Chapter 12. Antibacterial Agents

Aminoglycosides

2–3 h

>35 mg/L

Ototoxicity to vestibular and cochlear cells; nephrotoxicity causing proximal tubular damage and acute tubular necrosis; competitive neuromuscular blockade if given rapidly IV with other neuromuscular-blocking drugs. Threshold for toxic effects varies with the drug and dosage schedule.

2 h

>12 mg/L

2–3 h

>30 mg/L

0.5–1 g/d

2.5 h

>40–50 mg/L

2–2.5 h

>10 mg/L

Bacitracin

Unknown

Ototoxicity and nephrotoxicity

Carbapenems

Chronic; >1 g every 6 h

Hypersensitivity reactions; seizures associated with renal dysfunction and high doses.

1 h

4 h (2.5 h in ages 3 mo–12 y)

1 h

1 h

Cephalosporins

90–120 min

Unknown

Convulsions reported in patients with renal insufficiency; coagulopathy associated with cefazolin.

6 g/d

Proximal tubular necrosis

0.6–0.9 h

Neutropenia

102–156 min

3–4 mg/L

One case of symptomatic hepatitis. All these antibiotics have the N-methyltetra-zolethiol side chain, which may inhibit aldehyde dehydrogenase to cause a disulfiram-like interaction with ethanol (See Disulfiram) and coagulopathy (inhibition of vitamin K production).

30–60 min

3–4.6 h

114–150 min

72 min

4.3–4.6 h; extensive excretion in bile

IV bolus over <3–5 min

Pseudolithiasis (“gallbladder sludge”).

Should be administered IV over 30 minutes.

Chloramphenicol

4 h

>40 mg/L

Leukopenia, reticulocytopenia, circulatory collapse (“gray baby” syndrome)

Dapsone

10–50 h

As little as 100 mg in an 18-month-old

Methemoglobinemia, sulfhemoglobinemia, hemolysis; metabolic acidosis; hallucinations, confusion; hepatitis (See Dapsone)

Daptomycin

8–9 h

Chronic

A cyclic lipopeptide. Available only as an injection. May cause muscle pain, weakness, or asymptomatic elevation of the CK level.

Ethambutol

15 mg/kg/d

Optic neuritis, red-green color blindness, peripheral neuropathy

Ethionamide

1.92 ± 0.27 h

Chronic

Hypothyroid, hypoglycemia, photosensitivity, neurotoxic effects

Gramicidin

Unknown

Hemolysis

Isoniazid (INH)

0.5–4 h

1–2 g orally

Convulsions, metabolic acidosis (See Anion gap metabolic acidosis); hepatotoxicity and peripheral neuropathy with chronic use

Lincomycin, clindamycin

4.4–6.4 h

2.4–3 h

Unknown

Hypotension and cardiopulmonary arrest after rapid intravenous administration

Linezolid

4.5–5.5 h

Duration-related (>2 wk)

Thrombocytopenia, anemia; peripheral neuropathy. Linezolid is an inhibitor of monoamine oxidase (See Monoamine Oxidase Inhibitors).

Macrolides

Can prolong the QT interval and lead to torsade de pointes (atypical ventricular tachycardia).

68 h

Chronic

Least likely of the macrolides to induce torsade in animal studies.

3–4 h

Chronic

44 (16–55) h

Chronic

Hepatotoxicity

1.4 h

Unknown

Abdominal pain; idiosyncratic hepatotoxicity with estolate salt. Administration ...