avibactam and Cross-Infection

The activities of the novel β-lactam/non-β-lactam β-lactamase inhibitor combination ceftazidime/avibactam and comparators were evaluated against isolates from pneumonia in hospitalised patients including ventilated patients (PHP, pneumonia not designated as VABP; VABP, pneumonia in ventilated patients). Isolates were from the European-Mediterranean region (EuM), China and the USA collected in the SENTRY Antimicrobial Surveillance Program between 2009 and 2011 inclusive. A total of 2393 organisms from PHP were from the EuM, 888 from China and 3213 from the USA; from VABP patients there were 918, 97 and 692 organisms collected, respectively. Among Enterobacteriaceae from PHP, ceftazidime/avibactam MIC90 values against Escherichia coli ranged from 0.25-0.5mg/L and Klebsiella spp. MIC90 values were 0.5mg/L in each region. Among VABP isolates, MIC90 values for ceftazidime/avibactam against E. coli were 0.25mg/L; for Klebsiella spp. from VABP patients, MIC90 values were similar to those obtained against PHP isolates. The MIC of ceftazidime/avibactam was ≤8mg/L against 92-96% of Pseudomonas aeruginosa isolated from PHP patients. Isolates of P. aeruginosa from VABP patients were of lower susceptibility to all antibacterial agents (e.g. depending on region, meropenem susceptibilities were 51.2-69.4% in contrast to 68.3-76.7% among PHP patients). However, ceftazidime/avibactam inhibited 79.2-95.4% of VABP isolates at an MIC of ≤8mg/L. Acinetobacter spp. were resistant to many agents and only rates of susceptibility to colistin were >90% across all regions both for PHP and VABP isolates. Ceftazidime/avibactam was generally active against a high proportion of isolates resistant to ceftazidime from PHP and VAPB patients.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Ceftazidime; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitalization; Humans; Microbial Sensitivity Tests; Pneumonia, Bacterial; Respiration, Artificial

The activity of ceftazidime/avibactam and comparator agents was monitored at 73 medical centres across all nine US census bureau regions during 2012.. Bacterial isolates were collected from patients hospitalized with pneumonia, urinary tract infections (UTI), intra-abdominal infections (IAI) and bloodstream infections (BSI). The study protocol predetermined the target numbers of strains for each of the requested bacterial species that sites were to collect. Isolates were determined to be clinically relevant at the medical centre and only one isolate per patient episode was collected.. There were 1466 Gram-negative isolates from BSI, 3245 from pneumonia patients, 501 from IAI and 2356 from UTI. Ceftazidime/avibactam was active against Enterobacteriaceae from each infection type. The MIC90 values for ceftazidime/avibactam against Enterobacteriaceae isolates from BSI, pneumonia patients, IAI or UTI were 0.25 mg/L. The extended-spectrum cephalosporin resistance rates for Escherichia coli were 8.5% (UTI), 10.4% (IAI), 12.7% (BSI) and 17.5% (pneumonia patients). The extended-spectrum cephalosporin resistance rates for Klebsiella spp. were 13.0% (UTI), 13.9% (BSI), 16.3% (IAI) and 19.3% (pneumonia patients). A total of 96.5% of the Pseudomonas aeruginosa isolates from BSI, 95.8% from pneumonia patients, 96.3% from IAI and 98.7% from UTI exhibited a ceftazidime/avibactam MIC of ≤8 mg/L (CLSI susceptible breakpoint for ceftazidime when tested alone against P. aeruginosa). Most tested agents showed limited activity against Acinetobacter baumannii, except for colistin. A total of 31.2% of A. baumannii displayed ceftazidime/avibactam MIC values of ≤8 mg/L.. Ceftazidime/avibactam demonstrated potent broad-spectrum activity against Gram-negative pathogens collected in the USA during 2012 from BSI, pneumonia patients, IAI and UTI.

Topics: Academic Medical Centers; Azabicyclo Compounds; Ceftazidime; Cross Infection; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Intraabdominal Infections; Microbial Sensitivity Tests; Pneumonia; United States; Urinary Tract Infections

For an antibacterial agent to be considered for clinical studies in nosocomial pneumonia (NP), it should be active in the presence of pulmonary surfactant. Furthermore, owing to the common practice of treating such infections with more than one antibacterial agent, it should be free of antagonistic interactions with agents of other classes. The aim of this study was to demonstrate the effect of pulmonary surfactant on the activity of ceftazidime and ceftazidime-avibactam and to determine the interaction (if any) of ceftazidime-avibactam and six antimicrobial agents common in the treatment of NP. Minimum inhibitory concentration (MIC) determination for ceftazidime and ceftazidime-avibactam was performed with and without the presence of four concentrations of bovine pulmonary surfactant, and a chequerboard assay was used to determine any interaction between ceftazidime and ceftazidime-avibactam with tobramycin, levofloxacin, linezolid, vancomycin, tigecycline and colistin. Here we report that the in vitro antimicrobial activity of ceftazidime-avibactam against β-lactamase-producing Gram-negative bacteria remained unaltered in the presence of pulmonary surfactant at concentrations that antagonised the antimicrobial activity of daptomycin. Furthermore, in chequerboard interaction studies, an absence of antagonism was demonstrated between ceftazidime-avibactam and six antimicrobial agents of different classes when tested against aerobic species frequently isolated from NP. The results support the further investigation of ceftazidime-avibactam as a potential treatment for NP caused by susceptible bacteria.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Ceftazidime; Cross Infection; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Minocycline; Pneumonia, Bacterial; Pulmonary Surfactants; Tigecycline; Tobramycin

The in vitro activities of ceftaroline-avibactam, ceftaroline, and comparative agents were determined for a collection of bacterial pathogens frequently isolated from patients seeking care at 15 Canadian hospitals from January 2010 to December 2012. In total, 9,758 isolates were tested by using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (document M07-A9, 2012), with MICs interpreted by using CLSI breakpoints (document M100-S23, 2013). Ceftaroline-avibactam demonstrated potent activity (MIC90, ≤ 0.5 μg/ml) against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Morganella morganii, Citrobacter freundii, and Haemophilus influenzae; >99% of isolates of E. coli, K. pneumoniae, K. oxytoca, P. mirabilis, M. morganii, C. freundii, and H. influenzae were susceptible to ceftaroline-avibactam according to CLSI MIC interpretative criteria for ceftaroline. Ceftaroline was less active than ceftaroline-avibactam against all species of Enterobacteriaceae tested, with rates of susceptibility ranging from 93.9% (P. mirabilis) to 54.0% (S. marcescens). All isolates of methicillin-susceptible Staphylococcus aureus (MIC90, 0.25 μg/ml) and 99.6% of methicillin-resistant S. aureus isolates (MIC90, 1 μg/ml) were susceptible to ceftaroline; the addition of avibactam to ceftaroline did not alter its activity against staphylococci or streptococci. All isolates of Streptococcus pneumoniae (MIC90, 0.03 μg/ml), Streptococcus pyogenes (MIC90, ≤ 0.03 μg/ml), and Streptococcus agalactiae (MIC90, 0.015 μg/ml) tested were susceptible to ceftaroline. We conclude that combining avibactam with ceftaroline expanded its spectrum of activity to include most isolates of Enterobacteriaceae resistant to third-generation cephalosporins, including extended-spectrum β-lactamase (ESBL)- and AmpC-producing E. coli and ESBL-producing K. pneumoniae, while maintaining potent activity against staphylococci and streptococci.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Canada; Ceftaroline; Cephalosporins; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Microbial Sensitivity Tests; Public Health Surveillance; Retrospective Studies