Drug Reactions In Patients Research Articles

A case report of adolescent lactation due to the drug blonanserin

BackgroundSecond-generation antipsychotic drugs are increasingly used to treat depressive disorders with psychotic symptoms. In addition to effectively managing psychotic symptoms, second-generation antipsychotics can also result in adverse drug reactions in patients, which should not be underestimated.Case presentationWe report the case of 14 years old unmarried female patient with depression. At first, she started with moping and gradually developed into self-injury and whispering. After antidepressant treatment combined with the second-generation antipsychotic drug blonanserin, the patient’s psychotic and depressive symptoms improved significantly, while the patient developed lactation, which stopped after the medication was changed.ConclusionsAlthough Blonanserin’s clinical trials have reported rare adverse reactions like elevated prolactin levels and even lactation, caution is still needed in clinical application of the drug. This case is expected to improve psychiatrists’ choice of antidepressant therapy in combination with antipsychotic drugs.

Substituting with alternativeiodinated contrast medium to prevent recurrent adverse drug reactions associated with its use: a meta-analysis.

To systematically review and meta-analyze the recurrent rate of iodinated contrast medium (ICM)-associated adverse drug reactions (ADRs) and the preventive effect of using alternative ICM lacking a common carbamoyl side chain. A systematic literature search was conducted in the MEDLINE and EMBASE databases to identify studies that investigated the recurrence rate of ICM-associated ADRs or hypersensitivity reactions (HSRs). Studies that included patients who subsequently underwent contrast-enhanced computed tomography scans after their index reactions were included, while studies with overlapping cohorts were excluded. The first search was conducted on November 10, 2023. The pooled recurrence rate of ICM-associated ADR was determined using the DerSimonian-Laird random-effects model. Subgroup analyses were also conducted based on the substitution of ICM, with particular consideration given to the N-(2,3-dihydroxypropyl) carbamoyl side chain. A total of ten original articles were included in the analysis, collectively spanning from June 2001 to March 2021. The pooled recurrence rate of ICM-associated ADR was not significantly different from that of ICM-associated HSR (16.6% [95% CI, 7.8-31.9%] vs. 15.5% [95% CI, 10.8-21.8%], p = 0.87). In the subgroup analyses, the pooled odds ratio for ICM-associated recurrent ADR when using a different ICM compared with using the same ICM was 0.31 (95% CI, 0.21-0.45), which means a 69% reduction. Moreover, the pooled odds ratio for ICM-associated recurrent ADR when substituting ICMs with different side chains compared with substituting with common side chains was 0.65 (95% CI, 0.52-0.82), which means an additional 35% reduction. Substituting with an alternative ICM led to a 69% reduction in recurrent ADRs, with an additional 35% reduction observed when using ICM lacking a common carbamoyl side chain. Question No standardized guidelines exist for replacing previously used iodinated contrast medium (ICM) to prevent recurrent adverse reactions. Findings Using alternative contrast medium with a different carbamoyl side chain prevents adverse drug reactions effectively. Clinical relevance This study advocates using alternative ICM without a common carbamoyl side chain to prevent recurrent adverse drug reactions in patients with a history of such events.

Association between exposure to proton pump inhibitors and delirium: a descriptive and disproportionality analysis of VigiBase

ObjectivesProton pump inhibitor (PPI) exposure can lead to hyponatraemia, which is a common cause of delirium. An association between PPI exposure and delirium without hyponatraemia has been suggested in the...

Coadministration of Voriconazole and Rifabutin Can Increase the Risk of Adverse Drug Reactions in Patients with Multiple Infections.

Coinfection of tuberculosis or nontuberculous mycobacteria and Aspergillus presents a challenge in medication selection because of the pharmacokinetic interactions between rifampin and voriconazole. Some researchers have suggested the use of rifabutin as an alternative to rifampin because of its lower hepatic cytochrome P450 enzyme induction potency despite its contraindication to drug labels. This study presents clinical cases of voriconazole and rifabutin coadministration and their potential risks. This retrospective study was conducted using clinical data from patients who met the following criteria: (1) admitted to Seoul National University Hospital between July 2014 and August 2023 and (2) concurrently administered rifabutin and voriconazole for more than 5 days. Among the 6 patients analyzed, 4 experienced adverse drug reactions (ADRs). Three patients experienced visual and auditory hallucinations, lower extremity numbness, or delirious behavior. Two patients had prolonged the time from the start of the Q wave to the end of the T wave intervals, and 1 had elevated aspartate aminotransferase and alanine aminotransferase levels. In addition, 2 patients experienced severe nausea, poor oral intake, and weight loss. Despite receiving 1.81-fold the recommended voriconazole dosage, a therapeutic concentration (1.0-5.5 mg/L) was not achieved because of cytochrome P450 induction by rifabutin. However, during septic shock, the voriconazole concentration increased by 13.7- to 36-fold. Concurrent use of rifabutin and voriconazole was associated with ADRs, including the time from the start of the Q wave to the end of the T wave prolongation, hallucinations, and severe nausea. Moreover, initially, there was a significant decrease in voriconazole concentrations; however, these concentrations substantially increased during septic shock. Therefore, it is essential to monitor drug concentrations and ADRs during concurrent use of voriconazole and rifabutin.

Rituximab Therapy for Immune-Mediated Neurological Diseases: Our Experience at a Tertiary Care Centre.

Rituximab (RTX) is a monoclonal anti-CD20 chimeric antibody that inhibits B cell activity. However, it is an appealing substitute for traditional immunomodulatory drugs as a swiftly acting, targeted therapy with mounting evidence of efficacy and tolerance in numerous neuroinflammatory conditions. We discuss the scientific evidence for the use of RTX in neurological illnesses, as well as the dose, safety, and other practical elements of prescription. This study aims to assess and correlate the effects of RTX on immune-mediated neurological disorders. The primary objective of this study is to determine the outcomes in patients treated with RTX for the following conditions: myasthenia gravis (MG), autoimmune encephalitis, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disease (MOGAD), immune-mediated peripheral neuropathy, and inflammatory muscle disease. The secondary objective is to assess adverse drug reactions in patients treated with RTX. This is a prospective observational study conducted at a tertiary care centre. The data were analyzed for the period from May 2022 to May 2024. Approval was obtained from the institutional ethics committee before commencing the study, andwritten informed consent was obtained from all patients. A total of 56 patients were included in the study. The distribution of patients according to diseases is as follows: MG (17), MS (11), NMOSD (10), MOGAD (7), immune-mediated peripheral neuropathy (6), autoimmune encephalitis (3), and inflammatory muscle disease (2). However, one patient was lost to follow-up in the autoimmune encephalitis group. All patients experienced improvements in symptoms, and no relapse episodes have been reported except for one patient who had a relapse in the inflammatory muscle disease group. During the infusion process, some adverse drug reactions, such as chills and rigors, were observed, and two patients experienced major side effects, such as Pott's disease and cryptogenic organizing pneumonia. Nevertheless, overall, rituximab shows promise as an off-labelimmunosuppressive treatment for the aforementioned neurological immune-mediated diseases.

Pharmacodermia after use of Anti-Inflammatory: A Case Report

This case report aimed to show the interference of pharmacodermia in the increased use of anti-inflammatory drugs and evaluate the incidence of drug reactions in patients with evolution to cutaneous manifestations assuming multiple clinical aspects. An elderly patient on continuous use of bronchodilators, anticholinergics, and inhaled corticosteroids was hospitalized for pharmacodermia treatment after the use of anti-inflammatory drugs. The patient was admitted with a history of using Flancox (etodolac) for two days for low back pain, evolving suddenly with pruritic urticarial plaques in the trunk region, migrating to limbs and face. She mentioned being allergic to nimesulide, dipyrone, and penicillin during the anamnesis. The medication was immediately discontinued and intravenous corticosteroids (hydrocortisone 200 mg IV 8/8 h) were started associated with clinical support and antihistamine measures. The patient was discharged after seven days of hospitalization, with clinical improvement and remission of lesions. Corticosteroid suspension was prescribed with prednisone, Hixizine 25 mg, and promethazine.

Evaluation of severe adverse cutaneous drug reactions in patients admitted to tertiary care center: A cross-sectional study.

Adverse cutaneous drug reactions (ACDRs) are common and potentially life-threatening, while also hindering patient compliance to medications. Given the regional differences in patterns and prevalence of ACDRs, it is important to study the epidemiology, as well as the clinical and outcome patterns of patients with ACDRs in Iran. This cross-sectional study on ACDRs was conducted among hospitalized patients in a referral university hospital in the city of Isfahan, Iran. The patients' demographics, clinical information, and outcomes, including age, gender, past medical history, medication history, drug reaction with eosinophilia and systemic symptoms (DRESS) diagnosis, Steven-Johnson Syndrome (SJS) diagnosis, toxic epidermal necrosis (TEN) diagnosis, treatment regimen (steroids or intravenous immunoglobulin [IVIG]) and outcome information, including intensive care requirements, severe medical complications, or death, were obtained from medical records. A total of 195 patients with a mean age of 40 years and consisting of 61% females were included. Carbamazepine, lamotrigine, sodium valproate, and phenytoin are the most commonly reported medications. Rate of complications was 45% with DRESS, SJS, and TEN diagnosed in 26%, 47%, and 19%, respectively. Treatment was carried out with steroids and IVIG in 81% and 19%, respectively. Among patients, 15% required intensive care and 5% died. Diagnosis of TEN, older age, and baseline heart disease were predictors of mortality. Patients with SJS were younger and more likely to be males, and they were more likely to have eye complications. On the other hand, patients with the diagnosis of TEN were more likely to receive IVIG and intensive care, and had a higher mortality rate. Our study provides insight into the demographics and clinical patterns of Iranian patients with ACDRs. This will help in predicting rates of complications, treatments, and outcomes in patients and therefore make proper management decisions.

Safety and Efficacy of Treatments for COVID-19: A Pharmacovigilance Perspective

Objective: COVID-19 has generated the development of safe and effective against viral disease. In this context, the Pharmacovigilance emerges as a crucial tool to provide detailed follow-up of treatments administered to infected patients. The objective of this review is to understand the role and progress of pharmacovigilance in the COVID-19 pandemic by supporting healthcare professionals and providing information about possible Adverse Drug Reactions in patients. Methods: A review of Pharmacovigilance related to COVID-19 was conducted, addressing aspects such as the monitoring of Adverse Drug Reactions, virus structure and therapeutic advances, since 2019 to 2022, databases such as Pubmed, Scielo, Science Direct, JAMA y Redalyc were used, analyzing clinical trials, observational studies and case reports to assess the safety of drugs used in the treatments of COVID-19. Results: Pharmacovigilance provides information of risk and benefits of drugs. Reports have been implemented to detect Adverse Drug Reactions and seek pharmacological alternatives to reduce serius symptoms and complications. Conclusion: Pharmacovigilance in the COVID-19 pandemic requires efficient communication between healthcare professionals and pharmacists ensuring quality treatments and detecting possible Adverse Drug Reactions.

Meta-analysis of ACE inhibitor–induced angioedema identifies novel risk locus

Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited. We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology. By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE. Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort. The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.

Challenges in Drug and Hymenoptera Venom Hypersensitivity Diagnosis and Management in Mastocytosis.

Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy.

Kidney Function Decline and Serious Adverse Drug Reactions in Patients With CKD

Adverse drug reactions (ADRs) are common in patients with chronic kidney disease (CKD). The impact of kidney function decline on serious ADR risk has been poorly investigated. We comprehensively describe ADRs and assess the relationship between estimated glomerular filtration rate (eGFR) and serious ADR risk. Prospective cohort study. 3,033 participants in French Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort study, a nationwide sample of nephrology outpatients with moderate to advanced CKD. Demographic and biological data (including eGFR), medication prescriptions. ADRs (preventable or not) were prospectively identified from hospital discharge reports, medical records, and patient interviews. Expert pharmacologists used validated tools to adjudicate ADRs. Restricted cubic splines in fully adjusted cause-specific Cox proportional hazard models were used to evaluate the relationship between eGFR and the risk of serious ADRs (overall and by subtype). During a median follow-up period of 4.7 years, 360 patients experienced 488 serious ADRs. Kidney and urinary disorders (n=170) and hemorrhage (n=170) accounted for 70% of serious ADRs. The most common medications classes were antithrombotics and renin-angiotensin system inhibitors. The majority of those serious ADRs were associated with hospitalization (n=467), with 32 directly or indirectly associated with death and 22 associated with a life-threatening event. More than 27% of the 488 serious ADRs were preventable or potentially preventable. The eGFR is a major risk factor for serious ADRs. The risk of acute kidney injury was 2.2% higher and risk of bleeding ADRs was 8% higher for each 1mL/min/1.73m2 lower baseline eGFR. The results cannot be extrapolated to patients who are not being treated by a nephrologist. ADRs constitute a major cause of hospitalization in CKD patients for whom lower eGFR level is a major risk factor. Patients with chronic kidney disease (CKD) have complex clinical presentations, take multiple medications, and often receive inappropriate prescriptions. Using data from a large, prospective CKD cohort, we found a high incidence of serious adverse drug reactions (ADRs). The 2 most common serious ADRs were drug-induced acute kidney injury and bleeding. A large proportion of serious ADRs required hospital admission, and 11% led to death or were life threatening. Lower kidney function was a major risk factor for serious ADRs. Many of these serious ADRs were determined to be partly preventable through greater adherence to prescription guidelines. This report enhances our understanding of the potential toxicity of drugs taken by patients with moderate to advanced CKD. It emphasizes the importance of monitoring kidney function when prescribing drugs, particularly for high-risk medications such as antithrombotic agents.

Clinical profile of adverse drug reactions in patients admitted to internal medicine wards of a tertiary care hospital

Introduction: Adverse drug reactions (ADRs) are unwanted, often harmful reaction resulting from a pharmacological intervention that warrants treatment, prevention, and future precautions. ADRs are highly prevalent with 10%–20% of patients suffering from one when admitted. The aim of this study was to identify cases and provide data on the incidence, severity, causality, and preventability of ADRs in a clinical setting in various age groups. The study also aimed to identify ADR risk factors which can be used to create ADR risk prediction models for application in everyday clinical practice to proactively detect patients at risk of developing these reactions. Materials and Methods: This was an inpatient, prospective, observational cohort study in the internal medicine ward of a major tertiary care hospital. Once the institutional ethics approval was obtained, patients fulfilling the inclusion criteria were enrolled with informed consent. Their data were recorded in an ADR data form. These data were then analyzed using standardized scales to identify causality, severity, preventability, and avoidability along with specific risk factors and comparing them across age groups and drug classes. Results: One hundred and sixty-four patients were eligible and enrolled. Seventy percent of those suffering from ADRs were in the 30–60 years age group. Oral hypoglycemics and antituberculosis drugs were most commonly implicated, whereas metabolic and hepatic systems were the most frequent organ systems involved. Polypharmacy and hypertension were the most common risk factors identified. The cause of 96.3% of ADRs was probable, and 51.2% of the ADRs were categorized as severe. Nearly a fourth of the severe ADRs were categorized as life-threatening. A majority of the ADRs were treated by terminating the suspected drug, and 54% of patients recovered completely. 6.1% of the ADRs were definitely avoidable while 42.1% were unavoidable. Conclusion: This study clearly demonstrates the massive burden of ADRs, both on the patients and the hospitals. There is a dire need for a standardized, easily accessible means of mandatory reporting of ADRs, and that data need to be utilized to treat, decrease morbidity, and prevent ADRs by proactively anticipating them to ultimately improve patient care. The following core competencies are addressed in this article: Patient care, Medical knowledge, Interpersonal and communication skills, Practice-based learning and improvement, and Systems-based practice

Assessment of prescribing pattern and adverse drug reaction in patients receiving anticoagulant therapy: A prospective observational study.

Cardiovascular diseases (CVD) are the leading cause of death worldwide as well as a major blockade to sustainable human development. It is among the leading causes of morbidity and mortality. Anticoagulants are among the most essential life-saving drugs that are generally used in cardiology for the prevention and treatment of many CVD. To assess the prescribing pattern and adverse drug reaction (ADR) in patients receiving anticoagulant therapy for cardiac diseases. This was a Prospective Observational study conducted in the Department of Cardiology, SRM Medical College Hospital and Research Center, Kattankulathur including 88 patients for 6 months. Out of the 88 patients, the majority were males (73%) compared to females (27%), and the prevalence of CVD was found to be higher in patients above 40 years of age. Various categories of drugs prescribed to the patients were antiplatelets (14.88%), anticoagulants (8.79%), antianginal (13.82%), antihypertensives (15.7%), antihyperlipidemic (7.83%), thrombolytics (0.68%), Ionotropic agents (2.13%), antibiotics (5.31%), and other miscellaneous drugs (36.61%). The anticoagulant dosage regimens prescribed to the patients were categorized into monotherapy (9%), combinational therapy with antiplatelets (38%), and triple therapy (53%). The most commonly prescribed anticoagulant to the patients was Heparin (93.41%), followed by Warfarin (5.49%) and lastly Rivaroxaban (1.10%) respectively. From the details of the prescriptions analyzed, the average number of drugs per patient (prescription) was found to be 11.7. Heparin was found to be the most commonly used anticoagulant, Combination therapy of antiplatelets and antihypertensives was observed in most of the prescriptions, which is more effective than a single therapy. Polypharmacy was encountered in the study with an average number of 11.7 drugs per prescription. Several anticoagulant-related drug interactions were identified and there were two adverse drug reactions with Heparin. The prescribing pattern can be improved by reducing the number of drugs prescribed.

Investigation of the Association Between ITPA Gene 94C>A Sequence Variant and Kidney Transplant Rejection in Iranian Kidney Transplant Recipients.

Thiopurine prodrugs are commonly used in kidney transplant recipients. Inosine triphosphate pyrophosphatase is an enzyme encoded by the ITPA gene. Alteration of ITPA gene is one of the pharmacogenetic sequence variants possibly involved in thiopurine metabolism. The ITPA 94C>A sequence variant (C-to-A substitution at nucleotide 94) is associated with an increased risk of adverse drug reactions in patients treated with the thiopurine drug. The aim of the present study was to investigate the effect of the ITPA 94C>A gene sequence variant in kidney transplant recipients. The genotyping of the ITPA rs1127354 variant was performed by the polymerase chain reaction restriction fragment length polymorphism method in 140 kidney transplant recipients and in 100 control participants. Data were analyzed with SPSS statistical software. The results revealed a significant difference between control and nonrejection groups regarding the rs1127354 genotype and allele frequency. No significant difference was found between the rejection and nonrejection groups regarding the rs1127354 genotype and allele frequency. Also, a significant association was observed between the ageofthe control group and age of the rejection group. No significant differences between sex and underlying disease in patients with or without rejection were observed. We observed no significant differences between rejection and nonrejection transplant. Further studies are recommended, in a larger population and with different ethnicities.

Apoptosis and inflammatory genes variants in primary non-response to anti-TNF therapy in Crohn's disease patients.

Anti-TNF therapy has indeed revolutionized the treatment of Crohn's disease, leading to higher rates of response and remission in patients. However, a significant proportion of 20-40% of patients do not respond to the initial therapy, others experience a secondary loss of response with ongoing treatment. Adverse drug reactions also occur in some patients. The effectiveness of anti-TNF treatment may be influenced by genetic variability, including FCGR3A, ADAM17, TNFRSF1A, TNFRSF1B, FAS, FASL, IL1B, CASP9 , and MIF genes. In this article, we provide an overview of the current knowledge and findings in the pharmacogenetics of anti-TNF drugs in CD focusing on the aspect of apoptosis and inflammatory genes variants in primary non-response. Pharmacogenetic investigations have been conducted to identify genetic markers that can predict response to anti-TNF therapy. However, large multi-center validation studies and multi-loci algorithms development are required to effectively prognose the treatment effect. The identification of predictive markers of response to anti-TNF therapy can help clinicians make informed decisions about treatment options and minimize adverse drug reactions in patients.

Safe Introduction of Hydroxychloroquine Focusing on Early Intolerance Due to Adverse Drug Reactions in Patients with Systemic Lupus Erythematosus.

Objective This study explored the predictors of hydroxychloroquine intolerance and propose appropriate methods to initiate hydroxychloroquine in patients with systemic lupus erythematosus. Methods This retrospective study registered consecutive patients who were diagnosed with systemic lupus erythematosus and started treatment with hydroxychloroquine between 2015 and 2021. Any adverse events that required dose reduction or cessation of hydroxychloroquine, indicating intolerance to the drug, were recorded for up to 26 weeks after initiation of hydroxychloroquine. Results A total of 130 patients were included. Hydroxychloroquine intolerance due to adverse drug reactions was observed in 28 patients (21.5%), including gastrointestinal symptoms in 15 (11.5%) and cutaneous reactions in 7 (5.4%). Furthermore, the intolerance was observed more frequently in the maintenance group (patients treated daily with <20 mg prednisolone) than in the induction group (7.1% vs. 25.5%, p=0.04), and none of the patients in the induction group developed cutaneous reactions. The initial dose of hydroxychloroquine per ideal body weight was associated with hydroxychloroquine intolerance in a dose-dependent manner. Multivariable analyses revealed that the hydroxychloroquine dose per ideal body weight and higher levels of C4 predicted hydroxychloroquine intolerance. In particular, C4 levels were positively correlated with cutaneous reactions, whereas the dose of prednisolone was negatively correlated with gastrointestinal reactions. Conclusion Low-dose hydroxychloroquine may be optimal for induction in patients with systemic lupus erythematosus who have high C4 levels or are taking low doses of steroids.

The therapeutic concordance approach reduces adverse drug reactions in patients with resistant hypertension.

Adverse drug reactions (ADRs) remain among the leading causes of therapy-resistant hypertension (TRH) and uncontrolled blood pressure (BP). We have recently reported beneficial results in BP control in patients with TRH adopting an innovative approach, defined as therapeutic concordance, in which trained physicians and pharmacists reach a concordance with patients to make them more involved in the therapeutic decision-making process. The main scope of this study was to investigate whether the therapeutic concordance approach could lead to a reduction in ADR occurrence in TRH patients. The study was performed in a large population of hypertensive subjects of the Campania Salute Network in Italy (ClinicalTrials.gov Identifier: NCT02211365). We enrolled 4,943 patients who were firstly followed-up for 77.64 ± 34.44 months, allowing us to identify 564 subjects with TRH. Then, 282 of these patients agreed to participate in an investigation to test the impact of the therapeutic concordance approach on ADRs. At the end of this investigation, which had a follow-up of 91.91 ± 54.7 months, 213 patients (75.5%) remained uncontrolled while 69 patients (24.5%, p < 0.0001) reached an optimal BP control. Strikingly, during the first follow-up, patients had complained of a total of 194 ADRs, with an occurrence rate of 68.1% and the therapeutic concordance approach significantly reduced ADRs to 72 (25.5%). Our findings indicate that the therapeutic concordance approach significantly reduces ADRs in TRH patients.

Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis.

We evaluated the relationship between the pharmacokinetic parameters of linezolid (LZD) and development of adverse drug reactions (ADRs) in patients with pulmonary drug-resistant tuberculosis. A prospective cohort of adults with pulmonary multidrug-resistant tuberculosis with additional resistance to fluoroquinolone (MDR-TBFQ+) received treatment with bedaquiline, delamanid, clofazimine, and LZD. Blood samples were collected during weeks 8 and 16 at eight time points over 24 h. The pharmacokinetic parameters of LZD were measured using high-performance liquid chromatography and associated with ADRs. Of the 165 MDR-TBFQ+ patients on treatment, 78 patients developed LZD-associated anemia and 69 developed peripheral neuropathy. Twenty-three patients underwent intense pharmacokinetic testing. Plasma median trough concentration was 2.08 µg/mL and 3.41 µg/mL, (normal <2 µg/mL) and AUC0-24 was 184.5 µg/h/mL and 240.5 µg/h/mL at weeks 8 and 16, respectively, showing a linear relationship between duration of intake and plasma levels. Nineteen patients showed LZD-associated ADRs-nine at week 8, twelve at week 16, and two at both weeks 8 and 16. Thirteen of the nineteen had high plasma trough and peak concentrations of LZD. A strong association between LZD-associated ADRs and plasma LZD levels was noted. Trough concentration alone or combinations of trough with peak levels are potential targets for therapeutic drug monitoring.

A Case of Oral-Vancomycin-Induced Rash in a Patient with Acute Kidney Injury

Clostridioides difficile infection (CDI) is one of the most common hospital-acquired infections. Its incidence has increased during the last decade in the community among individuals with no previous risk factors; however, morbidity and mortality are still considered high in elderly patients. Oral Vancomycin and Fidaxomicin are the first lines of treatment for CDI. The systemic bioavailability of oral Vancomycin is thought to be undetectable due to its poor absorption in the gastrointestinal tract; therefore, routine monitoring is not warranted. Only 12 case reports were found in the literature that described adverse reactions associated with oral Vancomycin and its related risk factors. We present a case of a 66-year-old gentleman with severe CDI and acute renal failure who was started on oral Vancomycin upon admission. On day five of treatment, he developed leukocytosis associated with neutrophilia, eosinophilia, and atypical lymphocytes, with no evidence of active infection. Three days later, he developed a pruritic maculopapular rash in more than 50% of his body surface area. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) was ruled out since the patient only had three inclusion criteria for this diagnosis. No clear inciting agent was found. Oral Vancomycin was stopped and supportive treatment was supplied for a presumed Vancomycin-induced allergic reaction. The patient had an excellent response, with complete resolution of the rash and leukocytosis in less than 48 h. By reporting this case, we want to raise awareness among clinicians to remember that, albeit rare, oral Vancomycin can be the cause of adverse drug reactions in patients with severe illnesses.

Assessment of Amikacin- and Capreomycin-Related Adverse Drug Reactions in Patients with Multidrug-Resistant Tuberculosis and Exploring the Role of Genetic Factors.

Following the introduction of all-oral treatment regimens for patients with drug-resistant tuberculosis (TB), second-line injectable drug applications have been reduced in the last few years. However, they are still important for anti-TB therapy. This study aims to analyze the occurrence of amikacin- and capreomycin-related adverse drug reactions (ADR) in patients with multidrug-resistant tuberculosis (MDR-TB) and evaluate the role of multiple patient-, disease-, and therapy-related factors on the frequency of the observed adverse events. In addition, the possible role of genetic risk factors was studied by full-length mitochondrial DNA sequencing. Toward this aim, we retrospectively evaluated 47 patients with MDR-TB who received amikacin and/or capreomycin. In total, 16 (34.0%) patients developed ototoxicity and 13 (27.7%) developed nephrotoxicity, including 3 (6.4%) patients who experienced both adverse events. Ototoxicity development was more common in patients who received amikacin. No other factors showed a significant impact. Nephrotoxicity was likely associated with previous renal health impairment. Full mitochondrial genome sequencing did not reveal any specific ADR-associated variants, and results showed no differences in adverse event occurrence for any specific variants, mutation count, or mitochondrial haplogroup. The absence of the previously reported ototoxicity-related mtDNA variants in our patients with ototoxicity and nephrotoxicity highlighted the complex nature of the ADR occurrence.