State Center, IA, United States
State Center, IA, United States

Time filter

Source Type

Pfaller M.A.,45 Beaver Kreek Center | Castanheira M.,45 Beaver Kreek Center | Diekema D.J.,University of Iowa | Messer S.A.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
Journal of Clinical Microbiology | Year: 2011

When clinical susceptibility breakpoints (CBPs) are absent, establishing wild-type (WT) MIC distributions and epidemiological cutoff values (ECVs) provides a sensitive means for detecting emerging resistance. We determined species-specific ECVs for anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), fluconazole (FLC), posaconazole (PSC), and voriconazole (VRC) for six rarer Candida species (819 strains) using isolates obtained from the ARTEMIS Program and the SENTRY Antimicrobial Surveillance Program, all tested by a reference broth microdilution method. The calculated ECVs, expressed in μg/ml (and the percentages of isolates that had MICs less than or equal to the ECVs), for ANF, CSF, MCF, FLC, PSC, and VRC, respectively, were 0.12 (95.2), 0.12 (97.8), 0.12 (100.0), 0.5 (95.7), 0.12 (98.6), and 0.03 (100.0) for Candida dubliniensis; 4 (100.0), 2 (96.0), 2 (99.1), 8 (95.0), 0.5 (97.5), and 0.25 (98.0) for C. guilliermondii; 0.25 (98.9), 0.03 (98.0), 0.12 (97.5), 1 (99.1), 0.25 (99.1), and 0.015 (100.0) for C. kefyr; 2 (100.0), 1 (99.6), 0.5 (96.6), 2 (96.1), 0.25 (98.6), and 0.03 (96.6) for C. lusitaniae; and 2 (100.0), 0.5 (100.0), 1 (100.0), 2 (98.0), 0.25 (97.1), and 0.06 (98.0) for C. orthopsilosis, but for C. pelliculosa, ECVs could be determined only for CSF (0.12 [94.4]), FLC (4 [98.2]), PSC (2 [98.2]), and VRC (0.25 [98.2]). In the absence of species-specific CBP values, these WT MIC distributions and ECVs will be useful for monitoring the emergence of reduced susceptibility to the triazole and echinocandin antifungals. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Pfaller M.A.,45 Beaver Kreek Center | Moet G.J.,45 Beaver Kreek Center | Messer S.A.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center | And 2 more authors.
Journal of Clinical Microbiology | Year: 2011

Antifungal testing results from the SENTRY Antimicrobial Surveillance Program (2008 to 2009) were analyzed for regional variations of invasive Candida species infections. Among 2,085 cases from the Asian-Pacific (APAC) (51 cases), Latin American (LAM) (348 cases), European (EU) (750 cases), and North American (NAM) (936 cases) regions, Candida albicans predominated (48.4%), followed by C. glabrata (18.0%), C. parapsilosis (17.2%), C. tropicalis (10.5%), and C. krusei (1.9%). Resistance to echinocandins (anidulafungin [2.4%] and micafungin [1.9%]) and azoles (3.5 to 5.6%) was most prevalent among C. glabrata isolates, as determined using recently established CLSI breakpoint criteria. C. glabrata isolates were more common in NAM (23.5%), and C. albicans isolates were more common in APAC (56.9%), with C. parapsilosis (25.6%) and C. tropicalis (17.0%) being more prominent in LAM. Emerging resistance patterns among C. glabrata cases in NAM require focused surveillance. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Mendes R.E.,45 Beaver Kreek Center | Deshpande L.M.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center | Jones R.N.,Tufts University
Drug Resistance Updates | Year: 2014

Linezolid, approved for clinical use since 2000, has become an important addition to the anti-Gram-positive infection armamentarium. This oxazolidinone drug has in vitro and in vivo activity against essentially all Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). The in vitro activity of linezolid was well documented prior to its clinical application, and several ongoing surveillance studies demonstrated consistent and potent results during the subsequent years of clinical use. Emergence of resistance has been limited and associated with invasive procedures, deep organ involvement, presence of foreign material and mainly prolonged therapy. Non-susceptible organisms usually demonstrate alterations in the 23S rRNA target, which remain the main resistance mechanism observed in enterococci; although a few reports have described the detection of cfr-mediated resistance in Enterococcus faecalis. S. aureus isolates non-susceptible to linezolid remain rare in large surveillance studies. Most isolates harbour 23S rRNA mutations; however, cfr-carrying MRSA isolates have been observed in the United States and elsewhere. It is still uncertain whether the occurrences of such isolates are becoming more prevalent. Coagulase-negative isolates (CoNS) resistant to linezolid were uncommon following clinical approval. Surveillance data have indicated that CoNS isolates, mainly Staphylococcus epidermidis, currently account for the majority of Gram-positive organisms displaying elevated MIC results to linezolid. In addition, these isolates frequently demonstrate complex and numerous resistance mechanisms, such as alterations in the ribosomal proteins L3 and/or L4 and/or presence of cfr and/or modifications in 23S rRNA. The knowledge acquired during the past decades on this initially used oxazolidinone has been utilized for developing new candidate agents, such as tedizolid and radezolid, and as linezolid patents soon begin to expire, generic brands will certainly become available. These events will likely establish a new chapter for this successful class of antimicrobial agents. © 2014 Elsevier Ltd.


Woosley L.N.,45 Beaver Kreek Center | Castanheira M.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center | Jones R.N.,Tufts University
Antimicrobial Agents and Chemotherapy | Year: 2010

The in vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of the MICs and minimum bactericidal concentrations (MBCs), timed killing, single-step and multistep mutation rates, the erythromycin induction of resistance, postantibiotic effect (PAE), and drug interactions were performed for CEM-101; and the results were compared to those obtained with telithromycin, macrolides, and lincosamides. The MBCs of CEM-101 remained lower overall than those of telithromycin, and CEM-101 displayed a 2-fold greater potency than the ketolide. Timed-killing curve testing showed that CEM-101 had greater bactericidal activity than telithromycin (a ≥3-log 10-CFU/ml decrease in the initial inoculum at 24 h) against the staphylococcal isolates tested. The propensity of CEM-101 to cause resistance was low, as determined from the rates of resistance determined in single-step mutational studies (<10 -8 or 10 -9). In multipassaging studies, mutants of two strains (both of which were USA300 isolates) resistant to CEM-101 emerged. That number was comparable to the number resistant to clindamycin but less than the number resistant to telithromycin. Erythromycin induced CEM-101 resistance in Staphylococcus aureus and Streptococcus pneumoniae, similar to telithromycin; however, in seven of eight beta-hemolytic streptococci, CEM-101 resistance induction was not observed. CEM-101 showed a significant concentration- and exposure-dependent PAE against the strains tested, with the values ranging from 2.3 to 6.1 h for Gram-positive organisms (these times were longer than those for telithromycin). No antagonism was found in synergy analyses, with enhanced inhibition being most noted for combinations with CEM-101 and ceftriaxone, gentamicin, and trimethoprim- sulfamethoxazole. Overall, this new antimicrobial agent (CEM-101) showed good antimicrobial characteristics compared with those of the agents in its class and exhibited measured parameter values similar or superior to those of utilized comparators, indicating that CEM-101 warrants further clinical evaluation. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Pfaller M.A.,45 Beaver Kreek Center | Moet G.J.,45 Beaver Kreek Center | Messer S.A.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center | And 2 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Community-onset (CO) candidemia, defined as a positive blood culture taken at or within 2 days of hospital admission, represents a distinct clinical entity associated with substantial morbidity and mortality. Reference MIC results from the SENTRY Antimicrobial Surveillance Program (2008-2009) were analyzed to compare the antifungal resistance patterns and species distributions from patients with CO and nosocomial bloodstream infections (BSI) in 79 medical centers. Among 1,354 episodes of BSI, 494 (36.5%) were classified as CO and 860 (63.5%) as nosocomial in origin. More than 95% of the isolates from both BSI types were contributed by Candida albicans (48.4%), C. glabrata (18.2%), C. parapsilosis (17.1%), C. tropicalis (10.6%), and C. krusei (2.0%). C. albicans was more common in CO BSI (51.0%) than nosocomial BSI (46.9%), whereas C. parapsilosis and C. krusei were more common in nosocomial BSIs (18.1 and 2.7%, respectively) than in CO BSIs (15.4 and 0.8%, respectively). C. glabrata and C. tropicalis were comparable in both CO (18.4 and 10.5%, respectively) and nosocomial (18.1 and 10.6%, respectively) episodes. Resistance to azoles (fluconazole, posaconazole, and voriconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) was uncommon (<5%) in CO BSI using recently established Clinical and Laboratory Standards Institute breakpoint criteria. Resistance to echinocandins (anidulafungin [3.8%], caspofungin [5.1%], and micafungin [3.2%]) and azoles (fluconazole [7.7%], posaconazole [5.1%], and voriconazole [6.4%]) was most prevalent among nosocomial BSI isolates of C. glabrata. CO candidemia is not uncommon and appears to be increasing worldwide due to changing health care practices. Although resistance to the azoles and echinocandins remains uncommon among CO isolates, we demonstrate the emergence of nosocomial occurrences of C. glabrata expressing resistance to both monitored classes of antifungal agents. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Mendes R.E.,45 Beaver Kreek Center | Moet G.J.,45 Beaver Kreek Center | Janechek M.J.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
Antimicrobial Agents and Chemotherapy | Year: 2010

The activity of telavancin and comparators was assessed against a contemporary (2007 and 2008) global collection of 10,000 isolates of Staphylococcus aureus. Telavancin was very active against methicillin- susceptible and -resistant S. aureus (MSSA and MRSA, respectively; MIC 50/90 for both, 0.12/0.25 μg/ml; 100.0% susceptible). This agent was 2-, 4-, and 8-fold more potent than daptomycin (MIC 90, 0.5 μg/ml), vancomycin or quinupristin-dalfopristin (MIC 90, 1 μg/ml), and linezolid (MIC 90, 2 μg/ml) against MRSA, respectively. These data show a potent activity of telavancin tested against a current global collection of S. aureus. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Sader H.S.,45 Beaver Kreek Center | Farrell D.J.,45 Beaver Kreek Center | Flamm R.K.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
International Journal of Antimicrobial Agents | Year: 2014

Here we evaluated the frequency of occurrence and antimicrobial susceptibility patterns of Gram-negative bacteria isolated from patients hospitalised with pneumonia in medical centres in the USA (n = 28) and Europe and the Mediterranean region (EMR) (n = 25) in 2009-2012. Susceptibility testing was performed by reference broth microdilution methods. Overall, 12 851 isolates were collected (6873/5978 in USA/EMR). The same top 11 organisms were observed in both geographic regions, but in different rank orders, and Gram-negative organisms represented 61.5/76.1% of strains in USA/EMR. Pseudomonas aeruginosa was the most frequently isolated Gram-negative organism in both regions (20.9/20.9% of cases in USA/EMR) and showed reduced susceptibility to most antimicrobials tested, including ceftazidime (79.6/68.7% susceptibility in USA/EMR), meropenem (76.3/65.8%) and piperacillin/tazobactam (72.9/63.9%). Klebsiella spp. was isolated from 9.7/11.6% of cases and showed extended-spectrum β-lactamase (ESBL) phenotype rates of 19.5/35.1% in USA/EMR. Meropenem and amikacin were active against 62.3/78.7% and 60.8/85.2% of ESBL phenotype Klebsiella spp. from USA/EMR, respectively. Enterobacter spp. ranked fourth in the USA (5.9%) and sixth in EMR (5.5%), whereas Escherichia coli ranked fifth in the USA (5.5%) and third in EMR (11.8%). Acinetobacter spp. and Stenotrophomonas maltophilia combined were isolated from 8.0/10.7% of cases in USA/EMR. A significant increase in P. aeruginosa susceptibility to meropenem and a significant decrease in gentamicin susceptibility among Klebsiella spp. were noted in EMR. These results confirm that very few agents remain broadly active against the most frequently isolated Gram-negative organisms from patients with pneumonia in US and EMR medical centres. © 2014 Elsevier B.V. and the International Society of Chemotherapy.


Farrell D.J.,45 Beaver Kreek Center | Sader H.S.,45 Beaver Kreek Center | Flamm R.K.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
International Journal of Antimicrobial Agents | Year: 2014

During 2012, a total of 2968 isolates were consecutively collected from 59 medical centres in the USA and 15 European countries from hospitalised patients with pneumonia. Ceftolozane/tazobactam (tazobactam at a fixed concentration of 4 mg/L) and comparator agents were tested by reference methods, and MIC endpoints were interpreted by CLSI (2013) and EUCAST (2013) breakpoint criteria. Pseudomonas aeruginosa was the most common isolated pathogen (1019 strains; 34.3%), and ceftolozane/tazobactam was the most active β-lactam tested against P. aeruginosa (MIC50/90, 0.5/4 mg/L; 94.1% inhibited at ≤8 mg/L). P. aeruginosa exhibited moderate susceptibility to meropenem (MIC 50/90, 0.5/>8 mg/L; 73.7% susceptible), ceftazidime (MIC 50/90, 2/>32 mg/L; 73.6% susceptible), cefepime (MIC 50/90, 4/>16 mg/L; 76.5% susceptible), piperacillin/tazobactam (MIC50/90, 8/>64 mg/L; 69.5% susceptible), levofloxacin [MIC 50/90, 0.5/>4 mg/L; 69.9/61.0% susceptible (CLSI/EUCAST criteria)] and gentamicin (MIC50/90, 2/>8 mg/L; 80.7% susceptible). Ceftolozane/tazobactam exhibited activity against many ceftazidime-non- susceptible, meropenem-non-susceptible and piperacillin/tazobactam-non- susceptible, multidrug-resistant (MDR) and extensively drug-resistant (XDR) P. aeruginosa isolates. Ceftolozane/tazobactam was active (MIC50/90, 0.25/4 mg/L; 94.6% inhibited at ≤8 mg/L) against 1530 Enterobacteriaceae, including activity against many MDR and XDR strains. MDR and XDR prevalence varied widely between countries both for P. aeruginosa (24.1% MDR and 17.1% XDR overall) and Enterobacteriaceae (15.4% MDR and 2.7% XDR overall). All β-lactams had limited activity against Acinetobacter spp. and Stenotrophomonas maltophilia. Ceftolozane/tazobactam demonstrated greater in vitro activity than currently available cephalosporins, carbapenems and piperacillin/tazobactam when tested against P. aeruginosa. In addition, ceftolozane/tazobactam demonstrated greater activity than contemporary cephalosporins and piperacillin/tazobactam when tested against most Enterobacteriaceae. © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.


Farrell D.J.,45 Beaver Kreek Center | Flamm R.K.,45 Beaver Kreek Center | Sader H.S.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
International Journal of Antimicrobial Agents | Year: 2013

Ceftaroline, the active metabolite of the prodrug ceftaroline fosamil, is a novel cephalosporin exhibiting bactericidal activity in vitro against Gram-positive organisms, including meticillin-susceptible Staphylococcus aureus (MSSA), meticillin-resistant S. aureus (MRSA), β-haemolytic streptococci, viridans group streptococci (VGS) and Streptococcus pneumoniae, as well as against many common Gram-negative organisms. The objective of this study was to determine the spectrum and potency of ceftaroline against recent (2010) leading pathogens causing complicated skin and soft-tissue infections (cSSTIs) isolated in Europe. A total of 2438 isolates from the Assessing Worldwide Antimicrobial Resistance and Evaluation (AWARE) programme were identified as cSSTI pathogens. Isolates were collected from patients in 52 medical centres in 19 European countries. Reference susceptibility testing for ceftaroline and commonly used antimicrobials was performed by broth microdilution methodologies. Ceftaroline was very active overall against S. aureus (MIC50/90 = 0.25/1 mg/L) and inhibited 100.0% of isolates at a MIC of ≤2 mg/L. Activity against MRSA was documented (MIC50/90 = 1/2 mg/L) but was lower than that observed against MSSA (MIC50/90 = 0.25/0.25 mg/L). Ceftaroline was also very active against 460 β-haemolytic streptococci and 93 VGS (MIC90 = 0.015 mg/L and 0.06 mg/L, respectively). Ceftaroline was active against Escherichia coli (MIC50 = 0.12 mg/L) and Klebsiella pneumoniae (MIC50 = 0.06 mg/L) not expressing extended-spectrum β-lactamases, with activity similar to ceftriaxone and ceftazidime. In summary, this study documents the potent in vitro activity of ceftaroline when tested against recent pathogens isolated from patients with cSSTI in Europe. © 2013 Elsevier B.V. and the International Society of Chemotherapy.


Sader H.S.,45 Beaver Kreek Center | Farrell D.J.,45 Beaver Kreek Center | Flamm R.K.,45 Beaver Kreek Center | Jones R.N.,45 Beaver Kreek Center
International Journal of Antimicrobial Agents | Year: 2014

We report the results of 8 years (2005-2012) of the Daptomycin Surveillance Programme Worldwide. Consecutive non-duplicate bacterial isolates (prevalence design) were collected from patients with documented infections in 410 medical centres and were susceptibility tested by reference broth microdilution methods. A total of 164 457 Gram-positive isolates were evaluated, including 97 542 Staphylococcus aureus, 21 413 coagulase-negative staphylococci (CoNS), 29 619 enterococci and 15 883 β-haemolytic streptococci. The prevalence of daptomycin-non-susceptible isolates was extremely low for all species in all geographic regions. Overall, the highest occurrence of non-susceptible isolates was observed among CoNS (0.19%), followed by Enterococcus faecium (0.18%), S. aureus (0.05%), Enterococcus faecalis (0.02%) and β-haemolytic streptococci (0.00%). Moreover, no trend towards increased daptomycin resistance (non-susceptibility) was observed for any species in any geographic region during the study interval. Against S. aureus, the daptomycin MIC50/90 was 0.25/0.5 mg/L in all geographic regions (99.95% susceptible overall). Only 53 daptomycin-non-susceptible S. aureus isolates were observed and the vast majority (49; 92.5%) had a daptomycin MIC value only 1 log2 dilution above the published susceptible breakpoint. Daptomycin was also active against CoNS (MIC50/90, 0.25/0.5 mg/L; 99.81% susceptible), E. faecalis (MIC50/90, 1/2 mg/L; 99.98% susceptible), E. faecium (MIC 50/90, 2/4 mg/L; 99.82% susceptible) including vancomycin-non- susceptible isolates (4521 isolates; MIC50/90, 2/2 mg/L; 99.76% susceptible), and β-haemolytic streptococci (MIC50/90, ≤0.06/0.25 mg/L; 100.0% susceptible). In conclusion, daptomycin has remained very active against indicated species worldwide, and no significant year-to-year or regional variation in daptomycin activity has been detected. © 2014 Elsevier B.V. and the International Society of Chemotherapy.

Loading 45 Beaver Kreek Center collaborators
Loading 45 Beaver Kreek Center collaborators