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Matthew Geriak, Fadi Haddad, Khulood Rizvi, Warren Rose, Ravina Kullar, Kerry LaPlante, Marie Yu, Logan Vasina, Krista Ouellette, Marcus Zervos, Victor Nizet, George Sakoulas
Vancomycin (VAN) and daptomycin (DAP) are approved as monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up front DAP+CPT head-to-head vs. standard monotherapy as initial treatment.In a pilot study, we evaluated 40 adult patients who were randomized to receive DAP 6-8 mg/kg/d + CPT 600 mg IV q8 h (n=17) or standard monotherapy (n=23) with vancomycin (VAN, dosed to achieve serum trough concentrations 15-20 mg/L, n=21) or DAP 6-8 mg/kg/d (n=2)...
March 11, 2019: Antimicrobial Agents and Chemotherapy
Dimitra Sakoula, Boris Nowka, Eva Spieck, Holger Daims, Sebastian Lücker
The genus Nitrospira is considered to be the most widespread and abundant group of nitrite-oxidizing bacteria in many natural and man-made ecosystems. However, the ecophysiological versatility within this phylogenetic group remains highly understudied, mainly due to the lack of pure cultures and genomic data. To further expand our understanding of this biotechnologically important genus, we analyzed the high quality draft genome of " Nitrospira lenta " strain BS10, a sublineage II Nitrospira that was isolated from a municipal wastewater treatment plant in Hamburg, Germany...
2018: Standards in Genomic Sciences
George Sakoulas, Matthew Geriak, Victor Nizet
The majority of patients with reported penicillin allergy are not allergic when tested or challenged. Penicillin allergy testing has been shown to significantly reduce future annual healthcare expenditures. Data have emerged showing beta-lactams to be multi-dimensional antibacterial effects in vivo, far beyond what is appreciated in standard bacteriological susceptibility testing media. These include enhancing bacterial killing by the innate immune system. Supporting the clinical relevance of these secondary underappreciated effects are recent clinical and pharmaco-economic analyses that show worse outcomes in patients with reported penicillin allergies who receive non-beta lactam antibiotics when compared to their non-penicillin allergic counterparts...
July 9, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ioannis D Kampouris, Panayotis D Karayannakidis, Dimitra C Banti, Dimitra Sakoula, Dimitris Konstantinidis, Minas Yiangou, Petros E Samaras
Membrane biofouling, due to Soluble Microbial Products (SMP) and Extracellular Polymeric Substances (EPS) deposition, results in reduction of the performance of Membrane Bioreactors (MBRs). However, recently, a new method of biofouling control has been developed, utilizing the interference of the bacterial inter- and intra-species' communication. Bacteria use Quorum Sensing (QS) to regulate the production of SMP and EPS. Therefore, disruption of Quorum Sensing (Quorum Quenching: QQ), by enzymes or microorganisms, may be a simple mean to control membrane biofouling...
October 15, 2018: Water Research
Kumari S Choudhary, Nathan Mih, Jonathan Monk, Erol Kavvas, James T Yurkovich, George Sakoulas, Bernhard O Palsson
Two-component systems (TCSs) consist of a histidine kinase and a response regulator. Here, we evaluated the conservation of the AgrAC TCS among 149 completely sequenced Staphylococcus aureus strains. It is composed of four genes: agrBDCA . We found that: (i) AgrAC system ( agr ) was found in all but one of the 149 strains, (ii) the agr positive strains were further classified into four agr types based on AgrD protein sequences, (iii) the four agr types not only specified the chromosomal arrangement of the agr genes but also the sequence divergence of AgrC histidine kinase protein, which confers signal specificity, (iv) the sequence divergence was reflected in distinct structural properties especially in the transmembrane region and second extracellular binding domain, and (v) there was a strong correlation between the agr type and the virulence genomic profile of the organism...
2018: Frontiers in Microbiology
Zhuo Ma, Erica Lasek-Nesselquist, Jackson Lu, Ryan Schneider, Riddhi Shah, George Oliva, Janice Pata, Kathleen McDonough, Manjunath P Pai, Warren E Rose, George Sakoulas, Meenakshi Malik
The extensive use of daptomycin (DAP) for treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections in the last decade has led to the emergence of DAP non-susceptible (DNS) Staphylococcus aureus strains. A better understanding of the molecular changes underlying DAP-non-susceptibility is required for early diagnosis and intervention with alternate combination therapies. The phenotypic changes associated with DNS strains have been well established. However, the genotypic changes-especially the kinetics of expression of the genes responsible for DAP-non-susceptibility are not well understood...
2018: PloS One
Nivedita B Singh, Juwon Yim, Seyedehameneh Jahanbakhsh, George Sakoulas, Michael J Rybak
OBJECTIVE: Development of antimicrobial resistance during monotherapy of complicated methicillin-resistant Staphylococcus aureus bacteremia is problematic due to cross-resistance between vancomycin (VAN) and daptomycin, the only approved agents for this condition. Our objective was to demonstrate that development of resistance under conditions of suboptimal VAN (200 mg q 12 h) exposure in S. aureus can be attenuated by addition of cefazolin (CFZ). METHODS: Two strains of S...
August 2018: Diagnostic Microbiology and Infectious Disease
Brianne Zapata, Danya N Alvarez, Sabrina Farah, Cristina Garcia-de-la-Maria, Jose M Miro, George Sakoulas, Arnold S Bayer, Nagendra N Mishra
Among the viridans group streptococci, S. mitis-oralis strains are frequently resistant to multiple β-lactams and tolerant to vancomycin (VAN). This scenario has led to the proposed clinical use of newer agents, like daptomycin (DAP) for such S. mitis-oralis strains. However, recent recognition of the rapid and durable emergence of high-level DAP-resistance (DAP-R; DAP MICs > 256 µg/ml) induced by DAP exposures in vitro and in vivo has dampened enthusiasm for such approaches. In this study, we evaluated a broad range of DAP combination regimens in vitro for their capacity to prevent emergence of high-level DAP-R in a prototype S...
August 2018: Current Microbiology
Marguerite L Monogue, George Sakoulas, Victor Nizet, David P Nicolau
β-lactam-β-lactamase inhibitors (BLIs) have previously demonstrated antimicrobial activity against Acinetobacter baumannii (AB). Colistin retains the highest susceptibility rate against A. baumannii, and has demonstrated synergy with other antimicrobials, including β-lactam-BLIs. Therefore, we assessed the potential individual activity and synergistic combinations in vivo against carbapenem-susceptible (CS) and multidrug-resistant (MDR) A. baumannii isolates in neutropenic thigh and lung infection models...
2018: Pharmacology
Monika Kumaraswamy, Carter Do, George Sakoulas, Poochit Nonejuie, Guan Woei Tseng, Helen King, Joshua Fierer, Joe Pogliano, Victor Nizet
Endocarditis is a rare but serious manifestation of Listeria monocytogenes (LM). However, the optimal treatment strategy for LM endocarditis has yet to be established. Current antibiotic strategies for listeriosis include penicillin G or ampicillin (AMP) monotherapy, or AMP + gentamicin combination therapy which is often favored for endocarditis. The primary objective of our investigation was to assess the utility of AMP + ceftriaxone (CRO) and AMP + daptomycin (DAP) against LM, modeling less nephrotoxic antibiotic combinations traditionally used to manage resistant enterococcal endocarditis...
March 2018: International Journal of Antimicrobial Agents
Nicholas S Britt, Samad Tirmizi, David J Ritchie, Jeffrey E Topal, Dayna McManus, Victor Nizet, Ed Casabar, George Sakoulas
Background: Patients with end-stage renal disease (ESRD) requiring intermittent haemodialysis (IHD) are at high risk of MRSA bacteraemia (MRSA-B) and often fail first-line therapy. The safety, effectiveness and optimal dosing of telavancin for MRSA-B in this patient population are unclear. Objectives: We aimed to describe clinical outcomes of telavancin in the treatment of refractory MRSA-B in patients with ESRD requiring IHD. Patients and methods: This was a retrospective study of hospitalized patients at two tertiary care academic medical centres with recurrent or persistent (≥3 days) MRSA-B treated with telavancin monotherapy...
December 13, 2017: Journal of Antimicrobial Chemotherapy
George Sakoulas, Monika Kumaraswamy, Armin Kousha, Victor Nizet
This study examines the pharmacodynamics of antimicrobials that are used to treat Salmonella with each other and with key components of the innate immune system. Antimicrobial synergy was assessed using time-kill and checkerboard assays. Antimicrobial interactions with innate immunity were studied by employing cathelicidin LL-37, whole-blood, and neutrophil killing assays. Ceftriaxone and ciprofloxacin were found to be synergistic in vitro against Salmonella enterica serotype Newport. Ceftriaxone, ciprofloxacin, and azithromycin each demonstrated synergy with the human cathelicidin defense peptide LL-37 in killing Salmonella ...
November 2017: MSphere
Thomas J Dilworth, Warren E Rose, George Sakoulas, Arnold S Bayer
No abstract text is available yet for this article.
July 29, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Eric Wenzler, Fei Wang, Debra A Goff, Beth Prier, John Mellett, Julie E Mangino, Karri A Bauer
No abstract text is available yet for this article.
July 29, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Warren E Rose, Sanjay K Shukla, Andrew D Berti, Mary S Hayney, Kelsey M Henriquez, Andrea Ranzoni, Matthew A Cooper, Richard A Proctor, Victor Nizet, George Sakoulas
Background: Cell wall peptidoglycan stimulates interleukin 10 (IL-10) production in Staphylococcus aureus bacteremia (SaB) animal models, but clinical data are not available. This study evaluates the impact of intravascular bacterial cell numbers (ie, the level of bacteremia), in patients at the time of clinical presentation on IL-10 production and its association with S. aureus bacteremia (SaB) mortality. Methods: Blood and isolates were collected in 133 consecutive SaB patients...
May 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Aisling R Caffrey, Tristan T Timbrook, Eunsun Noh, George Sakoulas, Steven M Opal, Victor Nizet, Kerry L LaPlante
In addition to cholesterol-lowering capabilities, statins possess anti-inflammatory and immunomodulatory effects. We sought to quantify the real-world impact of different statin exposure patterns on clinical outcomes in Staphylococcus aureus bacteremia. We conducted a retrospective cohort study among hospitalized patients with positive S. aureus blood cultures receiving appropriate antibiotics within 48 h of culture collection (Veterans Affairs hospitals, 2002 to 2013). Three statin exposure groups were compared to nonusers: pretreated statin users initiating therapy in the 30 days prior to culture and either (i) continuing statin therapy after culture or (ii) not continuing after culture, and (iii) de novo users initiating at culture...
March 2017: Antimicrobial Agents and Chemotherapy
George Sakoulas, Warren Rose, Andrew Berti, Joshua Olson, Jason Munguia, Poochit Nonejuie, Eleanna Sakoulas, Michael J Rybak, Joseph Pogliano, Victor Nizet
We asked whether beta-lactamase inhibitors (BLIs) increased the activity of daptomycin (DAP) against methicillin-resistant Staphylococcus aureus (MRSA), the peptide antibiotic colistin (COL) against the emerging Gram-negative nosocomial pathogen Acinetobacter baumannii, and the human host defense peptide cathelicidin LL37 against either pathogen. DAP and LL37 kill curves were performed with or without BLIs against MRSA, vancomycin-intermediate S. aureus (VISA), and heterogeneous VISA (hVISA). COL and LL37 kill curves were performed against A...
February 2017: Antimicrobial Agents and Chemotherapy
Karl Evans R Henson, Juwon Yim, Jordan R Smith, George Sakoulas, Michael J Rybak
The evidence for using combination therapy for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections is growing. In this study, we investigated the synergistic effect of daptomycin (DAP) combined with piperacillin-tazobactam and ampicillin-sulbactam against MRSA in time-kill experiments. Six of eight strains demonstrated synergy between DAP and the β-lactam-β-lactamase inhibitor (BLI) combination. In 5/8 strains, the synergy occurred only in the presence of the BLI, highlighting a role for BLIs in peptide-β-lactam synergy...
January 2017: Antimicrobial Agents and Chemotherapy
George Sakoulas, Joshua Olson, Juwon Yim, Niedita B Singh, Monika Kumaraswamy, Diana T Quach, Michael J Rybak, Joseph Pogliano, Victor Nizet
Ertapenem and cefazolin were used in combination to successfully clear refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. In addition, recent work has demonstrated activity of combination therapy with beta-lactams from different classes against methicillin-resistant S. aureus (MRSA). The ertapenem-plus-cefazolin combination was evaluated for synergy in vitro and in vivo in a murine skin infection model using an index MSSA bloodstream isolate from a patient in whom persistent bacteremia was cleared with this combination and against a cadre of well-described research strains and clinical strains of MSSA and MRSA...
November 2016: Antimicrobial Agents and Chemotherapy
Ashley D Hall Snyder, Brian J Werth, Poochit Nonejuie, John P McRoberts, Joe Pogliano, George Sakoulas, Juwon Yim, Nivedita Singh, Michael J Rybak
Daptomycin (DAP) is being used more frequently to treat infections caused by vancomycin-resistant enterococcus (VRE). DAP tends to be less active against enterococci than staphylococci and may require high doses or combination therapy to be bactericidal. Fosfomycin (FOF) has activity against VRE and has demonstrated synergistic bactericidal activity with DAP in vitro The objective of this study was to evaluate the activity of DAP alone and in combination with FOF against VRE in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model...
October 2016: Antimicrobial Agents and Chemotherapy
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