Cause Of Bloodstream Infections Research Articles

PROPORTION OF ESBL AND CARBAPENEMASE PRODUCING ENTEROBACTERIACEAE CAUSING BLOODSTREAM INFECTIONS AND SHOWING MULTI DRUG RESISTANCE IN INFECTED PATIENTS IN TERTIARY CARE HOSPITAL AT AGARTALA, TRIPURA

BACKGROUND: Enrerobacteriaceae species are the major leading cause of bloodstream infections in many developing countries. Moreover, ESBL and Carbapenemase-producing Enterobacteriaceae species are often associated with high resistance to a wide class of antibiotics. There are few studies regarding the bloodstream infections causing by Enterobacteriaceae with the production of Extended-spectrum β-lactamases and Carbapenemase enzymes in Tripura, North-East India. This study aimed to determine the “ proportion of ESBL and carbapenemase-producing Enterobacteriaceae causing bloodstream infection and showing Multi-drug resistance (MDR) in infected patients'' in Tertiary care Hospital at Agartala, Tripura. METHOD: Blood samples were collected from all indoor and outdoor patients suspected of Bloodstream infection. Then specimens were inoculated in various culture media after that with this culture isolates we performed gram staining and many biochemical tests (as per CLSI guidelines) to identies the Enterobacteriaceae species. And the production of β-lactamases and Carbapenemase was conrmed by the combined disk test and Modied Hodge method. RESULTS: In this study out of 760 samples processed in the laboratory 77 (10.13%) was tested positive for bacteremia from which 42 (54.54%) blood specimens were infected by Enterobacteriaceae. The members of the Enterobacteriaceae family isolated in patient samples are E.coli (22/42, 52.38%), K. pneumoniae (11/42, 52.38%) others are Enterobacter spp. (8/42, 52.38%) and S.typhi(1/42, 2.38%). In all 42 Enterobacteriaceae species, 17 (40.47%) isolates were found ESBL positive on antibiotic screening which is conrmed by Combined disc diffusion test, and out of 17 Beta-lactamase producers 8 (47.05%) were E. coli, 5 (29.41%) were K. pneumoniae and 4 (23.52%) were Enterobacter spp. And among 42 isolates of Enterobacteriaceae 16 (38.09%) isolates showed Carbapenemase producers, in that 8 (50%) were E.coli, 5 (31.25%) were K. pneumoniae, and 3 (18.75%) were Enterobacter spp. CONCLUSION: This study aims to provide an early, rapid, and effective phenotypic method for identifying Multi-drug resistant (MDR) Bloodstream infections (BSIs) causing by the species of the Enterobacteriaceae family

Targeting Internalized Staphylococcus aureus Using Vancomycin-Loaded Nanoparticles to Treat Recurrent Bloodstream Infections

The bacterial pathogen Staphylococcus aureus is a leading cause of bloodstream infections, where patients often suffer from relapse despite antibiotic therapy. Traditional anti-staphylococcal drugs display reduced effectivity against internalised bacteria, but nanoparticles conjugated with antibiotics can overcome these challenges. In the present study, we aimed to characterise the internalisation and re-emergence of S. aureus from human endothelial cells and construct a new formulation of nanoparticles that target intracellular bacteria. Using an in vitro infection model, we demonstrated that S. aureus invades and persists within endothelial cells, mediated through bacterial extracellular surface adhesion, Fibronectin-binding protein A/B. After internalising, S. aureus localises to vacuoles as determined by transmission electron microscopy. Viable S. aureus emerges from endothelial cells after 48 h, supporting the notion that intracellular persistence contributes to infection relapses during bloodstream infections. Poly lactic-co-glycolic acid nanoparticles were formulated using a water-in-oil double emulsion method, which loaded 10% vancomycin HCl with 82.85% ± 12 encapsulation efficiency. These non-toxic nanoparticles were successfully taken up by cells and demonstrated a biphasic controlled release of 91 ± 4% vancomycin. They significantly reduced S. aureus intracellular growth within infected endothelial cells, which suggests future potential applications for targeting internalised bacteria and reducing mortality associated with bacteraemia.

Adhesion of Candida parapsilosis to Bovine Serum Albumin under Fluid Shear.

C. parapsilosis (Cp) is an emerging cause of bloodstream infections in certain populations. TheCandida clade, including Cp, is increasingly developing resistance to the first and the second line of antifungals. Cp is frequently isolated from hands and skin surfaces, as well as the GI tract. Colonization by Candida predisposes individuals to invasive bloodstream infections. To successfully colonize or invade the host, yeast must be able to rapidly adhere to the body surfaces to prevent elimination by host defense mechanisms. Here we describe a method to measure adhesion of Cp to immobilized proteins under physiologic fluid shear, using an end-point adhesion assay in a commercially available multichannel microfluidic device. This method is optimized to improve reproducibility, minimize subjectivity, and allow for the fluorescent quantification of individual isolates. We also demonstrate that some clinical isolates of Cp show increased adhesion when grown in conditions mimicking a mammalian host, whereas a frequently used lab strain, CDC317, is non-adhesive under fluid shear.

Phylogroup stability contrasts with high within sequence type complex dynamics of Escherichia coli bloodstream infection isolates over a 12-year period

BackgroundEscherichia coli is the leading cause of bloodstream infections, associated with a significant mortality. Recent genomic analyses revealed that few clonal lineages are involved in bloodstream infections and captured the emergence of some of them. However, data on within sequence type (ST) population genetic structure evolution are rare.MethodsWe compared whole genome sequences of 912 E. coli isolates responsible for bloodstream infections from two multicenter clinical trials that were conducted in the Paris area, France, 12 years apart, in teaching hospitals belonging to the same institution (“Assistance Publique-Hôpitaux de Paris”). We analyzed the strains at different levels of granularity, i.e., the phylogroup, the ST complex (STc), and the within STc clone taking into consideration the evolutionary history, the resistance, and virulence gene content as well as the antigenic diversity of the strains.ResultsWe found a mix of stability and changes overtime, depending on the level of comparison. Overall, we observed an increase in antibiotic resistance associated to a restricted number of genetic determinants and in strain plasmidic content, whereas phylogroup distribution and virulence gene content remained constant. Focusing on STcs highlighted the pauci-clonality of the populations, with only 11 STcs responsible for more than 73% of the cases, dominated by five STcs (STc73, STc131, STc95, STc69, STc10). However, some STcs underwent dramatic variations, such as the global pandemic STc131, which replaced the previously predominant STc95. Moreover, within STc131, 95 and 69 genomic diversity analysis revealed a highly dynamic pattern, with reshuffling of the population linked to clonal replacement sometimes coupled with independent acquisitions of virulence factors such as the pap gene cluster bearing a papGII allele located on various pathogenicity islands. Additionally, STc10 exhibited huge antigenic diversity evidenced by numerous O:H serotype/fimH allele combinations, whichever the year of isolation.ConclusionsAltogether, these data suggest that the bloodstream niche is occupied by a wide but specific phylogenetic diversity and that highly specialized extra-intestinal clones undergo frequent turnover at the within ST level. Additional worldwide epidemiological studies overtime are needed in different geographical and ecological contexts to assess how generalizable these data are.

Timing for Step-Down Therapy of Candidemia in Non-Neutropenic Patients: An International Multi-Center Study.

BackgroundCandida bloodstream infection (BSI) remains one of the leading causes of BSI in critically ill and immunosuppressed cancer patients. In light of the changing epidemiology and rising resistant species, duration of treatment and appropriate timing of stepdown therapy from intravenous (IV) to oral antifungal agents are crucial for utmost disease control and overall survival.MethodWe performed a multicenter retrospective study, with 119 non-neutropenic patients enrolled from four different medical institutions in Brazil, Lebanon, Spain and the United States, to assess the duration of IV therapy and appropriate time to step-down to oral therapy in adult patients, 14 years of age and older, with documented candidemia. The analysis was done using the statistical program R and SAS v9.4. Descriptive statistics are presented as frequencies and tables and the Fisher exact test was used to test the association between the categorical variables: organism, cancer, country, antifungal drug and duration of therapy, and time of step-down.ResultsCandida albicans contributed to 45% of bloodstream infection versus 55% of infection caused by Candida non-albicans. The three most common Candida non-albicans are: Candida glabrata 24%, Candida parapsilosis 13% and Candida tropicalis 8%. Most (57%) of the patients were admitted to ICU, whereas 52% had underlying malignancy. Multivariate analysis showed that a stay at ICU or an underlying cancer requiring chemotherapy were independently associated with failure and death (p <0.001). The average total duration of therapy was 14 days in all patients and 16 days in those who responded and survived. Forty-five patients were stepped down to either fluconazole and/or voriconazole in association with clinical and microbiologic resolution of the candidemia. The average (and median) day of step-down was 5 days. Patients who had a stepdown had more favorable outcomes (78% survival) as compared to those with no stepdown (56% survival) (P = 0.022). However, the 20 patients who received 1–4 days of first IV treatment before a stepdown to oral azoles had a comparable outcome (20% mortality) to the 25 patients who received >5 days of treatment (24% mortality - p = 0.75).ConclusionOur data support the IDSA guidelines in that the total duration of treatment for candidemia should be at least 14 days after a negative blood culture. However, in non-neutropenic cancer patients with candidemia, a step-down to oral azole therapy can safely take place early (within 4 days of initiating IV therapy) as long as the patient had clinical and microbiologic resolution of the bloodstream infections.

Ceftolozane-tazobactam versus meropenem for definitive treatment of bloodstream infection due to extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales (\u201cMERINO-3\u201d): study protocol for a multicentre, open-label randomised non-inferiority trial

BackgroundExtended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli.MethodsThis study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected.DiscussionParticipants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024.Trial registrationThe MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.

Antibiotic Resistance, spa Typing and Clonal Analysis of Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Blood of Patients Hospitalized in the Czech Republic.

Staphylococcus aureus is one of the major causes of bloodstream infections. The aim of our study was to characterize methicillin-resistant Staphylococcus aureus (MRSA) isolates from blood of patients hospitalized in the Czech Republic between 2016 and 2018. All MRSA strains were tested for antibiotic susceptibility, analyzed by spa typing and clustered using a Based Upon Repeat Pattern (BURP) algorithm. The representative isolates of the four most common spa types and representative isolates of all spa clonal complexes were further typed by multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. The majority of MRSA strains were resistant to ciprofloxacin (94%), erythromycin (95.5%) and clindamycin (95.6%). Among the 618 strains analyzed, 52 different spa types were detected. BURP analysis divided them into six different clusters. The most common spa types were t003, t586, t014 and t002, all belonging to the CC5 (clonal complex). CC5 was the most abundant MLST CC of our study, comprising of 91.7% (n = 565) of spa-typeable isolates. Other CCs present in our study were CC398, CC22, CC8, CC45 and CC97. To our knowledge, this is the biggest nationwide study aimed at typing MRSA blood isolates from the Czech Republic.

Carbapenem-Resistant Enterobacteriaceae-Implications for Treating Acute Leukemias, a Subgroup of Hematological Malignancies.

Acute leukemias (AL) are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. Patients with AL are highly susceptible to infectious diseases due to the disease itself, factors attributed to treatment, and specific individual risk factors. Enterobacteriaceae presence (e.g., Klebsiella pneumonia and Escherichia coli) is a frequent cause of bloodstream infections in AL patients. Carbapenem-resistant Enterobacteriaceae (CRE) is an emerging health problem worldwide; however, the incidence of CRE varies greatly between different regions. Carbapenem resistance in Enterobacteriaceae is caused by different mechanisms, and CRE may display various resistance profiles. Bacterial co-expression of genes conferring resistance to both broad-spectrum β-lactam antibiotics (including carbapenems) and other classes of antibiotics may give rise to multidrug-resistant organisms (MDROs). The spread of CRE represents a major treatment challenge for clinicians due to lack of randomized clinical trials (RCTs), a limited number of antibiotics available, and the side-effects associated with them. Most research concerning CRE infections in AL patients are limited to case reports and retrospective reviews. Current research recommends treatment with older antibiotics, such as polymyxins, fosfomycin, older aminoglycosides, and in some cases carbapenems. To prevent the spread of resistant microbes, it is of pivotal interest to implement antibiotic stewardship to reduce broad-spectrum antibiotic treatment, but without giving too narrow a treatment to neutropenic infected patients.

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)