scholarly journals Activity of Omadacycline When Tested Against Gram-Positive Bacteria Isolated From Patients in the United States During 2015 as Part of a Global Surveillance Program.

2016 ◽  
Vol 3 (suppl_1) ◽  
Author(s):  
Robert K. Flamm ◽  
Rodrigo E. Mendes ◽  
Michael D. Huband ◽  
Helio S. Sader
2013 ◽  
Vol 58 (2) ◽  
pp. 1243-1247 ◽  
Author(s):  
Rodrigo E. Mendes ◽  
Robert K. Flamm ◽  
Patricia A. Hogan ◽  
James E. Ross ◽  
Ronald N. Jones

ABSTRACTThis study summarizes the linezolid susceptibility testing results for 7,429 Gram-positive pathogens from 60 U.S. sites collected during the 2012 sampling year for the LEADER Program. Linezolid showed potent activity when tested against 2,980Staphylococcus aureusisolates, inhibiting all but 3 at ≤2 μg/ml. Similarly, linezolid showed coverage against 99.5% of enterococci, as well as for all streptococci tested. These results confirm a long record of linezolid activity against U.S. Gram-positive isolates since regulatory approval in 2000.


2020 ◽  
Vol 64 (6) ◽  
Author(s):  
Robert K. Flamm ◽  
Leonard R. Duncan ◽  
Kamal A. Hamed ◽  
Jennifer I. Smart ◽  
Rodrigo E. Mendes ◽  
...  

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.


2008 ◽  
Vol 52 (7) ◽  
pp. 2383-2388 ◽  
Author(s):  
Deborah C. Draghi ◽  
Bret M. Benton ◽  
Kevin M. Krause ◽  
Clyde Thornsberry ◽  
Chris Pillar ◽  
...  

ABSTRACT Telavancin is an investigational, rapidly bactericidal lipoglycopeptide antibiotic that is being developed to treat serious infections caused by gram-positive bacteria. A baseline prospective surveillance study was conducted to assess telavancin activity, in comparison with other agents, against contemporary clinical isolates collected from 2004 to 2005 from across the United States. Nearly 4,000 isolates were collected, including staphylococci, enterococci, and streptococci (pneumococci, beta-hemolytic, and viridans). Telavancin had potent activity against Staphylococcus aureus and coagulase-negative staphylococci (MIC range, 0.03 to 1.0 μg/ml), independent of resistance to methicillin or to multiple agents. Telavancin activity was particularly potent against all streptococcal groups (MIC90s, 0.03 to 0.12 μg/ml). Telavancin had excellent activity against vancomycin-susceptible enterococci (MIC90, 1 μg/ml) and was active against VanB strains of vancomycin-resistant enterococci (MIC90, 2 μg/ml) but less active against VanA strains (MIC90, 8 to 16 μg/ml). Telavancin also demonstrated activity against vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains (MICs, 0.5 μg/ml to 1.0 μg/ml and 1.0 μg/ml to 4.0 μg/ml, respectively). These data may support the efficacy of telavancin for treatment of serious infections with a wide range of gram-positive organisms.


2003 ◽  
Vol 47 (5) ◽  
pp. 1689-1693 ◽  
Author(s):  
Ian A. Critchley ◽  
Renée S. Blosser-Middleton ◽  
Mark E. Jones ◽  
Clyde Thornsberry ◽  
Daniel F. Sahm ◽  
...  

ABSTRACT The activity of daptomycin was assessed by using 6,973 gram-positive bacteria isolated at 50 United States hospitals in 2000 and 2001. Among the isolates of Streptococcus pneumoniae (n = 1,163) collected, the rate of penicillin resistance was 16.1%; rates of oxacillin resistance among Staphylococcus aureus isolates (n = 1,018) and vancomycin resistance among Enterococcus faecium isolates (n = 368) were 30.0 and 59.5%, respectively. Multidrug-resistant (MDR) phenotypes (isolates resistant to three or more different chemical classes of antimicrobial agents) accounted for 14.2% of S. pneumoniae isolates, 27.1% of S. aureus isolates, and 58.4% of E. faecium isolates. For all gram-positive species tested, MICs at which 90% of the isolates tested were inhibited (MIC90s) and MIC ranges for directed-spectrum agents (daptomycin, quinupristin-dalfopristin, and linezolid) were identical or highly similar for isolates susceptible or resistant to other agents or MDR. Daptomycin had a MIC90 of 0.12 μg/ml for both penicillin-susceptible and -resistant isolates of S. pneumoniae. Against oxacillin-resistant S. aureus daptomycin had a MIC90 of 0.5 μg/ml, and it had a MIC90 of 4 μg/ml against both vancomycin-susceptible and -resistant E. faecium. The MIC90s for daptomycin and other directed-spectrum agents were unaffected by the regional or anatomical origin of isolates or patient demographic parameters (patient age, gender, and inpatient or outpatient care). Our results confirm the gram-positive spectrum of activity of daptomycin and that its activity is independent of susceptibility or resistance to commonly prescribed and tested antimicrobial agents. This study may serve as a baseline to monitor future changes in the susceptibility of gram-positive species to daptomycin following its introduction into clinical use.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S323-S323
Author(s):  
Helio S Sader ◽  
Rodrigo E Mendes ◽  
Michael A Pfaller ◽  
Robert K Flamm

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.


2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Michael A. Pfaller ◽  
Michael D. Huband ◽  
Dee Shortridge ◽  
Robert K. Flamm

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.


2006 ◽  
Vol 54 (2) ◽  
pp. 149-153 ◽  
Author(s):  
Ronald N. Jones ◽  
Matthew G. Stilwell ◽  
Helio S. Sader ◽  
Thomas R. Fritsche ◽  
Beth P. Goldstein

2005 ◽  
Vol 49 (12) ◽  
pp. 5024-5032 ◽  
Author(s):  
Deborah C. Draghi ◽  
Daniel J. Sheehan ◽  
Patricia Hogan ◽  
Daniel F. Sahm

ABSTRACT Since the approval of linezolid in 2000, sporadic reports of resistance have been given and a greater understanding of the underlying mechanisms of resistance has been gained. However, since these developments, an updated status of the in vitro activity of linezolid against gram-positive organisms from the United States has not been reported. The LEADER 2004 surveillance initiative was undertaken to obtain current and representative data on the activity of linezolid against key species, including isolates with significant resistance phenotypes. Organisms were isolated during 2004 and included 2,872 Staphylococcus aureus, 496 coagulase-negative staphylococcus (CNS), 428 Enterococcus faecalis, 196 Enterococcus faecium, and 422 Streptococcus pneumoniae isolates. All S. aureus isolates (54.2% oxacillin resistant) were susceptible to linezolid (MIC90 = 2 μg/ml); MIC distributions were consistent, regardless of oxacillin or multidrug resistance status. For CNS, one nonsusceptible isolate was encountered (Staphylococcus epidermidis; MIC = 32 μg/ml), but overall, the MIC90 (1 μg/ml) was lower than that obtained with S. aureus. For E. faecalis and E. faecium, 99.5% and 96.4% of isolates, respectively, were linezolid susceptible. Both species had an MIC90 of 2 μg/ml, and MIC distributions did not vary with the vancomycin susceptibility status of the populations analyzed. Linezolid nonsusceptibility was not encountered among the S. pneumoniae isolates. These findings indicate that linezolid nonsusceptibility has remained rare among staphylococci and uncommon and sporadic among enterococci. Nonetheless, careful and ongoing monitoring of the in vitro effectiveness of linezolid will be needed so that any changes to the current status may be detected as soon as possible.


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