Risk factors of drug-induced diseases. Part 2. Comorbid diseases and lifestyle factors

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

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Incidence and risk factors of anti‐tuberculosis drug induced liver injury (DILI): Large cohort study involving 4652 Chinese adult tuberculosis patients

Liver International ◽

10.1111/liv.14896 ◽

2021 ◽

Author(s):

Fanrong Jiang ◽

Huadong Yan ◽

Lili Liang ◽

Jingyuan Du ◽

Susu Jin ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Liver Injury ◽

Large Cohort ◽

Drug Induced ◽

Tuberculosis Patients ◽

Drug Induced Liver Injury ◽

Chinese Adult ◽

Large Cohort Study

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Smoking, drinking, diet and physical activity—modifiable lifestyle risk factors and their associations with age to first chronic disease

International Journal of Epidemiology ◽

10.1093/ije/dyz078 ◽

2019 ◽

Vol 49 (1) ◽

pp. 113-130 ◽

Cited By ~ 7

Author(s):

Ryan Ng ◽

Rinku Sutradhar ◽

Zhan Yao ◽

Walter P Wodchis ◽

Laura C Rosella

Keyword(s):

Risk Factors ◽

Chronic Disease ◽

Chronic Diseases ◽

Lifestyle Factors ◽

Competing Risk ◽

Chronic Obstructive ◽

Common Disease ◽

Heavy Smoking ◽

Lifestyle Risk Factors ◽

Lifestyle Risk

AbstractBackgroundThis study examined the incidence of a person’s first diagnosis of a selected chronic disease, and the relationships between modifiable lifestyle risk factors and age to first of six chronic diseases.MethodsOntario respondents from 2001 to 2010 of the Canadian Community Health Survey were followed up with administrative data until 2014 for congestive heart failure, chronic obstructive respiratory disease, diabetes, lung cancer, myocardial infarction and stroke. By sex, the cumulative incidence function of age to first chronic disease was calculated for the six chronic diseases individually and compositely. The associations between modifiable lifestyle risk factors (alcohol, body mass index, smoking, diet, physical inactivity) and age to first chronic disease were estimated using cause-specific Cox proportional hazards models and Fine-Gray competing risk models.ResultsDiabetes was the most common disease. By age 70.5 years (2015 world life expectancy), 50.9% of females and 58.1% of males had at least one disease and few had a death free of the selected diseases (3.4% females; 5.4% males). Of the lifestyle factors, heavy smoking had the strongest association with the risk of experiencing at least one chronic disease (cause-specific hazard ratio = 3.86; 95% confidence interval = 3.46, 4.31). The lifestyle factors were modelled for each disease separately, and the associations varied by chronic disease and sex.ConclusionsWe found that most individuals will have at least one of the six chronic diseases before dying. This study provides a novel approach using competing risk methods to examine the incidence of chronic diseases relative to the life course and how their incidences are associated with lifestyle behaviours.

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Spironolactone-Induced Agranulocytosis

Annals of Pharmacotherapy ◽

10.1177/106002809703100511 ◽

1997 ◽

Vol 31 (5) ◽

pp. 582-585 ◽

Cited By ~ 11

Author(s):

Anna M Whitling ◽

Pablo E Pérgola ◽

John Lee Sang ◽

Robert L Talbert

Keyword(s):

Risk Factors ◽

Adverse Effect ◽

Bone Marrow ◽

Leukocyte Count ◽

Laboratory Data ◽

University Hospital ◽

Drug Induced ◽

Bone Marrow Biopsies ◽

Case Summary ◽

Before And After

OBJECTIVE: TO report a case of agranulocytosis secondary to spironolactone in a patient with cryptogenic liver disease. CASE SUMMARY: A 58-year-old Hispanic woman with cryptogenic cirrhosis was admitted to University Hospital on October 31, 1995. Laboratory data revealed a leukocyte count of 1.0 × 103/mm3 and an absolute neutrophil count (ANC) of 10 cells/mm3. Prior to treatment with spironolactone, the leukocyte count was 10.2 × 103/mm3 and ANC 8400 cells/mm3. Agranulocytosis resolved 5 days following the discontinuation of spironolactone. Results from the bone marrow biopsies before and after treatment with spironolactone suggested that agranulocytosis was caused by the drug's toxic effect on the bone marrow. DISCUSSION: Drug-induced agranulocytosis is a serious adverse effect, occurring at a rate of approximately 6.2 cases per million persons each year. In addition to the case reported here, three other reports of agranulocytosis secondary to spironolactone have been published in the literature. Several factors have been identified that may increase a patient's risk for developing agranulocytosis, including increased age, hepatic or renal impairment, drag dosage and duration, and concurrent medications. CONCLUSIONS: Agranulocytosis secondary to spironolactone is a serious potential adverse effect. Patients with risk factors for developing this adverse effect should be closely monitored since early detection and discontinuation of spironolactone can improve prognosis.

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