Clinical and in vitro efficacy of colistin plus vancomycin and rifampin against colistin-resistant Acinetobacter baumannii causing ventilator-associated pneumonia

We present the case of a patient with ventilator-associated pneumonia (VAP) caused by a pan-resistant Acinetobacter baumannii successfully treated with the combination colistin plus vancomycin plus rifampin, whose in vitro activity was investigated by checkerboard method and killing testing. Furthermore, the serum bactericidal activity (SBA) was assessed. Our case shows that an innovative regimen consisting of colistin plus antimicrobials active only against Gram-positive microorganisms might represent a valid therapeutic option for severe infections caused by colistin-resistant A. baumannii

Changes in T cell effector functions over an 8-year period with TNF antagonists in patients with chronic inflammatory rheumatic diseases

The aim of the study was to clarify the effect of long-term anti-TNF therapy on T cell function in patients with rheumatologic immune-mediated inflammatory diseases (IMID). The production of IFNγ by T cells was evaluated at baseline and after 1, 2, 4, and 8 years of anti-TNF agents by means of a QuantiFERON-TB Gold In-Tube assay. The T cell proliferation and surface co-expression of CD25/CD134 in response to phytohaemagglutinin together with the in vitro impact of anti-TNF therapy on the functional capacity of T cells were evaluated after 8 years from the onset of the biological treatment. Age-matched healthy donors were enrolled as controls. The quantitative mitogen-induced IFNγ responses significantly increased with respect to baseline at each time point, apart from the determination after 4 years. We found an increased expression of CD25/CD134 in CD4+compared to CD8+T cells both in patients and controls. The in vitro addition of anti-TNF agents induced a significant decrease of both the IFNγ response and of CD25/CD134, whereas no effect on the intensity of the proliferative response was observed. Our data provide a biological basis for the reassuring issues on the safety of long-term anti-TNF treatment in patients with IMID

In-vitro evaluation of different antimicrobial combinations with and without colistin against carbapenem-resistant acinetobacter baumannii

Carbapenem-resistant Acinetobacter baumannii (CR-Ab) infections are associated with high morbidity and mortality. The aim of the study was to evaluate the in-vitro activity of different antimicrobial combinations (with and without colistin, COL) against clinical isolates of CR-Ab collected from patients with CR-Ab infection, including unconventional combinations such as COL + VANcomycin (VAN) and COL + rifampin (RIF). CR-Ab strains were collected from hospitalized patients at Sapienza University of Rome. Antimicrobial susceptibility patterns were determined throughout MIC50/90s whereas the synergistic activity was evaluated by qualitative (i.e., checkerboard) and quantitative (i.e., killing studies) methods. All the strains were found oxacillinase (OXA) producers and tigecycline (TIG) sensitive whereas 2 strains were resistant to COL. Application of the checkerboard method indicated complete synergism in COL combinations at different extension: 21.4%, 57.1%, 42.8%, 35.7% for COL + meropenem (MEM), COL + RIF, COL + VAN and COL + TIG, respectively, with the non-conventional combinations COL + VAN and COL + RIF exhibiting the highest rate of synergism. Regarding COL-free combination, complete synergism was observed in 35.7% of the strains for MEM + TIG. Killing studies showed that the combinations COL + MEM, COL + TIG and MEM + TIG were bactericidal and synergistic against both colistin-sensitive and low colistin-resistant strains whereas only the combinations COL + VAN and COL + RIF showed an early and durable bactericidal activity against all the tested strains, with absence of growth at 24 h. This study demonstrated that COL-based combinations lead to a high level of synergic and bactericidal activity, especially COL + VAN and COL + RIF, even in the presence of high level of COL resistance

Intracranial tuberculous mass lesions treated with thalidomide in an immunocompetent child from a low tuberculosis endemic country: A case report

Rationale: Tuberculous meningitis is a highly morbid, often fatal disease. Patient concern: We describe a case of an Italian child. Diagnoses: we diagnosed early a Tuberculous meningitis complicated by the occurrence of hydrocephalus, stroke, and paradoxical reaction with brain pseudo-abscesses. Interventions: The child started readily a specific therapy associated with steroids and thalidomide was introduced few month later. Outcomes: the patient had a favorable outcome without neurologic sequelae. Lessons: Despite the prompt specific anti-tubercular and adjuvant corticosteroid therapies, only the addition of thalidomide to the treatment allow to a favorable clinical outcome

Immunological diagnosis as an adjunctive tool for an early diagnosis of tuberculous meningitis of an immune competent child in a low tuberculosis endemic country: A case report

Background: Pediatric tuberculous meningitis is a highly morbid, often fatal disease. Its prompt diagnosis and treat - ment saves lives, in fact delays in the initiation of therapy have been associated with high mortality rates. Case presentation: This is a case of an Italian child who was diagnosed with tuberculous meningitis after a history of a month of headache, fatigue and weight loss. Cerebrospinal fluid analysis revealed a lymphocytic pleocytosis with predominance and decreased glucose concentration. Microscopy and conventional diagnostic tests to identify Myco - bacterium tuberculosis were negative, while a non classical method based on intracellular cytokine flow cytometry response of CD4 cells in cerebral spinal fluid helped us to address the diagnosis, that was subsequently confirmed by a nested polymerase chain reaction amplifying a 123 base pair fragment of the M. tuberculosis DNA. Conclusions: We diagnosed tuberculous meningitis at an early stage through an innovative immunological approach, supported by a nested polymerase chain reaction for detection of M. tuberculosis DNA. An early diagnosis is required in order to promptly initiate a therapy and to increase the patient’s surviva

Rapid decline of fasting glucose in HCV diabetic patients treated with direct-acting antiviral agents

Association between HCV infection and diabetes has been widely postulated. Little is known about the impact of direct acting antiviral agents (DAAs) on glycemic control. Aim of our study was to evaluate the glycemic control modifications in a case series of HCV+ diabetic population receiving DAAs. We retrospectively evaluated 149 HCV+ patients in two different institutions affiliated to the Sapienza University: Policlinico Umberto I of Rome and Ospedale Santa Maria Goretti of Latina. We were able to identify 29 patients with T2DM (19% of total population) who were receiving different IFN-free regimens. During-treatment fasting glucose values were available for 21 patients and analysis showed a statistically significant reduction (p=0,007), the reduction mean value was -52,86 mg/dl. An A1C value during treatment (week 4 or week 8 or week 12) was available for 10 patients and the analysis showed a statistically significant reduction (p=0,021) with a reduction mean value of -1,95%. 6 patients (23%) needed to reduce hypoglycemic drugs, 8 of 10 patients showed reduction of A1C, 14 of 21 patients (67%) showed reduced FG during treatment. FG and A1C reductions values were independent from which DAA was present in the regimen, HCV genotype, BMI and HIV status. In order to avoid hypoglycemic events, diabetic patients undergoing DAAs should be closely monitorized for reduction of hypoglycemic drugs. Furthermore, diabetes could be considered, in our opinion, as an element to prioritize treatment in those patients with no apparent liver disease

Recovery of interleukin-17 production from interleukin-15-stimulated CD4+ mononuclear cells in HIV-1-infected patients with sustained viral suppression

Interleukin-17 (IL-17) is a pro-inflammatory cytokine that is mainly produced by CD4 + T cells. The role of Th17 during the human immunodeficiency virus (HIV)-1 infection is still unclear, but HIV-1 infection can cause a preferential depletion of Th17 cells. It has been shown that IL-15 elicits IL-17 production from human peripheral blood mononuclear cells. We studied the effect of IL-15 stimulation in vitro on IL-17 production from CD4 + mononuclear cells of HIV-infected patients. We observed that IL-15 triggers, in a dose-dependent manner, IL-17 secretion. This effect was blocked by anti-IL-15 monoclonal antibody (P = 0.01). Interestingly, IL-17 production was significantly lower in patients with detectable plasma viremia when compared with successfully treated HIV-infected patients (P = 0.02) and healthy controls, respectively (P < 0.001). We also noticed a significant difference in IL-17 production between naive HIV-infected patients and patients with virological failure on combined antiretroviral therapy (cART) (P = 0.02). Our results suggest that IL-15 can induce IL-17 production from peripheral CD4 + mononuclear cells of HIV-infected patients. Persistent HIV plasma viremia could cause a severe perturbation of IL-17 production from CD4 + mononuclear cells. IL-17 production in HIV-infected patients could be recovered through a sustained suppression of the viral replication in the peripheral blood through cART

Clinical and in vitro efficacy of colistin plus vancomycin and rifampin against colistin-resistant Acinetobacter baumannii causing ventilator-associated pneumonia

We present the case of a patient with ventilator-associated pneumonia (VAP) caused by a pan-resistant Acinetobacter baumannii successfully treated with the combination colistin plus vancomycin plus rifampin, whose in vitro activity was investigated by checkerboard method and killing testing. Furthermore, the serum bactericidal activity (SBA) was assessed. Our case shows that an innovative regimen consisting of colistin plus antimicrobials active only against Gram-positive microorganisms might represent a valid therapeutic option for severe infections caused by colistin-resistant A. baumannii

Systemic adipokines, hepatokines and interleukin-6 in HCV-monoinfected and HCV/HIV coinfected patients treated with direct antiviral agents (DAAs)

In this study, we demonstrated that that altered levels ofadipokines/hepatokines in HCV-infected patients, including HIV coinfected, can be restored by treatment with direct antiviral agents (DAAs), thus indicating the important metabolic changes occurring during the eradication of this viral infection

Heart, COVID-19, and echocardiography.

AbstractAlthough clinical manifestations of coronavirus disease of 2019 (COVID‐19) mainly consist of respiratory symptoms, a severe cardiovascular damage may occur. Moreover, previous studies reported a correlation of cardiovascular metabolic diseases with severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and actually, many COVID‐19 patients show comorbidities (systemic hypertension, cardio‐cerebrovascular disease, and diabetes) and have a raised risk of death. The purpose of this review is to focus the cardiovascular effects of 2019‐nCoV on the base of the most recent specific literature and previous learnings from SARS and MERS and analyze the potential role of echocardiography during the current critical period and short‐ and long‐term follow‐up