North Liberty, IA, United States
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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 | Year: 2014

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.


Jones R.N.,345 Beaver Kreek Center | Farrell D.J.,345 Beaver Kreek Center | Mendes R.E.,345 Beaver Kreek Center | Sader H.S.,345 Beaver Kreek Center
Journal of Antimicrobial Chemotherapy | Year: 2011

Objectives: To document the spectrum of activity of ceftaroline, the active form of the prodrug, ceftaroline fosamil, a new cephalosporin with anti-methicillin-resistant staphylococcal activity, against a surveillance collection of clinical isolates obtained from the USA and Europe during 2008-09. Methods: A selected group of species associated with community-acquired pneumonia (CAP; 6496 of 17326 monitored strains) were tested for susceptibility in a central laboratory using CLSI broth microdilution methods. Organisms were sampled from 55 medical centres, 27 in the USA and 28 (12 countries) in Europe. Ceftaroline and comparator agents were tested and interpretations of MIC endpoints made by applying current CLSI (2010) and EUCAST (2010) breakpoint criteria. Results: Against 1340 Streptococcus pneumoniae, ceftaroline inhibited all isolates at ≤0.5 mg/L (MIC 50/90, ≤0.008/0.12 mg/L) and was 8-fold more active than ceftriaxone (MIC 90, 1 mg/L; only 79.2% coverage at EUCAST breakpoint). Haemophilus influenzae (n=584; MIC 50/90, ≤0.008/0.015 mg/L), Moraxella catarrhalis (n=377; MIC 50/90, 0.03-0.06/0.12 mg/L) and Staphylococcus aureus (n=590; MIC 50/90, 0.5/1 mg/L) were very susceptible to ceftaroline, regardless of b-lactamase production or multidrug resistance (MDR) patterns. The potency of ceftaroline against three species of Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae) was similar to that of ceftriaxone, ceftazidime and piperacillin/tazobactam. Only modest differences in rates of ceftaroline susceptibility (breakpoint ≤2 mg/L) were noted with extendedspectrum β-lactamase-negative Enterobacteriaceae strains between the USA and Europe (97.9% versus 97.0% for E. coli). Ceftaroline, like ceftriaxone, was not active against ceftazidime-resistant E. coli (10.2%-26.2% susceptible at ≤2 mg/L) or K. pneumoniae (5.3%-11.2%). Conclusions: The ceftaroline surveillance for 2008-09 (USA and Europe) documented low MIC 50/90 values for S. aureus isolates at 0.5/1 and 0.25/1 mg/L, respectively. More importantly, ceftaroline MIC 90 results for S. pneumoniae (0.12 mg/L), H. influenzae (0.015 mg/L) and M. catarrhalis (0.12 mg/L) were very low, all MICs being ≤0.5 mg/L. Ceftaroline exhibited promising high potency and wide coverage against Gram-positive and -negative pathogens known to cause CAP, especially isolates of MDR pneumococci and methicillin-resistant S. aureus. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Pfaller M.A.,345 Beaver Kreek Center | Farrell D.J.,345 Beaver Kreek Center | Sader H.S.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center
Clinical Infectious Diseases | Year: 2012

Ceftaroline fosamil, the prodrug form of the active metabolite ceftaroline, is a new broad-spectrum parenteral cephalosporin with antibacterial activity against the prevalent respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Bacterial resistance surveillance (5330 isolates) was conducted in the United States between 2008 and 2010 to assess the in vitro activity of ceftaroline and comparator antibacterial agents against invasive respiratory isolates of S. pneumoniae (3329 isolates), H. influenzae (1545 isolates), and M. catarrhalis (456 isolates). All organisms were cultured from patient infections in 71 US hospital laboratories and were submitted to a central reference monitor for broth microdilution testing by Clinical and Laboratory Standards Institute reference methods. Against S. pneumoniae, ceftaroline inhibited 98.7 of strains at the susceptible breakpoint of ≤0.25 μg/mL (50 minimum inhibitory concentration [MIC50], 0.01 μg/mL; 90 MIC [MIC90], 0.12 μg/mL) and was 16-fold more active than ceftriaxone (MIC90, 2 μg/mL). Among 70 ceftriaxone-resistant pneumococcal isolates, all were inhibited by ≤0.5 μg/mL of ceftaroline. Haemophilus influenzae (MIC50, ≤0.008 μg/mL; MIC90, 0.015 μg/mL) and M. catarrhalis (MIC50, 0.06 μg/mL; MIC90, 0.12 μg/mL) were very susceptible to ceftaroline regardless of -lactamase production. Whereas the high-level of activity of ceftaroline was maintained against S. pneumoniae and H. influenzae from 2008 through 2010, increased rates of nonsusceptibility were observed for amoxicillin/clavulanate, erythromycin, and levofloxacin among S. pneumoniae and for trimethoprim/sulfamethoxazole and azithromycin among H. influenzae. In summary, ceftaroline resistance surveillance (Assessing Worldwide Antimicrobial Resistance Evaluation [AWARE] Program) in the United States (2008-2010) documented in vitro sustained potency and spectrum against Gram-positive and Gram-negative pathogens known to cause community-acquired bacterial pneumonia. © The Author 2012. Published by Oxford University Press on behalf of the Infectious. Diseases Society of America. All rights reserved.


Sader H.S.,345 Beaver Kreek Center | Sader H.S.,Federal University of São Paulo | Farrell D.J.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center | Jones R.N.,Tufts University
International Journal of Antimicrobial Agents | Year: 2010

Skin and skin-structure infections (SSSIs) usually involve Gram-positive organisms. Prompt initiation of appropriate antimicrobial treatment is essential for achieving a favourable outcome in severe cases. Empirical antibacterial therapy should be based on several considerations, including patient risk factors, expected pathogens and local/regional susceptibility profiles, among others. In the present study, we evaluated the antimicrobial susceptibility patterns of Gram-positive bacteria isolated from patients with SSSIs hospitalised in European medical centres. A total of 3573 bacterial isolates were collected from 33 medical centres located in 13 European countries as well as Israel over a 6-year period (2003-2008) and were tested for susceptibility to daptomycin and other comparator agents by reference broth microdilution methods in a central laboratory. The most frequently isolated organisms were Staphylococcus aureus (71.1%), β-haemolytic streptococci (10.5%) and enterococci (9.3%). Overall, rates of meticillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) were 22.5% and 5.1%, respectively, but with great intercountry variation. The overall MRSA rate varied slightly during the study period, but with no overall tendency toward increase or decrease, whilst the overall VRE rate consistently increased from 1.5% in 2003 to 11.0% in 2008. Daptomycin and linezolid were the most active agents tested overall. All isolates monitored were considered susceptible to daptomycin, and only one isolate (Enterococcus faecium) was categorised as non-susceptible to linezolid. In conclusion, the results of this contemporary surveillance study indicate that daptomycin and linezolid retain sustained in vitro activity against Gram-positive cocci isolated from patients hospitalised with SSSI in numerous European medical centres. © 2010 Elsevier B.V. and the International Society of Chemotherapy.


Jones R.N.,345 Beaver Kreek Center
Clinical Infectious Diseases | Year: 2010

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.


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 | Year: 2010

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.


Castanheira M.,345 Beaver Kreek Center | Messer S.A.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center | Farrell D.J.,345 Beaver Kreek Center | Pfaller M.A.,345 Beaver Kreek Center
International Journal of Antimicrobial Agents | Year: 2014

In this study, 1717 fungal clinical isolates causing invasive fungal infections were evaluated against nine antifungal agents using Clinical and Laboratory Standards Institute (CLSI) reference broth microdilution methods. The isolates comprised 1487 Candida spp., 109 Aspergillus spp., 86 non-Candida yeasts (including 52 isolates of Cryptococcus neoformans) and 35 rare moulds obtained during 2012 from 72 hospitals worldwide. Echinocandin resistance among Candida spp. was low, and resistance rates to anidulafungin, caspofungin and micafungin varied from 0.0% to 2.8% among different species. Echinocandin-resistant Candida glabrata were shown to have fks mutations (fks2 HS1 F659Y, F659del, S663F and S663P), and fluconazole resistance was also observed in those strains. One Candida krusei and one Candida dubliniensis had L701M or S645P fks1 mutations, respectively. Candida tropicalis and C. glabrata had higher fluconazole resistance rates of 6.1% and 6.9%, respectively, compared with other Candida spp. Fluconazole-resistant C. tropicalis were collected in five countries (USA, China, Germany, Belgium and Thailand). Voriconazole was active against all Candida spp., inhibiting 91.2-99.7% of isolates using species-specific breakpoints. All agents except for the echinocandins and posaconazole were active against Cr. neoformans. Triazoles were active against other yeasts [MIC90 (minimum inhibitory concentration encompassing 90% of isolates tested), 2 μg/mL]. The echinocandins and the mould-active triazoles were active against Aspergillus [MIC/MEC90 (minimum effective concentration encompassing 90% of isolates tested) range, 0.015-2 μg/mL], but the activity of these agents was limited against uncommon mould species (MIC/MEC90 range, 4 μg/mL to >16 μg/mL). © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.


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 | Year: 2010

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.


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 | Year: 2010

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.


Pfaller M.A.,345 Beaver Kreek Center | Woosley L.N.,345 Beaver Kreek Center | Messer S.A.,345 Beaver Kreek Center | Jones R.N.,345 Beaver Kreek Center | Castanheira M.,345 Beaver Kreek Center
Mycopathologia | Year: 2012

The increasing diversity of opportunistic fungi causing serious invasive fungal infections (IFI) has been documented. Accurate identification (ID) is important in guiding therapy, determining prognosis for IFIs and in epidemiological surveys. We assessed the utility of PCR-based methods for the ID of yeasts and moulds that either were uncommon, failed conventional ID, or represented unusual biochemical or phenotypic profiles of common species. Among 1,790 viable fungal clinical isolates received during the SENTRY Program in 2010, 322 strains from 40 study sites had ID confirmed by molecular methods. Isolates were previously identified in participant institutions. Yeasts that were not confirmed by morphology on CHROMagar, growth at 45 °C (Candida albicans/dubliniensis), or assimilation of trehalose (C. glabrata) as well as non-Candida yeasts and all moulds were amplified and sequenced using primers amplifying one or more of the following genes: ITS, 28S, β-tubulin (Aspergillus spp.), TEF (Fusarium spp.), IGS (Trichosporon spp.). The isolates selected for molecular ID included 149 isolates of Candida species, 77 of Aspergillus species, 73 non-Candida yeasts, and 23 other moulds (a total of 41 different species). Overall, the ID determined by the submitting site was confirmed for 189 isolates (58. 7 %): Aspergillus spp. (64. 1 % correct); Candida spp. (60. 1 % correct); non-Candida yeasts (58. 9 % correct); non-Aspergillus moulds (30. 4 % correct). Species with high levels of concordance between conventional and molecular ID included A. fumigatus (95.0%), C. lusitaniae (100 %), C. dubliniensis (92. 3 %), C. kefyr (100 %), and C. neoformans (90. 2 %). Only 50. 0 % of isolates of C. albicans and 59. 1 % of C. glabrata selected due to unusual phenotypic or biochemical features were found to be correctly identified by the submitting site. Molecular methods for the identification of fungal pathogens are an important adjunct to the conventional identification of many less common clinically relevant yeasts and moulds including species of Candida with unusual or erroneous phenotypic or biochemical profiles. Molecular confirmation of fungal identification is essential in epidemiological surveys such as SENTRY. © 2012 Springer Science+Business Media B.V.

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