Learning lessons from adverse drug reactions in children

Drug toxicity is, unfortunately, a significant problem in children both in the hospital and in the community. Drug toxicity in children is different to that seen in adults. At least one in 500 children will experience an adverse drug reaction each year. For children in hospital, the risk is far greater (one in ten). Additionally, different and sometimes unique adverse drug reactions are seen in the paediatric age groups. Some of the major cases of drug toxicity historically have occurred in neonates. It is important that we understand the mechanism of action of adverse drug reactions. Greater understanding alongside rational prescribing should hopefully reduce drug toxicity in children in the future

Acute Liver Failure In A Term Neonate After Repeated Paracetamol Administration.

Severe hepatotoxicity caused by paracetamol is rare in neonates. We report a case of paracetamol-induced acute liver failure in a term neonate. A 26-day-old boy was admitted with intestinal bleeding, shock signs, slight liver enlargement, coagulopathy, metabolic acidosis (pH=7.21; bicarbonate: 7.1 mEq/L), hypoglycemia (18 mg/dL), increased serum aminotransferase activity (AST=4,039 IU/L; ALT=1,087 IU/L) and hyperbilirubinemia (total: 9.57 mg/dL; direct: 6.18 mg/dL) after receiving oral paracetamol (10 mg/kg/dose every 4 hours) for three consecutive days (total dose around 180 mg/kg; serum concentration 36-48 hours after the last dose of 77 µg/ mL). Apart from supportive measures, the patient was successfully treated with intravenous N-acetylcysteine infusion during 11 consecutive days, and was discharged on day 34. The follow-up revealed full recovery of clinical and of laboratory findings of hepatic function. The paracetamol pharmacokinetics and pharmacodynamics in neonates and infants differ substantially from those in older children and adults. Despite the reduced rates of metabolism by the P-450 CYP2E1 enzyme system and the increased ability to synthesize glutathione--which provides greater resistance after overdoses--, it is possible to produce hepatotoxic metabolites (N-acetyl-p-benzoquinone) that cause hepatocellular damage, if glutathione sources are depleted. Paracetamol clearance is reduced and the half-life of elimination is prolonged. Therefore, a particular dosing regimen should be followed due to the toxicity risk of cumulative doses. This report highlights the risk for severe hepatotoxicity in neonates after paracetamol multiple doses for more than two to three days.32144-

Management of Tuberculosis: a handbook for clinicians

This handbook, a distillation of recommendations from international TB guidelines and the accumulated clinical experience of its authors, provides practical information for clinicians involved in the care of patients with tuberculosis (TB) and other mycobacterial diseases. Topics covered are: management of drug-sensitive and drug-resistant TB; latent TB infection; pregnancy and TB; HIV and TB; nontuberculous mycobacterial infections; BCG vaccination and BCG installation for bladder cancer. The emphasis is on presenting a practical approach to the many clinical issues, common and uncommon, that arise in the day-to-day management of patients with mycobacterial infections. The handbook is primarily intended for specialists and trainee specialists working in the ward and in the outpatient clinic, but it should also appeal to pharmacists and nurses involved with TB care, and to students

Advances in Treatment and Outcomes of Patients with <em>Legionella</em> Infection

Manifestations of Legionella infections range from benign, mild disease to a more severe form with increased morbidity and mortality, especially in untreated patients. Despite diagnostic advances, clinical diagnosis remains elusive. Macrolides and respiratory fluoroquinolones remain the antibiotics of choice for treatment of Legionella; however, several new antibiotics are currently under development or in clinical trials. The recommended duration of antibiotics is 5–7 days; although, some critically ill or immunosuppressed patients may require longer treatment. In vivo resistance to these antibiotics is rare, and there is no evidence that combination therapy is more beneficial than monotherapy. Early suspicion, diagnosis, and treatment are paramount for improving outcomes

Environmental toxicants in breast milk of Norwegian mothers and gut bacteria composition and metabolites in their infants at 1&nbsp;month.

BACKGROUND:Early disruption of the microbial community may influence life-long health. Environmental toxicants can contaminate breast milk and the developing infant gut microbiome is directly exposed. We investigated whether environmental toxicants in breastmilk affect the composition and function of the infant gut microbiome at 1&nbsp;month. We measured environmental toxicants in breastmilk, fecal short-chain fatty acids (SCFAs), and gut microbial composition from 16S rRNA gene amplicon sequencing using samples from 267 mother-child pairs in the Norwegian Microbiota Cohort (NoMIC). We tested 28 chemical exposures: polychlorinated biphenyls (PCBs), polybrominated flame retardants (PBDEs), per- and polyfluoroalkyl substances (PFASs), and organochlorine pesticides. We assessed chemical exposure and alpha diversity/SCFAs using elastic net regression modeling and generalized linear models, adjusting for confounders, and variation in beta diversity (UniFrac), taxa abundance (ANCOM), and predicted metagenomes (PiCRUSt) in low, medium, and high exposed groups. RESULTS:PBDE-28 and the surfactant perfluorooctanesulfonic acid (PFOS) were associated with less microbiome diversity. Some sub-OTUs of Lactobacillus, an important genus in early life, were lower in abundance in samples from infants with relative "high" (&gt; 80th percentile) vs. "low" (&lt; 20th percentile) toxicant exposure in this cohort. Moreover, breast milk toxicants were associated with microbiome functionality, explaining up to 34% of variance in acetic and propionic SCFAs, essential signaling molecules. Per one standard deviation of exposure, PBDE-28 was associated with less propionic acid (- 24% [95% CI - 35% to - 14%] relative to the mean), and PCB-209 with less acetic acid (- 15% [95% CI - 29% to - 0.4%]). Conversely, PFOA and dioxin-like PCB-167 were associated with 61% (95% CI 35% to 87%) and 22% (95% CI 8% to 35%) more propionic and acetic acid, respectively. CONCLUSIONS:Environmental toxicant exposure may influence infant gut microbial function during a critical developmental window. Future studies are needed to replicate these novel findings and investigate whether this has any impact on child health

Microbiology and ecology are vitally important to premedical curricula

Despite the impact of the human microbiome on health, an appreciation of microbial ecology is yet to be translated into mainstream medical training and practice. The human microbiota plays a role in the development of the immune system, in the development and function of the brain, in digestion, and in host defense, and we anticipate that many more functions are yet to be discovered. We argue here that without formal exposure to microbiology and ecology—fields that explore the networks, interactions and dynamics between members of populations of microbes—vitally important links between the human microbiome and health will be overlooked. This educational shortfall has significant downstream effects on patient care and biomedical research, and we provide examples from current research highlighting the influence of the microbiome on human health. We conclude that formally incorporating microbiology and ecology into the premedical curricula is invaluable to the training of future health professionals and critical to the development of novel therapeutics and treatment practices

Fulminate Hepatic Failure in a 5 Year Old Female after Inappropriate Acetaminophen Treatment

BACKGROUND: Acetaminophen is a drug widely used in children because of its safety and efficacy. Although the risk of its toxicity is lower in children such reactions occur in pediatric patients from intentional overdoses and less frequently attributable to unintended inappropriate dosing. The aim of reporting this case is to attract the attention to the risk of the acetaminophen toxicity when administered in high doses.CASE PRESENTATION: We report here a 5 year old girl who developed fulminate liver failure with renal impairment and acute pancreatitis, as a result of acetaminophen toxicity caused from unintentional repeated supratherapeutic ingestion, with a total administered dose of 4800 mg in three consecutive days, 1600 mg/day, approximately 90 mg/kg/day. The blood level of acetaminophen after 10 hours of the last administered dose was 32 mg/l. The patient presented with high fever, jaundice, lethargic, agitating with abdominal pain accompanied by encephalopathy. The liver function test revealed with high level of alanine aminotransferase 5794 UI/l and aspartate aminotransferase 6000 UI/l. Early initiation of oral N-acetylcysteine (NAC) after biochemical evidence of liver toxicity was beneficial with rapid improvement of liver enzymes, hepatic function and encephalopathy. During the course of the illness the child developed acute pancreatitis with hyperamylasemia 255 UI/L and hyperlypasemia 514 UI/ L. Patient totally recovered within 29 days.CONCLUSION: Healthcare providers should considered probable acetaminophen toxicity in any child who has received the drug and presented with liver failure. When there is a high index of suspicion of acetaminophen toxicity NAC should be initiated and continued until there are no signs of hepatic dysfunction

Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV

Developed by the National Institutes of Health, the Centers for Disease Control and Prevention, and the HIV Medicine Association of the Infectious Diseases Society of America Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV\u2014A Working Group of the NIH Office of AIDS Research Advisory Council (OARAC).The Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV document is published in an electronic format and updated as relevant changes in prevention and treatment recommendations occur.All changes are developed by the subject-matter groups listed in the document. (Changes in group composition also are posted promptly.) These changes are reviewed by the editors and by relevant outside reviewers before the document is altered.How to Cite the Adult and Adolescent Opportunistic Infection Guidelines: Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and- adolescent-opportunistic-infection. Accessed (insert date) [include page numbers, table number, etc., if applicable].Publication date from document properties.guidelines-adult-adolescent-oi.pd

Hepatitis C and Risk of Adverse Treatment Outcomes among Patients with HIV and Multidrug-resistant Tuberculosis

BACKGROUND Multidrug-resistant (MDR) tuberculosis (TB) is a public health emergency that causes substantial morbidity and mortality. Treatment of MDR-TB requires 9-24 months of second-line regimens, has poor success rates, and frequently results in harmful side effects. Hepatitis C virus (HCV) co-infection is a common comorbidity among patients with MDR-TB/HIV and contributes to acute and chronic liver conditions, potentially increasing the risk of hepatotoxicity and adverse treatment outcomes. The aim of this study was to estimate the association between HCV co-infection and adverse MDR-TB treatment outcomes among patients with MDR-TB and HIV. METHODS We conducted a retrospective cohort study among MDR-TB patients co-infected with HIV receiving clinical care from Médecins Sans Frontières (MSF) in Yangon, Myanmar during 2009-2017. Eligible patients included adults aged ≥18 years who had final MDR-TB treatment outcome and HCV status documented. HCV status was determined by OraQuick® antibody test. Treatment outcome was classified as favorable (cured and treatment completed) or adverse (default, failed, died, not evaluated). RESULTS Among patients with MDR-TB and HIV (n=220), the overall treatment success rate was 65% (95%CI 59 – 71%) and 8% (95%CI 5-12%) had HCV. Co-infection with HCV was not significantly associated with adverse treatment outcome in unadjusted (OR 1.33, 95%CI 0.49 – 3.65) or adjusted analyses (aOR 1.43, 95%CI 0.50 – 4.03). CONCLUSION Whether patients with HIV/HCV co-infection require altered MDR-TB treatment regimens remains an important gap in knowledge. Additional research is needed to determine the relationship between the extent of hepatotoxicity due to HCV co-infection, interaction with second-line TB medications, and risk of poor MDR-TB treatment outcomes among patients with and without HIV