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BACKGROUND: Due to the ongoing opioid epidemic in the United States, deceased organ donors increasingly have a history of injection drug use (IDU), raising concerns about infectious risks to solid organ transplant (SOT) recipients. We sought to determine how recent IDU among deceased organ donors impacted donor culture results and recipient outcomes. METHODS: A retrospective cohort study was performed at three transplant centers. Exposed donors were those with “recent IDU” (in the prior 12 months). Primary outcomes included (1) positive donor cultures for bacteria or Candida species, (2) recipient bacterial or Candida infection within 3 months posttransplant, and (3) recipient graft failure or death within 12 months posttransplant. Mixed effects multivariable regression models were used to evaluate the relationship between recent donor IDU and each outcome. RESULTS: A total of 658 SOT recipients who received organs from 394 donors were included. Sixty-six (17%) donors had a history of recent IDU. Recent IDU in donors was associated with a significantly increased odds of donor culture positivity (aOR 3.65, 95% CI 1.06–12.60, p = .04) but was not associated with SOT recipient infection (aHR 0.98, 95% CI 0.71–1.36, p = .92) or graft failure or death (aHR 0.67, 95% CI 0.29–1.51, p = .33). CONCLUSION: Donors with recent IDU are more likely to have positive cultures, but their recipients’ outcomes are unaffected, suggesting organs from donors with recent IDU may be safely utilized.

The extent to which donor multidrug-resistant organisms (MDROs) affect organ utilization remains unclear. We performed a retrospective cohort study at 4 transplant centers between 2015 and 2016 to evaluate this question. All deceased donors who donated at least one organ were included. Exposed donors had at least one MDRO on culture. Unexposed donors had no MDRO-positive cultures. Only cultures obtained during the donor's terminal hospitalization were evaluated. Multivariable regression was used to determine the association between donor MDRO and (1) number of organs transplanted per donor and (2) the match run at which each organ was accepted. Subsequently, we restricted the analysis to donors with MDR-Gram-negative (GN) organisms. Of 440 total donors, 29 (7%) donors grew MDROs and 7 (2%) grew MDR-GNs. There was no significant association between donor MDRO and either measure of organ utilization. However, donor MDR-GNs were associated with a significant reduction in the number of organs transplanted per donor (incidence rate ratio 0.43, 95% confidence interval [CI] 0.39-0.48, P < .01), and organs were accepted significantly further down the match list (relative count 5.08, 95% CI 1.64-15.68, P = .01). Though donor MDR-GNs were infrequent in our study, their growing prevalence could meaningfully reduce the donor pool over time.

Donor infection or colonization with a multidrug-resistant organism (MDRO) affects organ utilization and recipient antibiotic management. Approaches to identifying donors at risk of carrying MDROs are unknown. We sought to determine the risk factors for MDROs among transplant donors. A multicenter retrospective cohort study was conducted at four transplant centers between 2015 and 2016. All deceased donors who donated at least one organ were included. Cultures obtained during the donor's terminal hospitalization and organ procurement were evaluated. The primary outcome was isolation of an MDRO on culture. Multivariable Cox regression was used to determine risk factors associated with time to donor MDRO. Of 440 total donors, 64 (15%) donors grew an MDRO on culture. Predictors of an MDRO on donor culture included hepatitis C viremia (hazard ratio [HR] 4.09, 95% confidence interval [CI] 1.71-9.78, P = .002), need for dialysis (HR 4.59, 95% CI 1.09-19.21, P = .037), prior hematopoietic cell transplant (HR 7.57, 95% CI 1.03-55.75, P = .047), and exposure to antibiotics with a narrow gram-negative spectrum (HR 1.13, 95% CI 1.00-1.27, P = .045). This is the first study to determine risk factors for MDROs among deceased donors and will be important for risk stratifying potential donors and informing transplant recipient prophylaxis.

Antibiotic use in deceased organ donors has not been previously described. In a retrospective cohort of 440 donors, we found 427 (97%) received at least one antibiotic course, 312 (71%) received broad-spectrum antibiotics, and 61 (14%) received potentially redundant antibiotics during their terminal hospitalization, suggesting a need for stewardship.

Background With the ongoing opioid epidemic in the US, there has been an increase in the proportion of deceased organ donors with a history of injection drug use (IDU), raising concern for additional infectious risks to transplantation.We sought to determine how recent IDU among deceased organ donors impacted donor culture results. Methods A retrospective cohort study was conducted at four transplant centers in Philadelphia between 1/1/2015 and 6/30/2016. All deceased organ donors who donated ≥ 1 organ to one of the centers were included. Exposed donors were those with a recent history of IDU (defined by use in the prior 12 months based on donor chart review). Unexposed donors were those with no recent history of IDU. The primary outcome was any positive donor culture (taken during the terminal hospitalization or at the time of organ procurement) for bacteria or Candida. Multivariable logistic regression was used to determine the association between recent IDU and donor culture positivity. Secondarily, the association between donor IDU and isolation of (1) a multidrug-resistant organism (MDRO) on culture, (2) Staphylococcus aureus on culture, (3) Candida on non-respiratory culture, and (4) bacteria or Candida on blood culture were determined. Results Of 394 total donors, 66 (17%) had a history of recent IDU and 343 (87%) had at least one positive donor culture. On multivariable analysis, recent IDU was associated with significantly increased odds of having at least one positive donor culture (aOR 3.6, 95% CI 1.1-11.9, P=0.04) and Candida on non-respiratory culture (aOR 2.6, 95% CI 1.1-6.2, P=0.03). However, recent IDU was not significantly associated with increased odds of MDRO on culture (OR 0.90, 95% CI 0.41-1.93, P=0.79), S. aureus on culture (OR 1.35, 95% CI 0.79-2.28, P=0.27), or positive blood culture (OR 0.79, 95% CI 0.32-1.95, P=0.60). Conclusion Donors with a recent history of IDU are more likely to have bacteria or Candida identified on cultures taken during their terminal hospitalization or at organ procurement. This increase does not appear to be driven by MDROs, S. aureus, or bloodstream infections but rather by Candida isolated from non-respiratory sites, potentially alleviating some fears surrounding the acceptance of solid organs from donors with a history of recent IDU. Disclosures Ebbing Lautenbach, MD, MPH, MSCE, Merck (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB)) Emily Blumberg, MD, Amplyx (Other Financial or Material Support, Member of Data and Safety Monitoring Board (DSMB))Hologic (Research Grant or Support)Merck (Grant/Research Support, Other Financial or Material Support, Member of Scientific Advisory Committee)Takeda (Research Grant or Support, Other Financial or Material Support, Member of Scientific Advisory Committee) Jennifer Han, MD, MSCE, GlaxoSmithKline (Employee, Shareholder) Judith A. Anesi, MD, MSCE, Nothing to disclose

Background Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections. Methods Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes. Results Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38). Conclusions Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

Background Multidrug-resistant Pseudomonas aeruginosa infections remain common in hospitals worldwide. We investigated the outcomes associated with the use of ceftolozane-tazobactam for the treatment of these infections. Methods Data were collected retrospectively from 20 hospitals across the United States about adults who received ceftolozane-tazobactam for the treatment of multidrug-resistant P aeruginosa infections of any source for at least 24 hours. The primary outcome was a composite of 30-day and inpatient mortality, and secondary outcomes were clinical success and microbiological cure. Multivariable regression analysis was conducted to determine factors associated with outcomes. Results Two-hundred five patients were included in the study. Severe illness and high degrees of comorbidity were common, with median Acute Physiology and Chronic Health Evaluation (APACHE) II scores of 19 (interquartile range [IQR], 11–24) and median Charlson Comorbidity Indexes of 4 (IQR, 3–6). Delayed initiation of ceftolozane-tazobactam was common with therapy started a median of 9 days after culture collection. Fifty-nine percent of patients had pneumonia. On susceptibility testing, 125 of 139 (89.9%) isolates were susceptible to ceftolozane-tazobactam. Mortality occurred in 39 patients (19%); clinical success and microbiological cure were 151 (73.7%) and 145 (70.7%), respectively. On multivariable regression analysis, starting ceftolozane-tazobactam within 4 days of culture collection was associated with survival (adjusted odds ratio [OR], 5.55; 95% confidence interval [CI], 2.14–14.40), clinical success (adjusted OR, 2.93; 95% CI, 1.40–6.10), and microbiological cure (adjusted OR, 2.59; 95% CI, 1.24–5.38). Conclusions Ceftolozane-tazobactam appeared to be effective in the treatment of multidrug-resistant P aeruginosa infections, particularly when initiated early after the onset of infection.

Background Ceftolozane/tazobactam (TOL-TAZ) is a novel cephalosporin antibiotic combined with a known β-lactamase inhibitor. It has activity against some extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and multidrug-resistant Pseudomonas aeruginosa (MDRPA). To date, little experience has been published on outcomes with TOL-TAZ for MDRPA infections in immunocompromised patients. Methods This was a retrospective study of adult patients (≥18 years) with an immunocompromising condition (solid-organ transplant; hematologic malignancy; solid tumors; metastatic cancer) at 20 academic medical centers who had microbiologically confirmed MDRPA isolated in culture and received TOL-TAZ for at least 24 hours. 30-day survival, in-hospital mortality, and the rates of microbiologic and clinical cure were assessed. Results Characteristic Result (N = 65) Immunocompromising condition:Solid-organ transplantSolid tumorLeukemiaLymphoma/multiple myelomaMetastatic cancer n(%)35 (53.8)20 (30.7)4 (6.1)3 (4.6)3 (4.6) Male, n(%) 38 (58.4) Age (median, IQR) 64 (20–87) Charlson Comorbidity Index (median, IQR) 6 (1–12) APACHE II score (median, IQR) 20 (4–41) ICU, n(%) 37(56.9) Hospital day index infection diagnosed (median, IQR) 17 (0–265) Hospital day TOL-TAZ started (median, IQR) 19 (0–284) 3grs q8hrs, n(%)1.5grs q8hrs, n(%) 23 (35.3)23 (35.3) Concomitant IV antibiotics, n(%)Aminoglycoside, n/N(%)Fluoroquinolone, n/N(%)Polymyxin, n/N(%)Β-lactam, n/N(%) 15 (23.0)7/15 (46.7)4/15 (26.7)3/15 (20)1/15 (6.6) TOL-TAZ susceptible isolates, n/N (%) 35/37 (94.6) Outcomes by primary infection Primary infection n (%) 30-day survival n/N(%) Microbiologic cure n/N(%) Clinical cure n/N(%) Pneumonia 33 (50.7) 30/33 (90.9) 24/33 (72.7) 28/33 (84.8) Wound/Bone/Joint 12 (18.4) 8/12 (66.6) 7/12 (58.3) 7/12 (58.3) UTI 9 (13.8) 7/9 (77.7) 7/9 (77.7) 8/9 (88.8) Intra-abdominal 7 (10.7) 7/7 (100) 7/7 (100) 4/7 (57.1) Bloodstream 4 (6.1) 4/4 (100) 4/4 (100) 4/4 (100) Overall outcomes, n(%) 30-day survival 56 (86.1) In-hospital mortality 17 (26.1) Microbiologic cure 49 (75.3) Clinical cure 51(78.4) Conclusion In this study of 65 critically-ill immunocompromised patients, the 30-day survival was 86.1%; clinical cure was78.4% and microbiologic cure 75.3%. TOL-TAZ is a viable option for immunocompromised patients with MDRPA infections. Disclosures J. Gallagher, Achaogen: Consultant, Consulting fee. Merck: Consultant, Grant Investigator and Speaker’s Bureau, Consulting fee and Research grant. Allergan: Consultant and Speaker’s Bureau, Consulting fee. Astellas: Consultant and Speaker’s Bureau, Consulting fee. Cempra: Consultant, Consulting fee. Cidara: Consultant, Consulting fee. CutisPharma: Consultant, Consulting fee. Paratek: Consultant, Consulting fee. Shionogi: Consultant, Consulting fee. Tetraphase: Consultant, Consulting fee. Theravance: Consultant, Consulting fee. The Medicines Company: Consultant, Consulting fee. Melinta: Speaker’s Bureau, Consulting fee.

Background Ceftolozane-tazobactam (TOL-TAZ) is a novel cephalosporin/β-lactamase inhibitor combination with potent activity against Pseudomonas aeruginosa, including MDRPA. TOL-TAZ use for MDRPA infections has not been well-studied. Methods We conducted a retrospective study to describe outcomes of patients treated with TOL-TAZ for MDR Pseudomonas aeruginosa infections at 3 academic medical centers. Patients were age ≥ 18 years who had MDRPA isolated in culture and received TOL-TAZ for at least 24 hours. The primary outcomes were 30-day and in-hospital mortality. Secondary outcomes were microbiological cure and clinical success. Microbiological cure was defined as negative culture at end of therapy; cure was presumed when clinical success occurred without follow-up cultures. Clinical success was defined as resolution of all signs and symptoms of infection. TOL-TAZ susceptibility results were collected when available. Results Characteristics Results (N = 34) Male gender, n(%)21 (61.8)Age (median, IQR)57 (42-66)Charlson Comorbidity Index (median, IQR)4 (2.25-5)APACHE II score (median, IQR)20 (13-26.8)ICU, n(%)23 (67.7)Solid organ transplant recipient, n(%)15 (44.1)Primary infection, n(%)Pneumonia22 (64.7)Bacteremia6 (17.6)Urinary tract4 (11.8)Wound4 (11.8)Intra-abdominal2 (5.8)Hospital day index infection diagnosed (median, IQR)8 (1-35)Hospital day TOL-TAZ started (median, IQR)18.5 (3-52)Patients receiving concomitant therapy for index pathogen, n(%)20 (58.8)Isolates susceptible to TOL-TAZ, n/N (%)16/17 (94)30-day mortality, n (%)7 (20.6)In-hospital mortality, n(%)8 (23.5)Microbiologic cure, n(%)21 (61.8)Clinical success, n(%)24 (70.6) Conclusion In this severely ill population with MDRPA infections, 79.4% and 76.5% of patients were alive at 30-days and at the end of their stay, respectively. Some patients had positive cultures despite clinical resolution. TOL-TAZ is a potential option for patients with MDRPA infections. Disclosures E. Molnar, Merck: Grant Investigator, Research grant. J. Gallagher, Merck: Consultant, Grant Investigator, Scientific Advisor and Speaker’s Bureau, Consulting fee, Educational grant and Speaker honorarium. Allergan: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. Astellas: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium. Achaogen: Scientific Advisor, Consulting fee. Cidara: Consultant, Consulting fee. Theravance: Scientific Advisor, Consulting fee. Paratek: Scientific Advisor, Consulting fee. The Medicines Company: Scientific Advisor, Consulting fee.

inTroDucTion Fibrosing mediastinitis (FM) is a rare disease of slowly progressive fibrosis that encases major mediastinal structures. Complications include obstruction of mediastinal vasculature, including main pulmonary arter ies, which may lead to l i fe-threatening hemodynamic compromise. In North America, the disease is usually a sequela of histoplasmosis. Because Histoplasma capsulatum (H. capsulatum) is found in the Ohio River Valley, physicians in Pennsylvania must be able to recognize and diagnose the disease.