cefepime

Inhibits bacterial cell wall synthesis.

Therapeutic effects:

Bactericidal action against susceptible bacteria.

Spectrum:

Similar to that of 2nd- and 3rd-generation cephalosporins, but activity against staphylococci is less, whereas activity against gram-negative pathogens is greater, even for organisms resistant to 1st-, 2nd-, and 3rd-generation cephalosporins.
Notable is increased action against:
- Enterobacter,
- Haemophilus influenzae (including β-lactamase-producing strains),
- Escherichia coli,
- Klebsiella pneumoniae,
- Neisseria,
- Proteus,
- Providencia,
- Pseudomonas aeruginosa,
- Serratia,
- Moraxella catarrhalis (including β-lactamase-producing strains).
Not active against methicillin-resistant staphylococci or enterococci.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed after IM administration; IV administration results in complete bioavailability.

Distribution: Widely distributed. Some CSF penetration.

Metabolism/Excretion: 85% excreted unchanged in urine.

Half-Life: Adults: 2 hr (↑ in renal impairment); Children 2 mo–6 yr: 1.7–1.9 hr.

Time/Action Profile ⬆ ⬇

( plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IM	rapid	1–2 hr	12 hr
IV	rapid	end of infusion	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to cephalosporins;
Serious hypersensitivity to penicillins.

Use Cautiously in:

History of GI disease, especially colitis;
Renal impairment (↓ dose/↑ dosing interval recommended if CCr ≤60 mL/min);
Hepatic impairment or poor nutritional status (may be at ↑ risk of bleeding);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Geri: Dose adjustment due to age-related ↓ in renal function may be necessary in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, pruritus, urticaria

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

Hemat: bleeding, eosinophilia, hemolytic anemia, neutropenia, thrombocytopenia

Local: pain at IM site, phlebitis at IV site

Neuro: aphasia, ENCEPHALOPATHY, headache, SEIZURES ( RISK IN RENAL IMPAIRMENT)↑ risk in renal impairment)

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), superinfection

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ excretion and ↑ levels.
Concurrent use of loop diuretics or aminoglycosides may ↑ risk of nephrotoxicity.

Route/Dosage ⬆ ⬇

IM (Adults ): Mild to moderate uncomplicated or complicated urinary tract infections due to Escherichia coli: 0.5–1 g every 12 hr.
IV (Adults ): Moderate to severe pneumonia: 1–2 g every 12 hr. Mild to moderate uncomplicated or complicated urinary tract infections: 0.5–1 g every 12 hr. Severe uncomplicated or complicated urinary tract infections, moderate to severe uncomplicated skin and skin structure infections, complicated intra-abdominal infections: 2 g every 12 hr. Empiric treatment of febrile neutropenia: 2 g every 8 hr.
IV (Children 1 mo–16 yr): Uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections, pneumonia: 50 mg/kg every 12 hr (not to exceed 2 g/dose). Febrile neutropenia: 50 mg/kg every 8 hr (not to exceed 2 g/dose).
IV (Neonates postnatal age ≥14 days): 50 mg/kg every 12 hr.
IV (Neonates postnatal age <14 days): 30 mg/kg every 12 hr; consider 50 mg/kg every 12 hr for Pseudomonas infections.

Renal Impairment

IM IV (Adults ): (See manufacturer’s specific recommendations) CCr 30–60 mL/min: 0.5–1 g every 24 hr or 2 g every 12–24 hr; CCr 11–29 mL/min: 0.5–2 g every 24 hr; CCr <11 mL/min: 250 mg–1 g every 24 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 1 g; 2 g
Premixed infusion: 1 g/50 mL D5W; 2 g/100 mL D5W

Assessment ⬆ ⬇

Assess for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and throughout therapy.
Before initiating therapy, obtain a history 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 initiating therapy. 1st dose may be given before receiving results.
Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these symptoms 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 wk following cessation of therapy.
Monitor for neurotoxic events, including encephalopathy, myoclonus, aphasia, seizures, and nonconvulsive status epilepticus, especially in patients with renal impairment and the elderly; dosage adjustment or discontinuation may be necessary. Institute seizure precautions as indicated.

Lab Test Considerations:

May cause positive results for Coombs test in patients receiving high doses or in neonates whose mothers were given cephalosporins before delivery.
- May ↑ AST, ALT, bilirubin, BUN, and serum creatinine.
- May rarely cause leukopenia, neutropenia, thrombocytopenia, and eosinophilia.

Implementation ⬆ ⬇

IM: Reconstitution: Reconstitute IM doses with sterile or bacteriostatic water for injection, 0.9% NaCl, or D5W. May be diluted with lidocaine to minimize injection discomfort.
- Inject deep into a well-developed muscle mass; massage well.
- IM route should only be used for treatment of mild to moderate uncomplicated or complicated urinary tract infections due to Escherichia coli.

IV Administration:

IV: Monitor injection site frequently for phlebitis (pain, redness, swelling). Change sites every 48–72 hr to prevent phlebitis.
- If aminoglycosides are administered concurrently, administer in separate sites, if possible, ≥1 hr apart. If 2nd site is unavailable, flush lines between medications.
Intermittent Infusion: Reconstitution: Reconstitute each 1 g or 2 g vial with 10 mL of sterile water for injection, 0.9% NaCl, or D5W. Diluent: Dilute further in 50–100 mL of D5W, 0.9% NaCl, D10W, D5/0.9% NaCl, or D5/LR. Solution is stable for 24 hr at room temperature and 7 days if refrigerated. Reconstituted solution color may darken depending on storage conditions; however, this does not affect potency. Concentration: Not to exceed 40 mg/mL.
Rate: Infuse over 20–30 min.
Y-Site Compatibility:
- amikacin
- aminocaproic acid
- amiodarone
- ampicillin/sulbactam
- anidulafungin
- arsenic trioxide
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- ceftolozane/tazobactam
- cyclophosphamide
- cytarabine
- dactinomycin
- daptomycin
- dexamethasone
- dexmedetomidine
- docetaxel
- doxorubicin liposomal
- eptifibatide
- eravacycline
- esmolol
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- gentamicin
- granisetron
- hetastarch
- hydrocortisone
- hydromorphone
- imipenem/cilastatin
- insulin, regular
- ketamine
- LR
- leucovorin calcium
- levofloxacin
- linezolid
- lorazepam
- melphalan
- meropenem/vaborbactam
- mesna
- methadone
- methotrexate
- methylprednisolone
- metoprolol
- metronidazole
- milrinone
- octreotide
- oxytocin
- paclitaxel
- palonosetron
- pamidronate
- piperacillin/tazobactam
- plazomicin
- potassium acetate
- remifentanil
- rocuronium
- sargramostim
- sodium acetate
- sodium bicarbonate
- sufentanil
- sulbactam/durlobactam
- tedizolid
- telavancin
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- trimethoprim/sulfamethoxazole
- valproate sodium
- vasopressin
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- acetylcysteine
- acyclovir
- alemtuzumab
- amphotericin B deoxycholate
- amphotericin B liposomal
- argatroban
- caspofungin
- chlorpromazine
- ciprofloxacin
- cisplatin
- dacarbazine
- daunorubicin
- dexrazoxane
- diazepam
- diltiazem
- diphenhydramine
- doxorubicin hydrochloride
- droperidol
- enalaprilat
- epirubicin
- erythromycin
- etoposide
- etoposide phosphate
- famotidine
- filgrastim
- floxuridine
- ganciclovir
- gemcitabine
- gemtuzumab ozogamicin
- haloperidol
- hydroxyzine
- idarubicin
- ifosfamide
- irinotecan
- isavuconazonium
- labetalol
- letermovir
- magnesium sulfate
- mannitol
- meperidine
- metoclopramide
- midazolam
- mitomycin
- mitoxantrone
- nalbuphine
- ondansetron
- oxaliplatin
- pantoprazole
- pemetrexed
- phenytoin
- prochlorperazine
- promethazine
- tacrolimus
- theophylline
- topotecan
- vecuronium
- vinblastine
- vincristine
- vinorelbine
- voriconazole

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects to patient. Inform patient of the importance of receiving the full course of therapy even if feeling better. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Advise patient to report immediately any signs/symptoms of encephalopathy (confusion, hallucinations, stupor, coma), stiffness, or seizures.
Advise patient to report signs and symptoms 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 fever and diarrhea develop, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. There are multiple significant possible drug-drug interactions.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇