North Liberty, Iowa, United States
North Liberty, Iowa, United States

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Castanheira M.,JMI Laboratories | Farrell S.E.,JMI Laboratories | Krause K.M.,Cerexa Inc. | Jones R.N.,JMI Laboratories | Sader H.S.,JMI Laboratories
Antimicrobial Agents and Chemotherapy | Year: 2014

Escherichia coli (328 isolates), Klebsiella pneumoniae (296), Klebsiella oxytoca (44), and Proteus mirabilis (33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-β-lactamase (ESBL) phenotypes were evaluated for the presence of β-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for K. pneumoniae (16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112 K. pneumoniae strains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried blaCTX-M. SHV genes encoding ESBL activity were detected among 176 isolates. Other β-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried>2 β-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ ml) were the most active agents tested. Overall, meropenem (MIC50,<0.06 μg/ml), ceftazidime-avibactam (MIC50, 0.12 to 0.5 μg/ml), and tigecycline (MIC50, 0.12 to 2 μg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all β-lactams tested. The diversity and increasing prevalence of β-lactamase-producing Enterobacteriaceae have been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals. Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Sader H.S.,JMI Laboratories | Flamm R.K.,JMI Laboratories | Jones R.N.,JMI Laboratories | Jones R.N.,Tufts University
Antimicrobial Agents and Chemotherapy | Year: 2013

Ceftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active against Enterobacteriaceae (4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including meropenem-nonsusceptible Klebsiella spp. and ceftazidimenonsusceptible Enterobacter cloacae strains (MIC90, 1 μg/ml for both). Ceftaroline-avibactam was also active against ceftriaxone-nonsusceptible Streptococcus pneumoniae (MIC90, 0.25 μg/ml) and methicillin-resistant Staphylococcus aureus (MIC90, 1 μg/ml). Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Gales A.C.,Federal University of São Paulo | Jones R.N.,JMI Laboratories | Sader H.S.,Federal University of São Paulo | Sader H.S.,JMI Laboratories
Journal of Antimicrobial Chemotherapy | Year: 2011

Objectives: To comparatively evaluate the antimicrobial activities of colistin and polymyxin B with those of other antimicrobials against a worldwide collection of 40625 Gram-negative bacilli. Methods: Antimicrobial susceptibility testing was performed and interpreted using the CLSI broth microdilution method except for colistin against Enterobacteriaceae. Results: The polymyxins showed potent in vitro activities (MIC 90, ≤0.5-1 mg/L) against this large collection of clinical isolates, with very low resistance rates (<0.1%-1.5%). Resistance to the polymyxins remained stable among organisms tested except for Klebsiella spp. isolates collected from the Asia-Pacific and Latin American regions, where a trend towards greater resistance was observed (P≤0.05). In addition, an important reduction in imipenem susceptibility among Acinetobacter spp. and Klebsiella spp. was demonstrated in most geographical regions. Conclusions: Although the polymyxins showed excellent in vitro activity against the vast majority of Gramnegative bacilli evaluated, a trend to greater resistance was observed in the Asia-Pacific and Latin American regions. Therefore, the clinical use of polymyxins must be cautious and surveillance monitored. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Farrell D.J.,JMI Laboratories
Journal of Clinical Gastroenterology | Year: 2013

Irritable bowel syndrome (IBS), a chronic, nonfatal illness is commonly encountered in clinical practice; however, treatment options are limited and often ineffectual. Despite this, there is increasing evidence that bacterial overgrowth in the bowel (dysbiosis) may be an etiological factor in IBS. This has lead to studies in which the antibiotic agent rifaximin has been used to reduce the microbial burden in the bowel, to some extent alleviating the symptoms of IBS. Rifaximin is a member of the rifamycin class of antibiotics, which when administered orally has the distinctions of being gut specific coupled with poor systemic absorption, characteristics that are suggested to limit the development of bacterial resistance. The rifamycins are currently used to treat serious human diseases including tuberculosis, meningococcal disease, methicillin-resistant Staphylococcus aureus and Clostridium difficile infections. The use of rifamycins in the treatment of these diseases is associated with the development of antibiotic resistance over time. When considering the importance of the rifamycins in the treatment of serious human diseases, the large number of patients affected by IBS, and the lack of scientific evidence available on the development of antibiotic resistance to rifaximin over the long-term when used in the gut, it is advisable that the use of rifaximin as a therapy for IBS should be limited to single, acute, short-term treatment. Copyright © 2013 by Lippincott Williams & Wilkins.


Sader H.S.,JMI Laboratories | Flamm R.K.,JMI Laboratories | Jones R.N.,JMI Laboratories
Diagnostic Microbiology and Infectious Disease | Year: 2013

Tigecycline was approved by the United States Food and Drug Administration in 2005 and has generally retained activity against resistant Gram-positive and Gram-negative organisms. We monitored the in vitro activity of this glycylcycline in 2011 for continued potency worldwide. A total of 22,005 unique clinical isolates were consecutively collected in North America (NA; 9232 isolates), Europe (EU; 6776), Latin America (LA; 2016), and Asia-Pacific region (APAC, 3981) and tested for susceptibility according to the reference broth microdilution method recommendations against tigecycline and numerous comparators. Oxacillin (methicillin) resistance rates in methicillin-resistant Staphylococcus aureus (MRSA) were 49.3%, 30.2%, 42.9%, and 37.8%, and vancomycin resistance rates in enterococci (VRE) were 27.0%, 11.3%, 6.3%, and 4.0% in NA, EU, LA, and APAC, respectively. All MRSA (2839) and >99% of VRE were susceptible to tigecycline. Among Escherichia coli, extended-spectrum β-lactamase (ESBL) rates varied from 12.6% in the NA to 57.4% in APAC, and only one strain was nonsusceptible to tigecycline. Tigecycline was active against ESBL phenotype (96.5-98.4% susceptible) and meropenem-nonsusceptible Klebsiella spp. (94.3-100.0% susceptible). Only 4 of 213 (1.9%) meropenem-nonsusceptible Klebsiella spp. were tigecycline-nonsusceptible, all with tigecycline minimum inhibitory concentration (MIC) of 4 μg/mL (intermediate). Among ceftazidime-nonsusceptible Enterobacter spp., 94.7-98.2% were susceptible to tigecycline. Meropenem-nonsusceptible Acinetobacter spp. varied from 51.2% in NA to 80.9% in APAC; and 83.8% (LA) to 93.9% (APAC) of strains were inhibited at a tigecycline MIC of ≤2 μg/mL. Tigecycline showed potent activity against Stenotrophomonas maltophilia (89.3-98.3% inhibited at ≤2 μg/mL). In summary, tigecycline has sustained potent activity and a broad-spectrum against clinically important bacteria causing infections worldwide, including multidrug-resistant organism subsets. © 2013 Elsevier Inc.


Jones R.N.,JMI Laboratories | Stilwell M.G.,JMI Laboratories
Diagnostic Microbiology and Infectious Disease | Year: 2013

Dalbavancin is an investigational lipoglycopeptide having an extended serum elimination half-life allowing once-weekly dosing. Data from testing 1357 strains of uncommonly isolated species expand the dalbavancin spectrum details as follows (MIC50/90): β-haemolytic streptococcal serogroups C, F, and G (≤0.03/≤0.03 μg/mL), 7 viridans group of streptococci (≤0.03/≤0.03-0.06 μg/mL), 5 Corynebacterium spp. (0.06/0.12 μg/mL), Listeria monocytogenes (0.06/0.12 μg/mL), and Micrococcus spp. (≤0.03/≤0.03 μg/mL). Among all reported isolates, 99.8% of tested strains were inhibited at dalbavancin MIC values at ≤0.12 μg/mL. Dalbavancin remains very potent against rarer Gram-positive pathogens, using in vitro test experience with organisms cultured through 2011. © 2013 Elsevier Inc.


Pfaller M.A.,JMI Laboratories | Messer S.A.,JMI Laboratories | Woosley L.N.,JMI Laboratories | Jones R.N.,JMI Laboratories | Castanheira M.,JMI Laboratories
Journal of Clinical Microbiology | Year: 2013

The SENTRY Antimicrobial Surveillance Program monitors global susceptibility and resistance rates of newer and established antifungal agents. We report the echinocandin and triazole antifungal susceptibility patterns for 3,418 contemporary clinical isolates of yeasts and molds. The isolates were obtained from 98 laboratories in 34 countries during 2010 and 2011. Yeasts not presumptively identified by CHROMagar, the trehalose test, or growth at 42°C and all molds were sequence identified using internal transcribed spacer (ITS) and 28S (yeasts) or ITS, translation elongation factor (TEF), and 28S (molds) genes. Susceptibility testing was performed against 7 antifungals (anidulafungin, caspofungin, micafungin, fluconazole, itraconazole, posaconazole, and voriconazole) using CLSI methods. Rates of resistance to all agents were determined using the new CLSI clinical breakpoints and epidemiological cutoff value criteria, as appropriate. Sequencing of fks hot spots was performed for echinocandin non-wildtype (WT) strains. Isolates included 3,107 from 21 Candida spp., 146 from 9 Aspergillus spp., 84 from Cryptococcus neoformans, 40 from 23 other mold species, and 41 from 9 other yeast species. Among Candida spp., resistance to the echinocandins was low (0.0 to 1.7%). Candida albicans and Candida glabrata that were resistant to anidulafungin, caspofungin, or micafungin were shown to have fks mutations. Resistance to fluconazole was low among the isolates of C. albicans (0.4%), Candida tropicalis (1.3%), and Candida parapsilosis (2.1%); however, 8.8% of C. glabrata isolates were resistant to fluconazole. Among echinocandin-resistant C. glabrata isolates from 2011, 38% were fluconazole resistant. Voriconazole was active against all Candida spp. except C. glabrata (10.5% non-WT), whereas posaconazole showed decreased activity against C. albicans (4.4%) and Candida krusei (15.2% non-WT). All agents except for the echinocandins were active against C. neoformans, and the triazoles were active against other yeasts (MIC90, 2 μg/ml). The echinocandins and triazoles were active against Aspergillus spp. (MIC90/minimum effective concentration [MEC90] range, 0.015 to 2 μg/ml), but the echinocandins were not active against other molds (MEC90 range, 4 to > 16 μg/ml). Overall, echinocandin and triazole resistance rates were low; however, the fluconazole and echinocandin coresistance among C. glabrata strains warrants continued close surveillance. Copyright © 2013, American Society for Microbiology.


Ross J.E.,JMI Laboratories | Mendes R.E.,JMI Laboratories | Jones R.N.,JMI Laboratories
Journal of Clinical Microbiology | Year: 2014

The telavancin broth microdilution susceptibility testing method was revised, which provides MIC results lower than those obtained by the previous method. This study was performed to reestablish the quality control ranges for telavancin when tested against the strains (updated MIC range) Staphylococcus aureus ATCC 29213 (0.03 to 0.12 μg/ml), Enterococcus faecalis ATCC 29212 (0.03 to 0.12 μg/ml), and Streptococcus pneumoniae ATCC 49619 (0.004 to 0.015 μg/ml). Copyright © 2014, American Society for Microbiology. All Rights Reserved.


Sader H.S.,JMI Laboratories | Flamm R.K.,JMI Laboratories | Jones R.N.,JMI Laboratories
Antimicrobial Agents and Chemotherapy | Year: 2013

Vancomycin, linezolid, and daptomycin are very active against staphylococci, but isolates with decreased susceptibility to these antimicrobial agents are isolated sporadically. A total of 19,350 Staphylococcus aureus isolates (51% methicillin resistant [MRSA]) and 3,270 coagulase-negative staphylococci (CoNS) were collected consecutively from 82 U.S. medical centers from January 2008 to December 2011 and tested for susceptibility against ceftaroline and comparator agents by the reference broth microdilution method. Among S. aureus strains, 14 isolates (0.07%) exhibited decreased susceptibility to linezolid (MIC, ≥8 μg/ml), 18 (0.09%) to daptomycin (MIC, ≥2 μg/ml), and 369 (1.9%) to vancomycin (MIC, ≥2 μg/ml; 368 isolates at 2 μg/ml and 1 at 4 μg/ml). Fifty-one (1.6%) CoNS were linezolid resistant (MIC, ≥8 μg/ml), and four (0.12%) were daptomycin nonsusceptible (MIC, ≥2 μg/ml). Ceftaroline was very active against S. aureus overall (MIC 50/90, 0.5/1 μg/ml; 98.5% susceptible), including MRSA (MIC50/90, 0.5/1 μg/ml; 97.2% susceptible). All daptomycin-nonsusceptible and 85.7% of linezolid-resistant S. aureus isolates were susceptible to ceftaroline. Against S. aureus isolates with a vancomycin MIC of ≥2 μg/ml, 91.9, 96.2, and 98.9% were susceptible to ceftaroline, daptomycin, and linezolid, respectively. CoNS strains were susceptible to ceftaroline (MIC50/90, 0.25/0.5 μg/ml; 99.1% inhibited at ≤1μg/ml), including methicillin-resistant (MIC 50/90, 0.25/0.5μg/ml), linezolid-resistant (MIC50/90, 0.5/0.5 μg/ml), and daptomycin-nonsusceptible (4 isolates; MIC range, 0.03 to 0.12 μg/ml) strains. In conclusion, ceftaroline demonstrated potent in vitro activity against staphylococci with reduced susceptibility to linezolid, daptomycin, or vancomycin, and it may represent a valuable treatment option for infections caused by these multidrug-resistant staphylococci. Copyright © 2013, American Society for Microbiology.


Jones R.N.,JMI Laboratories | Sader H.S.,JMI Laboratories | Flamm R.K.,JMI Laboratories
Diagnostic Microbiology and Infectious Disease | Year: 2013

Dalbavancin (DAL) is an investigational lipoglycopeptide with a prolonged serum half-life allowing once weekly dosing. DAL potency was assessed in the 2011 SENTRY Antimicrobial Surveillance Program among 1555 isolates sampled from all 9 US Census regions. Monitored Gram-positive cocci included Staphylococcus aureus (SA; 1,036/50.4% MRSA), coagulase-negative staphylococci (CoNS; 115), Enterococcus faecalis (25), E. faecium (31), Streptococcus pyogenes (155), Streptococcus agalactiae (153), and viridans group streptococci (VGS; 40). All susceptibility (S) testing used Clinical and Laboratory Standards Institute reference broth microdilution methods and interpretations. DAL (MIC50/90, 0.06/0.06 μg/mL) was 8- and 16-fold more active than daptomycin (DAP) and vancomycin (VAN), respectively against SA, with MSSA and MRSA having the same MIC90 results. CoNS was slightly more DAL-S (MIC50, ≤0.03μg/mL). The highest staphylococcal DAL MIC was only 0.25 μg/mL. β-Haemolytic streptococci (βHS) and VGS had DAL MIC results ranging from ≤0.03 to 0.25 μg/mL (MIC90, 0.06-0.12 μg/mL), and only enterococci showed elevated DAL MIC results. VanA phenotype-resistant E. faecalis or E. faecium had DAL MIC values at ≥1 μg/mL; VanB strains were DAL-S (MIC, ≤0.25 μg/mL). All cited DAL quantitative values were consistent with earlier surveillance data (2006-2009), without evidence of MIC creep. In conclusion, year 2011 SENTRY Program data for DAL documents sustained potent activity against SA, CoNS, βHS, VGS, and VAN-S enterococci, which averaged 4- to 32-fold greater than VAN, DAP, or linezolid. © 2013 Elsevier Inc.

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