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North Liberty, IA, United States

Hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) can be caused by a wide variety of bacteria that originate from the patient flora or the health care environment. We review the medical and microbiology literature and the results of the SENTRY Antimicrobial Surveillance Program (1997-2008) to establish the pathogens most likely to cause HABP or VABP. In all studies, a consistent 6 organisms (Staphylococcus aureus [28.0%], Pseudomonas aeruginosa [21.8%], Klebsiella species [9.8%], Escherichia coli [6.9%], Acinetobacter species [6.8%], and Enterobacter species [6.3%]) caused ~80% of episodes, with lower prevalences of Serratia species, Stenotrophomonas maltophilia, and community-acquired pathogens, such as pneumococci and Haemophilus influenzae. Slight changes in the pathogen order were noted among geographic regions; Latin America had an increased incidence of nonfermentative gram-negative bacilli. In addition, VABP isolates of the same species had a mean of 5%-10% less susceptibility to frequently used extended-spectrum antimicrobials, and the rate of drug resistance among HABP and VABP pathogens has been increasing by 1% per year (2004-2008). In conclusion, the empirical treatment of HABP and VABP due to prevailing bacterial causes and emerging drug resistance has become more challenging and requires use of multidrug empirical treatment regimens for routine clinical practice. These facts have profound impact on the choices of comparison therapies to be applied in contemporary new drug clinical trials for pneumonia. © 2010 by the Infectious Diseases Society of America. All rights reserved. Source

Jones R.N.,345 Beaver Kreek Center | Jones R.N.,Tufts University | Mendes R.E.,345 Beaver Kreek Center | Sader H.S.,345 Beaver Kreek Center
Journal of Antimicrobial Chemotherapy

Objectives: To assess the spectrum and potency of ceftaroline, a novel anti-methicillin-resistant staphylococcal cephalosporin, against a 2008 surveillance collection of clinical isolates from patients in the USA and Europe. Methods: A collection of 14169 isolates of various bacterial species from complicated skin and skin structure infections (cSSSIs) was tested for susceptibility to ceftaroline and 19 comparator agents in a central reference laboratory using CLSI broth microdilution methods. Organisms were received from 55 medical centres; 27 in the USA and 28 in Europe (12 countries, including Israel). The clonality of isolates of Staphylococcus aureus with elevated ceftaroline MICs (4 mg/L) was determined by PFGE and single and multilocus sequence typing, and the mechanism of ceftaroline non-susceptibility was assessed by molecular methods (PCR amplification and sequencing). Results: Ceftaroline, the active component of the parenteral prodrug ceftaroline fosamil, was active against 2988 methicillin-resistant S. aureus (MRSA) isolates, with an MIC 90 of 1 mg/L. The MIC 90 for methicillin-susceptible strains was 0.25-0.5 mg/L. Ceftaroline was additionally active against coagulase-negative staphylococci (MIC 90,0.5-1mg/L), Enterococcus faecalis (MIC 50 ,2mg/L), β-haemolytic and viridans group streptococci (MIC 90, 0.015-0.25 mg/L) and three commonly isolated Enterobacteriaceae (Escherichia coli, Klebsiella spp. and Proteus mirabilis; MIC 90 values of 0.25 to .16 mg/L). All but four isolates of MRSA (0.13%) had ceftaroline MIC values of ≤2mg/L. The isolates for which ceftaroline MICs were 4 mg/L were clonal (single Greek hospital) and had detectable mecA mutations (N146K, N204K, E150K and H351N). Conclusions: The ceftaroline yearly (2008) surveillance for the USA and Europe documented low MIC 50/90 values for MRSA isolates at 1/1 and 1/2 mg/L, respectively. Ceftaroline demonstrated promising potency and coverage against Gram-positive and -negative pathogens known to cause cSSSIs, including MRSA and β-haemolytic streptococci. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Farrell D.J.,345 Beaver Kreek Center | Castanheira M.,345 Beaver Kreek Center | Sader H.S.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center | Jones R.N.,Tufts University
Journal of Infection

Objectives: Solithromycin (formerly CEM-101) is a novel fluoroketolide with potent activity against bacterial pathogens that are susceptible or resistant to other MLS B-ketolide agents. The objective of this study was to assess the activity of solithromycin and comparator antimicrobials against a large number and variety of contemporary clinical bacterial pathogens collected in the United States (USA) and Europe during 2009. Method: During 2009, a total of 10,670 non-duplicated clinical isolates were collected from 52 medical centers located in the USA (27 centers; 6228 isolates) and Europe (25 centers; 4442 isolates). Susceptibility testing and interpretation were performed using CLSI reference methods. Results: Among 1363 Streptococcus pneumoniae isolates, 99.9% of the strains displayed solithromycin MIC values at ≤0.5 mg/L, and 100% were inhibited at an MIC of 1 mg/L. Solithromycin demonstrated activity and potency against Haemophilus influenzae comparable to azithromycin (MIC 50, 1 mg/L and MIC 90, 2 mg/L) and was very potent against all 313 Moraxella catarrhalis isolated (MIC 50, 0.06 mg/L and MIC 90, 0.12 mg/L). Against 4729 Staphylococcus aureus isolates, solithromycin (MIC 50, 0.06 mg/L and MIC 90, >4 mg/L) activity was greater against methicillin-susceptible isolates (MIC 50, 0.06 mg/L and MIC 90, 0.06 mg/L) compared to methicillin-resistant isolates (MIC 50, 0.06 mg/L and MIC 90, >4 mg/L). Solithromycin was very active against all 757 β-haemolytic streptococci (MIC 50, ≤0.03 mg/L and MIC 90, 0.06 mg/L) and 310 viridans group streptococci (MIC 50, ≤0.03 mg/L and MIC 90, 0.06 mg/L) evaluated. Conclusion: This contemporary surveillance study utilizing clinical isolates shows that solithromycin exhibits favorable in vitro potency and spectrum of activity against bacterial pathogens most frequently isolated in community-acquired respiratory tract (CA-RTI) and skin and skin structure infections (SSSI). © 2010 The British Infection Association. Source

Barriere S.L.,Theravance | Farrell D.J.,345 Beaver Kreek Center | Rhomberg P.R.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center
Diagnostic Microbiology and Infectious Disease

Telavancin biological activity, determined by serum titers against a reference strain of Staphylococcus aureus, was maintained in the serum of subjects with severe renal impairment or end-stage renal disease suggesting that there is no apparent effect of renal function on in vitro activity of telavancin. © 2014 The Authors. Source

Mendes R.E.,345 Beaver Kreek Center | Sader H.S.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center | Jones R.N.,Tufts University
International Journal of Antimicrobial Agents

The activity of telavancin was evaluated against Staphylococcus spp. collected from European hospitals as part of an international surveillance study (2007-2008). A total of 7534 staphylococcal clinical isolates [5726 Staphylococcus aureus and 1808 coagulase-negative staphylococci (CoNS)] were included. Isolates were tested for susceptibility according to reference methods and minimum inhibitory concentration (MIC) values were interpreted based on Clinical and Laboratory Standards Institute (CLSI) 2010 and European Committee on Antimicrobial Susceptibility Testing (EUCAST) 2009 criteria. Telavancin breakpoints approved by the US Food and Drug Administration (FDA) were applied. Telavancin activity was evaluated against meticillin-resistant S. aureus (MRSA) displaying several antibiogram resistance patterns, including multidrug-resistant isolates. Telavancin was active against S. aureus [MIC 50/90 values (MICs for 50% and 90% of the isolates, respectively)=0.12/0.25mg/L; 100.0% susceptible] and CoNS (MIC 50/90=0.12/0.25mg/L), inhibiting all isolates at ≤0.5mg/L. Similar results were observed when S. aureus were stratified by year or country of origin (MIC 50/90=0.12/0.25mg/L). When MRSA isolates were clustered according to 48 different resistance patterns, telavancin showed consistent MIC 90 values (0.25mg/L) regardless of multidrug resistance. Amongst CoNS, telavancin was slightly more active against Staphylococcus capitis, Staphylococcus epidermidis, Staphylococcus hominis, Staphylococcus lugdunensis and Staphylococcus xylosus (MIC 50=0.12mg/L) compared with Staphylococcus haemolyticus, Staphylococcus saprophyticus and Staphylococcus warneri (MIC 50=0.25mg/L). Overall, telavancin exhibited MIC 90 results two- to eight-fold lower than comparators (daptomycin, quinupristin/dalfopristin, vancomycin and linezolid). Based upon MIC 90 values, telavancin demonstrated potent in vitro activity against a contemporary (2007-2008) collection of Staphylococcus spp. recovered from nearly 30 European medical centres. © 2010 Elsevier B.V. and the International Society of Chemotherapy. Source

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