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Sara A Buckman, Tamara Krekel, Anouk E Muller, John E Mazuski
The treatment of complicated intra-abdominal infections (cIAI) is increasingly challenging due to increased resistance of Gram-negative organisms. These multidrug resistant organisms lead to an increase in morbidity and mortality. This has led to renewed interest in use of older β-lactam antibiotics in combination with newer β-lactamase inhibitors. Ceftazidime-avibactam is one of the newest such combination antibiotics, which has been released for treatment of complicated intra-abdominal infections in combination with metronidazole...
October 19, 2016: Expert Opinion on Pharmacotherapy
Andre Arizpe, Kelly R Reveles, Shrina D Patel, Samuel L Aitken
Resistance to cephalosporins is now common among Gram-negative bacterial infections, including those caused by the Enterobacteriaceae and Pseudomonas aeruginosa, posing a major threat to public health. As resistance to the traditional drugs of choice for these infections, carbapenems, has also become increasingly common, interest in cefepime and piperacillin-tazobactam as carbapenem-sparing alternatives has increased. Additionally, the availability of the novel β-lactam-β-lactamase inhibitor combinations ceftolozane-tazobactam and ceftazidime-avibactam has added to the antimicrobial armamentarium available to treat these multidrug-resistant infections...
December 2016: Current Infectious Disease Reports
John J Veillette, James Truong, Steven C Forland
Limited data exist regarding optimal dosing of ceftazidime/avibactam (C/A) in patients with unique physiology, who were excluded from published clinical trials. Data are also lacking regarding clinical efficacy of C/A in patients with infections due to multidrug-resistant Gram-negative pathogens. To expand knowledge in these areas, we present pharmacokinetic data from two patients with KPC-producing Klebsiella pneumoniae bloodstream infections, both of whom had renal impairment, and one of whom was morbidly obese...
September 26, 2016: Pharmacotherapy
Gerard D Wright
Avycaz combines an older cephalosporin antibiotic, ceftazidime, and the β-lactamase inhibitor avibactam. Ceftazidime targets penicillin-binding proteins (PBPs) in the bacterial periplasm that are required for cell wall synthesis. Avibactam blocks β-lactamases (β-L) in the periplasm, which would otherwise inactivate the antibiotics resulting in drug resistance.
October 6, 2016: Cell
Elisa Torres-Del-Pliego, Elena Delgado-Mejía, Leire Gil-Alonso, Leonor Del Mar-Periáñez-Párraga
No abstract text is available yet for this article.
October 3, 2016: Enfermedades Infecciosas y Microbiología Clínica
Mazen S Bader, Mark Loeb, Annie A Brooks
Urinary tract infections (UTIs) caused by antibiotic-resistant Gram-negative bacteria are a growing concern due to limited therapeutic options. Gram-negative bacteria, specifically Enterobacteriaceae, are common causes of both community-acquired and hospital acquired UTIs. These organisms can acquire genes that encode for multiple antibiotic resistance mechanisms, including extended-spectrum-lactamases (ESBLs), AmpC- β -lactamase, and carbapenemases. The assessment of suspected UTI includes identification of characteristic symptoms or signs, urinalysis, dipstick or microscopic tests, and urine culture if indicated...
October 7, 2016: Postgraduate Medicine
Ryan K Shields, Brian A Potoski, Ghady Haidar, Binghua Hao, Yohei Doi, Liang Chen, Ellen G Press, Barry N Kreiswirth, Cornelius J Clancy, M Hong Nguyen
Thirty-seven carbapenem-resistant Enterobacteriaceae (CRE)-infected patients were treated with ceftazidime-avibactam. Clinical success and survival rates at 30-days were 59% (22/37) and 76% (28/37), respectively. In 23% (5/22) of clinical successes, CRE infections recurred within 90-days. Microbiologic failure rate was 27% (10/37). Ceftazidime-avibactam resistance was detected in 30% (3/10) of microbiologic failures.
September 13, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Brad Spellberg, Robert A Bonomo
No abstract text is available yet for this article.
September 13, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
P Salgado, F Gilsanz, E Maseda
The rapid spread of multidrug-resistant bacteria has become a serious threat, especially in critical care units, thereby prolonging the hospital stay. Enterobacteriaceae have a high capacity to adapt to any environment. Plasmids are the reason behind their expansion. The choice of empiric therapy for intra-abdominal or urinary infections requires knowledge of the intrinsic microbiological variability of each hospital or critical care unit, as well as the source of infection, safety or antibiotic toxicity, interaction with other drugs, the dosage regimen and the presence of risk factors...
September 2016: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
Ivan Gentile, Alberto Enrico Maraolo, Guglielmo Borgia
No abstract text is available yet for this article.
October 2016: Expert Review of Anti-infective Therapy
Elizabeth A Neuner, Jason C Gallagher
Carbapenem-Resistant Enterobacteriaceae (CRE) are an emerging healthcare crisis. Infections due to CRE are associated with high morbidity and mortality, especially in critically ill patients. Due to the multi-drug resistant nature of these infections only limited treatment options are available. Antimicrobials that have been described for the treatment of CRE infections include carbapenems, polymyxins, fosfomycin, tigecycline, aminoglycosides, and ceftazidime-avibactam. Given the limited treatment options it is imperative the pharmacokinetic and pharmacodynamics (PK-PD) characteristics of these agents are considered to optimize treatment regimens...
August 9, 2016: Virulence
Gökhan Metan, Murat Akova
PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide challenge and associated with a high mortality rate in critically ill patients. This review focused on rapid diagnosis, optimization of antimicrobial therapy, and implication of effective infection control precautions to reduce impact of CRE on vulnerable patients. RECENT FINDINGS: Several new diagnostic assays have recently been described for the early diagnosis of CRE. Retrospective studies are supportive for colistin plus meropenem combination for the treatment of CRE infections; however, solid evidence is still lacking...
August 31, 2016: Current Opinion in Infectious Diseases
Jose A Hidalgo, Celeste M Vinluan, Nishaal Antony
There has been greater interest in developing additional antimicrobial agents due to the increasing health care costs and resistance resulting from bacterial pathogens to currently available treatment options. Gram-negative organisms including Enterobacteriaceae and Pseudomonas aeruginosa are some of the most concerning threats due to their resistance mechanisms: extended-spectrum beta-lactamase production and Klebsiella pneumoniae carbapenemase enzymes. Ceftazidime is a third-generation broad-spectrum cephalosporin with activity against P...
2016: Drug Design, Development and Therapy
Juan F Mosley, Lillian L Smith, Crystal K Parke, Jamal A Brown, Alton L Wilson, Lydia V Gibbs
Ceftazidime-avibactam (Avycaz) for the treatment of complicated infections.
August 2016: P & T: a Peer-reviewed Journal for Formulary Management
John S Bradley, Jon Armstrong, Antonio Arrieta, Raafat Bishai, Shampa Das, Shirley Delair, Timi Edeki, William C Holmes, Jianguo Li, Kathryn S Moffett, Deepa Mukundan, Norma Perez, José R Romero, David Speicher, Janice E Sullivan, Diansong Zhou
This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12...
October 2016: Antimicrobial Agents and Chemotherapy
Marco Falcone, David Paterson
During the last decade infections caused by MDR Gram-negative bacteria (GNB) have become increasingly prevalent. Because of their high morbidity and mortality rates, these infections constitute a serious threat to public health worldwide. Ceftazidime/avibactam is a new approved agent combining ceftazidime and a novel β-lactamase inhibitor with activity against various β-lactamases produced by MDR GNB. Avibactam has a spectrum of inhibition of class A and C β-lactamases, including ESBLs, AmpC and Klebsiella pneumoniae carbapenemase (KPC) enzymes...
October 2016: Journal of Antimicrobial Chemotherapy
Henri Merdjan, Antoine Tarral, Shampa Das, Jianguo Li
Avibactam is a non-β-lactam β-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram-negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This Phase 1 study investigated the effect of renal impairment and hemodialysis on avibactam pharmacokinetics and safety. Healthy controls and subjects with increasing degrees of renal impairment received a single 30-minute IV-infusion of avibactam (100 mg)...
July 12, 2016: Journal of Clinical Pharmacology
Sushmita D Lahiri, Patricia A Bradford, Wright W Nichols, Richard A Alm
BACKGROUND: There exists a significant diversity among class A β-lactamases and the proliferation of these enzymes is a significant medical concern due to the ability of some members to efficiently hydrolyse both extended-spectrum cephalosporins and carbapenems. Avibactam is a novel non-β-lactam β-lactamase inhibitor that, in combination with ceftazidime, has recently obtained regulatory approval in the USA. Although avibactam is known to efficiently inhibit key class A enzymes, the diversity of this enzyme family warranted a more complete investigation to understand the breadth of the potential spectrum of inhibition...
October 2016: Journal of Antimicrobial Chemotherapy
Mariana Castanheira, Michelle A Griffin, Lalitagauri M Deshpande, Rodrigo E Mendes, Ronald N Jones, Robert K Flamm
No abstract text is available yet for this article.
September 2016: Antimicrobial Agents and Chemotherapy
Martine I Abboud, Christian Damblon, Jürgen Brem, Nicolas Smargiasso, Paola Mercuri, Bernard Gilbert, Anna M Rydzik, Timothy D W Claridge, Christopher J Schofield, Jean-Marie Frère
β-Lactamases are the most important mechanisms of resistance to the β-lactam antibacterials. There are two mechanistic classes of β-lactamases: the serine β-lactamases (SBLs) and the zinc-dependent metallo-β-lactamases (MBLs). Avibactam, the first clinically useful non-β-lactam β-lactamase inhibitor, is a broad-spectrum SBL inhibitor, which is used in combination with a cephalosporin antibiotic (ceftazidime). There are multiple reports on the interaction of avibactam with SBLs but few such studies with MBLs...
October 2016: Antimicrobial Agents and Chemotherapy
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