bluuebunny/crossref_metadata_2025 huggingface dataset:
Case–control Study Evaluating Risk Factors and Treatment Outcomes for Community-Acquired Urinary Tract Infections (UTI) Caused by Extended-Spectrum Β-Lactamase (ESBL)-Producing Pathogens
Authors: Lee Stephen , Fish Douglas N , Barber Gerard , Barron Michelle
Published: October 2017

Background

Community-acquired (CA) infections caused by ESBL-producing pathogens are becoming more common. Risk factors (RFs) for CA ESBLs have not been as extensively studied and remain relatively undefined. Recognition of patient-specific RFs for CA ESBL infections such as UTI can potentially improve patient outcomes through selection of more appropriate initial drug therapy. The objectives of this study were to identify RFs and associated treatment outcomes for CA UTI involving ESBLs.

Methods

Adult patients with CA ESBL UTI (cystitis) seen in the Emergency Department (ED) from 2009 through 2013 were retrospectively matched 1:1 with a control group of non-ESBL CA UTI based on age within 5 years, gender, and organism. The primary outcome was identification of RFs predictive of CA ESBL UTI. Secondary outcomes included comparison of ESBLs and controls in risk of inappropriate initial antibiotic therapy and need for additional follow-up to healthcare facilities (clinics, ED) within 14 days of initial treatment.

Results

Eighty-five patients were matched into each group. Compared with controls, CA ESBL UTI was associated with nursing home stay (P = 0.04), congestive heart failure (CHF, P = 0.04), hospitalization within the previous year (P = 0.04), and receipt of either any antibiotics or specifically, fluoroquinolones within the previous 3 months (P < 0.01 for both) by univariate analysis. Multivariate logistic regression identified hospitalization within 1 year (OR 3.8, 95% CI 1.7–8.7; P < 0.001), antibiotics within 3 months (OR 3.5, 95% CI 1.7–7.6; P < 0.001), and CHF (OR 4.9, 95% CI 1.3–24.7; P = 0.02) as significant RFs for ESBL CA UTI. Patients with CA ESBL infections were more likely to receive inappropriate initial antibiotics (OR 8.9, 95% CI 4.2–18.6; P < 0.0001) and, if treated inappropriately, to require repeat visits to healthcare facilities within 14 days (OR 11.4, 95% CI 2.6–50.8).

Conclusion

Previous hospitalization, previous antibiotics, and CHF were RFs associated with CA ESBL UTI. These patients were significantly more likely to be treated inappropriately and to require additional healthcare follow-up. Recognition of RFs for CA ESBL UTI may facilitate appropriate ED-based management and avoid additional resource utilization.

Disclosures

D. N. Fish, Merck & Co.: Grant Investigator, Research grant M. Barron, Merck & Co.: Grant Investigator, Research grant
Prevalence and Accuracy of Screening Test of Asymptomatic Bacteriuria During Pregnancy in Siriraj Hospital
Authors: Srisompong Jintana , Rahman Suraiya , Russameecharoen Kusol , Tongsai Sasima , Seenama Chakkrapong , Koomanachai Pornpan
Published: October 2017

Background

The early detection and treatment asymptomatic bacteriuria (ASB) during pregnancy prevents maternal and fetal complication. Thus the American College of OB-GYN recommends urine culture should be obtained at the first prenatal visit and the U.S. Preventive Services Task Force obtains urine culture during 12–16 weeks of gestation. The new antenatal care (ANC) model of Thai Ministry of Public Health uses screening at first ANC by urine dipstick. However, neither research nor routine ASB screen in Siriraj Hospital because there was low prevalence and all pregnancy been screened by the obstetricians.

Methods

Prospective cohort study was performed at the ANC clinic, OB-GYN department, Siriraj Hospital. Pregnancies of first antenatal care visit during January to December 2015 were enrolled. Urine culture (UC), Urine dipstick for nitrite (UDN), and Urine dipstick for leukocyte esterase (UDL), were performed. Subjects’ baseline characteristics until birth delivery were collected.

Results

Total 702 subjects were enrolled; median age, 28 yrs (range 16–45) and body mass index, 24.1 (range 14.0–44.3). The ASB prevalence was 2.3% (16 from 702) without significant difference between first, second, and thirdtrimester, P = 0.185. The most common organism was E. coli. Factors related to ASB were heart disease, P < 0.001 and having sexual intercourse during pregnancy, P = 0.005. The sensitivity and specificity of UDN and UDL were 37.5% and 99.0% and 56.3% and 55.7%, respectively. Positive predictive value and negative predictive value of UDN and UDL were 46.2% and 2.9% and 98.5% and 98.2%, respectively. No abnormal maternal and fetal outcomes were reported.

Conclusion

According to very low prevalence of ASB in Siriraj hospital, routine urine culture may be unnecessary for all antenatal pregnancy. However, heart disease and sexual intercourse during pregnancy should be considered for screening and treatment. However, further evaluation of outcome, i.e. UTI, maternal and fetal complication of non-screening for ASB should be studied.

Disclosures

All authors: No reported disclosures.
Are Urinalyses Used Inappropriately in the Diagnosis of Urinary Tract Infections?
Authors: Elshimy Ghada , Mariano Vincent , Joy Christina Mariyam , Kaur Parminder , Singhal Monisha
Published: October 2017

Background

One of the most readily available and cost effective tests in the diagnosis of urinary tract infections (UTI) is the urinalysis. Problems arise when antibiotic treatment is initiated in a patient who does not display typical signs and symptoms of UTI and for whom a urinalysis was obtained for other reasons.

Methods

This was a retrospective observational study carried out on 1000 patients with positive urine nitrite. Medical records were identified with subsequent analysis of urine culture and symptomatology. Recorded and analyzed data included: age, sex, location (emergency room (ER) or hospital ward), findings on urinalysis (pH, presence of leukocyte esterase(LE), epithelial cells, bacteria, and white blood cells (WBCs)) and antibiotic treatment.

Results

Of these 1000 patients with positive nitrite, we excluded 815 patients (81 had missing data, 466 met exclusion criteria and 268 had symptomatic UTI). 185 were found to not have any symptoms of a UTI. Inappropriate antibiotic treatment occurred in 108/185 patients (58.4%) and was significantly associated with greater amounts of bacteria and WBCs in the urinalyses (P = 0.008 and P = 0.029, respectively). It was also significantly more likely to occur in the ER than the hospital wards (92/147 treated in the ER vs. 16/37 treated on the hospital wards, P = 0.033). There was no significant association between antibiotic treatment and age, sex, urine pH, urine LE, and urine epithelial cell amounts (P > 0.05). Urine cultures were not obtained in 69.7% of patients. A positive urine culture was significantly associated with inappropriate antibiotic treatment (P = 0.0006). The two most common presenting complaints were psychiatric complaints (21.6%) and vaginal bleeding (14.6%).

Conclusion

Urinalysis can be an invaluable diagnostic tool, but must be used and interpreted appropriately. There is a misperception that pyuria with bacteriuria defines UTI. However, positive results on a urinalysis alone in an asymptomatic patient is not enough to diagnose a UTI, and antibiotic treatment is only indicated in specific circumstances as outlined by IDSA guidelines for the treatment of asymptomatic bacteriuria. Further education targeting appropriate interpretation of urinalyses and IDSA guidelines is needed to decrease the unnecessary use of antibiotics.

Disclosures

All authors: No reported disclosures.
The prognostic importance of platelet indices in patients with Crimean-Congo Hemorrhagic Fever
Authors: Aksoy Firdevs , Yilmaz Gürdal , Kaya Selcuk , Karahan Süleyman Caner , Koksal Iftihar
Published: October 2017

Background

Platelet count is an important tool for the diagnosis and prognosis of Crimean-Congo Hemorrhagic Fever (CCHF). The platelet indices plateletcrit, mean platelet volume (MPV) and platelet distribution width (PDW) are parameters obtained as part of the automated complete blood count. These parameters are of prognostic importance in several diseases. The aim of this study was to evaluate the platelet count and its relations with platelet indices in CCHF patients.

Methods

One hundred and forty-nine patients with confirmed CCHF were included in the study. Patients were divided into two groups (severe cases, patients who exhibited hemorrhage during their hospital stay, and mild/moderate cases with no hemorrhage during hospital stay). The demographic characteristics and laboratory test results of all patients were compared. P < 0.05 was regarded as statistically significant.

Results

Hemorrhaging was observed in 38.3% of patients during hospitalization. Platelet count, PCT and PDW values (respectively) on the first day of hospitalization were 43.3 ± 29.3, 0.06 ± 0.07%, and 17.4 ± 1.5% in the severe cases and 64.5 ± 35.4, 0.08 ± 0.03%, and 16.8 ± 1.5% in the mild/moderate cases, respectively (P < 0.05). The difference between MPV values was not statistically significant. At cutoff values at ROC analysis, platelet count (≤53000) and PCT(≤0.06) exhibited 73.7% and 71.9% sensitivity, respectively, and predicted a hemorrhagic disease course with a 80.9% negative predictive value. Seven of the severe patients died (P = 0.001). At cutoff values, platelet count (>31000) and PCT (>0.03) predicted patient survival with 100% specificity and 100% positive predictive value.

Conclusion

Our study shows that platelet count, PCT and PDW are parameters that may be used to determine disease severity. The platelet index, and particularly PCT, may be at least as useful as platelet count in helping clinicians identify severe cases.

Disclosures

All authors: No reported disclosures.
A Multidisciplinary Study of the Use and Outcomes Associated with Expanded Respiratory Viral Studies at a Mid-Sized Children’s Hospital
Authors: Zhu Chelsea , Sidiki Sabeen , Grider Brittany , Fink Brian , Hubbard Nicole , Mukundan Deepa
Published: October 2017

Background

Acute respiratory infection (ARI) is a leading cause of pediatric hospitalizations in the US and are generally caused by viruses, thus antibiotics are prescribed more often than needed. Identifying viral agents using the respiratory pathogen panel (RPP) can help with judicious use of antibiotics in hospitalized patients. ProMedica Toledo Children’s Hospital, a mid-sized pediatric hospital, began offering the RPP to patients in Dec 2014. This study was conducted to assess if the use of RPP would decrease the antibiotic days of therapy (DOT) and length of hospital stay for patients admitted for uncomplicated ARI and for those seen in the ED.

Methods

This was a retrospective analysis of pediatric hospital inpatient and ED data collected between December 16, 2013 and December 15, 2015. Patients before and after implementation of the RPP were compared. 299 and 263 pediatric patients between 1 month to 18 years of age with uncomplicated ARIs in the pre-RPP and post-RPP periods, respectively, were included for analysis. Similarly, 472 and 461 patients were included from the ED. Clinical data were collected by chart review. Analysis was performed using descriptive and inferential statistics.

Results

Out of 299 admitted patients in the post-RPP period, 63 (21.1%) patients did not receive the RPP (RPP-NT). 201 (67.2%) received it and tested positive (RPP-P), and 35 (11.7%) patients tested negative (RPP-N). RPP-N had an increased length of hospital stay (P = 0.055, borderline significance) and increased number of antibiotic DOT (P = 0.032) than RPP-P. Furthermore, we discovered that older patients (mean = 6.21 years) tested negative with RPP, while younger patients either did not receive the test (mean = 2.43 years) or tested positive (mean = 2.40 years). In the ED, RPP-P received fewer discharge prescriptions for antibiotics than RPP-N and RPP-NT (P < 0.01). The use of RPP was more prevalent in admitted patients than in ED patients (P = 0.01).

Conclusion

Our results suggest that the use of RPP effectively curbs unnecessary antibiotic use for pediatric patients with viral ARIs. Furthermore, age discrepancies among RPP-P, RPP-N, and RPP-NT warrant further study. Lastly, the results suggest that use of RPP in ED should be encouraged.

Disclosures

C. Zhu, IDSA Foundations Medical Scholars Program 2015–2016: Member, Educational scholarship.
A Mid-Turbinate Swab Appears Comparable to Nasopharyngeal Swabs for Quantitative Detection of RSV in Infants
Authors: Blaschke Anne J , Mckevitt Matthew , Ampofo Krow , Lewis Tammi , Chai Hao , Guo Ying , Dorsch Julianna , Vanderhoof Erin , Rosen Pricilla , Freimann Volker , Korgenski E Kent , Toback Seth , Chien Jason
Published: October 2017

Background

Respiratory Syncytial Virus (RSV) is the most common cause of bronchiolitis and pneumonia in infants and children. Diagnosis of RSV can be made by molecular detection of the virus in a swab of respiratory secretions. Nasopharyngeal (NP) swabs are the most frequent swab type validated for the detection of RSV, and are often considered the “gold standard” for quantification studies. However, NP sampling is invasive and uncomfortable. We sought to determine whether a less invasive method, a mid-turbinate (MT) swab, was comparable to NP sampling for quantification of RSV in infants.

Methods

We prospectively enrolled children < 24 months with a confirmed diagnosis of RSV and hospitalized at Primary Children’s Hospital (Salt Lake City, UT) during the 2015 – 2017 RSV seasons. Both an NP and MT swab were collected from each infant from different nostrils; subjects were randomized (1:1:1:1) as to the order of collection. After collection, parents were asked which collection method (NP vs. MT) they preferred. Viral loads were measured by real-time RT-qPCR. Correlation between the viral loads from the MT and NP swabs was examined. A mixed effect model was used to evaluate the mean (SD) viral loads.

Results

83 infants were enrolled and had swabs collected. Median age was 4 months [range 0–23]. 20 infants had swabs collected on multiple consecutive days. Median (Q1,Q3) duration of symptoms prior to enrollment was 5 days (4,7) Median (Q1,Q3) hospital stay length was 2 days (2,4). 1 infant was RSV negative according to the RT-qPCR assay. The mean (SD) viral loads were similar: 7.34 (1.26) and 7.09 (1.25) log10 copies/mL for 77 paired NP and MT swabs, respectively; see Figure 1 for median, range and quartiles. The correlation coefficient between the paired viral loads was high (0.82); see Figure 2 for Bland-Altman plot. Most parents (49/67 [73%]) who watched the swabbing preferred the MT to the NP swab.

Conclusion

MT swabs perform as well as NP swabs for the quantification of RSV in infants. The difference in mean viral load is small compared with the standard deviation. The less invasive MT swabs are preferred by parents for sampling. MT swabs have the potential to replace the NP swab as the “gold standard” for quantitative respiratory viral sampling.

Disclosures

A. J. Blaschke, Gilead Sciences, Inc: Investigator, Research support BioFire Diagnostics, LLC: Collaborator, I have intellectual property in BioFire Diagnostics through the University of Utah and Investigator, Licensing agreement or royalty and Research support
Quality Assessment of Cytomegalovirus PCR Testing at an Academic Tertiary Referral Hospital
Authors: Bluen Benjamin , Gancher Elizabeth , Epstein Shara , Krevolin Kyle , Lee Dong Heun
Published: October 2017

Background

Cytomegalovirus (CMV) Polymerase chain reaction (PCR) test is a valuable tool for diagnosis and therapeutic monitoring of CMV infection. Academic medical centers with a high volume of organ transplant and immunosuppressed patients often utilize CMV quantitative and qualitative PCR testing. CMV qualitative PCR typically does not alter clinical management, and positive CMV qualitative test often needs follow up quantitative test. Despite its lack of usefulness, CMV qualitative PCR is often over-ordered and may unnecessarily raise the cost of hospitalization. We evaluated utility of CMV PCR testing at a tertiary care medical center.

Methods

We reviewed CMV PCR testing done from June 2015-November 2016 at Hahnemann University Hospital in Philadelphia, PA. CMV qualitative test was performed at LabCorp and CMV quantitative test was done at Focus Labs. Data collected included demographics, length of stay, and immunosuppression. Selected patients had either CMV qualitative PCR positive without follow up quantitative PCR, or negative CMV qualitative PCR with unnecessary CMV quantitative PCR ordered.

Results

We evaluated 226 CMV PCR test results including 162 qualitative and 64 quantitative CMV PCR in 139 patients. 39 (28%) patients had superfluous CMV testing. Mean age was 52.6 years, 61% were male, 46% were African American. Mean length of stay was 24 days. A half (N = 19,49%) were immunocompromised. 28 (17.2%) results were positive for CMV qualitative PCR, 7 (25%) of whom follow up CMV quantitative PCR were not sent. Thirty-two patients had negative CMV qualitative testing yet had CMV quantitative PCR sent. Six had redundant CMV quantitative PCR tests within 7 days likely resulting from delayed result report from send out. After performing cost analysis, these unnecessary tests would have saved $3930.

Conclusion

In our cohort, significant unnecessary CMV testing resulted in increased health care cost and patient discomfort. Positive Qualitative CMV PCR without Quantitative testing impairs diagnosis and treatment follow up. Given complicated testing algorithm and limited value of CMV qualitative PCR testing in the adult population, we plan to simplify CMV testing to quantitative only and perform in house testing to shorten result time.

Disclosures

All authors: No reported disclosures.
Molecular Epidemiological Investigation of Human Parainfluenza 3 Virus Outbreak in a Pediatric Bone Marrow Transplantation Unit
Authors: Stapleton Patrick , Perusini Stephen , Thomas Angela , Science Michelle , Schechter-Finkelstein Tal , Gubbay Jonathan B , Patel Samir , Yau Yvonne
Published: October 2017

Background

Human parainfluenza virus 3 (hPIV3), a common cause of respiratory infections in children, can cause nosocomial outbreaks in patients undergoing hematopoietic stem cell transplantation, resulting in significant morbidity and mortality. Between July and August 2016, an increased number of hPIV3 infections were noted in a pediatric bone marrow transplant unit (BMT). Two patients were identified in late July and 4 patients in August. We undertook molecular typing of hPIV3 to determine whether cases represented multiple introductions of community virus strains or patient to patient transmission of a single strain. Previous reports of molecular typing have targeted either the F (fusion protein) gene or HN (hemagglutinin-neuraminidase) gene. We compared results using both methods direct from clinical specimens.

Methods

Nasopharyngeal (NP) swabs from 6 patients in BMT ward and 6 patients hospitalized on other wards had hPIV3 detected by the Luminex NxTAG Respiratory Pathogen Panel over 2 months. For the F gene a single pair of primers were used to first amplify then sequence a 278 basepair (bp) region by reverse-transcriptase PCR (RT-PCR). For HN gene a 1719 bp region was amplified using nested RT-PCR, then sequenced with 6 sets of overlapping primers. The resulting contigs were assembled manually with ContigExpress. Phylogenetic analysis of assembled sequences was performed in MEGA7 using the maximum likelihood method.

Results

For the HN gene sequence of 1715 bp was obtained for 10 of 12 patients (5 in each group). Phylogenetic analysis of HN sequences indicated 2 distinct hPIV3 lineages (Figure 1). The 5 BMT patients differed by a maximum of 1bp, while 5 samples from other wards differed by 14 to 57 bp. For the F gene only 98 bp of common sequence was obtained for 7 patients, all of whom had HN gene sequences available. Phylogenetic analysis of F gene sequence also supported the presence of 2 distinct lineages.

Conclusion

Molecular typing of hPIV3 suggests there was transmission of a single hPIV3 strain within the BMT unit despite protective isolation of all BMT patients in positive pressure single rooms and the use of contact and droplet precautions for infected cases. We found sequencing the HN gene more informative than sequencing the F gene.

Disclosures

All authors: No reported disclosures.
Meterology-driven Prediction of RSV/RHV Incidence in Rural Nepal
Authors: Scott Anna , Englund Janet , Chu Helen , Tielsch James , Tielsch James , Khatry Subarna , Leclerq Steven C , Shrestha Laxman , Kuypers Jane , Steinhoff Mark C , Katz Joanne
Published: October 2017

Background

Incidence of respiratory syncytial virus (RSV) and rhinovirus (RHV) varies throughout the year. We aim to quantify the relationship between weather variables (temperature, humidity, precipitation, and aerosol concentration) and disease incidence in order to quantify how outbreaks of RSV and RHV are related to seasonal or sub-seasonal meteorology, and if these relationships can predict viral outbreaks of RSV and RHV.

Methods

Health data were collected in a community-based, prospective randomized trial of maternal influenza immunization of pregnant women and their infants conducted in rural Nepal from 2011–2014. Adult illness episodes were defined as fever plus cough, sore throat, runny nose, and/or myalgia, with infant illness defined similarly but without fever requirement. Cases were identified through longitudinal household-based weekly surveillance. Temperature, humidity, precipitation, and fine particulate matter (PM 2.5) data come from reanalysis data products NCEP, Era-Interim, and Merra-2, which are produced by assimilating historical in-situ and satellite-based observations into a weather model.

Results

RSV exhibits a relationship with temperature after removing the seasonal cycle (r = -0.16, N = 208, P = 0.02), and RHV exhibits a strong relationship to daily temperature (r =-0.14, N =208, P = 0.05). When lagging meteorology by up to 15 weeks, correlations with disease count and weather improve (RSV: r_max = 0.45, P < 0.05; RHV: r_max = 0.15, P = 0.05). We use an SIR model forced by lagged meteorological variables to predict RSV and RHV, suggesting that disease burden can be predicted at lead times of weeks to months.

Conclusion

Meteorological variables are associated with RSV and RHV incidence in rural Nepal and can be used to drive predictive models with a lead time of several months.

Disclosures

J. Englund, Gilead: Consultant and Investigator, Research support Chimerix: Investigator, Research support Alios: Investigator, Research support Novavax: Investigator, Research support MedImmune: Investigator, Research support GlaxoSmithKline: Investigator, Research support
The Global Burden of Rotavirus Diarrheal Diseases: Results from the Global Burden of Diseases Study 2016
Authors: Khalil Ibrahim Abdel-Messih
Published: October 2017

Background

More than 1,300,000 deaths were attributable to diarrhea in 2015, with more than 400,000 of these deaths from children under 5 years of age. The Global Burden of Disease Study 2016 (GBD2016), an ongoing effort to measure global epidemiological trends, estimates diarrhea disease burden and the burden attributable to rotavirus and other enteric pathogens.

Methods

Diarrhea deaths are estimated using a suite of prediction models for all ages, both sexes, and for all countries and some subnational geographic areas from 1980 to 2016 using an ensemble modeling tool called CODEm. To estimate the burden of rotavirus, we calculated a population attributable fraction using a counter-factual approach by modeling the proportion of diarrheal cases that are positive for rotavirus and applying odds ratios describing the odds of diarrhea given rotavirus detection.

Results

In 2016, rotavirus was the leading cause of diarrhea mortality in children under 5 years old, responsible for 29.5% of diarrhea deaths in this age group (149,200 deaths, 95% Uncertainty Interval (UI): 119,200–189,400), and responsible for 15.3% of diarrhea deaths among all ages (202,300 deaths, 95% UI: 165,800–246,400). The population attributable fraction of diarrhea mortality due to rotavirus is generally stable across geographic regions. The global attributable fraction of rotavirus decreased by 24.2% (95% UI: 16.7–31.6%) between 2005 and 2016

Conclusion

The global deaths attributable to rotavirus in children under 5 is substantial and the burden in older children and adults may be unrecognized. GBD 2016 estimates describe epidemiological trends for rotavirus diarrhea and will inform evidence-based Public Health policy, to reduce the global burden of rotavirus. Our findings call for acceleration of delivery existing rotavirus vaccines and development of more affordable options for Low and Middle Income countries.

Disclosures

All authors: No reported disclosures.
Activity of the Novel Extended-spectrum β-Lactamase Inhibitor AAI101 in Combination with Cefepime Towards a Challenge Panel of Acinetobacter baumannii
Authors: Morrissey Ian , Magnet Sophie , Hawser Stephen , Shapiro Stuart , Seifert Harald , Higgins Paul
Published: October 2017

Background

AAI101 is a novel extended-spectrum β-lactamase inhibitor (BLI), active against ESBLs and a broad array of other BLs. AAI101 in combination with cefepime (FEP) is in Phase 2 development. Infections caused by A. baumannii, a pathogen endemic to the southern US and other global regions, are very challenging to treat, and often require combination therapy. This study examined the activity of FEP/AAI101 against a challenge set of A. baumannii clinical isolates enriched with OXA carbapenemase producers.

Methods

BLs in A. baumannii were identified by genotyping. Broth microdilution MICs and susceptibilities were obtained following CLSI methods and breakpoints (BPs), except for ceftazidime-avibactam (CAZ/AVI) where FDA P. aeruginosa BPs were used. CLSI FEP BPs were used for FEP/AAI101.

Results

All OXA-51 producers had the ISAba1 promoter. MIC90 data and % susceptibilities (%S) for FEP/AAI101 and comparators are shown in the Table: FEP/AAI101 was highly active against meropenem-susceptible (MPMs) isolates. FEP/AAI101 (AAI101 fixed at 8 µg/ml) covered 67% of OXA-51 and 53% of OXA-58 strains. Lower susceptibilities were obtained for OXA-23 and OXA-24/40 producers. FEP/AAI101 was the most active β-lactam product. Colistin (COL) was the only agent with consistently high activity against all A. baumannii isolates.

Conclusion

FEP/AAI101 was the most potent β-lactam product tested against clinical isolates of A. baumannii producing OXA-51 and OXA-58 β-lactamases. Infections by this difficult pathogen often require combination therapy, of which FEP-AAI101 may be a component.

Disclosures

S. Shapiro, Allecra: Employee, Salary
Ceftobiprole Activity When Tested Against Contemporary Bacteria Causing Bloodstream Infections in the US (2016)
Authors: Flamm Robert K , Duncan Leonard R , Shortridge Dee , Smart Jennifer I , Hamed Kamal , Mendes Rodrigo E , Sader Helio S
Published: October 2017

Background

Ceftobiprole medocaril (prodrug of ceftobiprole) is an advanced cephalosporin, approved for adults in multiple European countries for the treatment of hospital-acquired pneumonia (excluding ventilator-associated pneumonia) or community-acquired pneumonia. It is not approved in the US; however, it has achieved qualified infectious disease product status and two phase 3 studies supported by BARDA are planned to begin in the US in 2017.

Methods

A total of 2,787 Gram-positive (GP) and -negative (GN) isolates from bloodstream infections (BSI) from 30 medical centers in the SENTRY Antimicrobial Surveillance Program were evaluated. Isolates were collected in the US during 2016. Susceptibility (S) testing was performed by reference broth microdilution method against ceftobiprole and comparators. Isolates included 693 Staphylococcus aureus (SA), 216 coagulase-negative staphylococci (CoNS), 244 enterococci, 63 Streptococcus pneumoniae (SPN), 74 viridans group streptococci (VGS), 138 β-haemolytic streptococci (BHS), 1,105 Enterobacteriaceae (ENT), 129 Pseudomonas aeruginosa (PSA), 41 Acinetobacter spp. (ASP), 30 Stenotrophomonas maltophila, 19 Haemophilus spp. and 35 miscellaneous bacteria.

Results

Methicillin-resistant S. aureus (MRSA) S rates were lower than for methicillin-susceptible S. aureus (MSSA) for most agents. For levofloxacin (LEV) and erythromycin (ERY), the S rates were LEV: MRSA, 23.2%; MSSA, 86.1%; ERY: MRSA, 9.0%; MSSA, 69.3%. All MSSA and 99.0% of MRSA were S to ceftobiprole, while all MSSA and 96.5% of MRSA were S to ceftaroline (CPT). For CoNS, 98.1% of ceftobiprole MIC values were ≤2mg/L. Ceftobiprole was active against Enterococcus faecalis (96.1% ≤2mg/L) and not against E. faecium (18.9% ≤2mg/L). Against ENT, ceftobiprole (85.0%S) was similar in activity to ceftazidime (CAZ, 87.2%S) and cefepime (FEP, 88.9%S). The MIC50/90 values for ceftobiprole, FEP, and CAZ against PSA were identical at 2/16 mg/L.

Conclusion

Ceftobiprole exhibited potent in vitro activity against GP and GN isolates from contemporary BSI in the US. These results support further clinical evaluation of ceftobiprole for the treatment of BSI.

Disclosures

R. K. Flamm, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; L. R. Duncan, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; D. Shortridge, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; J. I. Smart, Basilea Pharmaceutica International Ltd.: Employee, Salary; K. Hamed, Basilea Pharmaceutica International Ltd.: Employee, Salary; R. E. Mendes, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant; H. S. Sader, Basilea Pharmaceutica International Ltd.: Research Contractor, Research grant
Activity of Antistaphylococcal Lysin CF-301 against Contemporary Staphylococcus aureus Clinical Isolates from the USA and Europe
Authors: Oh Jun , Traczewski Maria , Schuch Raymond
Published: October 2017

Background

CF-301 is a novel, recombinantly-produced bacteriophage-derived lysin (cell wall hydrolase) and is the first agent of this class in the US to enter into clinical development for the treatment of bacteremia including endocarditis due to S. aureus. Hallmark features of CF-301 include rapid and pathogen-specific bacteriolytic activity, synergy with antibiotics, biofilm-disrupting activity, a low propensity for resistance, and the capacity to suppress antibiotic resistance. This is the first report of an international surveillance study for CF-301.

Methods

349 methicillin-sensitive and –resistant S. aureus (MSSA and MRSA, respectively) isolates were collected from various infection sources at multiple hospitals from 2015–2017 throughout the US, Greece, Hungary and Italy. In addition to the contemporary isolates, a set of 149 MSSA and MRSA clinical isolates from 2011 were also obtained from US hospital sources. MICs for CF-301 were determined using a new antimicrobial susceptibility testing (AST) medium for broth microdilution recently endorsed by Clinical and Laboratory Standards Institute (CLSI) for use with CF-301. The testing medium consists of cation-adjusted Muller Hinton Broth supplemented with 25% horse serum and 0.5 mM DTT (CAMHB-HSD). Susceptibility to conventional antibiotics was also examined in this study using standard methodology (CLSI document M07-A10) and included: vancomycin, trimethoprim-sulfamethoxazole, daptomycin, oxacillin, linezolid, clindamycin, and cefazolin.

Results

CF-301 had MIC50, MIC90, and MIC100 values of 0.5, 1, and 2 μg/mL, respectively, against each set of contemporary MSSA (n = 176) and MRSA (n = 173) clinical isolates. There were no differences noted with respect to the geographic source (in the US and Europe) of isolates. Furthermore, the CF-301 MICs reported here for 2015–2017 isolates were identical to that observed for MSSA and MRSA isolates from 2011.

Conclusion

CF-301 demonstrated potent in vitro activity against a total of 498 clinical S. aureus isolates from a range of human infections (including bacteremia) and different geographies. Contemporary clinical isolates did not demonstrate reduced susceptibility to CF-301 compared with the 2011 isolates.

Disclosures

J. Oh, ContraFect Corp: Employee, Salary; R. Schuch, ContraFect Corp: Employee, Salary
In Vitro Activity of Lefamulin against S. aureus Collected Worldwide from Hospitalized Patients with Bacterial Pneumonia
Authors: Paukner Susanne , Flamm Robert K , Schuchert Jason , Gelone Steven P , Sader Helio S
Published: October 2017

Background

S. aureus (SA) is a well-recognized cause of pneumonia from both the community and hospital settings. The clinical management of SA pneumonia is complicated by the invasive infection it can cause and the high prevalence of methicillin-resistance (MR). Lefamulin (LEF) is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans. LEF is the first semi-synthetic pleuromutilin antibiotic for IV and oral use in humans and it specifically inhibits bacterial protein synthesis. LEF is currently in Phase 3 trials for the treatment of community-acquired bacterial pneumonia (CABP). This study investigated the in vitro activity of LEF and comparators against SA strains collected from patients hospitalized with pneumonia in 2015.

Methods

1273 unique SA isolates were collected from hospitalized patients with pneumonia worldwide in 28 countries (33 sites) in 2015 as part of the SENTRY surveillance program. Isolates included 401 hospital-acquired (HA) SA (259 from ICU, 152 from ventilator associated pneumonia, VAP). Susceptibility testing was conducted using the CLSI broth microdilution method and susceptibility was interpreted per CLSI 2017 breakpoint criteria.

Results

LEF was the most potent compound tested, with 99.7% of all SA isolates being inhibited at a concentration of ≤0.25 mg/L (MIC50/90 values of 0.06/0.12 mg/L) and irrespective of the collection source (ICU/non-ICU, VAP/non-VAP). 31.6% of isolates (n = 402) were MRSA of which 99.3% were inhibited at a LEF concentration of ≤0.25 µg/mL (MIC50/90, 0.06/0.12 mg/L). Susceptibility rates for all SA isolates were >90% for ceftaroline, vancomycin, linezolid and doxycycline. Susceptibility to azithromycin, levofloxacin and clindamycin was limited, particularly among MRSA (see Table).

Conclusion

SA strains collected from patients hospitalized with pneumonia including HAP and VAP were highly susceptible to LEF regardless of the resistance phenotype to the other antibiotics tested. Due to its potent activity against resistant SA and the most prevalent typical and atypical respiratory pathogens, as well as the availability of IV and oral formulations, LEF has the potential to play a role in the empiric treatment of CABP and supports evaluation in HAP and VAP caused by SA.

Disclosures

S. Paukner, Nabriva Therapeutics: Employee and Shareholder, Salary; R. K. Flamm, Nabriva Therapeutics: Research Contractor, Research grant; J. Schuchert, Nabriva Therapeutics: Research Contractor, Research grant; S. P. Gelone, Nabriva Therapeutics: Employee and Shareholder, Salary; H. S. Sader, The Medicines Company: Research Contractor, Research grant
In vitro Activity of Fosfomycin, Alone and Combined with Cefepime and Meropenem, Against Carbapenemase-Producing Gram-Negative Bacteria
Authors: Wiederhold Nathan P , Jorgensen James H , McElmeel Maria , Najvar Laura K , Catano Gabriel , Patterson Thomas F
Published: October 2017

Background

Multi-drug resistant (MDR) gram-negative bacteria are serious clinical threats. Fosfomycin (FOF) is an epoxide antibiotic that causes bacterial cell death via disruption of cell wall synthesis. The addition of fosfomycin has been shown to restore susceptibility to other agents against MDR P. aeruginosa. We evaluated the in vitro activity of the new IV fosfomycin formulation, alone and combined with cefepime (FEP) and meropenem (MEM), against carbapenemase-producing Enterobacteriaceae.

Methods

80 carbapenemase-producing isolates, including 31 metallo β-lactamase producing isolates (29 NDMs and 1 each IMP and VIM), 48 KPCs, and 1 OXA-48, were used. The in vitro susceptibility of FOF, FEP and MEM were tested by agar dilution with glucose-6 phosphate by CLSI methods. Combination testing was then performed against 25 representative isolates using fixed concentrations of FOF (8, 16, 32, and 64 mg/mL) at 0.25X the MIC of FOF alone with doubling dilutions of FEP and MEM.

Results

Reduced activity was observed for FEP and MEM against the carbapenemase-producing isolates (Table). 36.2% of the isolates were NDM1 and 60% were KPCs. A total of 92.5% of the isolates were resistant to either FEP or MEM. FOF plus MEM resulted in synergistic activity (4-fold reduction in MEM MIC at 0.25X FOF MIC) against 12 of 25 isolates used for combination testing, with no antagonism observed. For these 12 isolates, MEM MICs ranged from 2 to 16 mg/mL when combined with FOF vs. 16 to 128 mg/mL when tested alone. When combined with FEP, synergistic activity was also observed against 6 of the 25 isolates. However, antagonism was observed against 3 isolates with this combination.

Conclusion

The combination of FOF plus MEM resulted in synergistic activity against approximately half of the KPCs and metallo β-lactamase producing bacteria. Synergistic activity was observed less often with FOF plus FEP, although antagonism was uncommon. Further studies are warranted to determine the in vivo efficacy of FOF combinations. Table: MICs Alone

Disclosures

All authors: No reported disclosures.
Activity of Ceftolozane-Tazobactam (C/T) against Escherichia coli Isolates from U.S. Veterans in Relation to Co-resistance and Sequence Type 131 (ST131) H30/H30Rx Status
Authors: Johnston Brian D , Thuras Paul , Johnson James R
Published: October 2017

Background

E. coli ST131, with its resistance-associated H30 and H30Rx clonal subsets, causes most antimicrobial-resistant E. coli infections, especially among veterans. The activity of the novel combination agent C/T against ST131 is undefined.

Methods

E. coli clinical isolates (n = 595), including (per VAMC) 10 each ciprofloxacin-resistant and susceptible isolates, plus archived ESBL isolates, were collected from 24 VAMCs across the U.S. (2011). ST131, H30, and H30Rx were detected by clonal PCR. Microdilution MICs were determined for C/T and 5 comparators (piperacillin-tazobactam [TZP], levofloxacin [LVX], gentamicin [GEN], ceftazidime [CAZ], and meropenem [MEM]). Categorical resistance and MICs were compared statistically with resistance category and H30/H30Rx status.

Results

Total resistance prevalence was < 5% for C/T (3.5%) and MEM (0%), vs. from 7.9% (TZP) to 59% (LVX) for other comparators (Table 1). Resistance prevalence generally increased by resistance category from FQ-S through FQ-R to ESBL, and by clonal subgroup from non-H30 through H30 to H30Rx.

Conclusion

C/T is broadly active against E. coli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30/H30Rx status; it outperformed all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing agent against multidrug-resistant E. coli ST131 infections.

Disclosures

B. D. Johnston, Merck Sharpe & Dohme, Corp.: Collaborator, Research support Actavis: Collaborator, Research support; J. R. Johnson, Merck: Grant Investigator, Research grant Grant Investigator, Research grant
Activity of Meropenem-Vaborbactam Against Enterobacteriaceae Isolates Carrying blaKPC Collected Worldwide
Authors: Castanheira Mariana , Mendes Rodrigo E , Duncan Leonard R , Woosley Leah N , Flamm Robert K
Published: October 2017

Background

Meropenem-vaborbactam (MER-VAB) is a carbapenem-β-lactamase inhibitor combination with enhanced activity against KPC-producing Enterobacteriaceae recently evaluated in a phase 3 clinical trials for cUTIs and infections due to CRE. We analyzed the activity of MER-VAB against 517 isolates carrying blaKPC collected worldwide during 2014–16.

Methods

Enterobacteriaceae isolates (n = 34,069) from 34 countries were susceptibility (S) tested by reference broth microdilution method for MER-VAB (at fixed 8 µg/mL) and comparators. Carbapenem-resistant Enterobacteriaceae (CRE; CLSI criteria) were submitted to PCR/Sanger sequencing or next-generation sequencing for blaKPC screening.

Results

A total of 517 (1.5%) carried blaKPC and 6 variants were observed: 293 blaKPC-3, 218 blaKPC-2, 2 blaKPC-4, 2 blaKPC-17, and 1 each of blaKPC-2-like and blaKPC-12. Isolates were mainly K. pneumoniae (437), but also 32 E. cloacae, 13 K. oxytoca, 12 E. coli, 12 S. marcescens, and 4 other species. Isolates carrying blaKPC were detected in 17 countries. The occurrence ranged from <0.1% to 11.3%, being higher in Brazil, Italy (9.3%), Poland (5.6%), and Argentina (5.2%). MER-VAB inhibited 514/517 (99.4%) isolates carrying blaKPC at ≤8 µg/mL and this compound was the most active agent tested against these isolates (MIC50/90, 0.12/1 µg/mL). Three isolates displaying elevated MER-VAB MIC values (>8 µg/mL) co-harbored blaNDM-1 or blaOXA-48-like in addition to blaKPC or had a missense mutation on OmpK35. MER alone (MIC50/90, 32/>32 µg/mL), imipenem (MIC50/90, >8/>8 µg/mL), and doripenem (MIC50/90, >4/>4 µg/mL) were not active against isolates harboring blaKPC. Amikacin (MIC50/90, 16/>32 µg/mL) and gentamicin (MIC50/90, 2/>8) µg/mL inhibited only 54.9% and 57.3% of the isolates (CLSI breakpoint). Colistin (MIC50/90, ≤0.5/>8 µg/mL; 70.4% S/EUCAST breakpoint) and tigecycline (MIC50/90, 0.5/1 µg/mL; 99.4% S/US FDA criteria) were the most active comparators.

Conclusion

The occurrence of blaKPC is still low overall, but can be as high as 5–10% in a few countries and occur in species other than Klebsiella. KPC-producers are highly resistant to available antimicrobial agents and MER-VAB will be a useful alternative to treat infections caused by these organisms.

Disclosures

M. Castanheira, Rempex, a wholly owned subsidiary of The Medicines Company: Research Contractor, Research grant; R. E. Mendes, Rempex, a wholly owned subsidiary of The Medicines Company: Research Contractor, Research grant; L. R. Duncan, Rempex, a wholly owned subsidiary of The Medicines Company: Research Contractor, Research grant; L. N. Woosley, Rempex, a wholly owned subsidiary of The Medicines Company: Research Contractor, Research grant; R. K. Flamm, Rempex, a wholly owned subsidiary of The Medicines Company: Research Contractor, Research grant
Change in Bacterial Diversity of Fecal Microbiota Drives Mortality in a Hamster Model of Antibiotic-induced Clostridium difficile Colitis
Authors: Burdet Charles , Nguyen Thu Thuy , Saint-Lu Nathalie , Sayah-Jeanne Sakina , Hugon Perrine , Sablier-Gallis Frédérique , Ferreira Stéphanie , Andremont Antoine , Mentré France , Gunzburg Jean De
Published: October 2017

Background

C. difficile (C diff) infection results from antibiotic-induced changes in colonic microbiota. DAV131A, an oral adsorbent-based product, can sequester antibiotic (AB) residues in the gut and reduce mortality in a hamster model of moxifloxacin (MXF) or clindamycin (CM) induced C diffcolitis. We studied the link between changes of the bacterial diversity within the fecal microbiota and mortality in this model.

Methods

Male Syrian hamsters were administered 30 mg/kg MXF or 5 mg/kg CM subcutaneously once a day for 5 days (D1 to D5) and orally infected at D3 with 104C diffspores. They were orally administered various doses of DAV131A (0, and 200 to 900 mg/kg twice a day), from D1 to D8. Survival was monitored up to D16 and feces were collected (D1 and D3) to characterize the microbiota by 16S rRNA gene profiling. Changes of various α- (Shannon, Observed OTUs and Chao1) and β- (Bray-Curtis dissimilarity and [un]weighted UniFrac) diversity indices between D1 and D3 were obtained for each animal. We analyzed links between (i) DAV131A dose and changes of bacterial diversity and (ii) changes of bacterial diversity and mortality using non parametric tests and logistic regression.

Results

Data from 70 and 60 animals were available in the MXF and CM studies, among which 10 and 28 died, respectively. Increasing doses of DAV131A reduced mortality from 100% to 0% and reduced changes in bacterial diversity of the fecal microbiota. Very strong predictors of mortality were changes in Shannon and unweighted UniFrac indices, which were markedly less affected in hamsters who survived (see table below median (min; max) according to vital status and area under the ROC curve, AUROC).

Conclusion

The extent of AB-induced changes in gut bacterial diversity correlated with increased mortality in a hamster model of C diff colitis. Higher doses of DAV131A protected fecal microbiota disruption and hence mortality.

Disclosures

C. Burdet, Da Volterra: Consultant and Research Contractor, Consulting fee; N. Saint-Lu, Da Volterra: Employee, Salary; S. Sayah-Jeanne, Da Volterra: Employee, Salary; P. Hugon, Da Volterra: Employee, Salary; F. Sablier-Gallis, Da Volterra: Employee, Salary; S. Ferreira, Genoscreen: Employee, Salary; A. Andremont, Da Volterra: Consultant, Consulting fee; F. Mentré, Da Volterra: Consultant and Research Contractor, Consulting fee; J. De Gunzburg, Da Volterra: Consultant and Shareholder, Consulting fee
Factors Affecting Effectiveness of Fecal Microbiota Transplant
Authors: Mosby Danielle , Mcgraw Patty , Duffalo Chad , Drees Marci , Depalma Fedele , Herdman Christine , Myerson Scott , Bacon Alfred E
Published: October 2017

Background

Fecal microbiota transplant (FMT) is an effective treatment for relapsing Clostridium difficile infection (CDI). With more widespread use of this intervention, variable cure rates (70–95%) have been observed. We conducted this study to identify specific patient- and procedure-level factors affecting FMT effectiveness, hypothesizing that those patients with higher comorbidity, inadequate bowel preparation, and shorter retention of transplant would fail more frequently.

Methods

At our 2-hospital, >1100-bed community-based academic center, we prospectively followed patients pre/post-FMT between June 2014-April 2017. To undergo FMT, patients must have ≥2 CDI relapses and failed vancomycin taper. We entered all FMT patients into a registry and followed them regularly for up to 1 year, collecting age, Charlson Comorbidity Index, number of CDI relapses, Boston bowel prep score, and stool retention time. FMT donor stool was obtained from OpenBiome (Boston, MA). We defined failure as recurrent CDI requiring treatment ≤8 weeks after FMT. We used 1-sided t-tests to test our hypotheses.

Results

During the study period, 41 patients (mean age 65 years, SD 17.6) underwent FMT. Most (37, 90%) were performed via colonoscopy, 1 via upper endoscopy, and 3 via oral preparation (capsules). FMT failure occurred in 10 patients (24.4%). Nearly half (n = 20) reported adverse events, including constipation, gas, abdominal pain, blood in stool, and fatigue. Three patients expired from comorbid disease, and 3 were lost to follow-up. Patients with higher Charlson scores failed more frequently (P = 0.04), and history of tumor (P = 0.03) and pulmonary disease (P = 0.04) were both associated with failure. No other factors, including age, retention time, and Boston bowel prep score, were associated with failure.

Conclusion

This study found that patients with multiple comorbid conditions, as defined by the Charlson index, are at risk for FMT failure. However, quality of bowel prep and retention time did not predict FMT failure. Future studies should include larger samples of FMT patients to determine whether specific comorbidities such as history of tumor and pulmonary disease are clinically significant predictors of FMT failure.

Disclosures

All authors: No reported disclosures.