Duration Of Bacteremia Research Articles

Clinical Implications of the Skip Phenomenon in Patients with Persistent Staphylococcus aureus Bacteremia.

Intermittent negative blood cultures, known as the skip phenomenon (SP), frequently occur in patients with Staphylococcus aureus bacteremia (SAB), yet the clinical implications of SP in persistent SAB are not well understood. In this retrospective cohort study conducted at four university hospitals, SP was observed in 25 (11.3%) of 221 patients with persistent SAB. Infections involving methicillin-resistant S. aureus (MRSA) were more prevalent in patients with SP, who also experienced longer durations of bacteremia and delayed active antibiotic therapy compared with those without SP. The 30-day in-hospital mortality was lower in patients with SP than in those without SP (12.0% vs. 30.6%, respectively, p = 0.052). The median time from the initiation of active antibiotic therapy to the occurrence of SP was 6 days, and from SP to the last positive blood culture was 7 days. The duration of bacteremia and MRSA were independent predictors of SP. These findings suggest that SP can cause the duration of bacteremia to be underestimated by more than 1 week, indicating that confirmation of serial negative blood cultures might be necessary to reliably rule out SP in patients with prolonged MRSA bacteremia.

Elizabethkingia bloodstream infections in severely immunocompromised patients: persistent, relapsing and associated with high mortality.

Elizabethkingia species are uncommon causes of bloodstream infections, representing a true opportunistic and multi-drug-resistant pathogen to immunocompromised or vulnerable hosts. Despite this, data are lacking regarding optimal management strategy for infections with this organism, which is associated with significant mortality and morbidity. We describe patient characteristics, management and outcomes in this case series. All inpatients at the Royal Brisbane and Women's Hospital with a positive blood culture for Elizabethkingia spp. were identified by database query. Clinical information including medical history, source of infection, attempts at source control and outcome were collected. Laboratory data including duration of bacteraemia and antimicrobial susceptibility testing were also collected. All patients had severe defects of innate and adaptive immunity. Targeted therapy was started promptly and efforts at source identification and control were appropriately pursued. Despite this, outcomes were generally poor. A previously unrecognized presentation of relapsing infection was described in one case, requiring long-term suppressive antimicrobials to control. One case died as a result of infection and one case was cured, but died soon after due to complications of immunosuppression. Treatment of these organisms is challenging due to limited effective therapy, development of on treatment resistance and profound host immunocompromise. Up-front use of multiple, optimally dosed antimicrobials, attempting source control and attempting to restore host immune function all appear to be key to achieving good outcomes.

Characteristics, Treatment, and Outcomes of Invasive Group A Streptococcal Infections

Background: Group A Streptococcus (GAS; Streptococcus pyogenes) is an important human pathogen that can cause life-threatening invasive disease, ranging from skin/soft tissue infections to infective endocarditis. In the fall of 2022, the Center for Disease Control & Prevention (CDC) issued an alert due to a global increase in invasive GAS infections, particularly among children and adults with co-morbidities. An increase in invasive disease was observed at our five-hospital healthcare system in Southeast Michigan. The objective of this study was to describe characteristics of patients with invasive GAS and characterize treatment and outcomes of disease. Methods: This was a retrospective cross-sectional study of patients from June 2013 to August 2023 with positive blood cultures for GAS. Patients were identified using a data query for positive blood cultures for GAS through Microsoft SQL Server. Patients with age < 1 8 years, polymicrobial bacteremia, incomplete data, or who were enrolled in hospice and/or died within 48-hours of admission were excluded. Collected variables included: demographics, infection characteristics (syndrome, duration of bacteremia), microbiological characteristics (antimicrobial susceptibility testing; AST), antimicrobial treatment (empiric and final, antitoxin therapy), and clinical outcomes (length of hospital stay [LOS], treatment-associated adverse events, 30-day mortality and infection-related readmission). Results: 250 patients were included (Table 1). More than half were male with median age of 57.5 years. Diabetes mellitus (38%) and chronic kidney disease (23%) were common comorbidities [Table 1]. Persons experiencing homelessness and persons who use injection drugs accounted for 9% and 13% of the cases, respectively. The most common infective syndrome accompanying bacteremia was cellulitis (57%). The majority of patients received vancomycin for empiric therapy (81%) and penicillin (38%) or cephalosporin (36%) for final regimen [Table 2]. A total of 79 GAS isolates (32%) were clindamycin resistant. Clindamycin was included in the empiric regimen of 20 (8%) patients, the final regimen in 44 (18%) of patients, and as antitoxin adjunct therapy in 135 (54%) of patients. A third (33%) of patients received no antitoxin. The average duration of antitoxin therapy was 3.6 days and antimicrobial therapy 19.9 days. The mean LOS was 11.4 days (Table 3). Thirty nine (16%) patients had treatment failure and 8 (3%) experienced C. difficile infection within 30 days of antimicrobial treatment. Thirty-day mortality was 11%; of these, 9% had in-hospital mortality. Conclusions: Invasive GAS infection confers significant morbidity and mortality, and ongoing research is needed to determine the best treatment regimens in the era of increasing clindamycin resistance.

Carbapenem combination therapy versus standard of care for persistent methicillin-susceptible Staphylococcus aureus bacteraemia.

Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63-6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119-2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610-2.678), P = 0.608]. Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.

The obesity paradox in patients with major burn injuries: a single tertiary burn centre review

Introduction: The obesity paradox is a phenomenon described in medical literature where overweight and obese patients have improved survival and better health outcomes. The obesity paradox is of curiosity to many clinicians as the general consensus in medicine has been that a higher body mass index results in poorer health outcomes in both medical and surgical conditions. The aim of this study is to determine whether the obesity paradox exists in our patients with major burn injuries. To our knowledge, this has not been previously investigated in the Australian major burn population. Methods: This is a retrospective study involving patients with major burn injuries &gt; 20 per cent total body surface area admitted to the Victorian Adult Burns Service (Melbourne, Australia) from 1 January 2016 to 31 December 2020 (five-year period). Information collected included patient demographics, weight and height, and nature of burn injuries. Primary outcome of interest was inpatient mortality, and secondary outcomes included hospital length of stay, intensive care unit length of stay, duration of ventilation support required and presence of bacteraemia. Results: A total of 1704 patients were admitted, of whom 165 patients met inclusion criteria for analysis. The vast majority of 31 patients (18.8%) who died during admission were palliated. The obesity paradox did not exist in this study population. Furthermore, although not statistically significant, higher levels of body mass index showed increased risk of mortality. There was no significant association between body mass index and hospital length of stay (p = 0.16), intensive care unit length of stay (p = 0.72), duration of ventilation support (p = 0.62) nor bacteraemia (p = 0.68). Conclusion: The emerging evidence regarding the obesity paradox in the burn surgery literature is inconsistent. We contend that differences in burn management, including palliation of patients with major burn injuries, contribute to these findings.

Genomic investigation and clinical correlates of the in vitro β-lactam: NaHCO3 responsiveness phenotype among methicillin-resistant Staphylococcus aureus isolates from a randomized clinical trial.

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to β-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with β-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a β-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a β-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro β-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a β-lactam.

Low-Risk Staphylococcus aureus Bacteremia Patients Do Not Require Routine Diagnostic Imaging: A Multicenter, Retrospective, Cohort Study.

Stratification to categorize patients with Staphylococcus aureus bacteremia (SAB) as low or high risk for metastatic infection may direct diagnostic evaluation and enable personalized management. We investigated the frequency of metastatic infections in low-risk SAB patients, their clinical relevance, and whether omission of routine imaging is associated with worse outcomes. We performed a retrospective cohort study at 7 Dutch hospitals among adult patients with low-risk SAB, defined as hospital-acquired infection without treatment delay, absence of prosthetic material, short duration of bacteremia, and rapid defervescence. Primary outcome was the proportion of patients whose treatment plan changed due to detected metastatic infections, as evaluated by both actual therapy administered and by linking a adjudicated diagnosis to guideline-recommended treatment. Secondary outcomes were 90-day relapse-free survival and factors associated with the performance of diagnostic imaging. Of 377 patients included, 298 (79%) underwent diagnostic imaging. In 15 of these 298 patients (5.0%), imaging findings during patient admission had been interpreted as metastatic infections that should extend treatment. Using the final adjudicated diagnosis, 4 patients (1.3%) had clinically relevant metastatic infection. In a multilevel multivariable logistic regression analysis, 90-day relapse-free survival was similar between patients without imaging and those who underwent imaging (81.0% versus 83.6%; adjusted odds ratio, 0.749; 95% confidence interval, .373-1.504). Our study advocates risk stratification for the management of SAB patients. Prerequisites are follow-up blood cultures, bedside infectious diseases consultation, and a critical review of disease evolution. Using this approach, routine imaging could be omitted in low-risk patients.

Clinical Impact of Vancomycin MIC on Outcomes in Patients With Coagulase-negative Staphylococcal Bacteremia

Coagulase-negative staphylococci (CoNS) are Gram-positive organisms that are a known component of normal skin flora and the most common cause of nosocomial bacteremia. For CoNS species, the vancomycin MIC breakpoint for susceptibility set by the Clinical and Laboratory Standards Institute is ≤4 µg/mL. There has been published reports of vancomycin heteroresistance in CoNS with vancomycin MICs of 2 to 4 µg/mL. The aim of this retrospective cohort analysis was to assess the clinical impact of vancomycin MICs <2 µg/mL versus ≥2 µg/mL in adult patients with CoNS bloodstream infections. Adult patients admitted to University Medical Center New Orleans with a blood culture positive for CoNS were assessed. The primary outcome was difference in 30-day mortality. Secondary outcomes were in-hospital, all-cause mortality; duration of bacteremia; hospital length of stay; and percentage of oxacillin-resistant CoNS. There was no difference in mortality in the vancomycin MIC <2 µg/mL group versus the vancomycin MIC ≥2 µg/mL group at 30 days (15.4% vs 17.4%; P = 1). In-hospital, all-cause mortality was also not different between groups (11.5% vs 13%; P = 1). Hospital length of stay between groups was 28.2 days versus 21 days (P = 0.692). Median duration of bacteremia was 1 day in both groups (P = 0.975), and median scheduled duration of antibiotic therapy was 14.9 days and 19.5 days (P = 0.385). The source and mode of acquisition of CoNS were similar between groups. Of all CoNS isolates, 58.7% (44 of 75) were oxacillin resistant. Staphylococcus epidermidis was the most common CoNS species at 66.7% (50 of 75). Of all isolates, 30.7% (23 of 75) had a vancomycin MIC ≥2 µg/mL, and 87% (20 of 23) of these were S. epidermidis. There was a higher percentage of S. epidermidis in the vancomycin MIC ≥2 µg/mL group than in the MIC <2 µg/mL group (87% vs 57.7%; P = 0.012). CoNS with a vancomycin MIC ≥2 µg/mL were also more likely to be oxacillin resistant (78.3% vs 50%; P = 0.005). There was no difference in clinical outcomes in adult patients with a CoNS bloodstream infection with a vancomycin MIC <2 µg/mL versus ≥2 µg/mL. At present, vancomycin remains appropriate empiric therapy for CoNS bloodstream infection. Further research is needed to determine if there is a true clinical impact of a vancomycin MIC ≥2 µg/mL in CoNS infections.

Comparative effectiveness of empirical antibiotic treatments in methicillin-susceptible Staphylococcus aureus infective endocarditis: A post hoc analysis of a prospective French cohort study

ObjectivesThe empirical treatment of infective endocarditis is still debated. The aim of this study was to compare the impact of empirical treatment with antistaphylococcal penicillin (ASP) or cefazolin vs. other treatments in methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis. MethodsA post hoc analysis of a prospective cohort study of patients hospitalized in a French reference centre with MSSA endocarditis was conducted between 2013 and 2022. The primary outcome was the duration of bacteraemia under treatment. ResultsOf the 208 patients included, 101 patients (48.6%) were classified in the reference group (ASP or cefazolin) and 107 (52.4%) in the non-reference group. Empirical treatment with ASP/cefazolin was associated with a shorter duration of bacteraemia compared to other treatments (3.6 d vs. 4.6 d, P = 0.01). This difference was not corrected by the addition of an aminoglycoside (3.6 d vs. 4.7 d, P < 0.01). In multivariate analysis, empirical treatment with ASP/cefazolin was associated with a duration of bacteraemia ≤72 h (P = 0.02), whereas endocarditis on native valves (P = 0.01), and intracardiac abscess were associated with longer duration of bacteraemia (P = 0.01). ConclusionsEmpirical treatment of endocarditis with ASP or Cefazolin is more effective than other treatments in MSSA endocarditis, even when the other treatments are combined with aminoglycosides.

Clinical and Microbiological Characteristics of ST72 Methicillin-Susceptible Staphylococcus aureus: Comparison with ST72 Methicillin-Resistant S. aureus.

Sequence type 72 (ST72) is the predominant community-associated methicillin-resistant Staphylococcus aureus (MRSA) genotype in Korea. With an increasing prevalence of the ST72 S. aureus lineage, regardless of methicillin resistance, it is crucial to understand the clinical and microbiological characteristics of ST72 methicillin-susceptible S. aureus (MSSA) as well as ST72 MRSA. In this retrospective cohort study, data from patients with S. aureus bacteremia (SAB) who were admitted to a tertiary hospital in Korea from March 2007 to December 2018 were collected. Multilocus sequence typing was used to identify ST72 isolates. The clinical and microbiological characteristics of ST72 MSSA were compared with those of ST72 MRSA among patients infected with SAB. Among the 442 SAB patients with ST72, 157 (35.5%) were infected with MSSA and 285 (64.5%) were infected with MRSA. There was a significant increase in the proportion of ST72 MSSA in both the community and hospital settings. Compared to ST72 MRSA, ST72 MSSA isolates were less likely to have multidrug resistance. The main infection foci, infection severity, and duration of bacteremia did not differ significantly between the two groups. The 90-day recurrence rate was significantly lower in the MSSA group (2.5% vs. 8.4%, P=0.03), while the 90-day mortality rate was comparable (28.0% vs. 23.9%, P=0.40). ST72 MSSA had similar clinical features as ST72 MRSA in terms of infection site, severity, and 90-day mortality. Despite exhibiting lower levels of antibiotic resistance, ST72 MSSA has increased in the hospital environment concurrently with ST72 MRSA.

154. Impact of Rapid Blood Culture Identification (BCID) PCR Panel on Optimal Antibiotic Use in Methicillin-Susceptible Staphylococcus aureus (MSSA) Bacteremia

Abstract Background Optimal anti-MSSA antibiotic choices are nafcillin, oxacillin, and cefazolin. Vancomycin, often used empirically for S. aureus infections, and other broad-spectrum β-lactam antibiotics, such as piperacillin/tazobactam and ceftriaxone, are linked with suboptimal outcomes compared to anti-MSSA β-lactam therapy. BCID PCR testing allows for faster pathogen identification, which may improve antibiotic use and clinical outcomes. The objective of this study was to assess the impact of BioFire BCID PCR panel implementation on antibiotic use and clinical outcomes in patients with MSSA bacteremia. Methods This was a retrospective chart review of adult inpatients with MSSA bacteremia during the pre-PCR (Jun 2018 - Dec 2019) and post-PCR (Jun 2020 - Dec 2021) study periods. Patients were excluded if they did not have PCR testing performed (post-PCR group only), never achieved optimal antibiotic therapy, had a polymicrobial infection, had positive blood cultures in the prior 90 days, underwent penicillin-skin testing or β-lactam desensitization, or were transitioned to comfort care or deceased within 24 hours of the gram stain. The primary endpoint was the difference in time to starting optimal MSSA antibiotic therapy (oxacillin or cefazolin) between the pre-PCR and post-PCR groups. Secondary endpoints included duration of anti-MRSA antibiotic use, in-hospital mortality, hospital and ICU lengths of stay, duration of bacteremia, and 30-day MSSA-related and all-cause readmissions. Results A total of 200 patients were included in the study, with 100 patients in each group. Time to optimal therapy was reduced by 19.9 hours in the post-PCR group (p &amp;lt; 0.001). Fewer patients in the post-PCR group were initiated on empiric anti-MRSA antibiotic therapy than in the pre-PCR group (84% vs 98%, respectively, p = 0.001). PCR implementation was also associated with shorter empiric anti-MRSA antibiotic use and duration of bacteremia. There were no significant differences in length of stay, in-hospital mortality, or 30-day MSSA-related or all-cause readmissions (Table 1). Table 1: Primary and Secondary Endpoints Conclusion In patients with MSSA bacteremia, BCID PCR panel testing decreased time to optimal MSSA antibiotic therapy and reduced durations of bacteremia and empiric anti-MRSA antibiotic therapy, including vancomycin. Disclosures All Authors: No reported disclosures

95. What To Do With Prolonged Bacteremia in Staphylococcus aureus Osteoarticular Infection? A Retrospective Analysis at Two Children's Hospitals

Abstract Background Staphylococcus aureus is the most frequent cause of osteoarticular infection (OAI, including hematogenous osteomyelitis and septic arthritis) in children and is commonly associated with bacteremia. Current guidelines suggest that persistent bacteremia may warrant more aggressive treatment, however, data supporting this are limited. We retrospectively evaluated the management and outcomes of children with S. aureus OAI with respect to bacteremia duration. Methods Cases were identified through prospective S. aureus surveillance studies at Texas Children’s and St. Louis Children’s Hospitals. Children &amp;lt; 18 years old with OAI secondary to S. aureus from 2011-2021 were eligible. Prolonged bacteremia was defined a priori as the upper quartile of duration. Orthopedic complications included pathologic fractures, avascular necrosis, angular deformity and chronic osteomyelitis. Results Overall, 532 cases were identified of which 343 (64.5%) had ≥1 positive blood culture; 61 developed orthopedic complications (11.4%, Figure 1). The median duration of bacteremia in the cohort was 1 day (IQR: 1-3 days). Patients with prolonged (≥ 3 days) and non-prolonged bacteremia were similar in terms of demographics. Children with prolonged bacteremia had a longer duration of fever in hospital (median 6 vs. 3 days, p&amp;lt; 0.001), more often had MRSA, pyomyositis and venous thromboses and were less often transitioned to oral therapy (Figure 2). Duration of bacteremia also influenced discharge antibiotic choice (Figure 3). Within the subset of patients with prolonged bacteremia, those who were transitioned to oral therapy had similar outcomes to those treated with prolonged intravenous antibiotics; such patients received a median of 11.5 days (IQR: 6-23) of IV therapy prior to discharge (median 7 days [IQR: 4-20] after last positive blood culture). Conclusion Prolonged bacteremia in the setting of S. aureus OAI greatly impacts management and should prompt evaluation for other foci of infection. However, our data show that a subset of children with S. aureus OAI and prolonged bacteremia can be safely transitioned to oral antibiotics after a period of IV therapy. Additional work is needed to delineate optimal management of OAI with prolonged bacteremia. Disclosures Jonathon C. McNeil, MD, Allergan: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support Kristina G. Hulten, PhD, Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Honoraria

2402. Evaluating Clinical Outcomes of Adjunctive Beta-Lactam Use in Vancomycin-Resistant Enterococcus Infective Endocarditis

Abstract Background Vancomycin resistant enterococcus (VRE) infective endocarditis (IE) is associated with poor outcomes. There are limited data to guide the antimicrobial choice and duration of therapy. Several in vitro and limited clinical studies demonstrate the synergistic effect of β-lactams with other agents, particularly daptomycin, in this setting. We sought to compare clinical outcomes in patients with VRE IE treated with adjunctive β-lactam therapy. Methods This was an IRB-approved, retrospective, single-center cohort study. The study included patients ≥18 years of age diagnosed with VRE IE via modified Duke criteria from 2011-2021. Data were collected by electronic medical record review. Descriptive statistics were obtained. The primary outcome was 90-day treatment failure compared between those receiving and not receiving adjunctive β-lactams. Treatment failure was defined as recurrence of bloodstream infection (BSI) or death within 90 days of diagnosis. Failure-free survival was analyzed by Kaplan-Meier curve with log-rank test. Results A total of 32 cases were identified. 12 received adjunctive β-lactams. Mean age was 67 years, and 71% were male. 13 (41%) had a prosthetic valve and 6 (19%) had a CIED (Table 1). A majority (78%) had E. faecium IE. Mean duration of bacteremia was 9 days (Table 2). About one-third had treatment failure with 7 deaths and 4 BSI recurrences. Adjunctive β-lactams included ampicillin (3), cefepime (1), ceftaroline (6) and ceftriaxone (2). There was no statistical difference in failure-free survival in patients treated with adjunctive β-lactam therapy (Figure 1). The results were similar when restricted only to those who received daptomycin with or without adjunctive β-lactam therapy.Table 1.Patient CharacteristicsTable 2.Disease characteristics Figure 1. Kaplan-Meier curve comparing failure-free survival between patients who were primary treated with adjunctive β-lactams versus non-adjunctive therapy. The p-value is calculated via the log-rank test. Conclusion VRE IE is associated with poor prognosis, including high rates of mortality and relapses. In our experience, adjunctive B-lactam use did not result in improved outcome. Limitations include small sample size, and heterogenous antibiotic use. More prospective randomized data are needed. Disclosures All Authors: No reported disclosures

High Incidence of Metastatic Infections in Panton-Valentine Leucocidin-Negative, Community-Acquired Methicillin-Resistant Staphylococcus aureus Bacteremia: An 11-Year Retrospective Study in Japan.

Panton-Valentine leucocidin (PVL)-negative community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) was originally disseminated in Japan and has since replaced healthcare-associated MRSA (HA-MRSA). However, the clinical characteristics of CA-MRSA bacteremia (CA-MRSAB) compared with those of HA-MRSA bacteremia (HA-MRSAB) are unknown. We aim to clarify differences and investigate associations between the clinical manifestations and virulence genes associated with plasma-biofilm formation in PVL-negative CA-MRSA. From 2011 to 2021, when CA-MRSA dramatically replaced HA-MRSA, 79 MRSA strains were collected from blood cultures and analyzed via SCCmec typing and targeted virulence gene (lukSF-PV, cna, and fnbB) detection. The incidence of metastatic infection was significantly higher in CA-MRSAB than in HA-MRSAB. PVL genes were all negative, although cna and fnbB were positive in 55.6% (20/36) and 50% (18/36) of CA-MRSA strains and 3.7% (1/27) and 7.4% (2/27) of HA-MRSA strains, respectively. cna and fnbB carriage were not associated with the development of metastatic infections in MRSAB; however, the bacteremia duration was significantly longer in CA-MRSAB harboring cna. CA-MRSAB may be more likely to cause metastatic infections than HA-MRSAB. Since CA-MRSA is dominant in Japan, suspected metastatic infection foci should be identified by computed tomography, magnetic resonance imaging, and echocardiography when treating MRSAB.

Factors for mortality in patients with persistent Staphylococcus aureus bacteremia: The importance of treatment response rather than bacteremia duration.

The criteria for antibiotic failure in persistent Staphylococcus aureus bacteremia (SAB) are unclear, but treatment response and bacteremia duration are commonly used indicators of antibiotic failure. We evaluated the effects of treatment response and bacteremia duration on mortality in persistent SAB. We retrospectively identified patients with persistent SAB in four university-affiliated hospitals between 2017 and 2021. Bacteremia duration was calculated from the first day of active antibiotic therapy, and persistent SAB was defined as bacteremia lasting for 2 or more days. Defervescence and Pitt bacteremia score (PBS) were used to evaluate treatment response at treatment day 4. The primary outcome was 30-day in-hospital mortality. Time-dependent multivariable Cox regression analysis and subgroup analysis according to methicillin resistance were performed. A total of 221 patients was included in the study, and the 30-day in-hospital mortality was 28.5%. There was no significant difference in bacteremia duration between survived and deceased patients. Independent factors for mortality included age, Charlson comorbidity index, initial PBS, pneumonia, and removal of the eradicable focus. PBS at treatment day 4≥3 was the strongest risk factor (adjusted hazard ratio [HR]=4.260), but defervescence was not. Bacteremia duration was not an independent factor except for 13 days or more of methicillin-resistant SAB (adjusted HR=1.064). In patients with persistent SAB, PBS at treatment day 4 was associated with 30-day in-hospital mortality rather than defervescence and bacteremia duration. The results of this study could help determine early intensified treatment strategies in persistent SAB patients.

Effectiveness of adjunctive rifampicin for treatment of Staphylococcus aureus bacteraemia: a systematic review and meta-analysis of randomized controlled trials.

To assess whether the addition of rifampicin to conventional treatment of Staphylococcus aureus bacteraemia (SAB) reduces bacteriological or clinical failure or death. PubMed, Embase and Cochrane CENTRAL databases were searched from inception to 31 December 2022. Reference lists and PubMed citations of eligible studies were checked. Two study authors independently identified randomized controlled trials (RCTs) involving adult participants with SAB, in which an intervention group received adjunctive rifampicin and the control group received usual care with or without a placebo. Dichotomous data (bacteriological and clinical failure and deaths) were analysed and pooled across studies using risk ratio (RR) with 95% confidence intervals (CI) using a Mantel-Haenszel random-effect model. The key variable of interest being whether rifampicin was used. Six RCTs including 894 participants-of which 758 (85%) were from one trial-met the inclusion criteria. The addition of rifampicin to conventional treatment of SAB significantly reduced bacteriological failure by 59% (RR 0.41, 95% CI 0.21-0.81, I2 = 0%, number need to treat 27). However, it did not reduce clinical failure (RR 0.70, 95% CI 0.47-1.03, I2 = 0%) or deaths (RR 0.96, 95% CI 0.70-1.32, I2 = 0%). Further, it did not reduce the duration of bacteraemia, or the length of hospital stay. Adjunctive rifampicin reduced SAB recurrences (1% versus 4%, P = 0.01). Emergence of rifampicin resistance during treatment was uncommon (<1%). Although adjunctive rifampicin reduced the risk of bacteriological failure and recurrences, we found no mortality benefit to support its use in SAB.

Daptomycin Plus Oxacillin for Persistent Methicillin-Susceptible Staphylococcus aureus Bacteremia.

The preferred antibiotic salvage regimen for persistent methicillin-susceptible Staphylococcus aureus bacteremia (MSSAB) is unclear. Ertapenem with cefazolin or an antistaphylococcal penicillin has been primarily described, but identifying alternative carbapenem-sparing options may support antibiotic stewardship efforts and decrease the risk of antibiotic-associated Clostridioides difficile infection. We sought to evaluate the effectiveness and safety of daptomycin plus oxacillin (D/O) for persistent MSSAB. This was a single-center, retrospective cohort of patients with persistent MSSAB who received D/O between January 1, 2014, and January 1, 2023. Adult patients were included if they had blood cultures positive for MSSA ≥72 hours and received D/O combination for ≥48 hours. Patients were excluded if they were pregnant, incarcerated, or received another antibiotic considered to have excellent activity against MSSA. The primary outcome was time to MSSA bacteremia clearance post-daptomycin initiation. Secondary outcomes included microbiological cure, hospital length of stay, 90-day all-cause mortality, MSSA bacteremia-related mortality, 90-day readmission for MSSAB, and incidence of antibiotic-associated adverse effects. Time to MSSAB clearance post-D/O initiation was plotted using Kaplan-Meier estimation. Seven unique patient encounters were identified including 4 with endocarditis. Despite a median MSSA bacteremia duration of 7.8 days, median clearance was 2 days post-daptomycin initiation. All achieved microbiological cure, and no adverse effects were reported. Ninety-day all-cause mortality, MSSAB-related mortality, and 90-day readmission for MSSAB occurred in 28.6%, 14.3%, and 14.3% of patients, respectively. D/O was an effective, well-tolerated salvage regimen in this cohort and may represent a carbapenem-sparing option for persistent MSSAB.

Management and outcomes of heart transplant candidates with bloodstream infection on temporary mechanical circulatory support

The outcomes and management of bloodstream infection (BSI) in patients on temporary mechanical circulatory support (TMCS) awaiting heart transplant (HT) are poorly understood. We present outcomes of patients on TMCS with BSI (TMCS-I) relative to matched uninfected patients (TMCS-U) and discuss their management. Between 1/1/2013-4/30/2023, N=136 patients were bridged to transplant with TMCS at Emory Transplant Center. Twenty-one (15.4%) were TMCS-I. Two (9.5%) had infective endocarditis. Median duration of antimicrobial treatment was 24 days (IQR 28.3). All TMCS-I were re-activated for transplant within 48-72 hours of negative blood cultures. None developed recurrent BSI. Post-transplant survival did not differ between TMCS-I and TMCS-U (P=0.38). HT for TMCS-I may be safe as soon as blood cultures clear. Duration of antimicrobial therapy is individualized and depends on the organism, duration of bacteremia, presence of endocarditis, and timing of HT. Additional research is needed to determine optimal duration of treatment.

Bacteremia following different oral procedures: Systematic review and meta-analysis.

To evaluate the timing, duration and incidence of bacteremia following invasive dental procedures (IDPs) or activities of daily living (ADL). Eight databases were searched for randomized (RCTs) and nonrandomized controlled trials (nRCTs) evaluating bacteremia before and after IDPs or ADL in healthy individuals. The risk of bias was assessed by RoB 2.0 and ROBINS-I. For the meta-analysis, the primary outcomes were the timing and duration of bacteremia. The secondary outcome was the incidence of bacteremia, measuring the proportion of patients with bacteremia within 5 min after the end of the procedure compared with baseline. We included 64 nRCTs and 25 RCTs. Peak bacteremia occurred within 5 min after the procedure and then decreased over time. Dental extractions showed the highest incidence of bacteremia (62%-66%), followed by scaling and root planing (SRP) (44%-36%) and oral health procedures (OHP) (e.g., dental prophylaxis and dental probing without SRP) (27%-28%). Other ADL (flossing and chewing) (16%) and toothbrushing (8%-26%) resulted in bacteremia as well. The majority of studies had some concerns RCTs or moderate risk of bias nRCTs. Dental extractions, SRP and OHP, are associated with the highest frequency of bacteremia. Toothbrushing, flossing, and chewing also caused bacteremia in lower frequency.

Comparative effectiveness of β-lactams for empirical treatment of methicillin-susceptible Staphylococcus aureus bacteraemia: a prospective cohort study.

Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.