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Abstract Background Multi-drug resistant (MDR) pathogens are a continuously evolving threat for which there are limited effective treatment modalities. Omadacycline (OMC) is a novel oral and intravenously administered aminomethylcycline with potent in-vitro activity against MDR gram-negative and gram-positive pathogens. Post-marketing data investigating its potential place in the antibiotic armamentarium is limited. This study aimed at describing the clinical success and tolerability of patients receiving OMC for various infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to March 30, 2022. We included all patients ≥ 18 years of age that received OMC for any infection not related to Mycobacterium spp. for ≥72 hours. The primary outcome was clinical success at 30 days, defined as survival, the absence of persistence or re-emergence of infection during or after therapy, and the absence of escalation or alteration of OMC. Incidence of adverse effects while on OMC and reasons for OMC utilization were also analyzed. Results This analysis included 19 patients from 10 distinct academic centers. The median age was 50 years (IQR, 37-63), 58% were male, 63% were Caucasian, and the median APACHE II, Charlson and SOFA scores were 10 (IQR 5-12.5), 4 (IQR 2-6.3), and 1 (IQR 0 – 2.25), respectively. Most patients had a bone and joint (8/19, 42.1%) or intra-abdominal infections (4/19, 21.1%), all with positive cultures. Eight patients (44.1%) had a polymicrobial infection and 4 (22.2%) had bacteremia. The most common pathogens encountered were Carbapenem-resistant A. baumannii (5/19, 27.8%), E. coli (5/19, 27.8%), Vancomycin-resistant Enterococcus spp. (4/19, 22.2%), and K. pneumoniae (3/19, 16.7%). Clinical success was observed in 14 patients (74%) and 7 (36.8%) received combination therapy. Adverse drug reactions were reported in 3 patients (15.8%) and of those patients, none discontinued therapy. Reasons for prescribing OMC were mostly attributed to oral availability (12/14, 85.7%) and resistance to other agents (7/14, 50%). Conclusion OMC demonstrated clinical effectiveness and safety against a large number of MDR pathogens. More robust, prospective, comparative studies are needed to confirm our preliminary findings. Disclosures P. Brandon Bookstaver, PharmD, Spero Therapeutics: Advisor/Consultant.

A 68-year-old man with a history of keratoconus was referred for evaluation of a choroidal lesion in his left eye. Fundus autofluorescence demonstrated hyperautofluorescence in a leopard-spotting pattern. What would you do next?

Background: Common bile duct (CBD) stones associated with cholecystitis can be treated by single-stage CBD exploration at the time of cholecystectomy or a two-stage approach with endoscopic stone extraction before or after cholecystectomy. The ideal management remains a matter of debate. The aim of this study is to analyze our outcomes with transcystic laparoscopic common bile duct exploration (LCBDE). Material and Methods: A retrospective review of patients who underwent transcystic LCBDE between 2015 and 2019 was performed. Results: A total of 106 patients underwent transcystic LCBDE over 5 years. We performed 1192 laparoscopic cholecystectomies with cholangiograms from March 2015 to December 2019. Fifteen patients had a preoperative endoscopic retrograde cholangiopancreatography (ERCP) for CBD stones seen on magnetic resonance cholangiopancreatography that during laparoscopic cholecystectomy with intraoperative cholangiogram (IOC), there were stones and/or sludge found in the CBD, which required clearance through a transcystic approach. Of the 91 patients who did not have a preoperative ERCP, clearance of the CBD was successful through a transcystic approach in 78 patients (86%). In the 13 patients that intraoperative clearance was not achieved ( n = 13, 14%), a postoperative ERCP was performed. A total of 28 patients underwent either pre- or postoperative ERCP ( n = 28, 26%). Choledochotomy was not performed in any of the patients. The mean operative time was 127 minutes (127 ± 48). The mean hospital length of stay (LOS) was 4 days (3.9 ± 2.8) with a median LOS of 3 days. Complications observed include wound infection ( n = 2, 2%), pancreatitis after ERCP ( n = 1, 1%), pneumonia ( n = 1, 1%), and right hepatic duct injury ( n = 1, 1%). Conclusion: Transcystic LCBDE is an effective and safe option for treatment of CBD stones. While a transcystic approach does not guarantee clearance of the CBD, it avoids the morbidity associated with a choledochotomy and can often prevent patients from having to undergo an additional procedure.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701