Cause Of Bloodstream Infections Research Articles

Design, Synthesis and Anticandidal Evaluation of Indazole and Pyrazole Derivatives.

Candidiasis, caused by yeasts of the genus Candida, is the second cause of superficial and mucosal infections and the fourth cause of bloodstream infections. Although some antifungal drugs to treat candidiasis are available, resistant strains to current therapies are emerging. Therefore, the search for new candicidal compounds is certainly a priority. In this regard, a series of indazole and pyrazole derivatives were designed in this work, employing bioisosteric replacement, homologation, and molecular simplification as new anticandidal agents. Compounds were synthesized and evaluated against C. albicans, C. glabrata, and C. tropicalis strains. The series of 3-phenyl-1H-indazole moiety (10a–i) demonstrated to have the best broad anticandidal activity. Particularly, compound 10g, with N,N-diethylcarboxamide substituent, was the most active against C. albicans and both miconazole susceptible and resistant C. glabrata species. Therefore, the 3-phenyl-1H-indazole scaffold represents an opportunity for the development of new anticandidal agents with a new chemotype.

Preconceptual Priming Overrides Susceptibility to Escherichia coli Systemic Infection during Pregnancy.

ABSTRACTMaternal sepsis is a leading cause of morbidity and mortality during pregnancy. Escherichia coli is a primary cause of bacteremia in women and occurs more frequently during pregnancy. Several key outstanding questions remain regarding how to identify women at highest infection risk and how to boost immunity against E. coli infection during pregnancy. Here, we show that pregnancy-induced susceptibility to E. coli systemic infection extends to rodents as a model of human infection. Mice infected during pregnancy contain >100-fold-more recoverable bacteria in target tissues than nonpregnant controls. Infection leads to near complete fetal wastage that parallels placental plus congenital fetal invasion. Susceptibility in maternal tissues positively correlates with the number of concepti, suggesting important contributions by expanded placental-fetal target tissue. Remarkably, these pregnancy-induced susceptibility phenotypes are also efficiently overturned in mice with resolved sublethal infection prior to pregnancy. Preconceptual infection primes the accumulation of E. coli-specific IgG and IgM antibodies, and adoptive transfer of serum containing these antibodies to naive recipient mice protects against fetal wastage. Together, these results suggest that the lack of E. coli immunity may help discriminate individuals at risk during pregnancy, and that overriding susceptibility to E. coli prenatal infection by preconceptual priming is a potential strategy for boosting immunity in this physiological window of vulnerability.

Antimicrobial susceptibility testing of Eggerthella lenta blood culture isolates at a university hospital in Belgium from 2004 to 2018

ObjectivesEggerthella lenta is a Gram-positive anaerobic bacillus that is an important cause of bloodstream infections. This study aims to test the susceptibility of Eggerthella lenta blood culture isolates to commonly used antibiotics for the empirical treatment of anaerobic infections. MethodsIn total, 49 positive blood cultures for Eggerthella lenta were retrospectively included from patients hospitalised at the Universitair Ziekenhuis Brussel, Belgium, between 2004 and 2018. Identification was done by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) system. Antimicrobial susceptibility testing was performed using the reference agar dilution method according to Clinical and Laboratory Standards Institute (CLSI) guidelines with Brucella agar supplemented with 5 μg/mL hemin, 1 μg/mL vitamin K1 and 5% laked sheep blood.The minimal inhibitory concentrations were interpreted using the EUCAST breakpoints. Clinical characteristics were collected by reviewing the patient’s medical records. ResultsAll isolates were susceptible to amoxicillin-clavulanate, metronidazole and meropenem. Eighty-eight % of them were susceptible to clindamycin and 94% (20% S, 74% I) were susceptible to piperacillin-tazobactam. The mean age of the patients was 64 (±20) and they showed a 30-day mortality of 27%. The source of infection was in 65.3% of the cases abdominal, 20.4% were sacral pressure ulcers and 14.3% were unknown causes.While all isolates were fully susceptible at standard dosing regimen to amoxicillin-clavulanate, most were only susceptible at increased exposure or resistant to piperacillin-tazobactam. ConclusionsOur results suggest to be careful with the use of piperacillin-tazobactam and clindamycin in the empirical treatment of Eggerthella lenta infections.

Antimicrobial Resistance Patterns and Antibiotic Use during Hospital Conversion in the COVID-19 Pandemic.

Objective: To describe empirical antimicrobial prescription on admission in patients with severe COVID-19, the prevalence of Hospital-Acquired Infections, and the susceptibility patterns of the causing organisms. Methods: In this prospective cohort study in a tertiary care center in Mexico City, we included consecutive patients admitted with severe COVID-19 between March 20th and June 10th and evaluated empirical antimicrobial prescription and the occurrence of HAI. Results: 794 patients with severe COVID-19 were admitted during the study period. Empiric antibiotic treatment was started in 92% of patients (731/794); the most frequent regimes were amoxicillin-clavulanate plus atypical coverage in 341 (46.6%) and ceftriaxone plus atypical coverage in 213 (29.1%). We identified 110 HAI episodes in 74/656 patients (11.3%). Ventilator-associated pneumonia (VAP) was the most frequent HAI, in 56/110 (50.9%), followed by bloodstream infections (BSI), in 32/110 (29.1%). The most frequent cause of VAP were Enterobacteriaceae in 48/69 (69.6%), followed by non-fermenter gram-negative bacilli in 18/69 (26.1%). The most frequent cause of BSI was coagulase negative staphylococci, in 14/35 (40.0%), followed by Enterobacter complex in 7/35 (20%). Death occurred in 30/74 (40.5%) patients with one or more HAI episodes and in 193/584 (33.0%) patients without any HAI episode (p < 0.05). Conclusion: A high frequency of empiric antibiotic treatment in patients admitted with COVID-19 was seen. VAP and BSI were the most frequent hospital-acquired infections, due to Enterobacteriaceae and coagulase negative staphylococci, respectively.

Prevalence and antibiogram of non-fermenting Gram-negative bacilli in blood stream infections: Study in a tertiary care centre, Western Uttar Pradesh, India.

Non-fermenting Gram-negative bacilli (NFGNB) are emerging as important cause of blood stream infections. We aimed to determine the prevalence and antibiotic susceptibility pattern of NFGNB isolated from blood of patients with sepsis. We found, in 176 patients, the most common to be Pseudomonas aeruginosa (74) and Acinetobacter baumanii complex (39) followed by Stenotrophomonas maltophilia (16), Sphingomonas paucimobilis (6), Burkholderia cepacia (5) and Ochrobactrum anthropic (1). Generally, organisms showed a good sensitivity towards colistin, carbapenems and fluoroquinolones, whereas cephalosporins were ineffective.

Impact of an Antimicrobial Stewardship Program-bundled initiative utilizing Accelerate Pheno\u2122 system in the management of patients with aerobic Gram-negative bacilli bacteremia

PurposeGram-negative bacteria (GNB) are a leading cause of bloodstream infections (BSI) and management is complicated by antibiotic resistance. The Accelerate Pheno™ system (ACC) can provide rapid organism identification and antimicrobial susceptibility testing (AST).MethodsA retrospective, pre-intervention/post-intervention study was conducted to compare management of non-critically ill patients with GNB BSI before and after implementation of a bundled initiative. This bundled initiative included dissemination of a clinical decision algorithm, ACC testing on all GNB isolated from blood cultures, real-time communication of results to the Antimicrobial Stewardship Program (ASP), and prospective audit with feedback by the ASP. The pre-intervention period was January 2018 through December 2018, and the post-intervention period was May 2019 through February 2020.ResultsSeventy-seven and 129 patients were included in the pre-intervention and post-intervention cohorts, respectively. When compared with the pre-intervention group, the time from Gram stain to AST decreased from 46.1 to 6.9 h (p < 0.001), and the time to definitive therapy (TTDT) improved from 32.6 to 10.5 h (p < 0.001). Implementation led to shorter median total duration of antibiotic therapy (14.2 vs 9.5 days; p < 0.001) and mean hospital length of stay (7.9 vs 5.3 days; p = 0.047) without an increase in 30-day readmissions (22.1% vs 14%; p = 0.13).ConclusionImplementation of an ASP-bundled approach incorporating the ACC aimed at optimizing antibiotic therapy in the management GNB BSI in non-critically ill patients led to reduced TTDT, shorter duration of antibiotic therapy, and shorter hospital length of stay without adversely affecting readmission rates.

Changing epidemiology and risk factors for candidemia in critically ill patients

Background/Aim: Candidemia is a common cause of bloodstream infections in critically ill patients, resulting in high mortality and morbidity. This retrospective case-control study was designed to identify epidemiological characteristics and risk factors for candidemia in an intensive care unit. Methods: A total of 166 patients hospitalized in the intensive care unit between January 2013 and December 2017 were included in this case-control study. Candidemia was defined as at least one positive blood culture for Candida spp. with fever or other clinical findings consistent with infection. Patients who acquired candidemia more than 48 hours after admission represented the case group (n=83). Control group (n=83) consisted of case-matching patients who were hospitalized during the same period and did not develop candidemia. Results: In the candidemia group Candida albicans (57.8%) was the most common species, followed by Candida glabrata (13.3%) and Candida parapsilosis (12%). The rate of C. albicans decreased from 69.2% to 50% during the five-year study period. Out of 83 candidemia infections, 36 (43.4%) were associated with central venous catheters. C. parapsilosis had an increasing rate in parallel with central venous catheter-associated candidemia rates. When comparing cases and controls, in univariate analysis, Sequential Organ Failure Assessment (SOFA) score, blood transfusion, central venous catheter placement, intubation, gastrointestinal surgery and total parenteral nutrition were significantly more common in the candidemia group (P<0.05 for each). The rate of the patients whose Candida scores were higher or equal to 3, was significantly higher in candidemia group (P=0.03). According to the multivariate analysis, SOFA scores (P<0.001, OR:1.25, 95% CI:1.15-1.37), gastrointestinal surgery (P=0.03, OR:2.60, 95% CI:1.10-6.12), central venous catheter (P=0.04, OR:2.62, 95% CI:1.05-6.57) and total parenteral nutrition (P=0.02, OR:2.61, 95% CI:1.12-6.06) were independent risk factors for candidemia, while enteral feeding (P=0.02, OR:0.27, 95% CI:0.09-0.80) was protective against. Conclusion: The result of our study is an evidence of the changing epidemiology of candidemia, which showed a shift towards non-albicans Candida spp. over the years. The increasing rate of C. parapsilosis and central venous catheter-associated candidemia has highlighted the need for more attention to the central line care and hand hygiene. Our study also revealed that critically ill patients with high SOFA score, gastrointestinal surgery, central venous catheter, and total parenteral nutrition have an elevated risk for developing candidemia. Unless necessary, limitation of total parenteral nutrition, and ensuring the earlier implementation of enteral feeding may be protective from candidemia.

1566. In vitro Activities of Ceftaroline and Comparator Agents against Gram-positive Bacterial Pathogens Causing Blood Stream Infections in a Global Population: ATLAS Surveillance Program 2012-2018

BackgroundTypical gram-positive organisms causing bloodstream infections (BSI) include Staphylococcus aureus (methicillin-susceptible [MSSA] and -nonsusceptible [MRSA]), coagulase negative staphylococci, Streptococcus pneumoniae and beta hemolytic streptococci. The parenteral cephem ceftaroline fosamil is approved for treatment of patients with community-acquired bacterial pneumonia caused by S. pneumoniae (including cases with concurrent bacteremia), MSSA, Haemophilus influenzae, and some species of Enterobacterales. Limited data have been published on the in vitro activity of ceftaroline against recent gram-positive clinical isolates known to be frequent bacterial causes of blood stream infections.MethodsStandard CLSI broth microdilution MIC determinations (M07) were performed with ceftaroline and comparator agents. MICs were interpreted using 2020 CLSI MIC breakpoints. Clinically relevant, non-duplicate, isolates cultured from blood by clinical laboratories in 2012-2018 were tested by the ATLAS (Antimicrobial Testing Leadership and Surveillance) program central laboratory (IHMA, Inc., Schaumburg, IL, USA). In total, 10,998 non-duplicate isolates of S. aureus, S. epidermidis, S. pneumoniae and beta hemolytic streptococci from BSI collected between 2012 and 2018 were tested. Isolates came from (n/%): Asia/South Pacific (1,739/15.8%), Europe (5,448/49.5%), Latin America (1,805/16.4%), MidEast/Africa (861/7.8%), and North America (1,145/10.4%).ResultsCeftaroline and comparator agent activities are summarized in the following table.Table ConclusionGreater than 98% of S. pneumoniae, S. epidermidis, beta-hemolytic streptococci and MSSA isolates included in a 2012-2018 collection of gram-positive blood stream pathogens were susceptible to ceftaroline. 91.4% of MRSA were susceptible, and 8.6% isolates categorized as susceptible-dose dependent (MIC, 2-4 ug/mL); two isolates (one each from Thailand and S. Korea) were resistant to ceftaroline (MIC >4 ug/mL). Ceftaroline continues to demonstrate potent in vitro activity against clinically relevant pathogens associated with BSI.Disclosures Greg Stone, PhD, AztraZeneca (Shareholder, Former Employee)Pfizer, Inc. (Employee) Daniel F. Sahm, PhD, IHMA (Employee)Pfizer, Inc. (Consultant)Shionogi & Co., Ltd. (Independent Contractor)

291. Impact of Surveillance and Offered Infectious Diseases Consults for Staphylococcus aureus Bacteremia on Quality of Care Indicators

Background Staphylococcus aureus bacteremia (SAB) remains the leading cause of bloodstream infections and is associated with 20–40% mortality. Past studies demonstrated that Infectious Diseases (ID) consultation is associated with better adherence to quality of care indicators (QCIs), including follow-up blood cultures, echocardiography, early source control, and appropriate choice and duration of antibiotics. A 2014 quality improvement project at Medstar Washington Hospital Center (MWHC) by Narsana et al. showed significantly better adherence to SAB QCIs among patients with ID consults and a non-significant trend towards lower mortality. In 2015, MWHC instituted a policy advocating ID consultation for all SAB patients, and active surveillance was performed by the ID Section to offer prompt consults prospectively. Our study aimed to assess the impact of this policy and the proactively offered ID consults on adherence to SAB QCIs and mortality rates amongst patients with SAB with and without ID consults.MethodsWe retrospectively reviewed 557 patients diagnosed with SAB between July 1st, 2015 - June 30th, 2018. Data included follow-up blood cultures, echocardiography, presence of a focal source of infection, use of appropriate antibiotics, measurement of vancomycin levels, duration of therapy, death during hospitalization, and presence of an ID consultation. Chi-Square and Fisher exact tests, and t-test and Wilcoxon rank sum test were used to analyze categorical and continuous variables, respectively.ResultsA total of 513 patients were included in the analysis, 88% (n=453) of whom had ID consultations. Patients with ID consultations were more likely to have a focal source of infection (84% vs. 50%, p < 0.0001), echocardiography (97% vs. 56%, p < 0.0001), use of a beta-lactam antibiotic for methicillin-susceptible S. aureus (90% vs 65%, p < 0.0001), and a longer duration of therapy (33 vs 9 days, p< 0.0001). Mortality was lower among patients with ID consults (16% vs. 23%, p=0.1495), but the difference was not statistically significant.Table 1 ConclusionOur study demonstrates that ID consultation is associated with better adherence to SAB QCIs, with a trend towards lower mortality. Hospital systems should support mandatory ID consultation for patients with Staphylococcus aureus bacteremia.Disclosures All Authors: No reported disclosures

270. Clinical Outcomes of Ceftriaxone versus Penicillin G for Complicated Viridans Group Streptococci Bacteremia

BackgroundViridans group streptococci (VGS) is an infrequent yet significant cause of bloodstream infections, and complicated cases may require prolonged antibiotic therapy. Ceftriaxone (CTX) and penicillin G (PCN G) are both considered first line options for VGS infections, but comparisons between these agents are limited. We evaluated the clinical outcomes amongst patients treated with CTX and PCN G for complicated VGS bacteremia.MethodsThis was a single-center, retrospective study of adult patients with ≥1 positive VGS blood culture who were treated with either CTX or PCN G/ampicillin (both included in PCN G arm) between January 2013 and June 2019. The primary outcome was a composite of safety endpoints, including hospital readmission due to VGS or an adverse event (AE) from therapy, Clostridioides difficile infections, treatment modification or discontinuation due to an antibiotic-related AE, and development of extended-spectrum beta lactamase resistance. Secondary outcomes included the individual safety endpoints, VGS bacteremia recurrence, hospital readmission, and all-cause mortality.ResultsOf 328 patients screened for inclusion, 94 patients met eligibility criteria (CTX n= 64, PCN G n=34). Median age was 68 years (IQR 56–81) and 68% were male. Study patients did not present with critical illness, as reflected by a median Pitt bacteremia score of 0 in the CTX and 1 in the PCN G arms, P=0.764. Streptococcus mitis was the most common VGS isolate and infective endocarditis (IE) was the predominant source of infection. CTX was not significantly associated with increased risk of the primary outcome (14% vs. 27%; P= 0.139). The driver of the composite outcome was hospital readmission due to VGS bacteremia or therapy complications. Results were similar in the subgroup of patients with IE (12.5% vs. 23.5%). No secondary endpoints differed significantly between groups. On multivariate analysis, source removal was a protective factor of the primary outcome (OR 0.1; 95% CI 0.020–0.6771; P= 0.017).ConclusionDespite potential safety concerns with the prolonged use of CTX in complicated VGS bacteremia, this study did not demonstrate a higher rate of treatment failure, adverse events, or resistance. These findings warrant further exploration.Disclosures All Authors: No reported disclosures

1449. Frequency and Antimicrobial Susceptibility of Coagulase-Negative Staphylococcal (CoNS) Species Isolated from Clinical Specimens in United States and European Hospitals

BackgroundCoNS represent an important cause of bloodstream infections, osteoarticular infections, foreign-body-associated infections and endocarditis. We evaluated the frequency of CoNS species and the activity of dalbavancin (DALB) in comparison to vancomycin (VAN), daptomycin (DAP) and other agents against a large collection of CoNS isolates.Methods5,088 CoNS isolates causing clinically significant infection were consecutively collected from 122 medical centers located in the United States (79 centers) and Europe (43 centers in 21 nations) over 6 years (2014-2019) and susceptibility tested by CLSI broth microdilution methods against DALB and comparators. Species identification was confirmed by MALDI-TOF.ResultsMost isolates were from bloodstream (BSI; 53.5%) or skin/skin structure infections (28.5%). S. epidermidis was the most common species overall (54.6%; Table) and for BSI (61.3%). The second most common species were S. lugdunensis overall (12.3%) and S. hominis for BSI (14.7%). DALB (MIC50/90, 0.03/0.06 mg/L) inhibited > 99.9% of CoNS isolates at the susceptible (S) breakpoint established by CLSI for S. aureus (≤ 0.25 mg/L) and was 8-fold more active than DAP (MIC50/90, 0.25/0.5 mg/L; 99.9% S) and 32-fold more active than VAN (MIC50/90, 1/2 mg/L; > 99.9% S). Linezolid was active against 98.7% of isolates (MIC50/90, 0.5/1 mg/L). All species were inhibited at ≤0.25 mg/L of DALB, except S. epidermidis (> 99.9%) and S. warneri (98.9%; Table). The most DALB-S species were S. capitis and S. simulans (MIC50/90, 0.015/0.03 mg/L for both species), whereas the highest DALB MIC50/90 values were observed with S. haemolyticus and S. saprophyticus (MIC50/90, 0.06/0.12 mg/L and highest MIC of 0.25 mg/L for both species). In contrast, 47.8% of S. epidermidis and 34.7% S. haemolyticus exhibited decreased susceptibility to VAN (MIC ≥ 2 mg/L), and 23.2% of S. capitis and 28.4% of S. warneri showed decreased susceptibility to DAP (MIC ≥ 1 mg/L). Overall oxacillin-S rate was 39.3%, varying from 3.0% for S. saprophyticus to 95.4% for S. lugdunensis. In general, BSI isolates were slightly less S than non-BSI isolates.ConclusionAntimicrobial susceptibility varied widely among CoNS species. DALB exhibited potent in vitro activity against all CoNS species.Table 1 Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Jennifer M. Streit, BS, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support) S. J. Ryan Arends, PhD, Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

664. LiaX as a Surrogate Marker of Daptomycin Susceptibility in Multidrug-Resistant Enterococcus faecium Recovered from Cancer Patients

BackgroundVancomycin-resistant Enterococcus faecium (VREfm) are leading causes of bloodstream infections (BSI) in patients (pts) with hematological malignancies (HM). Daptomycin (DAP) is commonly used to treat VRE BSI, but DAP non-susceptibility (DAP-NS) in pts with HM is increasing. Current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility. DAP triggers the LiaFSR cell membrane stress response pathway, resulting in the extracellular release of the protein LiaX, a novel protein that functions as a regulator of the membrane response. We postulated that detection of extracellular LiaX correlates with DAP-NS in clinical strains of VREfm.MethodsWe used 6 well-characterized VREfm BSI isolates (2 DAP-S, 4 DAP-NS) as reference strains to optimize a whole-cell indirect enzyme-linked immunosorbent assay (ELISA) method for LiaX detection. We assessed limit of detection and reproducibility of the ELISA LiaX method. We then assessed 54 clinical VREfm BSI isolates from pts with cancer for validation. We determined DAP MICs by broth microdilution (BMD). We collected clinical and microbiological details by chart reviewResultsThe 6 reference strains showed high reproducibility with low coefficient of variation. All DAP-NS reference strains had increased detection of LiaX (p< 0.0001) compared to DAP-S reference strains. Of the 54 isolates from pts, most pts (83.3%) had HM. The source of 62.9% of VRE BSIs was determined to be gastrointestinal. Six of the 54 isolates were DAP-NS by BMD MIC. The LiaX test and MIC had categorical agreement on 56% of isolates. Of the isolates with disagreement, 19 isolates were susceptible by MIC (median 2 μg/ml) but non-susceptible by LiaX ELISA, and 5 isolates were non-susceptible by MIC (6, 8, 8, 8, and 16 μg/ml, respectively) but susceptible by LiaX ELISA.Whole-cell indirect LiaX ELISA A405nm of Efm reference strains shows ability to differentiate DAP susceptible MICs from DAP resistant MICs. DAP susceptible (MIC=2 μg/ml) Efm strains are shown in green and DAP resistant (MIC≥8 μg/ml) strains in red. DAP-S reference strains have no LiaFSR mutations. The dotted line indicates an example cutoff for DAP-S/R in this assay. *p<0.05, **p<0.0001 by unpaired t-test. Coefficieint of variance for each reference is <15%. ConclusionDetection of extracellular LiaX has important discrepancies with DAP MIC. Interestingly, LiaX may be a surrogate marker to detect strains with heightened DAP-mediated cell membrane response and potentially identify strains predisposed to DAP therapy failure. Further characterization of the discrepant isolates by genomic analyses and time-kill assays are warranted to fully validate the performance of LiaX ELISA.Disclosures Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

278. Comparison of Oral Cephalexin Versus Oral Levofloxacin for Treatment of Uncomplicated Enterobacterales Bacteremia

BackgroundAerobic gram-negative rods (GNR) are a common cause of bloodstream infections. While the use of oral antibiotics as step-down therapy for GNR bacteremia is generally accepted, there is debate as to which agents are best. Fluoroquinolones have high oral bioavailability but also have concerns for toxicity, while oral beta-lactams have lower achievable blood concentrations and require more frequent dosing. At Kaweah Delta Medical Center, patients are transitioned from IV antibiotics to oral levofloxacin or cephalexin. The purpose of this study is to determine if these two oral agents are comparable when used as step-down therapy for uncomplicated GNR bacteremia.MethodsThis was a single-center, retrospective study of adult patients who were admitted from May 2018 - May 2019 with a positive GNR blood culture. The primary objective was to assess treatment failure defined as a composite outcome of readmission due to recurrent bacteremia or mortality within 60-days. Secondary outcomes included subsequent Clostridioides difficile infection, emergence of resistant GNR bacteria, and hospital length of stay.ResultsA total of 82 patients met inclusion criteria. The combined median age of both treatment groups was 58.2 years (interquartile range [IQR], 46.7–73.5) and greater than 60% of patients were female. Most patients were Hispanic (45.1%) or non-Hispanic white (43.9%). The most common documented source of GNR bacteremia was the urinary tract (74.4%), and the most frequently recovered organism was Escherichia coli (78.0%). Patients were treated with IV antibiotics for a median treatment duration of 4 days (IQR, 4–5) and oral antibiotics for a median treatment duration of 10 days (IQR, 7.3–11) and 9 days (IQR, 7–11) for cephalexin and levofloxacin, respectively. The composite outcome occurred in 2 patients (4.3%) from the cephalexin group and 0 patients from the levofloxacin group (p=0.50). Positive cultures for resistant GNR were found for 3 patients in the cephalexin group. No patients developed subsequent C. difficile infections. ConclusionPatients who received cephalexin or levofloxacin did not have a significant difference in the composite primary outcome. These findings suggest that oral cephalexin is an effective step-down option to treat uncomplicated GNR bacteremia.Disclosures All Authors: No reported disclosures

Clonal diversity of methicillin-resistant Staphylococcus aureus (MRSA) from bloodstream infections in northern Japan: Identification of spermidine N-acetyltransferase gene (speG) in staphylococcal cassette chromosomes (SCCs) associated with type II and IV SCCmec

ObjectivesMethicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of bloodstream infections (BSIs). We aimed to study molecular epidemiological characteristics of MRSA isolates from BSIs in northern Japan to elucidate the recent trend of their clonal diversity. MethodsMRSA isolates (n = 277) were collected from blood samples of patients who attended healthcare facilities in Hokkaido, the northern main island of Japan, for a two-year period from August 2017. Genotypes, virulence factors/drug-resistance determinants, and structure of SCCmec complex were analysed by PCR and sequencing analysis. ResultsSCCmec-IIa (n = 171, 61.7%) with coagulase genotype (coa-) II, ST5/ST764/ST2389 was the most common genetic trait, followed by SCCmec-IVa (n = 78, 28.2%), and IVl (n = 10, 3.6%). Among the MRSA-IVa, 14 isolates (5.1% of all the isolates) had genetic features identical to USA300 clone (ST8/coa-IIIa/spa-t008 having ΦSa2USA and ACME-I), while PVL/ACME-negative MRSA-IVa isolates (n = 64) were classified into coa-IIa/IIIa/VIIa/VIIb, with coa-VIIa/spa-t1784/ST1 being dominant. Other minor clones included ST8-SCCmec-I, and ST30/ST45/ST81/ST121/ST1232-SCCmec-V, among which the ST1232 isolate harboured PVL genes. Spermidine N-acetyltransferase gene (speG), which is typically present in ACME-I of USA300 clone, was also identified in two isolates, ACME-II’-positive ST764-MRSA-IIa and ACME-negative ST1-MRSA-IVa, showing resistance to spermine. speG of these isolates was located in additional SCCs adjacent to SCCmec. ConclusionsOur present study revealed clonal diversity of MRSA from BSIs in Japan, with increased prevalence of ST8-USA300. Distinct types of speG-carrying SCCs associated with SCCmec-II or IV were identified.

(1,3)-β-D-glucan is able to predict therapeutic failure of patients with candidemia and not only mortality.

Candidemia is a major cause of bloodstream infection in tertiary hospitals worldwide and fungal biomarkers may provide early diagnosis. To evaluate the performance of (1-3)-β-D-glucan (BDG) in the diagnosis of candidemia and its ability to predict therapeutic failure. This was a prospective, multi-centre study conducted in 3 Brazilian hospitals. Clinical outcome was evaluated along 2weeks of treatment, and therapeutic failure was defined as the occurrence of persistent candidemia, Candida deep-seated infection or death. Baseline BDG detection was performed with the Fungitell® assay (Associates of Cape Cod, Falmouth-USA). We enrolled a total of 71 patients with candidemia and a control group with 110 healthy volunteers. The sensitivity and specificity of BDG for diagnosing candidemia were as follows: 71.8% (95% confidence interval [95% CI] 59.7% - 81.5%) and 98.2% (95% CI 92.9% - 99.7%), respectively. The only predictor of therapeutic failure was a higher BDG value at diagnosis of candidemia; a value>226pg/mL predicted failure with sensitivity and specificity of 75% and 78%, respectively. A high baseline serum BDG value was associated with therapeutic failure.

Antibiogram of klebsiella pneumoniae recovered from blood stream infection at tertiary care hospital, Baroda, Gujarat

Introduction: Antimicrobial abuse is a serious risk factor for the emergence of multi-drug-resistant (MDR) pathogens. Multidrug resistant (MDR) Klebsiella pneumoniae is an increasing cause of blood stream infections in India and in other developing countries. Aim: This study was undertaken to determine the prevalence of Klebsiella pneumoniae in blood stream infections and their susceptibility pattern at S. S. G. Hospital, Baroda. Material and Methods: 169 isolates of Klebsiella pneumoniae were obtained from blood culture samples from hospitalized patients. K.pneumoniae species were identified based on biochemical reactions. Their sensitivity pattern were checked by Kirby-bauer disc diffusion technique as per CLSI guideline. Antimicrobial discs used were Ceftazidime (30µg), Cefotaxime (30µg), Imipenem (10 µg), Levofloxacin (5 µg), Aztreonam (30 µg), Co-trimoxzole (25 µg), Ampicilin (10 µg), Gentamicin (10 µg), Amikacin (30 µg), Doxycycline (30 µg). Results: 950 blood cultures were studied from suspected patients and the prevalence of K. pneumoniae among them was checked with its antimicrobial susceptibility at Department of Microbiology, Tertiary care hospital, Gujarat. Among 950 suspected patients in the study period, K.pneumoniae was found in 169 blood culture samples. Conclusion: Infections with K.pneumoniae are increasing, particularly among paediatric patients. This pathogen is usually multidrug-resistant and there are limited treatment options available. This result warns us for implementation of infection control measures to limit intra-institutional spread of these organisms. Keyword: K.pneumoniae, Antimicrobial tests, Infection control.

Epidemiological profile of candida isolated from septicemic patients

Introduction: Candida is an important cause of blood stream infections (BSI). It ranks fourth in the United States and seventh in Europe. It is a leading cause of morbidity and mortality in critically ill patients. There is an epidemiological shift from a predominance of Candida albicans to non albicans Candida species in recent decades. Speciation of Candida can help in better approach towards outcome of the patients and to know the intrinsic resistance of various Candida species to antifungal agents. Objectives: To determine the epidemiological profile of Candida infection in septicemic patients and to identify the Candida species isolated. Materials and Methods: A hospital based descriptive study was conducted over a period of 2 years in a tertiary care centre. Candida was isolated in blood culture from 54 patients. Candida isolates were identified to the species level, using both conventional and automated techniques. Results: The most common Candida species isolated were C.parapsilosis complex, C.tropicalis, C.albicans, C.krusei, C.glabrata, C.haemulonii, C.firmetaria and C.guillermondii var membranifaciens. Significant risk factors for candidemia includes HIV/AIDS, diabetes, antibiotic therapy, chemotherapy, presence of intravascular catheters, malignancy, surgery, parenteral nutrition. 51.85% of the patients received antifungal therapy with Fluconazole (71.43%) being the most common treatment option which is followed by Voriconazole (10.71%) and Amphotericin B (7.14%). Conclusion: Candidemia is a significant cause of mortality with C. parapsilosis and C. tropicalis being the predominant pathogens. This study shows a significant epidemiological shift to higher isolation of non albicans Candida species. Keywords: Candida species, Epidemiological profile, Septicemic, Risk factors.

Epidemiology of bloodstream infection among paediatric population in Hospital Kuala Lumpur from January 2016 until December 2017

Background: Bloodstream infection (BSI) is a major cause of morbidity and mortality. The classification of infection into community-acquired, hospital-acquired, and healthcare-associated infection provides an educated guess on the possible etiological agents and appropriate empirical antimicrobial therapy to be instituted. This study aims to determine the etiological agents, the antimicrobial susceptibility patterns and the classification of infections among the paediatric population. Methods & Materials: A total of 5549 blood cultures were received from the paediatric population from January 2016 to December 2017. Negative blood cultures of 4534 were excluded, 309 blood cultures with poor identification/missing data/repetitive isolates were excluded. A further 403 isolates were excluded as contaminant organisms. A total of 303 isolates were included in this study which was obtained from 238 patients. The patients’ microbiological worksheets and medical notes were reviewed to determine the antimicrobial susceptibility patterns, demographic data, classification of infection and the outcome (survival versus death). Results: Most of the patients were in the age group of one to less than five years old (41%) with 58% male and 85% Malay patients. Common causes of BSI were Staphylococcus aureus (17%), followed by Klebsiella pneumoniae (15%), Acinetobacter baumanii (10%), Pseudomonas aeruginosa (10%) and Escherichia coli (6%). Sixty percent of BSI episodes were caused by gram-negative bacteria, 34% by gram-positive bacteria and 6% by fungi. Most of the infections were classified as hospital-acquired infections (72%), followed by healthcare-associated (20%) and community-acquired infections (8%). There were 33% of methicillin-resistant S. aureus, 53% of extended-spectrum beta-lactamase (ESBL) producing K. pneumoniae and 33% of ESBL producing Escherichia coli. The overall case fatality rate (CFR) was 27% with the highest CFR caused by Serratia marcescens (53.3%). Conclusion: The majority of bloodstream infections are hospital-acquired. Improvement in prevention strategies and revisions in antibiotic policies are important to overcome it.

In vitro evaluation of anti-fungal activity of tropicamide against strains of Candida spp. resistant to fluconazole in planktonic and biofilm form

Candida spp. is considered to be the third or fourth most common cause of bloodstream infections associated with healthcare services in the world. Currently, several strains exhibit resistance to the traditional treatments, making the development of new therapeutic molecules necessary. Drug repositioning is an alternative that can be used to work around problems such as toxicity, cost and time in the development of new drugs. This study aims to evaluate the in vitro antifungal effect of tropicamide, molecule of anticholinergic action, against planktonic cells of Candida spp. and biofilm of C.albicans. Six strains of different Candida species were used to determine the minimum inhibitory concentration (MIC) of tropicamide and fluconazole according to CLSI document M27-A3 and one strain of C.albicans was used to evaluate the activity of tropicamide against biofilms. In concentrations of 64μg/mL, the tropicamide exhibited 50% of inhibitory activity in planktonic cell and in concentrations of 128μg/mL is able to inhibit the formation of C.albicans biofilm. Despite the inhibitory activity shown at the present study, the use of a larger number of strains, as well as in vivo cytotoxicity assays, is necessary to confirm the hypothesis that tropicamide can be used as an adjuvant agent in the treatment of infections by the Candida genus.

Comparative Genome Analysis Reveals the Molecular Basis of Niche Adaptation of Staphylococcus epidermidis Strains.

Staphylococcus epidermidis is one of the most commonly isolated species from human skin and the second leading cause of bloodstream infections. Here, we performed a large-scale comparative study without any pre-assigned reference to identify genomic determinants associated with the diversity and adaptation of S. epidermidis strains to various environments. Pan-genome of S. epidermidis was open with 435 core proteins and had a pan-genome size of 8,034 proteins. Genome-wide phylogenetic tree showed high heterogeneity and suggested that routine whole genome sequencing was a powerful tool for analyzing the complex evolution of S. epidermidis and for investigating the infection sources. Comparative genome analyses demonstrated a range of antimicrobial resistance (AMR) genes, especially those within mobile genetic elements. The complicated host-bacterium and bacterium-bacterium relationships help S. epidermidis to play a vital role in balancing the epithelial microflora. The highly variable and dynamic nature of the S. epidermidis genome may contribute to its success in adapting to broad habitats. Genes related to biofilm formation and cell toxicity were significantly enriched in the blood and skin, demonstrating their potentials in identifying risk genotypes. This study gave a general landscape of S. epidermidis pan-genome and provided valuable insights into mechanisms for genome evolution and lifestyle adaptation of this ecologically flexible species.