Duration Of Bacteremia Research Articles

Penicillin versus anti-staphylococcal beta-lactams for penicillin-susceptible Staphylococcus aureus blood stream infections: a retrospective cohort study.

The objective of the study is to assess the efficacy and tolerability of penicillins compared to anti-staphylococcal beta-lactams for treatment of penicillin-susceptible Staphylococcus aureus bloodstream infections (PSSA BSI). A retrospective cohort study was conducted of 140 sequential PSSA BSI presenting to a local health district (90 cases included). Penicillin susceptibility was confirmed by disc diffusion, Vitek® and Nitrocefin beta-lactamase methods. Clinical information regarding comorbidities and infection complexity was recorded. Antibiotic choice, dosage and duration were reviewed. Outcomes were compared according to the definitive treatment with either penicillin or ASBLs. The primary outcome was 30-day mortality. Secondary outcomes included renal injury, microbiological relapse and treatment tolerability. Ninety patients met inclusion criteria and were included in subsequent analysis. Of PSSA BSI, 69% were community acquired. Eighty-two percent had complex PSSA infections. The average duration of bacteraemia was 2.8days (SD = 1.8days). Sixty-six patients received definitive penicillin treatment, with a mean of 3.5days of empiric antibiotics prior to penicillin. Twenty-four patients received definitive ASBL treatment (11 cefazolin, 13 flucloxacillin). There was no difference in 30-day mortality between groups (p = 1). There was no difference in renal injury (p > 0.5), hospital length of stay (p = 0.59) or microbiological relapse within 1year (p = 0.17). Penicillin treatment was well tolerated. Our data supports penicillin as a suitable and well-tolerated alternative to ASBL in managing complex PSSA BSI.

Association of Antibiotic Duration and Outcomes among NICU Infants with Invasive Staphylococcus aureus Infections

Background:Staphylococcus aureus is the second-leading cause of late-onset sepsis among infants in US neonatal intensive care units (NICUs). Management of S. aureus bacteremia and meningitis in infants varies widely due to the lack of standardized guidelines. We examined the association between initial antibiotic duration and recurrent S. aureus infection or death among NICU infants with S. aureus bacteremia and/or meningitis. Methods: We conducted a retrospective cohort study of infants in Pediatrix Medical Group NICUs from 1997 to 2018 with first episode of S. aureus bacteremia and/or meningitis, identified as having at least 1 blood or cerebrospinal fluid (CSF) culture growing only S. aureus at any point during their NICU stay. Excluded infants were those not started on antistaphylococcal therapy within 2 days of positive culture, those with had endocarditis or osteomyelitis, or those who died or were discharged during or up to 1 day after antibiotic cessation. Antibiotic cessation was defined as last day of antibiotic given if followed by at least 3 days without antibiotics. Multivariable logistic regression was used to analyze the association between antibiotic duration categorized as <14 or ≥14 days) and recurrent SA infection (within 12 weeks of antibiotic cessation, prior to hospital discharge), or death (within 7 days of antibiotic cessation and at discharge). Results: Of 4,086 infants included, 3,991 (98%) had S. aureus bacteremia only and 95 (2%) had meningitis ± bacteremia. Of those with bacteremia only, 2,017 (50.5%), and 17 (18%) of those with meningitis received <14 days antibiotics (Figure 1). Longer antibiotic duration was associated with lower gestational age, methicillin-resistance, severe illness and bacteremia duration of ≥4 days (Table 1). There was a significant association between <14 days antibiotics and recurrent infection (p = 0.04) and 7-day mortality (p = 0.02) in the meningitis cohort. Infants with SA bacteremia who received ≥14 days antibiotics had reduced odds of recurrent SA infection (OR 0.24, 95% CI 0.18-0.32) and death (OR 0.33, 95% CI 0.25-0.44), adjusting for post-natal age, gestational age, sex, methicillin-resistance, severe illness and duration of bacteremia (Table 2). Conclusions: In the largest study thus far examining antibiotic duration among hospitalized infants with S. aureus bacteremia and/or meningitis, ≥14 days antibiotics was associated with decreased odds of recurrent infection or death. Further studies are needed to define the optimal treatment duration and identify clinical factors distinguishing infants able to safely receive a shorter antibiotic duration.Funding: NoDisclosures: None

Evaluation of Ceftolozane/Tazobactam, Ceftazidime/Avibactam and Meropenem/Vaborbactam Against Multidrug-Resistant (MDR) Pseudomonas

Background: Data on the patient outcomes for newer β-lactam–β-lactamase inhibitor (BLBI) drugs compared to carbapenem-containing combination antibiotics for multidrug-resistant (MDR)–Pseudomonas aeruginosa infections are limited. Methods: This retrospective, case–control observational study was based on chart review of the patients managed at the University of Kentucky. Results: In total, 143 patients with MDRO Pseudomonas aeruginosa infections were identified and divided into 2 groups: 1 group received newer BLBI combinations with or without aminoglycosides or polymyxins, for at least 72 hours, and the control group received carbapenem containing combination antibiotics or other antibiotics. Baseline characteristics and patient outcomes are shown in Table 1. Discussion: The newer BLBI combinations group consisted of 60.8% MDR Pseudomonas bacteremia, whereas the control group had 68.4% of MDR Pseudomonas respiratory cultures. Overall, the use of newer BLBI combinations such as ceftazidime/avibactam, ceftolozane/tazobactam, and meropenem/vaborbactam was associated with lower rates of acute kidney injury (AKI), shorter LOS, and lower mortality rates compared to the control group, and these differences were statistically significant. Because the 2 populations of patient differed significantly based on the site of infection (sepsis vs pneumonia), the data were reanalyzed to evaluate the impact of therapy on the occurrence of AKI, LOS, and mortality based on the site of infection. Only those patients with sepsis who received the newer combination drugs had significantly better rates of AKI, lower LOS, and had lower rates of mortality. The 2 treatment arms were not statistically different when comparing patients with pneumonia. Additionally, the use of these new combination therapies did not make a difference regarding readmission rates or duration of bacteremia for the patients included in the study.Funding: NoDisclosures: None

Analysis of Later Stage Morbidity and Mortality after Pancreatic Surgery Because of Abdominal Trauma

Background: Pancreatic trauma surgery is a complicated surgical procedure for severe pancreatic injuries, accompanied by a high incidence of complications and mortality. This study was designed to explore the long-term prognosis of pancreatic surgery because of abdominal trauma. Patients and Methods: The clinical data of 103 patients who were admitted to Jinling Hospital between August 2012 and August 2019 who had pancreatic trauma surgery were analyzed retrospectively. Results: All admissions involved pancreatic trauma surgery performed at an outside hospital network, which later transferred patients to our institution because of post-operative later-stage complications. Eight patients received American Association for the Surgery of Trauma (AAST) grade 1 or 2 pancreatic injuries and 95 received AAST grade 3, 4, or 5 pancreatic injuries. The primary surgical management of pancreatic injuries included drainage of the pancreatic injury (n = 28), repair of the pancreas (n = 35), partial pancreatectomy (n = 15), pancreaticojejunostomy (n = 6), and pancreaticoduodenectomy (n = 19). The most common mechanism of trauma was motor vehicle collision (n = 72), crush injury (n = 26), and stab wound (n = 5). Of 103 patients suffered varying degrees of gastrointestinal fistulae and intra-abdominal infections, there were 66 cases of pancreatic fistulae (64.1%), 49 cases of enteric fistulae (47.6%), 26 cases of colonic fistulae (25.2%), 14 cases of gastric or gastrointestinal anastomotic fistulae (13.6%), and 13 cases of biliary fistulae (12.6%). Ninety-five patients survived and eight patients died after therapy; the mean length of intensive care unit stay was 33 days. The number of patients who underwent emergency pancreaticoduodenectomy (EPD), the incidence of blood transfusion, the number of fistulae per patient, and the duration of mechanical ventilation and bacteremia in the mortality group were substantially higher than in the survival group (p < 0.05 each). The patients who underwent EPD had more grade 5 pancreatic injuries, more blood transfusions, higher peak total bilirubin, greater numbers of fistulae and open abdomen, and longer duration of mechanical ventilation and mortality than other patients (p < 0.05 each). Conclusions: The grade of pancreatic injury was associated with mortality and post-operative complications. The post-operative mortality and occurrence of complications of EPD because of abdominal trauma were significant; use of damage control surgery could potentially reduce the morbidity and mortality related to this procedure.

Clinical Outcomes of Daptomycin Versus Anti-Staphylococcal Beta-Lactams in Definitive Treatment of Methicillin-susceptible Staphylococcus aureus Bloodstream Infections

ObjectivesStaphylococcus aureus (S. aureus) is the leading cause of bacteraemia and infective endocarditis worldwide. The preferred management of patients with methicillin-susceptible S. aureus (MSSA) bacteraemia includes definitive therapy with intravenous anti-staphylococcal beta-lactam (ASBL) antibiotics. Daptomycin (DAP) has been targeted as a viable substitute for beta-lactam allergic or intolerant patients. MethodsThis single-center retrospective cohort study assessed clinical outcomes of DAP compared with ASBL antibiotics [nafcillin (NAF) or cefazolin (CFZ)] for the treatment of MSSA bacteraemia in patients hospitalised from 01 November 2011 to 31 October 2018. The primary outcome was a composite of the following: clinical failure, MSSA recurrence and MSSA persistence or inpatient infection-related mortality. Secondary outcomes included duration of MSSA bacteraemia, infection-related length of stay, infection-related 90-day readmission, 30-day all-cause mortality, and adverse events necessitating a change in therapy. ResultsOf 89 patients with MSSA bacteraemia who were included: 29 received DAP, 30 received NAF and 30 received CFZ. There was no difference in the composite primary outcome in patients treated with DAP compared with ASBL (10% vs. 5%, P = 0.39). The DAP cohort had a longer hospital length of stay compared with the ASBL group (20 days vs. 11.5 days, P = 0.0007). No differences were detected between other secondary outcomes. ConclusionThis study suggests that DAP may serve as a comparable alternative to ASBLs for treatment of MSSA bacteraemia, as no differences in clinical outcomes were identified. Larger studies are needed to confirm these findings.

POS-566 CATHETER RELATED BLOODSTREAM INFECTION (CRBSI) IN A MIDDLE-EASTERN COHORT OF HEMODIALYSIS PATIENTS: AN ANALYSIS OF 5 YEARS OF FOLLOW UP DATA

Bloodstream infections (BSI) are the second commonest cause of morbidity and mortality in end stage renal failure (ESRF) patients. Dialysis catheters are believed to be the most common contributors to BSI in this cohort. Therefore, patients who are receiving hemodialysis via long term central venous catheters (CVC) are at significantly high risk of CRBSI and its associated morbidity and mortality. Although there are several studies on CRBSI from different cohorts around the world, long-term follow up data are scarce particularly from middle eastern cohorts. We aim to fill this knowledge gap as well as to develop an antibiogram and antibiotic stewardship for this unique cohort of patients. This is a single center retrospective longitudinal study of a middle eastern cohort receiving three times a week regular hemodialysis via permanent CVC in a large out-patient setting. We analyzed all the data from December 2015 to November 2020. Data on incidents of CRBSI, etiology, antimicrobial susceptibility, CRBSI risk factors, and comorbidities were collected. For the sake of our study, we defined CRBSI with the isolation of the same microorganism from the CVC and peripheral blood culture without any other apparent source. The incidence of CRBSI was expressed as incidence per 1000 catheter days. A total of 39 incidents of CRBSI were identified during these 5 years study period. Of the reported cases, 94% grew a single organism while 6% grew polymicrobial. Of the multitude of organisms isolated, 39% were gram positives while the rest were gram negatives. Staphylococcus aureus and enterococcus were predominant gram positives while pseudomonas and klebsiella were the predominant gram negatives. No case of MRSA or fungi were isolated. The distribution of organisms is illustrated in the bar chart below. Interestingly only 70% of cases presented with the typical triad of fever, rigors, and exit site exudates, while around 20% presented with only hypotension. 10% of the cases were completely asymptomatic and were only incidental findings. The incidence of CRBSI per 1000 catheter days was calculated for every month and as illustrated by the graph below, the CRBSI rates seem quite variable throughout this study period. However, interestingly, since the beginning of the COVID19 pandemic outbreak, the CRBSI rates are conspicuously low. This might be explainable by enhanced focus on hand hygiene by both the staff and the patients themselves during this pandemic. CRBSI incidences were higher among patients with longer duration of catheter use, previous bacteremia, old age, diabetes mellitus, and recent hospitalization.View Large Image Figure ViewerDownload Hi-res image Download (PPT) The incidence of CRBSI reported from our center seems to be comparable to other international centers around the world. The causative microorganisms and their antibiotic susceptibilities also seem to be in concordance with the rest of the world despite variations in geography, climate, and ethnicity. We conclude, that irrespective of the differences in the geographical location and study cohorts, strict adherence and attention to hand hygiene and infection control practices by both the staff and the patients are the keys to keeping CRBSI low.

#81: Care Process Measures and Outcomes of Percutaneous Pulmonary Valve Implantation-associated Infective Endocarditis

Abstract Background Percutaneous pulmonary valve implantation (PPVI) is being increasingly used as a minimally invasive corrective procedure for right ventricular outflow tract (RVOT) dysfunction. Ten-year survival following PPVI is estimated at over 90% due to the durability of the various bioprosthetic valves. However, infective endocarditis (IE) remains a potential complication of such valves with significant morbidity and mortality. We evaluated the presenting symptoms, clinical features, pathogens, and outcomes of patients with IE following PPVI to identify opportunities to improve early diagnosis and management. Methods A convenience sample of patients at a large Pediatric Cardiology practice in Northern Virginia was queried for PPVI and IE from January 1, 2016, to June 30, 2019. Manual chart review was done to extract clinical points of interest and descriptive analyses were performed. Patients were classified as having IE per modified Duke’s criteria. Results We identified 14 patients who underwent PPVI. Five of these patients (36%) developed IE. All IE patients had underlying Tetralogy of Fallot and none had previous episodes of IE. 60% of patients with IE were male with a median age of 26 years old (IQR 20–30). Four IE patients had a Melody valve and 1 had a SAPIEN valve. The median elapsed time between PPVI and IE diagnosis was 128 days (IQR 32–391) with a median duration of illness prior to the diagnosis of IE of 6 days (IQR 5–9). All IE patients had to present fever. 40% of IE patients had to present chest pain and 20% had presenting musculoskeletal pain. All IE patients had an elevated initial C-reactive protein (CRP) with a median value of 13.1 mg/dL (IQR 12.5–15.2). The median initial white blood cell count was 9.3 × 103/μL (IQR 8.1–10.3). The median duration of bacteremia was 1 day (IQR 1–2). A pathogen was recovered in all five IE patients with different organisms amongst the patients: coagulase-negative Staphylococcus species were recovered in patients who developed IE within 60 days from PPVI (Staphylococcus lugdunensis and Staphylococcus epidermidis) whereas coagulase-negative Staphylococcus species and oral commensal organisms were found in IE patients beyond 60 days from PPVI (Staphylococcus sanguinis, Gamella haemolysans, and Neisseria elongata). The initial echocardiogram did not show vegetations in any of the patients and 40% went on to have sternotomy with valve replacement. There were no deaths. Conclusions With an increase in PPVI, clinicians should have a high index of suspicion for IE in patients with underlying Tetralogy of Fallot who present with fever and elevated CRP, regardless of elapsed time from PPVI or valve type. Empiric antimicrobial therapy for suspected IE following PPVI should remain broad with other possible pathogens beyond coagulase-negative Staphylococcus species.

Vancomycin or Daptomycin Plus a β-Lactam Versus Vancomycin or Daptomycin Alone for Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: A Systematic Review and Meta-Analysis.

Aims: Several in vitro and in vivo studies demonstrated that adding a β-lactam to vancomycin (VAN) or daptomycin (DAP) can provide synergy against methicillin-resistant Staphylococcus aureus (MRSA). However, the results from clinical studies were controversial. The objective of this systematic review and meta-analysis was to compare the efficacy and safety of using VAN or DAP plus a β-lactam (combination therapy) and using VAN or DAP alone (monotherapy) in MRSA bloodstream infections. Methods: We included randomized controlled trials and observational studies evaluating whether combination therapy can improve clinical and microbiological outcomes and safety compared to monotherapy with VAN or DAP in MRSA-related bacteremia. Results: Literature search identified 3 randomized clinical trials and 10 observational studies involving at least 1,796 patients. There were no significant associations between the combination therapy and risk of mortality within 30 days (risk ratios [RRs], 1.10, 95% confidence interval [CI], 0.82-1.46), in-hospital mortality (RR, 0.59, 95% CI, 0.31-1.13) and mortality within 60-90 days (RR, 0.91, 95% CI, 0.64-1.29). There was also no evidence that there was a difference in length of hospital stay between the combination therapy and monotherapy (mean difference, -0.41 days, 95% CI, -3.41 to 2.59). However, compared with monotherapy, combination therapy seemed to have a shorter duration of bacteremia(mean difference, -1.06 days, 95% CI, -1.53 to -0.60), a lower risk of persistent bacteremia (RR, 0.63, 95% CI, 0.51-0.79) and a lower risk of bacteremia recurrence within 60-90 days (RR, 0.61, 95% CI, 0.40-0.92). There were no statistically significant differences in the total number of adverse events, including acute kidney injury (AKI) (RR, 1.52, 95% CI, 0.84-2.73), thrombocytopenia (RR, 1.13, 95% CI, 0.74-1.73), and diarrhea (RR, 1.36, 95% CI, 0.70-2.65), between patients with combination therapy and monotherapy. In subgroup analysis, when the analysis was limited to the studies comparing using DAP plus ceftaroline with monotherapy, we found that the former had a lower risk of mortality within 30 days. In addition, a subgroup analysis limited to randomized clinical trials showed that the combination therapy was associated with a higher risk of AKI compared with using VAN or DAP alone. Conclusions: Although adding a β-lactam to standard therapy seemed to experience a higher clearance compared with monotherapy in patients with MRSA bacteremia, the combination therapy did not increase survival benefits. Based on the available evidence, the combination therapy was not supported as the routine management of MRSA-related bacteremia, and both its harms and benefits should be taken into account.

Association between high vancomycin minimum inhibitory concentration and clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia- A retrospective cohort study.

The purpose of this study is to determine the role of high (≥ 1.5 mg/L) vancomycin minimum inhibitory concentration (VMIC) in predicting clinical outcomes in patients with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). A retrospective study was conducted at Mayo Clinic, Minnesota. Patients ≥ 18 years with a 3-month follow-up were included. Outcomes were defined as 30-day all-cause in-hospital mortality, median duration of bacteraemia, metastatic infectious complications, and relapse of MRSAB. A total of 475 patients with MRSAB were identified, and 93 (19.6%) of them had high VMIC isolates. Sixty-four percent of patients were male with a mean age of 69.0 years. Active solid organ malignancy and skin and soft tissue infection as source of MRSAB were associated with high VMIC, while septic arthritis as a complication was significantly associated with low VMIC on multivariate analysis. Eighty-one (17.1%) patients died within 30 days of hospitalization, with no significant difference in mortality rates between the two groups. In-hospital mortality, median duration of bacteraemia, and metastatic infectious complications were not significantly associated with high VMIC MRSAB.

Variable Release of Lipoteichoic Acid From Staphylococcus aureus Bloodstream Isolates Relates to Distinct Clinical Phenotypes, Strain Background, and Antibiotic Exposure.

BackgroundStaphylococcus aureus is a leading cause of bacterial bloodstream infections. The heterogeneity in patient outcomes in S. aureus bacteremia (SAB) can be attributed in part to strain characteristics, which may influence host response to infection. We specifically examined the relationship between lipoteichoic acid (LTA) release from S. aureus and disease phenotype, strain background, and antibiotic exposure.MethodsSeven strains of S. aureus causing different clinical phenotypes of bacteremia and two reference strains (LAC USA 300 and Mu3) were analyzed for LTA release at baseline and following exposure to antibiotics from different pharmacologic classes (vancomycin, ceftaroline, and tedizolid). LTA release was quantified by LTA-specific ELISA. Whole genome sequencing was performed on the clinical strains and analyzed using open-source bioinformatics tools.ResultsLipoteichoic acid release varied by 4-fold amongst the clinical strains and appeared to be related to duration of bacteremia, independent of MLST type. Low LTA releasing strains were isolated from patients who had prolonged duration of bacteremia and died. Antibiotic-mediated differences in LTA release appeared to be associated with MLST type, as ST8 strains released maximal LTA in response to tedizolid while other non-ST8 strains demonstrated high LTA release with vancomycin. Genetic variations related to the LTA biosynthesis pathway were detected in all non-ST8 strains, though ST8 strains showed no variations despite demonstrating differential LTA release.ConclusionOur findings provide the basis for future studies to evaluate the relationship between LTA release-mediated host immune response and clinical outcomes as well as the potential for antibiotic modulation of LTA release as a therapeutic strategy and deserve confirmation with larger number of strains with known clinical phenotypes.

Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Early&amp;nbsp;Platelet Dynamics During &lt;i&gt;Staphylococcus Aureus&lt;/i&gt; Bacteremia is Associated with Dysregulated Cytokine Response and Predictive of Microbial Persistence and Mortality

Background: Platelets play key roles in host immune response during sepsis. Microbial persistence and early dysregulated cytokine response predict poor outcomes in patients with Staphylococcus aureus bacteremia (SAB). Our objective was to determine the relationship between early platelet trends and cytokine response, microbial persistence and 30-day mortality in patients with SAB. Methods: A two-center observational study was conducted in hospitalized patients with monomicrobial SAB. Electronic medical records were reviewed for pertinent demographic, laboratory, and clinical information. Eligible subjects were grouped by platelet count at onset and Day 4 of SAB: normal platelet (NP, > 150 x 109/L) and thrombocytopenia (TC, < 150 x 109/L). The groups were compared for clinical characteristics and outcomes. Findings: 812 patients met inclusion criteria. The median age was 59 years with MRSA accounting for 34% of SAB. The most common comorbidities were hypertension followed by diabetes then renal disease. Thrombocytopenia (TC) occurred in 29% of patients at SAB onset: 15% (n = 120) were mild and 14% (n = 114) were moderate-tosevere (MS). Compared to patients with normal platelet (NP) at SAB onset (n = 578), higher proportion of patients with TC had alcohol use disorder (p = 0·015), active malignancy (p = 0·002), liver disease (p < 0·001), in addition to requiring intensive care unit (ICU) level of care during hospital stay (p < 0·001). TC patients had a longer duration of bacteremia (3 days vs 2 days; p = 0·008) and higher risk for 30-day mortality (18% vs 6%; p < 0·001) overall compared to those with NP. Changes in platelet count from SAB onset to Day 4 differed significantly between those with persistent (PB) versus resolving bacteremia (RB). Notably, patients who had NP at SAB onset but developed new onset of TC by Day 4 had a higher risk for 30-day mortality compared to those who maintained NP at Day 4 (20% vs 4%; p < 0·001). Those with recovery of their platelet count from TC to NP by Day 4 (n = 20) had their SAB shortened by one day (2 days vs 3 days; p = 0·413) and trended toward lower risk for 30-day mortality (5% vs 22%; p = 0·068) compared to those with sustained TC by Day 4 (n = 88). Interpretation: Our results suggest that platelet dynamics during early course of SAB are associated with dysregulated cytokine response and predictive of 30-day mortality. Future studies should be conducted to assess the impact of utilizing platelet count within the first four days of S. aureus bacteremia to guide clinical interventions and to further investigate S. aureus virulence factors that impair recovery of platelet count in patients with thrombocytopenia. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: The study protocol was approved by the institutional review boards at each of the study site.

266. Ceftriaxone Versus Cefazolin for the Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia

BackgroundFew studies have evaluated the use of ceftriaxone (CRO) in the treatment of Methicillin-sensitive Staphylococcus aureus (MSSA) infections. Available studies include a small number of patients with MSSA bacteremia, with conflicting results and several limitations. The purpose of this study was to compare the safety and efficacy of CRO versus cefazolin (CFZ) for patients with MSSA bacteremia.MethodsThis was a multi-center, single health-system retrospective cohort study. Patients were included if they were at least 18 years old, had a primary episode of MSSA bacteremia within Saint Luke’s Health System and received CRO or CEFZ as definitive therapy for MSSA bacteremia. Patients were excluded if they had a previous MSSA bacteremia within 6 months, a polymicrobial infection, received combination antimicrobial therapy as definitive therapy, started treatment at outside hospital, treated for less than 72 hours, or deemed palliative or comfort care. The primary endpoint was clinical cure at 7, 10, 14, and 28 days, or discharge, whichever came first. Secondary endpoints included time to clinical cure or discharge, treatment failure at 90 days, time to treatment failure, readmission due to recurrent MSSA bacteremia at 30 and 90 days, duration of bacteremia, discontinuation of definitive treatment due to adverse drug events, incidence of Clostridiodes difficile infection, and hospital length of stay.ResultsA total of 248 patients met inclusion criteria. Among these, 87 (35.1%) received CRO and 161 (64.9%) received CFZ as definitive therapy. Patient baseline and treatment characteristics are shown in Table 1. The primary outcome occurred in 75 (86.2%) patients in the CRO group vs 145 (90.1%) patients in the CFZ group (P= 0.359), even after adjusting for Charlson Comorbidity Index, Pitt bacteremia score and serum creatinine, (aOR=0.74, 95% CI 0.32 – 1.72; p=0.473). There were no differences in time to clinical cure or discharge, treatment failure at 90 days, or safety events between the two groups. Primary and secondary endpoints are included in Table 2.Table 1 Table 2 ConclusionOur study suggests that there is no clinical difference between CRO and CFZ for the treatment of MSSA bacteremia. Further studies are needed to confirm these findings.Disclosures All Authors: No reported disclosures

117. Adjunctive Daptomycin in the Treatment of staphylococcus Aureus Bacteremia

BackgroundBloodstream infections (BSI) caused by methicillin-susceptible Staphylococcus aureus (MSSA) are associated with significant morbidity and mortality. The objective of our study was to determine whether daptomycin given in combination with an anti-staphylococcal beta-lactam improved outcomes in MSSA BSI.MethodsA randomized, double blind, placebo-controlled trial was performed at two academic hospitals in Montreal, Canada. Patients ≥ 18 years of age with MSSA BSI receiving either cefazolin or cloxacillin monotherapy were considered for inclusion. In addition to the standard of care treatment, participants received a 5-day course of adjunctive daptomycin or placebo. The primary outcome was the duration of MSSA BSI in days.ResultsOf 318 participants screened, 115 were enrolled and 104 were included in the intention to treat analysis (median age 67 years; 34.5% female). The median duration of bacteremia was 2.04 days among patients who received daptomycin versus 1.65 days in those who received placebo (absolute difference 0.39 days, p=0.40). A modified intention to treat analysis involving participants who remained bacteremic at the time of enrollment found a median duration of bacteremia of 3.06 days among patients who received daptomycin versus 3.0 days in those who received placebo (absolute difference 0.06 days, p=0.77). Ninety-day mortality in the daptomycin arm was 18.9% vs. 17.7% in the placebo arm (p=1.0). There were no significant differences in the proportion of patients who developed renal failure, hepatotoxicity, or rhabdomyolysis between groups.ConclusionAmong patients with MSSA BSI, the administration of adjunctive daptomycin therapy to standard of care treatment did not shorten the duration of bacteremia.Disclosures All Authors: No reported disclosures

1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections

BackgroundMSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections.MethodsSixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts.ResultsTwenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578)ConclusionPrevious studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon.Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)

269. Clinical Characteristics and Outcomes of Persistent Staphylococcus aureus Bacteremia

Background Staphylococcus aureus bacteremia (SAB) is a leading cause of bacteremia and persistent SAB is associated with poor outcomes. We evaluated key clinical characteristics and outcomes associated with persistent SAB.MethodsWe reviewed patients enrolled in a prospective cohort of adult patients with S. aureus bacteremia at a tertiary hospital from August 2008 to December 2018. Clinical characteristics, outcomes, and microbiologic characteristics of patients with persistent bacteremia (≥ 3 d) were evaluated.ResultsOf the total 969 patients, 617 (63.7%) patients had persistent bacteremia. The median duration of bacteremia with persistent bacteremia was 5 days. The most common sources of persistent bacteremia were central venous catheter-related infection (33.4%) and bone and joint infection (14.9%). Methicillin resistant S. aureus (MRSA) isolates were analyzed in 372 (60.3%) patients and metastatic infections were 217 (35.2%) with persistent bacteremia. In the multivariate analysis, APACHE Ⅱ score (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03–1.10), Charlson comorbidity index score (aOR, 1.14; 95% CI, 1.04–1.25), liver cirrhosis (aOR, 2.47; 95% CI, 1.44–4.23), and S. aureus pneumonia (aOR, 3.04; 95% CI, 1.29–7.18) were independently associated with 30-d mortality. In persistent MRSA bacteremia, ST5-SCCmecⅡ was 59.7% (222/372) and agr dysfunction was 64.8% (241/372). After adjusting for confounding factors, APACHE Ⅱ score (aOR, 1.08; 95% confidence interval [CI], 1.04–1.12), liver cirrhosis (aOR, 3.09; 95% CI, 1.56–6.14), and S. aureus pneumonia (aOR, 4.37; 95% CI, 1.40–13.67) were independently associated with 30-d mortality.Table 1. Demographic and Clinical characteristics of Patients With Persistent Bacteremia Table 2. Microbiologic Characteristics and Genotypes in MRSA Isolates Responsible for Persistent Bacteremia Fig 1. Duration of Staphylococcus aureus bacteremia ConclusionIn persistent bacteremia, clinical factors, including APACHE Ⅱ score, Charlson comorbidity index score, liver cirrhosis, and S. aureus pneumonia contribute to 30-d mortality.Disclosures All Authors: No reported disclosures

292. Impact of the BACT/ALERT VIRTUO blood culture system in the management of Staphylococcus aureus bacteremia

Background Staphylococcus aureus bacteremia (SAB) is a major cause of mortality. Recovery of SA may be enhanced with new blood culture systems resulting in a longer observed duration of bacteremia.MethodsWe performed a 24-month retrospective study of adults hospitalized with SAB at a 1250-bed academic hospital. Between 1/2018-12/2018 the VersaTREK system was used and 1/2019-12/2019 the BACT/ALERT VIRTUO (VIRTUO) system was used. We excluded patients without an Infectious Diseases (ID) consult. We defined SAB duration as short (1–2 days), intermediate (3–6 days), or prolonged (>7 days). We compared SAB detection and management pre- and post-implementation of VIRTUO.Results456 patients had SAB during study period; 420 (92%) had ID consultation: 178 (42%) pre- and 242 (58%) post-implementation. Similar proportion of methicillin-resistant SAB was seen (44.9% pre- vs. 36.8% post-implementation, p=0.09). Post-implementation, patients were more likely to have intermediate (22.4% pre- vs. 40.1% post-implementation; p< 0.001) and prolonged SAB duration (3.9% pre- vs. 13.6% post-implementation; p< 0.001). Median time to positivity for the index blood culture was shorter (19.9 pre- vs. 15.0 hours post-implementation, p< 0.001). Dual anti-staphylococcal therapy was used more frequently in the post-implementation period (6.2% pre- vs. 15.7% post-implementation, p=0.003). No difference was noted in frequency of diagnostic studies (transesophageal echocardiography, magnetic resonance imaging, and computed tomography). Source control was similar (46.1% pre- vs. 45.0% post-implementation; p=0.84) but the median time to source-control was shorter post-implementation (4 pre- vs. 2 days post-implementation; p=0.02). Median planned duration of intravenous antibiotics did not vary between pre- and post-implementation periods (6 vs. 6 weeks, p=0.31). There was no difference in 90-day readmissions (38.2% pre- vs. 34.3% post-implementation; p=0.41).ConclusionVIRTUO blood culture system decreased time to positivity and increased frequency of prolonged SAB compared to the VersaTREK system. This resulted in increased use of dual anti-staphylococcal therapy and shorter time to source-control, but no difference in interventions, planned duration of antibiotics, or readmissions.Disclosures All Authors: No reported disclosures

1624. Real World Experience with Daptomycin (DAP) and Ceftaroline (CPT) Combination Therapy for Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus bacteremia is associated with significant mortality rates up to 30%. Guideline-recommended first-line therapy includes monotherapy with either vancomycin or DAP. Alternative regimens are recommended for persistent MRSA bacteremia of ≥ 7 days or earlier if evident clinical deterioration. The combination of DAP plus CPT has been investigated as salvage therapy due to its synergistic mechanism potential, but real-world data with the combination therapy is limited. The aim of this study was to evaluate the efficacy of DAP plus CPT combination therapy for the treatment of MRSA bacteremia and identify independent predictors of 30-day mortality.MethodsThis was a single center retrospective study of patients receiving DAP-CPT at any point in therapy for the treatment of MRSA bacteremia. Univariable and multivariable analyses were performed to identify independent predictors of 30-day mortality.ResultsSixty-five unique patients received DAP-CPT with a median time to combination therapy of 7 days. There were no significant independent predictors of 30-day mortality. The most common reason for combination therapy was persistent bacteremia (80%, 52/65). Bacteremia was cleared in 90.8% (59/65) of patients and the 30-day mortality rate was 15.4% (10/65). Median time to bacteremia clearance after combination switch was 3 days. Eleven patients received DAP-CPT within 72 hours of index culture. Median time to bacteremia clearance for patients switched to DAP-CPT within 72 hours versus after 72 hours did not differ (2 vs 3 days; P = 0.526), however the overall median duration of bacteremia was 4 and 11 days (P = 0.018). In a sub analysis, the median time of bacteremia clearance following combination therapy was significantly longer for patients receiving renal replacement therapy (5 vs 2 days; P = 0.04).ConclusionThere were no independent predictors of 30-day mortality identified. DAP-CPT combination therapy resulted in clearance of persistent bacteremia and may serve as an effective salvage therapy.Disclosures All Authors: No reported disclosures

Staphylococcus bacteremia without evidence of cardiac implantable electronic device infection

Staphylococcus bacteremia (SB) in the presence of a cardiac implantable electronic device (CIED) is frequently associated with CIED infection. In patients without clear CIED infection but SB, the role of empirical CIED removal is unclear. The purpose of this study was to describe the natural history of SB in the setting of a CIED and the effect of CIED removal on mortality in patients with concurrent SB without evidence of CIED infection. Three hundred sixty consecutive patients (mean age 61 ± 17 years; 255 (71%) men; 329 (92%) Staphylococcus aureus) with a CIED and concurrent SB were reviewed. At the initial presentation with SB, 178 patients had no evidence of CIED infection. Of these, 132 (74%) had another identified source of infection. Among the 178 patients without CIED infection, 18 (10%) had empirical CIED removal during the initial bacteremia. Among those who did not undergo CIED removal, SB subsequently relapsed in 19% and relapse rates were not different for those with or without another identifiable source at the initial presentation. Relapse was strongly associated with the duration of SB >1 day (odds ratio 9.99; 95% confidence interval 3.24-30.86). Despite the absence of CIED infection, 1-year mortality was 35% and empirical device removal during the initial presentation was associated with survival benefit (hazard ratio 0.28; 95% confidence interval 0.08-0.95). For patients with SB without evidence of CIED infection, relapse is predicted by the duration of bacteremia. Empirical CIED removal appears to be associated with a survival benefit, although there are likely clinical situations in which this could be deferred.

Follow-up Blood Cultures in Children With Staphylococcus aureus Bacteremia.

Staphylococcus aureus is a common pathogen seen in pediatric bloodstream infections. Currently, no evidence-based recommendations are used to guide decisions on the number of follow-up blood cultures (FUBCs) needed to demonstrate infection clearance. Unnecessary cultures increase the risk of false-positives, add to health care costs, and create additional trauma to children and their families. In this study, we examined risk factors for persistent S aureus bacteremia (SAB) and intermittent positive blood cultures (positive cultures obtained after a documented negative FUBC result) to determine the number of FUBCs needed to demonstrate infection clearance in children. Patients ≤18 years who were hospitalized with SAB at Texas Children's Hospital in 2018 were reviewed. We assessed the impact of an infectious disease diagnosis (central line-associated bloodstream infection, osteomyelitis, soft tissue infection, endocarditis, etc) and medical comorbidities on bacteremia duration. Patients with intermittent positive blood cultures were studied to determine the characteristics of this group and overall frequency of reversion to positive cultures. A total of 122 subjects met the inclusion criteria. The median duration of bacteremia was 1 day (interquartile range: 1-2 days). Only 19 patients (16%) had bacteremia lasting ≥3 days, all of whom had a diagnosis of central line-associated bloodstream infection, osteomyelitis, or endocarditis. Intermittent positive cultures occurred in 5% of patients, with positive cultures after 2 negative FUBC results seen in <1% of patients. Intermittent positive cultures were strongly associated with osteomyelitis and endocarditis. On the basis of our sample of children with SAB, additional blood cultures to document sterility are not necessary after 2 FUBC results are negative in well-appearing patients.