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Objectives: Omadacycline was tested against 7000 bacterial isolates collected prospectively from medical centres in the USA during 2019. Methods: Antimicrobial susceptibility testing was performed according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Results: Omadacycline was active against: Staphylococcus aureus (MIC50/90, 0.12/0.25 mg/L; 98.3% susceptible), including methicillin-resistant S. aureus (MRSA); Enterococcus faecalis (MIC50/90, 0.06/0.25 mg/L; 100.0% susceptible), including vancomycin-resistant enterococci (VRE); Streptococcus pneumoniae (MIC50/90, 0.06/0.06 mg/L; 99.8% susceptible); viridans group streptococci, including Streptococcus anginosus group (MIC50/90, 0.03/0.06 mg/L; 100.0% susceptible); β-haemolytic streptococci, including Streptococcus pyogenes (MIC50/90, 0.06/0.12 mg/L; 99.2% susceptible); Enterobacterales (MIC50/90, 1/8 mg/L; 86.9% inhibited at ≤4 mg/L), including Escherichia coli (MIC50/90, 0.5/2 mg/L; 99.6% inhibited at ≤4 mg/L); Enterobacter cloacae (MIC50/90, 2/4 mg/L; 98.5% susceptible); Klebsiella pneumoniae (MIC50/90, 1/4 mg/L; 93.2% susceptible); Acinetobacter baumannii (MIC50/90, 0.5/4 mg/L; 90.8% inhibited at ≤4 mg/L); Haemophilus influenzae (MIC50/90, 0.5/1 mg/L; 100.0% susceptible); and Moraxella catarrhalis (MIC50/90, ≤0.12/0.25 mg/L). Conclusion: The 2019 in vitro activity of omadacycline against key Gram-positive and Gram-negative pathogens has not changed compared with the prior 3 years of surveillance in the SENTRY Antimicrobial Surveillance Program. Omadacycline merits further study in serious infections where resistant pathogens may be encountered.

This article reviews available public data on the pre-COVID (2014–2018) residential broadband markets in the United States, and presents six data-driven stylized economic facts about these markets. Broadband was a significant household expenditure. There were very limited numbers of competing residential broadband Internet service providers (ISPs) in most local markets. Service prices have not decreased much over time. Quality competition seems quite important. There was very limited entry by new ISPs. Technological innovation in wireless drove much observed new entry.

Objective This study examined the in vitro activity of iclaprim and comparators against 40 Listeria monocytogenes clinical isolates mostly (95%) from patients with bloodstream infections (BSI) from the United States, Australia/New Zealand, Latin America, and Europe collected between 2012-2018 were tested. Methods Susceptibility testing was performed according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Minimum inhibitory concentration (MIC) interpretations were based on CLSI criteria. Results The iclaprim MIC90 value for all L. monocytogenes was 0.015 µg/ml. The MIC50/90 values for iclaprim were 4-fold lower than trimethoprim, the only FDA approved dihydrofolate reductase inhibitor, against all L. monocytogenes. Conclusions Iclaprim demonstrated lower MIC values than trimethoprim against a collection (2012-2018) of L. monocytogenes clinical isolates mostly from patients with blood stream infections from the United States, Australia/New Zealand, Latin America, and Europe.

Objectives Delafloxacin is a broad-spectrum anionic fluoroquinolone with activity against Gram-positive and Gram-negative organisms, including methicillin-resistant Staphylococcus aureus. Both oral and intravenous formulations were approved for use in the treatment of acute bacterial skin and skin-structure infections (ABSSSIs) due to Gram-positive and Gram-negative organisms by the US Food and Drug Administration (2017) and European Medicines Agency (2019), and for community-acquired bacterial pneumonia by the FDA (2019). The SENTRY Antimicrobial Surveillance Program has monitored the susceptibility of delafloxacin in the USA and Europe since 2014. The purpose of this study is to provide an update on delafloxacin activity against ABSSSI isolates primarily collected from hospitalised patients in Europe. Methods A total of 11,866 non-duplicate ABSSSI isolates were collected from 2014 to 2019 from 46 European medical centres in 24 countries. Susceptibilities were determined by broth microdilution. Results were interpreted using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints (2020). Results The most common isolate wasS. aureus (37.8%; n = 4484), followed by Escherichia coli (11.0%) and Streptococcus spp. (10.0%). Delafloxacin susceptibility for S. aureus was 92.4% (MIC50/90, ≤0.004/0.25 mg/L), streptococci 98.4% and E. coli 58.1%. Delafloxacin was more active against S. aureus than levofloxacin (84.0% intermediate; MIC50/90, 0.25/>4 mg/L) and moxifloxacin (84.3% susceptible; MIC50/90, ≤0.06/2 mg/L). Susceptibility of E. coli was similar for the three quinolones. Conclusions Delafloxacin had broad-spectrum activity and improved potency against Gram-positive pathogens compared with levofloxacin and moxifloxacin. These data suggest that delafloxacin may be a useful therapeutic choice for the most common causes of ABSSSI.

This study evaluated the in vitro antimicrobial activity of telavancin against a large collection of Gram-positive pathogens of clinical importance, which were collected worldwide from 2015 through...

The antimicrobial activities of several β-lactam agents were tested by broth microdilution alone and in combination with a new polymyxin analog, SPR741 (at a fixed concentration of 8 mg/L), against a challenge set of clinical isolates (202

Background POL7306 belongs to a new class of peptidomimetic outer-membrane-protein-targeting antibiotics with a novel mechanism of action. POL7306 is in development for the treatment of infections caused by antimicrobial-resistant Gram-negative bacteria and has demonstrated low cytotoxicity and nephrotoxicity. Methods A total of 891 isolates were collected by the SENTRY Antimicrobial Surveillance Program from 134 medical centres in Europe (n = 424; 41 centres in 18 nations), the USA (n = 411 isolates from 67 centres), the Asia-Pacific region (n = 24; 15 centres in 6 nations) and Latin America (n = 32; 11 centres in 9 nations) and included 558 Enterobacterales, 310 non-fermenters and 23 fastidious organisms. Susceptibility testing was performed using the reference broth microdilution method and the medium was supplemented with 0.002% polysorbate-80 for testing POL7306. Resistant subsets were characterized by WGS. Results POL7306 demonstrated potent in vitro activity against Enterobacterales [including carbapenem-resistant (MIC50/90, 0.06/0.25 mg/L), ESBL-producing (MIC50/90, 0.06/0.12 mg/L), KPC-producing (MIC50/90, 0.12/0.25 mg/L), MBL-producing (MIC50/90, 0.06/0.25 mg/L), colistin-non-susceptible, mcr-negative (MIC50/90, 0.5/2 mg/L) and mcr-positive (MIC50/90, 0.12/0.25 mg/L) Enterobacterales], Pseudomonas aeruginosa (MIC50/90, 0.25/0.25 mg/L), Acinetobacter baumannii (MIC50/90, 0.06/0.12 mg/L) and Stenotrophomonas maltophilia (MIC50/90, 0.06/0.25 mg/L). Conclusions POL7306 demonstrated potent activity against a large collection of Gram-negative organisms collected worldwide that included colistin-resistant, XDR and ESBL- and carbapenemase-producing isolates for which there are currently limited treatment options.

Bone and joint infections (BJIs) present significant treatment challenges. Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus, is approved in many European and other countries for the treatment of adults with community- and hospital-acquired pneumonia, excluding ventilator-associated pneumonia. In this study, the in vitro activity of ceftobiprole and comparators was evaluated against clinical isolates collected from BJIs in the USA from 2016 to 2020. Gram-positive pathogens made up 70.6% of all BJI isolates and included S. aureus (47.4% of all isolates), β-hemolytic streptococci, coagulase-negative staphylococci, and Enterococcus faecalis. Ceftobiprole was highly active against S. aureus (MIC

Tedizolid activity was compared with other agents with oral and intravenous formulations against community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Tedizolid (MIC50/90, 0.12/...

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions. Tedizolid (0.12 mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC

Ceftolozane-tazobactam is a combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. Ceftolozane-tazobactam was approved by the US Food and Drug Administration in 2014 and by the European Medicines Agency in 2015 for use in adults to treat complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections with metronidazole. Studies for paediatric indications are planned. The Programme to Assess Ceftolozane-Tazobactam Susceptibility monitors the resistance of ceftolozane-tazobactam to Gram-negative isolates worldwide. In total, 6240 Gram-negative isolates were collected between 2012 and 2016 from paediatric patients (

Bacterial skin infections result in significant morbidity and have contributed to enhanced health-care resource utilization. The problem is heightened by emerging antimicrobial resistance. Multiple novel agents active against resistant pathogens that cause skin infections—including dalbavancin, tedizolid phosphate, oritavancin, and delafloxacin—have been approved over the past 5 years. Common features of these agents include gram-positive activity and favorable safety. Of these agents, delafloxacin is unique in being active against both gram-positive and gram-negative pathogens that cause skin infections, including those resistant to other antimicrobial agents. It is, therefore, an effective option for the treatment of skin infections.

BackgroundThe SENTRY Antimicrobial Surveillance Program monitors the frequency of occurrence and antimicrobial susceptibility of organisms from various infection types worldwide. In this investigation, we evaluated the antimicrobial susceptibility of Streptococcus pneumoniae isolates collected worldwide over 20 years (1997–2016).MethodsA total of 65 993 isolates were consecutively collected (1 per infection episode) from North America (NA; n = 34 626; 2 nations), Europe (EUR; n = 19 123; 23 nations), the Asia-Pacific region (APAC; n = 7111; 10 nations), and Latin America (LATAM; n = 5133; 7 nations) and tested for susceptibility using reference broth microdilution methods. Resistant subgroups included multidrug-resistant (MDR; nonsusceptible to ≥3 classes of agents) and extensively drug-resistant (XDR; nonsusceptible to ≥5 classes).ResultsThe isolates were collected primarily from respiratory tract infections (77.3%), and 25.4% were from pediatric patients. Penicillin susceptibility (≤0.06 mg/L) rates varied from 70.7% in EUR to 52.4% in APAC for all years combined. In NA, there was a slight improvement in susceptibility for the first few years of the program, from 66.5% in 1997–1998 to 69.4% in 1999–2000, followed by a decline until 2011–2012 (57.0%). Similar declines in penicillin susceptibility rates were observed in all regions, with the lowest rates of 67.3% in EUR (2011–2012), 41.6% in the APAC region (2007–2008), and 48.2% in LATAM (2013–2014). These declines were followed by improved susceptibility rates in all regions in later program years, with susceptibility rates of 55.6% to 71.8% in 2015–2016 (65.8% overall). Susceptibility rates to ceftriaxone, erythromycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole followed a similar pattern, with a decrease in the first 12–14 years and a continued increase in the last 6–8 years of the program. MDR and XDR frequencies were highest in APAC (49.8% and 17.3% overall, respectively) and lowest in LATAM (10.8% and 1.9% overall, respectively). The most active agents for MDR/XDR isolates were ceftaroline (99.7%/99.1% susceptible), tigecycline (96.8%/95.9% susceptible), linezolid (100.0%/100.0% susceptible), and vancomycin (100.0%/100.0% susceptible).ConclusionsS. pneumoniae susceptibility to many antibiotics increased in all regions in the last few years, and these increases may be related to PCV13 immunization, which was introduced in 2010.

Surveillance represents an important informational tool for planning actions to monitor emerging antimicrobial resistance. Antimicrobial resistance surveillance (ARS) programs may have many different designs and can be grouped in 2 major categories based on their main objectives: (1) public health ARS programs and (2) industry-sponsored/product-oriented ARS programs. In general, public health ARS programs predominantly focus on health care and infection control, whereas industry ARS programs focus on an investigational or recently approved molecule(s). We reviewed the main characteristics of industry ARS programs and how these programs contribute to new drug development. Industry ARS programs are generally performed to comply with requirements from regulatory agencies responsible for commercial approval of antimicrobial agents, such as the US Food and Drug Administration, European Medicines Agency, and others. In contrast to public health ARS programs, which typically collect health care and diverse clinical data, industry ARS programs frequently collect the pathogens and perform the testing in a central laboratory setting. Global ARS programs with centralized testing play an important role in new antibacterial and antifungal drug development by providing information on the emergence and dissemination of resistant organisms, clones, and resistance determinants. Organisms collected by large ARS programs are extremely valuable to evaluate the potential of new agents and to calibrate susceptibility tests once a drug is approved for clinical use. These programs also can provide early evaluations of spectrum of activity and postmarketing trends required by regulatory agencies, and the programs may help drug companies to select appropriate dosing regimens and the appropriate geographic regions in which to perform clinical trials. Furthermore, these surveillance programs provide useful information on the potency and spectrum of new antimicrobial agents against indications and organisms in which clinicians have little or no experience. In summary, large ARS programs, such as the SENTRY Antimicrobial Surveillance Program, contribute key data for new drug development.

Background The management of endocarditis requires aggressive and prolonged antimicrobial treatment. We evaluated the in vitro activity of dalbavancin against bacteria from patients with infective endocarditis. Methods A total of 626 Gram-positive organisms were collected from patients with a diagnosis of bacterial endocarditis in the USA (n = 222) and Europe (n = 404) from 2007 to 2017 via the SENTRY Antimicrobial Surveillance Program and were tested for susceptibility to dalbavancin and comparators by broth microdilution. Results The most common organisms were Staphylococcus aureus (48.4%), Enterococcus faecalis (19.6%) and viridans group streptococci (VGS; 12.5%). Dalbavancin and daptomycin showed complete activity (100.0% susceptibility per CLSI criteria) against S. aureus, but dalbavancin MIC values were 4- to 8-fold lower. Vancomycin, linezolid and teicoplanin were also active against all S. aureus when CLSI criteria were applied. Ceftaroline was active against all MSSA (MIC90 0.25 mg/L) and 78.4% of MRSA isolates at ≤1 mg/L. All E. faecalis isolates were susceptible to ampicillin, daptomycin and linezolid, whereas 97.6% of isolates were susceptible to dalbavancin (MIC90 0.06 mg/L) and 96.7% were susceptible to vancomycin (MIC90 2 mg/L). All VGS and CoNS isolates were susceptible to dalbavancin, daptomycin, vancomycin and linezolid. Against Enterococcus faecium, 65.7% of isolates were inhibited by ≤0.25 mg/L dalbavancin and 62.9% were vancomycin susceptible. Conclusions Dalbavancin exhibited potent in vitro activity against a large collection of Gram-positive isolates recovered from patients with endocarditis in US and European medical centres. These results support further investigations to determine the role of dalbavancin in the treatment of infective endocarditis.

Fosfomycin and comparators were susceptibility tested against over 2200 contemporary clinical isolates from US medical centers. Fosfomycin was active against Enterobacterales (MIC50/90, 4/16 μg/mL), including multidrug-resistant isolates. Potent activity was exhibited against gram-positive organisms, including Staphylococcus aureus (MIC50/90, 4/8 μg/mL). Fosfomycin may provide a promising alternative option for treatment of infections where resistant bacteria may occur.

Pneumonia and skin and skin structure infections (SSSIs) caused by S. aureus can lead to serious bloodstream infections (BSIs). This study reports on potent telavancin in vitro activity (MIC90, 0.06 μg/mL; 100% susceptible) against 674 US S. aureus causing pneumonia or SSSI with associated BSI in hospitalized patients during 2012–2016.

KBP-7072 is a novel third-generation tetracycline (aminomethylcycline) antibacterial that overcomes common efflux and ribosomal protection resistance mechanisms that cause resistance in older-generation tetracyclines. KBP-7072 completed phase 1 clinical development studies for safety, tolerability, and pharmacokinetics (ClinicalTrials.gov identifier NCT02454361) and multiple ascending doses in healthy subjects (ClinicalTrials.gov identifier NCT02654626) in December 2015. Both oral and intravenous formulations of KBP-7072 are being developed. In this study, we evaluated the in vitro activities of KBP-7072 and comparator agents by CLSI document M07 (2018) broth microdilution against 531 recent geographically diverse and/or molecularly characterized Acinetobacter baumannii-A. calcoaceticus species complex (A. baumannii) isolates from the United States, Europe, Asia-Pacific (excluding China), and Latin America. A. baumannii isolates included carbapenem-resistant, colistin-resistant, tetracycline-resistant, and extended-spectrum-β-lactamase (ESBL)- and metallo-β-lactamase (MBL)-producing isolates. Overall, KBP-7072 (MIC50/90, 0.25/1 mg/liter) was comparable in activity to colistin (92.8%/92.8% susceptible [S] [CLSI/EUCAST]) against A. baumannii isolates, inhibiting 99.2% of isolates at ≤2 mg/liter and 97.6% of isolates at ≤1 mg/liter. KBP-7072 was equally active against A. baumannii isolates, including carbapenem-resistant, colistin-resistant, and tetracycline-resistant isolates, regardless of geographic location, and maintained activity against ESBL- and MBL-producing isolates. KBP-7072 outperformed comparator agents, including ceftazidime (40.3% S [CLSI]), gentamicin (48.2%/48.2% S [CLSI/EUCAST]), levofloxacin (39.5%/37.9% S [CLSI/EUCAST]), meropenem (42.0%/42.0% S [CLSI/EUCAST]), piperacillin-tazobactam (33.3% S [CLSI]), and all tetracycline-class comparator agents, which include doxycycline (67.3% S [CLSI]), minocycline (73.8% S [CLSI]), tetracycline (37.2% S [CLSI]), and tigecycline (79.5% inhibited by ≤2 mg/liter). The potent in vitro activity of KBP-7072 against recent geographically diverse, molecularly characterized, and drug-resistant A. baumannii isolates supports continued clinical development for the treatment of serious infections, including those caused by A. baumannii.

Gepotidacin (GSK2140944) is a first in class, novel triazaacenaphthylene bacterial type II topoisomerase inhibitor in Phase 3 clinical development for the treatment of gonorrhea and uncomplicated urinary tract infections (acute cystitis). This study tested the equivalency of minimal inhibitory concentrations (MICs) obtained by two reference susceptibility testing methods, agar dilution and broth microdilution, for gepotidacin when tested against various gram-positive and gram-negative organisms. Equivalency, measured as the essential agreement >89.9%, was established between the two methods for determining gepotidacin susceptibility results against Staphylococcus spp., Streptococcus spp., and Escherichia coli. However, for Neisseria gonorrhoeae and Haemophilus influenzae, equivalency was not established. Agar dilution remains the sole dilution reference method for determining gepotidacin MICs against N. gonorrhoeae.

High-level aminoglycoside resistance was noted in 30.0% of Enterococcus faecalis and 25.2% of Enterococcus faecium isolates. Only 3.3% and 2.1% of E. faecalis isolates had elevated daptomycin MIC (≥2 mg/liter) and vancomycin resistance, respectively. In contrast, 37.4% to 40.3% of E. faecium isolates exhibited these phenotypes. Tedizolid inhibited 98.9% to 100.0% of enterococci causing serious invasive infections, including resistant subsets.

Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane/tazobactam has been approved in >60 countries for treating complicated urinary tract infections, acute pyelonephritis, complicated intra-abdominal infections (with metronidazole), and hospital-acquired pneumonia, including ventilator-associated pneumonia in adults. We analyzed susceptibilities for 35,882 gram-negative isolates collected from patients in 35 US medical centers from 2012 to 2018. The rate of multi-drug resistant Enterobacterales was stable (9.5%–10.1%), while the P. aeruginosa multi-drug resistance rate increased from 15.5% in 2012 to 22.9% in 2018. The carbapenem-resistant Enterobacterales rates varied from 0.9% to 2.2% and extended-spectrum β-lactamase phenotypes increased from 10.5% to 16.8%. The most active drugs against P. aeruginosa were ceftolozane/tazobactam (95.8%–97.5% susceptible) and amikacin (93.9%–98.0%); against Enterobacterales, amikacin (97.9%–98.8%), meropenem (97.7%–98.8%), and ceftolozane/tazobactam (93.3%–95.6%) were the most active. These data suggest that ceftolozane/tazobactam has effective in vitro activity against organisms causing serious gram-negative infections.

Background The Program to Assess Ceftolozane/Tazobactam Susceptibility (PACTS) monitors the in vitro activity of ceftolozane/tazobactam and numerous antimicrobial agents against Gram-negative bacteria worldwide. Objectives To evaluate the activity of ceftolozane/tazobactam and resistance trends among Pseudomonas aeruginosa and Enterobacterales isolates in Europe between 2012 and 2018. Methods P. aeruginosa (7503) and Enterobacterales (30 582) isolates were collected from 53 medical centres in 26 countries in Europe and the Mediterranean region and tested for susceptibility by reference broth microdilution method in a central laboratory. MIC results were interpreted using EUCAST criteria. Results Ceftolozane/tazobactam was the most active compound tested against P. aeruginosa isolates after colistin, with overall susceptibility rates of 94.1% in Western Europe and 80.9% in Eastern Europe. Moreover, ceftolozane/tazobactam retained activity against 75.2% and 59.2% of meropenem-non-susceptible P. aeruginosa isolates in Western and Eastern Europe, respectively. Tobramycin was the third most active compound tested against P. aeruginosa, with susceptibility rates of 88.6% and 70.9% in Western and Eastern Europe, respectively. Ceftolozane/tazobactam was active against 94.5% of all Enterobacterales and 96.1% of meropenem-susceptible isolates from Western Europe. In Eastern Europe, ceftolozane/tazobactam was active against 79.4% of Enterobacterales overall and 86.2% of meropenem-susceptible isolates. Discussion Antimicrobial susceptibility rates for agents commonly used to treat serious systemic infections varied widely among nations and geographic regions and were generally lower in Eastern Europe compared with Western Europe. Ceftolozane/tazobactam demonstrated potent activity against P. aeruginosa, including MDR strains, and retained activity against most meropenem-susceptible Enterobacterales causing infection in European medical centres.

The current antimicrobial market and old (pre-2000) in vitro antimicrobial susceptibility test interpretative criteria (STIC) are not working properly. Malfunctioning susceptibility breakpoints and antimicrobial markets have serious implications for both patients (ie, from a safety and efficacy perspective) and antibiotic-focused pharmaceutical and biotechnology company economic viability. Poorly functioning STIC fail both patients and clinicians since they do not discriminate between likely effective and ineffective antimicrobial regimens. Poor economic viability fails patients and clinicians as it decreases the industry’s ability to develop antimicrobial agents that clinicians and patients urgently require now and in the future. Herein, we review how STIC for older antimicrobial agents were determined and how their correction can impact the perceived utility of old relative to new antimicrobial agents. Moreover, we describe the data and analysis needs to systematically reevaluate older STIC values. We call for professional infectious diseases societies, government agencies, and other consensus bodies interested in the appropriate use of antimicrobial agents to join an effort to systematically evaluate and, where warranted, correct STIC for all relevant antimicrobial agents. This effort will amplify the effects of other measures designed to increase appropriate antimicrobial use (ie, good antimicrobial stewardship), development, and regulation.

High-level aminoglycoside resistance was noted in 30.0% of Enterococcus faecalis and 25.2% of Enterococcus faecium isolates. Only 3.3% and 2.1% of E. faecalis isolates had elevated daptomycin MIC (≥2 mg/liter) and vancomycin resistance, respectively. In contrast, 37.4% to 40.3% of E. faecium isolates exhibited these phenotypes. Tedizolid inhibited 98.9% to 100.0% of enterococci causing serious invasive infections, including resistant subsets. Oxazolidinone resistance was mainly driven by G2576T; however, optrA and poxtA genes were also detected, including poxtA in the United States and Turkey.

This study evaluated the in vitro activity of ceftolozane-tazobactam and comparators against 2647 Enterobacteriaceae and 355 Pseudomonas aeruginosa nonduplicate isolates collected from hospitalized patients with bloodstream infections in US hospitals from 2013 to 2015.Ceftolozane-tazobactam (95.5% susceptible), amikacin (99.2% susceptible), and meropenem (98.4% susceptible) were the most active against Enterobacteriaceae. For Enterobacteriaceae, 1.4% (n = 37) were carbapenem-resistant (CRE), and 10.2% (n = 271) exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. The most common ESBL enzyme detected was blaCTX-M-15-like (n = 159). Whereas ceftolozane-tazobactam showed good activity against ESBL non-CRE phenotype Enterobacteriaceae (87.1% susceptible), it lacked useful activity against CRE strains. Ceftolozane-tazobactam was the most potent (MIC50/90, 0.5/1 mg/L) β-lactam agent tested against P. aeruginosa isolates, with 97.5% susceptible. Only colistin was more active (98.9% susceptible). Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae.

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 (MIC(50/90), 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.

Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a β-lactamase inhibitor. Ceftolozane-tazobactam has been approved for treatment of complicated urinary tract infections and acute pyelonephritis, for complicated intra-abdominal infections (with metronidazole) in adults, and for hospital-acquired bacterial pneumonia including ventilator-associated bacterial pneumonia. This study analyzed gram-negative pathogen susceptibility in US and European patients who are considered at risk for infections caused by pathogens resistant to commonly used antimicrobials: patients in the intensive care unit (ICU), patients on the hematology/oncology or transplant service who may be immunocompromised, and patients >65 years old (yo). ICU patients had the lowest susceptibility for Enterobacterales and PSA. The susceptibility for isolates from the immunocompromised and >65 yo groups was similar. Ceftolozane-tazobactam was the most active agent against PSA, with ≥90%S for >65 yo and immunocompromised, and >80%S for ICU. Meropenem and ceftolozane-tazobactam were the most active agents against Enterobacterales.

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 (MIC(50/90), 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 (MIC(50/90), 0.06/0.12 mg/liter), viridans group streptococci (MIC(50/90), 0.06/0.12 mg/liter), and beta-hemolytic streptococci (MIC(50/90), 0.12/0.25 mg/liter), regardless of species and susceptibility to penicillin, macrolides, or tetracycline. Omadacycline was active against all Enterobacterales tested (MIC(50/90), 1/8 mg/liter; 87.5% of isolates were inhibited at ≤4 mg/liter) except Proteus mirabilis (MIC(50/90), 16/>32 mg/liter) and indole-positive Proteus spp. (MIC(50/90), 8/32 mg/liter) and was most active against Escherichia coli (MIC(50/90), 0.5/2 mg/liter), Klebsiella oxytoca (MIC(50/90), 1/2 mg/liter), and Citrobacter spp. (MIC(50/90), 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 (MIC(50/90), 0.5/1 mg/liter), regardless of β-lactamase status, and against Moraxella catarrhalis (MIC(50/90), ≤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.

The activity of meropenem/vaborbactam was evaluated against 11 559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Antimicrobial susceptibility testing for meropenem/vaborbactam (inhibitor at 8 mg/L) and comparators was performed by the reference broth microdilution method. CRE isolates were screened for the presence of genes encoding carbapenemases, and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 isolates (63.3% of the CRE; 1.8% of the overall Enterobacteriaceae population) carried blaKPC, including genes encoding KPC-2 (90 isolates), KPC-3 (117 isolates) and KPC-17 (2 isolates). Overall, meropenem/vaborbactam (vaborbactam at 8 mg/L) inhibited 99.3% of all Enterobacteriaceae isolates at the US-FDA susceptibility breakpoint of ≤4/8 mg/L. Meropenem alone inhibited 96.9% of the isolates at the current CLSI susceptibility breakpoint of ≤2 mg/L. Susceptibility rates for comparator antimicrobial agents tested against Enterobacteriaceae isolates ranged from 82.1-98.2% applying the CLSI breakpoints. Against CRE isolates, meropenem/vaborbactam displayed MIC50/90 values at 0.5/32 mg/L, whereas meropenem MIC50/90 values were 16/>32 mg/L. Meropenem/vaborbactam was very active against KPC-producers, and 99.5% of these isolates were inhibited by ≤4/8 mg/L. The single resistant isolate was shown to harbour an outer membrane porin alteration. Meropenem/vaborbactam had limited activity against MBL-producing isolates (including 49 NDM-, 1 IMP-64- and 2 VIM-producers) and/or oxacillinases (47 OXA-48/-232) that were detected mainly in European countries. Meropenem/vaborbactam was active against contemporary CRE and wild-type Enterobacteriaceae collected worldwide and this combination demonstrated enhanced activity compared with meropenem and most comparator agents against CRE and KPC-producers.

The polymyxins are important agents for carbapenem-resistant Gram-negative bacilli. The United States Committee on Antimicrobial Susceptibility Testing breakpoint recommendations for colistin and polymyxin B are that isolates of Pseudomonas aeruginosa , Acinetobacter baumannii , and Enterobacteriaceae are considered susceptible at MIC values of ≤2 mg/liter. These recommendations are contingent upon dosing and testing strategies that are described in this commentary.

Ceftazidime-avibactam was approved by the US Food and Drug Administration in 2015 to treat complicated intra-abdominal and urinary tract infections in adults and is under clinical development for treating pediatric patients.Among 53,381 Gram-negative organisms (1 per patient) collected in 2011-2015, 8461 (15.9%) were from pediatric (≤17 years old) patients. The isolates were collected from 82 US medical centers and susceptibility tested against ceftazidime-avibactam (avibactam at fixed 4 μg/mL) and comparators by reference broth microdilution methods. Susceptibility results were stratified by patient age: ≤1 (3671 isolates); 2-5 (1900); 6-12 (1644) and 13-17 years old (1246). Enterobacteriaceae with an extended-spectrum β-lactamase (ESBL) screening-positive phenotype were evaluated by microarray-based assay for genes encoding ESBLs, KPC, NDM and transferable AmpC enzymes.Ceftazidime-avibactam inhibited99.9% of all Enterobacteriaceae at the ≤8 μg/mL susceptible break point and was highly active against ESBL screening-positive phenotype Escherichia coli and Klebsiella pneumoniae. Overall, 83.6% of ESBL screening-positive phenotype K. pneumoniae were susceptible to meropenem. Only 1 of 4724 Enterobacteriaceae (0.02%) isolates was nonsusceptible to ceftazidime-avibactam, an Enterobacter aerogenes with a ceftazidime-avibactam minimum inhibitory concentration (MIC) value of 16 μg/mL and negative results for all β-lactamase tested. Ceftazidime-avibactam was very active against Pseudomonas aeruginosa (MIC50/90, 1/4 μg/mL; 99.1% susceptible), including isolates nonsusceptible to meropenem (94.0% susceptible to ceftazidime-avibactam) or piperacillin-tazobactam (91.7% susceptible) or ceftazidime (89.6% susceptible). Ceftazidime-avibactam activity against P. aeruginosa did not vary substantially among age groups (98.8%-99.3% susceptible) or year of isolation (98.5%-100.0% susceptible).Ceftazidime-avibactam was very active against a large collection of Gram-negative bacilli isolated from pediatric patients, including P. aeruginosa and Enterobacteriaceae with an ESBL screening-positive phenotype and resistant to carbapenems.

Tigecycline and comparators were tested by the reference broth microdilution method against 33 348 non-duplicate bacterial isolates collected prospectively in 2016 from medical centres in the Asia-Pacific (3443 isolates), Europe (13 530 isolates), Latin America (3327 isolates) and the USA (13 048 isolates). Among 7098 Staphylococcus aureus isolates tested, >99.9% were inhibited by ≤0.5 mg/L tigecycline (MIC 50/90 , 0.06/0.12 mg/L), including >99.9% of methicillin-resistant S. aureus and 100.0% of methicillin-susceptible S. aureus . Tigecycline was slightly more active against Enterococcus faecium (MIC 50/90 , 0.03/0.06 mg/L) compared with Enterococcus faecalis (MIC 50/90 , 0.06/0.12 mg/L) and its activity was not adversely affected by vancomycin resistance when tested against these organisms. Tigecycline potency was comparable for Streptococcus pneumoniae (MIC 50/90 , 0.03/0.06 mg/L), viridans group streptococci (MIC 50/90 , 0.03/0.06 mg/L) and β-haemolytic streptococci (MIC 50/90 , 0.06/0.06 mg/L) regardless of species and penicillin susceptibility. Tigecycline was active against Enterobacteriaceae (MIC 50/90 , 0.25/1 mg/L; 97.8% inhibited at ≤2 mg/L) but was slightly less active against Enterobacteriaceae isolates expressing resistant phenotypes: carbapenem-resistant Enterobacteriaceae (MIC 50/90 , 0.5/2 mg/L; 98.0% susceptible); multidrug-resistant (MIC 50/90 , 0.5/2 mg/L; 93.1% susceptible); and extensively drug-resistant (MIC 50/90 , 0.5/4 mg/L; 87.8% susceptible). Tigecycline inhibited 74.4% of 888 Acinetobacter baumannii isolates at ≤2 mg/L (MIC 50/90 , 2/4 mg/L) and demonstrated good in vitro activity against Stenotrophomonas maltophilia (MIC 50/90 , 1/2 mg/L; 90.6% inhibited at ≤2 mg/L) Tigecycline was active against Haemophilus influenzae (MIC 50/90 , 0.12/0.25 mg/L) regardless of β-lactamase status. Tigecycline represents an important treatment option for resistant Gram-negative and Gram-positive bacterial infections.

Susceptibility testing of ceftobiprole and comparators against 12,240 isolates was performed following CLSI/EUCAST guidelines. The percentage of susceptible MRSA isolates was higher for ceftobiprole (96.5% susceptible) than for ceftaroline (86.2% susceptible). Both ceftobiprole (MIC50/90, 0.5/2 mg/L) and ceftaroline (MIC50/90, 0.25/1 mg/L) demonstrated potent activity against coagulase-negative staphylococci. Ceftobiprole demonstrated good potency against Enterococcus faecalis (MIC50/90 values of 0.5/2 mg/L); ceftaroline (MIC50/90, 2/8 mg/L) was 4-fold less active against these strains. Ceftobiprole activity was comparable to that of the other β-lactam agents tested against S. pneumoniae (MIC90, 0.5 mg/L vs 0.12-2 mg/L [other β-lactams]), viridans-group streptococci (MIC90,0.25 mg/L vs 0.006-1 mg/L [other β-lactams]), and β-hemolytic streptococci (MIC90,0.03 mg/L vs 0.015-0.06 mg/L [other β-lactams]). Overall, 73.8% of Enterobacteriaceae isolates tested were susceptible to ceftobiprole. Ceftobiprole inhibited 70.4% of P. aeruginosa at ≤4 mg/L and all isolates of Haemophilus influenzae and Moraxella catarrhalis at ≤ 0.5 mg/L. Ceftobiprole was active in vitro against a broad range of clinically-relevant contemporary Gram-positive and Gram-negative bacterial isolates.

To report the linezolid activity, resistance mechanisms and epidemiological typing of selected isolates observed during the 2016 Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) programme.A total of 8325 organisms were consecutively collected from 76 centres in 42 countries (excluding the USA). Broth microdilution susceptibility testing was performed and isolates displaying linezolid MICs of ≥4 mg/L were molecularly characterized.Linezolid inhibited 99.8% of all Gram-positive pathogens at the respective susceptible breakpoints and showed a modal MIC of 1 mg/L, except for CoNS, for which the modal MIC result was 0.5 mg/L. Among isolates displaying linezolid MICs of ≥4 mg/L, one Staphylococcus aureus (linezolid MIC of 4 mg/L) harboured cfr and belonged to ST72, while four CoNS (MICs of 16-32 mg/L; ST2) showed drug target alterations. Two Enterococcus faecium (ST117) from a single site in Rome were linezolid non-susceptible (MICs of 8 mg/L) and had G2576T mutations. Eight linezolid-non-susceptible Enterococcus faecalis (MICs of 4 mg/L; 4 sites in 4 countries; ST256, ST480, ST766 and ST775) carried optrA and isolates carrying optrA from the same medical centre were genetically related. One Streptococcus gallolyticus (MIC of 4 mg/L) and one Streptococcus mitis (MIC of 16 mg/L) carried optrA and G2576T mutations, respectively.These results document the continued long-term in vitro potency of linezolid. Alterations in the 23S rRNA and/or L3/L4 proteins remain the main oxazolidinone resistance mechanisms in E. faecium and CoNS, whereas optrA emerged as the sole mechanism in E. faecalis. Surveillance and infection control will be important strategies to detect optrA and prevent it from disseminating.

Background Osteomyelitis is a difficult-to-treat infection that regularly involves prolonged use of systemic antibiotics. Dalbavancin has demonstrated activity against Gram-positive isolates, and has been considered as a candidate for the treatment of osteomyelitis in adults and children. This study evaluated the activity of dalbavancin against pathogens isolated from bone and joint infections (BJI). Methods Eight hundred and one Staphylococcus aureus, 160 coagulase-negative staphylococci (CoNS), 164 β-haemolytic streptococci (BHS), 82 Enterococcus faecalis and 45 viridans group streptococci (VGS) causing BJI were collected consecutively (2011–2016) and tested for susceptibility by broth microdilution methods. Results S. aureus (64.0%) was the most common pathogen associated with BJI, followed by BHS (13.1%) and CoNS (12.8%). All S. aureus (33.3% meticillin-resistant) isolates were susceptible to dalbavancin, linezolid and vancomycin, while daptomycin and clindamycin showed susceptibility rates of 99.5% and 89.0%, respectively. The minimum inhibitory concentration (MIC) results for dalbavancin were at least eight-fold lower than these comparators against all S. aureus. Dalbavancin was the most potent agent against CoNS (63.1% meticillin-resistant), followed by daptomycin, linezolid and vancomycin. All E. faecalis isolates were inhibited by dalbavancin at ≤0.25 mg/L (US Food and Drug Administration susceptibility breakpoint), except for three vancomycin-resistant isolates. High susceptibility rates for ampicillin (98.8%), daptomycin (100.0%), linezolid (100.0%) and vancomycin (95.1%) were obtained against E. faecalis. Dalbavancin was very active against BHS (MIC90 ≤0.03 µg/mL), and was the most active agent against VGS (highest MIC ≤0.06 mg/L). Ceftriaxone, daptomycin and vancomycin were also active (93.3–100.0% susceptible) against VGS, whereas clindamycin (84.4% susceptible) had marginal activity. Conclusion Dalbavancin appears to be a viable candidate for treating BJI/osteomyelitis caused by Gram-positive cocci.

The aim of this study was to evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Enterobacteriaceae and Pseudomonas aeruginosa isolates from patients in the Asia-Pacific (APAC) region with healthcare-associated infections. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. A total of 1963 Gram-negative organisms (489 P. aeruginosa and 1474 Enterobacteriaceae) were consecutively collected using a prevalence-based approach from 14 medical centres in the APAC region. Antimicrobial susceptibility testing was performed by broth microdilution method as described by the CLSI and the results were interpreted according to EUCAST and CLSI breakpoint criteria. Ceftolozane/tazobactam [MIC 50/90 , 0.25/4 µg/mL; 89.2/85.8% susceptible (CLSI/EUCAST)] and meropenem [MIC 50/90 , ≤0.06/≤0.06 µg/mL; 96.3/96.5% susceptible (CLSI/EUCAST)] were the most active compounds tested against Enterobacteriaceae. Isolates displayed susceptibility rates to other β-lactam agents ranging from 85.8/81.0% for piperacillin/tazobactam to 74.4/72.7% for cefepime and 72.8/68.1% for ceftazidime using CLSI/EUCAST breakpoints. Among the Enterobacteriaceae isolates, 3.6% were carbapenem-resistant Enterobacteriaceae (CRE) and 25.6% exhibited an extended-spectrum β-lactamase (ESBL) non-CRE phenotype. Ceftolozane/tazobactam showed good activity against ESBL non-CRE phenotype strains of Enterobacteriaceae (MIC 50/90 , 0.5/16 µg/mL), but not against isolates with a CRE phenotype (MIC 50/90 , >32/>32 µg/mL). Ceftolozane/tazobactam was the most potent (MIC 50/90 , 0.5/4 µg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 90.8% at an MIC of ≤4 µg/mL. Pseudomonas aeruginosa exhibited high rates of susceptibility to amikacin [91.2/89.4% (CLSI/EUCAST)] and colistin [98.4/100.0% (CLSI/EUCAST)]. Ceftolozane/tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins when tested against Enterobacteriaceae.

This study evaluated the in vitro activity of ceftolozane-tazobactam and comparator agents tested against Latin American isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients with health care-associated infections. Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor.A total of 2415 Gram-negative organisms (537 P. aeruginosa and 1878 Enterobacteriaceae) were consecutively collected in 12 medical centers located in four Latin American countries. The organisms were tested for susceptibility by broth microdilution methods as described by the CLSI M07-A10 document and the results interpreted according to EUCAST and CLSI breakpoint criteria. Results: Ceftolozane-tazobactam (MIC50/90, 0.25/32 μg/mL; 84.2% susceptible) and meropenem (MIC50/90, ≤0.06/0.12 μg/mL; 92.6% susceptible) were the most active compounds tested against Enterobacteriaceae. Among the Enterobacteriaceae isolates tested, 6.6% were carbapenem-resistant Enterobacteriaceae and 26.4% exhibited an extended-spectrum β-lactamase non-carbapenem-resistant phenotype. Whereas ceftolozane-tazobactam showed good activity against extended-spectrum beta-lactamase, non-carbapenem-resistant phenotype strains of Enterobacteriaceae (MIC50/90, 0.5/>32 μg/mL), it lacked useful activity against strains with a (MIC50/90, >32/>32 μg/mL; 1.6% S) carbapenem-resistant phenotype. Ceftolozane-tazobactam was the most potent (MIC50//90, 0.5/16 μg/mL) β-lactam agent tested against P. aeruginosa isolates, inhibiting 86.8% at an MIC of ≤4 μg/mL. P. aeruginosa exhibited high rates of resistance to cefepime (16.0%), ceftazidime (23.6%), meropenem (28.3%), and piperacillin-tazobactam (16.4%). Conclusions: Ceftolozane-tazobactam was the most active β-lactam agent tested against P. aeruginosa and demonstrated higher in vitro activity than available cephalosporins and piperacillin-tazobactam when tested against Enterobacteriaceae. Keywords: Ceftolozane-tazobactam, Drug resistance, Enterobacteriaceae, P. aeruginosa, Latin America, Surveillance

Background Unusual non-glucose fermenting Gram-negative (NFGN) pathogens, including Burkholderia cepacia species complex, Achromobacter spp, Alcaligenes spp, Aeromonas spp, and other genera, can cause serious hospital-acquired infections in immunocompromised patients. Some genera are inherently resistant to common drug classes and can acquire other resistance mechanisms, making them difficult to treat. In this study, we analyzed the susceptibility of NFGN isolates to minocycline (MIN). Isolates were collected as part of the SENTRY Antimicrobial Surveillance Program from 2014-2019. Methods From 2014-2019, unusual NFGN isolates were collected from hospitalized patients in 102 hospitals in 35 countries on 4 continents. Hospitals submitted 1 isolate per patient per infection episode that met local criteria for being the likely causative pathogen. Identification was performed by the submitting laboratory and confirmed by JMI Laboratories with matrix-assisted laser desorption ionization-time of flight mass spectrometry or other molecular methods as required. Isolates were tested for MIN susceptibility using the CLSI broth microdilution method at JMI Laboratories. All infection types were included in the susceptibility analysis. Results The most common infection from which the NFGN were isolated was pneumonia. The top 5 NFGN species were Achromobacter xylosoxidans (n=202), Burkholderia cepacia species complex (n=199), unspeciated Achromobacter (n=190), Aeromonas spp (n=127), including Aeromonas hydrophila (n=35), Chryseobacterium spp (n=59), and Alcaligenes faecalis (n=42). The % susceptible and MIC50/90 values of MIN for these species are shown in the table. Conclusion MIN had > 85% susceptible for the most frequently isolated unusual NFGN, including 92% susceptible for Achromobacter spp. and 85.9% for B. cepacia. These data suggest that MIN remains a useful treatment option for infections caused by unusual NFGN. Activities of MIN when tested against NFGN isolates Disclosures S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Robert K. Flamm, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)