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1.
New Microbiol ; 45(1): 62-72, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35403848

ABSTRACT

Convalescent plasma (CP) therapy might be effective in patients with haematological malignanciesand B-cell depletion. We report a single-centre experience of COVID-19 patients with non-Hodgkinlymphoma and absence of B-cells as a consequence of anti-CD20 therapy successfully treated withCP from October 2020 to May 2021. CP was given in the presence of pneumonia with respiratoryfailure despite standard treatment and consisted of three infusions on an alternate-day basis. A reviewof the current literature on this topic was also performed. Six patients were identified (medianage 59.5 years (range 50-73)). The last anti-CD20 drug administration occurred 60 days before infection(range 0-360). CP was administered after a median of 51 days (range 9-120) from SARS-CoV-2diagnosis, with an early improvement in all but one subject. We suggest a possible clinical benefitof convalescent CP treatment in COVID-19 patients with haematological malignancies and B-celldepletion having persistent/recurrent pneumonia.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Humans , Immunization, Passive , Lymphocytes
2.
JAC Antimicrob Resist ; 4(1): dlac022, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35265842

ABSTRACT

Objectives: To explore the real-life performance of meropenem/vaborbactam for treating serious KPC-producing Klebsiella pneumoniae infections, including those resistant to ceftazidime/avibactam. Methods: A retrospective observational cohort study was conducted in 12 Italian hospitals. Enrolled patients had K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) infections (59.5% of which were ceftazidime/avibactam resistant). Patients who received ≥72 h of meropenem/vaborbactam therapy (with or without other antimicrobials) in a compassionate-use setting were included. Results: The 37 infections (all hospital-acquired) were mainly bacteraemic (BSIs, n = 23) or lower respiratory tract infections (LRTIs, n = 10). Clinical cure was achieved in 28 (75.6%) cases and microbiologically confirmed in all 25 with follow-up cultures. Three (10.7%) of the 28 clinical cures (all BSIs, 2/3 microbiologically confirmed) were followed by in-hospital recurrences after meropenem/vaborbactam was discontinued (median interval: 18 days). All three recurrences were susceptible to meropenem/vaborbactam and successfully managed with meropenem/vaborbactam combined with colistin or fosfomycin. Nine patients (24.3%) (all with BSIs or LRTIs) died in hospital with persistent signs of infection. Most were aged over 60 years, with high comorbidity burdens and INCREMENT scores ≥8. Only one had received meropenem/vaborbactam monotherapy. Six began meropenem/vaborbactam therapy >48 h after infection onset. Outcomes were unrelated to the isolate's ceftazidime/avibactam susceptibility status. The single adverse event observed consisted of severe leukopenia with thrombocytopenia. Conclusions: With the well-known limitations of real-life retrospective studies, our results support previous findings indicating that meropenem/vaborbactam therapy will be a safe, effective tool for managing serious KPC-Kp infections, including the increasing proportion displaying resistance to ceftazidime/avibactam.

3.
Thromb Haemost ; 2022 Mar 04.
Article in English | MEDLINE | ID: mdl-35253143

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV2)-related pneumonia is associated with venous and arterial thrombosis . Aim of the study was to find-out a new score for predicting thrombosis in patients with SARS-CoV-2. METHODS: We included a cohort of 674 patients affected by SARS-CoV-2, not requiring intensive care units, and followed-up during the hospitalization until discharge. Routinary analyses performed at in-hospital admission included also serum albumin and D-dimer while arterial and venous thromboses were the end-points of the study. RESULTS: During the follow-up thrombotic events 110 were registered; patients with thrombotic events were older and had lower albumin and higher D-dimer, compared to thrombotic event-free ones. On multivariable logistic regression with step by stepwise procedure age, serum albumin, D-dimer, were independently associated with thrombotic events. The linear combination of age, D-dimer, albumin allowed to build-up the ADA score, whose AUC was 0.752 (95% CI, 0.708-0.795). ADA score was internally validated by bootstrap sampling procedure giving an AUC of 0.752 (95% CI: 0.708 - 0.794). CONCLUSIONS: Combination of age, D-dimer, albumin in the ADA score allows identifying SARS-CoV-2 patients at higher risk of thrombotic events.

4.
Antibiotics (Basel) ; 11(2)2022 Feb 10.
Article in English | MEDLINE | ID: mdl-35203827

ABSTRACT

AIM: The aim of the study was to evaluate the in vitro activity of N-acetylcysteine (NAC), alone or in combination with beta-lactams, against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) and Acinetobacter baumannii (CR-Ab). METHODS: The antibacterial activity of each compound was tested by broth microdilution and the synergism was evaluated by the checkerboard method. Killing studies of NAC alone and in combination with beta-lactams were performed. Bacterial morphological changes were investigated with scanning electron microscopy (SEM). RESULTS: Overall, 30 strains were included (15 CR-Kp and 15 CR-Ab). The NAC Minimal Inhibitory Concentrations (MIC)50/90 were 5/5 and 2.5/5 mg/mL for CR-Kp and CR-Ab, respectively. For both microorganisms, NAC, in addition to beta-lactams (meropenem for CR-Kp, meropenem and ampicillin/sulbactam for CR-Ab, respectively), was able to enhance their activity. The killing studies showed a rapid and concentration-dependent activity of NAC alone; the addition of NAC to meropenem or ampicillin/sulbactam at subinhibitory concentrations induced a fast and lasting bactericidal activity that persisted over time. The SEM analyses showed evident morphological alterations of the bacterial cells following incubation with NAC, alone and in combination with meropenem. CONCLUSIONS: NAC demonstrated a high in vitro activity against CR-Kp and CR-Ab and was able to enhance beta-lactams' susceptibility in the tested strains. The preliminary data on the SEM analyses confirmed the in vitro results.

6.
Infez Med ; 29(3): 408-415, 2021.
Article in English | MEDLINE | ID: mdl-35146346

ABSTRACT

INTRODUCTION: There is the need of a simple but highly reliable score system for stratifying the risk of mortality and Intensive Care Unit (ICU) transfer in patients with SARS-CoV-2 pneumonia at the Emergency Room. PURPOSE: In this study, the ability of CURB-65, extended CURB-65, PSI and CALL scores and C-Reactive Protein (CRP) to predict intra-hospital mortality and ICU admission in patients with SARS-CoV-2 pneumonia were evaluated. METHODS: During March-May 2020, a retrospective, single-center study including all consecutive adult patients with diagnosis of SARS-CoV-2 pneumonia was conducted. Clinical, laboratory and radiological data as well as CURB-65, expanded CURB-65, PSI and CALL scores were calculated based on data recorded at hospital admission. RESULTS: Overall, 224 patients with documented SARS-CoV-2 pneumonia were included in the study. As for intrahospital mortality (24/224, 11%), PSI performed better than all the other tested scores, which showed lower AUC values (AUC=0.890 for PSI versus AUC=0.885, AUC=0.858 and AUC=0.743 for expanded CURB-65, CURB-65 and CALL scores, respectively). Of note, the addition of hypoalbuminemia to the CURB-65 score increased the prediction value of intra-hospital mortality (AUC=0.905). All the tested scores were less predictive for the need of ICU transfer (26/224, 12%), with the best AUC for extended CURB-65 score (AUC= 0.708). CONCLUSION: The addition of albumin level to the easy-to-calculate CURB-65 score at hospital admission is able to improve the quality of prediction of intra-hospital mortality in patients with SARS-CoV-2 pneumonia.

7.
Clin Transl Gastroenterol ; 13(1): e00448, 2022 01 13.
Article in English | MEDLINE | ID: mdl-35029168
8.
Eur J Clin Microbiol Infect Dis ; 41(3): 495-500, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34988712

ABSTRACT

The objective was to study ceftazidime-avibactam resistant and susceptible Klebsiella pneumoniae isolated from a patient admitted to the Policlinico Umberto I of Rome for SARS-CoV2. Data on the evolution of patient's conditions, antimicrobial therapies, and microbiological data were collected. Whole-genome sequencing performed by Illumina and Nanopore sequencing methods were used to type the strains. During the hospitalization, a SARS-CoV2-infected patient was colonized by a KPC-producing K. pneumoniae strain and empirically treated with ceftazidime-avibactam (CZA) when presenting spiking fever symptoms. Successively, ST2502 CZA-resistant strain producing the KPC-31 variant gave a pulmonary infection to the patient. The infection was treated with high doses of meropenem. The KPC-31-producing strain disappeared but the patient remained colonized by a KPC-3-producing K. pneumoniae strain. An interplay between highly conserved KPC-31- and KPC-3-producing ST2502 strains occurred in the SARS-CoV2 patient during the hospitalization, selected by CZA and carbapenem treatments, respectively.


Subject(s)
Anti-Bacterial Agents , COVID-19 , Klebsiella Infections , Meropenem , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , COVID-19/complications , Ceftazidime/therapeutic use , Drug Combinations , Humans , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/genetics , Meropenem/therapeutic use , Microbial Sensitivity Tests , beta-Lactamases/genetics
9.
Antibiotics (Basel) ; 10(12)2021 Nov 30.
Article in English | MEDLINE | ID: mdl-34943687

ABSTRACT

The worldwide propagation of antimicrobial resistance represents one of the biggest threats to global health and development. Multi-drug-resistant organisms (MDROs), including carbapenem-resistant non-fermenting Gram-negatives and Enterobacterales, present a heterogeneous and mutating spread. Infections by MDRO are often associated with an unfavorable outcome, especially among critically ill populations. The polymyxins represented the backbone of antibiotic regimens for Gram-negative MDROs in recent decades, but their use presents multiple pitfalls. Luckily, new agents with potent activity against MDROs have become available in recent times and more are yet to come. Now, we have the duty to make the best use of these new therapeutic tools in order not to prematurely compromise their effectiveness and at the same time improve patients' outcomes. We reviewed the current literature on ceftazidime/avibactam, meropenem/vaborbactam and cefiderocol, focusing on antimicrobial spectrum, on the prevalence and mechanisms of resistance development and on the main in vitro and clinical experiences available so far. Subsequently, we performed a step-by-step construction of a speculative algorithm for a reasoned prescription of these new antibiotics, contemplating both empirical and targeted use. Attention was specifically posed on patients with life-risk conditions and in settings with elevated prevalence of MDRO.

10.
Int J Environ Res Public Health ; 18(22)2021 11 13.
Article in English | MEDLINE | ID: mdl-34831702

ABSTRACT

Nowadays only a few studies on biological and environmental risk among healthcare workers are available in literature. The present study aims to assess the health operator's risk of contact with microorganisms during necropsy activities, to evaluate the efficiency of current protections, to identify possible new sources of contact, and to point out possible preventive measures. In addition, considering the current pandemic scenario, the risk of transmission of SARS-CoV-2 infection in the dissection room is assessed. The objectives were pursued through two distinct monitoring campaigns carried out in different periods through sampling performed both on the corpses and at the environmental level.

11.
Front Microbiol ; 12: 750460, 2021.
Article in English | MEDLINE | ID: mdl-34777301

ABSTRACT

Implant-associated infections are characterized by microbial biofilm formation on implant surface, which renders the microbiological diagnosis challenging and requires, in the majority of cases, a complete device removal along with a prolonged antimicrobial therapy. Traditional cultures have shown unsatisfactory sensitivity and a significant advance in the field has been represented by both the application of the sonication technique for the detachment of live bacteria from biofilm and the implementation of metabolic and molecular assays. However, despite the recent progresses in the microbiological diagnosis have considerably reduced the rate of culture-negative infections, still their reported incidence is not negligible. Overall, several culture- and non-culture based methods have been developed for diagnosis optimization, which mostly relies on pre-operative and intra-operative (i.e., removed implants and surrounding tissues) samples. This review outlines the principal culture- and non-culture based methods for the diagnosis of the causative agents of implant-associated infections and gives an overview on their application in the clinical practice. Furthermore, advantages and disadvantages of each method are described.

12.
Thromb Haemost ; 2021 Nov 10.
Article in English | MEDLINE | ID: mdl-34758488

ABSTRACT

BACKGROUND: It is still unclear if patients with community-acquired pneumonia (CAP) and coronavirus disease 2019 (COVID-19) have different rate, typology, and impact of thrombosis on survival. METHODS: In this multicentre observational cohort study 1.138 patients, hospitalized for CAP (n=559) or COVID-19 (n=579) from 7 clinical centres in Italy, were included in the study. Consecutive adult patients (age ≥18 years) with confirmed COVID-19 related pneumonia, with or without mechanical ventilation, hospitalized from 1st March 2020 to 30 April 2020, were enrolled. Covid-19 was diagnosed based on the WHO interim guidance. Patients were followed-up until discharge or in-hospital death, registering the occurrence of thrombotic events including ischemic/embolic events. RESULTS: During the in-hospital stay, 11.4% of CAP and 15.5% of COVID-19 patients experienced thrombotic events (p=0.046). In CAP patients all the events were arterial thromboses, while in COVID-19 patients 8.3% were venous and 7.2% arterial thromboses. During the in-hospital follow-up, 3% of CAP patients and 17% of COVID-19 patients died (p<0.001). The highest mortality rate was found among COVID-19 patients with thrombotic events (47.6% vs 13.4% in thrombotic-event free patients; p<0.001). In CAP, 13.8% of patients experiencing thrombotic events died vs. 1.8% of thrombotic event-free ones (p<0.001). A multivariable COX-regression analysis confirmed a higher risk of death in COVID-19 patients with thrombotic events (HR 2.1; 95% CI: 1.4-3.3; p<0.001). CONCLUSIONS: Compared with CAP, COVID-19 is characterized by a higher burden of thrombotic events, different thrombosis typology and higher risk of thrombosis-related in-hospital mortality.

14.
Front Microbiol ; 12: 749685, 2021.
Article in English | MEDLINE | ID: mdl-34745053

ABSTRACT

Infections caused by Gram-positive bacteria are a major public health problem due to their increasing resistance to antibiotics. Staphylococcus and Enterococcus species' resistance and pathogenicity are enhanced by their ability to form biofilm. The biofilm lifestyle represents a significant obstacle to treatment because bacterial cells become highly tolerant to a wide range of antimicrobial compounds normally effective against their planktonic forms. Thus, novel therapeutic strategies targeting biofilms are urgently needed. The lipoglycopeptide dalbavancin is a long-acting agent for treating acute bacterial skin and skin structure infections caused by a broad range of Gram-positive pathogens. Recent studies have shown promising activity of dalbavancin against Gram-positive biofilms, including methicillin-resistant S. aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), and vancomycin-susceptible enterococci. This review outlines the mechanisms regulating biofilm development in Staphylococcus and Enterococcus species and the clinical impact of biofilm-related infections. In addition, it discusses the clinical implications and potential therapeutic perspectives of the long-acting drug dalbavancin against biofilm-forming Gram-positive pathogens.

17.
Infect Drug Resist ; 14: 3459-3476, 2021.
Article in English | MEDLINE | ID: mdl-34511939

ABSTRACT

This review takes into consideration the principal vaccines developed against the SARS-CoV-2 in this unprecedented period of Covid-19 pandemic. We evaluated the mechanism of action of each vaccine as well as the efficacy, the safety and the storage temperature. In addition, the problem of the dose units, the vaccinal strategy, the activity of alternative compounds such as the monoclonal antibodies and especially the issue of the virus variants were also described in detail. Four vaccines are currently used in Italy: Pfizer-BioNTech mRNA BNT162b2 (Comirnaty) (USA), Moderna mRNA 1273 (USA), Astra-Zeneca ChAdOx1-S (recombinant) viral vector adenovirus belonging to Oxford (UK) and Pomezia (Italy), Janssen (two recombinant viral vector adenoviruses) belonging to Johnson & Johnson (USA). The efficacy of Pfizer and Moderna for preventing disease or severe disease results 95-87.5% and 94.5-100%, respectively. The efficacy of Astra-Zeneca and Janssen is about 70% and 65%, respectively; in the case of Janssen, it depends on the geographical area ranging from 72% to 57%. The problem of the administrated doses (one dose, two doses from the same vaccine or from different vaccines, half dose) is also discussed. The vaccination strategy based on the age group remains the simplest, most transparent and fair criterion. This strategy is also based on accelerating the administration of the vaccines, so that as many subjects as possible can be vaccinated quickly for achieving the "herd immunity". The monoclonal antibodies appeared to be a valid solution for the treatment of Covid-19 disease. Two antibodies (bamlanivimab and etesevimab) have just been approved by the FDA. They could also be used for the infection by virus variants which represent a big problem due to their higher transmissibility and virulence and to their lower response to the vaccines.

18.
J Clin Med ; 10(17)2021 Sep 06.
Article in English | MEDLINE | ID: mdl-34501466

ABSTRACT

INTRODUCTION: E-selectin is a recognized marker of endothelial activation; however, its place in Coronavirus Disease 2019 (COVID-19) has not been fully explored. Aims of the study are to compare sE-selectin values among the Intensive Care Unit (ICU)-admitted and non-admitted, survived and non-survived patients and those with or without thrombosis. METHODS: A single-center study of patients with COVID-19 hospitalized at Policlinico Umberto I (Rome) from March to May 2020 was performed. Simple and multiple logistic regression models were developed. RESULTS: One hundred patients were included, with a median age (IQR) of 65 years (58-78). Twenty-nine (29%) were admitted to ICU, twenty-eight (28%) died and nineteen (19%) had a thrombotic event. The median value (IQR) of sE-selectin was 26.1 ng/mL (18.1-35). sE-selectin values did not differ between deceased and survivors (p = 0.06) and among patients with or without a thrombotic event (p = 0.22). Compared with patients who did not receive ICU treatments, patients requiring ICU care had higher levels of sE-selectin (36.6 vs. 24.1 ng/mL; p < 0.001). In the multiple logistic regression model, sE-selectin levels > 33 ng/mL, PaO2/FiO2 < 200 and PaO2/FiO2 200-300 were significantly associated with an increased risk of ICU admission. sE-selectin values significantly correlated with a neutrophil count (R = 0.32 (p = 0.001)) and the number of days from the symptoms onset to hospitalization (R = 0.28 (p = 0.004)). CONCLUSIONS: sE-selectin levels are predictive of ICU admission in COVID-19 patients. Since data on the relation between sE-selectin and COVID-19 are scarce, this study aims to contribute toward the comprehension of the pathogenic aspects of COVID-19 disease, giving a possible clinical marker able to predict its severity.

19.
PLoS One ; 16(9): e0257376, 2021.
Article in English | MEDLINE | ID: mdl-34506608

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of Tocilizumab (with or without corticosteroids) in a real-life context among moderate-to-severe COVID-19 patients hospitalized at the Infectious Diseases ward of two hospitals in Lazio region, Italy, during the first wave of SARS-CoV-2 pandemic. METHOD: We conducted a retrospective cohort study among moderate-to-severe COVID-19 pneumonia to assess the influence of tocilizumab (with or without corticosteroids) on: 1) primary composite outcome: risk for death/invasive mechanical ventilation/ICU-transfer at 14 days from hospital admission; 2) secondary outcome: COVID-related death only. Both outcomes were also assessed at 28 days and restricted to baseline more severe cases. We also evaluated the safety of tocilizumab. RESULTS: Overall, 412 patients were recruited, being affected by mild (6.8%), moderate (66.3%) or severe (26.9%) COVID-19 at baseline. The median participant' age was 63 years, 56.5% were men, the sum of comorbidities was 1.34 (±1.44), and the median time from symptom onset to hospital admission was 7 [3-10] days. Patients were subdivided in 4 treatment groups: standard of care (SoC) only (n = 172), SoC plus corticosteroid (n = 65), SoC plus tocilizumab (n = 50), SoC plus tocilizumab and corticosteroid (n = 125). Twenty-six (6.3%) patients underwent intubation, and 37 (9%) COVID-related deaths were recorded. After adjusting for several factors, multivariate analysis showed that tocilizumab (with or without corticosteroids) was associated to improved primary and secondary outcomes at 14 days, and at 28-days only when tocilizumab administered without corticosteroid. Among more severe cases the protective effect of tocilizumab (± corticosteroids) was observed at both time-points. No safety concerns were recorded. CONCLUSION: Although contrasting results from randomized clinical trials to date, in our experience tocilizumab was a safe and efficacious therapeutic option for patients with moderate-to-severe COVID-19 pneumonia. Its efficacy was improved by the concomitant administration of corticosteroids in patients affected by severe-COVID-19 pneumonia at baseline.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , COVID-19/drug therapy , Pandemics , Adult , Aged , Cohort Studies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Retrospective Studies , Treatment Outcome
20.
Front Immunol ; 12: 708149, 2021.
Article in English | MEDLINE | ID: mdl-34335624

ABSTRACT

Microbial translocation (MT) and intestinal damage (ID) are poorly explored in COVID-19. Aims were to assess whether alteration of gut permeability and cell integrity characterize COVID-19 patients, whether it is more pronounced in severe infections and whether it influences the development of subsequent bloodstream infection (BSI). Furthermore, we looked at the potential predictive role of TM and ID markers on Intensive Care Unit (ICU) admission and in-hospital mortality. Over March-July 2020, 45 COVID-19 patients were enrolled. Markers of MT [LPB (Lipopolysacharide Binding Protein) and EndoCab IgM] and ID [I-FABP (Intestinal Fatty Acid Binding Protein)] were evaluated at COVID-19 diagnosis and after 7 days. As a control group, age- and gender-matched healthy donors (HDs) enrolled during the same study period were included. Median age was 66 (56-71) years. Twenty-one (46.6%) were admitted to ICU and mortality was 22% (10/45). Compared to HD, a high degree of MT and ID was observed. ICU patients had higher levels of MT, but not of ID, than non-ICU ones. Likewise, patients with BSI had lower EndoCab IgM than non-BSI. Interestingly, patients with high degree of MT and low ID were likely to be admitted to ICU (AUC 0.822). Patients with COVID-19 exhibited high level of MT, especially subjects admitted to ICU. COVID-19 is associated with gut permeability.


Subject(s)
COVID-19/metabolism , Intestinal Mucosa/metabolism , SARS-CoV-2/physiology , Acute-Phase Proteins/metabolism , Aged , Biomarkers/metabolism , COVID-19/diagnosis , COVID-19/mortality , COVID-19/pathology , Carrier Proteins/metabolism , Disease Progression , Fatty Acid-Binding Proteins/metabolism , Female , Humans , Intensive Care Units , Intestinal Mucosa/pathology , Male , Membrane Glycoproteins/metabolism , Middle Aged , Predictive Value of Tests , Prognosis , Survival Analysis , Tight Junctions/metabolism
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