Paired Blood Cultures Research Articles

Gastrointestinal colonization of meticillin-resistant Staphylococcus aureus: an unrecognized burden upon hospital infection control

Meticillin-resistant Staphylococcus aureus (MRSA) has become endemic in many healthcare settings. To analyse the incidence, risk factors, outcomes, and genomic relatedness of patients with newly diagnosed gastrointestinal colonization of MRSA. Epidemiology and genetic analysis by whole-genome sequencing (WGS) in a hospital network in Hong Kong. Between October 1st, 2015 and December 31st, 2018, a total of 919 (2.7%) of 34,667 patients had newly diagnosed gastrointestinal MRSA colonization by admission screening. The incidence was 0.67 ± 0.32 per 1000 patient-days per quarter. Including patients with gastrointestinal MRSA colonization, the overall burden of MRSA increased by 59.2%, with an addition of 4727 MRSA patient-days during the study period. Patients referred from residential care home for the elderly, with history of hospitalization in the past six months, and consumption of fluoroquinolones, cephalosporins, and proton-pump inhibitors in the preceding six months were found to be independent risk factors by multivariate analysis in the case-control analysis. The median survival of cases was significantly shorter than that of controls (860 vs 1507 days, P < 0.001). Of 919 patients, 127 (13.8%) developed symptomatic MRSA infection in a median of 112 days. Of 19 patients with paired MRSA faecal and blood culture isolates subjected to WGS, clonality was found in 16 (84.2%) pairs of MRSA isolates. MRSA ST45 constituted 44.7% (17/38) of MRSA isolates. Gastrointestinal MRSA colonization may contribute to adverse clinical outcomes and pose an unrecognized burden upon hospital infection control.

Impact of Paired Central and Peripheral Blood Cultures in Children With Cancer.

Children with cancer require central venous access which carries risk for line-related infections. The necessity of peripheral and central blood cultures is debated for those with fevers. We evaluated and described results for first episode of paired blood cultures from children with cancer who have a central venous line using retrospective database. Blood culture results, laboratory data, and medical outcomes were included. Descriptive analyses of blood culture results and clinical data were performed. There were 190 episodes of paired positive blood cultures with 167 true positive episodes. Of the true positive episodes, 104 (62.3%) were positive in both central and peripheral cultures, 42 (25.1%) were positive in central only cultures, and 21 (12.6%) were positive in peripheral cultures only. Intensive care unit admission within 48 hours after blood cultures (n=33) differed significantly: 28.7% for both central and peripheral, 10% for central only, and 0% for peripheral only (P=0.009). Central line removal (n=34) differed by type of positivity but was not significant: 22.1% for both central and peripheral, 23.8% for central only, and 4.8% for peripheral only (P=0.15). Peripheral blood cultures provided important medical information yet had differences in short-term clinical outcomes. Further evaluation of medical decision making is warranted.

Taurolidine lock in the treatment of colonization and infection of totally implanted venous access devices in cancer patients.

Taurolidine lock is known to be effective in preventing catheter-related infections in a variety of venous access devices, including long term venous access devices for chemotherapy. Though, literature about the use of taurolidine for treating catheter colonization or catheter-related blood stream infection is scarce. We have retrospectively reviewed the safety and efficacy of 2% taurolidine lock for treatment of catheter-colonization and of catheter-related bloodstream infection in cancer patients with totally implanted venous access devices. Diagnosis of colonization or catheter-related infection was based on paired peripheral and central blood cultures, according to the method of Delayed Time to Positivity. We recorded 24 cases of catheter-related infection and two cases of colonization. Taurolidine lock-associated with systemic antibiotic therapy-was successful in treating all cases of catheter-related infection, with disappearance of clinical symptoms, normalization of laboratory values, and eventually negative blood cultures. Taurolidine lock was also safe and effective in treating device colonization. No adverse effect was reported. In our retrospective analysis, 2% taurolidine lock was completely safe and highly effective in the treatment of both catheter-colonization and catheter-related bloodstream infection in cancer patients with totally implanted venous access devices.

Melioidosis complicated with pericardial effusion - An emerging disease with a rare presentation

Melioidosis, caused by a non-fermenting gram negative bacilli, can mimic a variety of diseases due to its diverse clinical presentation. The incidence of cardiac involvement in melioidosis is less than 1%. We report a rare case of melioidosis in a 65 year old male with chronic kidney disease who presented with fever and pericardial effusion which was misdiagnosed and treated as tuberculous pericardial effusion. Later, on isolation of from paired blood culture samples, pericardial fluid and also from pleural fluid confirmed the diagnosis of disseminated melioidosis. The patient was treated with intravenous ceftazidime after which clinical improvement was observed. Cardiac melioidosis should always be considered in the differential diagnosis of tuberculous pericardial effusion and it should be ruled out before the start of anti-tubercular treatment. This will prevent unnecessary exposure to anti-tubercular drugs and also aids to start early treatment for melioidosis thereby reducing the mortality.

Implementation of Automated Blood Culture With Quality Assurance in a Resource-Limited Setting.

Background: Blood cultures (BC) have a high clinical relevance and are a priority specimen for surveillance of antimicrobial resistance. Manual BC are still most frequently used in resource-limited settings. Data on automated BC performance in Africa are scarce. We implemented automated BC at a surveillance site of the African Network for improved Diagnostics, Epidemiology and Management of Common Infectious Agents (ANDEMIA).Methods: Between June 2017 and January 2018, pairs of automated BC (BacT/ALERT®FA Plus) and manual BC (brain-heart infusion broth) were compared at a University hospital in Bouaké, Côte d'Ivoire. BC were inoculated each with a target blood volume of 10 ml from the same venipuncture. Automated BC were incubated for up to 5 days, manual BC for up to 10 days. Terminal subcultures were performed for manual BC only. The two systems were compared regarding yield, contamination, and turnaround time. For quality assurance, isolates were retested in a German routine microbiological laboratory.Results: BC sampling was increased from on average 24 BC to 63 BC per month. A total of 337 matched pairs of BC were included. Automated BC was positive in 36.5%, manual BC in 24.0% (p-value < 0.01), proportion of contamination was 47.9 and 43.8%, respectively (p-value = 1.0). Turnaround time of positive BC was shortened by 2.5 days with automated compared to manual BC (p < 0.01). Most common detected pathogens in both systems were Klebsiella spp. (26.0%) and Staphylococcus aureus (18.2%). Most contaminants were members of the skin flora. Retesting of 162 isolates was concordant in 79.6% on family level.Conclusions: Implementing automated BC in a resource-limited setting is possible and improves microbiological diagnostic performance. Automated BC increased yield and shortened turnaround times. Regular training and mentorship of clinicians has to be intensified to increase number and quality of BC. Pre-analytical training to improve diagnostic stewardship is essential when implementing a new microbiological method. Retesting highlighted that manual identification and antimicrobial susceptibility testing can be of good quality and sustainable. The implementation of automated tools should be decided individually according to economic considerations, number of samples, stable supply chain of consumables, and technical sustainability.

Role of single, paired and multiple specimens in the outcome of automated blood culture system – A 2 years study from South India

Automated blood culture (BC) system remains the best approach for early definitive management of sepsis. A retrospective analysis of samples received over 2 years was done to compare the sensitivity of single, paired and multiple BC sets. A total of 24,955 samples were received, of which 11,355 were single, 12,555 were paired and 1045 were multiple. BC sensitivity increased from 32.3% to 87% when samples increased from one to two, and a rise of another 13% with four sample sets (P &lt; 0.0001). There is higher chance of missing positives if only a single BC sample was collected.

Genetic relatedness of Streptococcus dysgalactiae isolates causing recurrent bacteraemia

Introduction. Streptococcus dysgalactiae subspecies equisimilis (SDSE) is becoming increasingly recognized as an important human pathogen. Recurrent bacteremia with SDSE has been described previously.Aim. The aims of the study were to establish the genetic relatedness of SDSE isolates with emm-type stG643 that had caused recurrent bacteraemia in three patients and to search for signs of horizontal gene transfer of the emm gene in a collection of SDSE stG643 genomes.Hypothesis. Recurring SDSE bacteremia is caused by the same clone in one patient.Methodology. Whole genome sequencing of 22 clinical SDSE stG643 isolates was performed, including three paired blood culture isolates and sixteen isolates from various sites. All assemblies were aligned to a reference assembly and SNPs were extracted. A total of 53 SDSE genomes were downloaded from GenBank. Two phylogenetic trees, including all 75 SDSE isolates, were created. One tree was based on the emm gene only and one tree was based on all variable positions in the genomes.Results. The genomes from the three pairs of SDSE isolates showed high sequence similarity (1-17 SNPs difference between the pairs), whereas the median SNP difference between the 22 isolates in our collection was 1694 (range 1-11257). The paired isolates were retrieved with 7-53 months between episodes. The 22 SDSE isolates from our collection formed a cluster in the phylogenetic tree based on the emm gene, while they were more scattered in the tree based on all variable positions.Conclusions. Our results show that the paired isolates were of the same clonal origin, which in turn supports carriage between bacteraemia episodes. The phylogenetic analysis indicates that horizontal gene transfer of the emm-gene between some of the SDSE isolates has occurred.

Frequency and Antifungal Susceptibility Pattern of Candida Species Causing Candidemia in Bone Marrow Transplant Unit

To determine the frequency and antifungal susceptibility pattern of Candida species causing candidemia or blood stream infections (BSI) in immunocompromised patients of a bone marrow transplant unit. The study was conducted at the Department of Microbiology, Armed Forces Institute of Pathology (AFIP), Rawalpindi in collaboration with Armed Forces Bone Marrow Transplant Center (AFBMTC), Rawalpindi, from 1st June 2019 to 31st December 2019. A total 256 paired blood culture samples from patients of all ages, irrespective of gender were collected during a period of seven months. The samples were processed as recommended Clinical &amp; Laboratory Standard Institute (CLSI) guidelines. Antifungal susceptibility by break point MICs was performed through VITEK® 2 system (version: 08.01) for Fluconazole, Itraconazole and Amphotericin B. Of the total 256 blood cultures, 46 (17.97%) were positive for Candida species. The susceptibility of C. albicans was 100% to Amphotericin B, 90% to Fluconazole and 10% to Itraconazole, while C. tropicalis showed sensitivity of 92%, 88% and 0% against Amphotericin B, Fluconazole and Itraconazole, respectively. C. parapsilosis was found sensitive to Amphotericin B while resistance to Fluconazole and Itraconazole.Frequency of candidemia among immunocompromised patients is 17.9%. C. tropicalis and C. albicans are the two most common Candida species involved in blood stream infections in our setup. Fluconazole and Amphotericin B, both were found susceptible and can be used as empirical therapy.

1173. Ocular Candidiasis in Patients with Candidemia Diagnosed by Blood Culture Versus T2Candida® Assay

BackgroundOcular candidiasis (OC) is a serious complication of candidemia. Current guidelines recommend dilated fundoscopic exam (DFE) in all patients with candidemia. In this study, we examined characteristics and outcomes of patients at UAB Medical Center with candidemia diagnosed by blood culture (BC) or T2Candida® rapid diagnostic assay (T2C) who were found to have evidence of fungal disease on ophthalmologic exam.MethodsPatients from 2016-2019 with either 1) at least one positive BC for Candida species or 2) positive T2C assay and negative or no paired BC were identified and retrospectively reviewed. Patients with additional positive BC or T2C within 60 days were excluded from the analysis. Data collected included risk factors for candidemia, causative Candida species, and whether DFE was performed after diagnosis. Patients with evidence of OC by exam were compared by type of ocular involvement (chorioretinitis vs. vitritis), whether visual symptoms were present, and whether intravitreal injection was performed.ResultsA total of 360 episodes of candidemia diagnosed by BC and 288 by T2C alone were included. Of those who underwent DFE, 33 BC patients (12.9%) had findings concerning for OC compared to 18 (8.9%) T2C patients (p=0.177) (Table 2). T2C patients with OC were younger, were more likely to have a prolonged ICU stay and to be mechanically ventilated, and were less likely to be on TPN compared to the BC group. Identification of C. parapsilosis was significantly more common in T2C patients (Table 1). There were no significant differences in presence of visual symptoms, type of ocular involvement, need for intravitreal injection, or 30-day mortality (Table 3).Table 1. Demographics and risk factors Table 2. Episodes of candidemia and ocular candidiasis by year Table 3. Ocular findings and outcomes ConclusionThe frequency of ocular disease was similar between groups. Significantly more T2C patients had candidemia due to C. parapsilosis, and the groups differed in terms of risk factors for candidemia. There were no differences in frequency of intravitreal injection, severity of eye disease, or mortality. Despite recent concerns about the necessity of DFE in asymptomatic patients with candidemia, we believe these results emphasize the importance of performing DFE in candidemic patients and also support the practice of doing so in patients with positive T2C even in the absence of positive blood cultures.Disclosures Peter Pappas, MD, SCYNEXIS, Inc. (Consultant, Advisor or Review Panel member, Research Grant or Support) Todd P. McCarty, MD, Amplyx (Scientific Research Study Investigator)Cidara (Scientific Research Study Investigator)

First comprehensive study on neonatal septicaemia at secondary-level public health-care facilities in Central India: An eye opener

Background: In India secondary-level public health-care facilities (HCF)-District Hospitals, are not equipped either with a microbiological laboratory or a robust Infection control program. The present study was initiated to investigate the epidemiology of neonatal septicaemia in SNCUs (Special new-born care units) situated at various District Hospitals of Chhattisgarh (a state in Central India) in terms of Blood Stream Infection (BSI) rates, pathogen profile and their antimicrobial sensitivity patterns. Methods & Materials: The study was conducted from October 2017 through June 2019 at the Department of Microbiology, All India Institute of Medical Sciences (AIIMS), Raipur, a tertiary level healthcare teaching institute in collaboration with 23 SNCUs. Paired blood samples (0.5–1.0 ml) were collected in paediatric aerobic blood culture bottles (BacT/ALERT PF Plus, BioMerieux Inc. Durham, NC, USA) and transported to the laboratory, where culture and identification was performed by automated ID and AST system (Vitek 2 ID/AST system, BioMerieux Inc. Durham, USA) and by manual methods using standard laboratory protocol. Results: Paired blood cultures were received from 2843 neonates; out of which 1645 (58%) were sterile, 388 (13.6%) grew contaminants and 810 grew pathogens, indicating BSI rate of 28.4%. Gram negative bacilli were the most commonly encountered pathogens (382/810, 47.2%), with more than half being multi drug resistant (211/382, 55.2%). Klebsiella pneumoniae was the commonest isolate (n = 253). Amongst the gram- positive cocci (253/810, 31.2%) coagulase negative staphylococcus (CoNS) was commonest. Only 17 (6.7%) Methicillin Resistant Staphylococcus aureus and one Streptococcus agalactiae were isolated. Candida spp. accounted for 21.6% (175/810) pathogen, predominated by non-albicans candida (161/175). 18% of the Candida spp. were resistant to Fluconazole, while 1.2% were MDR. A fall in NMR (neonatal mortality rate) and antibiotic usage rate was observed in almost all the units after the microbiology laboratory support was initiated. Conclusion: The secondary-level public health-care facilities have a very high rate of laboratory proven neonatal septicemia with an alarmingly high AMR (Antimicrobial resistance) rate, both among bacterial and fungal isolates. This warrants urgent intervention for reducing neonatal septicaemia by microbiology laboratory support, optimising infection control practices and implementing AMSP (antimicrobial stewardship program).

A diagnostic algorithm for detection of urinary tract infections in hospitalized patients with bacteriuria: The "Triple F" approach supported by Procalcitonin and paired blood and urine cultures.

For acute medicine physicians, distinguishing between asymptomatic bacteriuria (ABU) and clinically relevant urinary tract infections (UTI) is challenging, resulting in overtreatment of ABU and under-recognition of urinary-source bacteraemia without genitourinary symptoms (USB). We conducted a retrospective analysis of ED encounters in a university hospital between October 2013 and September 2018 who met the following inclusion criteria: Suspected UTI with simultaneous collection of paired urinary cultures and blood cultures (PUB) and determination of Procalcitonin (PCT). We sought to develop a simple algorithm based on clinical signs and PCT for the management of suspected UTI. Individual patient presentations were retrospectively evaluated by a clinical “triple F” algorithm (F1 =“fever”, F2 =“failure”, F3 =“focus”) supported by PCT and PUB. We identified 183 ED patients meeting the inclusion criteria. We introduced the term UTI with systemic involvement (SUTI) with three degrees of diagnostic certainty: bacteremic UTI (24.0%; 44/183), probable SUTI (14.2%; 26/183) and possible SUTI (27.9%; 51/183). In bacteremic UTI, half of patients (54.5%; 24/44) presented without genitourinary symptoms. Discordant bacteraemia was diagnosed in 16 patients (24.6% of all bacteremic patients). An alternative focus was identified in 67 patients, five patients presented with S. aureus bacteremia. 62 patients were diagnosed with possible UTI (n = 20) or ABU (n = 42). Using the proposed “triple F” algorithm, dichotomised PCT of < 0.25 pg/ml had a negative predictive value of 88.7% and 96.2% for bacteraemia und accordant bacteraemia respectively. The application of the algorithm to our cohort could have resulted in 33.3% reduction of BCs. Using the diagnostic categories “possible” or “probable” SUTI as a trigger for initiation of antimicrobial treatment would have reduced or streamlined antimicrobial use in 30.6% and 58.5% of cases, respectively. In conclusion, the “3F” algorithm supported by PCT and PUB is a promising diagnostic and antimicrobial stewardship tool.

The Addition of Anaerobic Blood Cultures for Pediatric Patients with Concerns for Bloodstream Infections: Prevalence and Time to Positive Cultures.

Anaerobes are an important but uncommon cause of bloodstream infections (BSIs). For pediatric patients, routine inclusion of an anaerobic blood culture alongside the aerobic remains controversial. We implemented automatic anaerobic blood culture alongside aerobic blood cultures in a pediatric emergency department (ED) and sought to determine changes in recovery of obligate and facultative anaerobes. This was a cohort study in a pediatric ED (August 2015 to July 2018) that began in February 2017. Blood culture positivity results for true pathogens and contaminants were assessed, along with a secondary outcome of time to positivity (TTP) of blood culture. A total of 14,180 blood cultures (5,202 preimplementation and 8,978 postimplementation) were collected, with 8.8% (456) and 7.1% (635) positive cultures in the pre- and postimplementation phases, respectively. Of 635 positive cultures in the postimplementation phase, aerobic blood cultures recovered 7.6% (349/4,615), whereas anaerobic blood cultures recovered 6.6% (286/4,363). In 211/421 (50.0%) paired blood cultures, an organism was recovered in both cultures. The number of cases where organisms were only recovered from an aerobic or an anaerobic bottle in the paired cultures were 126 (30.0%) and 84 (20.0%), respectively. The TTP was comparable regardless of bottle type. Recovery of true pathogens from blood cultures was approximately 7 h faster than recovery of contaminants. Although inclusion of anaerobic blood cultures only recovered 2 (0.69%) obligate anaerobes, it did allow for recovery of clinically significant pathogens that were negative in aerobic blood cultures and supports the routine collection of both bottles in pediatric patients with a concern of bloodstream infections.

Assessment of a rapid diagnostic test to exclude bacteraemia and effect on clinical decision-making for antimicrobial therapy

Unnecessary antimicrobial treatment promotes the emergence of resistance. Early confirmation that a blood culture is negative could shorten antibiotic courses. The Cognitor Minus test, performed on blood culture samples after 12 hours incubation has a negative predictive value (NPV) of 99.5%. The aim of this study was to determine if earlier confirmation of negative blood culture result would shorten antibiotic treatment. Paired blood cultures were taken in the Critical Care Unit at a teaching hospital. The Cognitor Minus test was performed on one set >12 hours incubation but results kept blind. Clinicians were asked after 24 and 48 hours whether a result excluding bacteraemia or fungaemia would affect decisions to continue or stop antimicrobial treatment. Over 6 months, 125 patients were enrolled. The median time from start of incubation to Cognitor Minus test was 27.1 hours. When compared to 5 day blood culture results from both the control and test samples, Cognitor Minus gave NPVs of 99% and 100% respectively. Test results would have reduced antibiotic treatment in 14% (17/119) of patients at 24 and 48 hours (24% at either time) compared with routine blood culture. The availability of rapid tests to exclude bacteraemia may be of benefit in antimicrobial stewardship.

Blood stream infections in hematopoietic stem cell transplant patients: A 2-year study from India

Background: Hematopoietic stem cell transplant (HSCT) recipients are particularly prone to bloodstream infections (BSIs). This has been attributed to neutropenia and immune-suppression. Regardless of the improvements made in the management perspective, infection still plays a major role in morbidity and mortality in these patients. It has been related to the rise of multidrug-resistant organisms. Aim: The aim of this study was to determine the pattern of BSIs and the burden of antibiotic resistance in HSCT patients. Materials and Methods: We conducted this retrospective study for 2 years in 438 transplant events among 429 HSCT recipients who developed febrile neutropenia. Paired blood culture samples were collected on the onset of fever. Carbapenem-resistant Enterobacteriaceae (CRE) carriage rate was also determined in 127 patients. Results: BSIs were detected in 131 transplant events, which were classified as mucosal barrier injury laboratory-confirmed BSIs in 61, central line-associated, and other primary BSIs among 35 each. A diverse variety of 145 isolated organisms included Gram-negative and Gram-positive bacteria with 4 Candida species. All the Gram-negative isolates were susceptible to colistin, while 68.83% of CRE was detected. CRE carriage rate was observed in 37.80% of 127 individuals. Vancomycin resistance was noticed in 40% Enterococcus species. The overall mortality rate was 20.05%. Conclusions: Screening for CRE carriage in these patients could help in timely initiation of empirical colistin therapy. However, local epidemiology plays an important role in deciding the empirical antibiotic therapy.

224. Epidemiology of Bloodstream infections in a Cohort of Allogeneic Hematopoietic Stem Cell Transplant Patients from 2009 to 2018

BackgroundDue to severe immunosuppression, patients undergoing allogeneic hematopoietic stem cell transplantation (aSCT) are at increased risk of infection and especially bloodstream infections (BSI) remain a major cause of death. Knowledge of the specific epidemiology of pathogens and resistances is of utmost importance to optimize antimicrobial treatment strategies.MethodsBased on the Cologne Cohort of Neutropenic Patients (CoCoNut) database, we conducted a retrospective analysis of blood cultures collected within 100 days following transplantation of patients undergoing aSCT between January 2009 and December 2018 at the University Hospital of Cologne, Germany. Contamination of coagulase-negative Staphylococci (CoNS) isolates (single positive isolate within 5 days) was considered within the analysis.ResultsIn total, 843 aSCT patients were available for analysis (484/843 [57%] male). The median age was 53 (interquartile range [IQR] 43–62) years, predominant underlying diseases were acute myeloid leukemia (47%, 397/843), lymphoma (14%, 117/843), and acute lymphoblastic leukemia (11%, 89/843). Median inpatient stay was 39 (IQR 34–50) days, while 67/843 (8%) patients died. Antibacterial prophylaxis was administered in 289/843 (34%) and antifungal prophylaxis in 738/843 (88%) patients. BSI was diagnosed in 233/843 (28%) patients. In total, 5,489 pairs of blood cultures were taken (median 4 per patient, IQR 2–8), while a pathogen could only be detected in 922/5,489 (17%). Most frequent pathogens were CoNS (259/922, 28%), Enterococcus spp. (219/922, 24%), E. coli (132/922, 14%), Klebsiella spp. (44/922, 5%), P. aeruginosa (39/922, 4%), S. aureus (37/922, 4%), and Candida spp. (42/922, 5%). Polymicrobial infection was detected in 58/922 (6%) cases. Within Enterococci isolates, 24/219 (11%) were VRE. None of the Klebsiella, but 9/132 (7%) of E. coli isolates were ESBL positive. In 4/37 (11%) cases S. aureus isolates were MRSA.ConclusionPatients in the early phase after aSCT are at high risk of BSI with a predominantly gram-positive spectrum. Empirical antimicrobial treatment must consider pathogen epidemiology and resistance patterns while waiting for blood culture results.Disclosures All authors: No reported disclosures.

Performance of the T2Bacteria Panel for Diagnosing Bloodstream Infections: A Diagnostic Accuracy Study.

Blood cultures, the gold standard for diagnosing bloodstream infections (BSIs), are insensitive and limited by prolonged time to results. The T2Bacteria Panel (T2 Biosystems) is a direct-from-blood, nonculture test that identifies the most common ESKAPE bacteria (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli). To assess performance of the T2Bacteria Panel in diagnosing suspected BSIs in adults. Prospective patient enrollment (8 December 2015 through 4 August 2017). Eleven U.S. hospitals. 1427 patients for whom blood cultures were ordered as standard of care. Paired blood culture and T2Bacteria testing. Performance of T2Bacteria compared with a single set of blood cultures in diagnosing proven, probable, and possible BSIs caused by T2Bacteria-targeted organisms. Blood culture and T2Bacteria results were positive for targeted bacteria in 3% (39 of 1427) and 13% (181 of 1427) of patients, respectively. Mean times from start of blood culture incubation to positivity and species identification were 38.5 (SD, 32.8) and 71.7 (SD, 39.3) hours, respectively. Mean times to species identification with T2Bacteria were 3.61 (SD, 0.2) to 7.70 (SD, 1.38) hours, depending on the number of samples tested. Per-patient sensitivity and specificity of T2Bacteria for proven BSIs were 90% (95% CI, 76% to 96%) and 90% (CI, 88% to 91%), respectively; the negative predictive value was 99.7% (1242 of 1246). The rate of negative blood cultures with a positive T2Bacteria result was 10% (146 of 1427); 60% (88 of 146) of such results were associated with probable (n= 62) or possible (n= 26) BSIs. If probable BSIs and both probable and possible BSIs were assumed to be true positives missed by blood culture, per-patient specificity of T2Bacteria was 94% and 96%, respectively. Low prevalence of positive blood cultures, collection of a single set of culture specimens, and inability of T2Bacteria to detect nontargeted pathogens. The T2Bacteria Panel rapidly and accurately diagnoses BSIs caused by 5 common bacteria. T2 Biosystems.

Diagnostic Performance of T2Candida Among ICU Patients With Risk Factors for Invasive Candidiasis.

BackgroundInvasive candidiasis (IC) comprises candidemia and deep-seated candidiasis. Blood culture (BC) is the gold standard test, but sensitivity is low. T2Candida is a new diagnostic test. We investigated the performance of T2Candida, BC, and Candida mannan antigen (MAg) for detection of IC in a high-risk intensive care unit (ICU) population.MethodsOne-hundred twenty-six ICU patients at high risk of IC with sepsis despite 3 days of broad-spectrum antibiotics were included. Paired BC, T2Candida, and MAg were obtained twice weekly (334 sets). Patients were classified into proven, likely, possible, or unlikely IC based on patient record review.ResultsAt enrollment, 92 (77%) patients were receiving antifungal therapy (mainly fluconazole 66%). Fifteen (11.9%) patients were positive by BC (n = 4), T2Candida (n = 11), or MAg (n = 10). The T2Candida species distribution at inclusion (Candida albicans/Candida tropicalis: 8/11 [72.3%] and Candida glabrata/Candida krusei: 3/11 [27.3%]) was supported by the identification of BC or colonizing isolates in 10/11 cases. Patients were classified with proven (11), likely (6), possible (11), and unlikely (98) IC. Defining IC as proven/proven&likely/proven&likely&possible, respectively, the sensitivity was as follows: T2Candida (55%/59%/39%), BC (45%/29%/ 8%), and MAg (36%/41%/32%). The negative predictive value was similar across the tests for proven vs others and proven/likely vs others (94%–96% and 90%–95%, respectively). For test combinations including T2Candida, the sensitivity increased to 64%–65%, without hampering the positive predictive value.ConclusionsIn conclusion, although the diagnostic performance was modest for all the tests, the combination of T2Candida and BC seemed to have the best diagnostic performance, and thus implementation of T2Candida may improve the diagnosis of IC.

Increasing the volume of blood received in adult paired blood culture bottles at a regional public health laboratory: results of a quality improvement project to optimise the diagnosis of bacteraemia

BackgroundOptimising the diagnosis of bacteraemia has clinical, infection control and antimicrobial stewardship benefits. It's well documented that volume of blood received in blood culture bottles affects test sensitivity. The ability of blood cultures to detect bacteraemia is proportional to the volume of blood cultured. We undertook a period of baseline measurement and established that mean blood culture fill volume was inadequate. AimThe primary aim was to increase the percentage of adequately filled blood cultures (≥5ml) by 20% and increase the percentage of optimally filled bottles (8–10ml) by 10% in six months (by 1st August 2018). Our secondary aim was to increase the mean volume in blood culture bottles to 8ml (by 1st August 2018). We measured the clinical impact of this on test sensitivity by comparing blood culture positivity rate between adequately and inadequately filled bottles. MethodsFollowing a period of baseline measurement we implemented three phases of plan/do/study/act (PDSA) intervention cycles (including a small test pilot cycle). Interventions were focused around user education/engagement, real time user feedback and laboratory reporting. User questionnaires were administered to investigate knowledge and practice; further informing the interventions. Results & ConclusionBetween 1st March - 1st August 2018 the mean volume of blood inoculated into culture bottles rose from 5ml (95% CI 4.1–6.0ml) to 7.5ml (95% CI 6.4–8.5ml). The percentage of adequately-filled (≥5ml) blood culture bottles increased from 47% to 61% (absolute increase of 14%) and the percentage of optimally-filled (≥8ml) bottles increased from 16% to 29% (absolute increase of 13%). Although our project didn't fully meet its aims, we observed a significant and sustained improvement in filling of blood culture bottles.

Catheter-related infections in patients with acute type II intestinal failure admitted to a national centre: Incidence and outcomes

The management of intestinal failure (IF) requires safe and sustained delivery of parenteral nutrition (PN). The long-term maintenance of central venous catheter (CVC) access is therefore vital, with meticulous catheter care and salvage of infected CVCs being of prime importance. CVC-related infection and loss of intravenous access are important causes of morbidity and mortality in IF. Avoidance, prompt recognition and appropriate management of CVC-related infections are crucial components of IF care. However, there are few, if any, data on the occurrence of CVC-related infections in patients with acute, type 2, IF managed on a dedicated IF unit and no data on the salvage outcomes of infected CVCs in this group of patients. This is a retrospective observational study conducted between January 2011 and July 2017. All patients with acute, type 2 IF newly admitted to a national U.K. IF unit (IFU) during these dates were included. All patients admitted to the unit with a CVC in place underwent immediate 'screening' paired central and peripheral blood cultures on arrival before the CVC was used for any infusate. A prospectively maintained database was used to record all confirmed catheter-related blood stream infections (BSI)/colonisations, demographic and clinical data. Diagnosis of catheter-related BSI/colonisation was based on quantitative and qualitative analysis of paired central and peripheral blood cultures. A standardized 10-14-day catheter salvage treatment protocol involving antibiotic and urokinase CVC locks and systemic antibiotic administration was used to salvage any infected or colonised CVCs, as appropriate. The CVC was not used for PN until successful salvage had been confirmed by negative blood cultures drawn 48h after antibiotic completion. The development of a subsequent catheter-related BSI was recorded for all patients, both during the remaining in-patient stay on the IFU and after discharge home on PN. Of the 509 patients with type 2 IF admitted to the IFU during the study period, 341 (54% female; mean age 54.6 (range 16-86 years)) had an indwelling CVC that had been placed in the referring hospital. Surgical complications and mesenteric ischaemia were the most common underlying disease aetiologies. Sixty-five of 341 (19.1%) patients had an infected/colonised CVC on the initial screening set of blood cultures. A successful CVC salvage rate of 91% was achieved in this cohort after antibiotic therapy. The subsequent in-patient catheter-related BSI rate for those admitted with a CVC (n=341) on the IFU was 0.042 per 1000 catheter days, over a total of 23,548 in-patient catheter days. Two hundred and seventy nine of 341 patients were discharged on home PN (HPN); with a subsequent catheter-related BSI rate on HPN of 0.22 per 1000 catheter days (mean duration of HPN=778 catheter days (range:)) over a follow-up period of 216,944 out-patient catheter days. There was no increased risk of HPN-related catheter-related BSI (p=0.09) or mortality (p=0.4) in those admitted with an infected CVC. This is the first study to report catheter-related BSI/colonisation rates and salvage outcomes in patients with type 2 IF newly admitted to a dedicated IF Unit. We report that nearly one-fifth of all patients were referred with evidence of a catheter related BSI/colonisation; despite this, successful catheter salvage is possible and, with stringent CVC care, an extremely low subsequent catheter related BSI rates can be achieved and maintained during in-patient stay on a dedicated IF Unit and after discharge on HPN. These data provide novel evidence to support ESPEN recommendations that patients with type 2 IF are managed on a dedicated IF Unit.

A Novel Method of Serum Resistance by Escherichia coli That Causes Urosepsis.

ABSTRACTUropathogenic Escherichia coli (UPEC) is the most common cause of urinary tract infection, which in some patients can develop into life-threatening urosepsis. Serum resistance is a key virulence trait of strains that cause urosepsis. Recently, we identified a novel method of serum resistance in patients with Pseudomonas aeruginosa lung infections, where patients possessed antibodies that inhibited complement-mediated killing (instead of protecting against infection). These inhibitory antibodies were of the IgG2 subtype, specific to the O-antigen component of lipopolysaccharide (LPS) and coated the bacterial surface, preventing bacterial lysis by complement. As this mechanism could apply to any Gram-negative bacterial infection, we hypothesized that inhibitory antibodies may represent an uncharacterized mechanism of serum resistance in UPEC. To test this, 45 urosepsis patients with paired blood culture UPEC isolates were screened for serum titers of IgG2 specific for their cognate strain’s LPS. Eleven patients had sufficiently high titers of the antibody to inhibit serum-mediated killing of UPEC isolates by pooled healthy control sera. Depletion of IgG or removal of O-antigen restored sensitivity of the isolates to the cognate patient serum. Importantly, the isolates from these 11 patients were more sensitive to killing by serum than isolates from patients with no inhibitory antibodies. This suggests the presence of inhibitory antibodies may have allowed these strains to infect the bloodstream. The high prevalence of patients with inhibitory antibodies (24%) suggests that this phenomenon is an important mechanism of UPEC serum resistance. LPS-specific inhibitory antibodies have now been identified against three Gram-negative pathogens that cause disparate diseases.