In vitro comparison of currently available and investigational antiviral agents against pathogenic human double-stranded DNA viruses: A systematic literature review

Background: Double-stranded (ds) DNA virus infections often occur concomitantly in immunocompromised patients. We performed a systematic search of published in vitro activity for nine approved and investigational antivirals to understand the spectrum of in vitro activity against dsDNA viruses. / Methods: A literature search was performed (PubMed and the WoS Core Collection) using keywords related to: 1) targeted approved/developmental antivirals (acyclovir, artesunate, brincidofovir, cidofovir, cyclopropavir (filociclovir), foscarnet, ganciclovir, letermovir, and maribavir); 2) pathogenic dsDNA viruses; 3) in vitro activity. We summarized data from 210 publications. / Results: Activity against ≤3 viruses was documented for maribavir (cytomegalovirus, Epstein-Barr virus), and letermovir, while activity against > 3 viruses was shown for ganciclovir, cidofovir, acyclovir, foscarnet, cyclopropavir, artesunate, and brincidofovir. The EC50 values of brincidofovir were the lowest, ranging from 0.001 to 0.27 μM, for all viruses except papillomaviruses. The next most potent agents included cidofovir, ganciclovir, foscarnet, and acyclovir with EC50 values between 0.1 μM and >10 μM for cytomegalovirus, herpes simplex virus, and adenovirus. / Conclusion: Most of the identified antivirals had in vitro activity against more than one dsDNA virus. Brincidofovir and cidofovir have broad-spectrum activity, and brincidofovir has the lowest EC50 values. These findings could assist clinical practice and developmental research

Tigecycline use in serious nosocomial infections: a drug use evaluation

<p>Abstract</p> <p>Background</p> <p>Tigecycline is a novel antibiotic with activity against multidrug resistant bacteria. The aim of this study was to assess the efficacy of tigecycline use in serious hospital-acquired infections (HAI)</p> <p>Case presentation</p> <p>Prospective observational study of tigecycline use was conducted in a 1500 beds university hospital. From January 1, 2007 and January 31, 2010, 207 pts were treated with tigecycline for the following indications: intra-abdominal, pneumonia, bloodstream and complicated skin and soft tissue infections and febrile neutropenia. The therapy was targeted in 130/207 (63%) and empirical in 77/207 (37%) patients. All bacteria treated were susceptible to tigecycline. Median duration of tigecycline therapy was 13 days (range, 6-28). Clinical success was obtained in 151/207 (73%) cases, with the highest success rate recorded in intra-abdominal infections [81/99 (82%)]. Microbiological success was achieved in 100/129 (78%) treated patients. Adverse clinical events were seen in 16/207 patients (7.7%):</p> <p>Conclusions</p> <p>Considering the lack of data on tigecycline for critically ill patients, we think that the reported data of our clinical experience despite some limitations can be useful for clinicians.</p

Flocked nasal swab versus nasopharyngeal aspirate for detection of respiratory tract viruses in immunocompromised adults: a matched comparative study

<p>Abstract</p> <p>Background</p> <p>Several studies have compared nasal swabs to the more invasive nasopharyngeal aspirate (NPA) for detection of respiratory viruses. Mostly, the comparisons have been performed on immunocompetent children with upper respiratory tract symptoms. The results range from a relatively poor sensitivity for the swabs to an even higher sensitivity than for the NPA. We aimed to investigate the sensitivity of a flocked nasal swab (fNS) on immunocompromised adults with febrile neutropenia.</p> <p>Methods</p> <p>During 16 months, adults with a hematological disorder presenting with febrile neutropenia were enrolled in the study. Paired samples of the fNS and NPA were collected in the outer part of the nasal cavity and the nasopharynx, respectively. The samples were analyzed regarding a panel of 15 respiratory viruses by means of quantitative polymerase chain reaction. Furthermore, as an indirect measure of cell yield by either method, the copy number of the human beta actin gene was also determined. Cohen's kappa was calculated as a measure of agreement of the results obtained from either method. Wilcoxon signed-rank test was used for comparison of cell yield.</p> <p>Results</p> <p>A total of 98 paired samples from a total of 89 patients were collected. Twenty of the pairs had virus detected in at least one of the specimens; 11 in both, 7 in NPA only, and 2 in fNS only. For the fNS, the overall sensitivity for any virus and for rhinovirus only was 65% and 78%, respectively. NPA was significantly superior to the fNS in collecting epithelial cells.</p> <p>Conclusion</p> <p>We found the overall sensitivity of 65% to be too low to replace NPA with this sampling technique in this patient category.</p

Electrospinning polypropylene with an amino acid as a strategy to bind the antimicrobial peptide Cys-LC-LL-37

Hospital isolation gowns are increasingly competitive, with brands and manufacturers contesting consumer preferences. The textile materials in contact with the skin can acquire secretions and multiresistant microorganisms, causing discomfort and health risks, respectively. A new nanofibrous substrate---polypropylene grafted with l-Cys---was developed with an increased crystallinity, providing its surface with --SH hooks necessary to efficiently cross-link the antimicrobial peptide Cys-LC-LL-37 in order to protect against nosocomial pathogens and their spread to community. Furthermore, this application does not require environmental control of humidity, and it is not susceptible to enzyme and microorganism degradation.The authors acknowledge the Fundação para a Ciência e Tecnologia (FCT) for the PhD Grant SFRH/ BD/91444/2012 and Programa Operacional Capital Humano (POCH) and European Union for co-funding the work.info:eu-repo/semantics/publishedVersio

Viral Findings in Adult Hematological Patients with Neutropenia

BACKGROUND: Until recently, viral infections in patients with hematological malignancies were concerns primarily in allogeneic hematopoietic stem cell transplant (HSCT) recipients. During the last years, changed treatment regimens for non-transplanted patients with hematological malignancies have had potential to increase the incidence of viral infections in this group. In this study, we have prospectively investigated the prevalence of a broad range of respiratory viruses in nasopharyngeal aspirate (NPA) as well as viruses that commonly reactivate after allogeneic HSCT. METHODOLOGY/PRINCIPAL FINDINGS: Patients with hematological malignancies and therapy induced neutropenia (n = 159) were screened regarding a broad range of common respiratory viruses in the nasopharynx and for viruses commonly detected in severely immunosuppressed patients in peripheral blood. Quantitative PCR was used for detection of viruses. A viral pathogen was detected in 35% of the patients. The detection rate was rather similar in blood (22%) and NPA (18%) with polyoma BK virus and rhinovirus as dominating pathogens in blood and NPA, respectively. Patients with chronic lymphocytic leukemia (CLL) (p<0.01) and patients with fever (p<0.001) were overrepresented in the virus-positive group. Furthermore, viral findings in NPA were associated with upper respiratory symptoms (URTS) (p<0.0001). CONCLUSIONS/SIGNIFICANCE: Both respiratory viral infections and low titers of viruses in blood from patients with neutropenia were common. Patients with CLL and patients with fever were independently associated to these infections, and viral findings in NPA were associated to URTS indicating active infection. These findings motivate further studies on viruses' impact on this patient category and their potential role as causative agents of fever during neutropenia

Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: value of linezolid, tigecycline, daptomycin and vancomycin

Antibiotic-resistant organisms causing both hospital-and community-acquired complicated skin and soft-tissue infections (cSSTI) are increasingly reported. A substantial medical and economical burden associated with MRSA colonisation or infection has been documented. The number of currently available appropriate antimicrobial agents is limited. Good quality randomised, controlled clinical trial data on antibiotic efficacy and safety is available for cSSTI caused by MRSA. Linezolid, tigecycline, daptomycin and vancomycin showed efficacy and safety in MRSA-caused cSSTI. None of these drugs showed significant superiority in terms of clinical cure and eradication rates. To date, linezolid offers by far the greatest number of patients included in controlled trials with a strong tendency of superiority over vancomycin in terms of eradication and clinical success