scholarly journals 182. Back to The Future: Increasing Penicillin Susceptibility among Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S111-S111
Author(s):  
Jonathon C McNeil ◽  
Lauren Sommer ◽  
Jesus G Vallejo ◽  
Mary G Boyle ◽  
Kristina G Hulten ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Susceptibility Testing ◽  
Clinical Presentation ◽  
Multicenter Trial ◽  
Healthcare Research ◽  
Research Support ◽  
Children's Hospitals ◽  
Osteoarticular Infections ◽  
Children’S Hospitals ◽  
Research Grant

Abstract Background Starting in the late 1940s-1950s Staphylococcus aureus isolates gained resistance to penicillin largely through the acquisition of β-lactamases. In recent years, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the prevalence or clinical significance of PSSA in children. Acute hematogenous osteoarticular infections (AHOAIs, including osteomyelitis and septic arthritis) are the most common manifestation of invasive S. aureus disease in children. We investigated the prevalence of penicillin susceptibility among MSSA AHOAI isolates at two children’s hospitals. Methods MSSA AHOAI isolates were obtained through surveillance studies at Texas Children’s (TCH) and St. Louis Children’s Hospitals (SLCH) from 1/2011- 12/2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin susceptibility testing using macrobroth dilution. Isolates which were blaZ negative and had a penicillin MIC ≤ 0.125 μg/ml were regarded as PSSA. Results 329 unique isolates were available and included in the study. The median patient age was 9.2 years (IQR: 5.1-12.2). Overall, 22 isolates were found to be penicillin susceptible (6.7%). No PSSA isolates were detected prior to 2015 but increased yearly thereafter; by the final study year 20.4% of isolates were PSSA (p=0.001, Figure 1). Patients with PSSA isolates were slightly older than those with resistant isolates (median age 11.8 years vs. 9.1 years, p=0.08) and PSSA were more commonly identified at SLCH (12.9% vs. 5.2%, p=0.04). PSSA were similar to penicillin-resistant isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. For PSSA, the MIC90 for penicillin (0.06 μg/ml) was much lower than that for other β-lactams (Figure 2). The figure describes the relative frequency of penicillin susceptible S. aureus (PSSA) over time among MSSA osteoarticular infection isolates in children. Distribution of MICs to penicillin, ampicillin, cefazolin, cephalexin and oxacillin among PSSA isolates. Conclusion PSSA appears to be increasing among AHOAI isolates in US children, although geographic variability does occur. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. Penicillin susceptibility testing may serve as an avenue for future stewardship intervention in staphylococcal infections. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality (Research Grant or Support)Allergan (Grant/Research Support)Nabriva (Grant/Research Support, Other Financial or Material Support, Site PI for a multicenter trial) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support) Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support)

scholarly journals Analysis of Invasive Pneumococcal Infections Due to 13-Pneumococcal Conjugate Vaccine Serotypes at 8 US Children’s Hospitals During 2014 to 2016

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S67-S67
Author(s):  
Sheldon L Kaplan ◽  
William J Barson ◽  
Philana Ling Lin ◽  
Jose R Romero ◽  
John S Bradley ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Pneumococcal Disease ◽  
Age At Diagnosis ◽  
Pneumococcal Infections ◽  
Research Support ◽  
Children's Hospitals ◽  
Children’S Hospitals ◽  
The Us ◽  
Research Grant

Abstract Background The 13-Valent Pneumococcal Conjugate Vaccine (PCV13) was licensed in 2010 and is directed against serotypes (ST) 1,3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. Details of cases of invasive pneumococcal disease (IPD) due to PCV13 ST since 2010 in the US are sparse. We describe IPD cases due to PCV13 ST seen at 8 US children’s hospitals over years 2014 to 2016 which may aid in understanding why some IPD cases due to these ST have persisted. Methods Children with IPD have been prospectively identified at 8 children’s hospitals in the US since 1993. Data from 2014 through 2016 were analyzed. Demographic, clinical data and number and dates of PCV doses were collected on case report forms and isolates were sent to a central laboratory for serotyping. PCV doses are counted if IPD occurred > 2 weeks after a dose. Results PCV13 ST accounted for 19.7% (27/137), 26.8% (30/112) and 26% (33/127) of IPD cases in 2014, 2015 and 2016, respectively. ST 3, 19A and 19F accounted for 90% of the PCV13 ST IPD cases. >50% of the children had received ≤2 doses of PCV13 prior to IPD. (Table) Of the 30 children with 0 doses of PCV, 15 were of an age at diagnosis for which ≥ 2 doses of PCV was recommended. An underlying condition was noted in 18. For PCV13 ST, the types of IPD were pneumonia (n = 39), mastoiditis (n = 15), bacteremia (n = 15), meningitis (n = 12) and other sites of infection (n = 9). Whereas the numbers of yearly cases were similar for ST3 (12, 10, 13) and ST19A (8, 10, 6), the numbers for 19F increased slightly (3, 8, 10). Conclusion Four to 6 years after PCV13 was introduced, PCV13 ST (especially ST 3, 19A and 19F) accounted for about 25% of IPD in children. For all of the PCV13 ST, over half of these IPD cases occurred in children who had received ≤ 2 doses of the recommended PCV schedule; 25% of cases occurred in children who had not received any doses but were of the age at diagnosis that at least 2 PCV doses should have been received. Additional PCV13 ST IPD cases may be preventable if the PCV13 schedule is followed as recommended. Disclosures S. L. Kaplan, Pfizer: Grant Investigator and Speaker at PCV13 Launch Meeting in China, Research grant and Speaker honorarium; J. S. Bradley, Merck & Co., Inc.: Investigator, Research support

scholarly journals 852. The Cefazolin Inoculum Effect and Methicillin-Susceptible Staphylococcus aureus Osteoarticular Infections in Children: Does It Matter?

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S17-S18 ◽  
Author(s):  
Jonathan C McNeil ◽  
Lauren Sommer ◽  
Mary G Boyle ◽  
Patrick G. Hogan ◽  
Jesus G. Vallejo ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Subsequent Development ◽  
Source Control ◽  
Children's Hospitals ◽  
Osteoarticular Infections ◽  
Children’S Hospitals ◽  
Definitive Therapy ◽  
Inoculum Effect ◽  
Antibiotic Failure ◽  
Study Sites

Abstract Background Select methicillin-susceptible Staphylococcus aureus (MSSA) strains may produce β-lactamases with an affinity for first-generation cephalosporins (1GC). In the setting of a high inoculum, these β-lactamases may promote clinically meaningful cleavage of 1GCs, potentially resulting in antibiotic failure, a phenomenon known as the cefazolin inoculum effect (CIE). Acute hematogenous osteoarticular infections (AHOAIs, including osteomyelitis and septic arthritis) are the most common manifestation of invasive S. aureus infection in children. We evaluated the prevalence and potential impact of CIE among MSSA AHOAI isolates at two children’s hospitals. Methods MSSA AHOAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2018. Isolates were tested for CIE via a macrobroth dilution assay with an inoculum of 107 CFU/mL; CIE was defined as a cefazolin MIC ≥16 µg/mL. Isolates were characterized by accessary gene regulator group (agr). The subsequent development of chronic osteomyelitis (CO) was regarded as a clinically important outcome. Results A total of 287 cases were included and the median patient age was 8.6 years. 14.3% of isolates exhibited CIE; CIE prevalence was similar across study sites. 74.6% of patients received a 1GC as definitive therapy. CIE isolates were more often resistant to clindamycin, belonged to agr III and associated with CO (Figure 1); a numerically higher rate of CO was observed with CIE isolates regardless of definitive antibiotic choice (Figure 2). In multivariable analyses, bone abscesses, agr III, positive blood cultures, multiple surgeries, and delayed source control but not CIE were independently associated with CO (Figure 3); similar results were seen if analyses were restricted to only those receiving 1GC. Conclusion CIE is exhibited by 14.3% of MSSA AHOAI isolates in children. CIE is associated with agr III and clindamycin-resistant strains. agr III strains are independently associated with CO; thus negative outcomes reported with CIE may more accurately reflect strain-dependent virulence factors rather than true antibiotic failure. Further studies are necessary to better understand the clinical significance of these findings. Disclosures All Authors: No reported Disclosures.

scholarly journals 183. Decrease in Invasive Pneumococcal Disease in 7 United States Children’s Hospitals during the COVID-19 Pandemic

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S111-S112
Author(s):  
Adriana Sarmiento Clemente ◽  
Sheldon L Kaplan ◽  
William J Barson ◽  
Philana L Lin ◽  
Jose R Romero ◽  
...  
Keyword(s):  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Panel Member ◽  
Bone Culture ◽  
Research Support ◽  
Review Panel ◽  
Children's Hospitals ◽  
Children’S Hospitals ◽  
The U.S ◽  
Research Grant

Abstract Background During the 2020 SARS-CoV-2 pandemic, physical distancing and mask use guidelines were implemented resulting in a decline in the number of infections caused by influenza, respiratory syncytial virus and otitis media. A surveillance analysis from England and Taiwan showed a decline in invasive pneumococcal disease (IPD) (Clin Infect Dis. 2021;72: e65-75 and J Infect. 2021;82:296-297). We hypothesized that COVID mitigation efforts resulted in a decrease in incidence of pediatric IPD within the U.S. during 2020 compared to previous years. Methods We reviewed all cases of IPD among 7 children’s hospitals from the U.S. Pediatric Multicenter Pneumococcal Surveillance Group from 2017-2020. IPD was defined by the isolation of Streptococcus pneumoniae from normally sterile sites (eg. blood, cerebrospinal, pleural, synovial or peritoneal fluid). Pneumococcal pneumonia was defined as an abnormal chest radiograph in the presence of a positive blood, pleural fluid or lung culture. Mastoiditis was identified by positive middle ear, subperiosteal abscess or mastoid bone culture. Serotypes were determined by the capsular swelling method. Hospital admission numbers were obtained for incidence calculations. Statistical analyses were performed using STATA11. A p< 0.05 was considered significant. Results A total of 410 IPD cases were identified. The cumulative incidence of IPD (0-22 years of age) decreased from 99.2/100,000 admissions in 2017-2019 to 53.8/100,000 admissions in 2020 (risk ratio 0.54, CI: 0.40-0.72, p< 0.00001). Pneumococcal bacteremia and pneumonia decreased significantly in 2020 (p< 0.05), and although not statistically significant, there were fewer cases of meningitis and mastoiditis when compared to previous years (p=0.08) (Figure 1). Sex, race, age or presence of comorbidities were not significantly different between groups. Most common serotypes in 2020 were 35B, 3 and 15B/C (Figure 2). Conclusion The observed decline in IPD cases during the first year of the SARS-CoV-2 pandemic is likely associated with mask use and physical distancing limiting transmission of S. pneumoniae via droplets and viral infections frequently preceding IPD. These precautions might be useful in the future to decrease IPD, especially in high-risk patients. Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Tina Q. Tan, MD, GSK (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; ILiAD (Individual(s) Involved: Self): Advisor or Review Panel member; Merck (Individual(s) Involved: Self): Advisor or Review Panel member, Grant/Research Support; Moderna (Individual(s) Involved: Self): Advisor or Review Panel member; Pfizer (Individual(s) Involved: Self): Advisor or Review Panel member Pia S. Pannaraj, MD, MPH, Pfizer (Grant/Research Support)Sanofi-Pasteur (Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Larry Givner, MD, AstraZeneca (Advisor or Review Panel member) Kristina G. Hulten, PhD, Pfizer (Research Grant or Support)

scholarly journals 1267. Comparative activity of omadacycline against extended-spectrum beta-lactamase positive and negative Escherichia coli and Klebsiella pneumoniae strains recovered from urine specimens

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S650-S650
Author(s):  
Tyler J Stone ◽  
Abdullah Kilic ◽  
John Williamson ◽  
Elizabeth Palavecino ◽  
Elizabeth Palavecino
Keyword(s):  
Susceptibility Testing ◽  
Uncomplicated Urinary Tract Infection ◽  
Beta Lactamase ◽  
Oral Antibiotics ◽  
Research Support ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum ◽  
Urine Specimens ◽  
Research Grant

Abstract Background Omadacycline (OMC) is a novel tetracycline (TET) derivative antibiotic with activity against TET-resistant Enterobacterales. OMC is available in both oral and intravenous formulations and is has been studied as a treatment of uncomplicated urinary tract infection (UTI) and acute pyelonephritis. The purpose of this study was to evaluate OMC activity against extended-spectrum beta-lactamase (ESBL) positive and negative Enterobacterales strains recovered from urine specimens. Methods Urine samples from patients with suspected UTI were quantitatively plated onto blood agar and MacConkey agar plates in the microbiology lab of Wake Forest Baptist Medical Center. After overnight incubation, colonies were identified to the species level by MALDI-TOF system. Susceptibility testing was performed for isolates of E. coli and K. pneumoniae. OMC and TET susceptibility testing was performed by disk diffusion and gradient strip methodologies. Results were interpreted in accordance with the Clinical and Laboratory Standards Institute (CLSI) or Food and Drug Administration breakpoints. Isolates were tested in triplicate. ESBL screening and susceptibility testing to oral antibiotics commonly prescribed for UTI were performed by the MicroScan WalkAway System. Susceptibility rates and MIC50/90 were calculated and subsets of isolates were analyzed using descriptive statistics. Results A total of 204 isolates, including 102 E. coli and 102 K. pneumoniae, were tested. All but 1 isolate (99.5%) exhibited categorical agreement in results generated by the strip (Table 1) and disk (data not shown) methods and this was considered a minor error involving an intermediate result. OMC MIC90 for E. coli and K. pneumoniae were 6 µg/mL and >32 µg/mL, respectively. OMC displayed increased susceptibility rates compared to TET regardless of isolate species or ESBL positivity (Table 2). Table 1. Omadacycline Minimum Inhibitory Concentrations (MICs, µg/mL) Table 2. Susceptibilities of Oral Antibiotics Used to Treat UTI (% S) Conclusion OMC exhibits promising antimicrobial activity against TET-resistant and ESBL-positive E. coli and K. pneumoniae. OMC displays superior activity to ESBL positive E. coli when compared to ESBL positive K. pneumoniae. These data support the development of OMC as a much needed option in the treatment of UTI caused by resistant Enterobacterales. Disclosures Tyler J. Stone, PharmD, Paratek (Research Grant or Support) Abdullah Kilic, MD, Paratek (Grant/Research Support) John Williamson, PharmD, Paratek (Research Grant or Support) Elizabeth Palavecino, MD, Paratek (Grant/Research Support)Paratek (Grant/Research Support)

Antibiotic Management of Staphylococcus aureus Infections in US Children's Hospitals, 1999-2008

PEDIATRICS ◽  
2010 ◽  
Vol 125 (6) ◽  
pp. e1294-e1300 ◽  
Author(s):  
J. C. Herigon ◽  
A. L. Hersh ◽  
J. S. Gerber ◽  
T. E. Zaoutis ◽  
J. G. Newland
Keyword(s):  
Staphylococcus Aureus ◽  
Children's Hospitals ◽  
Children’S Hospitals ◽  
Antibiotic Management

scholarly journals 1126. Variability in Antibiotic Use in Children’s Hospitals in the United States

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S400-S401
Author(s):  
Hannah Griffith ◽  
Keerti Dantuluri ◽  
Cary Thurm ◽  
Derek Williams ◽  
Ritu Banerjee ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Use ◽  
Surgical Patients ◽  
Hospitalized Children ◽  
Medical Patients ◽  
Broad Spectrum Antibiotic ◽  
Children's Hospitals ◽  
Children’S Hospitals ◽  
Median Hospital ◽  
Research Grant

Abstract Background Understanding patterns of inpatient antibiotic use is necessary to enhance appropriate use and minimize preventable harm at hospitals. Few studies have characterized antibiotic use in the inpatient setting in children. Methods We conducted a cross-sectional study in children admitted to 51 freestanding US children’s hospitals included in the Pediatric Health Information System (PHIS). Overall and broad-spectrum antibiotic use (see Table) were measured using charge data, and prevalence of use was assessed on a single day of each 2017–2018 season over one year. Comparisons were made based on clinical setting (medical vs. surgical), clinical unit (PICU, NICU, and all others), hospital, and region. We assessed the relationship between antibiotic use and median hospital case-mix index (CMI), a surrogate for clinical complexity. Results Of 52769 hospitalized children assessed on a study day, 19174 (36%) received antibiotics, and 6575 (12%) received broad-spectrum antibiotics (table). Overall antibiotic use prevalence varied across hospitals from 22% to 52% (Figure 1). Median hospital CMI had no significant relationship with overall antibiotic use and only a weak correlation (ρ=0.29) with broad-spectrum antibiotic use (Figure 2). Antibiotic use prevalence varied minimally by season, ranging from 36% in fall to 37% in summer. Antibiotic use prevalence was 29% (9470/32436) among medical patients and 48% (9704/20333) among surgical patients. The antibiotics most commonly administered in medical patients were ceftriaxone and ampicillin, while surgical patients most commonly received cefazolin and vancomycin. Regional prevalence ranged from 33% (Midwest) to 40% (West). By unit, PICU patients had the highest prevalence of overall [58% (4006/6874)] and broad-spectrum [27% (1830/6874)] antibiotic use. Children with complex chronic conditions accounted for 63% of hospitalized children but represented 72% of children receiving any antibiotic and 85% of those receiving broad-spectrum antibiotics. Conclusion We observed large and apparently unexplained variability in antibiotic use prevalence among children’s hospitals, clinical settings, and regions. This indicates potential opportunities for enhanced antibiotic stewardship activities. Disclosures Ritu Banerjee, MD, PhD, Accelerate Diagnostics: Grant/Research Support; BioFire: Research Grant; Biomerieux: Research Grant; Roche: Research Grant

scholarly journals 1061. Comparison of the Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score to Predict Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S317-S318 ◽  
Author(s):  
Sarah Jorgensen ◽  
Evan J Zasowski ◽  
Trang D Trinh ◽  
Abdalhamid M Lagnf ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Predictive Value ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Apache Ii ◽  
Apache Ii Score ◽  
Health Evaluation ◽  
Research Support ◽  
C Statistic ◽  
Sensitivity Specificity ◽  
Research Grant

Abstract Background Methicillin-resistant Staphylococcus aureus bloodstream infection (MRSA BSI) is associated with high morbidity and mortality. The prediction of outcomes may have a profound impact on clinical decision making and risk stratification. The Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score (PBS) have been repeatedly described as independent predictors of mortality in MRSA BSI. The APACHE II is complex to calculate and many of the variables may not be pertinent to MRSA BSI. The PBS is a simple score using readily assessable variables. The comparative predictive performance of the two models in MRSA BSI has not been evaluated. Methods Retrospective, observational, singe-center cohort study in adults with MRSA BSI between 2008 and 2018. Patients who did not receive active therapy ≤72 hours of index culture were excluded. APACHE II and PBS were calculated using the worst physiological values recorded ≤24 hours of blood culture collection. Discriminatory ability for 30-day mortality was assessed using the c-statistic and was compared using the Hanley and McNeil method. The best cut-off point in each scoring system was determined using the Youden Index (J). Results A total of 455 patients were included. The median (IQR) PBS and APACHE II were 2 (0, 3) and 18 (11, 23), respectively. All-cause 30-day mortality was 16.3%. The c-statistic (95% CI) for the APACHE II vs. PBS in the overall cohort and stratified by ICU status were: 0.813 (0.763, 0.863) vs. 0.717 (0.653, 0.782), P = 0.0035; ICU 0.729 (0.610, 0.848) vs. 0.570 (0.442, 0.699), P = 0.026; and non-ICU 0.821 (0.761, 0.881) vs. 0.700 (0.614, 0.786),P = 0.0046, respectively. The APACHE II with the maximum J value was 21; sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for 30-day mortality were 81.08%, 72.97%, 36.81%, and 95.21%, respectively. The PBS with the maximum J value was 3; sensitivity, specificity, PPV, and NPV were 66.22%, 72.18%, 31.61%, and 91.67%, respectively. Conclusion The APACHE II was superior to the PBS in predicting 30-mortality in patients with MRSA BSI in the overall cohort and stratified by ICU status at BSI onset. Future research to develop a more practical scoring model with high discriminatory power is needed. Disclosures M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

scholarly journals 1073. Predictors of Vancomycin Switch or Escalation in Patients With Methicillin-Resistant Staphylococcus aureus Bloodstream Infection

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S321-S321
Author(s):  
Abdalhamid M Lagnf ◽  
Sarah Jorgensen ◽  
Evan J Zasowski ◽  
Trang D Trinh ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Logistic Regression ◽  
Infective Endocarditis ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Apache Ii ◽  
Research Support ◽  
Methicillin Resistant ◽  
Multivariable Logistic Regression ◽  
The Impact ◽  
Research Grant

Abstract Background Vancomycin (VAN) is the primary agent for the treatment methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI). VAN is frequently combined with or switched to a second anti-MRSA agent for the treatment of serious BSI because VAN monotherapy has been linked to treatment failures. We aimed to determine the potential risk factors for patients with MRSA BSI who switched or had therapy escalated. Methods This was a multicenter, retrospective cohort study of adults (≥18 years) initially treated with VAN (>24 hours) for MRSA BSI between 2006 and 2018. Patients with a respiratory source were excluded. Baseline clinical and infection characteristics were compared between patients who received VAN as the sole anti-MRSA agent and continued on VAN until discharge and patients who switched or had a second anti-MRSA agent added during their admission (switch/escalate group). Multivariable logistic regression was performed to identify independent predictors of therapy switch or escalation. Results A total of 195 patients were included (66 VAN and 129 switch/escalate). The mean (SD) age of the study population was 56 (15.5) years, 68.2% were male, and 81.0% were African-American. Most (80%) of patient had community-onset BSI. The median (IQR) Charlson Comorbidity index and Acute Physiology and Chronic Health Evaluation (APACHE) II scores were 3 (1–5) and 14 (8–20), respectively. The major sources of BSI were skin/soft tissue (24.6%), infective endocarditis (24.1%), and bone/joint (23.1%). Median (IQR) time to switch/escalation was 67 (44–97) hours. In multivariable logistic regression analysis, infective endocarditis (aOR 6.2, 95% CI 2.2–16), hospitalization in the past 90 days (aOR 2.0, 95% CI 1.0–4.0), and APACHE II (aOR 1.07, 95% CI 1.01–1.12) were independently associated with switch/escalation. Conclusion We have identified a number of baseline clinical and infection characteristics that should be taken into account for clinicians to predict the likelihood of switch or escalation in vancomycin treated patients with MRSA BSI. Further studies evaluating the impact of up front alternative therapies in these higher risk patients are needed. Disclosures S. L. Davis, Achaogen: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Melinta: Scientific Advisor, Consulting fee. Nabriva: Scientific Advisor, Consulting fee. Zavante: Scientific Advisor, Consulting fee. M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

scholarly journals 1227. Development of a Clinical Prediction Model for Mortality in Methicillin-Resistant Staphylococcus aureus Bacteremia

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S372-S372
Author(s):  
Sarah Jorgensen ◽  
Evan J Zasowski ◽  
Trang D Trinh ◽  
Abdalhamid M Lagnf ◽  
Sahil Bhatia ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Clinical Decision Making ◽  
Initial Evaluation ◽  
Youden Index ◽  
Apache Ii Score ◽  
Research Support ◽  
Methicillin Resistant ◽  
C Statistic ◽  
Research Grant

Abstract Background Methicillin-resistant Staphylococcus aureus bloodstream infection (MRSA BSI) is associated with high mortality despite advances in medical care. Mortality prediction may have a profound impact on clinical decision making and risk stratification. Widely used scoring systems such as the Acute Physiology and Chronic Health Evaluation (APACHE) II Score and the Pitt Bacteremia Score were derived in the general critical care and Gram-negative BSI populations, respectively and may be less precise in MRSA BSI. We sought to develop a predictive model (PM) for 30-day mortality in patients with MRSA BSI based on characteristics readily assessable at initial evaluation. Methods Retrospective, singe-center, cohort study in adults with MRSA BSI 2008 to 2018. Patients who did not receive active therapy within 72 hours of index culture were excluded. Independent baseline demographic, clinical and infection predictors of 30-day mortality were identified through multivariable logistic regression analysis with bootstrap resampling and coefficient shrinkage. The PM was derived using a regression coefficient-based scoring method. PM discriminatory ability was assessed using the c-statistic. The optimal threshold score was determined using the Youden Index (J). Results A total of 455 patients were included and 30-day mortality was 16.3%. The PM consisted of five variables and a potential total score of 33. Points were assigned as follows: age (9 points ≥90 years, 6 points 80–89 years, 5 points 70–79 years, 0 points <70 years); Glasgow Coma Scale (8 points ≤9, 5 points 10–13, 0 points ≥14); 7 points infective endocarditis or pneumonia; 5 points serum creatinine ≥ 3.5 dl/L; and four points respiratory rate <10 or >24. The PM c-statistic was 0.860 (95% CI 0.818, 0.902). The PM score with the maximum J value was 13. Thirty-day mortality was 5.2% vs. 44.5% for PM score <13 vs. ≥13 points, respectively (P < 0.001). The sensitivity, specificity, positive predictive value (PV), negative PV, and accuracy using a threshold of 13 points were 77.0%, 81.4%, 44.5%, 94.8%, and 80.7%, respectively. Conclusion Our findings demonstrate a weighted combination of five independent variables readily assessable at initial evaluation can be used to predict, with high discrimination, 30-d mortality in MRSA BSI. External validation is required before wide-spread clinical use. Disclosures M. J. Rybak, Allergan: Consultant, Grant Investigator and Speaker’s Bureau, Research grant and Research support. Achaogen: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Bayer: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Melinta: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support Theravance: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Sunovian: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. Zavante: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support. NIAID: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee, Research grant and Research support.

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