1282. Ceftolozane/Tazobactam Use in Critically Ill Patients Receiving Intermittent or Continuous Renal Replacement Therapy

Background Our hospital recommends ceftolozane/tazobactam (CT) as a broad-spectrum agent for treatment of Gram-negative bacilli in patients with a recent or current multidrug resistant (MDR) Pseudomonas infection. CT is utilized in patients who are on renal replacement therapy (RRT) yet little data exist on the efficacy in this population. Currently there are no FDA-approved dosing recommendations for patients on continuous veno-venous hemodialysis (CVVHD). The purpose of this study was to describe the indications, dosing and outcomes of patients on CT while receiving RRT. Methods All patients receiving CT from 2015-20 were included if on RRT, either CVVHD or intermittent hemodialysis (iHD). Clinical success was defined as the absence of pre-treatment signs/symptoms and/or no escalated antibiotic treatment within 48 hours of completing therapy. 30-day mortality was defined as death from any cause within 30 days of CT completion. Patients treated after 2019 approval of higher dosing for hospital-associated/ventilator-acquired pneumonia (HAP/VAP) were noted. Results 17 patients received 24 courses of CT while on RRT, 9 (53%) were immunocompromised. All patients were treated in the ICU for an MDR Pseudomonas infection. As shown in table 1, the most common indications were 49% HAP/VAP, 17% complicated intra-abdominal (cIAI), or 17% urinary tract infections (cUTI). 4 (24%) patients had additional treatment courses of CT started empirically when infection was suspected. Median time to initiation for all courses was 2 days after obtaining cultures and median duration was 7 days. 12 patients were on CVVHD (median flow rate 2.5L/hr) and 7 were on iHD. 2 patients received iHD after CVVHD. Median dose while on CVVHD was 1500mg every 8 hours. The median dose on iHD was that approved by FDA for cIAI and cUTI: 750mg x1 followed by 150mg every 8 hours. Clinical success was achieved in 12 (71%) patients and 30-day mortality was 8 (47%). Table 1: Details on first courses of CT for patients on RRT *Denotes treatment after 2019 FDA approval of 3g q8h for treatment of HAP/VAP in patients with normal renal function **Flow rate: Medium 1.5-2L/hr; High: >2.5L/hr +NA denotes patient that had passed away and therefore additional C/T courses were not applicable Conclusion This case series provides real-world results of outcomes for critically ill patients on RRT treated with CT. Clinical success rates were similar to other published literature despite the severity of illness of this cohort, which is corroborated by the high 30 day, all-cause mortality. Ultimately, further evaluation of CT dosing in patients on RRT is warranted. Disclosures Laura A. Puzniak, PhD, Merck & Co., Inc. (Employee) Kelly Harris, PharmD, BCPS, Merck & Co. Inc (Employee) Trevor C. Van Schooneveld, MD, FACP, BioFire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Insmed (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Scientific Research Study Investigator; Rebiotix (Individual(s) Involved: Self): Scientific Research Study Investigator Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Grant/Research Support) Scott J. Bergman, PharmD, FCCP, FIDSA, BCPS, BCIDP, Merck & Co., Inc (Individual(s) Involved: Self): Research Grant or Support

Pseudoaneurysm of the ascending aorta: case report of a donor-derived Pseudomonas infection in a heart transplant recipient

Background Mycotic aortic pseudoaneurysm is a rare complication after heart transplantation (HTX) with remarkable mortality. Intrathoracic infection is a well-documented predisposing factor for this disease. Staphylococcus aureus, Pseudomonas aeruginosa or Candida species are commonly isolated from resected specimens of the pseudoaneurysms. We demonstrate a unique case of mycotic pseudoaneurysm caused by presumably donor-derived Pseudomonas infection in a heart transplant recipient. Case presentation Our 67-year-old male patient treated with diabetes mellitus underwent HTX. The donor suffered from epiglottic abscess and pneumonia with known microorganisms including Pseudomonas, therefore both the donor and recipient received targeted antimicrobial therapy and prophylaxis. Five months after the uneventful HTX, lab test of the asymptomatic patient showed moderate, increasing C-reactive protein level without obviuos source of infection. Chest computed tomography showed a large (90 mm) saccular dilatation of the tubular portion of ascending aorta. Urgent surgical intervention identified a pseudoaneurysm, histological examinations and cultures of the resected aorta verified Pseudomonas aeruginosa aortitis, while all blood cultures remained negative. Retrospective interrogation of other transplanted organs of the donor supported donor-derived infection as the transport fluid of the right kidney grew Pseudomonas. The patient received 3 weeks of ceftazidime followed by 7 months of oral ciprofloxacin therapy. One year after the operation the patient was asymptomatic with normal inflammatory markers. Conclusions Donor-derived infection is a rare but potential cause of aortitis. Early diagnosis, surgical intervention and adjuvant antibiotic therapy seem to be the keys to successful management of mycotic pseudoaneurysms after HTX.

The role of Psl in the failure to eradicate Pseudomonas aeruginosa biofilms in children with cystic fibrosis

The exopolysaccharide Psl contributes to biofilm structure and antibiotic tolerance and may play a role in the failure to eradicate Pseudomonas aeruginosa from cystic fibrosis (CF) airways. The study objective was to determine whether there were any differences in Psl in P. aeruginosa isolates that were successfully eradicated compared to those that persisted, despite inhaled tobramycin treatment, in children with CF. Initial P. aeruginosa isolates were collected from children with CF undergoing eradication treatment, grown as biofilms and labeled with 3 anti-Psl monoclonal antibodies (Cam003/Psl0096, WapR001, WapR016) before confocal microscopy visualization. When grown as biofilms, P. aeruginosa isolates from children who failed antibiotic eradication therapy, had significantly increased Psl0096 binding compared to isolates from those who cleared P. aeruginosa. This was confirmed in P. aeruginosa isolates from the SickKids Eradication Cohort as well as the Early Pseudomonas Infection Control (EPIC) trial. Increased anti-Psl antibody binding was associated with bacterial aggregation and tobramycin tolerance. The biofilm matrix represents a potential therapeutic target to improve P. aeruginosa eradication treatment.

Therapeutic Approach of Chronic Pseudomonas Infection in Cystic Fibrosis—A Network Meta-Analysis

Pseudomonas infection is a major determinant of morbidity and mortality in cystic fibrosis (CF). Maintaining optimal lung function in CF patients carrying Pseudomonas remains a challenge. Our study aims to investigate the efficacy of antipseudomonal inhaled antibiotics in CF patients with chronic Pseudomonas infection. A Bayesian network meta-analysis of randomized controlled trials was conducted. The main outcomes were changes in: (a) forced respiratory volume (FEV1), (B) Pseudomonas aeruginosa sputum density, and (c) CF Questionnaire Revised Respiratory Symptom Score (CFQR-RSS) at 4 weeks follow-up. Eighteen trials which reported on treatment with aztreonam lysine, tobramycin, colistin, levofloxacin, fosfomycin/tobramycin, and amikacin in various dosages were eligible for inclusion. In terms of change in FEV1%, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 77, 76%, respectively). Regarding change in Pseudomonas sputum density, aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin phase, aztreonam lysine (t.i.d., 75 mg) with a 28-day run in the tobramycin phase had the highest probability of being the most effective treatment (SUCRAs were 90, 86%, respectively). Regarding change in CFQR-RSS, aztreonam lysine (t.i.d., 75 mg) and aztreonam lysine (b.i.d., 75 mg) with a 28-day run in the tobramycin inhalation solution phase had the highest probability of being the most effective treatments (SUCRA:74% and 72%, respectively). Regarding changes in FEV1% and Pseudomonas sputum density, aztreonam lysine with a run in tobramycin phase may be the best treatment option in treating chronic Pseudomonas in CF. According to CFQR-RSS no significant differences were found. Given the limitations of the studies included, validation trials are called for.

Pseudomonas-Contaminated Pool Triggering an Episode of Idiopathic Palmoplantar Hidradenitis

Idiopathic palmoplantar hidradenitis (IPPH) is a disorder that mainly affects the palms and soles of children. Although many cases have been reported to occur after recreational swimming activities, whether IPPH is caused by intense physical activity or by Pseudomonas infection has yet to be proven. We report a case of a 3-year-old girl who presented with IPPH after swimming in a pool with evidence of <i>P. aeruginosa</i> contamination, further solidifying the association between Pseudomonas and IPPH.

Case Report of Disseminated Pseudomonas Infection with Superadded Burkholderia Infection - A Battle Lost!

Pseudomonas aeruginosa is a gram-negative pathogen, that often causes nosocomial pneumonia in hospitalized patients. Most of these patients have risk factors for pseudomonas infection. Although uncommon, there have been case reports of previously healthy individuals who developed community-acquired pneumonia (CAP) caused by P. aeruginosa. Such cases have often rapidly progressive course and prove fatal. We, hereby, report a case of pseudomonas pneumonia in a 29-year old immunocompetent patient, who developed disseminated infection and superinfection with yet another nosocomial pathogen, Burkholderia cepacia, eventually leading to septic shock and death, despite appropriate antibiotic therapy.