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International Journal of Antimicrobial Agents

Inga Fröding, John Karlsson Valik, Ludvig Bolinder, Pontus Nauclér, Christian G Giske
BACKGROUND: In severe infections, time to appropriate therapy is decisive for survival. Patients with bloodstream infection with extended-spectrum β-lactamase-producing Enterobacterales (EPE BSI) often receive inadequate empiric treatment. OBJECTIVES: We aimed to identify risk factors, evaluate a previously suggested risk score, and suggest a new score for facilitating empiric treatment choice. METHODS: We assessed predictors for EPE BSI through a retrospective case-control design, and evaluated diagnostic performance of the two scores...
February 16, 2019: International Journal of Antimicrobial Agents
Shadab Parvez, Lama Misba, Quazi T Ahmad, Asad U Khan
No abstract text is available yet for this article.
February 12, 2019: International Journal of Antimicrobial Agents
Gaetana Sterrantino, Vanni Borghi, Anna Paola Callegaro, Bianca Bruzzone, Francesco Saladini, Franco Maggiolo, Gaetano Maffongelli, Massimo Andreoni, Michele De Gennaro, Nicola Gianotti, Patrizia Bagnarelli, Alessandra Vergori, Andrea Antinori, Maurizio Zazzi, Mauro Zaccarelli
INTRODUCTION: Our aim was to investigate the prevalence of DOR resistance mutations in NNRTI experienced patients. METHODS: DOR resistance was assessed in samples from patients NNRTI-experienced who underwent genotypic test for virologic failure from the Antiretroviral Response Cohort Analysis (ARCA) database. Intermediate DOR resistance was defined as detection of any of V106A/M, Y188C/H, V108I, K103N plus P225H. High level resistance to DOR was defined as detection of any of Y188L, M230L, G190E, V106A/M plus F227L, V106A/M plus L234I...
February 12, 2019: International Journal of Antimicrobial Agents
Sergio García-Fernández, María García-Castillo, German Bou, Jorge Calvo, Emilia Cercenado, Mercedes Delgado, Cristina Pitart, Xavier Mulet, Nuria Tormo, Diego López Mendoza, Jazmín Díaz-Regañón, Rafael Cantón
Patients in intensive care units (ICUs) present a high risk of developing an infection caused by multi-drug resistant (MDR) bacteria. Consequently, new antimicrobials and combinations are needed. We evaluated the activity of ceftolozane-tazobactam against Enterobacterales (n=400) and Pseudomonas aeruginosa (n=80) isolates collected from patients in Spanish intensive care units (ICUs) with complicated urinary tract infections (cUTI) and complicated intra-abdominal infections (cIAI). Overall susceptibility of ceftolozane-tazobactam in P...
February 12, 2019: International Journal of Antimicrobial Agents
Alba Cecilia Ruiz-Gaitán, Emilia Cantón, Marcelo Ernesto Fernández-Rivero, Paula Ramírez, Javier Pemán
Candida auris is an emerging pathogen causing candidaemia outbreaks in several countries for which azole, amphotericin-B, and echinocandin resistance has been reported. We have determined the eight agents' antifungal susceptibilities of 73 C. auris Spanish isolates (56 bloodstreams and 17 urine), using three methods. First, Isolates were identified by ITS sequencing and then, MICs of fluconazole, isavuconazole, itraconazole, posaconazole, voriconazole, anidulafungin, micafungin, and amphotericin-B were determined by EUCAST and SensititreYeastOne® (SYO) (only bloodstream isolates), and Liofilchem® MIC Test Strip (all isolates)...
February 12, 2019: International Journal of Antimicrobial Agents
Jasmin Binder, Jürgen Held, Sven Krappmann
Fungi have evolved specific export activities to balance intracellular levels of the toxic ion fluoride, while the first-line antimycotic voriconazole contains fluorine. We aimed to explore whether impaired fluoride export might result in altered susceptibilities of the human pathogenic mould Aspergillus fumigatus towards this antifungal compound. Functional characterisation of the putative fluoride exporter in A. fumigatus was carried out in the context of azole resistance by generating deletion strains that were assessed for their resistance against fluoride and voriconazole...
February 11, 2019: International Journal of Antimicrobial Agents
Eve Todesco, Nesrine Day, Corinne Amiel, Stéphane Elaerts, Véronique Schneider, Laurent Roudiere, Stéphane Hue, Jean-Yves Liotier, Julie Bottero, Thomas L'yavanc, Michel Ohayon, Daniel Gosset, Vincent Thibault, Laure Surgers, Julie Chas, Sepideh Akhavan, Annie Velter, Christine Katlama, Georges Kreplak, Anne-Geneviève Marcelin, Marc-Antoine Valantin
BACKGROUND: Increasing incidence of hepatitis C virus (HCV) infection in HIV-positive men having sex with men (MSM) has been described in recent years. We performed phylogenetic analyses of acute HCV infections to characterize the dynamics during the epidemic in Paris and evaluated associated sexually transmitted infections (STI). METHODS: Sanger Sequencing of polymerase gene was performed. Maximum likelihood phylogenies were reconstructed using FastTree 2.1 under a GTR+CAT model...
February 8, 2019: International Journal of Antimicrobial Agents
Charles-Edouard Luyt, Morgane Faure, Isabelle Bonnet, Sébastien Besset, Florent Huang, Helga Junot, Guillaume Hékimian, Matthieu Schmidt, Nicolas Bréchot, Alain Combes, Alexandra Aubry, Julien Mayaux, Jean Chastre
PURPOSE: To evaluate the use of non-carbapenem antibiotics to treat severe extended-spectrum β-lactamase-producing Enterobacteriaceae infections in intensive care unit (ICU) patients. METHODS: This retrospective observational study conducted in 2 ICUs compared outcomes of patients with extended-spectrum β-lactamase-producing Enterobacteriaceae infections administered a carbapenem or a non-carbapenem antibiotic as their definitive treatment. The primary outcome was treatment failure within 30 days, a composite endpoint of extended-spectrum β-lactamase-producing Enterobacteriaceae-infection recurrence and day-30 mortality...
February 8, 2019: International Journal of Antimicrobial Agents
Dee Shortridge, Leonard R Duncan, Michael A Pfaller, Robert K Flamm
Ceftolozane-tazobactam (C-T) is a combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved by the US Food and Drug Administration in 2014 and by the European Medicine Agency in 2015 for use in adults to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections with metronidazole. Studies for paediatric indications are planned. The Programme to Assess Ceftolozane-tazobactam Susceptibility monitors C-T resistance to Gram-negative (GN) isolates worldwide...
February 1, 2019: International Journal of Antimicrobial Agents
Antoine Grillon, Angeline Chabaud, Gilles Zambardi, Isabelle Caniaux, François Jehl
Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) do not completely predict the bactericidal nature of the antimicrobial agent. Patients with pathogens having MICs near the clinical breakpoint experience a higher risk of clinical failure. Here, we defined an indicator, Breakpoint to MIC Quotient (BMQ), that incorporates MIC and the European Committee on Antimicrobial Susceptibility Testing breakpoint. BMQ was inversely correlated with MBC in our antibiotic combinations against Enterobacteriaceae strains (Spearman coefficient ≤-0...
February 1, 2019: International Journal of Antimicrobial Agents
G Ralph Corey, Mark H Wilcox, Jesus Gonzalez, Alena Jandourek, David J Wilson, H David Friedland, Shampa Das, Joseph Iaconis, Matthew Dryden
BACKGROUND: Post-hoc analysis compared pharmacokinetics and clinical outcomes of ceftaroline fosamil 600 mg every 12 (q12h) versus every 8 hours (q8h), in patients with acute bacterial skin and skin structure infections (ABSSSI) and signs of sepsis. METHODS: Clinical outcomes at test-of-cure in patients with ABSSSI and systemic inflammatory signs/systemic inflammatory response (SIRS), and ceftaroline minimum inhibitory concentrations (MICs) against baseline pathogens were compared between COVERS (ceftaroline fosamil 600 mg q8h, 2-h infusion) and the CANVAS 1 and 2 trials (ceftaroline fosamil 600 mg q12h, 1-h infusion)...
February 1, 2019: International Journal of Antimicrobial Agents
Christopher J Destache, David J Guervil, Keith S Kaye
BACKGROUND: The clinical experience of ceftaroline fosamil (CPT-F) therapy for gram-positive infective endocarditis is reported from CAPTURE, a retrospective study conducted in the United States. METHODS: Data, including patient demographics, medical history, risk factors, microbiological etiology, and clinical outcomes, were collected by review of patient charts between September 2013 and February 2015. RESULTS: Patients (n=55) with gram-positive endocarditis were treated with CPT-F...
January 31, 2019: International Journal of Antimicrobial Agents
Awo Afi Kwapong, Paul Stapleton, Simon Gibbons
Bacterial conjugation is the main mechanism for the transfer of multiple antibiotic resistance genes among pathogenic microorganisms. This process could be controlled by compounds that inhibit bacterial conjugation. In this study, the effect of allyl isothiocyanate, L-sulforaphane, benzyl isothiocyanate, phenylethyl isothiocyanate and 4-methoxyphenyl isothiocyanate on the conjugation of broad host range plasmids, which harbor various resistance genes in Escherichia coli were investigated; pKM101 (IncN), TP114 (IncI2 ), pUB307 (IncP) and the low copy number IncW plasmid R7K...
January 24, 2019: International Journal of Antimicrobial Agents
Anaïs Potron, Maxime Bour, Pauline Triponney, Joris Muller, Christelle Koebel, Rémy Bonnin, Patrick Plésiat
Here we report a hospital outbreak due to an extensively drug-resistant (XDR), OXA-72-producing strain of A. baumannii. The isolates were found to be genotypically indistinguishable by whole-genome MLST, and to belong to the international clonal complex CC2. One of these isolates sequentially developed a high resistance to colistin and rifampicin under treatment as a result of mutations in genes pmrB and rpoB, respectively. The blaOXA-72 gene was localized on a 10-kb transferable plasmid, named pAB-STR-1, whose sequence is nearly identical to that of another plasmid previously found in Lithuanian strains, pAB120...
January 24, 2019: International Journal of Antimicrobial Agents
Joan Gomez-Junyent, Eva Benavent, Yanik Sierra, Cristina El Haj, Laura Soldevila, Benjamin Torrejon, Raul Rigo-Bonnin, Fe Tubau, Javier Ariza, Oscar Murillo
Ceftolozane/tazobactam is a potential tool for infections by MDR Pseudomonas aeruginosa, but its efficacy against some difficult-to-treat infections has not been well defined. Using an in vitro pharmacodynamic biofilm model, we evaluated the comparative efficacy of ceftolozane/tazobactam against MDR/XDR P. aeruginosa strains, alone and in combination with colistin. Simulated regimens of ceftolozane/tazobactam (2g/1g every 8h), meropenem (2g every 8h) and ceftazidime (2g every 8h), alone and in combination with colistin (continuous infusion) were evaluated against three colistin-susceptible and ceftazidime-resistant strains: MDR-HUB1, ceftolozane/tazobactam- and meropenem-susceptible; XDR-HUB2, ceftolozane/tazobactam-susceptible and meropenem-resistant; MDR-HUB3, ceftolozane/tazobactam-resistant and meropenem-susceptible...
January 22, 2019: International Journal of Antimicrobial Agents
Shawn T Clark, Utkarshna Sinha, Yu Zhang, Pauline W Wang, Sylva L Donaldson, Bryan Coburn, Valerie J Waters, Yvonne C W Yau, D Elizabeth Tullis, David S Guttman, David M Hwang
Determining the mechanisms that modulate β-lactam resistance in clinical P. aeruginosa isolates can be challenging, as the molecular profiles identified in mutation- or expression-based resistance determinant screens may not correlate with in vitro phenotypes. One of the lesser studied resistance mechanisms in P. aeruginosa is the modification of penicillin binding protein 3 (pbpB/ftsI). Here, we report that nonsynonymous polymorphisms within pbpB frequently occur among β-lactam resistant sputum isolates, and are associated with unique antibiotic susceptibility patterns...
January 18, 2019: International Journal of Antimicrobial Agents
Anne-Grete Märtson, Anette Veringa, Martijn Bakker, Edwin R van den Heuvel, Daan J Touw, Tjip S van der Werf, Lambert F R Span, Jan-Willem C Alffenaar
During inflammation, several cytochrome P450 enzymes are downregulated. Recently it was shown that voriconazole metabolism is reduced during inflammation. Posaconazole, another triazole with broad-spectrum antifungal activity, is metabolised only to a limited extent by cytochrome P450 enzymes and to a wider extent by phase 2 enzyme systems. The aim of this study was to investigate posaconazole concentrations during inflammation. Patients aged ≥18 years receiving posaconazole prophylaxis or treatment for fungal infections were enrolled in a prospective observational study...
January 11, 2019: International Journal of Antimicrobial Agents
Li Wen Loo, Yi Xin Liew, Winnie Lee, Lai Wei Lee, Piotr Chlebicki, Andrea Lay-Hoon Kwa
BACKGROUND: Overprescribing of antibiotics in patients with no bacterial infection is of growing global concern. It's important for timely Antimicrobial Stewardship Program (ASP) intervention to discontinue antibiotics in patients whose symptoms can be explained by non-infective causes, without availability of bacterial cultures and susceptibilities reports. Our study aims to evaluate clinical outcomes and safety of early ASP review in these patients. METHODS: Retrospective review of ASP database (January 2010 to December 2014) was conducted, to identify patients whom ASP recommended discontinuation of empiric antibiotics within 24hours of prescribing...
January 10, 2019: International Journal of Antimicrobial Agents
Michail N Mavros, Nikoletta A Theochari, Margarita Kyriakidou, Konstantinos P Economopoulos, Jack A Sava, Matthew E Falagas
Complicated intra-abdominal infections (cIAIs) are common and confer significant morbidity, mortality, and cost. In this era of evolving antimicrobial resistance, selection of appropriate empiric antimicrobials is paramount. This systematic review and meta-analysis of randomized controlled trials compares the effectiveness and safety of fluoroquinolone (FQ) versus beta-lactam (BL)-based regimens for the treatment of patients with cIAIs. The primary outcomes were treatment success in the clinically-evaluable (CE) and all-cause mortality in the intention-to-treat (ITT) population...
January 10, 2019: International Journal of Antimicrobial Agents
Chung-Yen Huang, Ronan W Hsieh, Hung-Teng Yen, Tzu-Chun Hsu, Chun-Yu Chen, Yee-Chun Chen, Chien-Chang Lee
Current practice of long-term antibiotic use in patients with osteomyelitis is controversial. Recent studies showed short-term antibiotic use to be non-inferior to long-term use, but the results of these studies have been inconsistent. In this review, the PubMed and Embase databases were searched from inception through to June 2018 for randomised controlled trials (RCTs), cohort studies or case-control studies comparing two different durations of antibiotic use. Short antibiotic courses were defined as antibiotics administered for a shorter period than the recommended 4-6 weeks...
January 10, 2019: International Journal of Antimicrobial Agents
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