#73: Outcomes of Children with Osteoarticular Infections Treated with Trimethoprim–Sulfamethoxazole

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Lydia Duvall ◽  
Brooks Platt ◽  
Michelle Kussin ◽  
James B Wood
Keyword(s):  
Adverse Drug Events ◽  
Guideline Development ◽  
Severe Disease ◽  
Treatment Options ◽  
Kidney Injury ◽  
Oral Antibiotic ◽  
Related Complication ◽  
Treatment Regimens ◽  
Osteoarticular Infections

Abstract Background Early transition to oral antibiotic therapy for the treatment of children with osteoarticular infections (OAI; osteomyelitis [OM], septic arthritis [SA]) has become increasingly common, yet the choice of optimal regimen remains a challenge. With increasing resistance, poor palatability, and reported allergies to commonly used oral antibiotics, including anti-Staphylococcal penicillins and clindamycin, the treatment options for children with OAI are limited. Trimethoprim–sulfamethoxazole (TMP-SMX) is a commonly used antibiotic, with activity against frequently encountered pathogens causing OAI, yet data regarding outcomes of children with OAI treated with TMP-SMX is limited. Thus, we sought to describe the characteristics and outcomes of children with OAI, at our institution, treated with TMP-SMX. Methods Records of children aged ≤18 years old, admitted to Riley Hospital for Children between 2010 and 2018, treated with TMP-SMX for acute OAI were reviewed. Patients were identified by ICD-9/-10 codes and order for TMP-SMX. Patients were excluded if they did not receive TMP-SMX for treatment of OAI, had symptoms >30 days, or had an alternative diagnosis. Demographic, clinical, and outpatient/follow-up data were recorded. Treatment was considered successful if the patient completed treatment with TMP-SMX, and there was no evidence of infection at the end of therapy. Treatment failure was defined as the inability to tolerate the medication, development of an infection-related complication, recurrent or chronic osteomyelitis. Additionally, significant adverse drug events were recorded. Results Eighty-three subjects were identified; however, after screening, 21 subjects were deemed eligible. The majority were non-Hispanic white, males, with a median age of 1.5 years (Interquartile range [IQR], 1–3 years) (Table 1). Twelve patients (57%) had OM, seven (33%) SA, and two (10%) had both OM and SA. A pathogen was recovered in 12 patients (57%), with Staphylococcus aureus being most common. All S. aureus isolates were methicillin resistant, and three were clindamycin resistant. The median duration of intravenous antibiotics prior to discharge was 3 days (IQR 2–4 days). All patients were transitioned to a TMP-SMX containing regimen prior to discharge. The median dose of TMP-SMX was 12.7 mg/kg/day (IQR 11.3–14.9). Reasons for choosing TMP-SMX varied, with the majority (62%) being physician preference. Treatment regimens varied with the majority (62%) receiving TMP-SMX monotherapy. Two patients developed adverse drug reactions attributed to TMP-SMX. Of the 18 patients that completed follow-up, 14 (78%) successfully completed treatment with TMP-SMX. Three patients developed recurrent infections and one patient was unable to finish therapy with TMP-SMX due to developing acute kidney injury. Conclusions In our study, TMP-SMX was well tolerated; however, only 78% of patients were successfully treated. The majority of treatment failures had prolonged bacteremia due to MRSA perhaps suggesting a higher bacterial burden. The poor outcome in these patients is likely multifactorial, and antibiotic contribution is unknown. TMP-SMX may be a reasonable treatment option for children with OAI when the disease is mild; however, caution should be exercised with severe disease, especially when associated with bacteremia. Prospective, randomized control trials are needed to aid in guideline development and understand the role of TMP-SMX in the treatment of children with OAI.

scholarly journals The Indirect Implication of SARS-CoV-2 Resulting in Kayexalate Toxicity in a Patient with Acute Kidney Injury

2021 ◽  
Vol 5 (1) ◽  
pp. 6-13
Author(s):  
Charles E. Middleton IV ◽  
William Daley ◽  
Neha Varshney
Keyword(s):  
Acute Kidney Injury ◽  
Virus Disease ◽  
Severe Disease ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Subsequent Treatment ◽  
Gastrointestinal Complications ◽  
Treatment Regimens ◽  
Organ Systems ◽  
Life Threatening

The clinical features of corona virus disease 2019 (COVID-19) are variable, but the majority of patients experience mild flu-like symptoms. The cases of severe disease include complications such as progressive pneumonia, acute kidney injury, multi-organ failure, and even death. This paper explores the association between COVID-19 and its effect on multiple organ systems and how the subsequent treatment of this disease can itself lead to morbidity and mortality. We present a case which emphasizes the life threatening gastrointestinal complications associated with treatment of acute kidney injury (AKI) in a patient with COVID-19. We conclude that the patients whose treatment regimens utilize medical resins should be closely monitored for gastrointestinal complications so as to mitigate the known adverse effects associated with these drugs, such as colonic mucosal ulceration, perforation, or even death.

Bladder cancer

2019 ◽  
Vol 13 (6) ◽  
pp. 271-277
Author(s):  
Ian Peate
Keyword(s):  
Bladder Cancer ◽  
Treatment Options ◽  
Older Person ◽  
Multiple Choice Questions ◽  
Men And Women ◽  
Treatment Regimens ◽  
Common Cancer ◽  
The One ◽  
The Uk

This article is the one in the cancer series that discusses bladder cancer. Bladder cancer can occur in men and women; however, in the UK, there are more men with bladder cancer than women. It is also a disease of the older person. This article provides an introduction that discusses the condition. An overview of the anatomy of the bladder and ureters is provided. In 2015, bladder cancer was the 10th most common cancer in the UK and was responsible for 3% of all new cancer cases. Diagnosis and treatment options are discussed, with an emphasis on ensuring that the patient is key in any decisions that are made about treatment regimens. The importance of follow-up after treatment is also discussed. A glossary of terms is provided and five multiple-choice questions are included to enhance learning and application to practice.

Pembrolizumab (pembro) for advanced biliary adenocarcinoma: Results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4079-4079 ◽  
Author(s):  
Yung-Jue Bang ◽  
Makoto Ueno ◽  
David Malka ◽  
Hyun Cheol Chung ◽  
Adnan Nagrial ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Phase 1 ◽  
Treatment Options ◽  
Inflammatory Cells ◽  
Infusion Reaction ◽  
Positive Staining ◽  
Treatment Regimens ◽  
Grade 5 ◽  
Ecog Ps

4079 Background: Antitumor activity with pembro, an anti–PD-1 antibody, has been observed in patients (pts) with advanced/metastatic biliary tract cancers (BTC), who have limited treatment options. We present follow-up data from pts with advanced BTC treated with pembro in the KN158 (NCT02628067; phase 2) and KN028 (NCT02054806; phase 1) studies. Methods: Eligible pts ≥18 y in the KN158/KN028 BTC cohorts had histologically/cytologically confirmed incurable advanced BTC that progressed after/failed any number of prior standard treatment regimens, measurable disease per RECIST v1.1, ECOG PS of 0/1, and no prior immunotherapy. PD-L1–positivity (membranous PD-L1 expression in ≥1% of tumor and associated inflammatory cells or positive staining in stroma) was required for eligibility in KN028, but not KN158. Pts received pembro 200 mg Q3W (KN158) or 10 mg/kg Q2W (KN028) for up to 2 y. Radiographic imaging occurred Q9W for 12 mo (KN158) or Q8W for 6 mo (KN028) and Q12W thereafter. Primary efficacy endpoint in both studies was ORR by RECIST 1.1. Response assessed by independent central review is reported. Results: Median (range) follow-up was 7.5 (0.6–29.5) mo in the 104 pts from KN158 and 6.5 (0.6–33.1) mo in the 24 pts from KN028 with BTC. All pts in KN028 and 61 in KN158 had PD-L1–positive tumors. No pt had MSI-H tumors (not assessed in KN028). In KN158, ORR was 5.8% (6/104, all PR [including 1 pt with PD-L1–negative tumor]; 95% CI, 2.1%–12.1%) and median duration of response (DOR) was not reached (NR; range, 6.2 to 23.2+ mo). Median OS and PFS were 7.4 mo (95% CI, 5.5–9.6) and 2.0 mo (95% CI, 1.9–2.1). 12-mo OS rate was 32.7%. In KN028, ORR was 13.0% (3/23, all PR; 95% CI, 2.8%‒33.6%) and median DOR was NR (range, 21.5 to 29.4+ mo). Median OS and PFS were 6.2 mo (95% CI, 3.8‒10.3) and 1.8 mo (95% CI, 1.4‒3.7), respectively. 12-mo OS rate was 27.6%. Grade 3–5 treatment-related AEs occurred in 13.5% in KN158 (1 pt had grade 5 renal failure) and 16.7% of pts in KN028 (no grade 5). 18.3% in KN158 and 20.8% of pts in KN028 had an immune-mediated AE or infusion reaction. Conclusions: Pembro provides durable antitumor activity, regardless of PD-L1 expression, and manageable toxicity in a subset of pts with advanced BTC. Clinical trial information: NCT02054806 and NCT02628067.

scholarly journals Metformin Improves Relevant Disease Parameters in an Autosomal Dominant Polycystic Kidney Disease Mouse Model

2021 ◽  
Author(s):  
Nuria M Pastor-Soler ◽  
Hui Li ◽  
Jessica Pham ◽  
Daniel Rivera ◽  
Pei-Yin Ho ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Autosomal Dominant ◽  
Severe Disease ◽  
Treatment Options ◽  
Kidney Injury ◽  
Polycystic Kidney ◽  
Gene And Protein Expression ◽  
Autosomal Dominant Polycystic Kidney

Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in the PKD1 or PKD2 genes encoding polycystins, presents with progressive development of kidney cysts and eventual end-stage kidney disease (ESKD) with limited treatment options. Previous work showed that metformin reduces cyst growth in rapid ADPKD mouse models via inhibition of CFTR-mediated fluid secretion, mTOR, and cAMP pathways. The present study importantly tested the effectiveness of metformin as a therapy for ADPKD in a more clinically relevant Pkd1RC/RC mouse model, homozygous for the R3277C knock-in point mutation in the Pkd1 gene. This mutation causes ADPKD in humans. Pkd1RC/RC male and female mice, which have slow progression to ESKD, received metformin (300 mg/kg/day in drinking water vs. water alone) from 3 to 9 or 12 months of age. As previously reported, Pkd1RC/RC females had a more severe disease phenotype than males. Metformin treatment reduced the ratio of total kidney weight to body weight relative to age- and sex-matched untreated controls at both 9 and 12 months and reduced cystic index in females at 9 months. Metformin also increased glomerular filtration rate (GFR), lowered systolic blood pressure, improved anemia, and lowered blood urea nitrogen levels relative to controls in both sexes. Moreover, metformin reduced gene expression of key inflammatory markers and both gene and protein expression of kidney injury marker-1 and cyclin-dependent kinase-1 vs. untreated controls. Altogether, these findings suggest several beneficial effects of metformin in this highly relevant slowly progressive ADPKD mouse model, which may help inform new ADPKD therapies in patients.

Outcome Of Chronic Lymphocytic Leukemia (CLL) Patients That Failed Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2880-2880
Author(s):  
Ohad Benjamini ◽  
Uri Rozovski ◽  
Preetesh Jain ◽  
William G. Wierda ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Treatment Modality ◽  
Treatment Options ◽  
Salvage Treatment ◽  
Treatment Regimens ◽  
Immune Manipulation ◽  
Btk Inhibitor

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-SCT) has become a therapeutic option for patients (pts) with high risk CLL. The major cause of allo-SCT failure is relapse or disease progression. No standard treatment is available for pts who failed allo-SCT and post-SCT immune manipulation, and the prognosis of these pts is largely unknown. Methods We performed a retrospective intention-to-treat analysis of pts with CLL who failed allo-SCT and post-SCT immune manipulation between 1998 and 2012 and were referred to the Leukemia Department at MD Anderson Cancer Center for further treatment. Results Seventy-three pts with CLL (n=40, 55%) or Richter's transformation (RT, n=33, 45%) who failed or progressed after allo-SCT were referred for further management at a median of 7 months (range 0-85 months) after allo-SCT. Most pts (n=63, 86%) had received non-myeloablative conditioning and 32 (44%) received post allo-SCT donor lymphocyte infusion (DLI). Six patients (8%) had early (4 pts) or late (2 pts) graft failure. Fifty four (74%) pts were male and the median age at time of failure/progression was 59 yrs (range 32–73 yrs). Of the 73 pts, 68 (93%) received salvage therapy, 1 pt died before treatment was initiated, and 4 pts were considering treatment options at time of last follow-up. A median of 2 treatment regimens (range 0 - 8) were administered between time of post-SCT progression and last follow-up. The most common salvage treatment regimens were chemo-immunotherapy with rituximab (R): R-HyperCVAD (n=24, 33%), OFAR (n=13, 18%), FCR, FBR, PCR, BR (n=24, 33%), immune-modulators thalidomide or lenalidomide (n=21, 29%), alemtuzumab with or without chemotherapy (n=12, 16%), and Bruton's Tyrosine Kinase (BTK) inhibitor (n=5, 7%). At time of last follow up, 26 pts (36%) were alive. The median overall survival (OS) from time of progression after allo-SCT was 33 months (95% CI, 27– 39) and 60% of the pts were alive 2 years from time of progression. Median OS after allo-SCT failure/progression was 53 months (95% CI, 9–97) for CLL pts and 28 months (95% CI, 12–44) for pts with RT (Log Rank: P<0.0001) (Figure 1). Only 4 pts achieved CR following first salvage treatment. The OS of these pts was 152, 41, 26+, 38+ months (the latter 2 are still alive). Pts with partial response (PR), no-response (NR) or progression after first salvage treatment had similar OS. To identify the best treatment modality we analyzed the OS from progression and from time of initiation of treatment to last follow-up of all regimens used. We found that patients treated with either FCR, alemtuzumab or combination chemotherapy did not have significant difference in OS. Remarkably, 4 of 5 pts treated with BTK inhibitor were alive at time of last follow-up. Univariable analyses showed shorter OS for pts with a higher ECOG performance status (PS; P=0.036), low hemoglobin (Hb) (P=0.0001), low albumin (P=0.0001), complex cytogenetic abnormalities at last follow up (P=0.026) and RT (P=0.0001). The multivariable Cox model analyses including age, sex, previous DLI, unfavorable cytogenetic abnormalities before or after allo-SCT, albumin, absolute lymphocyte count and platelet count, identified only Hb (P=0.009, 95% CI; 0.58 - 0.93), ECOG 3 (P=0.036, 95% CI; 1.12 - 30.04) and RT (P=0.002, 95% CI: 1.51 - 6.50) as independently associated with shorter OS. Conclusions The median OS of pts with high-risk CLL or RT from time of allo-SCT failure/progression was 33 months. The longest OS was observed in pts who attained CR after first salvage treatment (4/73, 6%). At the time of analysis, the 50% OS of pts treated with BTK inhibitors was not reached, however, no treatment modality appeared to be superior. Future studies of treatment options for pts that progress after allo-SCT are warranted. Disclosures: Off Label Use: Ibrutinib for CLL therapy.

#18: Brincidofovir for the Treatment of Disseminated Human Adenovirus Infection in Pediatric Solid-organ Transplant Recipients

2021 ◽  
Vol 10 (Supplement_1) ◽  
pp. S3-S3
Author(s):  
Jackson Londeree ◽  
Rouba Garro ◽  
Rene Romero ◽  
Roshan George ◽  
Pamela Winterberg ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Severe Disease ◽  
Treatment Options ◽  
Graft Loss ◽  
Clinical Specimen ◽  
Antiviral Drug ◽  
Solid Organ Transplantation ◽  
Kidney Injury ◽  
Human Adenovirus ◽  
Solid Organ

Abstract Background Human adenovirus (HAdV) viremia can cause significant morbidity among pediatric patients undergoing solid-organ transplantation (SOT). Currently, there are no US Food and Drug Administration (FDA)-approved treatments for HAdV infections, and historically the mainstay of treatment has been decreasing immunosuppression with antiviral therapies reserved for those with severe disease. Brincidofovir (BCV) is an investigational antiviral drug with potency against HAdV. We describe four cases of disseminated HAdV infection treated with (BCV) among pediatric SOT patients. Methods We retrospectively reviewed 4 cases of severe disseminated HAdV infection, which occurred between 2018 and 2019, in a tertiary pediatric transplant center. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. Baseline clinical characteristics, disease course, treatment, and outcomes were reviewed. Results Four pediatric SOT patients (2 kidneys, 1 dual kidney/liver, and 1 liver) ranging in age from 9 months to 19 years were diagnosed with HAdV infection (Table 1). Patients presented with varied symptoms from 12 to 912 days post-transplant. Peak HAdV viral load ranged from 37,000 to &gt;1,000,000 copies/mL. All patients had disseminated disease with evidence of graft involvement and varying degrees of acute kidney injury (AKI) making them candidates for BCV therapy over cidofovir to avoid nephrotoxicity. Three out of four patients received cidofovir prior to conversion to BCV. IRB-approved compassionate use of BCV was dosed at 2 mg/kg (max 100 mg) twice weekly PO along with reduced immunosuppression. Resolution of symptoms and HAdV viremia was seen at a mean of 21.5 days (range 15–32) of therapy. All patients had resolution of AKI with a return to baseline creatinine after therapy. Conclusions Though HAdV infection in pediatric SOT patients is uncommon, a subset of patients experience severe disease, morbidity, and graft loss. Currently, HAdV is not routinely monitored in pediatric SOT transplant patients. Although supportive care and decreased immunosuppression remain as the most important component of therapy, BCV was well tolerated and efficacious in our series. Further research is needed to better understand risk factors for HAdV infection and potential antiviral treatment options to improve patient outcomes.

scholarly journals Implications of Antiphospholipid and Antineutrophilic Cytoplasmic Antibodies in the Context of Postinfectious Glomerulonephritis

2017 ◽  
Vol 2017 ◽  
pp. 1-3
Author(s):  
Daniel Leifer ◽  
Lavjay Butani
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Normal Renal Function ◽  
Antiphospholipid Antibodies ◽  
Severe Disease ◽  
Kidney Injury ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Common Occurrence ◽  
Postinfectious Glomerulonephritis

While antineutrophil cytoplasmic antibody (ANCA) positivity has been documented in some patients with postinfectious glomerulonephritis (PIGN) and is associated with more severe disease, antiphospholipid antibodies (APA) are not known to be a common occurrence. We describe a child with severe acute kidney injury who was noted to have prolonged positivity of both ANCA and APA; a renal biopsy showed noncrescentic immune complex mediated glomerulonephritis with subepithelial deposits compatible with PIGN. He recovered without maintenance immunosuppressive therapy and at last follow-up had normal renal function. We discuss the cooccurrence and implications of ANCA and APA in children with PIGN.

scholarly journals Hormonal Defects Are Common during Puumala Hantavirus Infection and Associate with Disease Severity and Biomarkers of Altered Haemostasis

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1818
Author(s):  
Marlene Tarvainen ◽  
Satu Mäkelä ◽  
Outi Laine ◽  
Ilkka Pörsti ◽  
Sari Risku ◽  
...  
Keyword(s):  
Acute Phase ◽  
Severe Disease ◽  
Kidney Injury ◽  
Hantavirus Infection ◽  
Overt Hypothyroidism ◽  
Severe Thrombocytopenia ◽  
Normal Thyroid Function ◽  
Coagulation Abnormalities ◽  
The One

Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.

scholarly journals Outcome of Acute Kidney Injury with Different Treatment Options: Long-Term Follow-up

2010 ◽  
Vol 5 (10) ◽  
pp. 1755-1762 ◽  
Author(s):  
An M. Van Berendoncks ◽  
Monique M. Elseviers ◽  
Robert L. Lins ◽  
Keyword(s):  
Acute Kidney Injury ◽  
Treatment Options ◽  
Kidney Injury ◽  
Long Term Follow Up

Comparative Effectiveness of Vancomycin Versus Linezolid for the Treatment of Acute Pulmonary Exacerbations of Cystic Fibrosis

2019 ◽  
Vol 54 (3) ◽  
pp. 197-204 ◽  
Author(s):  
Nicholas M. Fusco ◽  
Calvin J. Meaney ◽  
Carla A. Frederick ◽  
William A. Prescott
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Adverse Drug Events ◽  
Treatment Options ◽  
Forced Expiratory Volume ◽  
Median Percentage ◽  
Median Percentage Change ◽  
Pulmonary Exacerbations ◽  
Viable Treatment

Background: Data are limited regarding the preferred antibiotics for treatment of acute pulmonary exacerbations (APEs) of cystic fibrosis (CF), when methicillin-resistant Staphylococcus aureus (MRSA) is suspected. Objective: To compare the rate of return to baseline lung function among individuals with APEs of CF treated with either vancomycin or linezolid. Methods: This retrospective study included individuals hospitalized for APEs of CF from May 1, 2015, to April 30, 2017 who were infected with MRSA and treated with vancomycin or linezolid. The primary outcome was the return to baseline lung function, as measured by forced expiratory volume in 1 s (FEV1). Descriptive and inferential statistics were used. All tests were 2-tailed with α set at 0.05. Results: A total of 122 encounters were included (vancomycin: n = 66; linezolid: n = 66). No difference existed in return to baseline FEV1 between vancomycin (53 [80.3%]) and linezolid (50 [75.8%]; P = 0.53); nor was there a difference in median percentage change in FEV1 from admission to follow-up between vancomycin (24.7%) and linezolid (20.7%; P = 0.61). Adverse drug events occurred more frequently in patient encounters treated with vancomycin (10 [15.2%]) compared with linezolid (2 [3%]; P = 0.002). Conclusion and Relevance: Our study observed no difference in the effectiveness of vancomycin compared with linezolid in terms of change in lung function for APEs of CF. The rate of adverse drug events was low. In individuals with CF infected with MRSA who are experiencing an APE, either vancomycin or linezolid appear to be viable treatment options.

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