Brain abscess caused by Actinomyces turicensis in a non-immunocompromised adult patient: a case report and systematic review of the literature.

BACKGROUND: Actinomyces turicensis is rarely responsible of clinically relevant infections in human. Infection is often misdiagnosed as malignancy, tuberculosis, or nocardiosis, therefore delaying the correct identification and treatment. Here we report a case of a 55-year-old immunocompetent adult with brain abscess caused by A. turicensis. A systematic review of A. turicensis infections was performed. METHODS: A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases MEDLINE, Embase, Web of Science, CINAHL, Clinicaltrials.gov and Canadian Agency for Drugs and Technology in Health (CADTH) were searched for all relevant literature. RESULTS: Search identified 47 eligible records, for a total of 67 patients. A. turicensis infection was most frequently reported in the anogenital area (n = 21), causing acute bacterial skin and skin structure infections (ABSSSI) including Fournier's gangrene (n = 12), pulmonary infections (n = 8), gynecological infections (n = 6), cervicofacial district infections (n = 5), intrabdominal or breast infections (n = 8), urinary tract infections (n = 3), vertebral column infections (n = 2) central nervous system infections (n = 2), endocarditis (n = 1). Infections were mostly presenting as abscesses (n = 36), with or without concomitant bacteremia (n = 7). Fever and local signs of inflammation were present in over 60% of the cases. Treatment usually involved surgical drainage followed by antibiotic therapy (n = 51). Antimicrobial treatments most frequently included amoxicillin (+clavulanate), ampicillin/sulbactam, metronidazole or cephalosporins. Eighty-nine percent of the patients underwent a full recovery. Two fatal cases were reported. CONCLUSIONS: To the best of our knowledge, we hereby present the first case of a brain abscess caused by A. turicensis and P. mirabilis. Brain involvement by A. turicensis is rare and may result from hematogenous spread or by dissemination of a contiguous infection. The infection might be difficult to diagnose and therefore treatment may be delayed. Nevertheless, the pathogen is often readily treatable. Diagnosis of actinomycosis is challenging and requires prompt microbiological identification. Surgical excision and drainage and antibiotic treatment usually allow for full recovery.

Real-life Data on Cefiderocol Efficacy and Safety to Treat Multidrug-Resistant Acinetobacter baumannii Infections.

Background: The objective of this study was to expand real-life data on cefiderocol efficacy to treat multidrug-resistant Acinetobacter baumannii infections. Methods: This was a retrospective monocentric study including patients hospitalized (>24 hours) at Policlinico Tor Vergata, Rome, Italy, between May 1, 2021, and September 1, 2022, treated with cefiderocol (>48 hours). The primary objective was early clinical improvement at 48-72 hours from cefiderocol start; secondary objectives were clinical success (composite outcome of infection resolution and 14-day survival), breakthrough infection, overall 30-day mortality, and cefiderocol-related adverse events. Results: Eleven patients were enrolled; 91% males (10/11), with a median age (interquartile range [IQR]) of 69 (59-71) years, 91% had ≥1 comorbidity, and 72.7% (8/11) were hospitalized in internal medicine wards. Six patients with bloodstream infection (54.5%; 4 primary, 2 central line-associated), 2 with pneumonia (18.2%), 2 with urinary tract infections (18.2%), and 1 with intra-abdominal infection (9.1%) were treated. Four patients (36.3%) presented with septic shock at cefiderocol start. Cefiderocol was used as monotherapy in 3/11 patients (27.3%), was combined with colistin in all the other 8 cases, and was used in triple combination with tigecycline in 2 patients. The median duration of treatment (IQR) was 12 (10-14) days. Early clinical improvement was documented in 8/11 patients (72.7%), clinical success in 8/11 patients (72.7%). Overall 30-day mortality was 27.3% (3/11), with death occurring a median (IQR) of 19 (17.5-20.5) days after the start of therapy. No cefiderocol-related adverse events were documented. Conclusions: Cefiderocol seems to be a safe and effective option for multidrug-resistant Acinetobacter baumannii infections.

Resistance to Ceftazidime/Avibactam in Klebsiella pneumoniae KPC-Producing Isolates: A Real-Life Observational Study.

Background: Ceftazidime/avibactam (CAZ-AVI) resistance amongst Enterobacterales is worryingly increasing worldwide. Objectives: The aim of this study was to collect and describe real-life data on CAZ-AVI-resistant Klebsiella pneumoniae (KP) isolates in our University Hospital, with the ultimate goal of evaluating possible risk factors related to the acquisition of resistance. Methods: This is a retrospective observational study, including unique Klebsiella pneumoniae (KP) isolates resistant to CAZ-AVI (CAZ-AVI-R) and producing only KPC, collected from July 2019 to August 2021 at Policlinico Tor Vergata, Rome, Italy. The pathogen's list was obtained from the microbiology laboratory; clinical charts of the corresponding patients were reviewed to collect demographic and clinical data. Subjects treated as outpatients or hospitalized for <48 h were excluded. Patients were then divided into two groups: S group, if they had a prior isolate of CAZ-AVI-susceptible KP-KPC, and R group, if the first documented isolate of KP-KPC was resistant to CAZ-AVI. Results: Forty-six unique isolates corresponding to 46 patients were included in the study. The majority of patients (60.9%) were hospitalized in an intensive care unit, 32.6% in internal medicine wards and 6.5% in surgical wards. A total of 15 (32.6%) isolates were collected from rectal swabs, representing a colonization. Amongst clinically relevant infections, pneumonia and urinary tract infections were the most commonly found (5/46, 10.9% each). Half of the patients received CAZ-AVI prior to isolation of the KP-KPC CAZ-AVI-R (23/46). This percentage was significantly higher in patients in the S group compared to patients in the R group (69.3% S group vs. 25% R group, p = 0.003). No differences between the two groups were documented in the use of renal replacement therapy or in the infection site. The clinically relevant CAZ-AVI-R KP infections (22/46, 47.8%) were all treated with a combination therapy, 65% including colistin and 55% including CAZ-AVI, with an overall clinical success of 38.1%. Conclusions: Prior use of CAZ-AVI was associated with the emergence of drug resistance.

Increased Mild Vaccine-Related Side Effects and Higher Specific Antibody Titers in Health Care Workers with Previous SARS-CoV-2 Infection after the mRNA BNT162b2 Vaccine.

Background: to evaluate whether prior SARS-CoV-2 infection affects side effects and specific antibody production after vaccination with BNT162b2. Methods: We included 1106 health care workers vaccinated with BNT162b2. We assessed whether prior SARS-CoV-2 infection affects the number and type of side effects and performed a nested case−control analysis comparing plasma levels of specific IgG titers between SARS-CoV-2-naïve and previously infected subjects after the first and the second vaccine doses. Results: After the first dose, SARS-CoV-2-naïve subjects experienced side effects more often than SARS-CoV-2 naïve subjects. Individuals with prior SARS-CoV-2 infection more often reported pain at the injection site, weakness, and fever than SARS-CoV-2-naïve subjects. After the second dose, the frequency of side effects was similar in the two groups. All subjects with prior SARS-CoV-2 infection developed either a high (>100 AU/mL) or intermediate (10−100 AU/mL) antibody titer. Among SARS-CoV-2-naïve subjects, the majority developed an intermediate titer. After the second dose, a high (>2000 AU/mL) antibody titer was more common among subjects with prior SARS-CoV-2 infection. Conclusions: vaccine-related side effects and a higher anti-SARS-CoV-2-RBD IgG titer were more common in subjects with previous infection than in SARS-CoV-2-naïve after the first, but not after the second dose of the BNT162b2 vaccine.

In Patients with Severe COVID-19, the Profound Decrease in the Peripheral Blood T-Cell Subsets Is Correlated with an Increase of QuantiFERON-TB Gold Plus Indeterminate Rates and Reflecting a Reduced Interferon-Gamma Production.

Increased rates of indeterminate QuantiFERON-TB Gold Plus Assay (QFT-Plus) were demonstrated in patients hospitalized with Coronavirus Disease (COVID)-19. We aimed to define the prevalence and characteristics of hospitalized COVID-19 patients with indeterminate QFT-Plus. A retrospective study was performed including hospitalized COVID-19 patients, stratified in survivors and non-survivors, non-severe and severe according to the maximal oxygen supply required. Statistical analysis was performed using JASP ver0.14.1 and GraphPad Prism ver8.2.1. A total of 420 patients were included, median age: 65 years, males: 66.4%. The QFT-Plus was indeterminate in 22.1% of patients. Increased rate of indeterminate QFT-Plus was found in non-survivors (p = 0.013) and in severe COVID-19 patients (p < 0.001). Considering the Mitogen-Nil condition of the QFT-Plus, an impaired production of interferon-gamma (IFN-γ) was found in non-survivors (p < 0.001) and in severe COVID-19 patients (p < 0.001). A positive correlation between IFN-γ levels in the Mitogen-Nil condition and the absolute counts of CD3+ (p < 0.001), CD4+ (p < 0.001), and CD8+ (p < 0.001) T-lymphocytes was found. At the multivariable analysis, CD3+ T-cell absolute counts and CD4/CD8 ratio were confirmed as independent predictors of indeterminate results at the QFT-Plus. Our study confirmed the increased rate of indeterminate QFT-Plus in COVID-19 patients, mainly depending on the peripheral blood T-lymphocyte depletion found in the most severe cases.

Baseline T-lymphocyte subset absolute counts can predict both outcome and severity in SARS-CoV-2 infected patients: a single center study.

The aim of this study was to evaluate the role of baseline lymphocyte subset counts in predicting the outcome and severity of COVID-19 patients. Hospitalized patients confirmed to be infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) were included and classified according to in-hospital mortality (survivors/nonsurvivors) and the maximal oxygen support/ventilation supply required (nonsevere/severe). Demographics, clinical and laboratory data, and peripheral blood lymphocyte subsets were retrospectively analyzed. Overall, 160 patients were retrospectively included in the study. T-lymphocyte subset (total CD3+, CD3+ CD4+, CD3+ CD8+, CD3+ CD4+ CD8+ double positive [DP] and CD3+ CD4- CD8- double negative [DN]) absolute counts were decreased in nonsurvivors and in patients with severe disease compared to survivors and nonsevere patients (p < 0.001). Multivariable logistic regression analysis showed that absolute counts of CD3+ T-lymphocytes < 524 cells/µl, CD3+ CD4+ < 369 cells/µl, and the number of T-lymphocyte subsets below the cutoff (T-lymphocyte subset index [TLSI]) were independent predictors of in-hospital mortality. Baseline T-lymphocyte subset counts and TLSI were also predictive of disease severity (CD3+ < 733 cells/µl; CD3+ CD4+ < 426 cells/µl; CD3+ CD8+ < 262 cells/µl; CD3+ DP < 4.5 cells/µl; CD3+ DN < 18.5 cells/µl). The evaluation of peripheral T-lymphocyte absolute counts in the early stages of COVID-19 might represent a useful tool for identifying patients at increased risk of unfavorable outcomes.

Mild clinical manifestations of SARS-CoV-2 related pneumonia in two patients with multiple sclerosis under treatment with ocrelizumab.

BACKGROUND: Recently SARS-CoV-2 has spread worldwide causing a pandemic. Little is known about disease severity in immunocompromised hosts and people receiving disease modifying therapies (DMTs). In the last decades DMTs have been widely employed, and ocrelizumab represents one of the newest therapies for the relapsing remitting and progressive forms of multiple sclerosis (MS). OBJECTIVES: to describe SARS-CoV-2 related pneumonia in two MS patients under ocrelizumab treatment. METHODS: Case series. RESULTS: Patients showed a mild clinical course of SARS-CoV-2 related pneumonia without complications or sequelae. CONCLUSION: Ocrelizumab treatment is not necessarily associated to increased severity in MS patients with SARS-CoV-2 infection.