Repeated Blood Cultures Research Articles

Immune-Mediated Non-Infectious Periaortitis After Aortic Graft Replacement Surgery: A Case Report Highlighting the Need for Immunosuppressive Therapy.

BACKGROUND A non-infectious inflammatory reaction against replaced aortic graft for aortic dissection often manifests as fever, malaise, and peri-graft effusion. It usually lasts less than 1 month and subsides spontaneously without immunosuppressive treatment. CASE REPORT A 49-year-old man underwent ascending aorta and total arch replacement for acute thoracic aortic dissection. He had fever, malaise, nausea, and elevated serum C-reactive protein for 1 month postoperatively. Pathological examination of the aorta revealed no aortitis, and repeated blood cultures were negative. We also noted periaortic graft fluid collection, and a small amount of pleural and pericardial effusions. We suspected post-pericardiotomy syndrome. Colchicine and prednisolone were administered, with an excellent clinical response. Three weeks after discontinuation of a 7-week prednisolone treatment, the same symptoms recurred and gradually worsened. Prednisolone was restarted 6 months after the first surgery, with good clinical response. Thereafter, he developed left-sided weakness and dysarthria, being diagnosed as ischemic stroke. Contrast-enhanced computed tomography revealed fluid collection with contrast leak around the aortic grafts, suggesting peel dehiscence, and thrombus formation in anastomotic pseudoaneurysm. He underwent surgical repair. He was diagnosed with non-infectious periaortitis, likely due to an immune reaction to the grafts, based on an excellent clinical response to immunosuppressive therapy. CONCLUSIONS We report a case of non-infectious periaortitis around a thoracic aortic graft, probably with an immune-mediated mechanism, requiring immunosuppressive treatment. When fever persists after aortic graft replacement surgery, non-infectious periaortitis should be considered and immunosuppressive treatment should be considered to prevent critical complications of anastomotic pseudoaneurysm and graft dehiscence.

Simultaneous Multifocal Intracranial Haemorrhages Associated with Staphylococcus Aureus Endocarditis: A Plausible Role for Diclofenac Administration.

Intracranial haemorrhage may complicate infective endocarditis, caused by ruptured mycotic aneurysms or haemorrhagic transformation of brain septic emboli. The risk of intracranial bleeding may increase with the use of non-steroidal anti-inflammatory agent (NSAIDs). We report on a 53-year-old male patient with a past history of intravenous drug abuse, who was treated with diclofenac (75 mg IM) for a few hours of preceding fever and arthralgia. Seven hours later he was hospitalised with impaired consciousness and hemiparesis. Evaluation revealed multiple intracranial haemorrhages, at least one originating from a mycotic aneurysm. Repeated blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA), and echocardiography revealed a vegetation on the mitral valve, establishing the diagnosis of bacterial endocarditis. The abrupt simultaneous multifocal intracranial bleeds shortly following the administration of NSAIDs for a few hours of febrile disease, one clearly originating from a mycotic aneurism, are exceptional. This raises a possibility of a role for diclofenac the intracranial bleeding diathesis in this unique clinical presentation. Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis (IE) might be added to the long list of potential adverse outcomes of NSAID administration, and the possibility of IE should be considered before their administration for febrile disease of undetermined cause. Intracranial haemorrhage in the set-up of undiagnosed infective endocarditis might be added to the long list of potential adverse outcomes of NSAID administration.The possibility of infective endocarditis should be considered before the administration of NSAIDs for febrile disease of an undetermined cause.

The Yield, Safety, and Cost-effectiveness of Decreasing Repeat Blood Cultures Beyond 48 Hours in a Pediatric Hematology-Oncology Unit.

Clear recommendations are needed on when repeat blood cultures (BCxs) in hospitalized children with cancer should be obtained. We reviewed all BCx obtained on the Hematology-Oncology Unit at Riley Hospital for Children, regardless of reason for patient admission or neutropenia status, between January 2015 and February 2021. Patients with positive BCx within 48 hours of initial cultures, history of stem cell transplant, or admitted to the intensive care unit were excluded. Medical records of patients with new positive BCx drawn >48 hours after initial BCx were reviewed. Seven (1.2%) hospitalization episodes grew new pathogens, or commensals treated as pathogens, on cultures beyond 48 hours. All patients with new, true pathogens were hemodynamically unstable or had recurrent fever when the new positive BCx was obtained. Twenty-three (4.0%) hospitalization episodes had contaminant cultures beyond 48 hours, with 74 (5.4%) of 1362 BCx collected beyond 48 hours being contaminated, resulting in an additional cost of $210,519 from increased length of stay. In conclusion, repeat BCx beyond 48 hours in pediatric hematology-oncology patients with negative initial cultures are low yield and costly. Repeat BCx can be safely and cost-effectively ceased after 48 hours of negative cultures in hemodynamically and clinically stable patients.

Predictors of Positive Repeat Blood Cultures in Patients With Gram-Negative Bacilli Bacteremia

Introduction Bloodstream infections occur commonly in the United States and are associated with significant morbidity and mortality. Bacteremia caused by gram-positive organisms has established guidelines for the use of follow-up blood cultures (FUBCs), whereas the use of FUBCs in bacteremia due to gram-negative bacilli (GNBs) does not. One study showed that positive FUBCs were more common in gram-positive coccus bacteremia (21%) than in GNB bacteremia (6%), calling into question the overall clinical utility of using FUBCs in GNB bacteremia. We investigated the factors associated with positive FUBCs in patients with GNB bacteremia in our institution to better guide clinical practice. Methods We used a case-control design for this study. We included patients 18 years or older admitted to our hospitals between January 1, 2014, and December 31, 2018, for a duration of ≥24 hours and who had a positive blood culture (BC) for GNB. Cases were defined as any patient with a positive FUBC drawn ≥24 hours after the initial positive BC. Control subjects were defined as patients with a negative FUBC after an initial positive BC. Characteristics of cases and control subjects were compared using descriptive statistics. A multivariable regression model using stepwise variable selection was used to identify factors significantly associated with having a positive FUBC. Results We identified 70 cases meeting the inclusion criteria. We compared these 70 cases with 528 control subjects. The cases and control subjects did not differ significantly in age, sex, race, or other predefined comorbid conditions. Significant predictors for having a positive FUBC included (1) organism resistance to initial antibiotic therapy (odds ratio [OR], 3.26; P = 0.035), (2) glomerular filtration rate less than 30 mL/min (OR, 2.35; P = 0.010), (3) initial admission to critical care unit (OR, 1.72; P = 0.049), (4) central line–associated infection (OR, 3.99; P = 0.004), (5) Klebsiella group infection (OR, 2.18; P = 0.015), and (6) Serratia marcescens infection (OR, 3.53; P = 0.037). Initial discordant BC was a negative predictive factor (OR, 0.44; P = 0.018). Follow-up blood culture drawn more than 48 hours after the initial positive BC had a lower likelihood of being positive than those drawn 24 to 48 hours after the initial BC (OR, 0.59; P = 0.037). Discussion We identified 6 independent risk factors for positive FUBCs as delineated previously. These factors provide guidance for further research and for future guideline development. The timing of the FUBCs had a significant impact on positivity. Follow-up blood cultures in GNB bacteremia should be obtained more than 48 hours after the initial positive BC.

P26 Epidemiology and risk factors associated with and clinical approach to Staphylococcus aureus bacteraemia at North West Anglia Foundation Trust (NWAFT)

Abstract Background Staphylococcus aureus bacteraemia (SAB) is associated with high mortality and morbidity. Certain patient groups are predisposed to developing SAB. Careful monitoring of these patients for persistence of bacteraemia and development of complications is important to improve prognosis. There is international consensus on (i) treating patients with at least 2 weeks of IV antibiotics, (ii) performing echocardiography to evaluate for infective endocarditis and (iii) repeating blood cultures 2–4 days after initiating empirical treatment. Adherence to trust antimicrobial guidelines is also imperative to national antimicrobial stewardship. Objectives To characterize patients at risk of SAB and make recommendations to reduce the incidence and complications of SAB. Methods Retrospective review of case notes of patients whose blood culture results were positive for S. aureus from April to September 2022 in NWAFT. 57 results from 51 patients aged 0 to 96 years were included. The four audit standards were compliance with (i) trust empirical antimicrobial guidelines, (ii) 2-week duration of IV therapy, (iii) echocardiography evaluation for endocarditis, and (iv) repeat blood cultures 48–96 hours after initiating empirical treatment. Patients who were on palliative pathway were excluded from analysis of standards two to four. Prognostic outcomes were examined in terms of hospital readmission, recurrence and mortality. Results 36 patients (70.6%) were found to harbour known risk factors, with the presence of indwelling prosthetic devices (83.3%) and type 2 diabetes (25.0%) being the most common. The most frequent sources of infection were unknown (27.5%) as well as the skin or soft tissue (17.6%). MRSA bacteraemia accounted for 10.5% of all cases. The compliances with (i) trust empirical antimicrobial guidelines, (ii) 2-week duration of IV therapy, (iii) echocardiography evaluation of endocarditis and (iv) repeat blood cultures 48–96 hours after initial blood culture were 52.8%, 75.0%, 57.8% and 66.0%, respectively. Rates of hospital readmission, recurrence and mortality were 39.5%, 11.4% and 35.3%, respectively. Conclusions The incidence of SAB correlates with the presence of risk factors, and SAB is associated with adverse outcomes. There was partial compliance with the audited outcomes. Introduction of trust SAB guidelines to guide clinical approach and adherence to local antimicrobial prescribing guidelines are imperative to improving patient outcomes.

Neonatal Salmonella Meningitis With Subdural Empyema: A Case Report.

To the Editors: Salmonella species can cause a variety of neonatal infections which are most prevalent in sub-Saharan Africa. Salmonella meningitis is associated with long-term neurologic sequelae1 including seizures, hydrocephalus, subdural effusions, empyema, ventriculitis, hemorrhage and abscess.2 The present case describes a neonate with Salmonella meningitis with subdural empyema. A 12-day-old full-term female presented to the emergency department for a 1-day history of fever, decreased feeding, and a shorter, gasp-like breathing pattern. The baby was tachycardic and febrile. Per patient’s mother, both she and the infant’s brother were suffering from diarrhea 3 days before onset of the infant’s symptoms. A full sepsis workup was initiated, including blood, urine and cerebrospinal fluid cultures. The patient was empirically started on intravenous ampicillin and gentamicin pending culture results. Additionally, a respiratory pathogen panel via polymerase chain reaction performed on the same day indicated positive results for coronavirus disease 2019 (COVID-19). The patient was admitted for further management of presumed neonatal sepsis and respiratory monitoring of COVID-19 infection. The patient was subsequently found to have positive blood culture and cerebrospinal fluid gram stain for Gram-negative rods. Speciation and sensitivities later grew Salmonella species with sensitivity to ampicillin and ceftriaxone. Magnetic resonance imaging of the brain was significant for diffuse right leptomeningeal enhancement consistent with meningitis and subdural empyema. No neurosurgical intervention was recommended. Ampicillin and gentamicin were discontinued after 3 days of treatment, and ceftazidime was started for treatment of salmonella meningitis. Ceftriaxone was considered as the standard treatment for invasive Salmonella infection, but was inappropriate due to mildly elevated bilirubin on admission (Table 1) and patient’s age. TABLE 1. - Admission Labs Complete blood count With Differential Day 1 of Admission White blood cell count 6.4 × 103/µL Hemoglobin/hematocrit 12.6/37.3 g/dL Platelets 564 × 103/µL Segmented neutrophils 40% Bands 24% Lymphocytes 26% Monocytes 7% Urinalysis Color Dark yellow Specific gravity 1.021 pH 7.0 Protein 2+ Glucose Trace Ketones Negative Bilirubin Negative Blood Negative Nitrites Negative Urobilinogen 0.2 Leukocyte esterase 2+ Urine microscopy White blood cells >50 Red blood cells 11.1 Squamous epithelial 5.3 Bacteria 40 Casts 3.9 Chemistry Sodium 138 mmol/L Potassium 4.1 mmol/L Chloride 107 mmol/L Bicarbonate 22 mmol/L Blood urea nitrogen/creatinine 8/0.37 mg/dL Glucose 108 mg/dL Total bilirubin 9.6 mg/dL Total protein 6.2 g/dL Albumin 3.1 g/dL Alanine transaminase/aspartate transaminase 18/23 Units/L Alkaline phosphatase 143 Units/L Cerebrospinal fluid Color Cloudy White blood cells 667 cu/mm Red blood cells 42,500 cu/mm Segmented neutrophils 90% Lymphocytes 8% Monocytes 1% Eosinophils 1% Basophils 0% Inflammatory markers C-reactive protein (admission) 3.06 mg/dL C reactive protein (hospital day #2) 25 mg/dL On the third day of admission, a repeat respiratory pathogen panel showed the patient to be COVID-19 negative, and it was concluded that the initial positive test was likely a false positive. Repeat blood cultures drawn on day 4 of admission were negative. On day 8 of admission, a peripherally inserted central catheter line was placed for long-term parenteral antibiotics. On day 10 of admission, ceftazidime was discontinued and switched to ceftriaxone after a repeat complete metabolic panel showed normalized bilirubin levels. Ceftriaxone was selected (in lieu of ampicillin) to minimize peripherally inserted central catheter line access thereby reducing probability of central line–associated bacterial infection. Inflammatory markers and bilirubin were trended closely due to use of ceftriaxone. A 6-week course of treatment was completed with no further complications and improvement of radiologic findings. The patient was discharged with no apparent neurological deficits. Her development was ascertained by phone call and the child continues to develop typically. Previous case reports indicate that third generation cephalosporins are ideal for management of salmonella meningitis due to their bactericidal properties.3,4 This case offers a suggested treatment course of neonates with transition from ceftazidime to ceftriaxone showing satisfactory results in the treatment of neonatal Salmonella sepsis and meningitis complicated by empyema. ACKNOWLEDGMENTS The authors thank the patient and family for their participation in this report.

A Retrospective Study of Staphylococcus aureus Bacteremia in a Tertiary Hospital and Factors Associated with Mortality.

Staphylococcus aureus bacteremia (SAB) is a severe infection frequently associated with significant morbidity and mortality. Recent studies have shown that SAB mortality has decreased during the last decades. However, about 25% of patients suffering from the disease will ultimately die. Hence, there is an urgent need for more timely and efficient treatment of patients with SAB. The aim of the present study was to retrospectively evaluate a cohort of SAB patients hospitalized in a tertiary hospital and to identify factors independently associated with mortality. All 256 SAB patients hospitalized from January 2005 to December 2021 in the University Hospital of Heraklion, Greece, were evaluated. Their median age was 72 years, while 101 (39.5%) were female. Most SAB patients were cared for in medical wards (80.5%). The infection was community-acquired in 49.5%. Among all strains 37.9% were methicillin-resistant S. aureus (MRSA), however, definite treatment with an antistaphylococcal penicillin was given only in 22% of patients. Only 14.4% of patients had a repeat blood culture after the initiation of antimicrobial treatment. Infective endocarditis was present in 8%. In-hospital mortality has reached 15.9%. Female gender, older age, higher McCabe score, previous antimicrobial use, presence of a central venous catheter, neutropenia, severe sepsis, septic shock, and MRSA SAB were positively associated with in-hospital mortality, while monomicrobial bacteremia was negatively associated. The multivariate logistic regression model identified only severe sepsis (p = 0.05, odds ratio = 12.294) and septic shock (p = 0.007, odds ratio 57.18) to be independently positively associated with in-hospital mortality. The evaluation revealed high rates of inappropriate empirical antimicrobial treatment and non-adherence to guidelines, as shown, by the lack of repeat blood cultures. These data underline the urgent need for interventions with antimicrobial stewardship, increased involvement of infectious diseases physicians, educational sessions, and creation and implementation of local guidelines for improvement of the necessary steps for timely and efficient SAB treatment. Optimization of diagnostic techniques is needed to overcome challenges such as heteroresistance that may affect treatment. Clinicians should be aware of the factors associated with mortality in patients with SAB to identify those who are at a higher risk and optimize medical management.

On culture and blood cultures

Dogma is defined as “a belief or set of beliefs that is accepted by the members of a group without being questioned or doubted” (https://www.britannica.com/dictionary/dogma; accessed May 2, 2023). Everyone who has worked in different healthcare institutions, maybe even in different countries, knows that there are local ‘dogmas’ that are not evidence-based.( 1 Hofmaenner D.A. Singer M. Challenging management dogma where evidence is non-existent, weak or outdated. Intensive Care Med. 2022; 48: 548-558 Crossref PubMed Scopus (7) Google Scholar ) Indeed, one may identify dogmas as such only once one has been confronted with other, possibly opposing ‘dogmas’ elsewhere. The question of whether, for which patients, at what interval(s), and how often to repeat blood cultures in the case of Gram-negative bacteremia may be an example. We, the authors of this commentary, are used to settings where local culture holds that follow-up blood cultures (FUBCs) should be reserved for Staphylococcus aureus bacteremia (for endovascular-infection risk stratification) or for patients without improvement despite antibiotic therapy (Fig. 1).

Malignancy-driven hypercoagulability: a fatal combination.

A 78-year-old woman, known with type 2 diabetes and paroxysmal atrial fibrillation, presented with fatigue, weight loss, and confusion. There was no fever, but physical examination revealed extensive petechiae and a loud systolic and diastolic heart murmur. Lab results showed acute kidney failure (creatinine 2.64 mg/dL) and mild inflammation [C-reactive protein (CRP) 26.8 mg/L]. Coagulation tests were found to be abnormal with elevated D-dimers (>7000 µg/L), international normalized ratio (INR) of 3.8, and marked thrombocytopaenia (41.000/µL) suggesting disseminated intravascular coagulation. Due to deteriorating neurological status, a computed tomography (CT) scan of the brain was performed which showed diffuse ischaemic lesions suspicious for a cardioembolic source. Transoesophageal echocardiography demonstrated very thick non-mobile vegetations on the aortic valve, causing severe valvular regurgitation (Figure 1A–C). The leaflets of the mitral valve were also thickened with the presence of mobile structures on the atrial side, highly suggestive of endocarditis (Figure 1A). Repeated blood cultures were negative.

Nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia in the absence of intracranial devices: a case report

BackgroundCoagulase-negative staphylococci can cause hospital-acquired infections, especially in immunocompromised hosts. Bacterial meningitis is a potentially fatal infection of the central nervous system, causing high mortality and morbidity. In general, the causative agents of meningitis, coagulase-negative staphylococci, are associated with direct implantation of a foreign body and the presence of a cerebrospinal fluid (CSF) shunt. Here, we describe a case of nosocomial meningitis caused by Staphylococcus haemolyticus in a child with neutropenia who had no intracranial foreign devices.Case presentationA 15-year-old boy with relapsed acute myeloid leukemia undergoing chemotherapy through a central venous catheter developed fever on Day 13 post-initiation of chemotherapy. There was no history of implantation of neurosurgical devices. Two blood cultures obtained on Day 14 were positive for Staphylococcus haemolyticus. Clinical improvement was noted, and treatment with vancomycin and removal of the central venous catheter resulted in negative repeat blood cultures on Day 18. However, the patient developed a tendency for somnolence and improper speech, along with persistent fever on Day 26. A lumber puncture was performed on Day 27, resulting in positive culture of Staphylococcus haemolyticus. He was diagnosed with meningitis and the dosage of vancomycin was increased. A repeat CSF culture was positive for Staphylococcus haemolyticus on Day 40, so oral rifampicin was added. CSF findings on Day 46 revealed a low concentration of vancomycin, and treatment was switched from vancomycin plus rifampicin to linezolid. After Day 46, four subsequent cerebrospinal fluid tests of the CSF showed no growth of Staphylococcus haemolyticus. The patient’s symptoms were improved on Day 52. Brain and spinal magnetic resonance images was taken and it showed no abnormalities. Linezolid was continued until Day 72. The patient was discharged without any complications on Day 72.ConclusionsTo the best of our knowledge, this is the first reported case of Staphylococcus haemolyticus meningitis in a patient without a neurosurgical device. Typical symptoms or signs may be absent in a patient with meningitis who also has neutropenia. Repeated tests of the CSF, and prolonged duration of antibiotics should be considered if atypical pathogens are detected in immunocompromised hosts.

Clearance of blood stream infections in patients receiving extracorporeal membrane oxygenation: a retrospective single-center cohort study

BackgroundThere are limited data on the treatment of blood stream infections (BSIs) in patients receiving extracorporeal membrane oxygenation (ECMO). Current guidance recommends documenting clearance only in fungal and Gram-positive BSIs. This study investigates the incidence and clinical significance of blood stream infections with positive repeat cultures (BSIPRC) in ECMO as well as clinical factors that may predict positive repeat cultures.MethodsAll BSIs in patients receiving ECMO at Brooke Army Medical Center between September 2012 and October 2021 were included in this study. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture.ResultsA total of 60 patients developed 87 BSI (38.5 BSI per 1000 ECMO days). Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. Fever, leukocytosis, and vasopressor requirement on day of repeat culture were not associated with persistent positivity. There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (58% vs. 63%, p = 0.78). 19% of patients with Gram-negative bacteremia had BSIPRC, and gram-negative bacteremia in general was associated with an 83% morality.ConclusionsThere were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSI was associated with high mortality in patients with Gram-negative bacteremia. Given high incidence of positive repeat cultures being seen in Gram-negative BSIs, repeat blood cultures have utility for all BSIs in patients receiving ECMO.

Spontaneous tensor fascia lata abscess caused by Parvimonas micra presenting as lateral hip pain.

Dear Editor, Parvimonas micra is a gram-positive obligate anaerobic bacterial species and known flora of the human oral cavity, respiratory system, gastrointestinal tract, and the female genitourinary tract.[1,2] It was originally identified in 1933 as Peptostreptococcus micros, underwent a reclassification in 1999 to Micromonas micros and ultimately was reclassified as P. micra in 2006.[1,3]Parvimonas micra has been implemented as an infectious organism in case reports of spondylodiscitis, vertebral osteomyelitis, iliopsoas abscess, hepatic abscess, endocarditis, empyema, meningitis, brain abscess and septic arthritis.[1–3] Although multiple areas of infection by P. micra have been described, tensor fascia lata infection has not been described.[4] A patient with no significant past medical history presented to our outpatient multidisciplinary pain center complaining of left hip pain. He was seen in the emergency department the day prior. X-ray of the hip was performed which did not reveal any acute pathology. His pain had been present for one week and had been worsening in intensity. He did not describe any radiation of the pain to the lower legs and denied any recent trauma to the area. He described swelling and fullness of the hip worsened with movement and relieved by rest. His physical examination was only positive for tenderness of palpation over the left greater trochanter. Due to a presumed diagnosis of greater trochanteric bursitis, conservative measures were pursued. He was prescribed naproxen 500 mg twice a day as needed, tizanidine 2 mg three times per day as needed, topical EMLA to the painful area. He was also instructed to start physical therapy and was provided a referral for the same. He was discharged from the emergency department after this visit. Nearly two weeks later, the patient presented to the emergency department with left thigh erythema and swelling. His laboratory work was significant for ESR of 115 and CRP of 16, white counts were 8.2. On exam, in the ED, he was afebrile and physical exam was positive for erythema, tenderness to palpation over the left thigh. Several pustules overlying the area along with areas of induration and fluctuance were noted. A CT with contrast of the left hip was performed which demonstrated a 20 × 10 × 6.5 cm rim enhancing fluid collection in the proximal lateral left thigh/gluteal region abutting and extending along the fascia lata of the thigh, dissecting into the substance of the tensor fasciae lata muscle and extending into the deep subcutaneous tissues [Figure 1]. The patient was started on broad-spectrum IV antibiotics and scheduled for incision and drainage in the operating room by general surgery. Drains were placed and the wound closed by secondary intention. Cultures from the operating room (anaerobic- tissue and abscess) yielded P. micra. Repeat blood cultures were negative at 5 days. The patient was kept on vancomycin and piperacillin/tazobactam for 3 days and transitioned to oral trimethoprim and sulfamethoxazole at discharge.Figure 1: Coronal view of left thigh CT demonstrating abscessThis case represents an unusual occurrence of P. micra abscess requiring prompt recognition of the abscess and prudent microbial identification. Financial support and sponsorship Nil. Conflicts of interest Dr. Shaparin reports the following disclosures outside the submitted manuscript; he was a consultant for Averitas Pharma and AcelRx Pharmaceuticals and has received research grant funding from Grunenthal and Heron Therapeutics. Dr. Koushik has served as a consultant for AcelRx Pharmaceuticals.

Timing and mid-term outcomes of using leadless pacemakers as replacement for infected cardiac implantable electronic devices.

Cardiac implantable electronic device (CIED) infections have a high morbidity and mortality and are an indication of device extraction. As a replacement, leadless pacemakers (LPs) may be preferable due to a low infection risk, but mid-term data on reinfections is lacking. Moreover, early LP reimplantation in pacemaker-dependent patients would circumvent the need for temporary pacemakers. We included all patients with LP implantation as a replacement for an infected CIED, between January 2013 and December 2021. The occurrence of reinfection was assessed during standard follow-up visits. Twenty-nine patients (mean age 81 ± 9years) were included, of which 21 (73%) had a pocket infection, 7 (24%) endocarditis, and 1 (3%) a systemic infection without endocarditis. All LP implantations were successful. LPs were implanted before extraction (n = 4, 13%), simultaneously with extraction (n = 5, 17%) and after extraction (n = 20, 70%). No reinfection occurred during the follow-up of median 32months (IQR 13-66months). Repeat blood cultures obtained in 9 (30%) patients and transthoracic echocardiography in all 7 patients with pacemaker endocarditis were negative for reinfection. In a subset of 6 LPs extracted during follow-up due to early battery depletion, prophylactically after the battery advisory or due to non-capture (median 36months (range 0-67months) post-implantation), histopathologic examination of tissues around the LPs showed no signs of infection. After replacing infected CIEDs for an LP, no reinfections occurred in over 2.5years follow-up. These results confirm that in case of CIED infection, the LP is an appealing replacement device. LP implantation before CIED extraction is feasible.

2015. Challenges in Assessing Blood Stream Infection Clearance in Patients Receiving Extracorporeal Membrane Oxygenation

Abstract Background There is a limited published data on the treatment of blood stream infections (BSI) in patients receiving extracorporeal membrane oxygenation (ECMO). Traditionally, the management of only fungal and Gram-positive BSIs require follow-up blood cultures to document clearance. The presence of large retained cannulas in ECMO create concern for persistent bacteremia. This study investigates whether certain variables are predictive of blood stream infections with positive repeat cultures (BSIPRC) and if BSIPRC is associated with increased mortality. Methods All positive blood cultures from patients receiving ECMO at Brooke Army Medical Center identified between September 2012 and October 2021 were included in this study. Blood cultures were excluded if they were determined to be contaminants by the primary team. For each positive blood culture, charts were retrospectively reviewed. Date of clearance was defined as the first negative blood culture after a positive. BSIPRC was defined as re-isolation of the same organism on repeat blood cultures following an initial positive blood culture. Results A total of 60 patients and 87 BSI were investigated (38.5 BSI per 1000 ECMO days). Gram-positive (GP) organisms caused a majority of BSI (n=52, 60%) followed by Gram-negative (GN) (n=22, 25%) and fungal (n=13, 15%) infections. Of the 80 (92%) BSIs who had repeat blood cultures drawn, patients had BSIPRC in 35 (44%) of cases. There were no clinical features that differentiated patients with positive repeat cultures (Table). There was no difference in survival to discharge for patients with BSIPRC as compared to single day BSI (20 (58%) vs. 28 (63%), p=0.78). In 6 patients with BSIPRC with Gram-negative organisms, two (33%) died before clearance and five (83%) died before decannulation. Characteristics of patients and all blood stream infections. Conclusion There were no clinical findings that differentiated patients with BSIPRC from those who had a single day of positivity. BSIPRC was associated with high mortality in patients with Gram-negative bacteremia. In the absence of clear predicative factors in demonstrating clearance of BSI, repeat blood cultures may be necessary. Future studies are needed to determine why Gram-negative BSIPRC are associated with a high mortality. Disclosures All Authors: No reported disclosures.

917. Infectious Diseases Consult Improves Management of Candidemia

Abstract Background Infectious Diseases consultations (IDC) have been associated with improved outcomes in multiple disease states with high morbidity/mortality like invasive candidiasis. This study evaluated management of candidemia at Carilion Clinic in patient with and without IDC. Methods A retrospective, observational cohort study was performed among hospitalized patients with candidemia who either received or did not receive an IDC between January 2014 and August 2020. Patients included had Candida species from at least one blood culture. Exclusions were death or transfer to a palliative care plan within 48 hours of culture, cultures from an outside facility, and patients that were pregnant or incarcerated. The primary outcome was a composite of all-cause mortality and recurrent candidemia within 90 days. Secondary outcomes included compliance with candidemia management bundle items such as echocardiography, ophthalmologic evaluation, receipt of susceptible antifungal, source control and repeated blood cultures. Results A total of 194 patients were included in the study. The population was 50.3% male sex and mean ± standard deviation age was 57.8 ± 17.2 years. In the study timeframe, 131 patients received an IDC while 62 did not receive an IDC. ICU level of care, vasopressor requirement and Candida Score ≥ 3 were all similar between the two groups. Candida albicans was the most common species in IDC and non-IDC groups (48.1% vs. 41.1%). Empiric therapy was more commonly an echinocandin in 138/194 (71.1%) and definitive therapy was fluconazole in 117/194 (60.3%). An improved primary composite outcome was observed in the IDC group (34.9% vs. 21.4%, p = 0.043). Patients receiving IDC had a higher rate of repeated cultures (100% vs. 92%) and ophthalmologic examination (54.2% vs. 20.6%). More patients in the IDC group were found to have infective endocarditis (10.7% vs. 1.6%, p = 0.04) as they were more likely to have echocardiographic imaging (86.2% vs. 57.1%, p< 0.0001). The median time to susceptible antifungal was 43 (27-61) hours without ICD and 35 (27-52) hours compared in those with IDC. Conclusion A more comprehensive workup by IDC was associated with more identification of endocarditis and less recurrence of candidemia within 90 days. Disclosures Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Nathan Everson, PharmD, BCIDP, Merck: Advisor/Consultant|Merck: Grant/Research Support Lauren McDaniel, PharmD, BCIDP, Merck: Grant/Research Support.

1521. Non-faecium Non-faecalis enterococcal bloodstream infections in patients with cancer

Abstract Background Non-E. faecium non-E. faecalis (NFF) enterococci are a heterogeneous group of organisms consisting of enterococci with intrinsic low-level vancomycin resistance as well as several other species known to infect humans. Patients with cancer are at increased risk for bloodstream infections (BSIs) with NFF enterococci, but their optimal treatment and outcomes have not been extensively described. Methods We conducted a retrospective review of patients (pts) with blood cultures positive for all NFF by searching the microbiology database at a major cancer center in Houston, TX from 2016 to 2021. Patients were included if they were ≥ 18 years old, had ≥ 1 blood culture with NFF enterococci, and had a repeat blood culture within 7 days (d) of the index culture, to permit outcome analysis. Outcomes were a) in-hospital mortality, b) microbiological failure (blood culture clearance >4 d after index culture), and c) recurrence of bacteremia (new positive blood culture < 14 d after eradication). Results Sixty-two unique pts had NFF enterococcal BSI. Patients with hematological malignancy made up 53.2% of the cohort (78% had leukemia). The majority (83%) of solid malignancies were pancreatic, biliary, or intestinal in origin. In the 30 d preceding NFF enterococcal BSI, 79% of pts had exposure to antibiotics. The NFF species isolated were E. gallinarum (50%), E. casseliflavus (30.6%), E. avium (11.3%), E. raffinosus (3.2%), E. hirae (3.2%), and E. durans (1.6%). Only 23.3% of NFF enterococci were susceptible to vancomycin, and 53.8% were susceptible to linezolid. Most (62.9%) pts received combination therapy; the most frequent was daptomycin plus a beta-lactam (33.9%). Bacteremia recurred in 8.1% of pts, 27.4% had in-hospital mortality, and 4.8% had microbiological failure. Conclusion This retrospective review provides preliminary insight into the treatments, and outcomes of cancer pts with NFF enterococcal BSIs. The NFF enterococci isolates in this study had a higher rate of linezolid non-susceptibility than previously reported. Molecular investigation of these NFF enterococcal isolates is needed to elucidate the mechanisms and transmission of antibiotic resistance. Comparison of BSIs caused by NFF enterococci to E. faecium/E. faecalis will provide insight to physicians caring for these pts. Disclosures Cesar A. Arias, MD, PhD, Entasis: Grant/Research Support|MeMed Diagnostics Ltd: Grant/Research Support|Merck: Grant/Research Support.

1340. Yield of Repeat Blood Cultures beyond 48 Hours after Negative Initial Cultures in Patients Hospitalized on a Pediatric Hematology/Oncology Unit

Abstract Background Repeat blood cultures (BCxs) beyond 48 hours are often obtained despite negative initial BCxs in hospitalized pediatric hematology/oncology patients. This study seeks to determine the yield of repeat BCxs after negative initial cultures in these patients and to characterize new positive BCxs beyond 48 hours and the clinical contexts in which they were obtained. Methods A retrospective review utilizing MedMined Inc. Data Mining Surveillance database was conducted on all BCxs obtained on hospitalized patients on the pediatric hematology/oncology unit at Riley Hospital for Children in Indianapolis, IN from January 2015 to February 2021. Exclusion criteria are shown in Fig. 1. Patient episodes in which a new pathogen (or commensal treated by the primary team as a pathogen) was identified on a repeat BCx more than 48 hours after negative initial BCxs were further investigated via electronic medical record review. Results A total of 1,362 BCx sets were obtained beyond 48 hours in 792 patient hospitalizations, resulting in 303 positive BCxs (Fig. 2). Of these positive cultures, 193 were the same pathogen cultured on day 0 and 74 were contaminant cultures (in 4.0% (23/573) of patient hospitalizations without a positive BCx before 48 hours). Only 36 (2.6%) of positive BCxs beyond 48 hours were determined to be new pathogens, or commensals treated as pathogens, that were not cultured before 48 hours, corresponding to seven patient hospitalizations (1.2% (7/573) of patient hospitalizations without a positive BCx before 48 hours). The majority (6/7) of these patients were neutropenic and on broad spectrum antibiotics when the new positive BCxs were obtained. Fever pattern was prolonged in one patient and recurrent in six. No deaths occurred in these seven patients. All patients with new, true pathogens on BCxs beyond 48 hours (n=5) were either hemodynamically unstable (n=3) or had clinical changes (n=2, mucositis, diarrhea) the day the new positive BCx was drawn. Conclusion The yield of repeat BCxs beyond 48 hours in hospitalized pediatric hematology/oncology patients with negative initial BCxs is low, while the associated costs are high. Repeat BCxs beyond 48 hours after negative initial cultures need not be obtained in febrile patients that remain hemodynamically stable and without clinical changes. Disclosures Cassandra S. Prather, MD, Eli Lilly and Company: Spouse is employed by Eli Lilly and Company. Spouse owns stock in the company.|Eli Lilly and Company: Stocks/Bonds.

589. Clinical Outcomes of Twice versus Thrice daily Metronidazole Dosing for Bacteroides Bloodstream Infections

Abstract Background The optimal metronidazole dose for the treatment of Bacteroides spp. has not been defined. The purpose of this study was to evaluate the utility of a twice (BID), rather than thrice (TID) daily metronidazole dosing strategy among patients with bacteremia due to Bacteroides spp. Methods Adult, hospitalized patients with bacteremia secondary to Bacteroides spp. between October 2010 and June 2021 were assessed across 11 hospitals. The primary endpoint was clinical failure which was a composite of all-cause 30-day mortality, escalation of antimicrobial therapy, 30-day readmission or recurrence due to an anaerobic infection, positive repeat blood cultures for Bacteroides spp., or failure to resolve leukocytosis or fever. Results 208 patients were included; 68 received metronidazole 500mg BID and 140 patients received metronidazole 500mg TID (Figure). Patient age, Charlson comorbidity index, and Pitt Bacteremia score were similar among patients receiving BID vs TID dosing (Table 1). On balance, patients who received BID dosing were more likely to receive oral metronidazole and had shorter lengths of hospitalization prior to bacteremia. Overall, there was no significant difference between rates of clinical failure or other outcomes between patients who received BID versus TID metronidazole dosing (Table 2). In the multivariate model, neither the use of TID dosing (OR = 0.74; 95% CI = 0.33–1.65; P=0.457), time to treatment initiation (OR = 1; 95% CI = 0.81–1.22; P=0.968), days of initial non-metronidazole anaerobic therapy (OR = 0.91; 95% CI = 0.59–1.34; P=0.646), pre-infection length of stay (OR = 1.02; 95% CI = 0.99–1.05; P=0.106), admission prior to 2016 (OR = 1.09; 95% CI = 0.49–2.39; P=0.829), or initial oral metronidazole use (OR = 0.45; 95% CI = 0.18–1.03; P=0.066) were significantly associated with clinical failure. Figure 1:Inclusion and exclusion Non-metronidazole anaerobic coverage consisted of a beta-lactam/beta-lactamase inhibitor, cefoxitin, or a carbapenem Table 1:Demographics and baseline characteristicsTable 2:Clinical outcomes*Patients were considered to have escalated antimicrobial therapy if, in the setting of ongoing signs of infections, antimicrobial therapy was either broadened or the frequency of metronidazole was increased from twice daily to thrice daily. Conclusion In the largest study to date of patients with Bacteroides spp. bacteremia treated with metronidazole, there was no significant difference between BID and TID metronidazole dosing strategies. In the absence of a clear benefit, metronidazole 500mg BID is a reasonable dosing strategy in lieu 500mg TID for infections due to Bacteroides spp. Disclosures Ryan K. Shields, PharmD, MS, Infectious Disease Connect: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Roche: Grant/Research Support.

412: CLINICAL EFFICACY OF INTRAVENOUS PUSH ADMINISTRATION OF BETA-LACTAMS IN GRAM-NEGATIVE BACTEREMIA

Introduction: An intravenous fluid shortage in 2017 prompted health systems to conserve small volume fluids. One strategy to minimize utilization included administering antibiotics as intravenous push (IVP). Pharmacokinetic studies have compared the two administration strategies but a paucity of data exists regarding the clinical efficacy of IVP administration of beta-lactams. The purpose of this study is to compare the clinical efficacy of IVP versus IVPB administration of beta-lactams for the treatment of gram-negative bacteremia. Methods: This retrospective study included adult patients that received aztreonam, cefepime, ceftriaxone, or meropenem for empiric treatment of gram-negative bacteremia between January 1, 2016 and September 15, 2021. The primary outcome was clinical cure at 7 days or discharge, whichever occurred first. Clinical cure was defined as being alive, afebrile, and having an improved or stable SOFA score. Secondary outcomes included the rate of negative repeat blood cultures (if drawn), in-hospital mortality up to 30 days, and hospital and ICU length of stay (LOS). Results: This study included 227 patients were included of which 141 patients received IVP administration and 86 received IVPB administration. The majority of the patients had an E. coli bacteremia (60.8%) from a urinary source (74%). Clinical cure was achieved in 121 (85.8%) of the IVP patients and 77 (89.5%) of the IVPB patients (p=0.415). Repeat cultures were drawn in 44.7% of the IVP group and 53.5% of the IVPB group in which 100% and 97.8%, respectively, were negative (p=0.239). In-hospital mortality (2.1 vs 1.2%, p=0.591), hospital LOS (6.5 vs 6.3 days, p=0.741), and ICU LOS (3.2 vs 3.3 days, p=0.951) were not different between groups. Conclusions: We found no difference in rate of clinical cure between IVPB and IVP Intravenous push administration of beta-lactams. The study sample size may limit broad application of these findings and larger studies are warranted.

Association of Repeated Blood Cultures With Mortality in Adult Patients With Gram-Negative Bacilli Bacteremia: A Systematic Review and Meta-analysis.

Performing repeat blood cultures after an initial positive culture (ie, follow-up blood cultures [FUBCs]) in patients with gram-negative bacilli (GNB) bacteremia is controversial. We aimed to comprehensively review the association of FUBCs with improvement in patient-relevant clinical outcomes in GNB bacteremia. We performed a systematic review and random-effects meta-analysis to calculate summary effect estimates. We used hazard ratios as the effect measure. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were length of treatment and length of hospital stay. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials (Central) without language restrictions from inception to April 29, 2022. Original clinical studies evaluating the association between FUBCs and mortality in adult patients with GNB bacteremia were included. FUBC details were reviewed. Two independent reviewers used the Risk of Bias in Non-randomised Studies of Interventions tool. We identified 9 eligible retrospective studies. In total, 7778 hospitalized patients with GNB bacteremia were included. The studies were clinically heterogeneous and had a critical risk of bias. The utilization of FUBCs varied across studies (18%-89%). Random-effects meta-analysis of covariate-adjusted estimates found that FUBC use was associated with reduced mortality. Although not a result of the meta-analysis, lengths of treatment and hospital stay were longer for patients with FUBCs than for those without. Adverse events were not reported. FUBC acquisition was associated with lower mortality and longer hospital stay and treatment duration in GNB bacteremia. The risk of bias was critical, and no firm data were available to support mechanisms.