Immunogenicity and safety of a third dose of anti-SARS-CoV-2 BNT16b2 vaccine in liver transplant recipients.

BACKGROUND & AIMS: A strategy to improve the low rate of anti-SARS-CoV-2 mRNA vaccine-induced immunogenicity in liver transplant recipients (LTs) is urgently needed. METHODS: We analysed the rate of positive (≥0.8 U/ml) anti-SARS-CoV-2 receptor domain-binding protein (RBD) antibody response 2 months after a third dose of the BNT16b2 vaccine in 107 LTs who completed the second vaccine dose 7 months earlier. RESULTS: A positive anti-SARS-CoV-2-s-RBD antibody response after the third vaccine dose was detected in 98 (91.6%) LTs compared to 82 (76.6%) after the second vaccine dose (p = .003). The median of anti-SARS-CoV-2 RBD antibody titres increased from 22.9 U/ml 6 months after the second to 3500 U/ml 2 months after the third vaccine dose (p < .001). Fourteen (14.3%) responder patients presented antibody titres <100 U/ml, 57 (58.2%) between 100 and 9999 U/ml and 27 (27.6%) ≥10 000 U/ml. Seropositivity after the second dose was maintained after the third dose. Independent predictors of antibody response failure after the third vaccine dose were taking a higher daily dose of mycophenolate mofetil (MMF, p < .001) and had a lower (<60 ml/min/1.73 m2 ) estimated glomerular filtration rate (p = .007). Nine (9.1%) LTs experienced symptomatic SARS-CoV-2 infection after the third vaccine dose. Median antibody titres were not statistically different between infected and not infected LTs (1325 vs 3515 U/ml, p = .678). CONCLUSIONS: The third dose of the BNT16b2 vaccine increased the number of LTs who developed a positive anti-SARS-CoV-2 s-RBD antibody response. A proportion of patients remained unresponsive, mainly for modifiable factors, such as the use of MMF or multiple immunosuppressants.

Past COVID-19 and immunosuppressive regimens affect the long-term response to anti-SARS-CoV-2 vaccination in liver transplant recipients.

BACKGROUND & AIMS: The long-term immunogenicity of anti-SARS-CoV-2 vaccines in liver transplant (LT) recipients is unknown. We aimed to assess the long-term antibody response of the Pfizer-BioNTech® BNT162b2 vaccine in LT recipients compared to controls. METHODS: LT recipients underwent anti-SARS-CoV-2 anti-receptor-binding domain protein IgG (anti-RBD) and anti-nucleocapsid protein IgG antibody (anti-N) measurements at the first and 1, 4 and 6 months after the second vaccination dose. RESULTS: One hundred forty-three LT recipients and 58 controls were enrolled. At baseline, 131/143 (91.6%) LT recipients tested anti-N negative (COVID-19 naïve), and 12/143 (8.4%) tested positive (COVID-19 recovered) compared to negative controls. Among COVID-19 naïve, 22.1% were anti-RBD positives 1 month after the first vaccine dose, while 66.4%, 77%, and 78.8% were 1, 4 and 6 months following the second vaccine dose. In contrast, 100% of controls were positive at 4 months (p <0.001). The median anti-RBD titer 4 months after the second vaccine dose was significantly lower (32 U/ml) in COVID-19 naïve than in controls (852 U/ml, p <0.0001). A higher daily dose of mycophenolate mofetil (MMF) (p <0.001), higher frequency of ascites (p = 0.012), and lower serum leukocyte count (p = 0.016) were independent predictors of anti-RBD negativity at 6 months. All COVID-19 recovered patients tested positive for anti-RBD at each time point. The median antibody titer was similar in those taking MMF (9,400 U/ml, 11,925 U/ml, 13,305 U/ml, and 10,095 U/ml) or not taking MMF (13,950 U/ml, 9,575 U/ml, 3,500 U/ml, 2,835 U/ml, p = NS) 3 weeks after the first and 1, 4 and 6 months after the second vaccine dose, respectively. CONCLUSIONS: In COVID-19-naïve LT recipients, the immunogenicity of anti-SARS-CoV-2 vaccination was significantly lower than that in controls. MMF was the main determinant of vaccination failure in SARS-CoV-2-naïve patients. LAY SUMMARY: The immunogenicity of anti-SARS-CoV-2 vaccination in liver transplant recipients is currently unknown. Herein, we show that liver transplant recipients who have not previously had COVID-19 are less likely to mount effective antibody responses to vaccination than a control population. The main determinant of vaccination failure was the use of the immunosuppressive drug mycophenolate mofetil.

Clinical characteristics and outcome of 125 polymicrobial bloodstream infections in hematological patients: an 11-year epidemiologic survey.

BACKGROUND: Polymicrobial bloodstream infections (pBSI) occurring in hematological patients are still poorly understood, and specific information are very limited. OBJECTIVES AND METHODS: In this epidemiologic survey, we describe clinical characteristics and outcome of 125 consecutive pBSI occurred in oncohematological patients. Polymicrobial bloodstream infections (pBSI) were defined with the isolation of 2 or more bacteria from blood culture specimens obtained within 72 h. RESULTS: Over an 11-year period, we documented 500 bacterial bloodstream infections (BSI) in 4542 hospital admissions and 25% (125) of these were pBSI. Most common underlying hematological disease was acute myeloid leukemia and 89% of patients had severe neutropenia. Fifty pBSI (40%) occurred in patients undergoing a stem cell transplantation (SCT), mostly within 30 days from transplant (42/50-84%). Principal bacterial association was Gram-positive plus Gram-negative (57%). Resolution rate of pBSI was 82%, without differences between SCT and non-SCT cases. pBSI-related mortality was 15% (6% in SCT cases). Septic shock occurred in 16% of cases and septic shock-related mortality was 65% (75% in SCT cases and 63% in non-SCT cases; p = 0.6). Multidrug-resistant (MDR) bacteria were involved in 22% of pBSI and the MDR-pBSI-related mortality was significantly higher in SCT patients (p = 0.007). CONCLUSIONS: This observational study highlights that pBSI is not a rare bloodstream infectious complication in oncohematological patients. pBSI-related mortality is lower than 20%, but, if septic shock occurs, mortality reaches 65%. MDR bacteria were involved in 22% of cases and pBSI-MDR-related mortality was significantly higher in SCT patients.

The Fall in Antibody Response to SARS-CoV-2: a Longitudinal Study of Asymptomatic to Critically Ill Patients Up to 10 Months after Recovery.

The aim of this study was to assess the long-term dynamics and factors associated with the serological response against the severe acute respiratory syndrome coronavirus 2 after primary infection. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with coronavirus disease 2019 (COVID-19) attending Udine Hospital (Italy) during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), mostly with mild COVID-19 (370, 68.3%). Patients were followed for a median of 302 days (interquartile range, 186 to 311). The overall seroconversion rate within 2 months was 32% for IgM and 90% for IgG. Seroreversion was observed in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of long-term immunity both for IgM (ß, linear regression coefficient, 1.10, P = 0.001; ß 5.15 P = 0.014; ß 43.84 P = 0.021, respectively) and for IgG (ß 1.43 P < 0.001; ß 10.46 P < 0.001; ß 46.79 P < 0.001, respectively), whereas the initial IgG peak was associated only with IgG duration (ß 1.12, P < 0.001). IgM antibodies disappeared at 4 months, and IgG antibodies declined in about half of patients 10 months after acute COVID-19. These effects varied depending on the intensity of the initial antibody response, age, and burden of acute COVID-19.

Low risk of reinfections and relation with serological response after recovery from the first wave of COVID-19.

The aim of the study was to assess reinfection rates in relation to long-term antibody dynamics against SARS-CoV-2 after the first wave. A prospective longitudinal study with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult in- and outpatients with COVID-19 attending Udine Hospital (Italy) from March to May 2020. During the follow-up, reinfections were collected. A total of 546 unselected individuals with COVID-19 acquired from March to May 2020 were included (292 female, mean age 53 years). After a median follow-up of 10 months (IQR 6.2-10.4), reinfection occurred in 6 (1.1%) patients, median age of 44.5 years (IQR 33‒49). All had a previous history of mild COVID-19 (all were healthcare workers) and reinfection occurred a median of 9 months (IQR 8.2‒10.2) after the onset of the first episode. Patients with reinfection were either seronegative (2/56, n = 3.6%), seroreverted (2/137, 1.5%), or seropositive (2/353, 0.6%) (p = 0.085). All reinfections were mild (n = 5) or asymptomatic (n = 1). After reinfection, none of patients developed IgM response and only two had a transitory boosted IgG immunization response. In an unselected population after the first wave of COVID-19, after a prolonged observation period (mean 10 months), reinfection was very uncommon; occurred in patients with a previous history of mild infection, mostly with weak or absent serological response; and manifested with mild or asymptomatic clinical presentation.

Real-Time Therapeutic Drug Monitoring-Based Pharmacokinetic/Pharmacodynamic Optimization of Complex Antimicrobial Therapy in a Critically Ill Morbidly Obese Patient. Grand Round/A Case Study.

The authors present the case of a critically ill morbidly obese patient (body mass index, 51.2 kg/m) who suffered from methicillin-resistant Staphylococcus epidermidis, and Candida albicans bloodstream infections. Initial treatment with caspofungin and daptomycin was deemed inappropriate, because blood cultures remained positive for both isolates after 14 days. The clinical pharmacological consultant suggested adding fluconazole and ceftobiprole to the ongoing antimicrobial therapy, and starting a real-time therapeutic drug monitoring program of daptomycin, ceftobiprole, and fluconazole, aimed at optimizing plasma exposures. Punctual minimum inhibitory concentration knowledge on the clinical isolates allowed attainment of the desired pharmacodynamic efficacy targets. Within few days, the patient greatly improved, as blood cultures became negative, and the inflammatory markers decreased to near normal values. This is a proof-of-concept of the importance of a therapeutic drug monitoring-based multidisciplinary approach in the proper management of complex antimicrobial therapy in special populations.

Factors associated with the development of septic shock in patients with candidemia: a post hoc analysis from two prospective cohorts.

BACKGROUND: Almost one third of the patients with candidemia develop septic shock. The understanding why some patients do and others do not develop septic shock is very limited. The objective of this study was to identify variables associated with septic shock development in a large population of patients with candidemia. METHODS: A post hoc analysis was performed on two prospective, multicenter cohort of patients with candidemia from 12 hospitals in Spain and Italy. All episodes occurring from September 2016 to February 2018 were analyzed to assess variables associated with septic shock development defined according to The Third International Consensus Definition for Sepsis and Septic Shock (Sepsis-3). RESULTS: Of 317 candidemic patients, 99 (31.2%) presented septic shock attributable to candidemia. Multivariate logistic regression analysis identifies the following factors associated with septic shock development: age > 50 years (OR 2.57, 95% CI 1.03-6.41, p = 0.04), abdominal source of the infection (OR 2.18, 95% CI 1.04-4.55, p = 0.04), and admission to a general ward at the time of candidemia onset (OR 0.21, 95% CI, 0.12-0.44, p = 0.001). Septic shock development was independently associated with a greater risk of 30-day mortality (OR 2.14, 95% CI 1.08-4.24, p = 0.02). CONCLUSIONS: Age and abdominal source of the infection are the most important factors significantly associated with the development of septic shock in patients with candidemia. Our findings suggest that host factors and source of the infection may be more important for development of septic shock than intrinsic virulence factors of organisms.

Treatment of Candida infections with fluconazole in adult liver transplant recipients: Is TDM-guided dosing adaptation helpful?

BACKGROUND: Fluconazole represents a common antifungal option for the treatment of Candida infections in liver transplant recipients. Although adequate antifungal exposure is known to correlate with favorable outcomes in patients with invasive candidiasis, therapeutic drug monitoring (TDM) of fluconazole is currently not recommended. METHODS: We conducted a retrospective study including adult liver transplant recipients receiving fluconazole for invasive candidiasis and undergoing TDM. We assessed the correlation between clinical variables, fluconazole trough plasma levels (Cmin ), and outcome. RESULTS: Twenty-seven patients (74% males; median age 57 years) were included. Abdominal candidiasis was the most frequent infection (56%). Median duration of fluconazole therapy was 17 days (IQR 9-21). Fluconazole median Cmin was 11.0 mg/L (range 2.4-30.6 mg/L). Five (19%) patients required TDM-guided fluconazole dose increase. All-cause in hospital mortality was 33%. Fluconazole Cmin >11 mg/L significantly correlated with clinical success (OR 8.78, 95% CI 1.13-67.8, P = 0.04). CONCLUSIONS: Our study identified decreased fluconazole Cmin as a factor associated with negative outcomes in liver transplant recipients with Candida infection. TDM of fluconazole may be advisable in this patient population.

Ceftolozane/tazobactam for the treatment of MDR Pseudomonas aeruginosa left ventricular assist device infection as a bridge to heart transplant.

BACKGROUND: Ceftolozane/tazobactam (C/T) is a novel antibiotic with enhanced microbiological activity against multidrug-resistant (MDR) gram-negative bacteria, including MDR Pseudomonas aeruginosa. CASE REPORT: Five months after left ventricular assist device (LVAD) implantation, a 49-year old man developed fever and blood culture was positive for MDR P. aeruginosa, susceptible only to aminoglycosides, ciprofloxacin and colistin. A diagnosis of LVAD-related infection was made based on persistent bacteremia associated with moderate 18 F-fluorodeoxyglucose positron emission tomography/CT uptake in the left ventricular apex. Disk diffusion testing for C/T was performed (MIC 2 µg/mL) and intravenous antibiotic therapy with C/T and amikacin was started, with clinical and microbiological response. Initial conservative management with 6 weeks of systemic antibiotic therapy was attempted, but the patient relapsed one month after antibiotic discontinuation. Priority for transplantation was given and after 4 weeks of antibiotic therapy (C/T + amikacin), LVAD removal and heart transplant were performed, with no infection relapse. CONCLUSIONS: We reported the first off-label use of C/T in the management of MDR P. aeruginosa LVAD infection as a bridge to heart transplant. C/T has shown potent anti-pseudomonal activity and good safety profile making this drug as a good candidate for suppressive strategy in intravascular device-associated bloodstream infections caused by MDR P. aeruginosa.

Risk Factors and Outcomes of Infections by Multidrug-Resistant Gram-Negative Bacteria in Patients Undergoing Hematopoietic Stem Cell Transplantation.

The objective of this study was to determine risk factors and outcomes of infections by multidrug-resistant gram-negative (MDR GN) bacteria in 241 recipients of hematopoietic stem cell transplantation (HSCT). The cumulative incidence of infections was 10.5% (95% CI, 12.0% to 25.8%), with 57% of infections occurring during the period of severe neutropenia (neutrophil count < .1 × 106/L). In multivariate analysis, allogeneic transplant and colonization with MDR GN bacteria at admission to the transplant unit were significantly associated with an increased risk of infection. Although we observed neither transplant-related mortality (TRM) nor deaths due to infections by MDR GN bacteria after autologous transplant, in the allogeneic setting a significant difference was reported in terms of overall survival (OS) and TRM between patients who developed infections and those who did not (1-year OS, 39% versus 68%; 1-year TRM, 42% versus 19%). In multivariate analysis, refractory disease and development of grades III to IV graft-versus-host disease (GVHD) were factors that affected both TRM and OS, whereas occurrence of infections by MDR GN pathogens significantly reduced OS. We conclude that eligibility to allogeneic HSCT in MDR GN bacteria carriers should be carefully evaluated together with all other factors that independently influence outcome (disease status, donor, and GVHD risk).

Population Pharmacokinetics of High-Dose Continuous-Infusion Meropenem and Considerations for Use in the Treatment of Infections Due to KPC-Producing Klebsiella pneumoniae.

We assessed the population pharmacokinetics of high-dose continuous-infusion (HDCI) meropenem in a cohort of patients with Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) infections. Monte Carlo simulations were used to define the permissible HDCI meropenem regimens that could be safely considered for the treatment of KPC-Kp infections due to meropenem-resistant strains. Permissible doses were arbitrarily defined as those associated with a ≤10% to 15% likelihood of meropenem steady-state concentrations (Css) of >100 mg/liter. Probabilities of target attainment (PTA) of four incremental pharmacodynamic determinants for meropenem efficacy (100% T>1×MIC, 100% T>2×MIC, 100% T>3×MIC, and 100% T>4×MIC, where "T>MIC" represents the time during which the plasma concentration of this time-dependent antibacterial agent is maintained above the MIC for the pathogen) in relation to different classes of renal function were calculated. The cumulative fractions of response (CFR) for the permissible HDCI meropenem regimens were calculated against the MIC distribution of the KPC-Kp clinical isolates that were collected routinely at our University Hospital between 2013 and 2016 (n = 169). Ninety-seven meropenem Css were included in the analysis. The final model included creatinine clearance (CrCL) as a covariate and explained 94% of the population variability. Monte Carlo simulations based on licensed dosages of up to 6 g/day predicted an acceptable PTA (>80%) of 100% T>1×MIC against KPC-Kp with a meropenem MIC of ≤32 mg/liter in patients with a CrCL level of <130 ml/min. Dosages of 8 g/day were needed for achieving the same target in patients with CrCL at levels of 130 to 200 ml/min. In dealing with pathogens with a meropenem MIC of 64 mg/liter, HDCI regimens using meropenem at higher than licensed levels should be considered. In these cases, real-time therapeutic drug monitoring could be a useful adjunct for optimized care. The predicted CFR were >75% in all of the classes of renal function.

Current antibiotic management of prosthetic joint infections in Italy: the 'Udine strategy'.

The rate of prosthetic joint infections followed and cured at our institution is constantly increasing, in line with epidemiological data from the recent literature. This is probably related to the greater number of knee and hip prostheses implanted every year. For intermediate and late infections, only the two-stage approach is applied, as this demonstrates the best outcome in our experience. Particular attention is paid to microbiological isolation of the pathogen: multiple samples of tissue are collected during the interventions, and kept in culture for a longer period of time than usual. Sonication of prosthetic devices is used to enhance the sensitivity and specificity of the microbiological cultures. Histological examination influences surgical choices either towards implantation of a new prosthesis or replacement of the spacer. An empirical antibiotic backbone of a glycopeptide/lipopeptide and rifampicin is chosen, due to the leading role of Gram-positive bacteria in this setting and the high incidence of methicillin resistance in our centre (>30%), followed by an antibiotic regimen containing linezolid. If specific risk factors are present, an anti-Gram-negative drug is added to the regimen. Duration of therapy depends upon the approach that is chosen, usually being 6 weeks when the prosthesis is removed. Despite at the moment being limited by its small sample size, data from our experience confirms that our empirical approach may represent a valid choice during the early phase of treatment, by keeping linezolid for a step-down therapy of shorter duration (4 weeks).

Gut Microbiome Disruption Following SARS-CoV-2: A Review.

COVID-19 has been associated with having a negative impact on patients' gut microbiome during both active disease and in the post-acute phase. In acute COVID-19, rapid alteration of the gut microbiome composition was observed, showing on one side a reduction in beneficial symbionts (e.g., Roseburia, Lachnospiraceae) and on the other side an increase in opportunistic pathogens such as Enterococcus and Proteobacteria. Alpha diversity tends to decrease, especially initially with symptom onset and hospital admission. Although clinical recovery appears to align with improved gut homeostasis, this process could take several weeks, even in mild infections. Moreover, patients with COVID-19 post-acute syndrome showed changes in gut microbiome composition, with specific signatures associated with decreased respiratory function up to 12 months following acute disease. Potential treatments, especially probiotic-based therapy, are under investigation. Open questions remain on the possibility to use gut microbiome data to predict disease progression and on potential confounders that may impair result interpretation (e.g., concomitant therapies in the acute phase; reinfection, vaccines, and occurrence of novel conditions or diseases in the post-acute syndrome). Understanding the relationships between gut microbiome dynamics and disease progression may contribute to better understanding post-COVID syndrome pathogenesis or inform personalized treatment that can affect specific targets or microbiome markers.

Antibody response and risk of reinfection over 2 years among the patients with first wave of COVID-19.

OBJECTIVES: To describe the dynamics and factors related to natural and hybrid humoral response against the SARS-CoV-2 and risk of reinfection among first-wave patients. METHODS: A prospective longitudinal study with periodic serological follow-up after acute onset of all recovered patients with SARS-CoV-2 infection cared in Udine Hospital (March-May 2020). Nucleocapsid (N) protein and spike receptor-binding domain (S-RBD) antibody tests were used to distinguish natural and vaccine-induced response. RESULTS: Overall, 153 patients (66 men, mean age 56 years) were followed for a median of 27.3 (interquartile range 26.9-27.8) months. Seroreversion was 98.5% (95% CI: 96.8-99.4) for SARS-CoV-2-N IgM at 1 year and 57.4% (95% CI: 51.5-63.5) for SARS-CoV-2-N IgG at 2 years. Initial serological response (hazard ratio [HR]: 0.99, 95% CI: 0.99-0.99, p 0.002 for IgM and HR: 0.97, 95% CI: 0.97-0.98, p < 0.001 for IgG) and severity of acute infection (HR: 0.62, 95% CI: 0.39-0.96, p 0.033 for IgM and HR: 0.60, 95% CI: 0.37-0.99, p < 0.001 for IgG) were independently associated with persistent SARS-CoV-2-N IgM/IgG response. Older age and smoker status were associated with long-term SARS-CoV-2-N IgM and SARS-CoV-2-N IgG, respectively (HR: 0.75, 95% CI: 0.57-0.98, p 0.038; HR: 1.77, 95% CI: 1.19-2.61, p 0.004 respectively). All patients maintained SARS-CoV-2-S-RBD IgG response at 24-month follow-up. Reinfections occurred in 25 of 153 (16.3%) patients, mostly during the omicron circulation. Reinfection rates did not differ significantly between SARS-CoV-2-N IgG seronegative and seropositive patients (14/89, 15.7% vs. 10/62, 16.1%, p 0.947). Unvaccinated patients had higher risk of reinfection (4/7, 57.1% vs. vaccinated 21/146, 14.4%, p 0.014). DISCUSSION: First-wave patients had durable natural humoral immunity in 40% and anti-S-RBD response in 100% up to 2 years after infection. Natural humoral response alone was not protective against reinfections with omicron SARS-CoV-2 variants, whereas vaccination was effective to reduce the risk of a new infection.

An Aminoglycoside-Sparing Regimen with Double Beta-Lactam to Successfully Treat Granulicatella adiacens Prosthetic Aortic Valve Endocarditis-Time to Change Paradigm?

(1) Background: Granulicatella adiacens is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment strategy, and partially due to higher rates of complications, such as heart failure, peripheral septic embolism, and peri-valvular abscess, as well as a higher rate of valve replacement. Depending on the affected valve (native valve endocarditisNVE, or prosthetic valve endocarditisPVE), the American Heart Association (AHA) 2015 treatment guidelines (GLs) suggest penicillin G, ampicillin, or ceftriaxone plus gentamicin (2 weeks for NVE and up to 6 weeks for PVE), while vancomycin alone may be a reasonable alternative in patients who are intolerant of ß-lactam therapy. The European Society of Cardiology (ESC) 2023 GLs recommend treating NVE with penicillin G, ceftriaxone, or vancomycin for 6 weeks, suggesting combined with an aminoglycoside (AG) for at least the first 2 weeks only for PVE; likewise, the same recommendations for IE due to Enterococcus faecalis. (2) Methods: Starting from the case of a 51-year-old man with G. adiacens aortic bio-prosthesis IE who was successfully treated with aortic valve replacement combined with double beta-lactams, an AG-sparing regimen, we performed microbiology tests in order to validate this potential treatment change. (3) Results: As for E. faecalis IE, we found that the combination of ampicillin plus cephalosporines (like ceftriaxone or ceftobiprole) showed a synergistic effect in vitro, probably due to wider binding to penicillin-binding proteins (PBPs), thus contributing to enhanced bacterial killing and good clinical outcome, as well as avoiding the risk of nephrotoxicity due to AG association therapy. (4) Conclusions: Further studies are required to confirm this hypothesis, but double beta-lactams and an adequate sourcecontrol could be a choice in treating G. adiacens IE.

Worrisome trend of new multiple mechanisms of linezolid resistance in staphylococcal clones diffused in Italy.

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (cfr, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).

Epidemiology, species distribution, antifungal susceptibility, and outcome of candidemia across five sites in Italy and Spain.

Candidemia has become an important bloodstream infection that is frequently associated with high rates of mortality and morbidity, and its growing incidence is related to complex medical and surgical procedures. We conducted a multicenter study in five tertiary care teaching hospitals in Italy and Spain and evaluated the epidemiology, species distribution, antifungal susceptibilities, and outcomes of candidemia episodes. In the period of 2008 to 2010, 995 episodes of candidemia were identified in these hospitals. The overall incidence of candidemia was 1.55 cases per 1,000 admissions and remained stable during the 3-year analysis. Candida albicans was the leading agent of infection (58.4%), followed by Candida parapsilosis complex (19.5%), Candida tropicalis (9.3%), and Candida glabrata (8.3%). The majority of the candidemia episodes were found in the internal medicine department (49.6%), followed by the surgical ward, the intensive care unit (ICU), and the hemato-oncology ward. Out of 955 patients who were eligible for evaluation, 381 (39.9%) died within 30 days from the onset of candidemia. Important differences in the 30-day mortality rates were noted between institutions: the lowest mortality rate was in the Barcelona hospital, and the highest rate was in the Udine hospital (33.6% versus 51%, respectively; P = 0.0005). Overall, 5.1% of the 955 isolates tested were resistant or susceptible dose dependent (SDD) to fluconazole, with minor differences between the hospitals in Italy and Spain (5.7% versus 3.5%, respectively; P = 0.2). Higher MICs for caspofungin were found, especially with C. parapsilosis complex (MIC90, 1 µg/ml). Amphotericin B had the lowest MICs. This report shows that candidemia is a significant source of morbidity in Europe, causing a substantial burden of disease and mortality.

Post-COVID-19 Syndrome 2 Years After the First Wave: The Role of Humoral Response, Vaccination and Reinfection.

Background: The aim of this study was to describe the long-term evolution of post-COVID-19 syndrome over 2 years after the onset of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in survivors of the first wave. Methods: This prospective study was based on interviews and investigated post-COVID-19 syndrome 6, 12, and 24 months after the disease onset in all adult in- and outpatients with COVID-19 followed at Udine Hospital (Italy) during the first wave (March-May 2020). Humoral response, vaccination status, and reinfection were assessed. Results: Overall, 230 patients (53.5% female; mean age 54.7 years) were interviewed 2.3 years (standard deviation = 0.11) after acute onset. Post-COVID-19 syndrome was observed in 36.1% of patients (n = 83) at 2 years. The most common persistent symptoms were fatigue (14.4%), rheumatological (14.4%), and psychiatric symptoms (9.6%). Overall, 55.4% (46 of 83) of long haulers searched for healthcare system support and 21 (45.7%) were visited by a specialist. Female gender (odds ratio [OR] = 2.50, P = .005), a proportional increase in the number of symptoms during acute COVID-19 (OR = 1.40, P = .001), and the presence of comorbidities (OR = 1.57, P = .004) were all independent risk factors for post-COVID-19 syndrome. Vaccination and reinfection had no impact on post-COVID-19 syndrome dynamics. The presence of receptor-binding domain (RBD) SARS-CoV-2 immunoglobulin G (IgG) and non-RBD SARS-CoV-2 IgG titers were not associated with the occurrence of post-COVID-19 syndrome. Conclusions: Two years after COVID-19, the burden of persistent symptoms remains high among in- and outpatients' population infected during the first wave. Post-COVID-19 dynamic does not seem to be influenced by SARS-CoV-2 immunization status and reinfection.