Michael Pfaller

Michael Pfaller
JMI Laboratories · mycology

M.D.

About

965
Publications
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88,112
Citations
Citations since 2017
76 Research Items
19035 Citations
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201720182019202020212022202301,0002,0003,000

Publications

Publications (965)
Article
Full-text available
Background Omadacycline (OMC) is a novel tetracycline class (aminomethylcycline) antibacterial FDA approved for treatment of acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) caused by indicated organisms. OMC is active against bacterial isolates expressing resistance to tetracycline, penic...
Article
Full-text available
Background Manogepix is a new antifungal with a novel mechanism of action and potent in vitro activity against Candida (except C. krusei), Aspergillus, and rare mold isolates. The manogepix prodrug fosmanogepix is in Phase 2 development for the treatment of invasive mold infections caused by Aspergillus and rare molds (NCT04240886) and has complete...
Article
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Background Azole resistance in Aspergillus fumigatus (AFM) is mainly associated with mutations in cyp51A and its promoter region or its homologue cyp51B. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against 660 AFM collected during 2017–2020. Methods Isolates from Europe...
Article
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Background Invasive fungal infection (IFI) is associated with high mortality rates in critically ill patients. Appropriate antifungal treatment is crucial for managing IFI. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against contemporary moulds from ICU and non-ICU patien...
Article
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Purpose: To evaluate the in vitro activity of ceftolozane/tazobactam and comparator agents tested against Pseudomonas aeruginosa and Enterobacterales isolates from hospitalised patients in Asia. Ceftolozane/tazobactam is an antipseudomonal cephalosporin combined with a well-established β-lactamase inhibitor. Methods: A total of 2038 Gram-negativ...
Article
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We evaluated the in vitro activity of manogepix and comparator agents against 1,435 contemporary fungal isolates collected worldwide from 73 medical centers in North America, Europe, the Asia-Pacific region, and Latin America during 2020. Of the isolates tested, 74.7% were Candida spp.; 3.7% were non-Candida yeasts, including 27 Cryptococcus neofor...
Article
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Combination antifungal therapy is widely used but not well understood. We analyzed the spectrophotometric readings from a multicenter study conducted by the New York State Department of Health to further characterize the in vitro interactions of the major classes of antifungal agents against Candida spp. Loewe additivity-based fractional inhibitory...
Article
Objectives : Ceftolozane-tazobactam (C-T) is an anti-pseudomonal cephalosporin combined with a well-described β-lactamase inhibitor. C-T has enhanced activity against Pseudomonas aeruginosa, and activity against Enterobacterales isolates that produce extended-spectrum β-lactamases (ESBL) or AmpC cephalosporinases. In this study, we analysed the sus...
Article
As bone and joint infections (BJIs) frequently require prolonged, systemic antibiotic use, tedizolid is an attractive candidate for BJI therapy in adults and children. Tedizolid activity was evaluated against 1,193 Gram-positive isolates causing BJI in American (USA), European (EUR), Latin American (LATAM), and Asian-Pacific (APAC) medical centers....
Article
Background: Rezafungin, a new echinocandin with an extended half-life, exhibits potent activity against Candida spp. Aside from the MIC, specific interactions between antifungal and isolate, including the duration of anti-infective activity, may impact dose interval choices and infection outcome. Objectives: We evaluated rezafungin and micafungi...
Article
What is this summary about? Fungi are types of microbes that include molds and yeasts. Fungal infections can make people ill and can even cause death, especially in older people. They can be treated using antifungal drugs, but some fungi are drug resistant. This means the drug cannot kill the fungi. This is a summary based on a study that looked at...
Article
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Studies demonstrated the impact of the COVID-19 pandemic in the prevalence and susceptibility profiles of bacterial and fungal organisms. We analyzed 4821 invasive fungal isolates collected during 2018, 2019, and 2020 in 48 hospitals worldwide to evaluate the impact of this event in the occurrence and susceptibility rates of common fungal species....
Article
Objectives We evaluated the azole resistance mechanisms and epidemiology of fluconazole-resistant C. glabrata from a global survey. Methods A total of 2,992 Candida spp. isolates collected during 2018-2019 were susceptibility tested by the broth microdilution reference method following CLSI guidelines. Fluconazole-resistant C. glabrata isolates we...
Article
Bone and joint infections (BJIs) present significant treatment challenges. Ceftobiprole, a broad-spectrum cephalosporin with activity against methicillin-resistant Staphylococcus aureus (MRSA), is approved in many European and other countries for the treatment of adults with community- and hospital-acquired pneumonia, excluding ventilator-associate...
Article
Rezafungin is a new echinocandin under development for the treatment of candidemia and invasive candidiasis. CLSI recently approved provisional susceptible-only breakpoints and epidemiological cutoff values for Candida spp. and rezafungin. The activities of rezafungin and comparators against 2019 to 2020 invasive fungal isolates was evaluated by ap...
Article
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Background Multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA) present significant treatment challenges and can cause serious morbidity and mortality. Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced cephalosporin approved in many European and other countries for the treatment of adu...
Article
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Background Rezafungin (RZF) is a new echinocandin (ECH) with a long half-life and front-loaded drug exposure that allow for once-weekly intravenous administration. RZF is under Phase 3 development for the treatment of candidemia and invasive candidiasis and the prevention of invasive fungal disease caused by Candida, Aspergillus, and Pneumocystis s...
Article
We utilized the SENTRY surveillance database from 2017 through 2019 to address pathogen frequency and antifungal resistance among 4,497 clinical isolates of fungi from patients who were either ≥65 years (2,170 isolates) or between 18 and 64 years of age (2,327 isolates). The younger population was more frequently infected with non-Candida yeasts an...
Article
Objectives Omadacycline was tested against 7,000 bacterial isolates collected prospectively from medical centers in the United States during 2019. Methods Susceptibility testing followed Clinical and Laboratory Standards Institute guidelines. Results Omadacycline was active against Staphylococcus aureus (MIC50/90, 0.12/0.25 mg/L; 98.3% susceptibl...
Article
Full-text available
Objectives This study evaluated the in vitro activity of KBP-7072 against 413 contemporary surveillance isolates, including subsets with known tetracycline resistance genes. Materials In total, 105 Klebsiella pneumoniae (51 tetracycline resistant), 103 Escherichia coli (52 tetracycline resistant), 103 Staphylococcus aureus (51 tetracycline resista...
Article
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Objectives : To report on the activity of ceftolozane-tazobactam and comparators against P. aeruginosa isolates collected from hospitalized patients with pneumonia in US intensive care units between 2015 through 2018. Activity against all P. aeruginosa and common resistant phenotypes are described to better inform decision-making and support antimi...
Article
The epidemiology of invasive filamentous fungal diseases requires monitoring due to changes in susceptibility patterns of new and established antifungal agents that may affect clinical practices. We evaluated the activity of posaconazole against 2,157 invasive moulds collected worldwide from 2010 to 2017. The isolates included 1,775 Aspergillus spp...
Article
Life-threatening infections can be caused by a fungus called Candida auris (shortened to C. auris) that is found in the hospital environment. This study looked at how well different drugs could treat C. auris infection. Samples were collected from 36 people who had C. auris infection. The samples were treated with single drugs and in combination. W...
Article
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Antifungal surveillance is an important tool to monitor the prevalence of uncommon fungal species and increasing antifungal resistance throughout the world, but data comparing results across several different Asian countries are scarce. In this study, 372 invasive molds collected in the Asia-Western Pacific region in 2011–2019 were susceptibility t...
Article
Objectives Manogepix, the active moiety of the prodrug fosmanogepix, is a novel antifungal with activity against major fungal pathogens including Candida (except C. krusei), Aspergillus, and difficult-to-treat/rare moulds. We tested manogepix and comparators against 2,669 contemporary (2018-2019) fungal isolates collected from 82 medical centers lo...
Article
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Objectives The activity of mould-active azoles was evaluated against 397 filamentous fungi causing invasive mould infections (IMI) worldwide. In addition, a tentative posaconazole epidemiological cut-off value (ECV) against Aspergillus fumigatus was investigated. Methods Isolates were susceptibility tested by the CLSI reference broth microdilution...
Article
We evaluated 35 azole‐nonwildtype A. fumigatus isolates that were collected during 2017‐2018 using whole genome sequencing (WGS) to detect alterations in the genes involved in the ergosterol biosynthesis as well as other genes associated with azole resistance. Among 297 A. fumigatus isolates collected worldwide, 36 isolates displayed nonwildtype MI...
Article
Background Outbreaks of fungal bloodstream infection (BSI) are uncommon among hemodialysis patients. We investigated an outbreak of Candida tropicalis BSIs involving patients at 3 of 4 affiliated hemodialysis units. Methods An investigation included a review of records of patients with C. tropicalis BSI, a case-control study, and cultures of medic...
Article
A total of 15 Candida auris isolates from the SENTRY Antimicrobial Surveillance Program between 2006 and 2019 were combined with 21 isolates from other collections for the evaluation of antifungal susceptibility and synergy against anidulafungin plus voriconazole or isavuconazole using the checkerboard method. Surveillance isolates were analyzed fo...
Article
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Background Fox Chase Chemical Diversity Center (FCC) is developing non-peptide analogs of host defense proteins for the treatment of invasive fungal infections mainly caused by Candida (CAN) and Aspergillus (ASP). We evaluated the activity of 6 novel compounds and 2 comparators against 150 isolates from 15 fungal groups. Methods Susceptibility tes...
Article
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Background Omadacycline (OMC) is a new aminomethylcycline antibacterial drug belonging to the tetracycline class, for intravenous or oral administration. It is well tolerated and has proven effective in the treatment of a variety of bacterial infections. OMC is active against bacterial strains expressing the most common clinically relevant tetracyc...
Article
Full-text available
Background Bone and joint infections (BJIs) cause serious morbidity and mortality and present significant treatment challenges. Ceftobiprole medocaril, the prodrug of ceftobiprole, is an advanced cephalosporin approved in many European and non-European countries for the treatment of adults with community- and hospital-acquired pneumonia, excluding...
Article
Full-text available
Background Existing antifungal agents are active against many common fungal pathogens; however, breakthrough fungal infections occur and often involve less frequently encountered yeast and mould isolates. These rarer isolates tend to exhibit diminished susceptibility to current agents. Manogepix (MGX, APX001A) is a novel inhibitor of the fungal Gwt...
Article
Full-text available
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...
Article
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...
Article
Full-text available
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 stu...
Article
Full-text available
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 identifie...
Article
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 agai...
Article
Full-text available
We evaluated the activity of rezafungin and comparators using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods against worldwide collection of 2,205 invasive fungal isolates recovered from 2016-2018. Candida spp. (1,904 isolates; 6 species), Cryptococcus neoformans (73), Aspergillus fumigatus (183) and Aspergillus flav...
Article
The SENTRY Antimicrobial Surveillance Program has monitored bloodstream infections (BSIs) from patients in medical centers worldwide since 1997. In this report, we examine the frequency of occurrence and antimicrobial susceptibility profiles of 6741 bacterial and 222 fungal pathogens causing BSI in 16 medical centers from 2012 to 2017. These result...
Article
The increasing prevalence of uncommon fungal species and higher antifungal resistance has turned antifungal susceptibility testing into an important monitoring tool. In response, we evaluated the activity of isavuconazole against 522 clinical mold isolates collected worldwide in 2017-2018, including 436 Aspergillus spp. isolates and 86 non-Aspergil...
Article
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Background In 2016 USCAST, the National Advisory Committee (NAC) for the United States (US) to EUCAST, undertook the re-evaluation of the in vitro susceptibility (AST) test interpretive criteria (IC) for gentamicin (GM), tobramycin (TO) and amikacin (AK) against Enterobacteriaceae (ENT), P. aeruginosa (PSA) and S. aureus (SA) based on an analysis o...
Article
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Background In 2015 USCAST, the National Advisory Committee for the United States (US) to EUCAST, produced a report (Version 1.0) on their website (www.uscast.org) re-evaluating fluoroquinolone (FQ) breakpoint interpretive criteria (IC) based on analysis of current microbiology and pharmacokinetic/pharmacodynamic (PK/PD) data. EUCAST initiated a con...
Article
Full-text available
Background Echinocandins are the first-line treatment of candidemia. We evaluated the activity of rezafungin (RZF), a novel long-acting echinocandin with front-loaded drug exposure and extensive distribution to sites of infection, and comparators using CLSI broth microdilution methods against 709 invasive fungal isolates collected worldwide during...
Article
Full-text available
Background Omadacycline (OMC) was FDA approved to treat acute bacterial skin and skin structure infection (ABSSSI) and community-acquired bacterial pneumonia (CABP) for indicated organisms in 2018. Phase 2 OMC clinical trials for uncomplicated urinary tract infection (uUTI; NCT03425396) and acute pyelonephritis (NCT03757234) are ongoing. OMC is act...
Article
Full-text available
Objectives: Ceftolozane-tazobactam (C-T) is an antibacterial combination of an antipseudomonal cephalosporin and a β-lactamase inhibitor. C-T was approved in >60 countries for complicated urinary tract infections, acute pyelonephritis, and complicated intra-abdominal infections in combination with metronidazole. Data for Pseudomonas aeruginosa iso...
Article
This study evaluated the activity of echinocandins, azoles and amphotericin B against Candida spp. isolates and other yeasts and characterised azole resistance mechanisms in Candida parapsilosis and Candida tropicalis. Invasive Candida spp. isolates (n = 2936) collected in 60 hospitals worldwide during 2016-2017 underwent antifungal susceptibility...
Article
We evaluated the activity of minocycline and comparator agents against a large number of Stenotrophomonas maltophilia ( n = 1,289), Acinetobacter baumannii-Acinetobacter calcoaceticus species complex ( n = 1,081), and Burkholderia cepacia complex ( n = 101) collected during 2014 through 2018 from 87 U.S. medical centers spanning all nine census div...
Article
Full-text available
Objectives: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia. Methods: Patients with candidemia were identified by the electronic medical rec...
Article
Current antifungal agents cover a majority of opportunistic fungal pathogens; however, breakthrough invasive fungal infections continue to occur and increasingly involve relatively uncommon yeasts and molds, which often exhibit decreased susceptibility. APX001A (manogepix) is a first-in-class small-molecule inhibitor of the conserved fungal Gwt1 pr...
Article
Full-text available
Objectives: Candida auris emerged as a human pathogen in 2009 and has subsequently been identified around the world as a cause of invasive candidiasis. We did an analysis from a single institution in order to analyze risk factors and outcomes for C. auris candidemia. Methods: Patients with candidemia were identified by the electronic medical record...
Article
Full-text available
Background Pseudomonas aeruginosa remains an important cause of hospital-acquired infections in the United States and is frequently multidrug-resistant. The Infectious Diseases Society of America guidelines recommend empiric combination therapy that includes an anti-pseudomonal β-lactam with an aminoglycoside or fluoroquinolone likely to cover 95%...
Article
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 concentrati...
Article
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 =...
Article
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Bloodstream infection (BSI) organisms were consecutively collected from >200 medical centers in 45 nations between 1997 and 2016. Species identification and susceptibility testing followed Clinical and Laboratory Standards Institute broth microdilution methods at a central laboratory. Clinical data and isolates from 264,901 BSI episodes were collec...
Article
Full-text available
Delafloxacin, a recently approved anionic fluoroquinolone, was tested within an international resistance surveillance program. The in vitro susceptibilities of 7,914 indicated pathogens causing acute bacterial skin and skin structure infections (ABSSSI) were determined using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MIC...
Article
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Estimating epidemiological cutoff endpoints (ECVs/ECOFFS) may be hindered by the overlap of MICs for mutant and non-mutant strains (harboring or not harboring mutations, respectively). Posaconazole MIC distributions for Aspergillus fumigatus SC were collected from 26 laboratories (Australia, Canada, Europe, India, South/North America, Taiwan) and p...
Article
The in vitro activity of oritavancin was assessed against 44,715 gram-positive pathogens causing infections in European and United States (US) hospitals (2010-2014). There were no substantive differences (>±2-fold dilution) in oritavancin MIC50 or MIC90 values for different species/organism groups over time or by region. Oritavancin (99.9% suscepti...
Article
Omadacycline is an aminomethylcycline with in vitro activity against many gram-negative pathogens. Omadacycline and comparators were tested against Enterobacteriaceae from urinary tract infections (UTIs) selected from a 2014 global surveillance program and compared to results of isolates from 2010 surveillance. The omadacycline MIC50/90for Enteroba...
Article
Full-text available
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) demonstr...
Article
Objectives: 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 region (APAC) with health care associated infections (HAI). Ceftolozane-tazobactam is an antipseudomonal cephalosporin combined with a well-established...
Article
The activity of omadacycline and comparators when tested against a subset of Streptococcus pneumoniae from US and European regions of a 2014 global surveillance program (304 isolates) are reported. These MIC results were compared to those obtained when testing S. pneumoniae from 2010 surveillance (1,834 isolates). The omadacycline MIC50/90 for S. p...
Article
Objectives: To evaluate the in vitro activity of ceftolozane-tazobactam and comparator agents tested against isolates of Enterobacteriaceae and Pseudomonas aeruginosa from patients in Australia and New Zealand with healthcare-associated infection. Methods: A total of 1,459 gram-negative organisms (440P. aeruginosa and 1,019 Enterobacteriaceae) w...
Article
This study describes linezolid susceptibility testing results for 6,741 gram-positive pathogens from 60 U.S. sites collected during 2015 for the LEADER Program. In addition, the study summarizes linezolid in vitro activity, resistance mechanisms, and molecular typing obtained for 2011 to 2015. During 2015, linezolid showed potent activity when test...
Article
The activity of ceftolozane-tazobactam was compared to the activity of 7 antimicrobials against 3,851 Pseudomonas aeruginosa isolates collected from 32 US hospitals in the Program to Assess Ceftolozane-Tazobactam Susceptibility from 2012-2015. Ceftolozane-tazobactam and comparator susceptibilities were determined using the CLSI broth microdilution...
Article
A total of 18,386 organisms, including 13,224 Enterobacteriaceae, 3536 Pseudomonas aeruginosa, 1254 Acinetobacter spp., and 372 Stenotrophomonas maltophilia were collected from Western Europe (WEU; n = 10,021), Eastern Europe (EEU; n = 4957), and the Asia-Pacific region (APAC; n = 3408 [1052 from China]) in 2013–2014 as part of the SENTRY Antimicro...
Article
Omadacycline is a broad spectrum aminomethylcycline in late-stage clinical development for acute bacterial skin and skin structure infections and community-acquired pneumonia as both an oral and intravenous, once-daily formulation. In this report omadacycline and comparators were tested against 69,246 non-duplicate bacterial isolates collected pros...
Article
Full-text available
The in vitro activities of delafloxacin and comparator antimicrobial agents were tested against 6,485 bacterial isolates from medical centers in Europe (EU) and the United States (US) in 2014. Delafloxacin was the most potent agent tested against methicillin-susceptible S. aureus (MSSA), MRSA, Streptococcus pneumoniae, viridans group streptococci,...
Article
Full-text available
Objectives: To evaluate the in vitro activity of ceftolozane/tazobactam and comparators tested against European isolates of Enterobacteriaceae and Pseudomonas aeruginosa from hospitalized patients with urinary tract infection or intraabdominal infections. Methods: A total of 6553 Gram-negative organisms (603 P. aeruginosa and 5950 Enterobacteriacea...
Article
Full-text available
The activity of CD101 and comparators was evaluated against 606 invasive fungal isolates collected worldwide during 2014 using the CLSI method. All C. albicans (n=251), C. tropicalis (n=51), C. krusei (n=16), and C. dubliniensis (n=11) were inhibited by ≤0.12 μg/ml of CD101 and were susceptible or wild type to other echinocandins. Five C. glabrata...
Article
Omadacycline is a new broad spectrum aminomethylcycline in late stage clinical development for acute bacterial skin and skin structure infections (ABSSSI) and community-acquired pneumonia (CABP) as a once-daily formulation taken orally or intravenously. In this study, omadacycline and comparator agents were tested against 502 isolates of Staphyloco...
Article
Streptococcus pneumoniae isolates (2,614) were collected from patients at 135 U.S. Medical Centers during 2014. Isolates were evaluated for multidrug resistance to penicillin, ceftriaxone, erythromycin, tetracycline, trimethoprim-sulfamethoxazole, and levofloxacin. A single isolate (853008) demonstrated a ceftaroline nonsusceptible minimal inhibito...