Complications from antimicrobial use are diverse, and the vast
majority of adverse effects result from iatrogenic causes rather
than intentional overdose. The adverse effects seen from antimicrobials
include allergic reactions, drug interactions, secondary or side
effects, and, less commonly, toxic effects from acute overdoses.
Allergic reactions are common among antibiotics, which may be due
to the high frequency of their use, usually in a repeated, interrupted
fashion. Many antimicrobial adverse effects are difficult to predict.
Some adverse effects are due to a diluent or other
chemical constituent in the formulation of a drug. The most common
adverse effects of antimicrobial use include hypersensitivity reactions,
alterations in body microbial flora, interactions with other drugs,
and cutaneous manifestations (e.g., erythema multiforme). Iatrogenic
dosing errors commonly involve neonates and infants because of their
small weight where mathematic calculations of dose can be inaccurate
by several orders of magnitude.
This chapter focuses on the medical considerations of acute antimicrobial
overdose (Table 200-1).
200-1 Select Antimicrobial Toxicities and Their Specific
| Save Table
200-1 Select Antimicrobial Toxicities and Their Specific
|Drug||Acute Toxicity||Special Therapy for Symptomatic Overdose|
|Penicillins||Seizures (50 million units or more IV)||Benzodiazepines|
|Amoxicillin||Crystalluria, hematuria, acute renal failure||IV hydration|
|Macrolides||Prolonged QT interval, torsades de pointes arrhythmia||Magnesium sulfate|
|Vancomycin||“Red-man syndrome” (anaphylactoid response)||Slow or stop infusion, antihistamines|
|Isoniazid||Inhibition of γ-aminobutyric acid synthesis
and functional deficiency pyridoxine, seizures||Benzodiazepines, high-dose pyridoxine|
|Quinine (quinidine)||Sodium-potassium channel blockade, α-adrenergic antagonism,
hypoglycemia, ototoxicity, ophthalmic toxicity||Multidose activated charcoal, sodium bicarbonate, dextrose,
|Chloroquine||Seizures, QRS-complex and QT-interval prolongation, hypotension,
|Primaquine||Methemoglobinemia, hemolysis||Methylene blue|
Antimicrobial exposures are a frequent source of inquiry to poison
control centers but rarely result in life-threatening outcomes.
During 2008, the American Association of Poison Control Centers
received reports of 67,809 exposures to antimicrobials, but significant
morbidity was described in only 131 cases (0.01%), and
there was only one fatality.1 Poison control center
data are gathered passively and this report likely underrepresents
the true number of exposed persons.
Most patients who sustain an acute overdose of antimicrobials
remain asymptomatic. Observation and screening for coingestants
is generally required in most cases. Consultation with a medical
toxicologist or the regional poison control center is recommended
to assist in patient management and to aid in accurate statistical
tracking of toxic exposures. Asymptomatic antimicrobial ingestions
require minimal laboratory evaluation. As with all possible overdoses,
determining acetaminophen levels and obtaining an ECG is recommended
to screen for potentially dangerous coingestants.
Significant ingestion of drugs such as isoniazid, chloroquine,
and quinine, however, can result in severe toxicity. The history
should ideally include the amount and type of antimicrobial ingested.
Patients should also be asked about possible coingestants, and suicide
potential should be assessed. Ancillary testing should be based
on the substance ingested and clinical condition of the patient.
In most cases, measurement of drug levels is not helpful in the
management of the acute antimicrobial overdose but may be confirmatory
and is available for several antibiotics such as isoniazid, quinine,
and chloroquine. Measurement of electrolytes and glucose, as well
as obtaining an ECG, may assist in management of some antimicrobial
overdoses because they may alter electrolyte balance and prolong
QRS-complex or QT-interval durations. Depending on the drug involved,
specific testing may assist in assessing degree of toxicity and
in guiding therapy, such as methemoglobin concentrations in patients
with dapsone or chloroquine toxicity.
Unless there are contraindications, GI decontamination should
be initiated in all patients who are suspected of having ingested
a toxic amount of a potentially dangerous antimicrobial agent. Activated
charcoal is most beneficial when given within 1 hour of a toxic
ingestion.2 Activated charcoal can be given orally
or through a nasogastric tube to patients with an intact or protected
airway.2 Sorbitol is not routinely recommended
for use in GI decontamination.3 Repeated multidose
dose-activated charcoal without sorbitol is indicated in symptomatic
patients who have ingested dapsone or quinine.4 Hemodialysis
or hemoperfusion is effective at reducing concentrations of dapsone,
chloramphenicol, and, possibly, pentamidine, but neither is effective
at removing other antimicrobial agents.5–7
Aminoglycosides are not available in oral forms; therefore, acute
overdoses nearly always result from dosing errors.8 Although
rare aminoglycoside overdoses have caused toxicity, the vast majority
of these patients suffer minimal toxic effects. Aminoglycosides
may exacerbate neuromuscular blockade through inhibited release
of acetylcholine. Aminoglycosides are also associated with ototoxicity
and nephrotoxicity via unclear mechanisms, and these toxicities
correlate with elevated trough serum concentrations. Although all
aminoglycosides have the potential to damage vestibular and cochlear
sensory cells, neomycin is considered to be, by far, the most ototoxic.
Nephrotoxicity is associated with increased age, decreased renal
and liver function, high/prolonged/frequent doses,
high trough serum concentrations, and the presence of shock. Therapy
for acute aminoglycoside overdose is typically hydration and monitoring
of hearing and renal function. Hemodialysis has been used to enhance
elimination of aminoglycosides, but it is unclear what role it should
play in acute overdose because most patients recover with only supportive
Antimalarials—quinine, chloroquine, mefloquine,
and primaquine—are among the antimicrobial agents with
the greatest potential for toxic effects.9–13
The cardiac toxicity of quinine includes both sodium and potassium channel
antagonism, which may result in widened QRS-complex intervals, torsades
de pointes dysrhythmia, hypotension, syncope, and sudden death.
Quinine also has significant ocular toxicity in acute overdose, and
blindness may result from serum levels >10 to 15 micrograms/mL.12,13 Ototoxicity
from quinine can produce symptoms that range ...