A Typology of COVID-19 Data Gaps and Noise From Long-Term Care Facilities: Approximating the True Numbers.

Although there is agreement that COVID-19 has had devastating impacts in long-term care facilities (LTCFs), estimates of cases and deaths have varied widely with little attention to the causes of this variation. We developed a typology of data vulnerabilities and a strategy for approximating the true total of COVID-19 cases and deaths in LTCFs. Based on iterative qualitative consensus, we categorized LTCF reporting vulnerabilities and their potential impacts on accuracy. Concurrently, we compiled one dataset based on LTCF self-reports and one based on confirmatory matching with California's COVID-19 databases, including death certificates. Through March 2021, Alameda County LTCFs reported 6663 COVID-19 cases and 481 deaths. In contrast, our confirmatory matching file includes 5010 cases and 594 deaths, corresponding to 25% fewer cases but 23% more deaths. We argue that the higher (self-report) case total approximates the lower bound of true COVID-19 cases, and the higher (confirmed match) death total approximates the lower bound of true COVID-19 deaths, both of which are higher than state and federal counts. LTCFs other than nursing facilities accounted for 35% of cases and 29% of deaths. Improving the accuracy of COVID-19 figures, particularly across types of LTCFs, would better inform interventions for these vulnerable populations.

COVID-19 Across the Landscape of Long-Term Care in Alameda County: Heterogeneity and Disparities.

Throughout the pandemic, public health and long-term care professionals in our urban California county have linked local and state COVID-19 data and performed observational exploratory analyses of the impacts among our diverse long-term care facilities (LTCFs). Case counts from LTCFs through March 2021 included 4309 (65%) in skilled nursing facilities (SNFs), 1667 (25%) in residential care facilities for the elderly (RCFEs), and 273 (4%) in continuing care retirement communities (CCRCs). These cases led to 582 COVID-19 resident deaths and 12 staff deaths based on death certificates. Data on decedents' age, race, education, and country of birth reflected a hierarchy of wealth and socioeconomic status from CCRCs to RCFEs to SNFs. Mortality rates within SNFs were higher for non-Whites than Whites. Staff accounted for 42% of LTCF-associated COVID-19 cases, and over 75% of these staff were unlicensed. For all COVID-19 deaths in our jurisdiction, both LTCF and community, 82% of decedents were age 65 or over. Taking a comprehensive, population-based approach across our heterogenous LTCF landscape, we found socioeconomic disparities within COVID-19 cases and deaths of residents and staff. An improved data infrastructure linking public health and delivery systems would advance our understanding and potentiate life-saving interventions within this vulnerable ecosystem.

In vitro activity of tedizolid against clinical isolates of Staphylococcus lugdunensis and Staphylococcus haemolyticus from Europe and the United States.

Staphylococcus lugdunensis and Staphylococcus haemolyticus are unique among CoNS in that the former often causes aggressive disease, while the latter consistently exhibits high rates of multidrug resistance. We evaluated the in vitro susceptibility of contemporary (2012-2013) isolates from both pathogens to tedizolid and comparators, using standard methodology. Results were interpreted using CLSI and EUCAST breakpoints. Overall, 106 S. lugdunensis and 103 S. haemolyticus isolates were collected from 51 medical centers in the United States and 30 centers in 18 European countries. Tedizolid showed good activity against S. lugdunensis (MIC50/MIC90: 0.12/0.12 mg/L) and S. haemolyticus (MIC50/MIC90: 0.12/0.12 mg/L), inhibiting all isolates at MIC ≤0.25 mg/L. Based on the EUCAST breakpoint for staphylococci and when substituting the CLSI breakpoint for Staphylococcus aureus, all isolates were tedizolid susceptible. All isolates were also susceptible to linezolid, but the in vitro potency of tedizolid was 4-fold greater than that of linezolid against both S. lugdunensis and S. haemolyticus, based on MIC90 values. S. lugdunensis exhibited ≥99% susceptibility to vancomycin, teicoplanin, gentamicin, levofloxacin, and trimethoprim-sulfamethoxazole; 7% of isolates were resistant to tetracycline, 11% to clindamycin, and 2% were methicillin-resistant. S. haemolyticus exhibited high rates of resistance to commonly used anti-staphylococcal agents: 71% of isolates were resistant to methicillin, 36%-37% to clindamycin, and 30%-50% to gentamicin. These in vitro findings suggest that tedizolid could be an alternative treatment option for infections due to these medically important CoNS pathogens. Additional clinical evaluation and continued surveillance of tedizolid in vitro activity against S. lugdunensis and S. haemolyticus are warranted.

Short-Read Whole-Genome Sequencing for Laboratory-Based Surveillance of Bordetella pertussis.

Bordetella pertussis is a Gram-negative bacterium that causes respiratory infections in humans. Ongoing molecular surveillance of B. pertussis acellular vaccine (aP) antigens is critical for understanding the interaction between evolutionary pressures, disease pathogenesis, and vaccine effectiveness. Methods currently used to characterize aP components are relatively labor-intensive and low throughput. To address this challenge, we sought to derive aP antigen genotypes from minimally processed short-read whole-genome sequencing data generated from 40 clinical B. pertussis isolates and analyzed using the SRST2 bioinformatic package. SRST2 was able to identify aP antigen genotypes for all antigens with the exception of pertactin, possibly due to low read coverage in GC-rich low-complexity regions of variation. Two main genotypes were observed in addition to a singular third genotype that contained an 84-bp deletion that was identified by SRST2 despite the issues in allele calling. This method has the potential to generate large pools of B. pertussis molecular data that can be linked to clinical and epidemiological information to facilitate research of vaccine effectiveness and disease severity in the context of emerging vaccine antigen-deficient strains.

Prevalence of macrolide-lincosamide resistance and multidrug resistance phenotypes in streptococcal isolates causing infections in European hospitals: Evaluation of the in vitro activity of oritavancin and comparator agents.

The aim of this study was to evaluate the prevalence of resistance to erythromycin alone (M) and to erythromycin and clindamycin (cMLSB) as well as multidrug resistance (MDR) phenotypes (resistance to at least three classes of drugs) among clinical enterococci from European countries and adjacent geographic regions. The in vitro activity of oritavancin against these isolates was also evaluated. A total of 2569 streptococci collected from 12 European countries as well as Russia, Turkey and Israel were included. A total of 9.8%, 8.1% and 6.4% of ß-haemolytic streptococci (BHS) displayed M, cMLSB and MDR phenotypes, respectively. Oritavancin (99.4-100.0% susceptible) demonstrated modal minimum inhibitory concentration (MIC) (0.03mg/L) and MIC50 (0.03mg/L) values that were the same for all BHS or subsets, including MDR. The oritavancin MIC50 value of 0.06mg/L against Streptococcus dysgalactiae was similar to those of daptomycin and penicillin (MIC50≤0.06mg/L for both). Among viridans group streptococci (VGS), 28.3%, 12.7% and 11.6% showed M, cMLSB and MDR phenotypes, respectively. Oritavancin (99.9-100.0% susceptible; MIC50/90, ≤0.008/0.06mg/L) exhibited potent in vitro activity against VGS and resistant subsets, as did vancomycin (MIC50/90, 0.5/0.5-1mg/L), daptomycin (MIC50/90, 0.25-0.5/0.5-1mg/L) and linezolid (MIC50/90, 0.5-1/1mg/L). In conclusion, rates of resistance phenotypes were higher in VGS than BHS. Oritavancin demonstrated in vitro potencies that were similar to or greater than those of comparators against this recent collection of streptococci, including drug-resistant subsets, from European and adjacent countries.

Longitudinal (2001-14) analysis of enterococci and VRE causing invasive infections in European and US hospitals, including a contemporary (2010-13) analysis of oritavancin in vitro potency.

OBJECTIVES: The objective of this study was to evaluate the prevalence and in vitro susceptibility of enterococci and VRE among bloodstream infections in European and US hospitals over time. METHODS: Isolates recovered from the blood of infected patients in Europe (72 996) and the USA (67 725) between 2001 and 2014 were included in the prevalence analysis. A subset (2349) collected during 2011-13 was used for the in vitro activity analysis. RESULTS: Enterococcus faecium rates increased in Europe (from 1.4% in 2001 to 4.3% in 2014). These rates also increased in the USA (from 3.0% in 2001 to 5.4% in 2010), with decreasing prevalence (4.6% in 2011 to 3.6% in 2014) in later years. Enterococcus faecalis rates remained stable in Europe, but rose in the USA from 6.9% in 2001 to 8.8% in 2009, declining later (from 7.4% to 5.0%). VRE rates among E. faecalis did not vary in either region, while VRE rates among E. faecium increased in Europe (from 4.7% to 20.3%). US VRE rates among E. faecium increased until 2010 (60.0% in 2001 to 80.7% in 2010), decreasing from 75.1% in 2011 to 68.4% in 2013. Oritavancin demonstrated activity against vancomycin-susceptible E. faecalis (MIC50/90, 0.015/0.06 mg/L; 99.5% susceptible) and vancomycin-resistant E. faecalis (MIC50/90, 0.25/0.5 mg/L). Oritavancin showed MIC50, MIC90 and MIC100 values of 0.03, 0.12 and 0.25 mg/L, respectively, for VanA E. faecium. CONCLUSIONS: Rates of E. faecium and VRE increased in Europe. Although still elevated, VRE rates appeared to show a decreasing trend in the USA since 2010. Oritavancin demonstrated activity against enterococci, including VRE.

In Vitro Activity of Delafloxacin Tested against Isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the United States (2014) were tested against delafloxacin and comparator agents. Delafloxacin was the most potent agent tested. MIC50 and MIC90 values against all S. pneumoniae isolates were 0.008 and 0.015 µg/ml. Delafloxacin susceptibility was not affected by ß-lactamase status against H. influenzae and M. catarrhalis.

In vitro spectrum of pexiganan activity; bactericidal action and resistance selection tested against pathogens with elevated MIC values to topical agents.

Pexiganan, in Phase 3 clinical development for topical use, exhibited bactericidal activity in vitro against Gram-positive and -negative isolates and was also shown to have a low potential for resistance development in broth serial passage experiments. Susceptibility studies were performed against bacterial isolates (110 total from 2004 to 2013; primarily from skin and soft tissue infections) selected for elevated MIC values (non-wildtype [WT] distributions) to bacitracin, polymyxin B, neomycin, mupirocin, retapamulin, fusidic acid, or gentamicin. A narrow range of pexiganan MIC values (4-32 µg/mL) against Staphylococcus aureus was observed (MIC50 and MIC90 values, 16 µg/mL) with a pexiganan mode and MIC50 value for the subsets of isolates with non-WT MIC values to bacitracin and neomycin (n = 14), fusidic acid (n = 11), mupirocin (n = 12) and retapamulin (n = 11) at 16 µg/mL. For coagulase-negative staphylococci (CoNS), the pexiganan mode and MIC50 values were 4 µg/mL. The pexiganan mode and MIC50 for each non-WT CoNS subset was also 4 µg/mL. Pexiganan MIC values for Enterococcus faecium was 8 µg/mL, but E. faecalis isolates exhibited MIC values that ranged from 128-256 µg/mL. Pexiganan was active against ß-hemolytic streptococci including non-WT subsets (MIC range, 4-64 µg/mL). MIC values for pexiganan varied by species for viridans group streptococci, with highest values occurring for Streptococcus oralis. The broad bactericidal spectrum of pexiganan activity and low potential for resistance selection offers the possibility that this experimental agent may be able to play an important role in the current environment of emerging multi-drug resistant pathogens.

Activities of Tedizolid and Linezolid Determined by the Reference Broth Microdilution Method against 3,032 Gram-Positive Bacterial Isolates Collected in Asia-Pacific, Eastern Europe, and Latin American Countries in 2014.

Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect of MIC endpoint criteria on the results of testing the oxazolidinones tedizolid and linezolid, MIC endpoint values were read by two methods: (i) reading the MIC at the first well where the trailing began without regard for pinpoint trailing, according to CLSI M07-A10 and M100-S26 document instructions for reading linezolid (i.e., 80% inhibition of growth; these reads were designated tedizolid 80 and linezolid 80), and (ii) at 100% inhibition of growth (designated tedizolid 100 and linezolid 100). All Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis isolates were inhibited at tedizolid 80 and 100 MIC values of 0.25 and 0.5, 0.25 and 0.25, 0.25 and 0.5, 0.12 and 0.25, and 0.5 and 1 µg/ml, respectively. Generally, MIC50 and MIC90 results for tedizolid 80 and linezolid 80 were one doubling dilution lower than those read at 100% inhibition. Tedizolid was 4- to 8-fold more potent than linezolid against all the isolates tested regardless of the MIC endpoint criterion used. Despite the differences in potency, >99.9% of isolates tested in this survey were susceptible to both linezolid and tedizolid using CLSI and EUCAST interpretive criteria. In conclusion, tedizolid demonstrated greater in vitro potency than linezolid against Gram-positive pathogens isolated from patients in medical centers across the Asia-Pacific region, Eastern Europe, and Latin America.

Tigecycline antimicrobial activity tested against clinical bacteria from Latin American medical centres: results from SENTRY Antimicrobial Surveillance Program (2011-2014).

Bacterial organisms (n = 13,494) were consecutively collected in 2011-2014 from 21 Latin American medical centres (11 nations). Antimicrobial susceptibility was determined by broth microdilution at a central laboratory. Tigecycline was very active against Gram-positive organisms, with MIC50/90 values of 0.06/0.06 µg/mL for Staphylococcus aureus (n = 2878), 0.06/0.12 µg/mL for coagulase-negative staphylococci (n = 880), 0.06/0.06 µg/mL for enterococci (n = 708) and ≤0.03/≤0.03-0.06 µg/mL for streptococci (n = 1352). All Gram-positive species exhibited 100.0% susceptibility (FDA and/or EUCAST criteria), except for Streptococcus pneumoniae (99.8% susceptible). The S. aureus oxacillin resistance rate varied from 28.0% (Brazil) to 55.0% (Argentina), and the overall vancomycin resistance rate was 15.5% (Enterococcus faecium, 50.3%; and Enterococcus faecalis, 2.3%). The E. faecium vancomycin resistance rate varied from a low (26.3%) in Argentina to a high (71.7%) in Brazil. Against Enterobacteriaceae (n = 4543), tigecycline MIC50/90 values were 0.25/1 µg/mL; 98.3% and 94.2% of strains were considered susceptible according to FDA and EUCAST breakpoints, respectively. Overall, 37.7% and 57.3% of Escherichia coli and Klebsiella pneumoniae exhibited the CLSI ESBL screening phenotype. The highest CLSI ESBL screening phenotype rates among E. coli and Klebsiella spp. strains were observed for isolates collected from Mexico (69.9%) and Chile (69.9%), respectively. Occurrence of carbapenem-resistant Enterobacteriaceae was substantially higher in Brazil (9.0%) and Argentina (6.3%) compared with Chile and Mexico (0.4-0.7%). Tigecycline was also active against Acinetobacter spp. (MIC50/90, 1/2 µg/mL; 92.3/72.1% inhibited at ≤2/≤1 µg/mL) and Stenotrophomonas maltophilia (MIC50/90, 0.5/2 µg/mL; 91.5/83.0% inhibited at ≤2/≤1 µg/mL).

In Vitro Activity of Lefamulin Tested against Streptococcus pneumoniae with Defined Serotypes, Including Multidrug-Resistant Isolates Causing Lower Respiratory Tract Infections in the United States.

Lefamulin was evaluated against various Streptococcus pneumoniae serotypes that were collected from adults with lower respiratory tract infections. Lefamulin exhibited MIC50 and MIC90 values of 0.12 and 0.25 µg/ml, respectively, against the entire collection (n = 822). Similar results were obtained for lefamulin against each of the most common serotypes as well as against multidrug-resistant isolates and strains that are nonsusceptible to ceftriaxone or erythromycin. These data support the clinical development of lefamulin for the treatment of community-acquired respiratory tract infections.

In vitro activity of dalbavancin against multidrug-resistant Staphylococcus aureus and streptococci from patients with documented infections in Europe and surrounding regions (2011-2013).

The in vitro activity of dalbavancin was evaluated against 9303 Staphylococcus aureus and 2670 streptococci, including multidrug-resistant (MDR) isolates, collected from hospitalised patients in Europe and surrounding regions from 2011 to 2013. Dalbavancin recently received approval for the treatment of acute bacterial skin and skin-structure infections by the US Food and Drug Administration (FDA) and the European Medicines Agency. Bacterial identification was confirmed by standard microbiological methods (including MALDI-TOF), and susceptibility testing was performed by reference broth microdilution methods. Dalbavancin susceptibility interpretations followed FDA/EUCAST criteria. Meticillin-resistant S. aureus (MRSA) and streptococci exhibiting resistance to at least three other drug classes were considered as MDR. Dalbavancin was highly active (MIC50/90, 0.06/0.06 mg/L; ≥99.9% susceptible) against MDR and non-MDR MRSA isolates. Vancomycin, daptomycin and linezolid were also active (99.6-100.0% susceptible) against MDR MRSA, however MIC90 values for these drugs were 8- to 16-fold higher than dalbavancin (MIC90 values of 1, 0.5 and 1 mg/L, respectively). All viridans group streptococci (VGS) and ß-haemolytic streptococci were susceptible to dalbavancin regardless of resistance phenotype (MIC50/90 values of ≤0.03 mg/L and 0.06 mg/L, respectively). Dalbavancin MIC50/90 results (MIC50/90, ≤0.03/0.06 mg/L) against MDR VGS were at least eight-fold lower than those of vancomycin (MIC50/90, 0.5/1 mg/L), daptomycin (MIC50/90, 0.5/1 mg/L) and linezolid (MIC50/90, 0.5/1 mg/L). Overall, dalbavancin exhibited potent in vitro antibacterial activity against S. aureus and streptococci, including MDR phenotypes. Dalbavancin had the lowest MIC50/90 results against the isolates tested, relative to comparator agents, regardless of resistance phenotypes.

Results from the Solithromycin International Surveillance Program (2014).

Solithromycin, a fourth-generation macrolide (a fluoroketolide with enhanced activity against macrolide-resistant bacteria due to interaction with three ribosomal sites) and the first fluoroketolide, was tested against a 2014 collection of 6,115 isolates, including Streptococcus pneumoniae (1,713 isolates), Haemophilus influenzae (1,308), Moraxella catarrhalis (577), Staphylococcus aureus (1,024), and beta-hemolytic streptococci (1,493), by reference broth microdilution methods. The geographic samples included 2,748 isolates from the United States, 2,536 from Europe, 386 from Latin America, and 445 from the Asia-Pacific region. Solithromycin was observed to be very active against S. pneumoniae (MIC50/90, 0.008/0.12 µg/ml), demonstrating 2-fold greater activity than telithromycin (MIC50/90, 0.015/0.25 µg/ml) and 16- to >256-fold greater activity than azithromycin (MIC50/90, 0.12/>32 µg/ml), with all strains being inhibited at a solithromycin MIC of ≤1 µg/ml. Against H. influenzae, solithromycin showed potency identical to that of telithromycin (MIC50/90, 1/2 µg/ml), and both of these compounds were 2-fold less active than azithromycin (MIC50/90, 0.5/1 µg/ml). All but one of the M. catarrhalis isolates were inhibited by solithromycin at ≤0.25 µg/ml. Solithromycin inhibited 85.3% of S. aureus isolates at ≤1 µg/ml, and its activity was lower against methicillin-resistant (MIC50/90, 0.06/>32 µg/ml) than against methicillin-susceptible (MIC50/90, 0.06/0.06 µg/ml) isolates. Little variation in solithromycin activity was observed by geographic region for the species tested. Solithromycin was very active against beta-hemolytic streptococci (MIC50/90, 0.015/0.03 µg/ml), and all isolates were inhibited at MIC values of ≤0.5 µg/ml. In conclusion, solithromycin demonstrated potent activity against global and contemporary (2014) pathogens that represent the major causes of community-acquired bacterial pneumonia. These data support the continued clinical development of solithromycin for the treatment of this important indication.

Evolution of Ceftaroline-Resistant Mrsa in a Child with Cystic Fibrosis Following Repeated Antibiotic Exposure.

Ceftaroline is the first ß-lactam antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA). We describe a ceftaroline-resistant MRSA strain, isolated from a girl with cystic fibrosis after 22 ceftaroline treatment courses. MRSA genome sequencing documented a Tyr446Asn alteration in penicillin binding protein 2 that appeared responsible for resistance. Noncompartmental ceftaroline pharmacokinetic evaluation in our patient documented increased clearance and volume of distribution compared with adults.

Activity of Fusidic Acid Tested against Staphylococci Isolated from Patients in U.S. Medical Centers in 2014.

Fusidic acid (FA) activity was evaluated against 2,002 clinical staphylococcal isolates collected in U.S. hospitals during 2014. FA (MIC50/90, 0.12/0.12 µg/ml) inhibited 99.8% of Staphylococcus aureus isolates at ≤1 µg/ml. Only four S. aureus isolates displayed FA values of >2 µg/ml (three strains with fusC and one with an L461K substitution in fusA), and they were isolated from patients in four states. In conclusion, FA demonstrated sustained, potent activity against this recent collection of U.S. staphylococci.

Antimicrobial activity of ceftaroline and comparator agents when tested against numerous species of coagulase-negative Staphylococcus causing infection in US hospitals.

A total of 1593 coagulase-negative staphylococci (CoNS) considered clinically significant were collected from 71 US medical centers in 2013-2014 and tested for susceptibility by CLSI broth microdilution methods. Species identification was performed by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. Overall, 59.7% of isolates were oxacillin resistant (MRCoNS). Ceftaroline (MIC50/90, 0.25/0.5µg/mL) inhibited 99.2% of CoNS at ≤1µg/mL (susceptible breakpoint for Staphylococcus aureus), including 98.7% of MRCoNS, and the highest ceftaroline MIC value was 2µg/mL (13 isolates). Staphylococcus epidermidis represented 60.3% of the CoNS collection and was highly susceptible to ceftaroline (MIC50/90, 0.25/0.5µg/mL, 99.9% inhibited at ≤1µg/mL). All isolates of Staphylococcus capitis, Staphylococcus caprae, Staphylococcus hominis, Staphylococcus lugdunensis, Staphylococcus pettenkoferi, Staphylococcus simulans, and Staphylococcus warneri (MIC50/90, 0.06-0.25/0.25-0.5µg/mL) were inhibited at ceftaroline MIC of ≤1µg/mL. Staphylococcus haemolyticus represented only 4.8%, was atypically less susceptible to ceftaroline (MIC50/90, 0.5/2µg/mL, 87.0% inhibited at ≤1µg/mL), and accounted for 76.9% (10/13) of isolates with ceftaroline MIC >1µg/mL.

Oritavancin Activity Tested against Molecularly Characterized Staphylococci and Enterococci Displaying Elevated Linezolid MIC Results.

Oritavancin (MIC50/90, 0.03/0.06 to 0.12 µg/ml) had potent activity against linezolid-resistant staphylococci, as well as Enterococcus faecalis and Enterococcus faecium (oritavancin MIC50/90, 0.015/0.12 µg/ml against both species). All linezolid-resistant isolates were inhibited by oritavancin at ≤0.12 µg/ml. These results confirmed the absence of cross-resistance between linezolid and oritavancin in staphylococci and enterococci.

Antimicrobial Activity of Ceftaroline Tested against Staphylococcus aureus from Surgical Skin and Skin Structure Infections in US Medical Centers.

BACKGROUND: Ceftaroline fosamil is a novel cephalosporin approved by the United States Food and Drug Administration (US FDA) for treatment of acute bacterial skin and skin structure infection, including those caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of ceftaroline and comparator agents tested against S. aureus isolated from surgical skin and skin structure infections (SSSI). METHODS: Clinically substantial isolates (one/patient episode) from SSSI were consecutively collected from 64 medical centers in the United States over a 6-y period (2008-2013) and tested for susceptibility by broth microdilution methods against ceftaroline and several comparator agents. RESULTS: Among 794 strains tested, 50.5% were MRSA. Ceftaroline was active against all methicillin-susceptible Staphylococcus aureus (MSSA; minimal inhibitory concentration [MIC]90, 0.25 mcg/mL) and nearly all MRSA (MIC90, 1 mcg/mL). Against MSSA, ceftaroline was 16-fold more potent than ceftriaxone (MIC90, 4 mcg/mL) and the highest ceftaroline MIC was 0.5 mcg/mL. Among MRSA, 97.5% and 100.0% of strains were inhibited at ≤1 and ≤2 mcg/mL of ceftaroline. Furthermore, 27.4% and 67.5% of MRSA were resistant to clindamycin and levofloxacin, respectively. Daptomycin (MIC50/90, 0.25/0.5 mcg/mL), linezolid (MIC50/90, 1/2 mcg/mL), tigecycline (MIC50/90, 0.06/0.12 mcg/mL) and vancomycin (MIC50/90, 1/2 mcg/mL) were also highly active against S. aureus strains. CONCLUSIONS: Ceftaroline exhibited potent in vitro activity against S. aureus causing SSSI in a large number of US hospitals, including MRSA. On the basis of this in vitro data, ceftaroline fosamil may represent a valuable option for treatment of surgical SSSI, and should be further evaluated as an agent for surgical prophylaxis that would cover MRSA.

Antimicrobial Activities of Ceftaroline and Comparator Agents against Bacterial Organisms Causing Bacteremia in Patients with Skin and Skin Structure Infections in U.S. Medical Centers, 2008 to 2014.

We evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained wereStaphylococcus aureus(670 organisms [46.1%]),Escherichia coli(200 organisms [13.8%]), ß-hemolytic streptococci (ßHS) (138 organisms [9.5%]), andKlebsiella pneumoniae(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% forS. aureus(95.9% among methicillin-resistantS. aureus[MRSA]), 100.0% for ßHS, 86.5% forE. coli, and 89.0% forK. pneumoniae Ceftaroline and tigecycline provided the best overall coverage.