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BACKGROUND/AIMS: Hepatitis C virus (HCV) has been identified in tubular epithelial cells of infected patients; however, the presence of tubular dysfunction, which is a risk factor for chronic kidney disease (CKD), has never been examined in vivo. The present prospective longitudinal study aimed to estimate the prevalence of tubular dysfunction alone or with glomerular damage and its evolution after HCV clearance in cirrhotic patients. METHODS: One hundred and thirty-five consecutive Child-Pugh A cirrhotic patients were evaluated before antiviral treatment and 6 months after the end of therapy. Tubular dysfunction was evaluated by urinary alpha1-microglobulin to creatinine ratio (α1-MCR), and glomerular damage was assessed by urinary albumin to creatinine ratio (ACR). RESULTS: Almost all the patients (93.3%) showed a normal or mildly decreased e-GFR (KDIGO-G1/G2-categories). Tubular dysfunction was found in 23.7% (32/135) of patients, co-occurring with glomerular damage in 37.5% (12/32) of cases, while glomerular damage was found in 16.3% (22/135) of patients. In multiple logistic regression, glomerular damage and the concomitant presence of diabetes and hypertension were the only predictors significantly associated with tubular dysfunction. After HCV clearance, patients experienced a significant reduction of α1-MCR levels (21.0 vs 10.5 µg/mg, P = .009) and tubular dysfunction resolved in 57.1% of subjects. CONCLUSIONS: Tubular dysfunction is an unrecognized feature of HCV-related kidney disease in cirrhotic patients and its presence should be primarily investigated in subjects with glomerular damage, diabetes and hypertension, despite normal e-GFR. Tubular dysfunction resolves in the majority of cases after HCV clearance; however, it may persist after antiviral treatment and further studies should evaluate its long-term impact on kidney function.
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Hepatite C Crônica , Hepatite C , Antivirais/uso terapêutico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Estudos Longitudinais , Estudos Prospectivos , Resposta Viral SustentadaRESUMO
INTRODUCTION: Hepatitis E virus (HEV) is an emerging cause of autochthonous-acute-hepatitis and acute-on-chronic-liver-failure in western countries. Treatment is not routinely used, despite ribavirin has a good antiviral effect. In vitro sofosbuvir inhibits HEV replication, but clinical data are lacking. CASE REPORT: We report a case of acute-on-chronic-liver-failure due to HEV treated with sofosbuvir and ribavirin. The treatment was capable of rapidly inducing both HCV and HEV viral suppression. CONCLUSION: In conclusion, although more data are required before firm conclusions could be drawn, the combination of sofosbuvir and ribavirin in not immunosuppressed patients with acute hepatitis E may be able to clear HEV infection.
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Hepatite E/tratamento farmacológico , Hepatite E/transmissão , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/tratamento farmacológico , Insuficiência Hepática Crônica Agudizada/virologia , Biomarcadores , Coinfecção , Quimioterapia Combinada , Evolução Fatal , Hepatite E/diagnóstico , Hepatite E/virologia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Choque Séptico , Sofosbuvir/administração & dosagem , Resultado do Tratamento , Carga ViralRESUMO
Introduction: Real-life experience with imipenem/cilastatin/relebactam (IMI/REL) for the treatment of KPC-producing Klebsiella pneumoniae complex (KPC-Kp) and difficult-to-treat resistance (DTR) Pseudomonas aeruginosa (DTR-PA) infections is herein described. Methods: Adult patients with KPC-Kp or DTR-PA infections who received ≥48 h of IMI/REL were included. Clinical and microbiological outcomes were retrieved through the medical records. Primary outcome was clinical cure. Secondary outcomes included mortality from infection onset and adverse effects attributable to IMI/REL. Results: We included 10 patients with different infections caused by DTR-PA (n = 4), KPC-Kp [n = 5, of which 3 ceftazidime/avibactam-resistant (CTV-R KPC-Kp), 2 CTV susceptible (CTV-S KPC-Kp)] or both DTR-PA/KPC-Kp (n = 1) successfully treated with IMI/REL: 3 hospital-acquired pneumonia, 1 ventilator-associated pneumonia, 2 skin and soft tissue infections, 1 osteomyelitis, 2 bloodstream infections, 1 complicated urinary tract infection. Clinical cure was achieved in all cases. No patients died and no side effect were reported. Discussion: We reported the preliminary real-life experience on the successful and safe use of IMI/REL for the treatment of KPC-Kp or DTR-PA complicated infections, including pneumonia and bone infections.
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OBJECTIVE: A case of post-neurosurgical ventriculitis caused by a KPC-producing Klebsiella pneumoniae (KPC-Kp) with a ceftazidime/avibactam-resistant, meropenem-susceptible phenotype is reported. METHODS AND RESULTS: The patient had a concomitant bloodstream infection with a wild-type KPC-Kp with a ceftazidime/avibactam-susceptible, meropenem-resistant phenotype. Prolonged treatment with intravenous fosfomycin and meropenem/vaborbactam achieved clinical success. Therapeutic drug monitoring performed during the first days of treatment showed for the first time that vaborbactam efficiently penetrates cerebrospinal fluid. In contrast, meropenem was undetectable in cerebrospinal fluid at each sampling, suggesting that additional doses of meropenem may be required to appropriately prescribe meropenem/vaborbactam for central nervous system infections. Plasma and cerebrospinal fluid levels of fosfomycin were adequate, confirming the potential of this agent possibly even in the fight against multidrug-resistant organisms. CONCLUSIONS: This case highlights the need for therapeutic drug monitoring as a crucial tool for optimizing treatment in complicated cases where the pharmacokinetic behaviour of antibiotics is difficult to predict.
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Antibacterianos , Bacteriemia , Ácidos Borônicos , Ventriculite Cerebral , Fosfomicina , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Humanos , Fosfomicina/uso terapêutico , Fosfomicina/administração & dosagem , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Meropeném/administração & dosagem , Meropeném/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Ventriculite Cerebral/tratamento farmacológico , Ventriculite Cerebral/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Ácidos Borônicos/administração & dosagem , Testes de Sensibilidade Microbiana , Masculino , beta-Lactamases/metabolismo , Farmacorresistência Bacteriana Múltipla , Pessoa de Meia-Idade , Combinação de Medicamentos , Feminino , Procedimentos Neurocirúrgicos , Resultado do Tratamento , Compostos Heterocíclicos com 1 AnelRESUMO
INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) are a subtype of skin and soft tissue infections (SSTI), usually sustained by Gram-positive bacteria, whose incidence is high among children. ABSSSIs are responsible for a considerable number of hospitalizations. Moreover, as multidrug resistant (MDR) pathogens become widespread, the pediatric category seems burdened with an increased risk of resistance and treatment failure. AREAS COVERED: To obtain a view on the status of the field, we describe the clinical, epidemiological, and microbiological aspects of ABSSSI in children. Old and new treatment options were critically revised with a focus on the pharmacological characteristics of dalbavancin. Evidence on the use of dalbavancin in children was collected, analyzed, and summarized. EXPERT OPINION: Many of the therapeutic options available at the moment are characterized by the need for hospitalization or repeated intravenous infusions, safety issues, possible drug-drug interactions, and reduced efficacy on MDRs. Dalbavancin, the first long-acting molecule with strong activity against methicillin-resistant and also many vancomycin-resistant pathogens represents a game changer for adult ABSSSI. In pediatric settings, the available literature is still limited, but a growing body of evidence supports dalbavancin use in children with ABSSSI, demonstrating this drug to be safe and highly efficacious.
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Infecções por Bactérias Gram-Positivas , Dermatopatias Bacterianas , Infecções dos Tecidos Moles , Adulto , Humanos , Criança , Antibacterianos/efeitos adversos , Dermatopatias Bacterianas/tratamento farmacológico , Dermatopatias Bacterianas/microbiologia , Teicoplanina , Infecções dos Tecidos Moles/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/epidemiologiaRESUMO
Infectious endocarditis is a severe condition still characterized by a high morbidity and mortality rate. An early diagnosis may positively impact the outcome, so we need our diagnostic tools to match with the ever-changing epidemiologic and microbiologic landscape of infectious diseases. We read with great interest the update to the Modified Duke Criteria for the diagnosis of Infectious Endocarditis recently proposed by the International Society for Cardiovascular Infectious Diseases and decided to propose the addition of Erysipelothrix rhusiopathiae to the list of typical microorganisms causing Endocarditis. This pathogen is widespread distributed in the world, has a zoonotic origin, harbors virulence factors and a multidrug resistance phenotype. Moreover, its retrieval from blood seems to have an important correlation with the presence of Endocarditis. The inclusion of E. rhusiopathiae in the list of typical microorganisms may represent a further refinement of the Modified Duke Criteria, which represent a fundamental tool in the management of patients with suspected endocarditis.
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The overall low-quality evidence concerning the clinical benefits of different antibiotic regimens for the treatment of infective endocarditis (IE), which has made it difficult to strongly support or reject any regimen of antibiotic therapy, has led to a discrepancy between the available guidelines and clinical practice. In this complex scenario, very recently published guidelines have attempted to fill this gap. Indeed, in recent years several antimicrobials have entered the market, including ceftobiprole, ceftaroline, and the long-acting lipoglycopeptides dalbavancin and oritavancin. Despite being approved for different indications, real-world data on their use for the treatment of IE, alone or in combination, has accumulated over time. Furthermore, an old antibiotic, fosfomycin, has gained renewed interest for the treatment of complicated infections such as IE. In this narrative review, we focused on new antimicrobials and therapeutic strategies that we believe may provide important contributions to the advancement of Gram-positive IE treatment, providing a summary of the current in vitro, in vivo, and clinical evidence supporting their use in clinical practice.
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Background: Recently, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae (KPC-Kp) with resistance to ceftazidime/avibactam (CZA-R) has been described, including KPC variants that restore carbapenem susceptibility. The aim of the study was to analyze the clinical characteristics and outcomes of infections caused by CZA-R KPC-Kp. Methods: From 2019 to 2021, a retrospective 2-center study including patients with infections due to CZA-R KPC-Kp hospitalized at 2 academic hospitals in Rome was conducted. Demographic and clinical characteristics were collected. Principal outcome was 30-day all-cause mortality. Statistical analyses were performed with Stata-IC17 software. Results: Overall, 59 patients were included (mean age, 64.4 ± 14.6 years; mean Charlson comorbidity index score, 4.5 ± 2.7). Thirty-four patients (57.6%) had infections caused by CZA-R and meropenem (MEM)-susceptible strains. A previous CZA therapy was observed in 40 patients (67.8%), mostly in patients with MEM-susceptible KPC variant (79.4% vs 52%, P = .026). Primary bacteremia was observed in 28.8%, followed by urinary tract infections and pneumonia. At infection onset, septic shock was present in 15 subjects (25.4%). After adjustment for confounders, only the presence of septic shock was independently associated with mortality (P = .006). Conclusions: Infections due to CZA-R KPC-Kp often occur in patients who had previously received CZA, especially in the presence of strains susceptible to MEM. Nevertheless, one-third of patients had never received CZA before KPC-Kp CZA-R. Since the major driver for mortality was infection severity, understanding the optimal therapy in patients with KPC-Kp CZA-R infections is of crucial importance.
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OBJECTIVE: The risk of reinfection with SARS-CoV-2 has been rapidly increased with the circulation of concerns about variants. So, the aim of our study was to evaluate the factors that increase the risk of this reinfection in healthcare workers compared to those who have never been positive and those who have had only one positivity. METHODS: A case-control study was carried out at the Teaching Hospital Policlinico Umberto I in Rome, Sapienza University of Rome, in the period between 6 March 2020 and 3 June 2022. Cases are healthcare workers who have developed a reinfection with the SARS-CoV-2 virus, while controls were either healthcare workers who tested positive once or those who have never tested positive for SARS-CoV-2. RESULTS: 134 cases and 267 controls were recruited. Female gender is associated with a higher odds of developing reinfection (OR: 2.42; 95% CI: 1.38-4.25). Moreover, moderate or high alcohol consumption is associated with higher odds of reinfection (OR: 1.49; 95% CI: 1.19-1.87). Diabetes is also associated with higher odds of reinfection (OR: 3.45; 95% CI: 1.41-8.46). Finally, subjects with increased red blood cell counts have higher odds of reinfection (OR: 1.69; 95% CI: 1.21-2.25). CONCLUSION: From the prevention point of view, these findings indicate that particular attention should be paid to subjects with diabetes mellitus, women and alcoholic drinkers. These results could also suggest that contact tracing represents a fundamental approach model against the SARS-CoV-2 pandemic, together with the health information of participants.
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Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Talassemia beta/complicações , Adulto , Benzoatos/uso terapêutico , Crioglobulinemia/etiologia , Deferasirox , Desferroxamina/uso terapêutico , Técnicas de Imagem por Elasticidade , Feminino , Ferritinas/sangue , Hepatite C Crônica/complicações , Hepatite C Crônica/psicologia , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Masculino , Qualidade de Vida , Triazóis/uso terapêutico , Carga Viral , Talassemia beta/psicologiaRESUMO
This monocentric, retrospective, two-stage observational study aimed to recognize the risk factors for a poor outcome in patients hospitalized with SARS-CoV-2 infection, and to develop and validate a risk score that identifies subjects at risk of worsening, death, or both. The data of patients with SARS-CoV-2 infection during the first wave of the pandemic were collected and analyzed as a derivation cohort. Variables with predictive properties were used to construct a prognostic score, which was tried out on a validation cohort enrolled during the second wave. The derivation cohort included 494 patients; the median age was 62 and the overall fatality rate was 22.3%. In a multivariable analysis, age, oxygen saturation, neutrophil-to-lymphocyte ratio, C-reactive protein and lactate dehydrogenase were independent predictors of death and composed the score. A cutoff value of 3 demonstrated a sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 93.5%, 68.5%, 47.4% and 97.2% for death, and 84.9%, 84.5%, 79.6% and 87.9% for worsening, respectively. The validation cohort included 415 subjects. The score application showed a Se, Sp, PPV and NPV of 93.4%, 61.6%, 29.5% and 98.1% for death, and 81%, 76.3%, 72.1% and 84.1% for worsening, respectively. We propose a new clinical, easy and reliable score to predict the outcome in hospitalized SARS-CoV-2 patients.
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COVID-19 , COVID-19/diagnóstico , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
Despite the wide use of single-tablet regimens (STRs), few real-life data are available regarding the impact of pre-existent drug resistance on virological failure (VF). We aimed to fill this gap by analysing a large cohort of individuals selected from the ARCA database. The impact on VF of pre-existent resistance-associated mutations (RAMs) and cumulative genotypic susceptibility score (cGSS) before STR start was evaluated through survival analysis. Potential emergence of resistance at VF was also evaluated. Overall, 3916 individuals were included, comprising 678 treatment-naïve (G1), 2309 treatment-experienced aviraemic (G2) and 929 viraemic (G3), of whom 65.2% were treated with a STR based on efavirenz (35.2%) or rilpivirine (30.0%). At 2 years after starting a STR, the overall probability of VF was 5.9% in G1, 8.7% in G2 and 20.8% in G3. No impact of pre-existent resistance on VF was found in G1. The probability of VF was higher in patients with cGSS < 3 (reduced susceptibility to at least one drug) than in those with cGSS = 3 (full susceptibility to STR drugs) both in G2 and G3. A higher probability of VF was also found in the presence of pre-existent M184V (alone or in combination with pre-existent thymidine analogue mutations). Among patients who failed STR, a significant emergence of RAMs was found only in those exposed to EFV/FTC/TDF in G3 (specifically K103N and M184V). Our results confirm a high efficacy of STRs in clinical settings. Pre-existent resistance appears to influence virological efficacy of STRs in treatment-experienced individuals (both aviraemic and viraemic).
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Humanos , Comprimidos , Tenofovir/uso terapêutico , Carga ViralRESUMO
The spread of extremely-drug-resistant Klebsiella pneumoniae has become a major health threat worldwide. This is largely mediated by certain lineages, recognized as high-risk clones dispersed throughout the world. Analysis of an outbreak of nine ST15, NDM-1 metallo-ß-lactamase-producing K. pneumoniae was performed. An IncC plasmid carrying the blaNDM-1 gene also carried the rare rmtC gene, encoding for 16S rRNA methyltransferases (16RMTases), conferring resistance to all aminoglycosides. The global spread of New Delhi metallo (NDM) variants and their association with the 16RMTases among K. pneumoniae complete genomes available in GenBank was studied, and a complete overview of the association of 16RMTases and NDM in K. pneumoniae genomics was produced. NDM is often associated with16RMTases, and both are spreading in K. pneumoniae, conferring resistance to all beta-lactams and aminoglycosides. This analysis suggests that aminoglycosides have a limited future as a second-line treatment against NDM-producing K. pneumoniae.
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Infecções por Klebsiella , Klebsiella pneumoniae , Aminoglicosídeos/farmacologia , Antibacterianos/farmacologia , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla/genética , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/epidemiologia , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Plasmídeos/genética , RNA Ribossômico 16S/genética , beta-Lactamases/genéticaRESUMO
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.
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Gram-negative bacilli septic thrombosis (GNB-ST) represents a subtle and often misleading condition, potentially fatal if not recognized early and requiring prolonged antimicrobial therapy and anticoagulation. Herein, reported for the first time, is a very challenging case of Klebsiella producing carbapenemase (KPC)-producing K. pneumoniae (KPC-Kp) ST unresponsive to ceftazidime/avibactam (CZA) relapsed first with meropenem/vaborbactam (MVB) monotherapy and subsequently cured with MVB plus fosfomycin (FOS) combination. The present case highlights the possibility of CZA underexposure on the infected thrombus and the risk of in vivo emergence of CZA resistance in the setting of persistent bacteremia and sub-optimal anticoagulation. Pharmacokinetic analyses showed that both MVB and FOS were in the therapeutic range. In vitro studies demonstrated a high level of MVB + FOS synergism that possibly allowed definitive resolution of the endovascular infection.
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Bloodstream infections still constitute an outstanding cause of in-hospital morbidity and mortality, especially among critically ill patients. Follow up blood cultures (FUBCs) are widely recommended for proper management of Staphylococcus aureus and Candida spp. infections. On the other hand, their role is still a matter of controversy as far as Gram negative bacteremias are concerned. We revised, analyzed, and commented on the literature addressing this issue, to define the clinical settings in which the application of FUBCs could better reveal its value. The results of this review show that critically ill patients, endovascular and/or non-eradicable source of infection, isolation of a multi-drug resistant pathogen, end-stage renal disease, and immunodeficiencies are some factors that may predispose patients to persistent Gram negative bacteremia. An analysis of the different burdens that each of these factors have in this clinical setting allowed us to suggest which patients' FUBCs have the potential to modify treatment choices, prompt an early source control, and finally, improve clinical outcome.
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Since the most frequent symptoms of novel coronavirus 2019 disease (COVID-19) are common in influenza A/B (FLU), predictive models to distinguish between COVID-19 and FLU using standardized non-specific laboratory indicators are needed. The aim of our study was to evaluate whether a recently dynamic nomogram, established in the Chinese population and based on age, lymphocyte percentage and monocyte absolute count, might apply to a different context. We collected data from 299 patients (243 with COVID-19 and 56 with FLU) at Policlinico Umberto I, Sapienza University of Rome. The nomogram included age, lymphocyte percentage and monocyte absolute count to differentiate COVID-19 from FLU. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all associations. Multivariate logistic regression models were used to adjust for potential confounding. A p-value of less than 0.05 was considered statistically significant. Patients with COVID-19 had higher age, lymphocyte percentage and monocyte absolute count than patients with FLU. Although univariate analysis confirmed that age, lymphocyte percentage and monocyte absolute count were associated with COVID-19, only at multivariate analysis was monocyte count statistically significant as a predictive factor of COVID-19. Using receiver operating characteristic (ROC) curves, we found that a monocyte count >0.35x1000/mL showed an AUC of 0.680 (sensitivity 0.992, specificity 0.368). A dynamic nomogram including age, lymphocyte percentage and monocyte absolute count cannot be applied to our context, probably due to differences in demographic characteristics between Italian and Chinese populations. However, our data showed that monocyte absolute count is highly predictive of COVID-19, suggesting its potential role above all in settings where prompt PCR nasopharyngeal testing is lacking.