Methicillin-sensitive Staphylococcus Aureus Infections Research Articles

Epidemiology and temporal trends of infective endocarditis between 2006 and 2018 at a tertiary referral center

Abstract Introduction Despite modern diagnostics, targeted antibiotic therapy and surgical treatment the mortality rate of infective endocarditis (IE) remains high. In developed countries both the risk factors and pathogens have changed. Objective and methods In our retrospective study we analyzed the clinical and microbiological characteristics, short- and long-term all-cause mortality, and temporal trends of consecutive patients admitted with IE between 2006 and 2018. Results We included 537 cases in our study, the mean age was 55.9 ± 16.5 years (72.2% male). 325 (60.5%) cases were native left-sided IE, 14 (3%) cases were right-sided IE, 130 (24%) cases were prosthetic valve IE, 62 (11.5%) cases were intracardiac device-related IE and 6 (1%) other cases. The most common microorganisms were Staphylococci (n=175; 33%), including 104 cases of methicillin-sensitive Staphylococcus aureus (MSSA), 27 cases of methicillin-resistant Staphylococcus aureus (MRSA) and 44 cases of coagulase-negative Staphylococci. Streptococcus species were identified in 141 cases (26%), Enterococcus species in 88 cases (16%) and 72 cases (13%) were classified as blood culture-negative IE. In-hospital all-cause mortality was 14%, mortality at six months was 27%, at one-year was 31%, and at five-year was 45%. The incidence of MSSA infections increased over time (p=0.024), while coagulase-negative Staphylococci (p<0.001), and Streptococci (p=0.047) infections decreased. None of the observed mortality rates showed significant change over the study period. Predictors of mortality were advanced age (HR 1.37; p<0.001), impaired renal function (HR: 1.03; p<0.001), reduced ejection fraction on admission (HR 1.38; p<0.001), stroke (HR 1.74; p=0.001), and MRSA infection compared to Streptococci (HR 2.56; p=0.002). Conclusion During the observed 13-year period Staphylococci were the most common pathogens, with an increasing incidence of MSSA infection in our tertiary center. The mortality rate of IE remained high and showed no improvement over time.

Regional Variation of Infectious Agents Causing Endogenous Endophthalmitis in the United States: A National Database Analysis

To describe regional variation in microbes causing infectious endogenous endophthalmitis (EE) in the United States. This is a retrospective, national database analysis utilizing the 2002-2014 National Inpatient Sample database. Using the International Classification of Disease 9 codes, we identified cases with EE. Cases were stratified regionally into Northeast, South, West, or Midwest. Unadjusted chi-square analysis followed by adjusted multivariate logistic regression was performed to evaluate variation in demographic factors, comorbidities using the Elixhauser Comorbidity Index (ECI), microbial variation, mortality, and use of vitrectomy or enucleation by region. Proportion of microbes, mortality, and vitrectomy by region in addition to factors with significant odds ratios for mortality and for in-hospital vitrectomy. A total of 10 912 patients with infectious EE were identified, with 2063 cases in the Northeast (18.9%), 2145 cases in the Midwest (19.7%), 4134 cases in the South (37.9%), and 2570 cases in the West (23.6%). Chi-square analysis indicated significant regional variation in patient demographics, microbes causing the infection, ECI, mortality, and surgical intervention. The 4 most common microbes for all regions were methicillin-sensitive Staphylococcus aureus (MSSA), Streptococcus, Candida, and methicillin-resistant Staphylococcus aureus. Methicillin-sensitive S.aureus was the most common cause of EE in all regions, although the proportion of MSSA infection did not significantly vary by region (P= 0.03). Further, there was significant regional variation in the proportion of other microbes causing the infection (P < 0.001). Higher rates of vitrectomies were seen in the South and Midwest regions than that in the Northeast and West (P= 0.04). Regional variation exists in the infectious microbes causing EE. Further studies are needed to elucidate the etiology of these variations. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Effectiveness of Continuous Infusion Flucloxacillin in the Outpatient Parenteral Antimicrobial Therapy (OPAT) Setting in a UK Hospital: A Service Evaluation.

The availability of stability data for the use of continuous intravenous flucloxacillin in an elastomeric device has enabled the treatment of serious Methicillin Sensitive Staphylococcus aureus (MSSA) in the outpatient parenteral antimicrobial therapy (OPAT) setting. This service review aimed to evaluate current standard of care to establish the clinical effectiveness and complication rates associated with its use since its introduction at our institution. A retrospective review of clinical outcomes and adverse events/complications, was undertaken for all patients who received continuous infusion flucloxacillin for complicated MSSA infection between January 2019 and July 2022 via our OPAT service. Thirty-nine patients were included. An OPAT treatment outcome of 'Treatment aim attained uncomplicated' was achieved in 29/39 (74%) patients. Two patients had an OPAT treatment outcome of treatment aim not attained, both of which required unexpected hospital re-admission. An adverse event/complication occurred in 8 patients. There were two relapses in the 12-month follow-up period. Our review supports the assertion that continuous infusion flucloxacillin is clinically effective and well tolerated for the treatment of complicated MSSA infection in the OPAT setting.

Surveillance on meticillin-sensitive Staphylococcus aureus colonization and infection in a neonatal intensive care unit

Meticillin-sensitive Staphylococcus aureus (MSSA) infection is a significant health concern in neonatal intensive care units (NICUs). Bacterial colonization increases the risk of subsequent infection, leading to morbidity and mortality. To report the findings of a retrospective cohort study on the surveillance of MSSA colonization and infection in NICU patients. The weekly microbial surveillance results for MSSA colonization in the throat, nose, anus, and groin, as well as invasive and non-invasive MSSA infections, were analysed from November 2020 to June 2022. The MSSA infection and colonization risk were compared after adjustment for confounders by stepwise logistic regression analysis. Three hundred and eighty-three neonates were screened; 42.8% (N=164) were MSSA colonized. Significant risk factors for MSSA colonization were length of stay, vaginal delivery and extreme low gestational age <28 weeks (ELGAN) (all P<0.05). The surveillance detected 38 (9.9%) mild MSSA infections and 11 (2.9%) invasive MSSA infections. Neonatal colonization with MSSA is a major risk factor for MSSA infection overall (29.3% in colonized/infected vs 70.7% colonized/not-infected and 0.5% in not-colonized/infected vs 99.5% in not-colonized/not-infected infants) and invasive MSSA infections (6.1% in colonized/infected vs 93.9% in colonized/not-infected and 0.5% in non-colonized/infected vs 99.5% not-colonized/not-infected infants). Also, extreme low birth weight (<1000g), ELGAN and invasive ventilation were significant risk factors for MSSA infections (all, P<0.05). The link between postnatal MSSA colonization and subsequent MSSA infection offers possibilities for prevention. Additional research is needed to explore the association between vaginal birth and the pathogenesis of neonatal MSSA colonization.

Tannin extracted from Penthorum chinense Pursh, a potential drug with antimicrobial and antibiofilm effects against methicillin-sensitive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Staphylococcus aureus is an opportunistic pathogen. Due to the widespread use and abuse of antibiotics, various drug-resistant strains of S. aureus have emerged, with methicillin-resistant Staphylococcus aureus (MRSA) being the most prevalent. Bacterial biofilm is a significant contributor to bacterial infection and drug resistance. Consequently, bacterial biofilm formation has emerged as a therapeutic strategy. In this study, the chemical constituents, antimicrobial and antibiofilm properties of tannins isolated from Penthorum chinense Pursh (TPCP) were investigated. In vitro, TPCP exhibited antimicrobial properties. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA were 156.25 and 312.5 μg/mL, and 312.5 and 625 μg/mL, respectively. According to the growth curves, TPCP significantly inhibited the growth of MSSA and MRSA. The results of the crystal violet biofilm assay in conjunction with confocal laser scanning and scanning electron microscopy demonstrated that TPCP destroyed preformed MSSA and MRSA biofilms. TPCP significantly decreased the secretion of exopolysaccharides and extracellular DNA. Subsequently, the mechanism was investigated using RT-PCR. Examining the expression of icaA, cidA, sigB, agrA, and sarA genes in MRSA, we discovered that TPCP inhibited biofilm formation by affecting the quorum-sensing system in bacteria. Our study demonstrates that TPCP exerts antibacterial effects by disrupting the formation of bacterial biofilms, suggesting that TPCP has clinical potential as a novel antibacterial agent for the prevention and treatment of MSSA and MRSA infections.

Predicting Which Species of Bacteria Will Cause an Infection After Fracture Surgery.

The aim of this study was to develop and validate risk prediction models for deep surgical site infection (SSI) caused by specific bacterial pathogens after fracture fixation. A retrospective case-control study was conducted at a level I trauma center. Fifteen candidate predictors of the bacterial pathogens in deep SSI were evaluated to develop models of bacterial risk. The study included 441 patients with orthopedic trauma with deep SSI after fracture fixation and 576 control patients. The main outcome measurement was deep SSI cultures positive for methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S aureus (MRSA), gram-negative rods (GNRs), anaerobes, or polymicrobial infection within 1 year of injury. Prognostic models were developed for five bacterial pathogen outcomes. Mean area under the curve ranged from 0.70 (GNRs) to 0.74 (polymicrobial). Strong predictors of MRSA were American Society of Anesthesiologists (ASA) classification of III or greater (odds ratio [OR], 3.4; 95% CI, 1.6-8.0) and time to fixation greater than 7 days (OR, 3.4; 95% CI, 1.9-5.9). Gustilo type III fracture was the strongest predictor of MSSA (OR, 2.5; 95% CI, 1.6-3.9) and GNRs (OR, 3.4; 95% CI, 2.3-5.0). ASA classification of III or greater was the strongest predictor of polymicrobial infection (OR, 5.9; 95% CI, 2.7-15.5) and was associated with increased odds of GNRs (OR, 2.7; 95% CI, 1.5-5.5). Our models predict the risk of MRSA, MSSA, GNR, anaerobe, and polymicrobial infections in patients with fractures. The models might allow for modification of preoperative antibiotic selection based on the particular pathogen posing greatest risk for this patient population. [Orthopedics. 2024;47(1):e19-e25.].

Epidemiology of Methicillin-resistant and Methicillin-sensitive Staphylococcus aureus infections in Lebanon

Background. Methicillin-resistant Staphylococcus aureus (MRSA) is a prevalent pathogen associated with significant morbidity and mortality. In Lebanon, MRSA rates have recently started to rise. We aimed to determine risk factors for acquiring MRSA and Methicillin-sensitive Staphylococcus aureus (MSSA) infections and identify independent risk factors for in-hospital mortality among patients with S. aureus infection. Methods. We used a case-case-control study design that included patients with infections and compared them to uninfected controls. Two multivariable regression models were constructed to determine variables associated with acquiring MRSA and MSSA infections. We explored independent predictors of mortality in the overall population compared with the MRSA subgroup. Results. 356 patients with S. aureus infections were identified and compared to 208 uninfected controls. A recent history of surgery and underlying diabetes were independent risk factors for acquiring both infections. Having a urinary catheter for more than 6 days and steroid therapy were unique risk factors for MRSA infection (aOR 28.1, 95% CI 3.5-223.6 and 3.7, 95% CI 1.6-8.7, respectively). Risk factors exclusively associated with MRSA infection included ICU admission, acute renal failure, and malignancy. Conclusions. Risk factors associated with MRSA infection are distinct from those associated with MSSA infection. This can be used to risk stratify patients and will aid in choosing empirical antibiotic therapy.

Comparison of diagnosis and treatment of MSSA and MRSA osteomyelitis in children: a case–control study of 64 patients

BackgroundWe aimed to compare the clinical characteristics of acute osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) in children.MethodsWe retrospectively analyzed the data of 64 children treated between September 2017 and June 2021. Based on the bacterial culture results, they were divided into MRSA and MSSA infection groups. Both groups were treated with debridement and vacuum-assisted closure for negative pressure drainage. Parameters including clinical manifestations, number of operations, length of hospital stay, inflammatory indicators, and concurrent arthritis were compared between the two groups.ResultsIn the MRSA infection group, there was one case each of residual joint stiffness and pathological fracture. Conversely, the MSSA group had two cases of residual joint stiffness. The MRSA infection group was more prone to high fever (t = 3.61, P = 0.001), white blood cell count elevation (t = 2.41, P = 0.022), arthritis (X2 = 7.48, P = 0.013), metastatic abscess (X2 = 4.78, P = 0.042), and a shorter length of progression from onset to admission (t = − 2.04, P = 0.046); however, it required more surgeries (t = 2.68, P = 0.009) and longer hospital stay (t = 2.04, P = 0.045).ConclusionsPediatric acute osteomyelitis caused by MRSA is more prone to cause high fever and markedly elevated of white blood cell count, and is often accompanied with suppurative infection of adjacent joints and metastatic abscesses, thus requiring more surgeries and longer hospital stay.

MRSA Prophylaxis in Spine Surgery Decreases Postoperative Infections.

Retrospective cohort study. To compare infection rates before and after the implementation of a quality improvement protocol focused on methicillin-resistant Staphylococcus aureus (MRSA) screening and decolonization in patients undergoing lumbar fusion and/or decompression. Prior studies have demonstrated MRSA infections comprise a sizable portion of SSIs. Additional studies are required to improve our understanding of the risks and benefits of MRSA decolonization with vancomycin prophylaxis. A retrospective cohort analysis was conducted on patients who underwent spinal fusion or laminectomy before (2008-2011) and after (2013-2016) the implementation of an MRSA screening and treatment protocol. Odds ratios for MRSA, methicillin-sensitive Staphylococcus aureus (MSSA), and Vancomycin-resistant Enterococcus (VRE) infection before and after screening was calculated. Multivariate analysis assessed demographic characteristics as potential independent predictors of infection. A total of 8425 lumbar fusion and 2558 lumbar decompression cases met inclusion criteria resulting in a total cohort of 10,983 patients. There was a significant decrease in the overall rate of infections ( P <0.001), MRSA infections ( P <0.001), and MSSA infections ( P <0.001) after protocol implementation. Although VRE infections after protocol implementation were not significantly different ( P =0.066), VRE rates as a percentage of all postoperative infections were substantially increased (0 vs. 3.36%, P =0.007). On multivariate analysis, significant predictors of the infection included younger age (OR=0.94[0.92-0.95]), shorter length of procedure (OR=1.00[0.99-1.00]), spinal fusion (OR=18.56[8.22-53.28]), higher ASA class (OR=5.49[4.08-7.44]), male sex (OR=1.61[1.18-2.20]), and history of diabetes (OR=1.58[1.08-2.29]). The implemented quality improvement protocol demonstrated that preoperative prophylactically treating MRSA colonized patients decreased the rate of overall infections, MSSA infections, and MRSA infections. In addition, younger age, male sex, diabetic status, greater ASA scores, and spinal fusions were risk factors for postoperative infection.

Reducing Staphylococcus aureus infections in the neonatal intensive care unit.

Our neonatal intensive care unit (NICU) saw an increase in Staphylococcus aureus (SA) infections-methicillin-resistant SA (MRSA) infections increased from 2.1/10,000 patient days (PD) to 5.1/10,000 PD, and methicillin-sensitive SA (MSSA) infections from 1.2/10,000 PD to 3.9/10,000 PD. This quality improvement project aimed to decrease the rates of SA infections to less than 2.0/10,000 PD, and to determine the rate of SA decolonization. Infection prevention interventions targeted patient factors (SA surveillance, patient cohorting, decolonization protocol), provider factors (provider cohorting, enhanced hand hygiene) and environmental factors (room structure, equipment optimization). The rates of MRSA and MSSA infections decreased to 0.6/10,000 PD and 0.7 infections/10,000 PD respectively. Persistent decolonization of SA was successful in 67% of colonized patients. Specific interventions targeting patient, provider, and environmental factors, including the implementation of a SA decolonization protocol, were successful in decreasing the incidence of SA infections in neonates.

An Antibiotic-Loaded Hydrogel Demonstrates Efficacy as Prophylaxis and Treatment in a Large Animal Model of Orthopaedic Device-Related Infection.

Local antibiotic therapy is increasingly being recognised for its role in preventing and treating orthopaedic device-related infection (ODRI). A bioresorbable, injectable gentamicin-loaded hydrogel has been developed to deliver local antibiotics at the time of surgery with potential for both prevention and treatment of ODRI. In a prophylaxis model, the antibiotic hydrogel was compared with systemic perioperative antibiotic prophylaxis alone in twelve sheep (six per group) at the time of intramedullary (IM) nail insertion to the tibia, which was inoculated with methicillin-sensitive Staphylococcus aureus (MSSA). In a treatment model of single-stage revision surgery, adjunctive antibiotic-loaded hydrogel was compared with systemic antibiotics alone in a single stage revision of MSSA infection associated with a tibia intramedullary nail in eleven sheep (five/six per group). The primary endpoint was quantitative microbiological results of soft tissue, bone and sonicate fluid from explanted hardware at the time of euthanasia. At euthanasia, the control sheep that received no local antibiotics in the prophylaxis model were all culture-positive (median 1x108, range 7x106-3x108 colony forming units, CFU) while only two of six sheep receiving local gentamicin had any culture positive biopsies (median 1x101, range 0 - 1x105 CFU). For the treatment model, sheep receiving only systemic antibiotics were all culture-positive (median 8x105, range 2x103- 9x106 CFU) while only two of six sheep treated with gentamicin-loaded hydrogel had any culture positive biopsies (median 3x102, range 0 - 7x104 CFU). Local gentamicin concentrations measured in extracellular fluid in the tibial canal show a burst release of gentamicin from the hydrogel. Serum gentamicin concentrations peaked in both models at one day post application and were below detection limit thereafter. This study has demonstrated the effective use of a locally delivered antibiotic hydrogel for both the prevention and treatment of ODRI that is superior to that of systemic antibiotics alone. Future studies will endeavour to translate from preclinical to clinical research trials.

Comparative Clinical Outcomes of Patients with Diabetic Foot Infection Caused by Methicillin-Resistant Staphylococcus Aureus (MRSA) or Methicillin-Sensitive Staphylococcus Aureus (MSSA).

Few studies have addressed the interaction of specific pathogens with clinical outcomes in patients with diabetic foot infection (DFI). Our study aim was to compare the clinical outcomes among patients with DFI caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). We gathered the data of 75 consecutive patients admitted at specialized outpatients diabetic with mild or moderate DFI in which S. aureus was isolated from bone or soft tissue specimens in pure or as a part of the polymicrobial culture. Patients were divided into two groups: those with MRSA infection and those with MSSA infection. Patients with MRSA diabetic foot infections were significantly associated with male gender (86% vs. 64%, P = .029), higher SINBAD Classification Score (3.6 ± 0.99 points vs. 2.8 ± 1.06 points, P = .001), longer mean wound evolution [17.8 (3;29.5) weeks versus 9.1 (1;12) weeks, P = .008], bone involvement [18 (50%) versus 9 (23.1%), P = .015] and longer mean healing time [18.2(8;28) weeks versus 9.1 (1;12) weeks, P = .008]. In addition, male gender (OR 8.81, 95% CI 2.00-38.84) and SINBAD Classification Score (OR 2.70, 1.46-5.00) were identified as independent risk factors for MRSA DFI. Significant differences in the number of surgical procedures to resolve infection [15 (41.7%) versus 13 (33.3%), P = .456] or in the mean healing time after surgical treatment [10.5 weeks (6.7;16.5) versus 6.1 weeks (3;8.7), P = .068] were not observed among groups, suggesting that when treatment is based on early and surgical debridement, MRSA infections are not associated with worse prognosis. In conclusion MRSA DFI has importance in clinical outcomes such as time to healing. We propose that recent lines of research regarding the genetic virulence of strains of S. aureus could provide new insights into our results.

STAPHYLOCOCCUS-ASSOCIATED GLOMERULONEPHRITIS MIMICKING IGA VASCULITIS IN AN ADULT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Staphylococcus-associated glomerulonephritis (SAGN) is an immune complex–mediated glomerulonephritis (GN) which commonly presents with elevated creatinine, microscopic hematuria, and variable proteinuria; but on rare occasions may manifest as vasculitis that closely mimics Henoch-Schonlein Purpura (HSP). CASE PRESENTATION: A 62-year-old male with diabetes mellitus (DM) and liver cirrhosis presented with gangrene of the right hallux after a dog bite. Given concern for gas gangrene, he underwent Guillotine amputation. Blood cultures were positive for Methicillin sensitive staphylococcus aureus (MSSA). He was admitted to the ICU for septic shock and started on vasopressors and broad-spectrum antibiotics. His course was complicated by acute kidney injury (AKI) and a new onset diffuse palpable purpuric rash on day 3 of admission, for which a skin biopsy was performed. His serum creatinine was 1.4 mg/dl on admission and progressively worsened to 2.8 mg/dl requiring continuous renal replacement therapy (CRRT) initiation. Urinalysis showed 1+ protein with large blood and 20-40 red blood cells (RBC) per high power field. Urine microscopy revealed isomorphic RBC without red cell cast. Spot Urine protein-creatinine ratio was 0.4 mg/g. Immune work up was negative except for hypocomplementemia with C3 35 mg/dl, C4 8 mg/dl and CH50 19 unit/ml. Ultrasound abdomen showed cirrhosis. 2D-echocardiogram was negative for vegetations. Transesophageal echocardiogram and renal biopsy were not performed as patient was hemodynamically unstable. He remained critically ill and continued to decline despite initiation of CRRT and died due to refractory shock. Skin biopsy returned later, showing leukocytoclastic vasculitis with IgA deposition, confirming IgA vasculitis. DISCUSSION: SAGN is an immune complex mediated disease that occurs concurrently with staphylococcal infection. Pathophysiology is postulated to involve massive T cell and B cell activation by a staphylococcal superantigen. This leads to release of cytokines with overproduction of antibodies and systemic vasculitis with IgA-staphylococcal antigen immune complex formation and deposition. About 20% of the patients with SAGN present with leukocytoclastic vasculitis and can clinically mimic steroid responsive disease processes such as HSP or cryoglobulinemic vasculitis. Renal biopsy is essential to establish diagnosis as steroid and immunosuppression use in SAGN remain controversial and can worsen infection as well as renal disease. Unfortunately, renal biopsy could not be performed in this patient due to refractory shock; however, diagnosis of SAGN is being preferred owing to clinical characteristics like older age, DM, active MSSA infection and AKI with hypocomplementemia. CONCLUSIONS: It is important to make clinicians aware of the variable presentation of infection related GN, such as SAGN, HSP-nephritis, or post-streptococcal GN as treatment might differ. REFERENCE #1: 1. Akio Koyama, Kobayashi M et al. Glomerulonephritis associated with MRSA infection: A possible role of bacterial superantigen. Kidney International. Doi:10.1038/ki.1995.25 REFERENCE #2: 2. Tahrin Mahmood, Puckrin R et al. Staphylococcus-Associated Glomerulonephritis Mimicking Henoch-Schonlein Purpura and Cryoglobulinemic vasculitis in a patient with an epidural abscess: A case report and brief review of the literature. Can J Kidney Health Dis. 2018. Doi:10.1177/2054358118776325. DISCLOSURES: No relevant relationships by kalpana chintha, source=Web Response No relevant relationships by Stanley Dumond, source=Web Response No relevant relationships by Adam Green, source=Web Response No relevant relationships by Ananya Nanduri, source=Web Response No relevant relationships by Matk Sunga, source=Web Response

P143. Impact of preoperative MRSA screening on infection risk in spine patients

<h3>BACKGROUND CONTEXT</h3> Postoperative infection in the setting of spine surgery remains a significant concern for patients, surgeons, and health care institutions due to the associated morbidity, mortality, and societal costs. Prior studies have shown methicillin resistant staphylococcus aureus (MRSA) infection comprises a sizable portion of those infections. Given this information, the authors conducted a quality improvement protocol to screen and prophylactically treat elective spinal surgery patients colonized with MRSA. This study evaluates the changes in outcomes before and after the initiation of the protocol. <h3>PURPOSE</h3> The goal of this study is to compare the rates of infection before and after the implementation of a preoperative MRSA screening and treatment protocol for spine patients undergoing laminectomy or fusion. <h3>STUDY DESIGN/SETTING</h3> Retrospective cohort review. <h3>PATIENT SAMPLE</h3> A total of 26,614 spinal fusion and laminectomy cases were included, of which there were 72 MRSA infections. <h3>OUTCOME MEASURES</h3> Incidence and relative risk of surgical infection. <h3>METHODS</h3> A retrospective cohort analysis was conducted on patients who underwent spinal fusion and laminectomy before and after the implementation of the MRSA screening and treatment protocol. The relative risk of MRSA and methicillin sensitive staphylococcus aureus (MSSA) infection before and after screening was calculated. Additionally, multivariate analysis was used to assess demographic characteristics as potential independent predictors of infection. <h3>RESULTS</h3> The relative risk of all infections, including both MRSA and MSSA, was significantly lower post protocol than before its implementation (p < 0.001 for both). Patients with infection were significantly younger, had a shorter length of procedure, higher ASA class, and more likely to be diabetic (p < 0.001 for all). Multivariate logistic regression showed that age, length of procedure, and ASA class were independent predictors of infection. <h3>CONCLUSIONS</h3> The implemented quality improvement protocol demonstrated that prophylactically treating patients colonized MRSA infection preoperatively helped reduced the rate of infection, including both MRSA and MSSA infections, after spine surgery. <h3>FDA DEVICE/DRUG STATUS</h3> This abstract does not discuss or include any applicable devices or drugs.

De novo methicillin-resistant Staphylococcus aureus vs. methicillin-sensitive Staphylococcus aureus infections of the spine, similar clinical outcome, despite more severe presentation in surgical patients.

Vertebral osteomyelitis (VO) is a severe infection of the vertebral body and the adjacent disc space, where Staphylococcus aureus is most commonly isolated. The objective of this retrospective study was to determine risk factors for and compare outcome differences between de novo methicillin-resistant Staphylococcus aureus (MRSA) VO and methicillin-sensitive Staphylococcus aureus (MSSA) VO. A retrospective cohort study was performed by review of the electronic medical records of 4541 consecutive spine surgery patients. Among these 37 underwent surgical treatment of de novo MRSA and MSSA spinal infections. Patient demographics, pre- and postoperative neurological status (ASIA impairment score), surgical treatment, inflammatory laboratory values, nutritional status, comorbidities, antibiotics, hospital stay, ICU stay, reoperation, readmission, and complications were collected. A minimum follow-up (FU) of 12months was required. Among the 37 patients with de novo VO, 19 were MRSA and 18 were MSSA. Mean age was 52.4 and 52.9years in the MRSA and MSSA groups, respectively. Neurological deficits were found in 53% of patients with MRSA infection and in 17% of the patients with MSSA infection, which was statistically significant (p < 0.05). Chronic renal insufficiency and malnutrition were found to be significant risk factors for MRSA VO. Preoperative albumin was significantly lower in the MRSA group (p < 0.05). Patients suffering from spinal infection with chronic renal insufficiency and malnutrition should be watched more carefully for MRSA. The MRSA group did not show a significant difference with regard to final clinical outcome despite more severe presentation.

Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in Acutely Ill Children: A Retrospective Case-Control Study.

To test if admission clinical and laboratory variables could reliably discriminate community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from methicillin-sensitive Staphylococcus aureus (MSSA) infections in acutely ill children, and to describe the epidemiology, clinical features and outcomes among children with Staphylococcal infections admitted to the hospital. The authors conducted this retrospective case-control study comparing children with CA-MRSA and MSSA infections admitted to hospital between June 2014 and June 2017. They describe the evolving epidemiology and attempt to identify clinical and laboratory variables that can differentiate MRSA cases from MSSA controls. They used multivariate logistic regression to identify independent predictors of MRSA infection and Cox-proportional hazard analysis to compare survival times. Seventy-three children were enrolled, of which 35 had CA-MRSA and 38 had MSSA infections. Children in MRSA group were younger [median (IQR) age in months: 36 (12, 62) vs. 56 (37, 96); p = 0.032]. MRSA and MSSA groups had similar rate of skin and soft tissue involvement (SSTI) [62.9% vs. 54.1%; p = 0.449]. Median duration of illness was lower in MRSA, 6 vs. 8.5 d (p = 0.001). TLC of 8100 or less was 82% sensitive and 94% specific for MRSA sepsis at admission [AUROC = 0.64 (0.51-0.77), p = 0.04]. Mortality (8.6% vs. 10.5% p = 1.0) and length of ICU stay (7.2 vs. 9.3 d, p = 0.24) were similar in both. None of the admission variables were predictive of MRSA culture-positivity on regression analysis. The hospital-based incidence of CA-MRSA infections among children appears to be increasing. None of the admission clinical or laboratory variables could reliably identify CA-MRSA infections. As there seems to be no reliable way to differentiate children with MSSA and MRSA infections, physicians may consider empiric initiation of broad-spectrum antibiotics at admission to cover both MSSA and MRSA, especially in critically ill children with suspected Staphylococcal infections.

Frequency of Dosing of Cephalexin for Oral Step-Down Therapy of Pediatric Osteoarticular Infections Caused by Methicillin-Sensitive Staphylococcus Aureus.

Osteoarticular infections are one of the more common invasive bacterial infections encountered in children. There exist significant practice variations in both the diagnosis and treatment of such infections. However, the practice of transitioning from parenteral therapy to oral antibiotics has been well validated by several studies. For methicillin-sensitive Staphylococcus aureus (MSSA), cephalexin is often recommended. Prospective, controlled data regarding optimal dosing of cephalexin in pediatric osteomyelitis are not available. We sought to review our retrospective, uncontrolled data on four times daily (QID) versus three times daily (TID) dosing of cephalexin for pediatric osteoarticular infections. Children ≥1 month to <18 years of age admitted to Rady Children's Hospital-San Diego with a diagnosis of osteomyelitis or septic arthritis between January 1, 2002, and November 30, 2007, were identified and previously reported. Only patients with culture-positive MSSA infections are included in this report. Demographic and clinical data were manually extracted from the electronic medical record. Fifty-nine patients were treated with cephalexin and had records available for review through our electronic medical record. Thirty-eight patients (64.4%) were treated QID, and 21 patients (35.6%) were treated TID. Clinical cure was achieved in all patients with only one adverse event occurring in the QID group. In this retrospective chart review of children with osteoarticular infections caused by MSSA treated with cephalexin, similar clinical outcomes were found with QID versus TID dosing.

Population pharmacokinetics of cefazolin in critically ill children infected with methicillin-sensitive Staphylococcus aureus

ObjectivesCefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens. MethodsWe included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT > 4 ×MIC. ResultsThirty-nine patients with a median (range) age of 7 (0.1–17) years and a BW of 21 (2.8–79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m2 were the best schemes to reach the PK target of 100% fT> 4 ×MIC. ConclusionsIn critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT > 4 ×MIC in children with normal and augmented renal function.

217. Combination Salvage Therapy with Cefazolin Plus Ertapenem for Refractory Methicillin-Susceptible Staphylococcus aureus Bacteremia

BackgroundSuboptimal therapy against methicillin-sensitive Staphylococcus aureus (MSSA) may have catastrophic consequences in severe infections such as endocarditis or epidural abscess. High MSSA inocula have been associated with clinical failure in patients receiving cefazolin (CZ), particularly when used at low doses, associated with a CZ inoculum effect. We previously described that adding ertapenem (ETP) to CZ led to synergism against MSSA and sensitized the pathogen to host innate immune factors. Here we expand our experience with CZ plus ETP as salvage therapy for 11 cases of refractory MSSA bacteremia (lacking source control problems) and explore CZ+ETP combination in vitro and in vivo.MethodsSix available MSSA strains from patients treated with CZ+ETP for refractory bacteremia were tested in Mueller–Hinton Broth or RPMI media at standard (105 CFU/mL) or high (107 CFU/mL) inocula by MIC, checkerboard, and time-kill assays using ETP, CZ or nafcillin (NAF) alone vs. ETP+NAF or ETP+CZ. Disk diffusion synergy assays between CZ and ETP were also performed. CZ, ETP and CZ+ETP were tested in a rat endocarditis model using well described MSSA, TX0117 and TX0117c.Results11 consecutive patients with MSSA bacteremia (6 confirmed endocarditis) refractory to standard CZ or NAF rapidly cleared with CZ+ETP. 9 patients had daily positive blood cultures, and 8 cleared in ≤24 hr, including those with ≥2 cm vegetations. All 11 survived hospitalization. In MHB, 3/6 MSSA exhibited a CZ inoculum effect (CZ MIC >3 log2 in 107 vs. 105 CFU/mL), but only 1 showed a significant CZ inoculum effect in RPMI. CZ+ETP was significantly more efficacious than CZ in a rat model of MSSA endocarditis utilizing a strain displaying a CZ inoculum effect, despite only modest benefit observed in vitro for 6 MSSA isolates.ConclusionCZ+ETP combination therapy yielded profound clinical success in severe MSSA infections with high bacterial densities, as demonstrated by rapid bacteremia clearance. Enhanced efficacy was also observed in a rat endocarditis model. The anti-staphylococcal activity of CZ+ETP in vivo exceeded that observed in vitro, consistent with our prior observations of host innate immune cooperativity with the regimen. CZ+ETP warrants further study for the treatment of refractory MSSA bacteremia and endocarditis.Disclosures All authors: No reported disclosures.

1216. Cost-Effectiveness of Penicillin Skin Allergy Testing in Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia

Backgroundβ-Lactams remain the gold standard for treatment of MSSA bacteremia due to superior outcomes compared with vancomycin. Approximately nine in 10 patients receiving penicillin skin testing (PST) will be de-labeled of a penicillin allergy and able to receive a β-lactam antibiotic. The study aims to evaluate the cost-effectiveness of penicillin allergy confirmation during acute care admission for methicillin-sensitive staphylococcus aureus (MSSA) bacteremia through a PST service.MethodsA decision tree analysis was used to compare a PST intervention in patients with a registeredpenicillin allergy during an inpatient admission for MSSA bacteremia vs. usual care (No PST). The model was created from the health sector perspective with a 1-year time horizon. Patients with a penicillin allergy label were expected to receive vancomycin while patients with no penicillin allergy were expected to receive cefazolin. Potential inpatient, outpatient, and adverse reaction costs were considered in all arms of the model. The effects were measured in quality adjusted life years (QALY) and were calculated for patients who were cured, hospitalized, experienced severe adverse events, or died from MSSA infection.ResultsPatients who received PST services had a mean yearly cost of $12,802, mean quality adjusted life years (QALY) of 0.70, and mean cost/QALY of $18,311. The comparator group not receiving PST services had a mean yearly cost of $12,264, mean quality adjusted life years (QALY) of 0.64, and mean cost/QALY of $19,192. The model produced a final base case ICERof $8,966/QALY for receiving a PST during a hospital admission for the treatment of methicillin-sensitive staphylococcus aureus (MSSA) bacteremia.ConclusionPenicillin allergy confirmation through PST services was cost-effective for patients with a reported penicillin allergy admitted for MSSA bacteremia. Additional research to determine potential benefits of PST services beyond one year could further improve the cost-effectiveness of this intervention.Disclosures S. Meninger, ALK-Abelló: Grant Investigator, Research grant. E. Heil, ALK-Abelló: Grant Investigator, Research grant. T. J. Mattingly II, ALK-Abelló: Grant Investigator, Research grant.