Two cases of misleading Epstein-Barr virus infection and the role of EBV-DNA.

Two atypical cases of infectious mononucleosis in two teenagers with initially negative serology and non-evocative blood examinations are reported. The first patient had recently traveled to Africa, and Epstein-Barr virus negative serology led us to make many extensive investigations. The second patient complained of asthenia for a month, and PET/CT was performed to suspicion of lymphoma. PET scan revealed hypermetabolic lymph nodes in the supradiaphragmatic and subdiaphragmatic stations, along with18F-FDG uptake in the spleen and pharynx, raising more suspicion of lymphoma. Fortunately, Epstein-Barr virus DNA testing was performed and turned positive in both cases, and Epstein-Barr virus serology subsequently became positive. Diagnosing EBV infection can be challenging in rare cases, as EBV-specific serology may be negative in the early stages and confounding factors may be present. Therefore, Epstein-Barr virus DNA testing should be considered early in the diagnostic algorithm to prevent unnecessary investigations in similar cases.

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia.

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

Screening for Latent Tuberculosis Infection in People Living with HIV: TUBHIVIT Project, a Multicenter Italian Study.

BACKGROUND: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. METHODS: We performed a prospective study in five referral centers for HIV care in Italy. PLHIV who consented Tto participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI who started chemoprophylaxis were followed until the end of therapy. RESULTS: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, and 6 were lost to follow-up before discriminating between latent and active TB. Among the PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Sepsis in Patients Hospitalized in Sicily, Italy, over the Period of 2016-2020: A Retrospective Study.

Background: Epidemiological data regarding the incidence and mortality of sepsis are scarcely available. The present study aimed to delineate the epidemiology of sepsis and related mortality among patients hospitalized in Sicily, Italy. Methods: Data on the discharge forms of all patients with sepsis in all Sicilian hospitals from January 2016 to December 2020 were retrospectively collected. Results: In Sicily, 15,373 hospitalizations associated with sepsis occurred from 2016 to 2020, with an overall in-hospital mortality rate of 36.3%. The percentage of hospitalizations associated with sepsis represented 0.65% of all admissions, with an increase over the years. Most patients were admitted to non-surgical and non-infectious disease units, accounting for 50.3% of total admissions. Stratification of patients according to age, intensive care unit (ICU) admission, and presence of septic shock revealed variations in in-hospital mortality rates. Among adult ICU-admitted patients with septic shock, mortality was highest at 81.0%, followed by non-ICU adult patients with septic shock (63.5%), ICU pediatric patients with septic shock (56.7%), ICU adult patients without septic shock (43.9%), non-ICU pediatric patients with septic shock (37.9%), non-ICU adult patients without septic shock (17.9%), ICU pediatric patients without septic shock (10.4%), and non-ICU pediatric patients without septic shock (1%).

COVID-19: The Development and Validation of a New Mortality Risk Score.

Background: The coronavirus disease 2019 (COVID-19) pandemic has found the whole world unprepared for its correct management. Italy was the first European country to experience the spread of the SARS-CoV-2 virus at the end of February 2020. As a result of hospital overcrowding, the quality of care delivered was not always optimal. A substantial number of patients admitted to non-ICU units could have been treated at home. It would have been extremely useful to have a score that, based on personal and clinical characteristics and simple blood tests, could have predicted with sufficient reliability the probability that a patient had or did not have a disease that could have led to their death. This study aims to develop a scoring system to identify which patients with COVID-19 are at high mortality risk upon hospital admission, to expedite and enhance clinical decision making. Methods: A retrospective analysis was performed to develop a multivariable prognostic prediction model. Results: Derivation and external validation cohorts were obtained from two Italian University Hospital databases, including 388 (10.31% deceased) and 1357 (7.68% deceased) patients with confirmed COVID-19, respectively. A multivariable logistic model was used to select seven variables associated with in-hospital death (age, baseline oxygen saturation, hemoglobin value, white blood cell count, percentage of neutrophils, platelet count, and creatinine value). Calibration and discrimination were satisfactory with a cumulative AUC for prediction mortality of 0.924 (95% CI: 0.893-0.944) in derivation cohorts and 0.808 (95% CI: 0.886-0.828) in external validation cohorts. The risk score obtained was compared with the ISARIC 4C Mortality Score, and with all the other most important scores considered so far, to evaluate the risk of death of patients with COVID-19. It performed better than all the above scores to evaluate the predictability of dying. Its sensitivity, specificity, and AUC were higher than the other COVID-19 scoring systems when the latter were calculated for the 388 patients in our derivation cohort. Conclusions: In conclusion, the CZ-COVID-19 Score may help all physicians by identifying those COVID-19 patients who require more attention to provide better therapeutic regimens or, on the contrary, by identifying those patients for whom hospitalization is not necessary and who could therefore be sent home without overcrowding healthcare facilities. We developed and validated a new risk score based on seven variables for upon-hospital admission of COVID-19 patients. It is very simple to calculate and performs better than all the other similar scores to evaluate the predictability of dying.

Acute Cytomegalovirus Infection Associated With Erythema Multiforme-Like Eruption: A Case Report.

Human cytomegalovirus infection usually proceeds asymptomatically in immunocompetent patients. In symptomatic forms, mononucleosis syndrome is the most common manifestation. However, atypical cases of cytomegalovirus infections in immunocompetent subjects are reported in the literature. Here, we describe a case of cytomegalovirus-related mononucleosis syndrome that presented with an atypical erythema multiforme-like skin rash and high fever. Very few cases have been described in the literature previously. In our case, the diagnosis was supported by specific serology, and human cytomegalovirus DNA was detected in the blood sample. The clinical picture resolved without the administration of antiviral therapy.

An Uncommon Case of Syphilis With Simultaneous, Different Lesions: Moth-Eaten Alopecia, Syphilitic Keratoderma, and Psoriasiform Syphilis.

Syphilis is a re-emerging disease, and an increasing number of cases are being reported in Italy and worldwide. In this report, we present a case of a male patient with secondary syphilis characterized by the heterogenicity of the lesions: hyperkeratosis, psoriasiform-like lesions, papules, macules, and patchy alopecia on the scalp. The patient had applied several topical antimicrobials and steroid medicaments and taken oral acyclovir, which yielded no relief, for a previous wrong diagnosis. At the time of his presentation to our clinic, syphilis was suspected and confirmed by serology. The administration of a single intramuscular dose of penicillin led to a full recovery in three weeks. Screening for HIV and other sexually transmitted infections returned negative. Clinicians should maintain a high index of suspicion for syphilis when encountering sexually active patients with atypical skin manifestations.

Imported malaria in pregnancy in Europe: A systematic review of the literature of the last 25 years.

BACKGROUND: Malaria during pregnancy is associated with a greater risk of complications for the mother and fetus. The aim of the study is to analyze the features of imported cases of malaria in pregnant women in Europe and evaluate which factors are associated with a non-favourable outcome. METHODS: A computerized search of the literature was performed combining the terms plasmod*, malaria, pregnan*, maternal, gravid, parturient, expectant, and congenital, from January 1997 to July 2023. RESULTS: 28 articles reporting 57 cases of malaria in pregnant women immigrant in non-endemic areas were included. The patients mainly came from Sub-Saharan Africa. There were 10 asymptomatic cases, while the predominant clinical syndrome among the symptomatic women was fever associated with anaemia. The median latency period from permanence in endemic areas and diagnosis in European countries was 180 days (IQR 15-730). Pregnancy outcomes were favourable in 35 cases (61 %): all term pregnancies, no low-birth-weight newborns. There were 4 abortions; 1 child was delivered pre-term; 7 babies were reported to have a low birth weight; 10 cases of congenital malaria were documented. P. falciparum was found with a higher frequency in women with a favourable outcome, while P. vivax was, in all cases, associated with a worse prognosis. CONCLUSIONS: Diagnosis of malaria in pregnant woman in non-endemic countries may be challenging and a delay in diagnosis may lead to an adverse outcome. Screening for malaria should be performed in pregnant women from endemic areas, especially if they present anaemia or fever.

Causes of hospitalization and predictors of in-hospital mortality among people living with HIV in Sicily-Italy between 2010 and 2021.

BACKGROUND: Despite the rising number of people living with human immunodeficiency virus (HIV), there is a lack of knowledge about the factors that lead to PLWHs being hospitalized in worldwide literature. Our study aimed to investigate PLWH admissions in Sicily (Italy) between January 2010 and September 2021 and to analyze the characteristics and risk factors for in-hospital mortality and differences between Italians and foreigners. METHODS: Data from the hospital discharge forms of all people living with HIV (PLWH) hospitalized in Sicilian hospitals were retrospectively collected. Age, sex, nationality, length of stay, acquired immunodeficiency syndrome (AIDS), and non-AIDS-related diseases were evaluated using univariate analysis according to in-hospital mortality rates. The factors associated with mortality were included in the logistic regression model. RESULTS: In total, 5281 admissions from 2726 PLWHs occurred, most of which were related to non-AIDS diseases. Approximately 20 % regarded foreign patients, mainly from Africa. Logistic regression analysis revealed an association between in-hospital mortality and some AIDS- and non-AIDS-related diseases (wasting syndrome, lymphomas, Kaposi sarcomas, progressive multifocal leukoencephalopathy, cryptococcosis, abscesses, sepsis, cardiovascular disease, nephropathy, and respiratory diseases). African patient admissions were significantly associated with tuberculosis, toxoplasmosis, Burkitt lymphoma, and hepatitis B diagnoses. CONCLUSIONS: Our study showed that most hospitalizations were related to non-AIDS-defining diseases, with differences between Italian and foreign patients, mainly from Africa.

Hemophagocytic lymphohistiocytosis secondary to histoplasmosis: A case report in a patient with AIDS and recent SARS-CoV-2 infection and minireview.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Intestinal Lesions Due to Rhodococcus equi in a Patient With Advanced Retroviral Disease and Pulmonary Infection: A Case of Colonic Malakoplakia.

In humans, Rhodococcus equi (R. equi) is a zoonotic infection usually involving immunocompromised subjects, only rarely affecting immunocompetent subjects. Herein, we describe an R. equi infection in a 50-year-old Russian man with acquired immune deficiency syndrome (AIDS) who presented with pulmonary cavitary lesions and clinical manifestation of colonic malakoplakia. A colonoscopy examination showed ulceration and mucosal erosion, and the histological findings confirmed the colonic malakoplakia. The patient recovered from pulmonary and gastrointestinal disease after four weeks of antibiotic treatment with intravenous ciprofloxacin and oral azithromycin and also underwent subsequent long-term oral antibiotic treatment to achieve clinical and immune restoration after antiretroviral therapy. Infectious disease pathology subspecialties should always consider R. equi chronic infection as a cause of malakoplakia in patients with AIDS. As only a few cases of colonic malakoplakia associated with R. equi are reported in the literature, these cases are important to describe, especially for clinical and treatment management.

Ceftazidime-Avibactam as Osteomyelitis Therapy: A Miniseries and Review of the Literature.

Bone and joint infections (BJIs) caused by multidrug-resistant gram-negative bacteria are becoming a concern due to limited therapeutic options. Although not approved for these indications, an ever-growing amount of evidence supports the efficacy and safety of ceftazidime-avibactam as a therapy for osteomyelitis and prosthetic joint infections. Here, we present three cases of difficult-to-treat resistant Pseudomonas aeruginosa osteomyelitis that were successfully treated with ceftazidime-avibactam alone or in combination therapy with fosfomycin and amikacin. Ceftazidime-avibactam was prescribed at a daily dose of 2.5 g every 8 h for 42 days in all cases. One potential drug-related adverse effect was observed, i.e., Clostridioides difficile infection, which occurred after fourteen days of treatment with ceftazidime-avibactam.

Multisystem Inflammatory Syndrome: A Case in an Adult With Controlled Lymphoma and a Persistent SARS-CoV-2 Infection.

Multisystem inflammatory syndrome (MIS) is a new and rare complication of COVID-19 that usually occurs in children. An increasing number of cases of MIS in adults are described in the literature. The condition is associated with high mortality, and treatment is non-standardized. Clinical pictures are heterogeneous, and diagnosis is very challenging. Here we describe a case of MIS in a 60-year-old man with previous follicular lymphoma treated with obinutuzumab and recent SARS-CoV-2 infections. He complained of an unknown fever and developed pancytopenia during the hospitalization, associated with a general clinical worsening. The patient was successfully treated with intravenous immunoglobulin and steroids.

Hospitalizations for tuberculosis in Sicily over the years 2009-2021: Clinical features, comorbidities, and predictors of mortality.

BACKGROUND: Very few data are available in the literature regarding tuberculosis (TB) hospitalization, and few studies have reported the clinical characteristics and comorbidities of admitted patients and burden and cost of hospitalization. In our study, we described the occurrence of TB hospital admissions in the southern Italian region of Sicily over 13 years (2009-2021), explored the characteristics of patients with TB, and determined the comorbidities associated with mortality. METHOD: Data on the hospital discharge of all patients with TB hospitalized in all Sicilian hospitals were retrospectively collected from hospital standard discharge forms. Age, sex, nationality, length of hospital stay, comorbidities, and TB localization were evaluated using univariate analysis according to in-hospital mortality. The factors associated with mortality were included in the logistic regression model. RESULTS: In Sicily, 3745 people were hospitalized for TB, with 5239 admissions and 166 deaths from 2009 to 2021. Most hospitalizations involved Italian-born people (46.3%), followed by African-born people (32.8%) and Eastern European-born people (14.1%). The average hospitalization cost was EUR 5259 ± 2592, with a median length of stay of 16 days (interquartile range, 8-30) days. Multivariate analysis showed that the development of acute kidney failure (adjusted odds ratio [aOR]=7.2, p < 0.001), alcohol consumption (aOR=8.9, p = 0.001), malignant tumors (aOR=2.1, p = 0.022), human immunodeficiency virus infection (aOR=3.4, p < 0.001), sepsis (aOR=15.2, p < 0.001), central nervous system involvement (aOR=9.9, p < 0.001), and miliary TB (aOR=2.5, p = 0.004) were independent predictors of mortality. CONCLUSION: TB in Sicily remains an important cause of hospitalization. HIV infection and comorbidities may complicate patient management and worsen patient outcomes.

Staphylococcus aureus and Coagulase-Negative Staphylococci from Bloodstream Infections: Frequency of Occurrence and Antimicrobial Resistance, 2018-2021.

BACKGROUND: The abuse of antibiotics during the SARS-CoV-2 pandemic might have disrupted efforts to curb the further development and spread of the antimicrobial resistance of Staphylococcus aureus infection and Staphylococcus spp. coagulase-negative (CoNS) agents of nosocomial bloodstream infections (NBSIs). The purpose of our work was to study the resistance patterns of Staphylococcus aureus and CoNS through the analysis of blood cultures in hospitalized SARS-CoV-2-positive and SARS-CoV-2-negative patients (pts.). MATERIALS AND METHODS: During the period January 2018-June 2021, a retrospective case-control study was performed on blood cultures positive for Staphylococcus spp. detected in 177 adult pts. (≥18 years old) hospitalized for >48 hours at Sant'Elia Hospital, Caltanissetta. RESULTS: Staphylococcus aureus was isolated in 33.9% of blood culture samples, and among CoNS, the most frequent strains were Staphylococcus capitis (18.6%) and Staphylococcus hominis (18.1%). Patients aged ≥ 65 years, with a greater number of males, comprised the SARS-CoV-2-negative pts. (71.8% vs. 52.2%, p = 0.0154). Among the SARS-CoV-2-positive patients, the significant resistance of Staphylococcus aureus was only observed for erythromycin (57.1%). The oxacillin resistance of Staphylococcus capitis was higher in SARS-CoV-2-positive than in negative pts. (90% and 78.3%, respectively). Comparing the two groups, we found an increase in resistance in SARS-CoV-2-negative patients for the following antibiotics: gentamicin for Staphylococcus aureus (p = 0.007), clindamycin and erythromycin (p = 0.012) for Staphylococcus hominis and oxacillin and rifampicin for Staphylococcus haemoliticus (p = 0.012). CONCLUSIONS: Our study confirms the relevance of oxacillin-resistant Staphylococcus aureus in being responsible for bloodstream infection and draws attention to highly oxacillin-resistant CoNS such as Staphylococcus capitis. The presence of resistant strains of CoNS in hospitals can be worrying, as it limits treatment options and worsens outcomes. The Infection Control Committee (ICC) recommends new treatment strategies to decrease colonization and infections. As part of the implementation of a bloodstream infection prevention program, the authors encourage the introduction of a report on the antimicrobial resistance of hospital bacteremia due to CoNS.

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis.

Clostridioides difficile infection (CDI) is a significant cause of morbidity and mortality, mostly in frail patients. Notification is not mandatory in Italy, and data on incidence, risk of death, and recurrence are lacking. The purpose of this study was to determine CDI incidence and risk factors for mortality and recurrence. The "ICD-9 00845" code in hospital-standardized discharged forms (H-SDF) and microbiology datasets were used to retrieve CDI cases at Policlinico Hospital, Palermo between 2013 and 2022. Incidence, ward distribution, recurrence rate, mortality, and coding rate were considered. The risk of death and recurrence was predicted through multivariable analysis. There were 275 CDIs, 75% hospital-acquired, the median time between admission and diagnosis was 13 days, and the median stay was 21 days. Incidence increased from 0.3 to 5.6% (an 18.7-fold increase) throughout the decade. Only 48.1% of cases were coded in H-SDF. The rate of severe/severe-complicated cases increased 1.9 times. Fidaxomicin was used in 17.1% and 24.7% of cases overall and since 2019. Overall and attributable mortalities were 11.3% and 4.7%, respectively. Median time between diagnosis and death was 11 days, and recurrence rate was 4%. Bezlotoxumab was administered in 64% of recurrences. Multivariable analysis revealed that only hemodialysis was associated with mortality. No statistically significant association in predicting recurrence risk emerged. We advocate for CDI notification to become mandatory and recommend coding CDI diagnosis in H-SDF to aid in infection rate monitoring. Maximum attention should be paid to preventing people on hemodialysis from getting CDI.

A case of syphilis associated with immune reconstitution inflammatory syndrome and review of the literature.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) associated with syphilis has rarely been described in HIV-infected patients. Diagnosis can be challenging because it is not always possible to discern it from a recent infection or a worsening of an undiagnosed one. CASE PRESENTATION: An HIV-positive 42-year-old man with a poor compliance history of antiretroviral therapy presented at our unit and complained of ocular symptoms. Ocular syphilis diagnosis was posed after initial misdiagnosing with cytomegalovirus infection, and antiretroviral therapy compliance improved after switching to a bictegravir-based regimen. Despite intravenous (IV) penicillin, we observed an initial worsening with the appearance of new skin lesions, and IRIS syphilis was suspected. In the literature, 14 cases of IRIS syphilis are described, all regarding male patients. Seven were HIV naïve to therapy, and 7 HIV-experienced with poor therapy compliance. Basal syphilis serology was negative in ten, with subsequent seroconversion after the development of IRIS. IRIS-syphilis development was observed after a median time of 28 days from ART initiation; 10 cases were considered "unmasking-IRIS" and 4 "paradoxical-IRIS". Skin and ocular involvement were the most often reported. In most cases, it was not necessary to use a systemic steroid. A good outcome was reported in 12. CONCLUSIONS: Syphilis should be considered in differential diagnosis with other diseases associated with IRIS. A negative syphilis serology before beginning antiretroviral therapy could convey the impression that syphilis has been ruled out. Whereas a high index of suspicion should be maintained when symptoms suggestive of syphilis, such as ocular and skin manifestations, are noticed after therapy has begun.