Ceftaroline Fosamil

J01D - Other beta-lactam antibacterials ATC J01DI02 Small molecule approved 2010 Parenteral Prodrug Natural product

Active form: Ceftaroline.

🧬 Cross-allergy: Cephalosporins

JFDA label: Zinforo 600mg Vial

Mechanism of Action

Inhibitor of Penicillin-binding protein 2a — Penicillin-binding protein 2a inhibitor; Inhibitor of Penicillin-binding protein 2x — Penicillin-binding protein 2x inhibitor; Inhibitor of Bacterial penicillin-binding protein — Bacterial penicillin-binding protein inhibitor

Target	Action	Gene / class
Bacterial penicillin-binding protein efficacy	INHIBITOR
Penicillin-binding protein 2a efficacy	INHIBITOR	mecA
Penicillin-binding protein 2x efficacy	INHIBITOR	pbpX · Unclassified protein

Indications

Approved

Pneumonia, community-acquired
Skin and skin structure infections

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.

Bacteria

Organism	Activity	MIC
Citrobacter freundii	Active	—
Citrobacter koseri	Active	—
Enterobacter aerogenes	Active	—
Enterobacter cloacae	Active	—
Enterobacterales	Susceptible	0.5 mg/L
Escherichia coli	Active	—
Haemophilus influenzae	Susceptible	0.5 mg/L
Haemophilus influenzae	Susceptible	0.03 mg/L
Haemophilus parainfluenzae	Active	—
Klebsiella oxytoca	Active	—
Klebsiella pneumoniae	Active	—
Moraxella catarrhalis	Active	—
Morganella morganii	Active	—
Proteus mirabilis	Active	—
Staphylococcus aureus	Susceptible	1.0 mg/L
Streptococcus agalactiae	Active	—
Streptococcus dysgalactiae	Active	—
Streptococcus pneumoniae	Susceptible	0.5 mg/L
Streptococcus pneumoniae	Susceptible	0.25 mg/L
Streptococcus pyogenes	Active	—
Staphylococcus aureus	Resistant	2.0 mg/L
Streptococcus pneumoniae	Resistant	1.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (beta-lactam, 5th generation, anti-MRSA cephalosporin)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	1
resistanceMechanisms	ESBL production,Carbapenemase,mecA overexpression

Contraindications

Source: Lexicomp

Known serious hypersensitivity to ceftaroline, other members of the cephalosporin class, or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Common Bradycardia, headache, pruritus, hyperglycemia, vomiting, nausea, constipation, abdominal pain (adults: Hematologic & oncologic: Anemia (adults: Hepatic: Increased serum ALT (infants, children, and ad

Other (1)

Very Common Hematologic & oncologic: Positive direct Coombs test

Dosing

Source: Lexicomp

Pneumonia, community-acquired: IV: 600 mg every 12 hours for 5 to 7 days Skin and skin structure infection: IV: 600 mg every 12 hours for 5 to 14 days

(For additional information see "Ceftaroline: Pediatric drug information") Pneumonia, community acquired: IV: Infants ≥2 months and Children 8 mg/kg/dose every 8 hours for 5 to 14 days Children ≥2 years and Adolescents ≤33 kg: 12 mg/kg/dose every 8 hours for 5 to 14 days >33 kg: 400 mg every 8 hours or 600 mg every 12 hours for 5 to 14 days Adolescents ≥18 years: Refer to adult dosing. Skin and skin structure infection: IV: Infants ≥2 months and Children 8 mg/kg/dose every 8 hours for 5 to 14 days Children ≥2 years and Adolescents ≤33 kg: 12 mg/kg/dose every 8 hours for 5 to 14 days >33 kg: 400 mg every 8 hours or 600 mg every 12 hours for 5 to 14 days Adolescents ≥18 years: Refer to adult dosing.

Refer to adult dosing.

Adult: Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes. CrCl >50 mL/minute: No dosage adjustment necessary. CrCl >30 to ≤50 mL/minute: 400 mg every 12 hours CrCl ≥15 to ≤30 mL/minute: 300 mg every 12 hours CrCl ESRD patients receiving hemodialysis: 200 mg every 12 hours; dose should be given after hemodialysis on dialysis days Infants ≥2 months, Children, and Adolescents Renal function may be estimated using the Schwartz equation. CrCl >50 mL/minute/1.73m2: No dosage adjustment necessary. CrCl 2: There are no dosage adjustments provided in the manufacturer's labeling; data are insufficient; use with caution; dosage adjustment may be necessary.

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). However, ceftaroline is primarily renally eliminated.

Warnings & Precautions

Source: Lexicomp

Hemolytic anemia

Seroconversion from a negative to a positive direct Coombs’ test has been reported. Hemolytic anemia was not reported in clinical studies; however, if anemia develops during or after treatment, consider drug-induced hemolytic anemia. Diagnostic tests should include a direct Coombs’ test. If hemolytic anemia is suspected, discontinue the drug and institute supportive care as clinically indicated.

Hypersensitivity

Serious hypersensitivity (anaphylactic) and skin reactions have occurred with ceftaroline. Use with caution in patients with a history of penicillin, cephalosporin, or carbapenem allergy. Maintain clinical supervision if given to penicillin or beta-lactam allergic patients; cross sensitivity among beta-lactam antibacterial agents has been reported. If a serious reaction occurs, discontinue the drug and institute supportive measures as clinically indicated.

Superinfection

Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis (including fatalities); CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:

Renal impairment

Use with caution in patients with renal impairment (CrCl ≤50 mL/minute); dosage adjustments recommended. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy & Lactation

Pregnancy

Adverse events have been observed in some animal reproduction studies.

Lactation

It is not known if ceftaroline fosamil is excreted in breast milk. The manufacturer recommends that caution be exercised when administering ceftaroline fosamil to nursing women.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C22H21N8O8PS4
Molecular weight	684.7 g/mol
IUPAC name	(6R,7R)-7-[[(2Z)-2-ethoxyimino-2-[5-(phosphonoamino)-1,2,4-thiadiazol-3-yl]acetyl]amino]-3-[[4-(1-methylpyridin-1-ium-4-yl)-1,3-thiazol-2-yl]sulfanyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
CAS	229016-73-3
PubChem CID	9852981
InChIKey	`ZCCUWMICIWSJIX-NQJJCJBVSA-N`
logP	-0.11 (XLogP 2.3)
Polar surface area	223.24 Å²
H-bond acceptors / donors	14 / 4
Drug-likeness (QED)	0.07
Lipinski violations	2

SMILES

CCO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(Sc3nc(-c4cc[n+](C)cc4)cs3)CS[C@H]12)c1nsc(NP(=O)(O)O)n1

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	2.18 h
Volume of distribution	0.527 L/kg
Protein binding	44.2%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OAT1 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)OAT1 (Substrate)OAT3 (Substrate)OCT2 (Substrate)P-gp (Substrate)

Drug–drug interactions (12, DDInter)

Interacting drug	Severity	Management
Amikacin	moderate
Amikacin (liposome)	moderate
Chloramphenicol	moderate
Dicoumarol	moderate
Ethinylestradiol	moderate
Gentamicin	moderate
Kanamycin	moderate
Mycophenolic acid	moderate
Neomycin	moderate
Picosulfuric acid	moderate
Streptomycin	moderate
Warfarin	moderate

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Zinforo	Vial 600 mg	10 vial	Khoury Drug Store	—