resonance Imaging and 18Ffluorodeoxyglucose Positron Emission Tomography - Computed Tomography (18FDG-PET/CT) can determine a more correct diagnosis and identify many of the endocarditis-related complications. Here, we describe a patient with aortic prosthetic valve and Enterococcus faecalis (EF) IE. Cerebral and spinal MRI and 18FDG-PET/CT, performed during the hospitalization, showed multi-organ silent periferic embolization. Furthermore, the cultural examination of the valvular surgical specimen revealed a methicillin-sensitive Staphylococcus aureus suggestive for polymicrobial endocarditis. Some Authors demonstrated a possible false-positive valve culture due to a postoperative contamination. Since contaminated cultures usually yield microorganisms compatible with endocarditis, such as coagulase-negative Staphylococci, viridans group Streptococcus species, may be difficult for the physician not to treat the patient. This case represents need for high level of suspicion to diagnose IE. Multimodality assessment improves the diagnosis and allows the detection of the complications. Moreover, a multidisciplinary team and specialized centers determine a better patient’s outcome.

Resumen La endocarditis infecciosa (EI) es una enfermedad poco frecuente pero severa, dada por una infección del endocardio. La incidencia anual oscila entre 3 y 7 por cada 100 000 personas-año, con una tasa de mortalidad general del 25%. Los estafilococos y los estreptococos representaron aproximadamente un 80% de los casos de EI. Los enterococos son la tercera causa, aportando aproximadamente 5% a 18% de todos los casos, y se vinculan cada vez más al contacto con la atención médica. El número creciente de dispositivos electrónicos cardiovasculares e implantes de válvulas protésicas, junto con los frecuentes procedimientos invasivos diagnósticos o terapéuticos en las personas ancianas, también podrían contribuir al incremento de EI en esta población. Los hemocultivos y los hallazgos ecocardiográficos son la piedra angular del diagnóstico de EI, confirmado o rechazado de acuerdo con los criterios modificados de Duke. Otras modalidades de imagenología tales como la Tomografía Computarizada Cardíaca (TCC), la Resonancia Magnética Cardíaca (RMC) y la Tomografía por Emisión de Positrones - Tomografía Computarizada con 18F-fluorodeoxiglucosa (18F-FDG PET/TC) pueden determinar un diagnóstico más preciso e identificar muchas de las complicaciones asociadas a la endocarditis. Aquí describimos un paciente con una válvula aórtica protésica y EI por EF. Una RM del cerebro y la columna vertebral y una 18F-FDG PET/TC practicadas durante la hospitalización evidenciaron embolia periférica multiorgánica silenciosa. Además, el examen por cultivo de la muestra quirúrgica valvular reveló Staphylococcus aureus sensible a la meticilina (SASM), sugestivo de endocarditis polimicrobiana. Algunos autores demostraron un posible falso positivo del cultivo valvular dado por contaminación postoperatoria. Ya que los cultivos contaminados generalmente producen microorganismos compatibles con la endocarditis, tales como estafilococos coagulasa negativos y estreptococos del grupo viridans, le puede resultar difícil al médico no tratar al paciente. Este caso representa la necesidad de tener un alto nivel de sospecha para diagnosticar la EI. La valoración multimodal mejora el diagnóstico y permite detectar complicaciones. Además, un equipo multidisciplinario y los centros especializados determinan un mejor desenlace para el paciente.

Imported rickettsioses in Italy.

BACKGROUND: In Italy few cases of rickettsioses have been reported in travellers and autochthonous cases are attributed predominantly to Rickettsia conorii, the agent of Mediterranean spotted fever. METHOD: The purpose of this study was to investigate some epidemiological and clinical features of tick-borne spotted fever group rickettsiosis acquired abroad or in Italy. Serum specimens collected prospectively from patients with suspected rickettsioses were tested by immunofluorescence assay. A definitive diagnosis was made on the basis of positive serological test results at the WHO collaborative centre for rickettsial diseases, Marseille, France. We compared the clinical features of patients with confirmed rickettsioses and those showing typical clinical symptoms/signs without definitive diagnose. RESULTS: Eight of 26 patients suspected cases had confirmed rickettsioses. All patients were travellers returning from southern Africa (75% Rickettsia africae). Inoculation eschars were significantly more common in patients with confirmed rickettsioses (p = 0.004). CONCLUSIONS: Our study demonstrates that R. africae is the most frequent rickettsia observed in Italian travellers. Prior to receiving the laboratory results, physicians should start empirical treatment on the basis of epidemiologic data (e.g., travel history to Africa), and clinical findings compatible with rickettsioses (e.g., eschars).

A case of aseptic pleuropericarditis in a patient with chronic plaque psoriasis under methotrexate therapy.

Methotrexate may rarely provoke serositis, even with low doses and after just a few weeks of therapy. We report here a rare case of pleuropericarditis due to methotrexate. The effusion resolved after the withdrawal of the drug and the beginning of anti-inflammatory therapy; there was no relapse during a 10-month follow-up.

A fatal case of encephalitis associated with Chikungunya virus infection.

An outbreak of Chikungunya fever occurred in north-east Italy in the summer of 2007. Only 1 fatal case was observed, in an 83-y-old male hospitalized with encephalitis. Viral genome was detected at high level (1.5 x 10(8) copies/ml) in the cerebrospinal fluid 7 d after symptoms onset.

Legionnaires' disease associated with macular rash: two cases.

Legionnaires' disease is an acute bacterial infection, generally sustained by Legionella pneumophila, which involves primarily the lower respiratory tract, although it is often associated with multi-systemic extrapulmonary manifestations. Afflicted patients may sometimes have gastrointestinal symptoms, liver function abnormalities, renal failure or central nervous system complications, while cutaneous manifestations are very uncommon and may include erythematous, maculopapular or petechial skin lesions. Pathogenesis of skin involvement in the setting of Legionnaires' disease is still uncertain, but may involve toxic or immunological mechanisms. Two exceptional cases of Legionella pneumonia complicated by diffuse, macular rash in two adult women are described, in association with severe peripheral polyneuropathy and flaccid quadriplegia in one case.