POEM, GPOEM, and ZPOEM.

Our tripartite narrative review discusses Peroral Endoscopic Myotomy (POEM), gastric POEM (GPOEM) and POEM for Zenker's diverticula (ZPOEM). POEM is the prototypical procedure that launched the novel "3rd space endoscopy" field of advanced endoscopy. It revolutionized achalasia therapy by offering a much less invasive version of the prior gold standard, the laparoscopic Heller myotomy (HM). We review in detail indications, outcomes, technique variations and comparative data between POEM and HM particularly with regard to the hotly debated issue of GERD. We then proceed to discuss two less illustrious but nevertheless important offshoots of the iconic POEM procedure: GPOEM for gastroparesis and ZPOEM for the treatment of hypopharyngeal diverticula. For GPOEM, we discuss the rationale of pylorus-directed therapies, briefly touch on GPOEM technique variations and then focus on the importance of proper patient selection and emerging data in this area. On the third and final part of our review, we discuss ZPOEM and expound on technique variations including our "ultra-short tunnel technique". Our review emphasizes that, despite the superiority of endoscopy over surgery for the treatment of hypopharyngeal diverticula, there is no clear evidence yet of the superiority of the newfangled ZPOEM technique compared to the conventional endoscopic myotomy technique practiced for over two decades prior to the advent of ZPOEM.

Learning Curve for Endoscopic Submucosal Dissection With an Untutored, Prevalence-Based Approach in the United States.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is widely used in Asia to resect early-stage gastrointestinal neoplasms, but use of ESD in Western countries is limited. We collected data on the learning curve for ESD at a high-volume referral center in the United States to guide development of training programs in the Americas and Europe. METHODS: We performed a retrospective analysis of consecutive ESDs performed by a single operator at a high-volume referral center in the United States from 2009 through 2017. ESD was performed in 540 lesions: 449 mucosal (10% esophageal, 13% gastric, 5% duodenal, 62% colonic, and 10% rectal) and 91 submucosal. We estimated case volumes required to achieve accepted proficiency benchmarks (>90% for en bloc resection and >80% for histologic margin-negative (R0) resection) and resection speeds >9cm2/hr. RESULTS: Pathology analysis of mucosal lesions identified 95 carcinomas, 346 premalignant lesions, and 8 others; the rate of en bloc resection increased from 76% in block 1 (50 cases) to a plateau of 98% after block 5 (250 cases). The rate of R0 resection improved from 45% in block 1 to >80% after block 5 (250 cases) and ∼95% after block 8 (400 cases). Based on cumulative sum analysis, approximately 170, 150, and 280 ESDs are required to consistently achieve a resection speed >9cm2/hr in esophagus, stomach, and colon, respectively. CONCLUSIONS: In an analysis of ESDs performed at a large referral center in the United States, we found that an untutored, prevalence-based approach allowed operators to achieve all proficiency benchmarks after ∼250 cases. Compared with Asia, ESD requires more time to learn in the West, where the untutored, prevalence-based approach requires resection of challenging lesions, such as colon lesions and previously manipulated lesions, in early stages of training.

Updated Systematic Review of Achalasia, with a Focus on POEM Therapy.

AIM: To systematically review clinical presentation, diagnosis, and therapy of achalasia, focusing on recent developments in high-resolution esophageal manometry (HREM) for diagnosis and peroral endoscopic myotomy (POEM) for therapy. METHODS: Systematic review of achalasia using computerized literature search via PubMed and Ovid of articles published since 2005 with keywords ("achalasia") AND ("high resolution" or "HREM" or "peroral endoscopic myotomy" or "POEM"). Two authors independently performed literature searches and incorporated articles into this review by consensus according to prospectively determined criteria. RESULTS: Achalasia is an uncommon esophageal motility disorder, usually manifested by dysphagia to solids and liquids, and sometimes manifested by chest pain, regurgitation, and weight loss. Symptoms often suggest more common disorders, such as gastroesophageal reflux disease (GERD), thus often delaying diagnosis. Achalasia is a predominantly idiopathic chronic disease. Diagnosis is typically suggested by barium swallow showing esophageal dilation; absent distal esophageal peristalsis; smoothly tapered narrowing ("bird's beak") at esophagogastric junction; and delayed passage of contrast into stomach. Diagnostic findings at high-resolution esophageal manometry (HREM) include: distal esophageal aperistalsis and integrated relaxation pressure (trough LES pressure during 4 s) > 15 mmHg. Achalasia is classified by HREM into: type 1 classic; type 2 compartmentalized high pressure in esophageal body, and type 3 spastic. This classification impacts therapeutic decisions. Esophagogastroduodenoscopy is required before therapy to assess esophagus and esophagogastric junction and to exclude distal esophageal malignancy. POEM is a revolutionizing achalasia therapy. POEM creates a myotomy via interventional endoscopy. Numerous studies demonstrate that POEM produces comparable, if not superior, results compared to standard laparoscopic Heller myotomy (LHM), as determined by LES pressure, dysphagia frequency, Eckardt score, hospital length of stay, therapy durability, and incidence of GERD. Other therapies, including botulinum toxin injection and pneumatic dilation, have moderately less efficacy and much less durability than POEM. CONCLUSION: This comprehensive review suggests that POEM is equivalent or perhaps superior to LHM for achalasia in terms of cost efficiency, hospital length of stay, and relief of dysphagia, with comparable side effects. The data are, however, not conclusive due to sparse long-term follow-up and lack of randomized comparative clinical trials. POEM therapy is currently limited by a shortage of trained endoscopists.

Spiral enteroscopy-assisted ERCP in bariatric-length Roux-en-Y anatomy: a large single-center series and review of the literature (with video).

BACKGROUND: Deep enteroscopy-assisted ERCP (DEA-ERCP) in post-bariatric Roux-en-Y (RY) anatomy is challenging. Laparoscopy-assisted ERCP (LA-ERCP) and EUS-directed transgastric ERCP (EDGE) are technically easier and faster but are more invasive and morbid procedures. Therefore, we have used DEA-ERCP as our first-line approach, reserving EDGE and LA-ERCP for cases in which adjunctive techniques that cannot be performed through an enteroscope are required (eg, EUS-FNA, sleeve sphincter of Oddi manometry), or DEA-ERCP failures. The 2 main methods for DEA-ERCP are balloon- and spirus-assisted. Current literature on spiral enteroscopy ERCP (SE-ERCP) in bariatric RY anatomy is scant with low success rates reported. Our center has nearly exclusively used SE-ERCP for bariatric patients. Here, we report one of the largest such series to date. METHODS: This is a retrospective cohort study of consecutive patients with bariatric-length RY anatomy who had SE-ERCP from December 2009 to October 2016 at a tertiary care center, by one operator (S.N.S.). Primary outcomes included success at reaching the papilla, cannulation success, success of desired therapeutic intervention, and overall SE-ERCP success. RESULTS: Thirty-five SE-ERCPs were performed (28 in bariatric RY gastric bypass and 7 other long-limb RY surgical reconstructions). The papilla was reached in 86% (30/35) of cases. Cannulation success in patients in whom deep cannulation was indicated (28/30) was 100% (28/28 cases, including the 24 cases with native papilla). Therapeutic ERCP success was 100% (28/28). Overall SE-ERCP success was 86% (30/35). Median length of stay was 3 days. Median procedure time was 189 minutes. Reasons for SE-ERCP failures included RY anastomosis stricture, adhesions (2), long Roux limb, and redundant small bowel. Two of these patients underwent interventional radiology-guided percutaneous biliary drainage, 2 patients had laparoscopy-assisted ERCP, and 1 patient had EUS-guided antegrade cholangioscopy with sphincteroplasty and stone clearance. There were no adverse events. CONCLUSION: With sufficient allotted time (median procedure time ∼3 hours) and high operator experience (a single-operator volume that exceeds that of other published series), SE-ERCP is safe and effective in bariatric, long-limb RY patients with an overall success rate of 86%, which is higher than previously reported.

Per-oral endoscopic myotomy in patients with or without prior Heller's myotomy: comparing long-term outcomes in a large U.S. single-center cohort (with videos).

BACKGROUND AND AIMS: Heller's myotomy (HM) is one of the most effective treatments for esophageal achalasia. However, failures do exist, and the success rate tends to decrease with time. The efficacy of rescue treatments for patients with failed HM is limited. A few small-scale studies have reported outcomes of per-oral endoscopic myotomy (POEM) in these patients. We conducted this study to systematically assess feasibility, safety, and efficacy of POEM on patients who have had HM. METHODS: Patients at least 3 months out from POEM were selected from our prospective database: 318 consecutive POEMs performed from October 2009 to October 2016. The efficacy and safety of POEM were compared between the 46 patients with prior HM and the remaining 272 patients. RESULTS: Patients with prior HM had longer disease history, more advanced disease, more type I and less type II achalasia, lower before-POEM Eckardt scores, and lower before-POEM lower esophageal sphincter (LES) pressure (all P < .01). Procedure parameters and follow-up results (clinical success rate, Eckardt score, LES pressure, GERD score, esophagitis, and pH testing) showed no significant difference between the 2 groups. For the 46 HM-POEM patients, no clinically significant perioperative adverse events occurred. Their overall clinical success rate (Eckardt score ≤3 and no other treatment needed) was 95.7% at a median follow-up of 28 months. CONCLUSION: POEM as a rescue treatment for patients with achalasia who failed HM is feasible, safe, and highly effective. It should be the treatment of choice in managing these challenging cases at centers with a high level of experience with POEM.

Per oral endoscopic myotomy for the treatment of achalasia.

Per oral endoscopic myotomy (POEM) represents the culmination of natural orifice transluminal endoscopic surgery (NOTES) research, and its most successful application to date. Over a thousand POEMs have been performed globally with remarkable results in terms of clinical efficacy and safety. PURPOSE OF REVIEW: We examine the most recent literature concerning POEM since the last two comprehensive analyses [Natural Orifice Surgery Consortium for Assessment and Research (NOSCAR) White Paper, ASGE Preservation and Incorporation of Valuable endoscopic Innovations (PIVI)], and integrate this literature in the consensus POEM guidelines and perspective. These current works are largely centered on POEM operator learning curve, comparison of POEM and laparoscopic Heller myotomy (LHM) and extended application of POEM. RECENT FINDINGS: POEM and LHM are comparable in terms of efficacy (diminished dysphagia and Eckardt score) and complications including GERD. POEM has been successfully performed in a wide variety of patients including children, those with prior achalasia therapy and those with spastic esophageal disorders. SUMMARY: POEM has been validated as a treatment for achalasia. Issues remain regarding its longer term efficacy in comparison with LHM. Subsequent comparison trials are needed. VIDEO ABSTRACT: http://links.lww.com/COG/A14.

The light at the end of the tunnel: a single-operator learning curve analysis for per oral endoscopic myotomy.

BACKGROUND: Per oral endoscopic myotomy (POEM) represents a natural orifice transluminal endoscopic surgery approach to Heller myotomy. Our center was the first to offer POEM outside of Japan, allowing us to accumulate what is likely the highest single-operator POEM volume in the United States. OBJECTIVE: To define the POEM learning curve of a gastroenterologist by using a larger data set and more detailed statistical analysis than used in 2 other reports of POEM performed by surgeons. DESIGN: Prospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: We analyzed the first 93 consecutive POEMs on patients with achalasia aged >18 years without contraindications to POEM performed by a single operator from October 2009 to November 2013. INTERVENTIONS: (1) Efficiency estimation via cumulative sum (CUSUM) analysis, (2) mastery estimation via penalized basis-spline regression and CUSUM analysis, (3) correlation of operator experience with clinical outcomes (Eckardt score improvement, lower esophageal sphincter pressure reduction) and technical errors (accidental mucosotomy rate), and (4) unadjusted and adjusted regression analysis to assess how patient characteristics affected procedure time by using a generalized linear model. MAIN OUTCOME MEASUREMENTS: Clinical outcomes, procedure time, technical errors. RESULTS: Efficiency was attained after 40 POEMs and mastery after 60 POEMs. When we used the adjusted regression analysis, only case number (operator experience) significantly affected procedure time (P < .0001). Improvements in clinical outcomes were excellent but not significantly affected by operator experience, as was the case with accidental mucosotomies. Procedure time was not significantly affected by age, sex, achalasia stage, baseline lower esophageal sphincter pressure, baseline Eckardt score, prior treatment of achalasia, prior botulinum toxin injection, incidence of accidental mucosotomies, length of myotomy, or type of knife used (all P > .05). LIMITATIONS: Our analysis may underestimate the number of POEMs required to achieve mastery for operators with limited or no endoscopic submucosal dissection experience. CONCLUSION: These results offer thresholds for efficiency and mastery of a single gastroenterologist operator that may guide the efforts of novice POEM operators.

The International Per Oral Endoscopic Myotomy Survey (IPOEMS): a snapshot of the global POEM experience.

BACKGROUND: Per oral endoscopic myotomy (POEM) represents a Natural Orifice Transluminal Endoscopic Surgery (NOTES) approach to Heller myotomy. Even though we are now entering an exponential phase of growth with a large number of centers interested in POEM, published data to guide them are limited. As part of the July 2012 NOSCAR meeting, a conference was organized to review POEM and develop a consensus document. Authors SNS and TS who chaired the NOSCAR panel recognized the dearth of published data, which also may lag the rapid developments in POEM. Therefore, they undertook a survey of early POEM adopters around the world to rapidly obtain global, extensive, and current data on POEM. The raw survey data were made available to NOSCAR panel participants to assist with their presentations. We summarize the salient findings of the survey. METHODS: A comprehensive POEM survey was created and tested. The final survey instrument consisted of 197 questions that covered all aspects of POEM, including operator discipline, prior training, patient selection, setting, technique preference, results, adverse events, regulatory requirements, and perspectives on the future. An automated online response collector was used. RESULTS: The International Per Oral Endoscopic Myotomy Survey (IPOEMS) involved 16 expert centers, 7 in North America, 5 in Asia, 4 in Europe, including all high-volume centers (≥30 POEMs per center), as of July 2012. These centers had performed 841 POEMs. There were modest variations among centers in technique and periprocedural management, but all centers uniformly reported excellent efficacy and safety outcomes. CONCLUSIONS: The international POEM survey provides a "global snapshot" of the experience of early adopters. The excellent outcomes over a large cumulative volume of procedures are in line with those of published small series and lend further support to the notion that POEM represents a paradigm shift in the treatment of achalasia.

Unmet needs in Barret's esophagus diagnosis and treatment: a narrative review.

Background and Objective: This narrative review discusses Barrett's esophagus management in the context of perceived deficiencies or controversies. Barrett's adenocarcinoma incidence has not clearly been impacted by Barrett's screening and surveillance. Methods: The following report was derived from articles using PubMed and Google searches. The search was concentrated on Barrett's esophagus screening and management guidelines. Key Content and Findings: Comprehensive literature searches that highlight potential deficiencies or controversies regarding the current approach to Barrett's esophagus were employed. Esophageal adenocarcinoma incidence is rapidly increasing and this malignancy usually presents in an advanced and unresectable state. This is despite the significant expenditure of resources and time in endoscopic screening for and surveillance of Barrett's esophagus. Thus, more widespread screening for Barrett's esophagus may be considered. In addition, there are apparent inefficiencies and precision lack in the performance of endoscopic surveillance. This relates mainly to the lack of endoscopic cues for dysplasia. On the other hand, relatively low-risk subjects have frequent screening or surveillance procedures increasing cost. Lastly, endoscopic ablation for Barrett's with dysplasia has moderately good efficacy, especially for eradication of dysplasia, but mandates intensive post-therapy endoscopic surveillance. There is some concern for subsurface development of advanced Barrett's lesions. Fortunately, there is intense research in improving Barrett's esophagus diagnosis and treatment. Our narrative review will delineate deficiencies and potential measures to remedy them. Conclusions: In conclusion, screening for Barrett's esophagus and surveillance in Barrett's subjects have minimal established benefits, but proposed changes in screening practices and innovations in Barrett's esophagus endoscopic surveillance and dysplasia therapy have great promise.

Peroral endoscopic myotomy for achalasia.

Peroral endoscopic myotomy (POEM) for achalasia (sometimes also referred as E-POEM to distinguish it from its offshoots such as G-POEM for gastroparesis or Z-POEM for Zenker's diverticula) is the newest treatment modality but has already been well validated as a standard intervention for esophageal achalasia. POEM was conceived as a natural orifice transluminal endoscopic surgery (NOTES) procedure with an incisionless, endoscopic approach to myotomy. It matches or exceeds the efficacy of its surgical counterpart, the laparoscopic Heller myotomy, with superiority for type III (spastic) achalasia. However, there are issues, especially regarding GERD after POEM that will likely result in further refinements of technique and post-procedural care. We will summarize the current status of POEM including description of technique variations and review of comparative data vis a vis Heller myotomy (HM) and pneumatic dilation (PD) and we will delve into some of the seminal issues around GERD assessment, management and prevention.

Diarrhea and Coronavirus Disease 2019 Infection.

The global coronavirus disease-2019 (COVID-19) pandemic has caused significant morbidity and mortality, thoroughly affected daily living, and caused severe economic disruption throughout the world. Pulmonary symptoms predominate and account for most of the associated morbidity and mortality. However, extrapulmonary manifestations are common in COVID-19 infections, including gastrointestinal (GI) symptoms, such as diarrhea. Diarrhea affects approximately 10% to 20% of COVID-19 patients. Diarrhea can occasionally be the presenting and only COVID-19 symptom. Diarrhea in COVID-19 subjects is usually acute but is occasionally chronic. It is typically mild-to-moderate and nonbloody. It is usually much less clinically important than pulmonary or potential thrombotic disorders. Occasionally the diarrhea can be profuse and life-threatening. The entry receptor for COVID-19, angiotensin converting enzyme-2, is found throughout the GI tract, especially in the stomach and small intestine, which provides a pathophysiologic basis for local GI infection. COVID-19 virus has been documented in feces and in GI mucosa. Treatment of COVID-19 infection, especially antibiotic therapy, is a common culprit of the diarrhea, but secondary infections including bacteria, especially Clostridioides difficile, are sometimes implicated. Workup for diarrhea in hospitalized patients usually includes routine chemistries; basic metabolic panel; and a complete hemogram; sometimes stool studies, possibly including calprotectin or lactoferrin; and occasionally abdominal CT scan or colonoscopy. Treatment for the diarrhea is intravenous fluid infusion and electrolyte supplementation as necessary, and symptomatic antidiarrheal therapy, including Loperamide, kaolin-pectin, or possible alternatives. Superinfection with C difficile should be treated expeditiously. Diarrhea is prominent in post-COVID-19 (long COVID-19), and is occasionally noted after COVID-19 vaccination. The spectrum of diarrhea in COVID-19 patients is presently reviewed including the pathophysiology, clinical presentation, evaluation, and treatment.

Gastrointestinal Bleeding in COVID-19-Infected Patients.

COVID-19 infection is an ongoing catastrophic global pandemic with significant morbidity and mortality that affects most of the world population. Respiratory manifestations predominate and largely determine patient prognosis, but gastrointestinal (GI) manifestations also frequently contribute to patient morbidity and occasionally affect mortality. GI bleeding is usually noted after hospital admission and is often one aspect of this multisystem infectious disease. Although the theoretical risk of contracting COVID-19 from GI endoscopy performed on COVID-19-infected patients remains, the actual risk does not seem to be high. The introduction of PPE and widespread vaccination gradually increased the safety and frequency of performing GI endoscopy in COVID-19-infected patients. Three important aspects of GI bleeding in COVID-19-infected patients are (1) GI bleeding is often from mucosal erosions from mucosal infalammation that causes mild GI bleeding; (2) severe upper GI bleeding is often from PUD or stress gastritis from COVID-19 pneumonia; and (3) lower GI bleeding frequently arises from ischemic colitis associated with thromboses and hypercoagulopathy from COVID-19 infection. The literature concerning GI bleeding in COVID-19 patients is presently reviewed.

The Impact of COVID-19 Infection on Miscellaneous Inflammatory Disorders of the Gastrointestinal Tract.

The novel coronavirus pandemic of COVID-19 has emerged as a highly significant recent threat to global health with about 600,000,000 known infections and more than 6,450,000 deaths worldwide since its emergence in late 2019. COVID-19 symptoms are predominantly respiratory, with mortality largely related to pulmonary manifestations, but the virus also potentially infects all parts of the gastrointestinal tract with related symptoms and manifestations that affect patient treatment and outcome. COVID-19 can directly infect the gastrointestinal tract because of the presence of widespread angiotensin-converting enzyme 2 receptors in the stomach and small intestine that can cause local COVID-19 infection and associated inflammation. This work reviews the pathopysiology, clinical manifestations, workup, and treatment of miscellaneous inflammatory disorders of the gastrointestinal tract other than inflammatory bowel disease.

High yield of same-session EUS-guided liver biopsy by 19-gauge FNA needle in patients undergoing EUS to exclude biliary obstruction.

BACKGROUND: EUS-guided liver biopsy by Trucut yields variable specimen adequacy at high cost, limiting its utility. A modified EUS-guided technique with reliable adequacy could be a viable alternative to standard techniques in cost-effective clinical settings. OBJECTIVE: To describe our experience with EUS-guided liver biopsy by 19-gauge FNA, non-Trucut, needle in a cost-effective setting: patients with abnormal liver test results of unclear etiology referred for EUS to exclude biliary obstruction in whom an unrevealing EUS would have prompted a next-step liver biopsy by the referring physician. DESIGN: Prospective case series. SETTING: Tertiary-care teaching hospital. PATIENTS: Consecutive patients with abnormal liver tests referred for EUS. INTERVENTIONS: EUS-guided liver biopsy by 19-gauge FNA needle (non-Trucut). MAIN OUTCOME MEASUREMENTS: Diagnostic yield, specimen adequacy, and complications. An adequate specimen was defined as a length of 15 mm or longer and 6 or more complete portal tracts (CPTs). RESULTS: Between July 2008 and July 2011, 22 of 31 consecutive patients meeting inclusion criteria underwent unrevealing EUS with same-session EUS-guided liver biopsy by 19-gauge FNA needle. A median of 2 FNA passes (range 1-3) yielded a median specimen length of 36.9 mm (range 2-184.6 mm) with a median of 9 CPTs (range 1-73 CPTs). EUS-guided liver biopsies yielded a histologic diagnosis and adequate specimens in 20 of 22 patients (91%). Expanded experience led to improved specimen adequacy. There were no complications. LIMITATION: Small study size. CONCLUSIONS: EUS-guided liver biopsy by using a 19-gauge FNA needle appears to be feasible and safe and provides excellent diagnostic yield and specimen adequacy.

Evolving role of computed tomographic colonography in colon cancer screening and diagnosis.

Computed tomographic colonography (CTC) is a relatively new imaging modality for the examination of patients for colorectal polyps and cancer. It has been validated in its accuracy for the detection of colon cancer and larger polyps (more than likely premalignant). CTC, however, is not widely accepted as a primary screening modality in the United States at present by many third-party payers, including Medicare, and its exact role in screening is evolving. Moreover, there has been opposition to incorporating CTC as an accepted screening instrument, especially by gastroenterologists. Heretofore, optical colonoscopy has been the mainstay in this screening. We discuss these issues and the continuing controversies concerning CTC.

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase 2/3, randomized, open-label, active-control, multicenter study randomly assigned solithromycin (capsules, suspension or intravenous) or an appropriate comparator antibiotic in a 3:1 ratio (planned n = 400) to children 2 months to 17 years of age with CABP. Primary safety endpoints included treatment-emergent adverse events (AEs) and AE-related drug discontinuations. Secondary effectiveness endpoints included clinical improvement following treatment without additional antimicrobial therapy. RESULTS: Unrelated to safety, the sponsor stopped the trial prior to completion. Before discontinuation, 97 participants were randomly assigned to solithromycin (n = 73) or comparator (n = 24). There were 24 participants (34%, 95% CI, 23%-47%) with a treatment-emergent AE in the solithromycin group and 7 (29%, 95% CI, 13%-51%) in the comparator group. Infusion site pain and elevated liver enzymes were the most common related AEs with solithromycin. Study drug was discontinued due to AEs in 3 subjects (4.3%) in the solithromycin group and 1 (4.2%) in the comparator group. Forty participants (65%, 95% CI, 51%-76%) in the solithromycin group achieved clinical improvement on the last day of treatment versus 17 (81%, 95% CI, 58%-95%) in the comparator group. The proportion achieving clinical cure was 60% (95% CI, 47%-72%) and 68% (95% CI, 43%-87%) for the solithromycin and comparator groups, respectively. CONCLUSIONS: Intravenous and oral solithromycin were generally well-tolerated and associated with clinical improvement in the majority of participants treated for CABP.