Duration Of Bacteremia Research Articles

Prognostic significance of early platelet dynamics in Staphylococcus aureus bacteremia

BackgroundPlatelets are recognized as key immune effectors, but they are targets of bacterial virulence factors. In the present study, we aimed to examine the relationship between early platelet dynamics and the outcome of Staphylococcus aureus bacteremia (SAB).MethodElectronic medical records of adult patients hospitalized for SAB between July 2012 and November 2020 were retrospectively reviewed for relevant demographic, laboratory, and clinical data. The outcome endpoints were mortality and microbial persistence.ResultsAmong the 811 patients evaluated, 29% experienced thrombocytopenia on Day 1. Platelet count nadir occurred on Days 2–3 following SAB onset, and Day 4 was a determining point of platelet count trajectory and mortality. Mortality risk was 6% or less for those with normal platelet count by Day 4 regardless of whether they experienced thrombocytopenia on Day 1, but the risk increased to 16–21% for those who experienced thrombocytopenia on Day 4 regardless of whether they had normal platelet count on Day 1 or sustained thrombocytopenia. The duration of bacteremia was prolonged by one day (median 3 d vs. 2 d) for those with sustained thrombocytopenia compared to those without.ConclusionEarly platelet dynamics during SAB have prognostic significance and represent an early window for potential platelet-directed therapeutic interventions to improve outcome.

Outcomes of Daptomycin Plus Ceftaroline Versus Alternative Therapy for Persistent Methicillin-resistant Staphylococcus aureus (MRSA) Bacteraemia

ObjectivesThis study aimed to evaluate both efficacy and safety of combination therapy with daptomycin plus ceftaroline (DAP/CPT) versus alternative therapy in the treatment of persistent methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). MethodsThis retrospective, single-centre study investigated adult patients who underwent a change in antibiotic therapy for persistent MRSAB. Daptomycin plus ceftaroline was compared with alternative therapy after initial treatment with vancomycin or DAP monotherapy was modified. The primary outcome was in-hospital mortality, and several secondary efficacy and safety outcomes were evaluated. ResultsA total of 68 patients with persistent MRSAB had initial therapy switched to DAP/CPT (n = 43) or alternative therapy (n = 25). In-hospital mortality was similar with DAP/CPT versus alternative therapy (16.3% vs. 16%; P = 1.0). On average, the total duration of bacteraemia was numerically 1 day less in patients switched to DAP/CPT (11.4 days vs. 12.5 days; P = 0.5). Daptomycin plus ceftaroline was de-escalated in 81% of patients after receiving combination therapy for an average of 12.5 days. Secondary outcomes, including rates of adverse events and emergence of antimicrobial resistance, were similar between the two groups. ConclusionsSwitching to DAP/CPT after approximately 1 week of persistent MRSA bacteraemia may result in similar clinical outcomes when compared with alternative therapy. Rates of adverse events and emergence of antimicrobial resistance were low without a statistically significant difference observed between DAP/CPT and alternative therapy. These findings, as well as the impact of earlier switch or prolonged treatment with the combination, require further investigation.

Clinical and microbiological characteristics of rifampicin-resistant MRSA bacteraemia.

The clinical significance of rifampicin resistance in Staphylococcus aureus infections has not been demonstrated. Here, we evaluated the clinical characteristics of rifampicin-resistant S. aureus infection. Data were collected from adult patients who were hospitalized with MRSA bacteraemia between March 2007 and May 2020 at a tertiary hospital in South Korea. The clinical characteristics and treatment outcomes of patients infected with rifampicin-resistant MRSA were compared with those of rifampicin-susceptible isolates. All-cause death and recurrence of MRSA infection were assessed for 90 days. Of the 961 patients with MRSA bacteraemia, 61 (6.3%) were infected by rifampicin-resistant isolates. The type of infection focus and duration of bacteraemia did not significantly differ between the two groups. Rifampicin-resistant MRSA isolates were more likely to have multidrug resistance and a higher vancomycin MIC relative to the rifampicin-susceptible isolates. The 90-day recurrence rate was higher in the patients infected with rifampicin-resistant MRSA compared with those with rifampicin-susceptible MRSA (18.0% versus 6.2%, P < 0.001), whereas the 90-day mortality was comparable between the two groups (27.9% versus 29.2%, P = 0.94). After adjusting for potential confounding factors, rifampicin resistance was significantly associated with 90-day recurrence (subdistributional HR: 2.31; 95% CI: 1.05-5.10; P = 0.04). Rifampicin-resistant MRSA isolates showed distinct microbiological features in terms of multidrug resistance and a high vancomycin MIC. Although the management of MRSA bacteraemia was not significantly different between the two groups, recurrence was significantly more common in the rifampicin-resistant group. Rifampicin resistance may play a significant role in infection recurrence.

432: EFFICACY OF TARGETED VS. NONTARGETED BETA-LACTAM THERAPY FOR MSSA BACTEREMIA: A MATCHED COHORT STUDY

Introduction: Methicillin-susceptible Staphylococcus aureus (MSSA) is implicated in blood stream infections with high morbidity and mortality. Targeted treatment (TT) with nafcillin or cefazolin is considered first-line therapy, however patients may receive broad spectrum therapy for MSSA bacteremia for various reasons. We hypothesize non-targeted beta-lactams (NT) are less effective for blood culture clearance compared to TT for MSSA bacteremia. Methods: Critically ill patients >18 years old with an MSSA positive blood culture between 7/1/2014 and 12/31/2020 were included. Patients were identified retrospectively through the electronic medical record and must have received either a NT (ampicillin/sulbactam, ceftriaxone, cefepime, piperacillin/tazobactam, meropenem) or TT. The TT cohort included the receipt of or de-escalation to nafcillin or cefazolin within 72 hours of antibiotic initiation. Patients with lack of follow-up blood cultures, death, or discharge within 48 hours of positive culture were excluded. Patients were matched according to age, Charlson Comorbidity Index (CCI), presence of a central line, and source of bacteremia. The primary outcome was duration of bacteremia. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS) and inpatient mortality. Results: Of 423 patients, 178 were included based on matching criteria. The majority of patients were male (63%) and Caucasian (92%) with a median age of 56 (interquartile range [IQR], 47-65). Median CCI was 5 in both groups (IQR, 3-8). The most frequent NT were piperacillin/tazobactam (56%) and cefepime (34%). There was no significant difference in duration of bacteremia (3.4 vs 3.4 days, p=0.653), hospital LOS (18.9 vs 26.4 days, p=0.071), or ICU LOS (5.3 vs 5.9 days, p=0.966) in the TT vs NT cohorts, respectively. Patients in the TT cohort had significantly lower mortality compared to those in the NT cohort (12.4% vs 24.7%, p=0.034). Conclusions: ICU patients who received TT or NT had similar duration of bacteremia, hospital LOS, and ICU LOS. Exposure to NT was associated with increased mortality. Although these results should be validated prospectively, clinicians should be cognizant of this risk when evaluating those with MSSA bacteremia and consider de-escalation to TT as soon as clinically appropriate.

970. The Time for Action is Now: The Impact of Timing with Infectious Diseases Consultation for Staphylococcus aureus Bacteremia

Abstract Background Staphylococcus aureus bacteremia (SAB) is one of the leading causes of bloodstream infections complicated by metastatic diseases leading to extended lengths of stay (LOS). Infectious disease (ID) consultation is associated with greater adherence to standards of care and improved clinical outcomes. There are sparse data evaluating the impact of the timing for ID consult on SAB management. The purpose of this study was to compare the difference in clinical outcomes in patients with SAB who received an early (&amp;lt; 5 days) versus late (≥ 5 days) ID consult. Methods This was an IRB-approved, retrospective, cohort study in hospitalized adult patients with SAB who received an ID consultation between 2015 and 2020. The timing of the ID consult was defined from the order of the index positive blood culture to the placement of the consult. The composite primary endpoint included: identifying the source of SAB, follow-up cultures, obtaining an echo, use of parenteral therapy, and treatment duration. Secondary endpoints included mortality, recurrence, LOS, duration of bacteremia, and readmission rates (30, 60, and 90-day). A machine learning algorithm (MLA) was utilized to determine an alternative to the 5 days threshold for early vs late. Results A total of 321 patients with SAB were included with baseline characteristics (Table 1). The early group was more likely to meet the primary endpoint (62.5% vs. 28.3%, p &amp;lt; 0.001). The median duration of bacteremia and length of stay was shorter in the early group (p &amp;lt; 0.001) (Table 2). MLA determined an alternative threshold of ≤ 3.5 days for early ID consult. Multivariable analyses reported early ID consult in ≥ 5 days (adjusted OR: 6.42, 95% CI [3.20, 12.89]; p &amp;lt; 0.001) and ≤ 3.5 days (adjusted OR: 3.47, 95% CI [2.08, 5.81]; p &amp;lt; 0.001) as independent predictors for achieving the five quality care indicators (Table 3). Comparing the predefined definition of early infectious diseases consultation as &amp;lt; 5 days and late infectious diseases consultation as &amp;gt;= 5 days in univariate analyses to baseline and clinical characteristics. A comparison of an alternative threshold of 3.5 days was also performed in univariate analyses. PWID: persons who inject drugs; ESRD: end-stage renal disease; SD: standard deviation; IQR: interquartile range; MRSA: methicillin-resistant Staphylococcus aureus; ICU: intensive car unit. Comparing the predefined definition of early infectious diseases consultation as &amp;lt; 5 days and late infectious diseases consultation as &amp;gt;= 5 days in univariate analyses to primary and secondary endpoints. A comparison of an alternative threshold of 3.5 days was also performed in univariate analyses. Bivariate analyses were performed with covariates of interest that may be associated with five quality indicators of Staphylococcus aureus bacteremia management (composite primary endpoint). Multivariable analysis was performed to control for covariates statistically significant in the bivariate analyses. Early infectious diseases consultation &amp;lt; 5 days was an independent predictor for meeting the five quality indicators of SAB management. Another multivariable analysis confirmed early ID consultation &amp;lt;= 3.5 days as an independent predictor for meeting the five quality indicators of SAB management. Conclusion Patients with SAB who received an early ID consultation were more likely to achieve the quality care indicators and have a shorter duration of bacteremia and LOS. These data suggest that patients with SAB should have an ID consultation &amp;lt; 5 days from index culture acquisition. Future studies should evaluate if an earlier time frame of 3.5 days for ID consultation improves clinical outcomes. Disclosures All Authors: No reported disclosures.

1821. Clinical Characteristics of Staphylococcus aureus Bacteremia with the Skip Phenomenon: a Case Control Study.

Abstract Background Staphylococcus aureus bacteremia (SAB) is one of the most common causes of persistent bacteremia, which is associated with complicated disease and poor clinical outcome. “The skip phenomenon (SP)” was recently proposed concept which might exhibit fluctuating blood culture positivity, but its clinical significance remained to be clarified. The aim of the study was to evaluate the clinical characteristics of SAB with the SP. Methods This is a retrospective case-control study conducted at 1141-bed university hospital during 2006-2021. Adult inpatients with more than 3 days of SAB were included. Cases were patients with SP, and controls were the rest of the patients. Duration of bacteremia was defined as bacteremic days under active antibiotic therapy counting the first day as day 1. SP was defined as at least 1 day of negative blood cultures following documented S. aureus bacteremia and preceding recurrence of a positive blood culture, which was taken within 14 days from last positive culture. Patient characteristics including medical comorbidity, implanted hardware, and focus of infection were reviewed. Results Of the 149 patients, 17 (11.4%) had the SP. A total of 20 skip phenomenon episodes among 17 cases were observed. Three patients had 2 episodes of SP. Of the 20 episodes of the SP, 7 (35.0 %) were confirmed with single set, and 13 (65.0 %) were confirmed with 2 sets of negative blood culture. The median interval from first positive blood culture to first SP episode in each case was 7 days (interquartile range [IQR], 6-16 days). Of 20 episodes of SP, 18 (90.0 %) were accompanied with fever as an indication for taking blood culture. The cases (n=17) were more likely than controls (n=132) to have a longer duration of bacteremia (median [IQR], 14 [11–36] days, vs 4 [3–7] days; p &amp;lt; 0.001), and diabetes mellitus (52.9 % vs 25.0 %, p=0.023). There was no significant difference in deep-seated infection (64.7 % vs 48.5 %, p=0.303), methicillin resistance rate (76.5 % vs 50.0 %, p=0.068), and 90-day mortality (17.6 % vs 27.3 %, p=0.561) between cases and controls. Conclusion Our findings suggest that we should consider to take blood culture repeatedly when clinically indicated, even if we confirmed the negativity once before. Disclosures All Authors: No reported disclosures.

1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs

Abstract Background Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID. Methods We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria. Results Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone. Conclusion Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen. Disclosures All Authors: No reported disclosures.

1986. Multicenter evaluation of Staphylococcus aureus prosthetic valve infective endocarditis with and without gentamicin treatment: Is it time to revisit?

Abstract Background Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with high mortality. Gentamicin (GEN) with anti-staphylococcal antibiotics and rifampin are guideline recommendations for SA-PVIE extrapolated from in vitro data. GEN can lead to acute kidney injury (AKI), meanwhile, the clinical benefit on infection-related outcomes remains unclear. Therefore, we evaluated the impact of GEN on outcomes in SA-PVIE. Methods This is a multicenter, retrospective cohort conducted at HonorHealth and UCHealth systems. Adults admitted between January 2014-2022 with definite/possible SA-PVIE by Duke Criteria were included if they received ≥2 days of treatment within 2 days of index culture. Cohorts were stratified by GEN receipt. The primary outcome was 90-day all-cause mortality. The secondary outcomes were treatment failure (change in antimicrobials, abscess development, new indication for cardiac surgery), 30-day all-cause mortality, and incidence of AKI by KDIGO Criteria. Results Overall, 38 patients with definite (40%) and possible SA-PVIE (60%) met inclusion (13 GEN, 25 without GEN [no-GEN]). At baseline, 15 (40%) patients were in an ICU, median Pitt bacteremia score was 2, and methicillin-susceptible S. aureus predominated (71%). A total of 10 (26%) patients had valve surgery; median bacteremia duration was similar between GEN and no-GEN (4 vs 3 days, p = 0.26). Common antibiotics were vancomycin (95%), cefazolin (63%), and nafcillin (21%); rifampin was more common in GEN than no-GEN (20% vs 77%, p &amp;lt; 0.001). Baseline AKI (44% vs 46%) and renal impairment (8% vs 0%) were not different between GEN and no-GEN, respectively. GEN was initiated a median 3 days after index culture, most commonly as intermittent strategy (69%) with 3 mg/kg daily equivalent (84.6%). There was no statistical difference in treatment failure (23% vs 24%, p=0.17), 30-day mortality (20% vs 39%, p=0.22), or 90-day mortality (28% vs 43%, p=0.263) between GEN and no-GEN, respectively. Three in the (23%) GEN group experienced AKI, compared to 10 (40%) in no-GEN. Conclusion We did not find that the addition of GEN to SA-PVIE therapy enhanced mortality benefit, yet patients without GEN may live to experience adverse events. Further studies were warranted. Disclosures All Authors: No reported disclosures.

Comparing the Outcomes of Ceftaroline plus Vancomycin or Daptomycin Combination Therapy versus Vancomycin or Daptomycin Monotherapy in Adults with Methicillin-Resistant Staphylococcus aureus Bacteremia-A Meta-Analysis.

Introduction: Combination therapy with daptomycin plus ceftaroline to treat methicillin-resistant Staphylococcus aureus bacteremia has been reported to reduce methicillin-resistant Staphylococcus aureus bacteremia-related mortality. The purpose of the current meta-analysis was to compare the clinical outcome of methicillin-resistant Staphylococcus aureus bacteremia in patients treated with daptomycin or vancomycin plus ceftaroline combination therapy versus daptomycin or vancomycin monotherapy. Methods: Studies were included if they directly compared the efficacy of daptomycin or vancomycin plus ceftaroline combination therapy with that of daptomycin or vancomycin monotherapy in the treatment of methicillin-resistant Staphylococcus aureus bacteremia in adult patients. Results: One randomized controlled trial and five retrospective studies were included in the meta-analysis. The combination therapy group had an in-hospital mortality, duration of bacteremia, and adverse event rate similar to those patients who had monotherapy. There was less bacteremia recurrence in the combination group. Initial combination therapy with ceftaroline for the treatment of methicillin-resistant Staphylococcus aureus bacteremia showed a trend of reducing the risk of in-hospital mortality in the current meta-analysis. Conclusions: Randomized controlled trials are needed to further study the role of initial combination therapy with daptomycin or vancomycin plus ceftaroline in the treatment of methicillin-resistant Staphylococcus aureus bacteremia.

Comparison of Sequential Dalbavancin With Standard-of-Care Treatment for Staphylococcus aureus Bloodstream Infections.

BackgroundDalbavancin (DAL) is a long-acting lipoglycopeptide with activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA). This study investigates DAL as sequential therapy in S. aureus bloodstream infections (BSIs).MethodsWe conducted a retrospective cohort study from 2014 to 2021 comparing sequential DAL with standard-of-care therapy (SoC) for S. aureus BSI. The primary outcome was 90-day clinical failure (90-day all-cause mortality or 90-day recurrence). Secondary outcomes were incidence of acute kidney injury, creatinine phosphokinase elevations, catheter-related thrombosis, and hospital-acquired infections. Analyses were adjusted using inverse probability of treatment weighting (IPTW).ResultsOverall, 225 patients (45 DAL, 180 SoC) were included. DAL patients had a higher incidence of community-acquired infection and persons who use drugs; SoC patients had more comorbidities and a longer duration of bacteremia. MRSA incidence was similar between the DAL and SoC groups. The median length of stay was 16 days among DAL recipients compared with 24 days among SoC recipients. Central catheter placement was 17.8% compared with 57.2% in the SoC group. Ninety-day clinical failure occurred in 13.3% and 18.3% of participants in the DAL and SOC groups, respectively. In IPTW-adjusted analysis, sequential DAL was not associated with 90-day clinical failure (adjusted odds ratio, 0.94; 95% CI, 0.333–2.32).ConclusionsThis study provides preliminary evidence that select patients with S. aureus BSI treated with sequential DAL have similar clinical failure rates, with significant reductions in catheter placement and hospital length of stay compared with SoC. Further prospective evaluation is needed.

Ceftriaxone versus cefazolin for the treatment of methicillin-susceptible Staphylococcus aureus bacteraemia

Few studies have evaluated the use of ceftriaxone (CRO) in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. The purpose of this study was to compare the safety and efficacy of CRO versus cefazolin (CZO) for patients with MSSA bacteraemia. This was a multicentre, single health-system, retrospective study. Adult inpatients were included if they had a primary episode of MSSA bacteraemia and received CRO or CZO as definitive therapy. The primary endpoint was clinical cure at 28 days or at discharge, whichever came first. Secondary endpoints included treatment failure at 90 days, time to treatment failure, re-admission due to recurrent MSSA bacteraemia, duration of bacteraemia, discontinuation of treatment due to adverse drug events, and Clostridioides difficile infection. A total of 248 patients were included, of which 87 (35.1%) received CRO and 161 (64.9%) received CZO. There was no difference in the primary outcome of clinical cure at 28 days or at discharge between the CRO and CZO groups [75 (86.2%) vs. 145 (90.1%); P=0.359], even after adjusting for Charlson comorbidity index and Pitt bacteremia score (adjusted OR=1.35, 95% CI 0.58-3.12; P=0.49). There were no differences in time to clinical cure, treatment failure at 90 days or safety events between the two groups. In conclusion, our findings suggest no clinical difference between CRO and CZO for the definitive treatment of MSSA bacteraemia. Further prospective studies are needed to confirm these findings.

Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study

BackgroundBacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo.MethodsThis first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days.ResultsFifteen hemodialysis patients (3F/12 M, age 74.0 [68.0–78.5] years, dialysis vintage 28.0 [11.0–45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7–80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225–300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5–98.0] to 99.0 [98.0–99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [− 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant.ConclusionsSeraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies.Trail registration: ClinicalTrials.gov Identifier: NCT02914132, first posted September 26, 2016.

Early Transition to Oral Antimicrobial Therapy Among Children With Staphylococcus aureus Bacteremia and Acute Hematogenous Osteomyelitis.

Staphylococcus aureus bacteremia (SAB) is a frequent complication of acute hematogenous osteomyelitis (AHO) in children, but data on the optimal duration of parenteral antibiotics prior to transition to oral antibiotics remains sparse. We examined clinical outcomes associated with early transition to oral antimicrobial therapy among children admitted to our institution with AHO and SAB, and evaluated the utility of a severity of illness score (SIS) to guide treatment decisions in this setting. Children with AHO and SAB admitted to our institution between January 1, 2009, and December 31, 2018, were retrospectively reviewed and stratified according to a previously validated SIS into mild (0-3), moderate (4-7) and severe (8-10) cohorts. Groups were assessed for differences in treatment (eg, parenteral and oral antibiotic durations, surgeries) and clinical response (eg, bacteremia duration, acute kidney injury, length of stay and treatment failure). Among 246 children identified with AHO and SAB, median parenteral antibiotic duration differed significantly between mild (n = 80), moderate (n = 98) and severe (n = 68) cohorts (3.6 vs. 6.5 vs. 14.3 days; P ≤ 0.001). SIS cohorts also differed with regard to number of surgeries (0.4 vs. 1.0 vs. 2.1; P ≤ 0.001), duration of bacteremia (1.0 vs. 2.0 vs. 4.0 days; P ≤ 0.001), acute kidney injury (0.0% vs. 3.0% vs. 20.5%; P ≤ 0.001), hospital length of stay (4.8 vs. 7.4 vs. 16.4 days; P ≤ 0.001) and total duration of antibiotics (34.5 vs. 44.7 vs. 60.7 days; P ≤ 0.001). Early transition to oral antimicrobial therapy among mild or moderate SIS cohorts was not associated with treatment failure despite SAB. SAB is associated with a wide range of illness among children with AHO, and classification of severity may be useful for guiding treatment decisions. Early transition to oral antimicrobial therapy appears safe in children with mild or moderate AHO despite the presence of SAB.

Persistent Methicilin-Resistant Staphylococcus aureus Bacteremia: Resetting the Clock for Optimal Management.

A positive follow-up blood culture for methicillin-resistant Staphylococcus aureus (MRSA) while on seemingly appropriate therapy is a common and ominous development. However, the definition and management of persistent MRSA bacteremia is unstandardized. In this Opinion Paper, we identify the presence of bacteremia for > 1 calendar day as a "worry point" that should trigger an intensive diagnostic evaluation to identify metastatic infection sites. Next, we define the duration of MRSA bacteremia that likely constitutes antibiotic failure and outline a potential management algorithm for such patients. Finally, we propose pragmatic clinical trial designs to test treatment strategies for persistent MRSA bacteremia.

The Effectiveness of Combination Therapy for Treating Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Literature Review and a Meta-Analysis.

Background: This meta-analysis aims to evaluate the effectiveness of combination therapy for treating MSSA bacteremia. Methods: We searched Ovid MEDLINE, EMBASE, Cochrane CENTRAL, and clinicaltrials.gov for studies including adults with MSSA bacteremia. The monotherapy group used a first-line antibiotic active against MSSA and the combination group used a first-line antibiotic plus additional antibiotic/s. The primary outcome was all-cause mortality. Secondary outcomes included persistent bacteremia, duration of bacteremia, relapse, and adverse events. Random-effects models with inverse variance weighting were used to estimate pooled risk ratios (pRR). Heterogeneity was assessed using the I2 value and the Cochrane’s Q statistic. Results: A total of 12 studies (6 randomized controlled trials [RCTs]) were included. Combination therapy did not significantly reduce 30-day mortality (pRR 0.92, 95% CI, 0.70–1.20), 90-day mortality (pRR 0.89, 95% CI, 0.74–1.06), or any-time mortality (pRR 0.91, 95% CI, 0.76–1.08). Among patients with deep-seated infections, adjunctive rifampicin may reduce 90-day mortality (3 studies with moderate-high risk of bias; pRR 0.62, 95% CI, 0.42–0.92). For secondary outcomes, combination therapy decreased the risk of relapse (pRR 0.38, 95% CI, 0.22–0.66), but this benefit was not maintained when pooling RCTs (pRR 0.54, 95% CI, 0.12–2.51). Combination therapy was associated with an increased risk of adverse events (pRR 1.74, 95% CI, 1.31–2.31). Conclusions: Combination therapy not only did not decrease mortality in patients with MSSA bacteremia, but also increased the risk of adverse events. Combination therapy may reduce the risk of relapse, but additional high-quality studies are needed.

Potent Activity of Ertapenem Plus Cefazolin Within Staphylococcal Biofilms: A Contributing Factor in the Treatment of Methicillin-Susceptible Staphylococcus aureus Endocarditis.

BackgroundBesides antistaphylococcal beta-lactams and source control, there are limited validated antimicrobial salvage options in patients with prolonged methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, including infective endocarditis (IE).MethodsMSSA IE cases treated with ertapenem (ETP) plus cefazolin (CZ) were compared with matched IE cases treated with standard beta-lactam monotherapy. The bactericidal activity of ETP plus CZ was also compared with nafcillin (NAF), CZ, and ETP alone using an in vitro MSSA biofilm model.ResultsThe median duration of bacteremia experienced by patients (n = 12) while on CZ or NAF was 4 days (range 1–16 days) compared with 1 day (range 1–3 days) for patients (n = 5) treated with ETP + CZ (P = .01, Mann-Whitney U test). Cefazolin and NAF alone or in combination did not achieve biofilm eradication at clinically relevant concentrations. However, the addition of ETP to CZ led to bactericidal eradication within biofilms at standard dosing.ConclusionsErtapenem reduces CZ concentrations required to eradicate MSSA biofilms to those achievable in vivo by standard dosing, translating into shorter bacteremia duration in patients with MSSA endocarditis. Larger studies are needed to investigate ETP plus CZ therapy in the treatment of biofilm-related MSSA infections such as endocarditis.

Bacteremia after hepatectomy and biliary reconstruction for biliary cancer: the characteristics of bacteremia according to occurrence time and associated complications.

Bacteremia occurring after extensive hepatic resection and biliary reconstruction (Hx + Bx) for biliary cancer is a critical infectious complication. This study evaluated postoperative bacteremia and examined the potential usefulness of surveillance cultures. We retrospectively reviewed 179 patients who underwent Hx + Bx for biliary cancer from January 2008 to December 2018 in our department. Bacteremia occurred in 41 (23.0%) patients. Patients with bacteremia had a longer operation time and more frequent intraoperative transfusion and more frequently developed organ/space surgical site infection (SSI) than those without bacteremia. The most frequently isolated bacterial species from blood cultures were Enterococcus faecium (29.3%), Enterobacter cloacae (24.4%), and Enterococcus faecalis (22.0%). The SIRS duration of bacteremia associated with organ/space SSI was significantly longer than that of other infectious complications (median 96h vs. 48h; p = 0.043). Bacteremia associated with organ/space SSI occurred most often by postoperative day (POD) 30. The concordance rate of bacterial species between blood and surveillance cultures within POD 30 was 67-82%. Bacteremia associated with organ/space SSI required treatment for a long time and typically occurred by POD 30. Postoperative surveillance cultures obtained during this period may be useful for selecting initial antibiotic therapy because of their high concordance rate with blood cultures.

1239. Ceftaroline versus Vancomycin as First-Line Therapy for MRSA Bacteremia

BackgroundBeta-lactams have demonstrated superior outcomes over vancomycin in MSSA bacteremia. Despite this, studies of the anti-MRSA beta-lactam ceftaroline in MRSA bacteremia (MRSAB) are largely limited in size or focus on combination or salvage regimens. This study sought to further examine ceftaroline as first-line therapy for MRSAB.MethodsThis was a retrospective matched cohort study at the San Diego VA Medical Center between November 2010 and June 2020. Patients had to have received at least 72 hours of ceftaroline or vancomycin for MRSAB and less than 72 hours of prior MRSA therapy. Adjunct MRSA therapy was allowed only if routinely indicated for the infection (e.g. rifampin for prosthesis). Patients in the vancomycin group were matched 1:1 to patients in the ceftaroline group by age (+/- 10 years) and Pitt bacteremia score (+/- 1 point). The primary outcome was duration of bacteremia after initiation of MRSA therapy, including time on prior MRSA therapy.ResultsFifteen patients were included in each group, with a median age of 65 years and Pitt bacteremia score of 0. Patients in the ceftaroline group were more likely to have CKD; to have been on a different MRSA agent prior to initiation of the study drug, with a median of 1 day of prior treatment; and to have been on adjunctive rifampin or clindamycin. Though not significant, more patients in the ceftaroline group also had endovascular sources, uncontrolled sources, and longer durations of therapy. The median duration of bacteremia after initiation of MRSA therapy did not significantly differ between ceftaroline and vancomycin (4 vs. 3 days, p = 0.806). In addition, 30-day all-cause mortality, in-hospital mortality, 90-day readmission or treatment failure, inpatient length of stay, total duration of bacteremia, and rate of adverse events did not significantly differ between groups.ConclusionThis study suggests ceftaroline may be an appropriate first-line agent for the treatment of MRSA bacteremia with similar outcomes between groups despite the ceftaroline group likely experiencing more difficult-to-treat infections. However, it was not powered to detect differences between groups, and its retrospective nature has the potential to introduce bias. Prospective comparative studies are needed to corroborate these findings.Disclosures All Authors: No reported disclosures

204. Clinical Outcomes with Ceftaroline Monotherapy versus Daptomycin-Ceftaroline Combination Therapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with poor outcomes and increased mortality. Daptomycin (DAP) and ceftaroline (CPT) in combination has been explored as a potential treatment option and showed improved outcomes compared to vancomycin/standard therapy. CPT monotherapy has been evaluated as salvage therapy for MRSA bacteremia but, to our knowledge, not as a comparator to DAP-CPT combination therapy. The purpose of this study is to compare the clinical outcomes of DAP and CPT combination therapy to CPT monotherapy in the setting of MRSA bacteremia. MethodsA retrospective chart review of adult patients (≥ 18 years of age) admitted to University Health from January 2017 to December 2020 with a diagnosis of MRSA bacteremia was performed. Patients received either CPT monotherapy or DAP-CPT combination therapy for a minimum of 48 hours during their course of therapy. ResultsThirty-two patients met inclusion criteria and were evaluated. Primary source of infection was pulmonary in the CPT monotherapy group (n=7/24; 29.2%) and osteomyelitis in the DAP-CPT combination group (n= 4/8; 50.0%). Median duration of bacteremia was 8 days and 9 days in the CPT monotherapy and DAP-CPT combination group, respectively. Microbiological cure was achieved in 95.8% (n=23/24) of patients in the CPT monotherapy and 100% (n=8/8) of patients in the DAP-CPT combination group. Bacteremia relapse (30 day, p=0.62; 60 day, p=0.63), readmission rates (30 day, p=0.62; 60 day, p=0.63), and mortality rates (30 day, p=0.70; 90 day, p=0.85) were similar in both groups. There was no statistically significant difference in safety parameters, including incidence of acute kidney injury (p=1.00) and creatine kinase elevations (p=1.00). Bone marrow suppression after at least 72 hours of therapy, including anemia, leukopenia, and thrombocytopenia, was also not statistically significant between groups. ConclusionThis study was unable to find a statistically significant difference in clinical outcomes between patients receiving CPT monotherapy or DAP-CPT combination therapy. A large prospective, randomized controlled trial to assess CPT monotherapy and DAP-CPT combination therapy for the treatment of persistent MRSA bacteremia is warranted. Disclosures All Authors: No reported disclosures

ACTINOMYCES BACTEREMIA FROM PULMONARY ACTINOMYCOSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Actinomycosis is an infection caused by actinomyces species, an anaerobe colonized within the mouth and gastrointestinal tract. Actinomyces bacteremia is rare clinical finding of which the etiology, identification, and treatment are debated. We present a case report of a 59-year-old male with stage IV breast cancer who required intensive care for actinomyces bacteremia and acute hypoxic respiratory failure secondary to pulmonary actinomycosis. CASE PRESENTATION: A 59-year-old male presented to the hospital with respiratory distress. On initial evaluation, the patient was found to be obtunded and hypoxic, prompting endotracheal intubation. Pertinent history was significant for breast cancer managed with trastuzumab. Three months prior, the patient was diagnosed with trastuzumab induced lung disease of which he was treated with oral prednisone therapy. A CT scan of the chest was significant for bilateral ground glass opacities and a left upper lobe consolidation, the latter being new relative to a CT scan three months prior. Broad spectrum antibiotics and mechanical ventilation were initiated for a diagnosis of acute hypoxic respiratory failure secondary to a superimposed pneumonia. Blood cultures from admission revealed Actinomyces species, and the patient was diagnosed with Pulmonary Actinomycosis. Unfortunately, further identification of the species of Actinomyces isolated in the blood was unable to be obtained. The patient's oxygen requirements improved following antibiotic therapy and the patient was extubated after one week on mechanical ventilation. He was successfully discharged on amoxicillin with plans for a three to six month course. DISCUSSION: Actinomyces bacteremia is a rare finding that has debated clinical significance. Historically, treatment has always been warranted in the event that the patient exhibited signs of Actinomyces infection, with or without evidence of bacteremia. A 2016 retrospective analysis of patients found to have Actinomyces positive blood cultures reported 43 patients who did not receive treatment for Actinomyces bacteremia, all of which had no reported complications after discharge. Though, none of these patients exhibited evidence of an active Actinomycocis infection. Our patient developed an acute respiratory failure in the setting of known trastuzumab induced lung injury that previously did not require supplemental oxygen therapy. Blood isolates of Actinomyces species in conjunction with new pulmonary infiltrates suggested a superimposed pulmonary Actinomyces infection was the source. Because an active source of Actinomycosis infection was present, the decision to treat the patient with antibiotics was not called into question. CONCLUSIONS: Further studies on treatment indications and duration of Actinomyces bacteremia are need. REFERENCE #1: Jeffery-Smith A, Nic-Fhogartaigh C, Millar M. Is the Presence of Actinomyces spp. in Blood Culture Always Significant?. J Clin Microbiol. 2016;54(4):1137-1139. doi:10.1128/JCM.03074-15 REFERENCE #2: G.F. Mabeza, J. Macfarlane. Pulmonary actinomycosis. European Respiratory Journal Mar 2003, 21 (3) 545-551; DOI: 10.1183/09031936.03.00089103 REFERENCE #3: Mani RK, Mishra V, Singh PK, Pradhan D. Pulmonary actinomycosis: a clinical surprise! BMJ Case Rep. 2017;2017:bcr2016218959. Published 2017 Jan 27. doi:10.1136/bcr-2016-218959 DISCLOSURES: No relevant relationships by John Madara, source=Web Response No relevant relationships by Nathaniel Rosal, source=Web Response