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Drug burden index for antibiotics

Wolfgang W Wicha, William A Craig, David Andes
OBJECTIVES: To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of lefamulin in the neutropenic murine thigh infection model to ascertain (i) which PK/PD index best correlates with efficacy and (ii) whether the magnitude of the index that drives efficacy varies for different pathogens. METHODS: We evaluated the in vivo PK/PD of lefamulin against five Streptococcus pneumoniae and five Staphylococcus aureus strains using a neutropenic murine thigh infection model...
April 1, 2019: Journal of Antimicrobial Chemotherapy
Daniel Hassan, Calvin A Omolo, Ramesh Gannimani, Ayman Y Waddad, Chunderika Mocktar, Sanjeev Rambharose, Nikhil Agrawal, Thirumala Govender
The development of novel antibiotic systems is needed to address the methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of the study was to explore the novel nanoplex delivery method for vancomycin (VCM) against MRSA using dextran sulfate sodium salt (DXT) as a polyelectrolyte complexing agent. Nanoplexes were formulated by the self-assembling amphiphile polyelectrolyte complexation method and characterized. The size, polydispersity index (PDI), and zeta potential (ZP) of the optimized VCM nanoplexes were 84...
January 11, 2019: International Journal of Pharmaceutics
Alexander J Lepak, Miao Zhao, Qingmei Liu, Ping Wang, Yanli Wang, Justin C Bader, Paul G Ambrose, David R Andes
KBP-7072 is a novel aminomethylcycline antibiotic in clinical development for community-acquired pneumonia. The goal of present studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) magnitude correlated with efficacy in the murine pneumonia infection model against Staphylococcus aureus and Streptococcus pneumoniae KBP-7072 pharmacokinetic measures were performed in plasma and epithelial lining fluid (ELF) at 4-fold increasing doses from 1-256 mg/kg subcutaneously. Pharmacokinetic parameters were calculated using a noncompartmental model and were linear over the dose range...
December 17, 2018: Antimicrobial Agents and Chemotherapy
Bernardo Sousa-Pinto, António Cardoso-Fernandes, Luís Araújo, João Almeida Fonseca, Alberto Freitas, Luís Delgado
BACKGROUND: Penicillin allergy is commonly reported, but only a minority of claimants has a confirmed diagnosis. Nevertheless, patients labeled as having penicillin allergy are treated with second-line antibiotics, which are more expensive and less effective, possibly increasing the risk of drug-resistant infections. OBJECTIVE: To compare hospitalizations with and without registration of penicillin allergy concerning their morbidity and hospital resource use. METHODS: We analyzed a national administrative database containing a registration of all Portuguese hospitalizations from 2000 to 2014...
February 2018: Annals of Allergy, Asthma & Immunology
George L Drusano, Michael L Corrado, Gino Girardi, Evelyn J Ellis-Grosse, Richard G Wunderink, Helen Donnelly, Kenneth V Leeper, Mona Brown, Tasnova Malek, Robert Duncan Hite, Michelle Ferrari, Danijela Djureinovic, Marin H Kollef, Lisa Mayfield, Ann Doyle, Jean Chastre, Alain Combes, Thomas J Walsh, Krisztina Dorizas, Hassan Alnuaimat, Brooks Edward Morgan, Jordi Rello, Cristopher Alan Mazo Torre, Ronald N Jones, Robert K Flamm, Leah Woosley, Paul G Ambrose, Sujata Bhavnani, Christopher M Rubino, Catharine C Bulik, Arnold Louie, Michael Vicchiarelli, Colleen Berman
Ventilator-associated bacterial pneumonia (VABP) is a difficult therapeutic problem. Considerable controversy exists regarding the optimal chemotherapy for this entity. The recent guidelines of the Infectious Diseases Society of America and the American Thoracic Society recommend a 7-day therapeutic course for VABP based on the balance of no negative impact on all-cause mortality, less resistance emergence, and fewer antibiotic treatment days, counterbalanced with a higher relapse rate for patients whose pathogen is a nonfermenter...
January 2018: Antimicrobial Agents and Chemotherapy
C F Manthey, L Eckmann, V Fuhrmann
Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials...
November 2017: Expert Review of Clinical Pharmacology
Alexander J Lepak, Miao Zhao, Karen Marchillo, Jamie VanHecker, David R Andes
Omadacycline is a novel aminomethylcycline antibiotic in clinical development for community-acquired bacterial pneumonia (CABP). We used a neutropenic murine pneumonia infection model to characterize the in vivo pharmacodynamic activity of omadacycline against Streptococcus pneumoniae Four strains with various phenotypic resistances to other antimicrobials, including tetracyclines, were utilized. Drug concentration measurements were performed in the plasma and epithelial lining fluid (ELF) after administration of 0...
May 2017: Antimicrobial Agents and Chemotherapy
Sandhya Pranatharthiharan, Mitesh D Patel, Vinod C Malshe, Vaishali Pujari, Ajit Gorakshakar, Manisha Madkaikar, Kanjaksha Ghosh, Padma V Devarajan
We report asialoglycoprotein receptor (ASGPR)-targeted doxorubicin hydrochloride (Dox) nanoparticles (NPs) for hepatocellular carcinoma (HCC). Polyethylene sebacate (PES)-Gantrez® AN 119 Dox NPs of average size 220 nm with PDI < 0.62 and ∼20% Dox loading were prepared by modified nanoprecipitation. ASGPR ligands, pullulan (Pul), arabinogalactan (AGn), and the combination (Pul-AGn), were anchored by adsorption. Ligand anchoring enabled high liver uptake with a remarkable hepatocyte:nonparenchymal cell ratio of 85:15...
November 2017: Drug Delivery
Atim Udoh, Emmanuel E Effa, Olabisi Oduwole, Babasola O Okusanya, Obiamaka Okafo
BACKGROUND: A septic abortion refers to any abortion (spontaneous or induced) complicated by upper genital tract infection including endometritis or parametritis. The mainstay of treatment of septic abortion is antibiotic therapy alone or in combination with evacuation of retained products of conception. Regimens including broad-spectrum antibiotics are routinely recommended for treatment. However, there is no consensus on the most effective antibiotics alone or in combination to treat septic abortion...
July 1, 2016: Cochrane Database of Systematic Reviews
Jasmeet Singh Khara, Miles Priestman, Iria Uhía, Melissa Shea Hamilton, Nitya Krishnan, Ying Wang, Yi Yan Yang, Paul R Langford, Sandra M Newton, Brian D Robertson, Pui Lai Rachel Ee
OBJECTIVES: The emergence of MDR-TB, coupled with shrinking antibiotic pipelines, has increased demands for new antimicrobials with novel mechanisms of action. Antimicrobial peptides have increasingly been explored as promising alternatives to antibiotics, but their inherent poor in vivo stability remains an impediment to their clinical utility. We therefore systematically evaluated unnatural amino acid-modified peptides to design analogues with enhanced anti-mycobacterial activities...
August 2016: Journal of Antimicrobial Chemotherapy
Manon Belhassen, Jacques De Blic, Laurent Laforest, Valérie Laigle, Céline Chanut-Vogel, Liliane Lamezec, Jacques Brouard, Brigitte Fauroux, Gérard de Pouvourville, Marine Ginoux, Eric Van Ganse
Recurrent wheezing (RW) has a significant impact on infants, caregivers, and society, but morbidity and related medical resource utilization (MRU) have not been thoroughly explored. The burden of RW needs to be documented with population-based data. The objective was to assess the characteristics, medical management, and MRU of RW infants identified from national claims data. Infants aged from 6 to 24 months, receiving ≥2 dispensations of respiratory drugs within 3 months, and presenting a marker of poor control (index date), were selected...
April 2016: Medicine (Baltimore)
Emine Vezir, Emine Dibek Misirlioglu, Ersoy Civelek, Murat Capanoglu, Hakan Guvenir, Tayfur Ginis, Muge Toyran, Can N Kocabas
BACKGROUND: Skin testing has a limited role in the diagnosis of non-immediate beta-lactam hypersensitivity in children. The aim of this study was to report the results of oral provocation tests performed without skin tests in children with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics. METHODS: Oral provocation tests with suspected antibiotics were performed to patients with non-immediate mild cutaneous reactions without systemic symptoms caused by beta-lactam antibiotics...
February 2016: Pediatric Allergy and Immunology
Jonas Dewulf, François Vermeulen, Simeon Wanyama, Muriel Thomas, Marijke Proesmans, Lieven Dupont, Kris De Boeck
CFTR mutations are grouped according to disease-causing mechanism. Several studies demonstrated that patients having at least one mutation of class IV/V, present with a milder phenotype, but little is known about their relative treatment burden. We compared treatment burden between patients with two class I, II, or III mutations and patients with at least one mutation of class IV/V in the 2010 database of the Belgian CF Registry. We calculated a "Treatment Burden Index" (TBI) by assigning long term therapies to categories low, medium and high intensity, for differential weighing in the total score...
December 2015: Pediatric Pulmonology
Aquino Albino Nhantumbo, Vlademir Vicente Cantarelli, Juliana Caireão, Alcides Moniz Munguambe, Charlotte Elizabeth Comé, Gabriela do Carmo Pinto, Tomás Francisco Zimba, Inácio Mandomando, Cynthia Baltazar Semá, Cícero Dias, Milton Ozório Moraes, Eduardo Samo Gudo
BACKGROUND: In Sub-Saharan Africa, including Mozambique, acute bacterial meningitis (ABM) represents a main cause of childhood mortality. The burden of ABM is seriously underestimated because of the poor performance of culture sampling, the primary method of ABM surveillance in the region. Low quality cerebrospinal fluid (CSF) samples and frequent consumption of antibiotics prior to sample collection lead to a high rate of false-negative results. To our knowledge, this study is the first to determine the frequency of ABM in Mozambique using real-time polymerase chain reaction (qPCR) and to compare results to those of culture sampling...
2015: PloS One
Marya D Zilberberg, Andrew F Shorr, Scott T Micek, Marin H Kollef
BACKGROUND: With decreasing mortality in sepsis, attention has shifted to longer-term consequences associated with survivorship. Thirty-day readmission as a component of healthcare utilization is an important outcome. OBJECTIVE: To examine the frequency of and risk factors for 30-day readmission among patients surviving sepsis. DESIGN: Single-center retrospective cohort. METHODS/SETTING: We examined 30-day readmission risk among survivors of hospitalization with culture-positive severe sepsis or septic shock...
October 2015: Journal of Hospital Medicine: An Official Publication of the Society of Hospital Medicine
Robert Wilson, Antonio Anzueto, Marc Miravitlles, Pierre Arvis, Daniel Haverstock, Mila Trajanovic, Sanjay Sethi
BACKGROUND: Acute exacerbations represent a significant burden for patients with moderate-to-severe chronic obstructive pulmonary disease. Each exacerbation episode is frequently associated with a lengthy recovery and impaired quality of life. Prognostic factors for outpatients that may predict poor outcome after treatment with antibiotics recommended in the guidelines, are not fully understood. We aimed to identify pretherapy factors predictive of clinical failure in elderly (≥60 years old) outpatients with acute Anthonisen type 1 exacerbations...
2015: International Journal of Chronic Obstructive Pulmonary Disease
Hina Saini, Sanjay Chhibber, Kusum Harjai
Biofilm formation is becoming a predominant feature in nosocomial infections. Since biofilms are increasingly resistant to antibiotics, making monotherapy ineffective, combination therapy appears to be relevant for their eradication. This study assessed the potential of azithromycin (AZM) and ciprofloxacin (CIP) alone and in combination in vitro and in a mouse model of urinary tract infection (UTI) induced with biofilm cells of Pseudomonas aeruginosa. In vitro antibacterial and antibiofilm activities of antibiotics alone and in combination were assessed using the fractional inhibitory concentration index (FICI), time-kill analysis and confocal laser scanning microscopy (CLSM)...
April 2015: International Journal of Antimicrobial Agents
L Charles Bailey, Christopher B Forrest, Peixin Zhang, Thomas M Richards, Alice Livshits, Patricia A DeRusso
IMPORTANCE: Obesity in children and adults is associated with significant health burdens, making prevention a public health imperative. Infancy may be a critical period when environmental factors exert a lasting effect on the risk for obesity; identifying modifiable factors may help to reduce this risk. OBJECTIVE: To assess the impact of antibiotics prescribed in infancy (ages 0-23 months) on obesity in early childhood (ages 24-59 months). DESIGN, SETTING, AND PARTICIPANTS: We conducted a cohort study spanning 2001-2013 using electronic health records...
November 2014: JAMA Pediatrics
Konstantinos Nikolaos Stamatiou, Hippocrates Moschouris
PURPOSE: Chronic bacterial prostatitis displays a variety of symptoms (mainly local pain exhibiting vari­ability in origin and intensity). These symptoms often persist despite bacterial eradication. The purpose of this article is to exam the role of phytotherapeutic agents as complementary treatment in patients with bacterial prostatitis. MATERIALS AND METHODS: The material consisted of individuals with reported pelvic discomfort and genital pain with or without lower urinary tract symptoms (LUTS) and sexual dysfunction visiting our department from March 2009 to March 2011...
September 6, 2014: Urology Journal
Audrey Bernut, Vincent Le Moigne, Tiffany Lesne, Georges Lutfalla, Jean-Louis Herrmann, Laurent Kremer
Mycobacterium abscessus is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the in vivo therapeutic efficacy of the few potentially active antibiotics against M. abscessus was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the in vivo activity of drugs against acute M. abscessus infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent M...
July 2014: Antimicrobial Agents and Chemotherapy
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