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Activities of Omadacycline and Comparator Agents against Staphylococcus aureus Isolates from a Surveillance Program Conducted in North America and Europe.

ABSTRACT: Omadacycline is a new broad-spectrum aminomethylcycline in late-stage clinical development for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia as a once-daily formulation taken orally or intravenously. In this study, omadacycline and comparator agents were tested against 502 isolates of Staphylococcus aureus selected from a 2014 global surveillance program, and the results were compared with those for 7,740 isolates from a 2010 surveillance program. For the 2014 isolates, testing was completed on 252 isolates from Europe and 250 isolates from North America. Each set of isolates was composed of ∼100 hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA) isolates (isolated >48 h after hospital admission), 100 community-acquired MRSA (CA-MRSA) isolates (isolated <48 h after hospital admission), and 50 methicillin-susceptible S. aureus (MSSA) isolates. The omadacycline MIC50 and MIC90 for all S. aureus collected during 2014 was 0.12 and 0.12 μg/ml, respectively. The MIC90 values were identical for MRSA, HA-MRSA, and CA-MRSA (0.12 μg/ml). The MIC90 values for isolates from 2010 for S. aureus, MRSA, and CA-MRSA were 0.25 μg/ml (0.5 μg/ml for HA-MRSA; 87.8% were at ≤0.25 μg/ml). All 2014 and 2010 MRSA isolates were susceptible to vancomycin, and ≥99.8% were susceptible to daptomycin, linezolid, and tigecycline. The activity of omadacycline was similar for North American and European isolates, including MRSA (CA-MRSA or HA-MRSA). There was no evidence for emerging resistance to omadacycline between 2010 and 2014. The potent activity of omadacycline against S. aureus indicates that omadacycline merits further study in serious infections where multidrug resistance may be a concern.

SUBMITTER: Pfaller MA

PROVIDER: S-EPMC5328515 | biostudies-other | 2017 Mar

REPOSITORIES: biostudies-other

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Project description:BackgroundLyme disease incidence is increasing in Europe, the USA, and Canada. In 2010, a comparison of surveillance systems for Lyme disease (LD) in humans in 28 European countries showed that systems highly varied, making epidemiological comparisons difficult. Details by country were not published. In 2018, one of LD clinical manifestations, neuroborreliosis, was added under European Union (EU) surveillance to standardise definitions. In this study, we identified and compared, 10 years after the European inventory, the characteristics of national surveillance systems and policies for LD in humans, with additional countries.MethodsThirty-four European and North American countries were included. Information on national "traditional" systems (which compile data reported by clinicians and laboratories) and "public participatory" websites and mobile applications (which collect information directly from the public) were searched in MEDLINE, a systematic evidence map, and Google. An existing framework on LD surveillance was adapted to capture information on the administration level, indicators, reporting entities, coverage, and obligation to report.ResultsA surveillance system was found for 29 (85%) countries. Twenty-four had a traditional system alone, one had a public participatory system alone, and the remaining had both. Among countries with traditional systems, 23 (82%) administered them at the national level. Nineteen (68%) required mandatory reporting. Sixteen (57%) used both clinicians and laboratories as reporting entities. Eighteen (64%) employed case definitions, most of which considered both neuroborreliosis and erythema migrans (n = 14). Others monitored the number of positive laboratory tests and/or patient consultations. Public participatory systems were only implemented in countries employing either also sentinels or voluntary surveys, or no traditional system, suggesting their use as a complementary tool. Only 56% of EU countries had neuroborreliosis as an indicator.ConclusionThe situation remains similar to 2010 with persisting heterogeneity between systems, suggesting that countries prioritise different surveillance objectives for LD. Without a common indicator in Europe, it is difficult to get a clear epidemiological picture. We discuss four factors that potentially influence LD surveillance strategies: perceptions of severity, burden on resources, two-way communication, and the medical conflicts about LD. Addressing these with countries might help moving towards the adoption of common practices.

Project description:Azole resistance in Aspergillus fumigatus (AFM) is increasing and often associated with cyp51 alterations. We evaluated the activity of isavuconazole and other mold-active azoles against 731 AFM isolates causing invasive aspergillosis collected in Europe (EU; n = 449) and North America (NA; n = 282). Isolates were submitted to CLSI susceptibility testing and epidemiological cutoff value (ECV) criteria. A posaconazole ECV of 0.5 mg/L was used as no CLSI ECV was determined. Azole non-wild-type (NWT) isolates were submitted for cyp51 sequencing by whole genome sequencing. Overall, isavuconazole activity (92.7%/94.0% WT in EU/NA) was comparable to other azoles (WT rate range, 90.9%-96.4%/91.8%-98.6%, respectively), regardless of the region. A total of 79 (10.8%) azole NWT isolates were detected, and similar rates of these isolates were noted in EU (10.7%) and NA (11.0%). Although most AFM were WT to azoles, increasing azole NWT rates were observed in NA (from 6.0% in 2017 to 29.3% in 2021). Azole NWT rates varied from 4.9% (2019) to 20.6% (2018) in EU without an observed trend. cyp51 alterations occurred in 56.3%/54.8% of azole NWT from EU/NA, respectively. The cyp51A TR34/L98H alteration was observed only in EU isolates (72.0% of EU isolates), while cyp51A I242V occurred only in NA isolates (58.3%). Isavuconazole remained active (MIC, ≤1 mg/L) against 18.5/47.1% of azole NWT AFM exhibiting cyp51 alterations in EU/NA, along with voriconazole (29.6/82.4%; MIC, ≤1 mg/L) and posaconazole (48.1/88.2%; MIC, ≤0.5 mg/L). Fourteen different cyp51 alterations were detected in 44 of 79 NWT isolates. The in vitro activity of the azoles varied in AFM that displayed cyp51 alterations. IMPORTANCE A few microbiology laboratories perform antifungal susceptibility testing locally for systemically active antifungal agents. The identification of emerging azole-resistant Aspergillus fumigatus is worrisome. As such, there is a critical role for antifungal surveillance in tracking emerging resistance among both common and uncommon opportunistic fungi. Differences in the regional prevalence and antifungal resistance of these fungi render local epidemiological knowledge essential for the care of patients with a suspected invasive fungal infection.

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Activities of Omadacycline and Comparator Agents against Staphylococcus aureus Isolates from a Surveillance Program Conducted in North America and Europe.

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