bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbiology of Infected Walled-off Necrosis Following Severe Acute Pancreatitis
Authors: Chihara Shingo , Sahar Nadav , Kozarek Richard , Gluck Michael 
Published: October 2017

Abstract

Background
Formation of fluid collection occur in about 15–20% following severe acute pancreatitis. These fluid collections could become infected with bacterial and fungal organisms and form infected walled-off necrosis (WON). Management options for WON have evolved over the last decade from invasive surgical intervention to combined percutaneous and endoscopic approach (dual modality drainage (DMD). We describe the culture result of WON obtained with DMD.

Methods
The study was performed at Virginia Mason Medical Center, a tertiary medical center located in Seattle. We used a prospective, institutional review board-approved database which include onset of pancreatitis, size of WON, timing of drainage, duration of drain, culture result, antibiotics given, and patient information (gender, age and BMI). The data from December 2007 to December 2016 were analyzed. SAS was used for analysis.

Results
A total of 182 patients underwent DMD for symptomatic and infected walled off necrosis of which 76 grew organism with culture. Forty-two were monomicrobial while 34 were polymicrobial. For the monomicrobial isolates, coagulase negative staphylococcus was isolated most frequently (6), followed by Staphylococcus aureus (4) and viridans streptococcus (3). WON was significantly more likely to be seen in older patients (P = 0.008) and in obese patients (P = 0.06). The longest diameter of WON nor sex of the patient did not significantly factor into whether the culture grew no organism, one organism, or multiple organisms.

Conclusion
This is the largest data evaluating microbiology of infected walled off necrosis. Organisms isolated are mostly colonizers of skin and gastrointestinal tract. Positive cultures were seen more in obese and elder patients. Clinical correlation is needed when deciding whether to treat these organisms or not.

Disclosures
R. Kozarek, Boston Scientific: Investigator, Research support
Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa from ICU vs. non-ICU Isolates Collected in US Medical Centers
Authors: Shortridge Dee , Duncan Leonard R , Pfaller Michael A , Flamm Robert K 
Published: October 2017

Abstract

Background
Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of hospital-acquired pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. This study compares the activities of C-T and comparators against GN isolates from ICU patients and non-ICU patients.

Methods
A total of 3,100 GN ICU isolates and 3,271 isolates from non-ICU patients were collected from 30 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), cefepime (FEP), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). CLSI (2017) interpretive criteria were used for all except COL with Enterobacteriaceae (ENT), for which EUCAST (2017) criteria were used.

Results
The most common ENT species from ICU and non-ICU patients were similar. The 3 most common ENT for ICU and non-ICU isolates were Klebsiella pneumoniae, 24.1% and 25.8%; Escherichia coli, 19.4% and 18.2%; and Serratia marcescens, 14.7% and 14.3%, respectively. The most common non-enteric species was Pseudomonas aeruginosa (PSA) for ICU and non-ICU (72.7% and 78.2%). ICU ENT isolates generally had a lower %S than non-ICU (Table). ENT showed more variability than PSA for %S between ICU and non-ICU.

Conclusion
For ENT overall, MER and AMK were the most active, followed by C-T. Comparing ICU and non-ICU, MER and C-T were slightly more active vs. non-ICU ENT, while AMK %S was similar for both. For PSA, COL was the most active; C-T and AMK were similar. Activities between ICU and non-ICU isolates were similar for C-T and COL while AMK was more active vs. ICU isolates, and MER was more active vs. non-ICU. C-T showed potent activity against ICU and non-ICU isolates for ENT and PSA.

Disclosures
D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant
In Vitro Activity of Newer Antimicrobials and Relevant Comparators Vs. 349 Stenotrophomonas maltophilia Clinical Isolates Obtained from Patients in Canadian Hospitals (CANWARD, 2011–2016)
Authors: Walkty Andrew , Baxter Melanie , Adam Heather J , Lagace-Wiens Philippe , Karlowsky James , Zhanel George 
Published: October 2017

Abstract

Background
Stenotrophomonas maltophilia is a non-fermentative gram-negative bacillus that has emerged as an important opportunistic pathogen among hospitalized, debilitated patients. Treatment options for infections caused by this organism are limited because it is intrinsically resistant to antimicrobials from multiple different classes. The purpose of this study was to evaluate the in vitro activity of several newer antimicrobial agents (ceftazidime-avibactam [CZA], ceftolozane-tazobactam [C/T], moxifloxacin [MXF], tigecycline [TGC]) and relevant comparators [e.g., trimethoprim-sulfamethoxazole [TMP-SMX]) against a large collection of S. maltophilia clinical isolates obtained as part of an ongoing national surveillance study (CANWARD, 2011–2016).

Methods
From January 2011 to December 2016, inclusive, 12 to 15 sentinel hospitals across Canada submitted clinical isolates from patients attending ERs, medical and surgical wards, hospital clinics, and ICUs (CANWARD). Each center was asked to annually submit clinical isolates (consecutive, one per patient/infection site) from blood (100), respiratory (100), urine (25), and wound (25) infections. Susceptibility testing was performed using broth microdilution as described by CLSI. MICs were interpreted using CLSI breakpoints, where available.

Results
349 S. maltophilia clinical isolates were obtained as a part of CANWARD (86% from a respiratory source). The susceptibility profile of these isolates is presented below.

Conclusion
TMP-SMX continues to demonstrate excellent in-vitro activity against S. maltophilia clinical isolates. MXF and TGC may also prove useful in the treatment of infections caused by this pathogen.

Disclosures
G. Zhanel, Achaogen: Research relationship, Research support Astellas: Research relationship, Research support Merck Canada: Research relationship, Research support Merck USA: Research relationship, Research support Paratek Pharma: Research relationship, Research support Pharmascience: Research relationship, Research support Sunovion: Research relationship, Research support Tetraphase: Research relationship, Research support The Medicines Co.: Research relationship, Research support Zoetis: Research relationship, Research support
Assessment of the In Vitro Antifungal Activity of SCY-078 Against a Collection of C. parapsilosis Clinical Isolates
Authors: Barat Stephen , Angulo David , Borroto-Esoda Katyna , Ghannoum Mahmoud 
Published: October 2017

Abstract

Background
Global rates of candidemia caused by C. parapsilosis are increasing with differences detected between neonates and adult patients (50% vs. 12%, respectively) and across geographic regions (5% vs. 25% in Iceland and Spain, respectively). SCY-078 is a novel, oral and intravenous, triterpenoid glucan synthase inhibitor under development for the treatment of invasive candidiasis. This study evaluated the in vitro antifungal activity of SCY-078 against a collection of clinical C. parapsilosis isolates.

Methods
Retrospective analysis of data from 7 independent studies evaluating the activity of SCY-078 is presented. Data were available for 206 C. parapsilosis isolates collected between 2008 and 2015 in the US and EU. The collection included 186 wild-type isolates as well as 14 azole-resistant, and 6 echinocandin-resistant isolates. Minimum inhibitory concentrations (MIC) were determined according to the CLSI M27-A3 and EUCAST E.DEF 7.3 guidelines. Comparator compounds varied across studies and included fluconazole, micafungin (MCF), caspofungin (CSP), and anidulafungin (ANI). MIC50 and MIC90 values were defined as the concentrations inhibiting growth of 50% and 90% of isolates, respectively. Echinocandin and azole resistance were determined based on CLSI M27-A4 guidelines.

Results
The MIC50 values obtained for SCY-078 against the wild-type C. parapsilosis isolates across the 7 studies ranged from 0.25 to 1 μg/mL and the MIC90 values ranged from 0.25 -2 µg/mL. Among the echinocandins, MIC90 values ranged from 0.5 to 2 µg/mL (CSP), 1 to 4 µg/mL (MCF) and 2 to 4 µg/mL (ANI). SCY-078 was active against the 14 azole-resistant isolates (MIC ranging from 0.25 to 2 µg/mL). Similar activity was observed across the 6 echinocandin-resistant isolates with MIC values for SCY-078 ranging from 0.25 to 1 µg/mL. Among the 4 most recent studies in the US and EU (2013–2015) C. parapsilosis isolates represented 14 – 20% of the Candidaisolates; rates were similar in the EU and US.

Conclusion
SCY-078 demonstrated potent activity against C. parapsilosis clinical isolates. Notably, SCY-078 was effective against all the echinocandin and azole resistant C. parapsilosis isolates tested.

Disclosures
S. Barat, Scynexis, Inc: Employee, Salary; D. Angulo, Scynexis, Inc.: Employee, Salary; K. Borroto-Esoda, Scynexis Inc.: Consultant, Consulting fee; M. Ghannoum, Scynexis, Inc.: Consultant, Investigator and Scientific Advisor, Consulting fee, Research grant and Research support
In Vitro Activity of Eravacycline and Comparator Antimicrobials Against 143 Strains of Bacteroides Species.
Authors: Citron Diane , Tyrrell Kerin , Goldstein E 
Published: October 2017

Abstract

Background
Eravacycline (ERV is the first fully synthetic fluorocycline with activity against tetracycline (TET)-resistant organisms. In addition, it is 2–8 times more potent than tigecycline (TGC). Like other tetracyclines, it inhibits protein synthesis by binding to the 30S ribosomal subunit exhibiting a broad spectrum of activity. To further explore its activity, we tested 143 clinical isolates of Bacteroides and included TET, TGC and other drugs frequently used to treat serious infections.

Methods
Clinical isolates recovered during the past 3 years from patients in southern California were saved as pure cultures in 20% skim milk at −70°C. Prior to testing, they were transferred at least twice to ensure purity and good growth. Antimicrobials included ERV, TET, TGC, piperacillin-tazobactam (P-T), meropenem (MER), clindamycin (CLI), and metronidazole (MET). The method was agar dilution as described in the CLSI M11-A8 document for testing anaerobes using Brucella agar and incubation in the anaerobic chamber at 36°C for 44h. The MIC was defined as the lowest dilution that completely inhibited growth or resulted in a marked reduction compared with a drug-free growth control.

Results
The MIC90 values (µg/ml) for Bacteroides and Parabacteroides are presented in the table:

Conclusion
This study confirmed the improved activity of ERV over TGC against Bacteroides and suggests that ERV may be an appropriate choice for infections involving these organisms.

Disclosures
E. Goldstein, Tetraphase Pharmaceuticals: Research Contractor, Research grant
Activity of Tedizolid against Gram-Positive Clinical Isolates Causing Nosocomial- and Community-Acquired Infections in United States Hospitals (2014–2016)
Authors: Mendes Rodrigo E , Shortridge Dee , Arends S J Ryan , Sader Helio S , Castanheira Mariana , Flamm Robert K 
Published: October 2017

Abstract

Background
Tedizolid (TZD) was approved for the treatment of acute bacterial skin and skin structure infections and is also under investigation for the treatment of hospital-acquired (HA) bacterial pneumonia. The activity of TZD and comparators were evaluated against gram-positive (GP) pathogens causing community (CA)-acquired and HA infections in the US.

Methods
During the Surveillance of Tedizolid Activity and Resistance (STAR) Program, 10,091 GP isolates were recovered from patients in 31 US hospitals. Isolates were identified by standard biochemical algorithms and MALDI-TOF MS. Susceptibility (S) testing followed CLSI methods and CLSI/EUCAST interpretation. CA and HA infections were defined based on CDC criteria.

Results
TZD (MIC50/90, 0.12/0.12 µg/mL; 100.0%S) showed equivalent MIC50 and MIC90 values against MSSA and MRSA, regardless of infection type or origin of isolate (Table). Linezolid (LZD; MIC50/90, 0.5–1/1 µg/mL; 100.0%S), daptomycin (DAP; MIC50/90, 0.25/0.5 µg/mL; 99.5–100.0%S), vancomycin (VAN; MIC50/90, 0.5–1/1 µg/mL; 100.0%S) and trimethoprim-sulfamethoxazole (MIC50/90, ≤0.5/≤0.5 µg/mL; 93.0–99.5%S) were also active throughout against MSSA and MRSA, while MICs for other agents varied. TZD (MIC50/90, 0.12/0.25 µg/mL; 100.0%S) activities were consistent against E. faecalis causing various infections from different origins, as were LZD (MIC50/90, 1/1 µg/mL; 100.0%S), ampicillin (MIC50/90, 1/1–2 µg/mL; 100.0%S), DAP (MIC50/90, 1/1–2 µg/mL; 100.0%S), and VAN (MIC50/90, 1/2 µg/mL; 94.9–97.0%S), although these agents had MIC50 and MIC90 values 4- to 8-fold higher than TZD. TZD (MIC50/90, 0.12/0.25 µg/mL), LZD (MIC50/90, 1/1–2 µg/mL; 97.6–100.0%S) and DAP (MIC50/90, 1/2–4 µg/mL; 97.4–100.0%S) were active in vitro against E. faecium, regardless of infection type. S. pneumoniae isolates were S to several drugs tested, and ceftaroline showed the lowest MICs (MIC50/90, ≤0.015/0.06 µg/mL; 100.0%S).

Conclusion
TZD had potent in vitro activity against GP isolates causing CA and HA infections in US hospitals, regardless of infection site or bacterial species. The TZD in vitro potency was also generally higher than clinically available comparator agents.

Disclosures
R. E. Mendes, Merck: Research Contractor, Research grant; &#x2028;D. Shortridge, Merck: Research Contractor, Research grant; S. J. R. Arends, Merck: Research Contractor, Research grant; H. S. Sader, Merck: Research Contractor, Research grant; M. Castanheira, Merck: Research Contractor, Research grant; &#x2028;R. K. Flamm, Merck: Research Contractor, Research grant
Antimicrobial Activity of Ceftolozane–Tazobactam Tested against Contemporary (2012–2016) Enterobacteriaceae and Pseudomonas aeruginosa Isolates by US Census Division
Authors: Shortridge Dee , Duncan Leonard R , Pfaller Michael A , Flamm Robert K 
Published: October 2017

Abstract

Background
Ceftolozane-tazobactam (C-T) is a combination of a novel antipseudomonal cephalosporin and a well-described β-lactamase inhibitor. C-T was approved by the United States (US) Food and Drug Administration in 2014 for complicated urinary tract infections, including acute pyelonephritis and complicated intra-abdominal infections. C-T is currently in clinical trials for the treatment of nosocomial pneumonia. The Program to Assess Ceftolozane-Tazobactam Susceptibility (PACTS) monitors C-T resistance to gram-negative (GN) isolates worldwide. In this study, the activities of C-T and comparators vs. GN isolates from each of the 9 US Census divisions were compared.

Methods
A total of 18,856 Enterobacteriaceae (ENT) and 4,735 Pseudomonas aeruginosa (PSA) isolates were collected from 32 US hospitals in 2012–2016. Isolates were tested for susceptibility (S) to C-T and comparators by CLSI broth microdilution methodology in a central monitoring laboratory. Other antibiotics tested included amikacin (AMK), ceftazidime (CAZ), colistin (COL), meropenem (MER), and piperacillin-tazobactam (TZP). The following resistant phenotypes were analyzed for ENT: carbapenem resistant (CRE); extended-spectrum β-lactamase phenotype screen-positive (ESBL); and ESBL, nonCRE. or PSA, MER-nonsusceptible (NS), TZP-NS, and CAZ-NS isolates were analyzed. CLSI (2017) interpretive criteria were used.

Results
For all ENT, 94.2% were S to C-T, 91.5% were S to TZP, 98.0% were S to MER, and 98.8% were S to AMK; 1,697 (9.0%) were ESBL, nonCRE and 356 (1.9%) were CRE. For all PSA isolates, 97.4% were S to C-T, 99.3% were S to COL, 96.9% were S to AMK, and 81.2% were S to MER. The % C-T S for each division (DIV) are shown in the table. The % C-T S for ENT ranged from 98.1% (DIV 4) to 87.4% (DIV 2) and % C-T S for ESBL, nonCRE ranged from 93.8% in DIV 4 to 79.8% in DIV 7. For PSA, the % C-T S ranged from 99.6% in DIV 4 to 94.9% in DIV 9. Activity of C-T against PSA NS to MER, CAZ or TZP varied by division and was &gt;80% for all except DIV 9.

Conclusion
Against PSA, only COL was more active than C-T. C-T demonstrated potent activity against PSA NS to other β-lactams. For ENT, overall activity was good. For both PSA and ENT, C-T varied by DIV.

Disclosures
D. Shortridge, Merck: Research Contractor, Research grant; L. R. Duncan, Merck: Research Contractor, Research grant; M. A. Pfaller, Merck: Research Contractor, Research grant; R. K. Flamm, Merck: Research Contractor, Research grant
Effects of Iclaprim and Trimethoprim on Exotoxin Production by Methicillin-resistant Staphylococcus aureus
Authors: Bryant Amy , Katahira Eva , Huang David , Stevens Dennis 
Published: October 2017

Abstract

Background
Methicillin-resistant Staphylococcus aureus (MRSA) causes serious, often life-threatening, infections. Exotoxins such as alpha-hemolysin (AH), Panton Valentine leukocidin (PVL), and Toxic shock syndrome toxin 1 (TSST-1) mediate pathogenesis and inhibition of toxin production is an important consideration in choosing appropriate treatments. Vancomycin is recommended for severe MRSA infections; however, increasing vancomycin resistance, poor clinical outcomes and nephrotoxicity are serious concerns. Thus newer agents are needed, including those that block bacterial toxin production. In the current study, we compared the effects of sub-inhibitory doses (sub-MIC) of two folic acid inhibitor antibiotics (iclaprim, trimethoprim) with cell wall-active agents (nafcillin, vancomycin) on transcription and translation of AH, PVL and TSST-1 in two clinical MRSA isolates.

Methods
Community-acquired MRSA strains 1560 (a USA400 strain; AH+, TSST-1+, PVL-) and 04014 (CDC strain 368–04; AH+, TSST-1-, PVL+) were studied. MICs were determined by standard microbroth dilution. Gene expression was studied by northern blotting and/or qRT-PCR; toxins were quantitated by ELISA (PVL and TSST-1) and rabbit erythrocyte lysate assay (AH).

Results
In agreement with our previous findings, nafcillin increased production of AH, TSST-1, and PVL compared with untreated control cultures. In both MRSA strains, iclaprim and trimethoprim delayed the onset of mRNA production and shifted its peak production to later time points. Both iclaprim and trimethoprim suppressed AH production in both strains of MRSA and delayed, but did not reduce, maximal TSST-1 production in MRSA1560. Trimethoprim significantly increased maximal PVL production over both untreated and iclaprim-treated cultures.

Conclusion
The folic acid antagonist antibiotics, iclaprim and trimethoprim, altered both mRNA synthesis dynamics and protein toxin production in MRSA at concentrations below those that inhibit bacterial growth. These results, plus the fact that iclaprim is 15-fold more active than trimethoprim (MICs = 0.13 and 2.0 ug/ml, respectively), provide additional rationale for the use of iclaprim to treat complicated MRSA infections.

Disclosures
A. Bryant, Motif Biosciences: Grant Investigator, Research grant; D. Huang, Motif Bio: Employee, Salary; D. Stevens, Motif Biosciences: Grant Investigator, Research grant
Activity of Delafloxacin When Tested Against Bacterial Surveillance Isolates Collected in the US and Europe During 2014–2016 as Part of a Global Surveillance Program
Authors: Flamm Robert K , Shortridge Dee , Huband Michael D , McCurdy Sandra , Pfaller Michael A 
Published: October 2017

Abstract

Background
Delafloxacin (DLX) is an investigational anionic fluoroquinolone with an NDA that is under US FDA review to treat acute bacterial skin and skin structure infections and is undergoing Phase 3 studies to treat community-acquired bacterial pneumonia.

Methods
A total of 36,683 Gram-positive (GP) and -negative (GN) bacteria isolated during 2014–2016 were selected from medical centers in the US and Europe. Susceptibility testing (S) was performed by frozen-form broth microdilution methods for DLX and comparators.

Results
DLX was very active against Staphylococcus aureus (SA, n = 9,355; MIC50/90, 0.008/0.5 mg/L) while the levofloxacin (LEV) MIC50/90 was 0.25/&gt;4 mg/L (67.9%S). The MIC50/90 for methicillin-resistant SA (MRSA) was 0.12/1 mg/L. For MRSA, all isolates were S to vancomycin and daptomycin (DAP), linezolid and tigecycline (TGC) S was ≥99.9%. Decreased rates of S were noted for LEV (29.8%), clindamycin (72.9%), and erythromycin (17.3/17.8%; CLSI/EUCAST). Minocycline (MIC50/90, 0.12/0.25 mg/L), ceftaroline (MIC50/90, 0.25/0.5 mg/L), DAP (MIC50/90, 0.5/0.5 mg/L), and DLX (MIC50/90, 0.015/0.5 mg/L) were the most active agents tested against coagulase-negative staphylococci. Against Streptococcus pneumoniae (SPN), the MIC50/90 for DLX (0.015/0.03 mg/L) and TGC (0.03/0.06 mg/L) were the lowest among the agents tested. The DLX MIC50/90 values did not vary among the penicillin-S, -intermediate, and -R subgroups of SPN. The MIC50/90 values for DLX against S. pyogenes and S. agalactiae were 0.015/0.03 mg/L. DLX was highly active against Haemophilus influenzae. The DLX MIC50/90 (≤0.001/0.004 mg/L) was the same for β-lactamase positive and negative H. influenzae. Against Enterobacteriaceae, 76.0% of DLX MIC values were ≤1 mg/L. Susceptibility to LEV was 80.8%, and S to ceftriaxone, ceftazidime (CAZ), and cefepime ranged from 78.5–86.3%. A total of 72.6% of Pseudomonas aeruginosa isolates exhibited DLX MIC values ≤1 mg/L, while LEV S was 73.2% and CAZ was 81.6%. The MIC50/90 for both DLX and LEV were 0.5/&gt;4 mg/L, respectively.

Conclusion
DLX was active against a broad range of GP and GN bacteria, including MRSA and multidrug-resistant SPN. DLX merits further study as therapy in infections in which these organisms may occur.

Disclosures
R. K. Flamm, Melinta Therapeutics: Research Contractor, Research grant D. Shortridge, Melinta Therapeutics: Research Contractor, Research grant M. D. Huband, Melinta Therapeutics: Research Contractor, Research grant S. McCurdy, Melinta Therapeutics: Employee, Salary M. A. Pfaller, Melinta Therapeutics: Research Contractor, Research grant