EM Toxicology 9 - Antimicrobials

Question 1

obtain methemoglobin concentrations for patients with toxicity from

Answer 1

dapsone
chloroquine
sulfonamide
primaquine

Question 2

MDAC is indicated in

Answer 2

symptomatic patients who have ingested dapsone or quinine

Question 3

hemodialysis or hemoperfusion is effective at reducing concentrations of

Answer 3

dapsone
chloramphenicol
cefepime
pentamidine (possibly)

Question 4

remarks with penicillins or cephalosporins

Answer 4

may produce seizures through GABA inhibition

Question 5

amoxicillin overdose may produce

Answer 5

crystal-induced intertitial nephritis
hematuria
and renal failure

treatment is supportive with IV fluids

Question 6

sulfonamide toxicity may result in

Answer 6

methemoglobinemia

treat with methylene blue

Question 7

toxicity with this antimicrobial may reult in hypoglycemia

Answer 7

quinine (quinidine)
may also result in ototoxicity, ophthalmic toxicity

managed with
* MDAC
* sodium bicarbonate (target pH 7.55)
* dextrose
* octreotide

Question 8

remarks on isoniazid toxicity

Answer 8

results in GABA syntehsis inhibition and functional deficiency of pyridoxine –> seizures

treat with
* benzodiazepines
* high-dose PYRIDOXINE

Question 9

can cause pancreatitis

Answer 9

amoxicillin-clavulanate
and macrolides

both may also cause cholestatic hepatitis

Question 10

may produce disulfiram-like reaction

Answer 10

cephalosporins with the N-methylthiotetrazole side chain, such as cefazolin and *cefotetan**

Question 11

2 unique acute adverse reactions to procaine penicillin G

Answer 11

Jarisch-Herxheimer reaction
Hoigne’s syndrome

Question 12

Jarisch-Herxheimer reaction

Answer 12

Can begin within a few hours following antibiotic tx of Lyme disease or early syphilis
Results from antigen released from lysed bacteria
Headache, fever, myalgias, rash
Usually limited to 24 hours

Question 13

Hoigne’s syndrome

Answer 13

Begins within minutes after IM or IV injection of procaine penicillin G
Cause is unclear
Extreme apprehension, fear, hallucinations, illusions, hypertension and tachycardia, and seizures

Amoxicillin and ceftriaxone have been reported to produce a similar reaction

Question 14

Fluoroquinolone toxicity

Answer 14

QT prolongation and subsequent torsades de pointe

in children, potential abnormality with developing cartilage and bone, although data suggest the risk is very low

in adults, tendon rupture has been attributed to fluoroquinolone use, with levofloxacin accounting for more than all others combined

discontinue the antibiotic in those who complain of painful or swollen tendons

Question 15

linezolid toxicity

Answer 15

inhibits monoamine oxidase, and can lead to serotonin syndrome when used concurrently with other serotonergic meds

chronic therapy >28 days is associated with peripheral neuropathy and optic neuropatthy with loss of cenral vision and loss of color and visual acuity

also associated with pancytopenia

Question 16

macrolides toxicity

Answer 16

m/c a/e: GI distress

most imporant a/e: QT prolongation with potential for torsades de pointes (lesser extent for azithromycin)

also associated with high-frequency sensorineural hearing loss

and rarely pancreatitis

Question 16

antibiotics associated with rhabdomyolysis

Answer 16

trimethoprim-sulfamethoxazole

Question 17

red man syndrome

Answer 17

vancomycin
rarely, this syndrome can cause seizures and CV collapse

most symptoms resolve within 15 minutes when the infusion is stopped

continue infusion at slower rate or with increased dilution or with pretreatment with diphenhydramine

Question 18

chloroquine toxicity

Answer 18

Usually begins within 3 hours of ingestion with N/V and diarrhea

CV collapse may be precipitous with QRS widening and AV nodal blockade

Hypotension may be more severe than that seen with quinine overdose and is accompanied by respiratory depression and hypokalemia

aggressive supportive care is needed
early intubation, gastric lavage, deep sedation with BDZ
epinephrine to maintain SBP 100 mmHg

Question 19

may cause hemolytic anemia and methemoglobinemia

Answer 19

primaquine, especially in a G6PD deficient population

Question 20

quinine toxicity

Answer 20

cardiac toxicity
includes both sodium and potassium antagnism
which may result in widened QRS complex, QT prolongation and torasades depointes,
hypotension, syncopem and sudden death

blindness may result from serum levels >10-15 mcg/mL (31-46 mcmol/L)

deafness (tinnitus) and hypoglycemia (from hyperinsulinemia) may also occur

TX:
Mainstay is sodium bicarbonate to maintain serum pH 7.55
avoid class IA, IC, and III antidysrhythmic agents

Quinine overdose is one of the few drugs for which MDAC is truly indicated

Question 20

anti-TB drug that carries high morbidity and mortality in overdose

Answer 20

ISONIAZID
overdose typically begin with ataxia, nausea, and mental status changes which may be seen as early as 30 minutes after ingestion

Symptoms may progress to the 3 classic features of isoniazid overdose
Seizures, Metabolic acidosis, Coma

Question 21

seizures in isoniazid toxicity

Answer 21

typically follow acute isoniazid ingestions of greater than 20-30 mg/kg
GTC in nature
often refractory to standard anticonvulsive thearpy

MOA: functional def of B6 (pyridoxine) and inhibition of synthesis of GABA, the primary CNS inhibitory neurotransmitter

consider isoniazid overdose in patients with refractory seizures

Question 22

management of isoniazid toxicity

Answer 22

Isoniazid-induced seizures are treated with a combination of benzodiazepines and pyridoxine

PYRIDOXINE
gram-for-gram equivalent to th amount of isoniazide ingested
- If quantity is unkonwn, give 5 g IV in adults and 70 mg/kg (max 5 g) in pedia
- administered at a rate of approx 1g IV every 2-3 minutes until the seizures stop or the maximum dose has been given
- after the seizures have ceased, the remainder of the pyridoxine dose should be given over the following 4-6 hours to limit recurrent seizures
- If seizures persist after the full dose has been given, it may be repeated.

pyridoxine may also assist in reversing isoniazid-induced coma

Question 23

other remarks on isoniazid toxicity

Answer 23

phenytoin has no role in treating INH-induced seizures

there is little role for sodium bicarbonate tx of the metabolic acidosis resulting from INH toxicity

Question 24

disposition of isoniazid toxicity

Answer 24

because most INH-induced toxicity occurs within 2 hours of ingestion, patients who remain asymptoamtic for 6 hours after ED presentation are safe for medical clearance

Question 25

other anti-TB toxicity

Answer 25

Rifampin
infrequently causes severe toxictiy
most often assoc’d with GI symptoms
acute toxicity assoc’d with flushing, angioedema and neurologic effects (numbness, extremity pain, ataxia, weakness)

Ethambutol
primarily GI in nature
may cause unilateral or bilateral ocular toxcitiy (BOV, color perception disruption, loss of peripheral vision)

pyrazinamide is not associated with any toxic effects following acute overdose

Question 26

oseltamivir toxicity

Answer 26

assoc’d with QT prolongation, but there’s no evidence the drug causes TDP or should be avoided in patients with congenital long QT syndrome
- benign QT prolongation

may cause neuropsychiatric effects including depression, agitation, and hallucination withint 24 hours of the first dose