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Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance Program.

ABSTRACT: Omadacycline was tested against 21,000 bacterial isolates collected prospectively from medical centers in Europe and the United States during 2016. Omadacycline was active against Staphylococcus aureus (MIC50/MIC90, 0.12/0.25 mg/liter), including methicillin-resistant S. aureus (MRSA); streptococci (MIC50/MIC90, 0.06/0.12 mg/liter), including Streptococcus pneumoniae, viridans group streptococci, and beta-hemolytic streptococci; Enterobacteriaceae, including Escherichia coli (MIC50/MIC90, 0.5/2 mg/liter); Haemophilus influenzae (MIC50/MIC90, 1/1 mg/liter); and Moraxella catarrhalis (MIC50/MIC90, 0.25/0.25 mg/liter). Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

SUBMITTER: Pfaller MA

PROVIDER: S-EPMC5913935 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description: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 ?-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.

Project description:Omadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (1 per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent against Staphylococcus aureus (n = 689; MIC50/90, 0.12/0.25 mg/liter), including methicillin-resistant Staphylococcus aureus (MRSA; n = 299; MIC50/90, 0.12/0.5 mg/liter), and had similar activity across geographic regions. Omadacycline was very active against Streptococcus pneumoniae (highest MIC, 0.25 mg/liter), ?-hemolytic streptococci (highest MIC, 1 mg/liter), viridans group streptococci (highest MIC, 0.25 mg/liter), and Enterococcus spp. (highest MIC, 0.5 mg/liter) from all geographic regions. Overall, 53.8% of S. pneumoniae isolates were penicillin resistant (penicillin MIC, ?2 mg/liter) and 10.7% of enterococci (21.2% among E. faecium isolates) were vancomycin resistant. Omadacycline was active against Haemophilus influenzae (MIC50/90, 0.5/1 mg/liter) regardless of ?-lactamase production and was active against Moraxella catarrhalis (MIC50/90, ?0.12/0.25 mg/liter). Against Enterobacteriaceae, omadacycline was most active against Escherichia coli (MIC50/90, 1/2 mg/liter), Klebsiella oxytoca (MIC50/90, 1/4 mg/liter), and Enterobacter cloacae (MIC50/90, 2/4 mg/liter). Omadacycline had potent in vitro activity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan and retained activity against problem pathogens, such as MRSA, vancomycin-resistant enterococci (VRE), penicillin-resistant S. pneumoniae (PRSPN), and extended-spectrum ?-lactamase-producing E. coli The observed MIC profile in Chinese isolates was very similar to that seen in the U.S. and European surveillance studies.

Project description:We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. Candida (n?=?1,904 isolates; 6 species), Cryptococcus neoformans (n?=?73), Aspergillus fumigatus (n?=?183), and Aspergillus flavus (n?=?45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of Candida albicans isolates (MIC50/90, 0.03/0.06??g/ml), 95.7% of Candida glabrata isolates (MIC50/90, 0.06/0.12??g/ml), 97.4% of Candida tropicalis isolates (MIC50/90, 0.03/0.06??g/ml), 100.0% of Candida krusei isolates (MIC50/90, 0.03/0.06??g/ml), and 100.0% of Candida dubliniensis isolates (MIC50/90, 0.06/0.12??g/ml) at ?0.12??g/ml. All (329/329 [100.0%]) Candida parapsilosis isolates (MIC50/90,1/2??g/ml) were inhibited by rezafungin at ?4??g/ml. Fluconazole resistance was detected among 8.6% of C. glabrata isolates, 12.5% of C. parapsilosis isolates, 3.2% of C. dubliniensis isolates, and 2.6% of C. tropicalis isolates. The activity of rezafungin against these 6 Candida spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT Candida isolates. Good activity against C. neoformans was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against A. fumigatus and A. flavus These in vitro data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

Project description:BackgroundAntimicrobial resistance is a growing threat to the world's ability to prevent and treat infections. Links between quantitative antibiotic use and the emergence of bacterial resistance are well documented. This study presents benchmark antimicrobial use (AMU) rates for inpatient adult populations in acute-care hospitals across Canada.MethodsIn this retrospective surveillance study, acute-care adult hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP) submitted annual AMU data on all systemic antimicrobials from 2009 to 2016. Information specific to intensive care units (ICUs) and non-ICU wards were available for 2014-2016. Data were analyzed using defined daily doses (DDD) per 1000 patient days (DDD/1000pd).ResultsBetween 2009 and 2016, 16-18 CNISP adult hospitals participated each year and provided their AMU data (22 hospitals participated in ?1?year of surveillance; 11 in all years). From 2009 to 2016, there was a significant reduction in use (12%) (from 654 to 573 DDD/1000pd, p?=?0.03). Fluoroquinolones accounted for the majority of this decrease (47% reduction in combined oral and intravenous use, from 129 to 68 DDD/1000pd, p?<?0.002). The top five antimicrobials used in 2016 were cefazolin (78 DDD/1000pd), piperacillin-tazobactam (53 DDD/1000pd), ceftriaxone (49 DDD/1000pd), vancomycin (combined oral and intravenous use was 44 DDD/1000pd; 7% of vancomycin use was oral), and ciprofloxacin (combined oral and intravenous use: 42 DDD/1000pd). Among the top 10 antimicrobials used in 2016, ciprofloxacin and metronidazole use decreased significantly between 2009 and 2016 by 46% (p?= 0.002) and 26% (p?=?0.002) respectively. Ceftriaxone (85% increase, p?=?0.0008) and oral amoxicillin-clavulanate (140% increase, p?<?0.0001) use increased significantly but contributed only a small component (8.6 and 5.0%, respectively) of overall use.ConclusionsThis study represents the largest collection of dispensed antimicrobial use data among inpatients in Canada to date. Between 2009 and 2016, there was a significant 12% decrease in AMU, driven primarily by a 47% decrease in fluoroquinolone use. Modest absolute increases in parenteral ceftriaxone and oral amoxicillin-clavulanate use were noted but contributed a small amount of total AMU. Ongoing national surveillance is crucial for establishing benchmarks and antimicrobial stewardship guidelines.

Dataset Information

Surveillance of Omadacycline Activity Tested against Clinical Isolates from the United States and Europe as Part of the 2016 SENTRY Antimicrobial Surveillance Program.

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