Showing papers by "Maddalena Peghin published in 2020"

Inhaled Liposomal Antimicrobial Delivery in Lung Infections

Abstract: The management of difficult-to-treat acute and chronic respiratory infections (infections in cystic fibrosis, non-cystic fibrosis bronchiectasis, immunocompromised and mechanically ventilated patients) and difficult-to-treat pathogens (including multidrug-resistant strains) has become a challenge in clinical practice. The arsenal of conventional antibiotic drugs can be limited by tissue penetration, toxicities, or increasing antibiotic resistance. Inhaled antimicrobials are an interesting therapeutic approach for optimizing the management of respiratory infections. Due to extensive developments in liposome technology, a number of inhaled liposome-based antibiotic and antifungal formulations are available for human use and many products are undergoing clinical trials. Liposomes are biocompatible, biodegradable, and nontoxic vesicles able to encapsulate and carry antimicrobials, enhancing the therapeutic index of various agents and retention at the desired target within the lung. Liposomes reduce drug toxicity and improve tolerability, leading to better compliance and to decreased respiratory side effects. The aim of this article was to provide an up-to-date overview of nebulized liposomal antimicrobials for lung infections (with a special focus on liposomal amikacin, tobramycin, ciprofloxacin, and amphotericin B for inhalation), discussing the feasibility and therapeutic potential of these new strategies of preventing and treating bacteria, mycobacterial and fungal infections.

Treatment of Bloodstream Infections Due to Gram-Negative Bacteria with Difficult-to-Treat Resistance.

Abstract: The rising incidence of bloodstream infections (BSI) due to Gram-negative bacteria (GNB) with difficult-to-treat resistance (DTR) has been recognized as a global emergency. The aim of this review is to provide a comprehensive assessment of the mechanisms of antibiotic resistance, epidemiology and treatment options for BSI caused by GNB with DTR, namely extended-spectrum Beta-lactamase-producing Enterobacteriales; carbapenem-resistant Enterobacteriales; DTR Pseudomonas aeruginosa; and DTR Acinetobacter baumannii.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

Abstract: Background: We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa (PA) in neutropenic cancer patients. Methods: We performed a multicenter, retrospective cohort study including onco-hematological neutropenic patients with BSI due to PA conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict multidrug resistance of the causative pathogens. Results: Of a total of 1217 episodes of BSI due to PA, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (p=0.033). Predictors of MDRPA BSI were prior therapy with piperacillin/tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29-5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65-3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92-4.64), underlying hematological disease (OR, 2.09 95% CI, 1.26-3.44) and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65-3.91), whereas older age (OR, 0.98; 95% CI, 0.97-0.99) was found to be protective. Conclusions: Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDRPA. The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients, who may benefit from the early administration of a broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at low risk of resistance.

How to manage KPC infections

Abstract: Carbapenemase-producing Enterobacteriaceae represent an increasing global threat worldwide and Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. Risk stratification and rapid diagnostics laboratory workflows are of paramount importance and indication for therapy of KPC-KP infection must be individualized according to the baseline characteristics of the patient and severity of infection. The optimal treatment of infection because of KPC-KP organisms is uncertain and antibiotic options are limited. The knowledge of the patient's pathophysiology, infection site, and application of the pharmacokinetic/pharmacodynamic principles on the basis of minimum inhibitory concentration (MIC) has progressively gained major relevance. Combination therapies including high-dose meropenem, colistin, fosfomycin, tigecycline, and aminoglycosides are widely used, with suboptimal results. In the past few years, new antimicrobials targeting KPC-KP have been developed and are now at various stages of clinical research. However, their optimal use should be guaranteed in the long term for delaying, as much as possible, the emergence of resistance. Strict infection control measures remain necessary. The aim of this review is to discuss the challenges in the management and treatment of patients with infections because KPC-KP and provide an expert opinion.

Prevalencia de enfermedad colorrectal en la endocarditis infecciosa por Enterococcus faecalis: resultados de un estudio multicéntrico observacional

Abstract: Resumen Introduccion y objetivos El objetivo del estudio fue determinar la prevalencia de patologia colorrectal en los pacientes con endocarditis infecciosa por Enterococcus faecalis (EIEF). Metodos Se realizo un estudio observacional, retrospectivo y multicentrico en 4 hospitales de referencia. Se incluyeron todos los episodios consecutivos de EIEF definitivas en adultos desde el momento en que se empezo a realizar una colonoscopia por protocolo en cada centro participante hasta octubre de 2018. Se recogieron los hallazgos endoscopicos de patologia colorrectal potencialmente causante de una bacteriemia. Resultados Se incluyeron 103 pacientes con EIEF; 83 (81%) eran varones, la edad mediana era 76 [rango intercuartilico, 67-82] anos, y la mediana del indice de Charlson ajustado por edad fue 5 [rango intercuartilico, 4-7]. El presunto origen de la infeccion fue desconocido en 63 (61%), urinario en 20 (19%), digestivo en 13 (13%), bacteriemia de cateter en 5 (5%), y otros en 2 (2%). En 78 (76%) pacientes se realizo una colonoscopia, y en 47 (60%) habia hallazgos endoscopicos que indicaban un potencial foco de bacteriemia. Treinta y nueve (83%) tenian una enfermedad colorrectal neoplasica, y 8 (17%) no neoplasica. De los 45 pacientes con puerta de entrada desconocida y colonoscopia, un posible origen gastrointestinal se identifico en 64%. En el subgrupo de 25 con foco de entrada conocido y colonoscopia, excluyendo aquellos con enfermedad colorrectal ya previamente diagnosticada, 44% tenian patologia colorrectal. Conclusiones Realizar una colonoscopia en la EIEF, sin tener en cuenta la puerta de entrada, puede ayudar a diagnosticar la enfermedad colorrectal en estos pacientes y evitar una nueva bacteriemia (y eventualmente endocarditis infecciosa) por el mismo u otro microorganismo.

Prevalence of colorectal disease in Enterococcus faecalis infective endocarditis: results of an observational multicenter study

Abstract: Introduction and objectives The aim of this study was to determine the prevalence of colorectal disease in Enterococcus faecalis infective endocarditis (EFIE) patients. Methods An observational, retrospective, multicenter study was performed at 4 referral centers. From the moment that a colonoscopy was systematically performed in EFIE in each participating hospital until October 2018, we included all consecutive episodes of definite EFIE in adult patients. The outcome was an endoscopic finding of colorectal disease potentially causing bacteremia. Results A total of 103 patients with EFIE were included; 83 (81%) were male, the median age was 76 [interquartile range 67-82] years, and the median age-adjusted Charlson comorbidity index was 5 [interquartile range 4-7]. The presumed sources of infection were unknown in 63 (61%), urinary in 20 (19%), gastrointestinal in 13 (13%), catheter-related bacteremia in 5 (5%), and others in 2 (2%). Seventy-eight patients (76%) underwent a colonoscopy, and 47 (60%) had endoscopic findings indicating a potential source of bacteremia. Thirty-nine patients (83%) had a colorectal neoplastic disease, and 8 (7%) a nonneoplastic disease. Of the 45 with an unknown portal of entry who underwent a colonoscopy, gastrointestinal origin was identified in 64%. In the subgroup of 25 patients with a known source of infection and a colonoscopy, excluding those with previously diagnosed colorectal disease, 44% had colorectal disease. Conclusions Performing a colonoscopy in all EFIE patients, irrespective of the presumed source of infection, could be helpful to diagnose colorectal disease in these patients and to avoid a new bacteremia episode (and eventually infective endocarditis) by the same or a different microorganism.

Optimal Management of Complicated Infections in the Pediatric Patient: The Role and Utility of Ceftazidime/Avibactam.

Abstract: Antimicrobial resistance poses a substantial threat to global public health. The pursuit of new antibiotics has decreased and very few options have been investigated for the treatment of complicated multidrug-resistant Gram-negative (MDR-GN) infections in adult population and even less in pediatric patients. Ceftazidime-avibactam (CAZ-AVI) is novel cephalosporin/β-lactamase inhibitor (BL-BLI) combination with broad antibacterial spectrum. The aim of this review is to describe the current and future role CAZ-AVI in the pediatric population with suspected or confirmed MDR-GN infections.

Salvage heart transplantation for Mycoplasma hominis prosthetic valve endocarditis: A case report and review of the literature.

Abstract: Heart transplantation (HT) has been rarely performed in patients with infective endocarditis (IE) and is considered a "last resort" procedure. Orthotropic HT with bicaval technique was performed in a man with culture-negative endocarditis. Mycoplasma hominis was later detected using 16S ribosomal DNA PCR from surgically removed valve tissue. Literature review and previous results are summarized. HT may be considered as salvage treatment in selected patients with intractable IE. In cases when there is no growth in culture, 16S ribosomal DNA PCR sequencing can be used to identify the pathogen in excised valvular tissue. Mycoplasma spp. is extremely uncommon and difficult to diagnose cause of infective endocarditis (IE). There are no proposed or defined criteria for heart transplantation (HT) in patients with refractory IE, and HT has been rarely performed in this setting. We report a case of M hominis prosthetic valve endocarditis diagnosed by 16S ribosomal DNA PCR in a patient who underwent a salvage HT. We reviewed in the literature other cases of IE caused by Mycoplasma spp.

Risk Factors for Candidemia After Open Heart Surgery: Results From a Multicenter Case-Control Study.

Abstract: Background Candida species are among the most frequent causative agents of health care-associated bloodstream infections, with mortality >40% in critically ill patients. Specific populations of critically ill patients may present peculiar risk factors related to their reason for intensive care unit admission. The primary objective of the present study was to assess the predictors of candidemia after open heart surgery. Methods This retrospective, matched case-control study was conducted in 8 Italian hospitals from 2009 to 2016. The primary study objective was to assess factors associated with the development of candidemia after open heart surgery. Results Overall, 222 patients (74 cases and 148 controls) were included in the study. Candidemia developed at a median time (interquartile range) of 23 (14-36) days after surgery. In multivariable analysis, independent predictors of candidemia were New York Heart Association class III or IV (odds ratio [OR], 23.81; 95% CI, 5.73-98.95; P < .001), previous therapy with carbapenems (OR, 8.87; 95% CI, 2.57-30.67; P = .001), and previous therapy with fluoroquinolones (OR, 5.73; 95% CI, 1.61-20.41; P = .007). Crude 30-day mortality of candidemia was 53% (39/74). Septic shock was independently associated with mortality in the multivariable model (OR, 5.64; 95% CI, 1.91-16.63; P = .002). No association between prolonged cardiopulmonary bypass time and candidemia was observed in this study. Conclusions Previous broad-spectrum antibiotic therapy and high NYHA class were independent predictors of candidemia in cardiac surgery patients with prolonged postoperative intensive care unit stay.

Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature.

Abstract: Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severe Plasmodium falciparum cerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids. A systematic research of current literature related to PMNS was performed. 151 cases of PMNS were included, the majority of which occurred after severe P. falciparum infections. Four main clinical pattern were identified: 37% of the cases presented as “classical” PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms. PMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management.

Neuroinvasive West Nile Infection with an Unusual Clinical Presentation: A Single-Center Case Series

Abstract: The 2018 West Nile Virus (WNV) season in Europe was characterized by an extremely high infection rate and an exceptionally higher burden when compared to previous seasons. Overall, there was a 10.9-fold increase in incidence in Italy, with 577 human cases, 230 WNV neuroinvasive diseases (WNNV) and 42 WNV-attributed deaths. Methods: in this paper we retrospectively reported the neurological presentation of 7 patients admitted to University Hospital of Udine with a diagnosis of WNNV, especially focusing on two patients who presented with atypical severe brain stem involvement. Conclusions: the atypical features of some of these forms highlight the necessity to stay vigilant and suspect the diagnosis when confronted with neurological symptoms. We strongly encourage clinicians to consider WNNV in patients presenting with unexplained neurological symptoms in mild climate-areas at risk.