Torsades de pointes and QT prolongation Associated with Antibiotics
Methods
The authors queried the United States FDA Adverse Event Reporting System (FAERS) from 01/01/2015 to 12/31/2017 for reports of Torsade de points/QT prolongation (TdP/QT).
Reporting Odd Ratio (ROR) was calculated as the ratio of the odds of reporting TdP/QTP versus all other ADRs for a given drug, compared with these reporting odds for all other drugs present in FAERS
Results
FAERS contained 2,042,801 reports from January 1, 2015 to December 31, 2017. There were 3,960 TdP/QTP reports from the study period (0.19%).
Macrolides ROR 14 (95% CI 11.8-17.38)
Linezolid ROR 12 (95% CI 8.5-18)
Amikacin ROR 11.8 (5.57-24.97)
Imipenem-cilastatin ROR 6.6 (3.13-13.9)
Fluoroquinolones ROR 5.68 (95% CI 4.78-6.76)
Limitations:
These adverse events are voluntary reports
There might be other confounded by concomitant drugs such as ondansetron, azole anti-fungals, antipsychotics.
Bottom Line:
This study confimed the previously-known antibiotics to be associated with Torsades de pointes and QT prolongation (Macrolides, Linezolid, Imipenem and Fluoroquinolones). However, this study found new association between amikacin and Torsades de pointes/QT prolongation.
A 3 year old is bitten by a spider on his right ear which is causing him intense pain, tachycardia, and muscle cramping. Identify the spider. What is the treatment?
Rapid Assessment of the RV on Bedside Echo
There are several causes of acute RV dysfunction resulting in a patient presenting to the ER with unstable hemodynamics. Some of these include acute cor pulmonale, acute right sided myocardial infarction and acute submassive or massive pulmonary embolism. While bedside assessment of the LV function is often performed by the ED physician, simultaneous evaluation of the RV can provide crucial information that can help guide therapeutic decisions to prevent worsening of the patient’s clinical condition. A rough guideline to determine RV size and function is below using the apical 4 chamber view.
Normal RV size : <2/3 the size of the LV
Mildly enlarged RV : >2/3 the size of the LV, but not equal in size
Moderately enlarged RV: RV size = LV size
Severely enlarged RV: RV size > LV size
Patients who are found to have RV dilation should be given fluids in a judicious fashion as the RV is not tolerant of fluid overload. Early diagnosis of the cause of acute RV failure should be sought to guide definitive therapy, but early institution of inotropic support should be considered. Frequent reassessments of biventricular function during resuscitation should be performed.
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While chest X ray (CXR) is routinely obtained in the setting of traumatic injury, ultrasound (US) is a fast and reliable way to evaluate for life-threatening traumatic injuries requiring emergent intervention, and is supported by the Eastern Association for the Surgery of Trauma (EAST) guidelines. A recent Cochrane Review compared the test characteristics of chest US vs CXR for detection of traumatic pneumothorax when using Chest CT or thoracostomy as the gold standard.
There possible weaknesses of this study, including blinding in the original studies, and several studies may or may not have been at risk for bias as their risk of bias was ‘unclear’. However, the results were consistent across the studies analyzed and remained similar after sensitivity analysis.
Several anatomical as well as patient care issues may confound US findings for pneumothorax such as the presence of bleb, prior thoracic surgery or pathology, as well as main stem intubation.
A recent article in Pediatrics attempted to estimate the association between fluoroquinolone use and tendon injury in an adolescent population.
Fluoroquinolones are thought to negatively impact tendons and cartilage in the load-bearing joints of the lower limbs through collagen degradation, necrosis, and disruption of the extracellular matrix.
Population: 4.4 million adolescents aged 12–18 years with filled outpatient fluoroquinolone prescription vs. an oral broad-spectrum antibiotic for comparison.
Fluoroquinolones included ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin
Comparator antibiotics included amoxicillin-clavulanate, azithromycin, cefalexin, cefixime, cefdinir, nitrofurantoin, and bactrim.
Outcomes: Primary outcome was 90-day tendon rupture (Achilles, patellar, quadricep, patellar, tibial) identified by diagnosis and procedure codes. Secondary outcome was tendinitis.
Results: The weighted 90-day tendon rupture risk was 13.6 per 100 000 fluoroquinolone-treated adolescents and 11.6 per 100 000 comparator-treated adolescents.
Fluoroquinolone-associated excess risk: 1.9 per 100 000 adolescents; the corresponding number needed to treat to harm was 52 632.
The weighted 90-day tendinitis risk was 200.8 per 100 000 fluoroquinolone-treated adolescents and 178.1 per 100 000 comparator-treated adolescents
Fluoroquinolone-associated excess risk excess risk: 22.7 per 100 000 adolescents; the corresponding number needed to treat to harm was 4405.
Conclusion:
The excess risk of tendon rupture associated with fluoroquinolone treatment was extremely small, and these events were rare. On average, 50,000 adolescents would need to be treated with a fluoroquinolone for 1 additional tendon rupture to occur
The excess risk of tendinitis associated with fluoroquinolone treatment though larger was also small.
Besides tendon rupture, other more common potential adverse drug effects may be more important to consider for treatment decision-making, in adolescents without other risk factors for tendon injury.
Pulmonary Embolism
Trauma patients over age 65 should be cared for by a multidisciplinary trauma team. Here is another study affirming that patients over age 65 do worse when having similar injuries to those under 65. Interestingly, those under 65 had more operative repairs of their orthopedic injuries as well.
The authors conclude: “Although the ISS and NISS were similar, mortality was significantly higher among patients aged ≥ 65 years compared to patients < 65 years of age”.
Also it bears further investigation of why those under 65 received more operative repairs
