scholarly journals Variation in Potency and Spectrum of Tigecycline Activity against Bacterial Strains from U.S. Medical Centers since Its Approval for Clinical Use (2006 to 2012)

2014 ◽  
Vol 58 (4) ◽  
pp. 2274-2280 ◽  
Author(s):  
Helio S. Sader ◽  
David J. Farrell ◽  
Robert K. Flamm ◽  
Ronald N. Jones
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Clinical Use ◽  
Bacterial Strains ◽  
Gram Positive ◽  
Content Type ◽  
Highly Active ◽  
Medical Centers

ABSTRACTTigecycline was initially approved by the U.S. Food and Drug Administration (FDA) in June 2005. We assessed the evolution of tigecyclinein vitroactivities since the initial approval of tigecycline for clinical use by analyzing the results of 7 years (2006 to 2012) of data from the SENTRY Antimicrobial Surveillance Program in the United States. We also analyzed trends over time for key resistance phenotypes. The analyses included 68,608 unique clinical isolates collected from 29 medical centers and tested for susceptibility using reference broth microdilution methods. Tigecycline was highly active against Gram-positive organisms, with MIC50and MIC90values of 0.12 and 0.25 μg/ml forStaphylococcus aureus(28,278 strains; >99.9% susceptible), 0.06 to 0.12 and 0.12 to 0.25 μg/ml for enterococci (99.3 to 99.6% susceptible), and ≤0.03 and ≤0.03 to 0.06 μg/ml for streptococci (99.9 to 100.0% susceptible), respectively. When tested against 20,457Enterobacteriaceaestrains, tigecycline MIC50and MIC90values were 0.25 and 1 μg/ml, respectively (98.3% susceptible using U.S. FDA breakpoints). No trend toward increasing tigecycline resistance (nonsusceptibility) was observed for any species or group during the study period. The prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)Enterobacteriaceaeincreased from 4.4 and 0.5%, in 2006 to 8.5 and 1.5% in 2012, respectively. During the same period, the prevalence ofEscherichia coliandKlebsiellaspp. with an extended-spectrum β-lactamase (ESBL) phenotype increased from 5.8 and 9.1% to 11.1 and 20.4%, respectively, whereas rates of meropenem-nonsusceptibleKlebsiella pneumoniaeescalated from 2.2% in 2006 to 10.8% in 2012. The results of this investigation show that tigecycline generally retained potent activities against clinically important organisms isolated in U.S. institutions, including MDR organism subsets of Gram-positive and Gram-negative pathogens.

scholarly journals Arbekacin Activity against Contemporary Clinical Bacteria Isolated from Patients Hospitalized with Pneumonia

2015 ◽  
Vol 59 (6) ◽  
pp. 3263-3270 ◽  
Author(s):  
Helio S. Sader ◽  
Paul R. Rhomberg ◽  
David J. Farrell ◽  
Ronald N. Jones
Keyword(s):  
The United States ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Content Type ◽  
Microdilution Method ◽  
Medical Centers ◽  
Broth Microdilution Method ◽  
Mrsa Strains ◽  
Infection Types

ABSTRACTArbekacin is a broad-spectrum aminoglycoside licensed for systemic use in Japan and under clinical development as an inhalation solution in the United States. We evaluated the occurrence of organisms isolated from pneumonias in U.S. hospitalized patients (PHP), including ventilator-associated pneumonia (VAP), and thein vitroactivity of arbekacin. Organism frequency was evaluated from a collection of 2,203 bacterial isolates (339 from VAP) consecutively collected from 25 medical centers in 2012 through the SENTRY Antimicrobial Surveillance Program. Arbekacin activity was tested against 904 isolates from PHP collected in 2012 from 62 U.S. medical centers and 303 multidrug-resistant (MDR) organisms collected worldwide in 2009 and 2010 from various infection types. Susceptibility to arbekacin and comparator agents was evaluated by the reference broth microdilution method. The four most common organisms from PHP wereStaphylococcus aureus,Pseudomonas aeruginosa,Klebsiellaspp., andEnterobacterspp. The highest arbekacin MIC amongS. aureusisolates from PHP (43% methicillin-resistantS. aureus[MRSA]) was 4 μg/ml. AmongP. aeruginosaisolates from PHP, only one had an arbekacin MIC of >16 μg/ml (MIC50and MIC90, 1 and 4 μg/ml), and susceptibility rates for gentamicin, tobramycin, and amikacin were 88.0, 90.0, and 98.0%, respectively. Arbekacin (MIC50, 2 μg/ml) and tobramycin (MIC50, 4 μg/ml) were the most potent aminoglycosides tested againstAcinetobacter baumannii. AgainstEnterobacteriaceaefrom PHP, arbekacin and gentamicin (MIC50and MIC90, 0.25 to 1 and 1 to 8 μg/ml for both compounds) were generally more potent than tobramycin (MIC50and MIC90, 0.25 to 2 and 1 to 32 μg/ml) and amikacin (MIC50and MIC90, 1 to 2 and 2 to 32 μg/ml). Arbekacin also demonstrated potentin vitroactivity against a worldwide collection of well-characterized MDR Gram-negative and MRSA strains.

scholarly journals In VitroActivity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii

2015 ◽  
Vol 59 (4) ◽  
pp. 2280-2285 ◽  
Author(s):  
Robert K. Flamm ◽  
Paul R. Rhomberg ◽  
Ronald N. Jones ◽  
David J. Farrell
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acinetobacter Baumannii ◽  
Active Agent ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active ◽  
Bacterial Ribosome

ABSTRACTRX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis.Enterobacteriaceae(657),Pseudomonas aeruginosa(200), andAcinetobacter baumannii(202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% ofEnterobacteriaceaeisolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positiveProtea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active againstPseudomonas aeruginosaisolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active againstP. aeruginosathan tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent againstAcinetobacter baumannii(MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Isolates from Respiratory and Blood Specimens from Patients with Nosocomial Pneumonia, Including Ventilator-Associated Pneumonia, in a Phase 3 Clinical Trial

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Gregory G. Stone ◽  
Patricia A. Bradford ◽  
Margaret Tawadrous ◽  
Dianna Taylor ◽  
Mary Jane Cadatal ◽  
...  
Keyword(s):  
Nosocomial Pneumonia ◽  
Bacterial Pathogen ◽  
Multidrug Resistant ◽  
Ventilator Associated Pneumonia ◽  
Phase 3 ◽  
Gram Positive ◽  
Gram Negative ◽  
Content Type ◽  
Highly Active

ABSTRACT Nosocomial pneumonia (NP), including ventilator-associated pneumonia (VAP), is increasingly associated with multidrug-resistant Gram-negative pathogens. This study describes the in vitro activity of ceftazidime-avibactam, ceftazidime, and relevant comparator agents against bacterial pathogens isolated from patients with NP, including VAP, enrolled in a ceftazidime-avibactam phase 3 trial. Gram-positive pathogens were included if coisolated with a Gram-negative pathogen. In vitro susceptibility was determined at a central laboratory using Clinical and Laboratory Standards Institute broth microdilution methods. Of 817 randomized patients, 457 (55.9%) had ≥1 Gram-negative bacterial pathogen(s) isolated at baseline, and 149 (18.2%) had ≥1 Gram-positive pathogen(s) coisolated. The most common isolated pathogens were Klebsiella pneumoniae (18.8%), Pseudomonas aeruginosa (15.8%), and Staphylococcus aureus (11.5%). Ceftazidime-avibactam was highly active in vitro against 370 isolates of Enterobacteriaceae, with 98.6% susceptible (MIC90, 0.5 μg/ml) compared with 73.2% susceptible for ceftazidime (MIC90, >64 μg/ml). The percent susceptibility values for ceftazidime-avibactam and ceftazidime against 129 P. aeruginosa isolates were 88.4% and 72.9% (MIC90 values of 16 μg/ml and 64 μg/ml), respectively. Among ceftazidime-nonsusceptible Gram-negative isolates, ceftazidime-avibactam percent susceptibility values were 94.9% for 99 Enterobacteriaceae and 60.0% for 35 P. aeruginosa. MIC90 values for linezolid and vancomycin (permitted per protocol for Gram-positive coverage) were within their respective MIC susceptibility breakpoints against the Gram-positive pathogens isolated. This analysis demonstrates that ceftazidime-avibactam was active in vitro against the majority of Enterobacteriaceae and P. aeruginosa isolates from patients with NP, including VAP, in a phase 3 trial. (This study has been registered at ClinicalTrials.gov under identifier NCT01808092.)

scholarly journals Ceftobiprole Activity against Bacteria from Skin and Skin Structure Infections in the United States from 2016 through 2018

2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Generation Cephalosporin ◽  
Clinical Isolates ◽  
Surveillance Program ◽  
Coagulase Negative Staphylococci ◽  
Gram Positive ◽  
Content Type ◽  
Skin Structure ◽  
Highly Active

ABSTRACT Ceftobiprole medocaril is an advanced-generation cephalosporin prodrug that has qualified infectious disease product status granted by the US FDA and is currently being evaluated in phase 3 clinical trials in patients with acute bacterial skin and skin structure infections (ABSSSIs) and in patients with Staphylococcus aureus bacteremia. In this study, the activity of ceftobiprole and comparators was evaluated against more than 7,300 clinical isolates collected in the United States from 2016 through 2018 from patients with skin and skin structure infections. The major species/pathogen groups were S. aureus (53%), Enterobacterales (23%), Pseudomonas aeruginosa (7%), beta-hemolytic streptococci (6%), Enterococcus spp. (4%), and coagulase-negative staphylococci (2%). Ceftobiprole was highly active against S. aureus (MIC50/90, 0.5/1 mg/liter; 99.7% susceptible by EUCAST criteria; 42% methicillin-resistant S. aureus [MRSA]). Ceftobiprole also exhibited potent activity against other Gram-positive cocci. The overall susceptibility of Enterobacterales to ceftobiprole was 84.8% (>99.0% susceptible for isolate subsets that exhibited a non-extended-spectrum β-lactamase [ESBL] phenotype). A total of 74.4% of P. aeruginosa, 100% of beta-hemolytic streptococci and coagulase-negative staphylococci, and 99.6% of Enterococcus faecalis isolates were inhibited by ceftobiprole at ≤4 mg/liter. As expected, ceftobiprole was largely inactive against Enterobacterales that contained ESBL genes and Enterococcus faecium. Overall, ceftobiprole was highly active against most clinical isolates from the major Gram-positive and Gram-negative skin and skin structure pathogen groups collected at U.S. medical centers participating in the SENTRY Antimicrobial Surveillance Program during 2016 to 2018. The broad-spectrum activity of ceftobiprole, including potent activity against MRSA, supports its further evaluation for a potential ABSSSI indication.

scholarly journals Activity of Ceftaroline and Epidemiologic Trends in Staphylococcus aureus Isolates Collected from 43 Medical Centers in the United States in 2009

2011 ◽  
Vol 55 (9) ◽  
pp. 4154-4160 ◽  
Author(s):  
Sandra S. Richter ◽  
Kristopher P. Heilmann ◽  
Cassie L. Dohrn ◽  
Fathollah Riahi ◽  
Andrew J. Costello ◽  
...  
Keyword(s):  
United States ◽  
Staphylococcus Aureus ◽  
The United States ◽  
Surveillance Program ◽  
Content Type ◽  
Type Iv ◽  
Medical Centers ◽  
High Level ◽  
Resistance Rates

ABSTRACTAStaphylococcus aureussurveillance program was initiated in the United States to examine thein vitroactivity of ceftaroline and epidemiologic trends. Susceptibility testing by Clinical and Laboratory Standards Institute broth microdilution was performed on 4,210 clinically significant isolates collected in 2009 from 43 medical centers. All isolates were screened formecAby PCR and evaluated by pulsed-field gel electrophoresis. Methicillin-resistantS. aureus(MRSA) were analyzed for Panton-Valentine leukocidin (PVL) genes and the staphylococcal cassette chromosomemec(SCCmec) type. All isolates had ceftaroline MICs of ≤2 μg/ml with an MIC50of 0.5 and an MIC90of 1 μg/ml. The overall resistance rates, expressed as the percentages of isolates that were intermediate and resistant (or nonsusceptible), were as follows: ceftaroline, 1.0%; clindamycin, 30.2% (17.4% MIC ≥ 4 μg/ml; 12.8% inducible); daptomycin, 0.2%; erythromycin, 65.5%; levofloxacin, 39.9%; linezolid, 0.02%; oxacillin, 53.4%; tetracycline, 4.4%; tigecycline, 0%; trimethoprim-sulfamethoxazole, 1.6%; vancomycin, 0%; and high-level mupirocin, 2.2%. ThemecAPCR was positive for 53.4% of the isolates. The ceftaroline MIC90s were 0.25 μg/ml for methicillin-susceptibleS. aureusand 1 μg/ml for MRSA. Among the 2,247 MRSA isolates, 51% were USA300 (96.9% PVL positive, 99.7% SCCmectype IV) and 17% were USA100 (93.4% SCCmectype II). The resistance rates for the 1,137 USA300 MRSA isolates were as follows: erythromycin, 90.9%; levofloxacin, 49.1%; clindamycin, 7.6% (6.2% MIC ≥ 4 μg/ml; 1.4% inducible); tetracycline, 3.3%; trimethoprim-sulfamethoxazole, 0.8%; high-level mupirocin, 2.7%; daptomycin, 0.4%; and ceftaroline and linezolid, 0%. USA300 is the dominant clone causing MRSA infections in the United States. Ceftaroline demonstrated potentin vitroactivity against recentS. aureusclinical isolates, including MRSA, daptomycin-nonsusceptible, and linezolid-resistant strains.

scholarly journals Antibacterial Activity of Lefamulin against Pathogens Most Commonly Causing Community-Acquired Bacterial Pneumonia: SENTRY Antimicrobial Surveillance Program (2015–2016)

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Susanne Paukner ◽  
Steven P. Gelone ◽  
S. J. Ryan Arends ◽  
Robert K. Flamm ◽  
Helio S. Sader
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Pneumonia ◽  
Oral Treatment ◽  
Multidrug Resistant ◽  
Surveillance Program ◽  
Content Type ◽  
Highly Active ◽  
Antimicrobial Surveillance ◽  
Drug Resistant Strains

ABSTRACTLefamulin, the first semisynthetic pleuromutilin antibacterial for intravenous and oral treatment of community-acquired bacterial pneumonia (CABP), and comparators were evaluated forin vitroactivity against a global collection of pathogens commonly causing CABP (n= 8595) from the 2015 and 2016 SENTRY Antimicrobial Surveillance Program. Lefamulin was highly active against the pathogensStreptococcus pneumoniae, including multidrug-resistant and extensively drug-resistant strains (MIC50/90for total and resistant subsets, 0.06/0.12 μg/ml; 100% inhibited at ≤1 μg/ml),Staphylococcus aureus, including methicillin-resistantStaphylococcus aureus(MRSA; both MIC50/90, 0.06/0.12 μg/ml; 99.8% and 99.6% inhibited at ≤1 μg/ml, respectively),Haemophilus influenzae(MIC50/90, 0.5/1 μg/ml; 93.8% inhibited at ≤1 μg/ml), andMoraxella catarrhalis(MIC50/90, 0.06/0.12 μg/ml; 100% inhibited at ≤0.25 μg/ml), and its activity was unaffected by resistance to other antibacterial classes.

scholarly journals In Vitro Activity of Ceftazidime-Avibactam against Clinical Isolates of Enterobacteriaceae and Pseudomonas aeruginosa Collected in Asia-Pacific Countries: Results from the INFORM Global Surveillance Program, 2012 to 2015

2018 ◽  
Vol 62 (7) ◽  
Author(s):  
James A. Karlowsky ◽  
Krystyna M. Kazmierczak ◽  
Samuel K. Bouchillon ◽  
Boudewijn L. M. de Jonge ◽  
Gregory G. Stone ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Hong Kong ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Asia Pacific ◽  
Surveillance Program ◽  
Asia Pacific Region ◽  
Content Type ◽  
Medical Centers

ABSTRACT The in vitro activities of ceftazidime-avibactam and comparators against 9,149 isolates of Enterobacteriaceae and 2,038 isolates of Pseudomonas aeruginosa collected by 42 medical centers in nine countries in the Asia-Pacific region from 2012 to 2015 were determined as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance program. Antimicrobial susceptibility testing was conducted by Clinical and Laboratory Standards Institute (CLSI) broth microdilution, and isolate subset analysis was performed on the basis of the resistant phenotypes and β-lactamase content. Ceftazidime-avibactam demonstrated potent in vitro activity (MIC, ≤8 μg/ml) against all Enterobacteriaceae tested (99.0% susceptible) and was the most active against isolates that were metallo-β-lactamase (MBL) negative (99.8% susceptible). Against P. aeruginosa , 92.6% of all isolates and 96.1% of MBL-negative isolates were susceptible to ceftazidime-avibactam (MIC, ≤8 μg/ml). The rates of susceptibility to ceftazidime-avibactam ranged from 97.0% (Philippines) to 100% (Hong Kong, South Korea) for Enterobacteriaceae and from 83.1% (Thailand) to 100% (Hong Kong) among P. aeruginosa isolates, with lower susceptibilities being observed in countries where MBLs were more frequently encountered (Philippines, Thailand). Ceftazidime-avibactam inhibited 97.2 to 100% of Enterobacteriaceae isolates, per country, that carried serine β-lactamases, including extended-spectrum β-lactamases, AmpC cephalosporinases, and carbapenemases (KPC, GES, OXA-48-like). It also inhibited 91.3% of P. aeruginosa isolates that were carbapenem nonsusceptible in which no acquired β-lactamase was detected. Among MBL-negative Enterobacteriaceae isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 96.1, 87.7, 100, and 98.8% of isolates, respectively, and among MBL-negative P. aeruginosa isolates that were ceftazidime nonsusceptible, meropenem nonsusceptible, colistin resistant, and multidrug resistant, ceftazidime-avibactam inhibited 79.6, 83.6, 83.3, and 68.2% of isolates, respectively. Overall, clinical isolates of Enterobacteriaceae and P. aeruginosa collected in nine Asia-Pacific countries from 2012 to 2015 were highly susceptible to ceftazidime-avibactam.

scholarly journals 1081. Antimicrobial Activity of Dalbavancin Tested Against Gram-Positive Organisms Isolated From Patients With Infective Endocarditis in United States and European Medical Centers

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S323-S323
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Michael A Pfaller ◽  
Robert K Flamm
Keyword(s):  
United States ◽  
Infective Endocarditis ◽  
The United States ◽  
Vitro Activity ◽  
Surveillance Program ◽  
In Vitro Activity ◽  
Research Support ◽  
Gram Positive ◽  
Medical Centers

Abstract Background The management of endocarditis requires aggressive and prolonged antimicrobial treatment. Dalbavancin (DALBA) has demonstrated potent in vitro activity against Gram-positive (GP) organisms commonly responsible for endocarditis and is being evaluated for treatment of complicated bacteremia and infective endocarditis. Methods A total of 626 GP organisms were collected from patients with a diagnosis of bacterial endocarditis in the United States (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility (S) against DALBA and comparators by CLSI broth microdilution. Results The most common organisms were S. aureus (48.4%), E. faecalis (EF; 19.6%), and viridans group streptococci (VGS; 12.5%). DALBA and daptomycin (DAPTO) showed complete activity (100.0%S) against S. aureus, but DALBA MICs were 4- to 8-fold lower (table). Linezolid (LZD) and teicoplanin were also active against all SA; whereas vancomycin (VAN) and trimethoprim–sulfamethoxazole were active against 99.7% of isolates. Ceftaroline (CPT) exhibited potent activity against methicillin-susceptible S. aureus (MSSA; MIC90, 0.25 mg/L; 100.0%S) and inhibited 78.4% of methicillin-resistant S. aureus (MRSA) isolates at ≤1 mg/L. All EF isolates were S to ampicillin, DAPTO, and LZD, whereas 97.6% (120/123) of isolates were S to DALBA (MIC90, 0.06 mg/L) and 96.7%S to VAN (MIC90, 2 mg/L). Against EF, DALBA MIC values were 16- to 32-fold lower than DAPTO and VAN. All VGS and coagulase-negative staphylococcal (CoNS) isolates were S to DALBA, DAPTO, VAN, and LZD, and the highest CPT MICs were 0.5 mg/L for VGS and 4 mg/L for CoNS (93.5% inhibited at ≤1 mg/L). Against E. faecium (EFM), 65.7% of isolates were inhibited at ≤0.25 mg/L of DALBA and 62.9% were VAN-S. All EFM were S to DAPTO and LNZ. β-Hemolytic streptococci (BHS) was S to most antimicrobial agents, and only 66.7% of S. pneumoniae (SPN) isolates were PEN-S at ≤0.06 mg/L. Conclusion DALBA exhibited potent in vitro activity against a large collection of GP isolates recovered from patients with endocarditis in the United States and Europe medical centers. These results support further investigations to determine the role of DALBA in the treatment of infective endocarditis. Disclosures H. S. Sader, Allergan: Research Contractor, Research support. R. E. Mendes, Allergan: Research Contractor, Research support. M. A. Pfaller, Allergan: Research Contractor, Research support. R. K. Flamm, Allergan: Research Contractor, Research support.

scholarly journals Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe: Report from the SENTRY Antimicrobial Surveillance Program, 2016 to 2018

2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Dee Shortridge ◽  
Robert K. Flamm
Keyword(s):  
United States ◽  
Bacterial Infections ◽  
Klebsiella Oxytoca ◽  
The United States ◽  
Community Acquired Pneumonia ◽  
Surveillance Program ◽  
Gram Positive ◽  
Content Type ◽  
Medical Centers ◽  
Antimicrobial Susceptibility Tests

ABSTRACT Omadacycline is a broad-spectrum aminomethylcycline approved in October 2018 by the U.S. Food and Drug Administration for treating acute bacterial skin and skin structure infections and community-acquired pneumonia as both an oral and intravenous once-daily formulation. In this report, the activities of omadacycline and comparators were tested against 49,000 nonduplicate bacterial isolates collected prospectively during 2016 to 2018 from medical centers in Europe (24,500 isolates, 40 medical centers [19 countries]) and the United States (24,500 isolates, 33 medical centers [23 states and all 9 U.S. census divisions]). Omadacycline was tested by broth microdilution following the methods in Clinical and Laboratory Standards Institute document M07 (Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, 11th ed., 2018). Omadacycline (MIC50/90, 0.12/0.25 mg/liter) inhibited 98.6% of Staphylococcus aureus isolates at ≤0.5 mg/liter, including 96.3% of methicillin-resistant S. aureus isolates and 99.8% of methicillin-susceptible S. aureus isolates. Omadacycline potency was comparable for Streptococcus pneumoniae (MIC50/90, 0.06/0.12 mg/liter), viridans group streptococci (MIC50/90, 0.06/0.12 mg/liter), and beta-hemolytic streptococci (MIC50/90, 0.12/0.25 mg/liter), regardless of species and susceptibility to penicillin, macrolides, or tetracycline. Omadacycline was active against all Enterobacterales tested (MIC50/90, 1/8 mg/liter; 87.5% of isolates were inhibited at ≤4 mg/liter) except Proteus mirabilis (MIC50/90, 16/>32 mg/liter) and indole-positive Proteus spp. (MIC50/90, 8/32 mg/liter) and was most active against Escherichia coli (MIC50/90, 0.5/2 mg/liter), Klebsiella oxytoca (MIC50/90, 1/2 mg/liter), and Citrobacter spp. (MIC50/90, 1/4 mg/liter). Omadacycline inhibited 92.4% of Enterobacter cloacae species complex and 88.5% of Klebsiella pneumoniae isolates at ≤4 mg/liter. Omadacycline was active against Haemophilus influenzae (MIC50/90, 0.5/1 mg/liter), regardless of β-lactamase status, and against Moraxella catarrhalis (MIC50/90, ≤0.12/0.25 mg/liter). The potent activity of omadacycline against Gram-positive and -negative bacteria indicates that omadacycline merits further study in serious infections in which multidrug resistance and mixed Gram-positive and Gram-negative bacterial infections may be a concern.

scholarly journals In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
R. K. Flamm ◽  
P. R. Rhomberg ◽  
H. S. Sader
Keyword(s):  
Streptococcus Pneumoniae ◽  
The United States ◽  
Asia Pacific ◽  
Surveillance Program ◽  
The Novel ◽  
Content Type ◽  
Inducible Clindamycin Resistance ◽  
Highly Active ◽  
Medical Institutions

ABSTRACT Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in phase 2 development for treatment of community-acquired bacterial pneumonia (CABP). A total of 4,739 nonduplicate isolates were selected from a 2014 global surveillance program at medical institutions located in 43 countries within the United States, Europe, Latin America, and the Asia-Pacific region. Nafithromycin and comparator agents were used for susceptibility testing by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC50/90, 0.06/>2 μg/ml), including erythromycin-resistant strains exhibiting an inducible clindamycin resistance phenotype (MIC50/90, 0.06/0.06 μg/ml) and telithromycin-susceptible strains (MIC50/90, 0.06/0.06 μg/ml), but it exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC50/90, >2/>2 μg/ml). Nafithromycin was very active (MIC50/90, 0.015/0.06 μg/ml) against 1,911 Streptococcus pneumoniae strains, inhibiting all strains, with MIC values of ≤0.25 μg/ml. Telithromycin susceptibility was 99.9% for Streptococcus pneumoniae strains, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of S. pneumoniae strains were resistant to erythromycin, and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606 Streptococcus pyogenes strains (MIC50/90, 0.015/0.015 μg/ml), inhibiting 100.0% of isolates at ≤0.5 μg/ml, and MIC50/90 values (0.015/0.015 to 0.03 μg/ml) were similar for the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable in vitro activities against 1,002 Haemophilus influenzae isolates and 504 Moraxella catarrhalis isolates. Overall, nafithromycin showed potent in vitro activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for treatment of CABP.

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