ampicillin/sulbactam

Binds to bacterial cell wall, resulting in cell death; spectrum is broader than that of penicillin. Addition of sulbactam increases resistance to beta-lactamases, enzymes produced by bacteria that may inactivate ampicillin.

Therapeutic effects:

Bactericidal action.

Spectrum:

Active against:
- Streptococci,
- Pneumococci,
- Enterococci,
- Haemophilus influenzae,
- Escherichia coli,
- Proteus mirabilis,
- Neisseria meningitidis,
- N. gonorrhoeae,
- Shigella,
- Salmonella,
- Bacteroides fragilis,
- Moraxella catarrhalis.
Use should be reserved for infections caused by beta-lactamase–producing strains.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed from IM sites.

Distribution: Ampicillin diffuses readily into bile, blister and tissue fluids. Poor CSF penetration unless meninges are inflamed.

Metabolism/Excretion: Ampicillin is variably metabolized by the liver (12–50%). Renal excretion is also variable. Sulbactam is eliminated unchanged in urine.

Protein Binding: Ampicillin: 28%; sulbactam: 38%.

Half-Life: Ampicillin: 1–1.8 hr; sulbactam: 1–1.3 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IM	rapid	1 hr	6–8 hr
IV	immediate	end of infusion	6–8 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to penicillins or sulbactam;
History of cholestatic jaundice or hepatic impairment with ampicillin/sulbactam.

Use Cautiously in:

Severe renal impairment (↓ dosage if CCr <30 mL/min);
Epstein-Barr virus infection, acute lymphocytic leukemia, or cytomegalovirus infection (↑ risk of rash);
OB: Safety not established in pregnancy;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, ERYTHEMA MULTIFORME, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

GI: diarrhea, cholestasis, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), HEPATOTOXICITY, nausea, vomiting

Hemat: blood dyscrasias

Local: pain at injection site, phlebitis

Neuro: SEIZURES (HIGH DOSES)

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND MYOCARDIAL ISCHEMIA [WITH OR WITHOUT MI]), superinfection

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ renal excretion and ↑ levels of ampicillin—therapy may be combined for this purpose.
May potentiate the effect of warfarin.
Concurrent allopurinol therapy (↑ risk of rash).
May ↓ levels and effectiveness of hormonal contraceptives.

Route/Dosage ⬆ ⬇

Dosage based on ampicillin component
IM IV (Adults and Children ≥40 kg): 1–2 g ampicillin every 6–8 hr (not to exceed 12 g ampicillin/day).
IM IV (Children ≥1 yr): 100–200 mg ampicillin/kg/day divided every 6 hr; Meningitis: 200–400 mg ampicillin/kg/day divided every 6 hr; maximum dose: 8 g ampicillin/day.
IM IV (Infants >1 mo): 100–150 mg ampicillin/kg/day divided every 6 hr.

Renal Impairment

IM IV (Adults , Children, and Infants): CCr 15–29 mL/min: Administer every 12 hr; CCr 5–14: Administer every 24 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 1.5 g/vial (1 g ampicillin with 500 mg sulbactam); 3 g/vial (2 g ampicillin with 1 g sulbactam); 15 g/vial (10 g ampicillin with 5 g sulbactam)

Assessment ⬆ ⬇

Assess patient for infection (vital signs, wound appearance, sputum, urine, stool, and WBCs) at beginning and throughout therapy.
Obtain a history before initiating therapy to determine previous use of, and reactions to, penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity before therapy. First dose may be given before receiving results.
Monitor for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several mo following cessation of therapy
Monitor for rash, may lead to severe skin reactions.

Lab Test Considerations:

Monitor hepatic function periodically during therapy. May cause ↑ AST, ALT, LDH, bilirubin, alkaline phosphatase, BUN, and serum creatinine.
- May cause ↓ hemoglobin, hematocrit, RBC, WBC, neutrophils, and lymphocytes.
- May cause transient ↓ estradiol, total conjugated estriol, estriol-glucuronide, or conjugated estrone in pregnant women.
- May cause a false-positive Coombs’ test result.

Implementation ⬆ ⬇

IM: Reconstitute for IM use by adding 3.2 mL of sterile water or 0.5% or 2% lidocaine HCl to the 1.5-g vial or 6.4 mL to the 3-g vial. Administer within 1 hr of preparation, deep IM into well-developed muscle.

IV Administration:

Reconstitution: Reconstitute 1.5-g vial with 3.2 mL of sterile water for injection and the 3-g vial with 6.4 mL.Concentration: 375 mg ampicillin/sulbactam per mL.
Intermittent Infusion: Reconstitution: Reconstitute vials as per directions above.Diluent: Further dilute in 50–100 mL of 0.9% NaCl, D5W, D5/0.45% NaCl, or LR. Stability of solution varies from 2–8 hr at room temperature or 3–72 hr if refrigerated, depending on concentration and diluent.Concentration: Final concentration of infusion should be 3–45 mg of ampicillin/sulbactam per mL.
Rate: Infuse over 15–30 min.

Patient/Family Teaching ⬆ ⬇

Advise patient to report rash, signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several wk after discontinuation of medication.
Rep: Caution patients taking oral contraceptives to use an alternative or additional nonhormonal method of contraception while taking ampicillin/sulbactam and until next menstrual period. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Instruct the patient to notify health care professional if symptoms do not improve.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇