Abdallah Mughrabi’s research while affiliated with St. Elizabeth's Medical Center and other places

Background In the United States, more than 1 million CAUTIs are diagnosed each year, ranking among the top 5 most common healthcare-associated infections; however, our observations suggest that these numbers are inflated due to the lack of clear diagnostic guidelines. Most laboratories process urine cultures (UC) in reflex when a urinalysis (UA) sample shows 10 or more cells/µL. By adding specific criteria to decrease the number of UC, we decreased unnecessary use of antibiotics and overall cost from CAUTI misdiagnosis. Methods In this study, we enforced conditions that increase standards for reflex UC processing. These conditions included patient symptoms, presence of indwelling catheter, and levels of red blood and epithelial cells. We prospectively evaluated outcomes for patients whose UA samples did not meet our criteria. We suppressed UA samples that did not meet our criteria and did not report the culture results. Results Analysis of UC requests from 2020 to 2023 revealed several notable findings: 37% of the urine samples were approved for culture, 44% of those yielded positive results, and 56% showed either mixed flora or no bacterial growth. All UC samples that met criteria had white blood cell counts between 25 and 50 /HPF, with 91% displaying over 50 /HPF. Notably, none of the excluded samples resulted in patients developing urinary complications. Amongst the suppressed UC, 9% yielded positive culture results consistent with asymptomatic bacteriuria. We noticed CAUTI reductions from 31/year in 2018 to 8/year in 2023. Our intervention helped avoid unnecessary antibiotics use, decreasing the number of hospitals acquired Clostrioides difficile infections from 31 cases in 2018 to 9 cases in 2023. Conclusion The high rejection rate of UC samples suggests opportunities for optimizing appropriateness criteria to improve diagnostic yield and resource utilization. Further analysis of rejection reasons may help identify areas for clinician education regarding appropriate UC ordering. Disclosures All Authors: No reported disclosures

Purpose: This study examines whether excessive adipose tissue, as measured by the body mass index (BMI), is associated with higher systemic markers of inflammation and higher risk of severe acute organ failure among patients with coronavirus disease 2019 (COVID-19). Methods: This was a multicenter retrospective cohort study of 1370 hospitalized adults (18 years or older) with COVID-19 during the first wave of the pandemic. Patient-level variables were extracted from the electronic medical record. The primary predictor variable was the BMI at time of hospital admission, in accordance with the World Health Organization classification. Multivariable logistic regression analyses examined the association of BMI with the composite of acute respiratory distress syndrome (ARDS), as defined by the use of high-flow nasal canula, non-invasive ventilation, or mechanical ventilation, severe acute kidney injury (AKI), as defined by acute dialysis requirement, or in-hospital death. Results: After adjustment for important cofounders, the BMI stratum of > 40 kg/m² (compared to the BMI < 25 kg/m² reference group) was associated with higher odds for the composite of ARDS, severe AKI, or in-hospital death (adjusted odds ratio [ORadj] 1.69; 95% confidence interval [CI]1.03, 2.78). As a continuous variable, BMI (per 5-kg/m² increase) remained independently associated with the composite outcome (ORadj 1.13; 95% CI 1.03, 1.23); patients in higher BMI categories exhibited significantly higher peak levels of C-reactive protein (CRP), a systemic marker of inflammation (P = .01). In a sub-cohort of 889 patients, the association of BMI with the composite outcome was no longer significant after adjustment for the peak level of CRP. Conclusions: Among hospitalized patients with COVID-19, a higher BMI is associated with higher risk of severe organ failure or in-hospital death, which dissipates after adjustment for CRP level. This supports the hypothesis that inflammation is a downstream mediator of adipose tissue on acute organ dysfunction.

Background Serratia Marcescens causes serious infections. Carbapenems were preferred due to fear of inducible AmpC resistance. IDSA guidance now recommends ceftriaxone, and in high-burden cases, cefepime. Evidence on Serratia bacteremia treatment is limited. This study compares outcomes of cefepime or carbapenem (CPCT) vs. non-cefepime non-carbapanem containing definitive therapy (NCPCT) in non-ESBL Serratia bacteremia. Methods We retrospectively reviewed adults (≥18 years) with Serratia Marcescens bacteremia hospitalized in seven Massachusetts acute care hospitals (2015 - 2022) (Figure 1). Demographics, clinical course characteristics, and antibiotic therapy choices were obtained. Primary outcome was 30-day mortality, and secondary composite outcome was antimicrobial failure (Definitions in Table 1 and 2). Chi Square and Mann-Whitney U tests were computed using SPSS statistical package.Figure 1.Study exclusion flow-chart. ESBL phenotypically defined by ceftriaxone resistance (MIC <1) Results 69 out of 128 patients were included in the study. The mean age was 59.23 and 27.53% had IVDU disorder. 21.9 % of patients received CPCT while 78.1% were treated with NCPCT. Notably, more patients in the CPCT group received antibiotics in preceding 3 months, and had more ventilator associated pneumonia (VAP). Other baseline characteristics, bacteremia sources and severity of infection were similar between both groups (Table 1). CPCT patients had longer definitive therapy and more prolonged hospital stay, while more patients in the NCPCT group were switched to oral therapy (Table 2). Neither 30-day mortality rate (8.7% NCPCT vs. 5% CPCT, P= 0.602) nor antimicrobial failure rate (12.5 % NCPCT vs. 23.8% CPCT, P=0.238) was significantly different.Table 1.Clinical characteristics and bacteremia sources of patient with Serratia bacteremia treated with a cefepime or carbapenem versus a non-cefepime nor carbapenem therapy regimen. * Immunocompromised patients are those receiving immunosuppressants, chemotherapy, or transplants, having HIV with CD4+ T cell count <200 cells/mm3, neutropenia with ANC < 500 cells/mm3, or corticosteroid use with prednisone or equivalent >10 mg for ≥ 14 days. † Active IVDU is defined as Self-reported or clinical evidence (exam or urine toxicology screen) of active Injection Drug use. ‡ Recent surgery or procedure in the 30 days leading to the positive culture includes urological, Gastroenterological procedure (Endoscopy or Paracentesis), Gastroenterological surgery (Intra-abdominal surgery or peri-anal surgery), Neurosurgical, Respiratory, vascular or Musculoskeletal. § Hospital-acquired bacteremia is diagnosed when a positive blood culture obtained from patients hospitalized for 48 hours or longer. Healthcare-associated bacteremia was defined as a positive blood culture is obtained within 48 hours of hospital admission and the patient fulfills specific pre-defined criteria utilized in prior studies. Community-acquired bacteremia refers to positive a blood culture obtained within 48 hours after hospital admission in patients who do not fit the criteria for healthcare-associated infections. || Urological is defined by pyuria or positive urine cultures. All patients had Pyuria except for 3 patients, instead they had renal calculi and irritative urinary symptoms. Skin and/or soft tissue infection: Per noted clinical examination findings, with some cases supplemented by Serratia growth with Mod or High PMNs from clinical specimens. Ventilator associated pneumonia (VAP): mechanically ventilated for more than 48H before the positive respiratory cultures. Other cases had clinical evidence of infection around port of entry or blood cultures drawn from the line growing Serratia. Intra-abdominal infection included radiological evidence of abscess, diverticulitis, biliary Dilatation, or cholecystitis. All cases were found to have elevated alkaline phosphatase and/or bilirubin. Deep seated complicated infection included Infective endocarditis, septic arthritis, osteomyelitis, or epidural abscess. ¶ Source control included drainage or debridement of deep soft tissue infection, drainage of pleural effusion, drainage of intra-abdominal abscess, resolution of biliary obstruction, cholecystectomy, removal of vascular catheter, removal of indwelling catheter, resolution of urological obstruction and/or replacement of the nephrostomy tubeTable 2.Antibiotic choices and clinical outcomes of patient with Serratia bacteremia treated with a cefepime or carbapenem versus a non-cefepime nor carbapenem therapy regimen. * Empiric antibiotic therapy: Antibiotics administered before antimicrobial susceptibility testing (AST) results, with a minimum 48-hour of uninterrupted duration and appropriate dosing. † Duration of empiric therapy was counted from day one of first empiric therapy until day of AST result. Duration of total definitive antibiotic therapy was counted from day of AST results until last day of definitive antimicrobial therapy. ‡ Definitive antibiotic therapy (i.e., antibiotics administered after the AST results, also with a minimum of 48-hour duration). § Duration of antimicrobial spectrum therapy (DAST) was calculated as follows: In single definitive therapy, spectrum score, per Kakiuchi et al., 2021, was multiplied by the duration in days. In sequential and double antibiotic therapy, the DAST for each antibiotic were summed up. We excluded oral antibiotics prescribed upon discharge from this calculation. || Infection-related re-admission was defined when a patient is readmitted not solely for a procedure or surgery, and they experience fever, worsening leukocytosis, or required escalation of antimicrobial therapy from the definitive therapy of the index admission. ¶ Microbiological failure, microbiological relapse, in- hospital mortality, 30-day mortality, infection-related hospital readmission, or recurrent Serratia bateremia within 30 days. Microbiological failure refers to the growth of Serratia after 48 hours of definitive antibiotic therapy, while microbiological relapse is the regrowth of Serratia after a negative blood culture (Kunz Coyne et al., 2023). Note: Two patients had recurrence of Serratia bacteremia within 30 days, neither were resistant to third generation cephalosporins. Conclusion Our study found no significant difference in 30-day mortality or antimicrobial failure between CPCT and NCPCT groups. Furthermore, longer hospital stay was observed in CPCT patients, possibly due to cefepime and meropenem’s less suitability for outpatient antimicrobial therapy (OPAT). Our study is limited by its small size and the overlap in definitive antibiotic therapy. Our findings suggest narrower Beta-lactam therapy may be appropriate which may help early hospital discharge and less days of broad spectrum therapy. Prospective studies are needed to confirm these conclusions and contribute to safe antimicrobial stewardship. Disclosures All Authors: No reported disclosures

Background Carbapenems were commonly prescribed for "SPACE" organisms. Recent IDSA guidance recommends narrower-spectrum beta-lactams for lower AmpC-induction risk bacteria, like Serratia. Prior studies focused on other Enterobacterales, with limited evidence on Serratia bacteremia. This study compares carbapenem-containing (CBCT) and non-carbapenem-containing active empiric/definitive therapy (NCBCT) for Serratia bacteremia. Methods We retrospectively reviewed records of adults (age ≥18 years old) with Serratia bacteremia hospitalized in 7 hospitals in Massachusetts over 7 years (2015-2022). IRB approval was obtained. Baseline characteristics, treatment details and outcome variables were extracted from medical charts. Chi Square and Mann-Whitney U tests were computed using SPSS statistical package. Results 73 out of 128 patients were included in the study after applying exclusion criteria (Figure 1). Mean age was 58.8 years. CBCT was prescribed in 23.3%. No significant differences were observed in baseline characteristics, bacteremia sources or severity; however, CBCT patients had longer definitive therapy and more prolonged hospital stay (Table 1). The 30-day mortality rate was not significantly different between both groups (14.8% NCBCT vs. 0% CBCT, P=0.102). While there was no difference in antimicrobial failure with a relative risk of 1.415 (95% CI 0.38-5.26, P=0.603), the infection-related hospital readmission rate was significantly higher in the CBCT group. Study exclusion flow-chart. ESBL phenotypically defined by ceftriaxone resistance (MIC <1) Characteristics and outcomes of patient with Serratia bacteremia treated with a carbapenem versus a non-carbapenem therapy regimen. * Immunocompromised patients are those receiving immunosuppressants, chemotherapy, or transplants, having HIV with CD4+ T cell count <200 cells/mm3, neutropenia with ANC < 500 cells/mm3, or corticosteroid use with prednisone or equivalent >10 mg for ≥ 14 days. † Hospital-acquired bacteremia is diagnosed when a positive blood culture obtained from patients hospitalized for 48 hours or longer. Healthcare-associated bacteremia was defined as a positive blood culture is obtained within 48 hours of hospital admission and the patient fulfills specific pre-defined criteria utilized in prior studies. Community-acquired bacteremia refers to positive a blood culture obtained within 48 hours after hospital admission in patients who do not fit the criteria for healthcare-associated infections. ‡ Deep seated complicated infection included Infective endocarditis, septic arthritis, osteomyelitis, or epidural abscess § Empiric antibiotic therapy: Antibiotics administered before antimicrobial susceptibility testing (AST) results, with a minimum 48-hour of uninterrupted duration and appropriate dosing. || Definitive antibiotic therapy (i.e., antibiotics administered after the AST results, also with a minimum of 48-hour duration). ¶ Duration of total definitive antibiotic therapy was counted from day of AST results until last day of definitive antimicrobial therapy. # Microbiological failure, microbiological relapse, in- hospital mortality, 30-day mortality, infection-related hospital readmission, or recurrent Serratia bateremia within 30 days. Microbiological failure refers to the growth of Serratia after 48 hours of definitive antibiotic therapy, while microbiological relapse is the regrowth of Serratia after a negative blood culture (Kunz Coyne et al., 2023). Note: Two patients had recurrence of Serratia bacteremia within 30 days, neither were resistant to third generation cephalosporins. Δ Infection-related re-admission was defined when a patient is readmitted not solely for a procedure or surgery, and they experience fever, worsening leukocytosis, or required escalation of antimicrobial therapy from the definitive therapy of the index admission. Conclusion We observed no significant differences in antimicrobial failure or mortality between CBCT and NCBCT groups. Narrower beta-lactam therapy may be appropriate when possible. In fact, CBCT was associated with prolonged hospital length of stay, which may be due to challenges in switching to outpatient therapy and discharging to lower acuity care settings. CBCT was also associated with more infection-related readmissions, which could be attributed to patient characteristics (IVDU and deep-seated infections) and frequent dosing requirements of meropenem impacting adherence. Our retrospective study is limited by a small size and overlap in definitive therapy and further prospective studies are needed to confirm our findings. Disclosures All Authors: No reported disclosures

Background Serratia Marcescens causes serious infections. Carbapenems were prescribed due to the bacterium’s ability to develop inducible AmpC-mediated resistance. Recent IDSA guidance recommends ceftriaxone and in high-burden cases, cefepime. Evidence on the role of cefepime in the treatment of Serratia bacteremia is scarce. We aim to evaluate the outcomes of patients who received cefepime-containing empiric and/or definitive therapy (CFCT) to those receiving non-cefepime therapy (NCFCT). Methods This is a sub-analysis of a retrospective study of 7 Massachusetts acute care hospitals from January 1, 2015, to October 31, 2022. We included hospitalized adults (≥18 years) with Serratia Marcescens bacteremia. IRB approval was obtained. Demographics, clinical course characteristics, and choice of antibiotic therapy were collected. Primary outcome was 30-day mortality, and secondary outcome was composite antimicrobial failure (see Definitions in Table 1). Chi Square and Mann-Whitney U tests were computed using SPSS statistical package. Results The original Carbapenem-Serratia study had 73 out of 128 patients who met the inclusion criteria (Figure 1). The non-carbapenem group (n=56) was further studied for the purpose of this subanalysis and was divided into CFCT (n=15) and NCFCT (n=41). The two subgroups were similar in baseline comorbidities, severity measures, and sources of bacteremia (Table 1). Neither 30-day mortality nor the composite outcome of antimicrobial failure were significantly different with relative risks of 0.94 (95% CI 0.16 to 5.3, P=0.948) and 1.21 (95% CI 0.27 to 5.4, P=0.800), respectively. Study exclusion flow-chart with subanlaysis. ESBL phenotypically defined by ceftriaxone resistance (MIC <1). Characteristics and outcomes of patient with Serratia bacteremia treated with a cefepime versus non-cefepime nor carbapenem therapy regimen. * Immunocompromised patients are those receiving immunosuppressants, chemotherapy, or transplants, having HIV with CD4+ T cell count <200 cells/mm3, neutropenia with ANC < 500 cells/mm3, or corticosteroid use with prednisone or equivalent >10 mg for ≥ 14 days. † Hospital-acquired bacteremia is diagnosed when a positive blood culture obtained from patients hospitalized for 48 hours or longer. Healthcare-associated bacteremia was defined as a positive blood culture is obtained within 48 hours of hospital admission and the patient fulfills specific pre-defined criteria utilized in prior studies. Community-acquired bacteremia refers to positive a blood culture obtained within 48 hours after hospital admission in patients who do not fit the criteria for healthcare-associated infections. ‡ Deep seated complicated infection included Infective endocarditis, septic arthritis, osteomyelitis, or epidural abscess § Empiric antibiotic therapy: Antibiotics administered before antimicrobial susceptibility testing (AST) results, with a minimum 48-hour of uninterrupted duration and appropriate dosing. || Definitive antibiotic therapy (i.e., antibiotics administered after the AST results, also with a minimum of 48-hour duration). ¶ Duration of total definitive antibiotic therapy was counted from day of AST results until last day of definitive antimicrobial therapy. # Microbiological failure, microbiological relapse, in- hospital mortality, 30-day mortality, infection-related hospital readmission, or recurrent Serratia bateremia within 30 days. Microbiological failure refers to the growth of Serratia after 48 hours of definitive antibiotic therapy, while microbiological relapse is the regrowth of Serratia after a negative blood culture (Kunz Coyne et al., 2023). Note: Two patients had recurrence of Serratia bacteremia within 30 days, neither were resistant to third generation cephalosporins. Δ Infection-related re-admission was defined when a patient is readmitted not solely for a procedure or surgery, and they experience fever, worsening leukocytosis, or required escalation of antimicrobial therapy from the definitive therapy of the index admission. Conclusion Averting cefepime in the antimicrobial therapy of Serratia bacteremia is not associated with a significant increase in 30-day mortality or the composite outcome of antimicrobial failure. When applicable, a narrower beta-lactam therapy such as ceftriaxone may be appropriate. Limitations include a small sample size, with higher risk for type II error, and overlap in definitive antibiotic therapy. Further prospective studies are needed to confirm these findings, especially in patients with deep-seated infections. Disclosures All Authors: No reported disclosures

Pulmonary sequestration is a rare congenital condition. It is a dysplastic lung tissue with a separate systemic blood supply and without a bronchial tree connection. The emergence of a superimposed infection can lead to its diagnosis, such as Staphylococcus aureus, Pseudomonas aeruginosa, Nocardia asteroids and Aspergillus sp . pneumonia. Mycobacterium avium complex (MAC) superimposed disease is exceedingly rare. We report a case of a man in his third decade without known medical disorders presenting with a persistent cough. After an extensive microbiological workup, an MAC infection was diagnosed. An elevated carbohydrate antigen 19-9 (CA 19-9) was also noted. He was treated with antimycobacterial therapy and lobectomy resulting in clinical improvement and CA19-9 normalisation. This case illustrates the value of comprehensive microbiological investigations in patients with chronic respiratory symptoms and imaging findings that are not typical of bacterial pneumonia. Clinical studies remain needed to investigate the utility of CA 19-9 in a scoring system to guide MAC therapy.