International journal of antimicrobial agents
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The serum procalcitonin (PCT) concentration reflects both the systemic response to bacterial infection and its severity. However, its accuracy in distinguishing intensive care unit (ICU) patients with and without infection remains low owing to a lack of specificity and the time lapse between infection onset and the PCT rise. Hence, PCT cannot be used as a marker to start or withhold antibiotic therapy for ICU patients. ⋯ PCT-guided algorithms to guide antibiotic discontinuation were able to shorten antibiotic duration without impacting patient outcomes in several multicentre randomised studies. Notably, antibiotics can be stopped very early when PCT is low and remains low as this indicates that bacterial infection is unlikely. When PCT falls to <0.5 ng/mL or >80% from its peak value, antibiotics for non-localised infections can safely be stopped.
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Int. J. Antimicrob. Agents · Dec 2015
ReviewCan procalcitonin monitoring reduce the length of antibiotic treatment in bloodstream infections?
Antibiotic overconsumption and subsequent bacterial multidrug resistance are associated with increased mortality, length of hospitalisation and healthcare costs. Discontinuation of antibiotic treatment in severe infections, such as bloodstream infections (BSIs), is a demanding clinical decision. ⋯ Furthermore, the presented data indicate that PCT assessment is helpful in the diagnosis of infective endocarditis. In conclusion, monitoring of PCT together with evaluation of the clinical situation is a valuable tool in reducing the length of antimicrobial treatment in BSIs.
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Int. J. Antimicrob. Agents · Dec 2015
Can we transfer pharmacokinetics/pharmacodynamics of antimicrobials into clinical practice?
In critically ill patients there is extensive evidence of subtherapeutic antibiotic exposure from standard doses across different antibiotic classes. This can be a direct consequence of pharmacokinetic alterations emanating from the complex pathophysiological processes associated with severe infection. ⋯ In clinical practice, it is necessary to reduce the number of blood samples collected from the patient to a minimum because of the cost (personnel, devises and analysis). TDM to calculate PK/PD indices is easily feasible only when a single blood sample is adequate to perform the analysis.
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Int. J. Antimicrob. Agents · Nov 2015
Multicenter StudyIn vitro activity of ceftolozane/tazobactam against clinical isolates of Pseudomonas aeruginosa and Enterobacteriaceae recovered in Spanish medical centres: Results of the CENIT study.
Ceftolozane/tazobactam is a novel antimicrobial agent with activity against Pseudomonas aeruginosa, including drug-resistant strains, and other Gram-negative pathogens, including most extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. The CENIT study evaluated the in vitro activity of ceftolozane/tazobactam and comparators against clinical isolates of P. aeruginosa (n=500) and Enterobacteriaceae (n=500) collected from patients with complicated intra-abdominal, complicated urinary tract, lower respiratory tract or bloodstream infections in 10 medical centres in Spain (January-September 2013). Antimicrobial susceptibility was determined by the ISO broth microdilution method using commercial dry-form panels and results were interpreted per EUCAST and CLSI guidelines and for ceftolozane/tazobactam with FDA criteria. ⋯ Ceftolozane/tazobactam demonstrated excellent overall activity (MIC50/90, 0.25/0.5 mg/L) against all 250 Escherichia coli isolates, including isolates displaying a wild-type (MIC(90), 0.25/0.25 mg/L) or ESBL (MIC(50/90), 0.5/1mg/L) phenotype, and good activity against isolates displaying an AmpC-like phenotype (MIC range 0.25-4 mg/L). Ceftolozane/tazobactam demonstrated good overall activity (MIC(50/90), 0.25/4 mg/L) against all 104 Klebsiella spp. isolates, although activity was lower against those with an ESBL phenotype (MIC(50/90), 4/16 mg/L), and was inactive against the carbapenemase-producing isolates (MIC≥64 mg/L). Ceftolozane/tazobactam demonstrated excellent in vitro activity against most of the P. aeruginosa and Enterobacteriaceae clinical isolates obtained from medical centres in Spain, supporting the potential value of ceftolozane/tazobactam in treating infections due to these pathogens.
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Int. J. Antimicrob. Agents · Nov 2015
ReviewA resurgence of β-lactamase inhibitor combinations effective against multidrug-resistant Gram-negative pathogens.
β-Lactamase inhibitors (BLIs) have played an important role in combatting β-lactam resistance in Gram-negative bacteria, but their effectiveness has diminished with the evolution of diverse and deleterious varieties of β-lactamases. In this review, a new generation of BLIs and inhibitor combinations is presented, describing epidemiological information, pharmacodynamic studies, resistance identification and current clinical status. Novel serine BLIs of major interest include the non-β-lactams of the diazabicyclo[3.2.1]octanone (DBO) series. ⋯ Although effective inhibitor combinations are in development for the treatment of infections caused by Gram-negative bacteria with serine carbapenemases, better options are still necessary for pathogens that produce metallo-β-lactamases (MBLs). The aztreonam/avibactam combination demonstrates inhibitory activity against MBL-producing enteric bacteria owing to the stability of the monobactam to these enzymes, but resistance is still an issue for MBL-producing non-fermentative bacteria. Because all of the inhibitor combinations are being developed as parenteral drugs, an orally bioavailable combination would also be of interest.