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,
- Neisseria 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;
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 (AGEP), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME (EM), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN), 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; therapy may be combined for this purpose.
May ↑ risk of bleeding of warfarin.
Allopurinol may ↑ risk of rash.
May ↓ levels and effectiveness of hormonal contraceptives.

Route/Dosage ⬆ ⬇

Dosage based on ampicillin component. Contains 5 mEq (115 mg) sodium/1.5 g of ampicillin/sulbactam.
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, 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 hypersensitivity reactions (rash, urticaria, pruritus, flushing, dizziness, vomiting, abdominal pain) and angioedema (swelling of throat, lips, tongue, or face; dyspnea; wheezing; hoarseness). Discontinue drug immediately and provide supportive care. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor patients for development of severe cutaneous adverse reactions, including AGEP, DRESS, EM, SJS, and TEN. Advise patients of signs and symptoms of these reactions (prodrome of fever, flu-like symptoms, muscle or joint aches, mucosal lesions, progressive skin rash, blisters, lymphadenopathy, conjunctivitis). If a severe cutaneous adverse reaction is suspected, interrupt therapy until etiology of reaction is determined. Consultation with a dermatologist is recommended. If a severe cutaneous adverse reaction is confirmed, or for other Grade 4 skin reactions, permanently discontinue ampicillin/sulbactam.
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

Lab Test Considerations:

Monitor hepatic and renal function periodically during therapy. May ↑ AST, ALT, LDH, bilirubin, alkaline phosphatase, BUN, and serum creatinine.
- May ↓ 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 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:

IV Push: 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.
Rate: Administer over at least 10–15 min within 1 hr of reconstitution. More rapid administration may cause seizures.
Intermittent Infusion: Reconstitution: Reconstitute vials as per directions for IV push 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: 3–45 mg of ampicillin/sulbactam per mL.
Rate: Infuse over 15–30 min.
Y-Site Compatibility:
- alemtuzumab
- amifostine
- aminocaproic acid
- anidulafungin
- argatroban
- azithromycin
- bivalirudin
- bleomycin
- cangrelor
- carboplatin
- carmustine
- cefepime
- ceftolozane/tazobactam
- cisplatin
- cyclophosphamide
- cytarabine
- dactinomycin
- daptomycin
- dexmedetomidine
- dexrazoxane
- docetaxel
- doxorubicin liposomal
- eptifibatide
- etoposide
- etoposide phosphate
- filgrastim
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- gemcitabine
- gemtuzumab
- granisetron
- hydromorphone
- ifosfamide
- irinotecan
- letermovir
- leucovorin
- levofloxacin
- linezolid
- meropenem/vaborbactam
- mesna
- methadone
- methotrexate
- metronidazole
- milrinone
- mitomycin
- octreotide
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pantoprazole
- pemetrexed
- plazomicin
- potassium acetate
- remifentanil
- rituximab
- rocuronium
- sodium acetate
- tedizolid
- telavancin
- thiotepa
- tigecycline
- tirofiban
- trastuzumab
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zoledronic acid
Y-Site Incompatibility:
- acyclovir
- amiodarone
- amphotericin B deoxycholate
- amphotericin B lipid complex
- amphotericin B liposomal
- azathioprine
- caspofungin
- chlorpromazine
- ciprofloxacin
- dacarbazine
- dantrolene
- daunorubicin
- diazepam
- diazoxide
- dobutamine
- doxorubicin hydrochloride
- doxycycline
- epirubicin
- ganciclovir
- haloperidol
- hydralazine
- hydrocortisone
- hydroxyzine
- idarubicin
- isavuconazonium
- lorazepam
- methylprednisolone
- midazolam
- mitoxantrone
- mycophenolate
- nicardipine
- ondansetron
- papaverine
- pentamidine
- phenytoin
- prochlorperazine
- promethazine
- protamine
- sargramostim
- topotecan
- tranexamic acid
- trimethoprim/sulfamethoxazole
- verapamil
- vinorelbine
- If aminoglycosides and penicillins must be given concurrently, administer in separate sites at least 1 hr apart

Patient/Family Teaching ⬆ ⬇

Educate patient on reason and side effects of ampicillin/sulbactam. Instruct patients to take medication around the clock and to finish the drug completely as directed, even if feeling better. Advise patients that sharing of this medication may be dangerous. Advise patient to read Patient Information before starting therapy.
Instruct the patient to notify health care professional if symptoms do not improve.
Advise patient to report rash, signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
Instruct patient to notify health care professional if any rash (particularly with fever, flu-like symptoms, swollen lymph nodes) develops within the 1–2 wk of therapy.
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: Instruct women of reproductive potential taking oral contraceptives to use an alternate or additional method of contraception during therapy and until next menstrual period; may ↓ effectiveness of hormonal contraceptives. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇