Herein we report the case of hepatic amoebic abscesses in an HIV-positive Italian seaman with a history of promiscuous heterosexual intercourse. In October 2004, the patient was hospitalized because ...of fever and recurring abdominal pain. Abdominal ultrasonography revealed six hepatic hypoechoid oval lesions with hyperechoid margins. Stool samples were negative for parasites and bacteria, and serology for Entamoeba histolytica was also negative. Therapy with meropenem plus levofloxacin was initiated. After a partial resolution of clinical symptoms and reduction of three hepatic lesions, the patient was again hospitalized in December 2004, because of recurring intense pain at the right hypochondrium and fever. At this time, one hepatic lesion at the sixth segment was enlarged, two lesions were unchanged, and the remaining three smaller abscesses were resolved. Serum antibodies for E. histolytica and amoebic antigens on the largest abscess drainage were positive; moreover, E. histolytica was also identified on drainage fluid with polymerase chain reaction (PCR). Therapy with metronidazole followed by paromomycin improved both symptoms and radiographic images. This case report suggests that in HIV-infected patients, invasive amoebiasis should be considered and atypical aspects, such as multiple hepatic lesions, delayed positivity of serology for E. histolytica, and possible bacterial superinfection should be evaluated.
Therapy of acute hepatitis C (AHC) has not yet been standardized and several issues are still unresolved. This open, randomized, multicenter trial aimed to assess the efficacy and safety of a 24‐week ...course of pegylated IFN (Peg‐IFN) alpha‐2b versus a 12‐week course of Peg‐IFN alpha‐2b alone or with ribavirin (RBV) in AHC patients. One hundred and thirty HCV acutely infected patients who did not spontaneously resolve by week 12 after onset were consecutively enrolled and randomized to receive Peg‐IFN alpha‐2b monotherapy (1.5 μg/kg/week) for 24 or 12 weeks (arm 1, n = 44 and arm 2, n = 43, respectively) or in combination with RBV (10.6 mg/kg/day) for 12 weeks (arm 3, n = 43). The primary endpoint was undetectable HCV RNA at 6‐month posttreatment follow‐up (sustained virological response; SVR). All patients were followed for 48 weeks after therapy cessation. HCV RNA levels were determined by real‐time polymerase chain reaction (limit of detection: 15 IU/mL) at the central laboratory at baseline, week 4, end of treatment, and 6 and 12 months posttreatment. Using an intent‐to‐treat analysis, overall SVR rate was 71.5%. In particular, an SVR was achieved in 31 of 44 (70.5%), 31 of 43 (72.1%), and 31 of 43 (72.1%) patients in arms 1, 2, and 3, respectively (P = 0.898). Sixteen patients (12.3%) prematurely discontinued therapy or were lost to follow‐up; thus, sustained response rates with per‐protocol analysis were 81.6%, 81.6%, and 81.6% for patients in arms 1, 2, and 3 respectively. With multivariate analysis, virologic response at week 4 of treatment was an independent predictor of SVR. Peg‐IFN alpha‐2b was well tolerated. Conclusion: Peg‐IFN alpha‐2b induces a high SVR in chronically evolving AHC patients. Response rates were not influenced by combination therapy or treatment duration. (Hepatology 2014;59:2101‐2109)
Objective
To report the efficacy, tolerability, and pharmacokinetic effects of combined voriconazole and efavirenz treatment administered at therapeutic drug monitoring (TDM)–based adjusted doses to ...a patient with AIDS, cryptococcosis, and mild liver cirrhosis.
Case Summary
A 40-year-old man with AIDS (hemophiliac, antiretroviral-naïve, plasma HIV-RNA = 290,000 copies/mL, CD4+ lymphocytes = 0), hepatitis C virus–related liver cirrhosis (Child-Pugh class A), and cryptococcal meningitis was failing standard antifungal therapies. He received an antifungal–antiretroviral combination treatment based on the association of voriconazole plus efavirenz. Doses of both drugs were serially adjusted based on their plasma concentrations, which were evaluated at steady-state of each dose combination at least once (week 3.1 or later) as full concentration–time profile (samples collected at 0, 1, 2, 3, 4, 6, 8, 12 h postdose). Adequate concentrations of voriconazole in both plasma and cerebrospinal fluid were obtained and target plasma concentrations of efavirenz were achieved at the final dose adjustment (voriconazole 200 mg twice daily plus efavirenz 300 mg once daily, both administered orally). The patient showed prompt and stable suppression of cryptococcosis and plasma viremia of HIV at long-term follow-up (66 wk), with no significant adverse events.
Discussion
Standard therapies for cryptococcosis in patients with AIDS are often not effective. Voriconazole, despite its promising anticryptococcal efficacy, is currently not approved for cryptococcosis therapy in the US and Europe, nor is it recommended for combination with efavirenz due to the significant pharmacokinetic interactions between the 2 compounds. Thus far, published studies regarding the effects of voriconazole in human cryptococcosis are scarce and none has described the clinical and pharmacokinetic outcomes of a voriconazole/efavirenz combination in patients with AIDS, either with or without liver cirrhosis.
Conlusions
The combination of voriconazole and efavirenz at TDM-assisted doses may represent a valuable therapeutic option in AIDS patients with cryptococcosis and mild liver cirrhosis.
Summary Human infection with Aeromonas species is uncommon and most often due to trauma with exposure to contaminated water or soil. A 43-year-old HIV- and hepatitis C virus (HCV)-infected male, ...after a two-week course of corticosteroid therapy for an autoimmune anemia, developed diarrhea, dermatologic manifestations and a multiple organ dysfunction syndrome, resulting in death. Although stool samples were repeatedly negative, two sets of blood cultures obtained during a single peak of fever yielded the post-mortem isolation of a Gram-negative, oxidase-positive, β-hemolytic bacillus that was identified as Aeromonas sobria . Empiric antibiotic therapy was unsuccessful. Evaluation of the virulence-associated traits of the clinical isolate (adhesion, cytotoxicity activity, biofilm production) showed that the strain was a poor producer of recognized virulence factors, thereby indicating that the unfortunate coexistence of HIV infection, HCV-related liver cirrhosis and corticosteroids played a key role in the clinical course.
Community-acquired pneumonia (CAP) often represents a clinical emergency requiring prompt and adequate antimicrobial treatment. The choice of antimicrobials, however, is difficult due to the variety ...of potential pathogens and to the spread of drug-resistance. Hence, a correct therapeutic approach should be based on the knowledge of the most frequently reported etiologies for the different clinical conditions, specific patient risk factors and the treatment setting (home, hospital, intensive or non intensive care unit) chosen accordingly. The awareness of the local drug-resistance epidemiology and individual patient characteristics, such as age, history of antibiotic treatments and related adverse events, underlying diseases, concurrent therapies and expected adherence to treatment should also be considered. Lastly, an adequate CAP management should address other issues, including therapy duration, monitoring of its efficacy and adverse effects, and supportive measures. The guidelines for CAP management aim to provide the physician with the necessary knowledge and criteria to assist him in these crucial decisions, and their adoption result in a significant reduction of mortality, frequency and length of hospitalization, and costs. Herein, the authors review and discuss some of the main current guidelines for CAP management, highlighting their differences and similarities.
Abstract
Background: Metabolic syndrome (MS) represents a cluster of cardiovascular risk factors that has become a serious problem for HIV-1-infected patients. It has been proposed that disturbance ...of phosphate metabolism may represent a key feature of MS. Thus, we undertook the present study to investigate the relationship between phosphate levels and the presence of the characteristics of MS. Methods: One hundred and twenty-one HIV-1-infected patients were consecutively enrolled in a prospective, cross-sectional, single-centre study. Kidney tubular function was examined using tubular resorption of phosphate and normalized renal threshold phosphate concentration. Results: Univariate analysis showed that serum phosphate levels correlated negatively with systolic and diastolic blood pressure, glucose values, waist circumference, insulin, and triglycerides. Moreover, there was a positive relationship between phosphate and high-density lipoprotein (HDL) cholesterol. Multivariate analysis showed that insulin levels were correlated with serum phosphate concentration (r = − 0.24, p = 0.01). Conclusions: Our data show that HIV-1-infected patients with MS have lower phosphate levels.
Recent developments in bottom-up synthetic biology (e.g., lipid vesicle technology integrated with cell-free protein expression systems) allow the generation of semi-synthetic minimal cells (in ...short, synthetic cells, SCs) endowed with some distinctive capacities of natural cells. In particular, such approaches provide technological tools and conceptual frameworks for the design and engineering of programmable SCs capable of communicating with natural cells by exchanging chemical signals. Here we describe the generation of giant vesicle-based SCs which, via gene expression, synthesize in their aqueous lumen an enzyme that in turn produces a chemical signal. The latter is a small molecule, which is passively released in the medium and then perceived by the bacterium Pseudomonas aeruginosa, demonstrating that SCs and bacteria can communicate chemically. The results pave the way to a novel basic and applied research area where synthetic cells can communicate with natural cells, for example for exploring minimal cognition, developing chemical information technologies, and producing smart and programmable drug-producing/drug-delivery systems.
The bottom-up branch of synthetic biology includes-among others-innovative studies that combine cell-free protein synthesis with liposome technology to generate cell-like systems of minimal ...complexity, often referred to as synthetic cells. The functions of this type of synthetic cell derive from gene expression, hence they can be programmed in a modular, progressive and customizable manner by means of
designed genetic circuits. This experimental scenario is rapidly expanding and synthetic cell research already counts numerous successes. Here, we present a review focused on the exchange of chemical signals between liposome-based synthetic cells (operating by gene expression) and biological cells, as well as between two populations of synthetic cells. The review includes a short presentation of the "molecular communication technologies," briefly discussing their promises and challenges.
Abstract
The encapsulation of transcription–translation (TX–TL) machinery inside lipid vesicles and water-in-oil droplets leads to the construction of cytomimetic systems (often called ‘synthetic ...cells’) for synthetic biology and origins-of-life research. A number of recent reports have shown that protein synthesis inside these microcompartments is highly diverse in terms of rate and amount of synthesized protein. Here, we discuss the role of extrinsic stochastic effects (i.e. solute partition phenomena) as relevant factors contributing to this pattern. We evidence and discuss cases where between-compartment diversity seems to exceed the expected theoretical values. The need of accurate determination of solute content inside individual vesicles or droplets is emphasized, aiming at validating or rejecting the predictions calculated from the standard fluctuations theory. At the same time, we promote the integration of experiments and stochastic modeling to reveal the details of solute encapsulation and intra-compartment reactions.
Protein synthesis is at the core of bottom-up construction of artificial cellular mimics. Intriguingly, several reports have revealed that when a transcription–translation (TX–TL) kit is encapsulated ...inside lipid vesicles (or water-in-oil droplets), high between-vesicles diversity is observed in terms of protein synthesis rate and yield. Stochastic solute partition can be a major determinant of these observations. In order to verify that the variation of TX–TL components concentration brings about a variation of produced protein rate and yield, here we directly measure the performances of the ‘PURE system’ TX–TL kit variants. We report and share the kinetic traces of the enhanced Green Fluorescent Protein (eGFP) synthesis in bulk aqueous phase, for 27 combinatorial block-variants. The eGFP production is a sensitive function of TX–TL components concentration in the explored concentration range. Providing direct evidence that protein synthesis yield and rate actually mirror the TX–TL composition, this study supports the above-mentioned hypothesis on stochastic solute partition, without excluding, however, the contribution of other factors (e.g., inactivation of components).
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