Completion Of Antibiotic Therapy Research Articles

Nocardiosis in kidney transplant recipients: A tertiary care center experience

IntroductionKidney transplant recipients are at increased risk of opportunistic infections, including Nocardia. The incidence of nocardiosis in kidney transplant recipients is 0.4–1.3%. The data regarding its epidemiology and outcomes is limited. MethodsThis was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with Nocardia infection were included and followed. Results12 (1.1%) patients had a Nocardia infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. Nocardia infection occurred at a median of 26 months (range 4–235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (n = 5) cases had an episode of rejection in the preceding year of Nocardia diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced Nocardia recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (n = 4), and only one death was Nocardia-related. ConclusionNocardia may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for Nocardia prevention.

Elevated regulatory T cells after antibiotic treatment of infectious spondylodiscitis as biomarker of recovery?

Dysregulated systemic immune responses during infectious spondylodiscitis (IS) may impair microbial clearance and bone resorption. Therefore, the aim of the study was to examine whether circulating regulatory T cells (Tregs) are elevated during IS and whether their frequency is associated with alterations in T cells and the presence of markers of bone resorption in the blood. A total of 19 patients hospitalized with IS were enrolled in this prospective study. Blood specimens were obtained during hospitalization and 6 weeks and 3 months after discharge. Flow cytometric analysis of CD4 and CD8 T cell subsets, the percentage of Tregs and serum levels of collagen type I fragments (S-CrossLap) were performed. Out of 19 enrolled patients with IS, microbial etiology was confirmed in 15 (78.9%) patients. All patients were treated with antibiotics for a median of 42 days, and no therapy failure was observed. Next, a significant serum C-reactive protein (S-CRP) decrease during the follow-up was observed, whereas the frequencies of Tregs remained higher than those of controls at all-time points (p < 0.001). In addition, Tregs demonstrated a weak negative correlation with S-CRP and S-CrossLap levels were within the norm at all-time points. Circulating Tregs were elevated in patients with IS and this elevation persisted even after the completion of antibiotic therapy. Moreover, this elevation was not associated with treatment failure, altered T cells, or increased markers of bone resorption.

Clinical case of severe pseudomembranous colitis caused by pathogenic infection &lt;i&gt;Clostridium Difficile&lt;/i&gt;

Objective. Literature review of pseudomembranous colitis caused by pathogenic Clostridium difficile infection and description of a clinical case of pseudomembranous colitis.&#x0D; Materials and methods. A clinical case of a patient with pseudomembranous colitis is presented.&#x0D; Results. In a patient with multiple injuries and grade II shock, whose condition required numerous surgical interventions and intensive antibiotic therapy, after the completion of antibiotic therapy there appeared signs of pseudomembranous colitis loose stools (up to 5 times a day), fever up to 39 C, signs of endogenous intoxication, A C. difficile toxin was found in faeces. Antibiotic-associated colitis was diagnosed; metronidazole 500 mg 3 times a day, activated charcoal, infusion therapy were prescribed on the 12th day, the therapy led to recovery. During the subsequent reconstructive operation, lincomycin 600 mg was administered by infusion for prophylactic purposes, after which, 6 hours later, the patient developed a clinical picture of severe pseudomembranous colitis. A laboratory study of faeces again revealed toxin A C. difficile. The recurrence of the disease required a long-term treatment in the gastroenterology department.&#x0D; Conclusions. Pseudomembranous colitis is certainly a complex pathology that is a serious hospital-acquired infection. Accurate diagnosis requires correct assessment of the patients condition through clinical and laboratory diagnostic methods, correct prescription of conservative treatment and choice of surgical intervention tactics.

Effect of Gram Stain–Guided Initial Antibiotic Therapy on Clinical Response in Patients With Ventilator-Associated Pneumonia

Gram staining should provide immediate information for detecting causative pathogens. However, the effect of Gram staining on restricting the initial antibiotic choice has not been investigated in intensive care units (ICUs). To compare the clinical response to Gram stain-guided restrictive antibiotic therapy vs guideline-based broad-spectrum antibiotic treatment in patients with ventilator-associated pneumonia (VAP). This multicenter, open-label, noninferiority randomized clinical trial (Gram Stain-Guided Antibiotics Choice for VAP) was conducted in the ICUs of 12 tertiary referral hospitals in Japan from April 1, 2018, through May 31, 2020. Patients aged 15 years or older with a VAP diagnosis and a modified Clinical Pulmonary Infection Score of 5 or higher were included. The primary analysis was based on the per-protocol analysis population. Patients were randomized to Gram stain-guided antibiotic therapy or guideline-based antibiotic therapy (based on the 2016 Infectious Disease Society of America and American Thoracic Society clinical practice guidelines for VAP). The primary outcome was the clinical response rate; clinical response was defined as completion of antibiotic therapy within 14 days, improvement or lack of progression of baseline radiographic findings, resolution of signs and symptoms of pneumonia, and lack of antibiotic agent readministration, with a noninferiority margin of 20%. Secondary outcomes were the proportions of antipseudomonal agents and anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as initial antibiotic therapies; 28-day mortality, ICU-free days, ventilator-free days; and adverse events. In total, 206 patients (median [IQR] age, 69 [54-78] years; 141 men [68.4%]) were randomized to the Gram stain-guided group (n = 103) or guideline-based group (n = 103). Clinical response occurred in 79 patients (76.7%) in the Gram stain-guided group and 74 patients (71.8%) in the guideline-based group (risk difference, 0.05; 95% CI, -0.07 to 0.17; P < .001 for noninferiority). Reduced use of antipseudomonal agents (30.1%; 95% CI, 21.5%-39.9%; P < .001) and anti-MRSA agents (38.8%; 95% CI, 29.4%-48.9%; P < .001) was observed in the Gram stain-guided group vs guideline-based group. The 28-day cumulative incidence of mortality was 13.6% (n = 14) in the Gram stain-guided group vs 17.5% (n = 18) in the guideline-based group (P = .39). Escalation of antibiotics according to culture results was performed in 7 patients (6.8%) in the Gram stain-guided group and 1 patient (1.0%) in the guideline-based group (P = .03). There were no significant differences between the groups in ICU-free days, ventilator-free days, and adverse events. Results of this trial showed that Gram stain-guided treatment was noninferior to guideline-based treatment and significantly reduced the use of broad-spectrum antibiotics in patients with VAP. Gram staining can potentially ameliorate the multidrug-resistant organisms in the critical care setting. ClinicalTrials.gov Identifier: NCT03506113.

Antibiotic therapy completion for injection drug use-associated infective endocarditis at a center with routine addiction medicine consultation: a retrospective cohort study

BackgroundAddiction medicine consultation and medications for opioid use disorder are shown to improve outcomes for patients hospitalized with infective endocarditis associated with injection drug use. Existing studies describe settings where addiction medicine consultation and initiation of medications for opioid use disorder are not commonplace, and rates of antibiotic therapy completion are infrequently reported. This retrospective study sought to quantify antibiotic completion outcomes in a setting where these interventions are routinely implemented.MethodsMedical records of patients hospitalized with a diagnosis of bacteremia or infective endocarditis at an urban hospital between October 1, 2015 and December 31, 2017 were screened for active injection drug use within 6 months of hospitalization and infective endocarditis. Demographic and clinical parameters, receipt of antibiotics and medications for opioid use disorder, and details of re-hospitalizations within 1 year of discharge were recorded.ResultsOf 567 subjects screened for inclusion, 47 had infective endocarditis and active injection drug use. Addiction medicine consultation was completed for 41 patients (87.2%) and 23 (48.9%) received medications for opioid use disorder for the entire index admission. Forty-three patients (91.5%) survived to discharge, of which 28 (59.6%) completed antibiotic therapy. Twenty-nine survivors (67.4%) were re-hospitalized within 1 year due to infectious complications of injection drug use.ConclusionsAmong patients admitted to a center with routine addiction medicine consultation and initiation of medications for opioid use disorder, early truncation of antibiotic therapy and re-hospitalization were commonly observed.

188. Outcomes After Implementing the OPTIONS-DC Multidisciplinary Care Conference for Patients with Substance Use Disorders and Severe Bacterial Infections

BackgroundHospitalizations for patients with severe bacterial infections (SBI) and substance use disorders (SUDs) are increasing. To address the unique treatment challenges for these patients and balance appropriate medical therapy with patient goals, we implemented the OPTIONS-DC, a structured multidisciplinary discharge planning conference. All patients with SBI and SUD at our institution qualify for an OPTIONS-DC.MethodsWe performed a retrospective case-control study to evaluate differences and describe outcomes in patients who received an OPTIONS-DC compared to those who did not. Admissions were included if the patient was diagnosed with a SUD, a SBI requiring at least 2 weeks of antibiotics, consultation by infectious diseases and addiction medicine, and who were admitted between February 2018 and March 2020 (following implementation of OPTIONS-DC conferences). Patients were excluded for infected prosthetic material, pregnancy, or non-bacterial infection. Results173 admissions qualified for inclusion and 73 had at least one OPTIONS-DC. Unstable housing and psychiatric disease were common (table 1). Opioid and methamphetamine use disorders were most common and almost all SUDs were severe. Patients who received an OPTIONS-DC had less medical comorbidities, less unstable housing, and were more likely to have an opioid use disorder, use more than one substance, start MAT while inpatient, and have vertebral osteomyelitis or epidural abscess (table 2). Patients who had a conference had similar proportions of unexpected discharges (13.7% vs 17%), but a higher proportion of treatment completion (83.6% vs 69%), more days of antibiotic therapy remaining after discharge (13.9 vs 9.8 days), were more likely to discharge to an outpatient setting with family or medical support (30% vs 9%), and more likely to complete their antibiotic course with a long-acting injectable (27.4% vs 9%)(table 3). ConclusionNot all eligible patients received an OPTIONS-DC and there were significant differences in substances used, housing status and type of infections between those groups. Descriptive data suggest that OPTIONS-DC may reduce the duration of inpatient antibiotic treatment and increase likelihood of completion of antibiotic therapy, however this requires further study. Disclosures Amber C. Streifel, PharmD, BCPS, Melinta (Advisor or Review Panel member) Monica K. Sikka, MD, FG2 (Scientific Research Study Investigator)

Infective endocarditis caused by Pasteurella aerogenes possibly from a Dog

• P. aerogenes bacteremia should be aware exposure to domestic animals and pets . Pasteurella aerogenes is a gram-negative coccobacilli commensal in animals, rarely describe in human infection. We describe the first case of infective endocarditis caused by Pasteurella aerogenes , a rare pathogen in human infections that usually results from domestic animal bites. This is a case of a 21-year old Taiwanese man who initially presented headache and intermittent fever without any specific neurologic sign. Investigations revealed a diagnosis of infective endocarditis with mitral valve involvement and blood culture growing P. aerogenes . He recovered well after surgical intervention with the completion of antibiotic therapy. P. aerogenes cause human infection, mostly soft tissue infection by exposure to domestic animals and pets. Our case highlights that endocarditis should be considered in bacteremia with this pathogen.

Antibiotic Therapy for 6 or 12 Weeks for Prosthetic Joint Infection

BackgroundThe management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear.MethodsWe performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points.ResultsA total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events.ConclusionsAmong patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.)

Applying the new shoulder periprosthetic joint infection consensus definition to a case series of revision shoulder arthroplasty procedures to assess concordance between consensus definitions and diagnoses

As the number of shoulder arthroplasty procedures performed rises yearly, so does the number of periprosthetic joint infections (PJIs). In this study, PJI consensus definitions were compared and contrasted in a series of revision shoulder arthroplasty cases preoperatively diagnosed as PJI. Understanding the variations in these definitions may guide PJI diagnoses, thereby improving treatment strategies and patient outcomes in the setting of infected shoulder arthroplasty. All revision shoulder arthroplasty cases with preoperatively-diagnosed or suspected PJI (determined by procedure code) performed from 2008 – 2017 at a single institution by a single surgeon (fellowship-trained in shoulder and elbow surgery) were retrospectively evaluated. Following Institutional Review Board approval, patient demographic, treatment, and laboratory data were collected. Musculoskeletal Infection Society (MSIS; 2011) and International Consensus Meeting on Orthopaedic Infections (ICM; 2013, 2018 Revision, 2018 Shoulder) definitions of PJI were applied to the data. Statistical analysis assessed significant associations between culture status and PJI classification algorithm criteria. Thirty-seven patients with suspected PJI were identified; 24 culture-positive (CP) and 13 culture-negative (CN). In this series, the 2018 ICM Shoulder definition for definite infection was met at lower rates than all other definitions (CP; 71% vs. 96%; CN; 62% vs. 69%). 2018 ICM Shoulder major criteria showed stronger correlations to 2011 MSIS, 2013 ICM, and 2018 ICM Revision major criteria when “gross intra-articular pus” was excluded than when pus was included as a major criterion. 2018 ICM Revision cases determined to be infected were very strongly, positively, correlated with the 2018 ICM Shoulder cases determined to have definite or probable infections (ρ = 1.000, P < .0001). Additionally, cases classified as “definite” or “probable” infections with the 2018 ICM Shoulder definition were more likely to require reoperation for suspected recurrent infection after completion of antibiotic therapy. In this series, the 2018 ICM Shoulder definition and previous PJI definitions classified cases as PJI at similar rates. However, the inclusion of a third major criterion of “gross intra-articular pus” weakened the correlation with prior definitions. Level IV; Case Series.

Ceftriaxone and Doxycycline induced Seroconversion in Previously Seronegative Patient with Clinically Suspected Disseminated Lyme Disease: Case Report

We present a case of middle-aged woman whose health problems began 3 months after a registered tick bite in endemic area of Lyme borreliosis. First symptoms included fatigue, chills, cervical lymphadenopathy, neck pain and stiffness. Patient was afebrile. Lyme disease was excluded due to lack of erythema migrans and negative enzyme immunoassay test results for anti-Borrelia antibodies. During the next few months, her condition was getting worse and symptoms were accompanied with brain fog, dizziness, palpitations, irregular menstrual cycles, insomnia, panic attacks, headaches, and muscle aches. This led to multiple medical tests and examinations, but the diagnosis failed to be established. Finally, after occurrence of paresthesia and weakness of leg muscles, clinical diagnosis of disseminated Lyme borreliosis with nervous system involvement was suspected and antibiotic therapy was initiated. After the second dose of ceftriaxone, patient got fever and her condition worsened. However, ceftriaxone therapy was continued for a total of 5 days and was followed by 4 weeks of doxycycline therapy. Upon completion of antibiotic therapy, high specific anti-Borrelia antibodies were detected by Western blot and SeraSpot. Appearance of anti-Borrelia antibodies, in contrast to negative test results performed immediately before the therapy started, indicated seroconversion. 18 months after the therapy, patient was completely without the symptoms. This paper emphasizes importance of clinical evaluation of Lyme disease and shows a unique case of seroconversion in patient with symptoms of disseminated Lyme disease. Seroconversion was likely triggered by release of lipoproteins and other immunogenic molecules from Borrelia once the bacterial die-off began due to antibiotic therapy.

Влияние функционального состояния почек на соответствие рассчетных (модель) и реальных (лекарственное мониторирование) показателей фармакокинетики ванкомицина в условиях хирургического стационара

Изучены параметры фармакокинетики ванкомицина, полученные методом терапевтического лекарственного мониторинга и методом математического моделирования, у пациентов хирургического профиля с инфекционными осложнениями и нарушениями функции почек. Проведено проспективное обсервационное исследование на базе УКБ № 1 Первый МГМУ имени И. М. Сеченова. Включен 61 пациент с наличием гнойно-септических осложнений после оперативного вмешательства (возраст 60,59 ± 12,23, мужчины — 47, женщины — 14), разделенных на группы (1-я — с острым почечным повреждением (ОПП, n = 35; 66,6 %), 2-я — без ОПП (n = 26; 33,4 %). Параметры фармакокинетики ванкомицина оценивали методом математического моделирования и методом терапевтического лекарственного мониторинга с определением равновесных остаточных (Ctrough) и пиковых концентраций (Cpeak) методом ВЭЖХ. Расчетные значения (математическая модель) Ctrough через 48 ч от начала применения препарата были выше фактического уровня (терапевтический лекарственный мониторинг): (16,59 ± 8,4) и (11,32 ± 5,9) мкг/мл (p = 0,004). На момент завершения назначения ванкомицина различий нет (p = 0,092). Расчетные значения площади под фармакокинетической кривой (AUC) через 48 ч от начала антибактериальной терапии не отличались от данных терапевтического лекарственного мониторинга (p = 0,618), а на момент завершения терапии были меньше фактического уровня (347,03 ± 419,9) и (564,04 ± 180,8) мкг  ч/мл (p = 0,008). Погрешность расчетов фармкокинетических и фармакодинамических параметров при проведении математического моделирования может быть связана с высокой скоростью изменений функции почек у пациентов с ОПП и последующим риском неточности при расчете значений КК и Kel. Эти данные свидетельствуют о необходимости обязательного проведения терапевтического лекарственного мониторинга ванкомицина у пациентов с признаками острого нарушения функции почек, даже легкой и умеренной степени тяжести.

1357. Mycobacterium abscessus Native Tricuspid Valve Endocarditis. Is a 6-Week Course of Combination Antibiotic Therapy Enough?

BackgroundInfective endocarditis of the native heart valves due to M. abscessus has been reported in individuals who inject drugs. Only one case thus far has been reported with survival beyond 4 months after completion of antibiotic therapy. 24-year-old Caucasian woman with a history of intravenous drug use presented with intermittent fevers for 3–4 months. She was having chills, night sweats, and productive cough. She acknowledged using intravenous cocaine and heroin every few days after being discharged from our hospital 6 months previously when she was treated for tricuspid valve endocarditis. Chest radiograph demonstrated right lower lobe airspace disease suggestive of pneumonia. Three days later her blood cultures grew acid-fast bacilli, later identified as M. abscessus.MethodsShe was empirically treated with azithromycin, amikacin, and imipenem. Transthoracic and transesophageal echocardiograms were suggestive of tricuspid valve endocarditis. CT angiogram of the chest showed filling defects within several large right lower lobe pulmonary arteries and dense right lower lobe consolidation with pleural effusion. The patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and therapeutic thoracoscopy with drainage and thoracostomy tube placement. BAL cultures also grew AFB. Multiple sets of blood cultures drawn after commencement of antibiotic therapy during the hospital course were negative. Drug susceptibilities were available 3 weeks later. The isolate was susceptible to amikacin. Linezolid, imipenem, and cefoxitin exhibited intermediate activity, and TMP/SMX, ciprofloxacin, moxifloxacin, doxycycline, minocycline, and clarithromycin were reported resistant. Inducible erm gene was present. Azithromycin and linezolid were discontinued and tigecycline was added.ResultsPatient completed 6 weeks of antibiotics from the day of the first negative blood culture. Repeat TTE 1 month after completion of therapy revealed a decrease in tricuspid valve vegetation. Blood culture done 3 months later was sterile. AFB blood cultures done a year later did not report any growth.ConclusionThis case opens a debate, if in a selected group of patients, a short course of combination antibiotic therapy is enough to obtain cure. This will require further analysis. Disclosures All authors: No reported disclosures.

753. Outpatient Parenteral Antibiotic Therapy (OPAT) in a Large Urban Safety Net Hospital Setting: Therapy for Vulnerable Populations at Home

BackgroundAdoption of outpatient parenteral antibiotic therapy (OPAT) is accelerating due to proven safety and value, but experience in safety-net settings remains limited, especially in those with history of illicit drug use. Emerging reports from safety-net settings have featured OPAT delivered in nursing facilities, respite care centers, and infusion centers (including some persons who inject drugs [PWID]), but literature is sparse on home-based OPAT for vulnerable patients. In a new home antibiotics program at San Francisco General Hospital, we sought to describe early safety and efficacy outcomes among adults without active injection drug use but with high rates of substance use and comorbid illnesses.MethodsWe conducted a cohort study of patients discharged from a large urban county medical center and enrolled in an outpatient IV antibiotics program from September 2017 to January 2019. We collected demographic and clinical data and computed outcomes of safety (30- and 90-day readmission for infection, vascular access complications, and death) and efficacy (completion of antibiotic therapy).ResultsOverall, 47 courses of antibiotics were given to 45 patients. Of these, 39/47 (83%) of antibiotic courses were administered in a residential setting, and 8/47 (17%) via the hospital outpatient infusion center. Comorbid conditions were common, including 9/45 (20%) with hepatitis B/C and 8/45 (18%) with HIV (Table 1). Present or prior illicit drug use was seen in 17/45 patients (38%), including recent or active illicit drug use in 11/45 (24%) (Table 1). Most common indications for antibiotics were osteomyelitis and bacteremia (Table 2). Efficacy in the OPAT program was high: overall, 44/47 (94%) courses of outpatient IV antibiotics were completed, and the 30-day and 90-day readmission rates were 13% and 20% respectively, with zero 30-day readmissions related to OPAT (Table 3).ConclusionAn OPAT program embedded within a safety net hospital system delivering care in patients’ homes had high completion rate and low readmission rate, despite patients’ high prevalence of underlying comorbid conditions and noninjection illicit drug use. Home-based OPAT should be considered for broader adoption in safety-net hospital systems. Disclosures All authors: No reported disclosures.

2817 Efficacy of Fecal Microbial Transplant in Treatment of Recurrent Clostridioides difficileInfection in Community Hospitals in Las Vegas

INTRODUCTION: Fecal microbial transplant (FMT) has been established as an effective treatment for recurrent Clostridioides difficile infection (CDI); however, current treatment guidelines for recurrent CDI in the community hospital setting remain unclear. Recurrence is defined as resolution followed by recurrence of CDI symptoms within 2-8 weeks after discontinuing antibiotic treatment. Recurrent CDI is seen in 10-25% of patients most commonly within 30 days but up to 2 months after completion of antibiotic therapy. In 2013, a randomized control trial demonstrated 81% response rate to FMT therapy for recurrent CDI versus 31% with vancomycin alone. The goal of our study was to evaluate the efficacy of FMT as a treatment modality for recurrent CDI in the community hospital setting. METHODS: In a retrospective data collection study, 27 patients diagnosed with 2 or more recurrences of CDI were selected for cecal infusion of FMT at 3 different community hospitals in Las Vegas between March 2017 and December 2018. Donor feces were obtained from OpenBiome and prepared according to the manufacturer’s instructions. Patients were screened for HIV, HAV, HBV, HCV and enteric bacterial pathogens. Antibiotics were discontinued 24-48 hours prior to FMT. All patients underwent bowel preparation with 4 liters polyethylene glycol. 250 cc of donor feces was delivered into the cecum via colonoscopy. Patients were re-evaluated at 8-weeks follow-up visits. RESULTS: Of the 27 patients treated with cecal infusion of FMT, 18 were available for 8-weeks follow-up evaluations. 14 of these patients reported complete resolution of CDI symptoms without recurrence. 3 patients had refractory CDI. 1 patient had persistent diarrhea due to Crohn’s disease. 1 patient died of septic shock during a hospital readmission. 8 patients were lost to follow-up. CONCLUSION: This study demonstrated FMT was effective in 78% of patients with recurrent CDI in community hospitals. Of the 3 patients with refractory CDI, 1 responded to a second FMT, 1 failed two additional FMTs but ultimately responded to an extended course of vancomycin and 1 remains on an extended course of vancomycin. Our study was limited by missing data; 30% of our patients were lost to follow-up. Although high rates of inadequate bowel prep were observed, further studies are needed to explore the significance of poor prep on FMT outcomes. Overall, the response rate supports the use of FMT for recurrent CDI in community hospitals.

1605 Typhoid Fever: GI Bleed From an Ancient Disease

INTRODUCTION: Gastroenterologists periodically encounter ileocecal wall thickening in a patient with abdominal pain, fevers and gastrointestinal bleeding in an inpatient setting. A unifying diagnosis for a patient with these radiologic findings and symptoms could include inflammatory, infectious, or malignant etiologies. We present a case of a patient presenting in this way, who has found to have salmonella bacteremia as well as colonic and ileocecal valve ulcers on endoscopy. CASE DESCRIPTION/METHODS: A 51-year-old man with a past medical history notable for bladder cancer status-post BCG treatment presented with a three day history of crampy abdominal pain and fevers. He denied any diarrhea or vomiting. Exam was notable for a temperature of 102.7 and mild tenderness to palpation in lower abdomen. Admission labs were notable for normal leukocyte count and mildly elevated hepatocellular enzymes (AST 63, ALT 97). Due to his high fever, blood cultures were drawn. CT scan was notable for marked wall thickening at the ileocecal junction with enlarged regional lymph nodes. On the day after admission, he had a melenic stool and was scheduled for EGD and colonoscopy. EGD was unremarkable, but his colonoscopy was notable for two 3-5mm ulcers in the ascending colon as well as an ulcerated and inflamed ileocecal valve, which was unable to be intubated. Concern was for infectious or malignant etiology of these findings. Multiple blood cultures returned positive for Salmonella enterica with Vi antigen, shortly thereafter. He was treated with ceftriaxone and metronidazole for his bacteremia, and later transitioned to ciprofloxacin, with improvement in symptoms. Biopsies of the ulcers showed chronic active colitis. They were also notable for B and T cell clones which were concerning for lymphoma. To follow up on these concerns, he had repeat colonoscopy three weeks later which noted resolution of his ascending colon ulcerations and ileocecal valve inflammation. His terminal ileum was intubated and appeared normal. Biopsies of the ileocecal valve revealed benign colonic mucosa. After completion of antibiotic therapy, the patient denied any further symptoms. DISCUSSION: This case illustrates the importance of maintaining a broad differential in a patient with colonic inflammation on imaging and ulcerations noted on endoscopy. Also, this case highlights key features of typhoid colitis which can include GI hemorrhage with a predilection for right-sided colonic involvement.

1467. Clinical Significance of Microbiologic Treatment Failure Following Clinical Cure of Pneumonia

BackgroundMicrobiologic cure is a frequent outcome in pneumonia trials, but its clinical relevance remains poorly understood. We aimed to evaluate the association between microbiologic failure in pneumonia in the setting of clinical cure and recurrent pneumonia and mortality.MethodsRetrospective, single-center cohort study of adult patients hospitalized between January 1, 2008 and January 1, 2017. Patients with index pneumonia (defined as a positive respiratory culture and continuous receipt of ≥5 days of antibiotics) who demonstrated clinical cure (defined as cessation of all antibiotics for ≥48 hours and survival for 7 days following antibiotic completion) were included. All included patients had to have follow-up respiratory cultures obtained between 3 days before and 7 days after completion of antibiotic therapy. Patients with persistence of the inciting pathogen were classified as microbiologic failure and all others as microbiologic cure. Primary outcomes were 30-day mortality and a 30-day composite of mortality and/or recurrent pneumonia.ResultsOf 376 included patients, 61% had microbiologic cure compared with 39% with microbiologic failure. Mean age was 55.4 years, 62% of patients were male and 79% White. Mean antibiotic duration was 14.8 days. Sixty-one percent of patients were mechanically ventilated at the time of index pneumonia. The most common pathogens were Enterobacteriaceae (35%), Staphylococcus aureus (31%) and Pseudomonas aeruginosa (22%). In the microbiologic failure group, the primary composite outcome occurred in 18.9% of patients compared with 11.8% in the microbiologic cure group (OR 1.73, 95% CI 0.98–3.09) (Figure 1). All-cause 30-day mortality was greater in patients with microbiologic failure (16.2%) than microbiologic cure (8.3%) (OR 2.13, 95% CI 1.12–4.04). These associations were particularly strong among nonventilated patients (Figure 2). Rates of recurrent pneumonia were similar between groups.ConclusionPatients with clinical cure but microbiologic failure were more than twofold more likely to die 30 days after their index pneumonia than those with microbiologic cure. Patients with microbiologic failure who were not mechanically ventilated at the time of index pneumonia had a greater than fourfold increased mortality risk. Disclosures K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor, Consulting fee

Robust interferon signature and suppressed tissue repair gene expression in synovial tissue from patients with postinfectious, Borrelia burgdorferi-induced Lyme arthritis.

In most patients with Lyme arthritis (LA), antibiotic therapy results in Borrelia burgdorferi pathogen elimination, tissue repair, and return to homeostasis. However, despite spirochetal killing, some patients develop proliferative synovitis, characterised by synovial hyperplasia, inflammation, vascular damage, and fibrosis that persists for months to several years after antibiotic treatment, called postinfectious LA. In this study, we characterised the transcriptomes of postinfectious LA patients' synovial tissue, the target tissue of the immune response. High-throughput RNA sequencing to a depth of ~30 million reads per sample was used to profile gene expression in synovial tissue from 14 patients with postinfectious LA, compared with eight patients with other types of chronic inflammatory arthritis and five with minimally inflammatory osteoarthritis (OA). Synovium from postinfectious LA and other inflammatory arthritides shared gene signatures associated with antigen presentation, innate immune responses, and cell-mediated immune activation, whereas these responses were diminished in OA synovium. Unique to postinfectious LA was a particularly robust interferon-gamma (IFNγ) signature. Moreover, this heightened IFNγ signature inversely correlated with expression of genes involved in repair of damaged tissue, including genes associated with stromal cell proliferation and differentiation, neovascularisation, and extracellular matrix synthesis, which were markedly suppressed in postinfectious LA. Transcriptional observations were confirmed by cytokine profiling, histologic analyses, and clinical correlations. We propose that in patients with postinfectious LA, overexpression of IFNγ in synovium prevents appropriate repair of tissue damaged by B.burgdorferi infection, blocking return to tissue homeostasis long after completion of antibiotic therapy and resolution of active infection.

Active Tuberculosis Complicates the Diagnosis and Treatment of Fibrostenosing Crohnʼs Disease

62-year-old male with Crohn's disease (CD), presented for abdominal pain and weight loss. Patient was initially diagnosed with CD based of CTE 2 years prior. He was started on 5-ASA and lost to follow up. Upon re-presentation patient reported lower abdominal pain, hematochezia and weight loss. Lab evaluation negative. Colonoscopy showed a hepatic flexure stricture which could not be traversed. Biopsy showed mild to moderate chronic colitis with focal severe ulceration. CTE showed a 7 cm thickening and a focal hyper-enhancement of the ascending colon. We elected to resect due to his obstructive symptoms, weight loss and cancer risk. Surgery was to be followed by biologic therapy. In preparation for therapy QuantiFERON gold was positive. An ill-defined right upper lobe mass was seen on CXR. AFB in sputum confirmed active pulmonary tuberculosis. Active TB raised the possibility of an alternative diagnosis for the colonic stricture. The patient was started on 4 drug therapy. Following 10 weeks of therapy patient was deemed non-infectious and underwent a successful laparoscopic right hemicolectomy. Path showed focal mild to moderate chronic colitis with focal ulceration. Negative AFB stains. Post-op biologic therapy was anticipated. However, his active TB postponed initiation until completion of antibiotic therapy. As such the final plan was to perform colonoscopy 6 months post-op to assess for recurrent inflammation and if so would consider starting biologic therapy. The diagnostic dilemma of gastrointestinal TB and Crohn's disease is a common occurrence in TB endemic areas. It often presents similar to Crohn's disease with abdominal pain, weight loss, hematochezia, has similar imaging and endoscopic findings. It is important to differentiate between the two as they have opposing treatments. The risk of biologic therapy and re-activation of latent tuberculosis is well documented and screening for and surveying for TB is standard of care. But consideration of how to manage a patient with complicated Crohn's disease recently treated for active TB presents a dilemma. Biologic therapy is warranted to prevent recurrence of anastomotic stricture. A risk vs benefit discussion must be had and a suitable therapy individualized for the specific patient must be chosen. Vedolizumab, a gut specific, monoclonal antibody against a4b7 Integrin is considered to have a favorable safety profile with low incidence rates of serious infections.2057_A Figure 1. Histology2057_B Figure 2. Colon Resection Specimen

Impact of tigecycline versus imipenem–cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study

The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem–cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem–cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem–cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p < 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p < 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p < 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p < 0.001). In conclusion, compared to imipenem–cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.

Biomarker-based Assessment of Urinary Tract Infection in Persons with Spinal Cord Injury

BackgroundUrinary tract infection (UTI) is the most common infection and the second leading cause of death in spinal cord injury (SCI) patients. However, there is currently no consensus about the clinical criteria for UTI in SCI patients and the lack of a universal definition of asymptomatic bacteriuria (ABU) make the diagnosis even more complex and the treatment recommendations problematic. Prompt diagnosis and timely treatment of UTI are important to prevent possible progression to sepsis. Elevated concentrations of some biomarkers may be correlated with infection and their serial measurements may be helpful to assess the effectiveness of antibiotic therapy.MethodsFifteen SCI participants were enrolled for either lower UTI, upper UTI (pyelonephritis), ABU, or control. Patients suspected of having any inflammation or infection other than UTI were excluded. Participants were monitored for their serum procalcitonin (PCT) and c-reactive protein (CRP) levels initially and every 3 days once the UTI was confirmed and antibiotics prescribed. In addition, the urine was cultured initially and every three days in patients with UTI for correlation with biomarkers. UTI/ABU was assessed by patient’s physician.ResultsBoth mean initial PCT and CRP were significantly higher in patients with lower UTI (P = 0.027 and P = 0.001, respectively) and those with upper UTI (P = 0.044 and P < 0.0001, respectively) compared with control and ABU participants. PCT and CRP were generally reduced to the normal levels gradually during the course of antibiotic therapy for those patients with UTI that were placed on antibiotic therapy. Mean bacterial colonies grown from initial urine cultures in patients with upper or lower UTI were >100,000 CFU/mL. Control participants had urine cultures of ≤1,000 CFU/mL). Generally, cultures from UTI patients placed on antibiotics were negative for the organism(s) treated for during or after the completion of antibiotic therapy.ConclusionSerum concentrations of CRP and PCT may be used to aid in the early assessment of UTI in SCI patients in the absence of other sources of inflammation and/or infection. In general, CRP measurements are more pronounced than PCT measurements in patients with ABU or lower UTI. However, PCT levels elevate conspicuously in patient with pyelonephritis.Disclosures All authors: No reported disclosures.