56. High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose Trimethoprim-Sulfamethoxazole: An Opportunity for Antibiotic Stewardship

Background Trimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX. Methods IRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and > 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium < 135 mmol/L, hyperkalemia with potassium > 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed. Results Each group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received >1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2. Table 1. Baseline and Clinical Characteristics Table 2. Adverse Effects Conclusion Patients on IV TMP-SMX therapy were more likely to experience an ADE compared to PO, likely driven by the high volume of free water. Most patients on IV TMP-SMX were on other PO medications, suggesting a missed stewardship opportunity for IV to PO conversion to reduce patient harm. Disclosures Susan L. Davis, PharmD, Nothing to disclose Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)

COVID-19 Patients Symptoms: Gastrointestinal Presentations, Comorbidities and Outcome in a Canadian Hospital setting

Background: The Coronavirus disease 2019 (COVID-19) pandemic has had a significant global impact and Canada has seen significant morbidity and mortality nationwide. While public health interventions and provincially regulated health insurance coverage have been credited with minimizing transmission rates in Canada relative to neighboring countries, disease presentation has been presumed to be the same. Aim: We sought to determine factors associated with differences in gastrointestinal outcomes in COVID-19 patients at a Canadian hospital. Methods: We collected data from 192 hospital records of COVID-19 patients across seven Hamilton Health Sciences hospitals, a network of academic health centers located in Hamilton, Ontario serving one of the largest metropolitan areas in Canada. Statistical and correlative analysis of symptoms, comorbidities, and mortality were performed. Results: There were 192 patients. The mean age was 57.6 years (SD=21.0). For patients who died (n=27, 14%), mean age was 79.2 years old (SD=10.6) versus 54 years for survivors (SD=20.1). There was a higher mortality among patients with older age (p=0.000), long hospital stay (p=0.004), male patients (p=0.032), and patients in nursing homes (p=0.000). Patients with dyspnea (p=0.028) and hypertension (p=0.004) were more likely to have a poor outcome. Laboratory test values that were significant in determining outcomes were an elevated INR (p=0.007) and elevated creatinine (p=0.000). Cough and hypertension were the most common symptom and comorbidity, respectively. Diarrhea was the most prevalent (14.5%) gastrointestinal symptom. Impaired liver function was related to negative outcome (LR 5.6; p=0.018). Conclusion: In a Canadian cohort, elevated liver enzymes, prolonged INR and elevated creatinine were associated with poor prognosis. Hypertension was also linked to a higher likelihood of negative outcome.

Atrial fibrillation and stroke risk factors in patients with cardiac implantable electronic devices

Purpose. Determination the proportion and burden of new-onset atrial fibrillation (AF) in patients with cardiac implantable electronic devices (CIED) and without prior AF and assessing the incidence of risk factors for stroke in patients with AF.Methods. The medical history of 111 patients with CIED with remote monitoring function were analyzed. AF diagnosed by the device was interpreted by an arrhythmologist and cases of significant AF were selected. The group of patients with and without AF was compared for several factors. To clarify the influence of risk factors on the duration of AF, all AF cases were divided into 3 categories depending on the AF burden per day. The first group included patients with an AF burden per day of 0.1% or less (n=10, (45.5%)), the second - from 0.3% to 12.2% (n=7, (31.8%)), and the third group - with 100% (n=5, (22.7%)). Patients with a burden of 0.2%, 12.3-99.9% were absent.Results. Newly diagnosed AF was registered in 19.8% of cases. The risk of stroke among these patients was high - 2 [1; 3] points on the CHA2 DS2 -VASc for men, and 3 [2,75; 3,75] points for women. Hypertension of 2 and 3 degrees was recorded in all patients in the group with an AF burden of 100% per day. That significantly differed from the other 2 groups (p=0.043). In the group with an AF burden of 100%, the levels of NT-proBNP, D-dimer, and creatinine were significantly higher than in the other groups (p=0.037, p=0.031 and p=0.036, respectively). When analyzing the dependence of creatinine level on the presence of AF, the area under the ROC-curve was 0.653 with 95% confidence interval 0.528-0.779 (p=0.017). The proportion of right ventricular pacing in patients with ICD was higher in the group of patients with AF.Conclusion. AF occurs in 1/5 of patients with CIED. All patients with AF were potential candidates for anticoagulation due to their high risk of stroke. The daily burden of AF is positively correlated with the presence and degree of hypertension, as well as with markers of renal dysfunction, chronic heart failure, and thrombosis. Elevated creatinine levels are a predictor of AF.

Retrospective comparison of death or neurodevelopmental outcomes in extremely low birth weight preterm infants following different management options of haemodynamically significant patent ductus arteriosus

Background Optimal management of haemodynamically significant patent ductus arteriosus (HsPDA) in premature babies remains controversial. Our aim is to compare death and/or adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants with HsPDA who were managed with conservative [C], medical [M] and/or surgical [S] treatment, with secondary aim to examine short-term morbidities among [S] and [C] groups. The study also compared outcomes in very low birth weight (VLBW) infants with HsPDA and non-HsPDA. Methods A retrospective study of VLBW preterm infants born before 29 weeks in Singapore from 2007 to 2016 was conducted. Results A total of 474 VLBW infants were admitted in NUH from 2007 to 2016. Infants aged between 24 + 0 and 28 + 6 weeks of gestation, weighing ≤1500 g and diagnosed with patent ductus arteriosus (PDA) were included in the study, of which 172 infants (124 HsPDA and 48 non-HsPDA) were analyzed. Among infants with HsPDA, 17 infants were managed with [C], 83 with [M] and 24 with [S]. Mortality was not increased regardless of the presence of HsPDA or treatment received. Infants with non-HsPDA were less likely to have isolated speech delay (p < 0.05), but not global developmental delay (GDD). No significant differences in neurodevelopmental outcomes such as hearing loss, cerebral palsy (CP) and speech delay were found. [M + S] infants were at a higher risk of developing chronic lung disease (CLD) (OR 6.83, p < 0.05) and short-term growth failure compared to [C] infants. They were significantly shorter and had a smaller head circumference at discharge (p < 0.05). [M + S] infants also had elevated creatinine compared to those in group [C] (81.1 ± 24.1 vs 48.3 ± 11.8 umol/L, p < 0.000). Conclusions Compared to conservative management, infants requiring [M + S] treatment for HsPDA were more likely to have short-term complications such as CLD, elevated creatinine, and poorer growth. Despite a more turbulent postnatal course, death and/or adverse neurodevelopmental outcomes were not worse in infants managed with [M + S].

PSX-A-3 Late-Breaking: Analysis of serum chemistry for metabolic function in GnRH-II receptor knockdown and littermate control boars

Pigs are the only livestock species encoding functional proteins for both the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II), which are uniquely expressed in reproductive and non-reproductive tissues. To examine the physiological role of the GnRH-II/GnRHR-II system, we produced a swine line with reduced endogenous levels of GnRHR-II (GnRHR-II KD); males exhibit 70% diminished testicular GnRHR-II mRNA levels and 82% reduced circulating testosterone concentrations. Given that testosterone impacts metabolism, blood was collected from GnRHR-II KD (n = 5) and littermate control (n = 5) boars via indwelling jugular catheters, with serum isolated and subjected to veterinary diagnostic panels for metabolic analyte examination (PhysLab, Lincoln, NE). Statistical analyses utilized the MIXED procedure of SAS; the model included line as fixed and litter as random effects. Creatine kinase and blood urea nitrogen (BUN):creatinine ratios were elevated, creatinine was reduced (P &lt; 0.01), and thyroxine tended to be decreased (P &lt; 0.10) in GnRHR-II KD compared with control boars. Glucose, BUN, amylase, and lipase levels were not different. Liver products differed in transgenic versus control boars; levels of lactic dehydrogenase, aspartate and alanine aminotransferases (AST; ALT), and gamma-glutamyl transpeptidase were higher, whereas AST:ALT ratios, total protein, albumin, and globulin levels were lower (P &lt; 0.05) in GnRHR-II KD boars. Albumin:globulin ratios and bilirubin (total and direct) did not differ. Additionally, serum cholesterol was decreased (P &lt; 0.05), non-high density lipoproteins (HDLs) and low density lipoproteins (LDLs) tended to be decreased (P &lt; 0.10), and triglycerides, HDLs, and cholesterol:HDL ratios did not differ between GnRHR-II KD and control males. These data suggest metabolic disruption in GnRHR-II KD boars, which may be due to suppressed gonadal steroidogenesis or ubiquitous knockdown of GnRHR-II expression. Supported by USDA/NIFA AFRI (2017-67015-26508) and Hatch Multistate (NEB-26–244) funds. USDA is an equal opportunity provider and employer.

A Case of Idiopathic Recurrent Spontaneous Bladder Rupture

Background. A female patient presented four years following spontaneous bladder rupture with a recurrent spontaneous bladder rupture. Summary. Urinary bladder rupture is a condition usually caused by trauma or surgical instrumentation. Spontaneous bladder rupture is a much more uncommon condition and is associated with intoxication, radiation, stricture, or neurogenic bladder. We describe a case of a 40-year-old woman with a history of three caesarian sections with an idiopathic recurrent spontaneous bladder rupture. Originally, she presented with one day of worsening severe abdominal pain. CT showed possible ischemic bowel. She was taken to the operating room (OR) and found to have a bladder rupture. This was repaired, and she did well postoperatively. Four years later, she presented to the emergency department (ED) with one week of worsening abdominal pain that became severe acutely. Given that she had a similar issue four years prior the patient was suspicious, her bladder was again ruptured. CT cystogram showed contrast extravasation into the peritoneum. The patient was taken urgently to the operating room for an open repair of the bladder rupture. She did well following the procedure. Conclusion. Spontaneous bladder rupture is a surgical emergency and should be in the differential diagnosis of any patient with peritonitis with elevated creatinine and free intraperitoneal fluid. This diagnosis should especially be considered if the patient has a history pelvic radiation, neurogenic bladder, or intoxication. We submit that a history of multiple pelvic surgeries should be included in this list. CT cystogram is the diagnostic test of choice. Operative repair is generally the treatment for this condition.

Renal graft malakoplakia masquerading post-transplant lymphoproliferative disorder

A 45-year-old woman presented to us in March 2019 with complaints of fever and right lower quadrant abdominal pain for 1 month. She had undergone renal transplantation in 2017 for end-stage renal disease and developed four episodes of urinary tract infection in the next 16 months post transplantation, which were treated based on culture reports. She was subsequently kept on long-term prophylaxis with trimethoprim and sulfamethoxazole. Her present laboratory parameters showed a normal blood picture and elevated creatinine. Urine culture grew Escherichia coli. Non-contrast CT of the abdomen-pelvis revealed an endo-exophytic hyperdense mass in the graft kidney showing local infiltration and associated few regional lymph nodes. PET-CT revealed the soft-tissue mass and regional lymph nodes to be hypermetabolic, raising the possibility of lymphoma. However, biopsy showed features of malakoplakia. She was subsequently initiated on long-term antibiotic therapy and her immunosuppression decreased.

A case report of biochemistry and serum amyloid A in a moribund free-ranging Baltic herring gull (Larus argentatus) with necrotic wing fracture

An adult herring gull (Larus argentatus) found lethargic and moribund showed an open fracture of the right radius and ulna with necrosis of the surrounding tissue. Hematologic testing and plasma biochemical analysis revealed elevated creatinine kinase consistent with traumatic muscle damage in addition to hyperuricemia, hyperkalaemia, and hyperphosphatemia consistent with renal insufficiency. Increase in the acute phase protein Serum Amyloid A indicate a high degree of inflammation supported by leucocytosis, heterophilia, and hypoglycaemia pointing towards septicaemia. This case provides knowledge about Serum Amyloid A in gulls, and how bone fracture and secondary infection may affect gull blood haematology and biochemistry.

Colchicine-induced rhabdomyolysis: a review of 83 cases

A 74-year-old man with medical history significant for atrial fibrillation, hyperlipidaemia and coronary artery disease on atorvastatin presented to the emergency department with profound weakness. The patient reports he first noticed his weakness 4 weeks after starting colchicine, prescribed for recurrent pericarditis with pericardial effusion, a complication following recent coronary artery bypass grafting. The patient was also on prednisone therapy for presumed post-pericardiotomy syndrome. The weakness involved all four limbs but was more notable in the lower extremities, with preserved sensation and tenderness to palpation. Labs showed an elevated creatinine phosphokinase and serum creatinine consistent with rhabdomyolysis. Discontinuation of the offending medications, including colchicine and atorvastatin, as well as intravenous fluid resuscitation with physical rehabilitation, led to improvement in the patient’s symptoms. He was eventually discharged to a rehabilitation facility to continue physical therapy.

Predictors of In-hospital Mortality In Patients With RT-PCR Confirmed Lassa Fever Infection Treated At A National Treatment Center, South West Nigeria

Background: Lassa fever (LF) infection is one of the viral hemorrhagic fever diseases found mainly in Sub-Saharan West Africa, including Nigeria. The case fatality rate is 60% among patients with Lassa fever complicated by AKI in one center study in Nigeria. Clinical and laboratory parameter has been documented as predictors of mortality among confirmed Lassa fever infected patients. Therefore, we decided to conduct similar study in our hospital to determine predictors of inhospital mortality among Lassa fever infected patients. Aim: This study was designed to determine the in-hospital clinical and laboratory predictors of outcome among RT-PCR (Real Time- Polymerase Chain Reaction) diagnosed Lassa fever patients. Methodology: This was a descriptive retrospective study involving the assessment of records of confirmed LF infected patients that were managed at the center from December 2019 to December 2020. 147 medical case record files of patients were retrieved for this study. Results: We found in our hospital setting, altered sensorium (p=0.001), seizures (p=0.001), bleeding diathesis (p=0.001), oliguria (p=0.001), elevated urea (p=0.001), elevated creatinine (p=0.001), hypoalbuminaemia (P=0.001), elevated SGOT (P=0.008) as significant predictors on in-hospital mortality. Conclusion: This study has helped us to identify the clinical parameters such as bleeding, central nervous system affectation, oliguria, tachycardia, tachypnea, hypoxaemia and laboratory parameters such as, elevated urea, elevated creatinine, hypoalbuminaemia as predictors of in-hospital mortality in RT-PCR confirmed Lassa fever patients. We believe early recognition of derangements of these parameters and with prompt intervention shall help to improve standards of care and outcome.