Indications
Treatment of the following infections caused by susceptible
organisms: Skin and skin structure infections (not
cefixime), Urinary and gynecologic infections (not cefdinir
or cefditoren), Respiratory tract infections (not
cefdinir or cefditoren). Cefotaxime, ceftazidime, ceftriaxone: Meningitis and bone/joint infections. Cefotaxime,
ceftazidime, ceftriaxone: Intra-abdominal
infections and septicemia. Cefdinir, cefixime, cefpodoxime,
ceftriaxone: Otitis media. Cefotaxime, ceftriaxone:
Perioperative prophylaxis. Ceftazidime:
Febrile neutropenia. Cefotaxime, ceftriaxone: Lyme
disease.
Action
Bind to the bacterial cell wall membrane, causing cell
death. Therapeutic Effects: Bactericidal action
against susceptible bacteria. Spectrum: Similar to
that of second-generation cephalosporins, but activity
against staphylococci is less, whereas activity against
gram-negative pathogens is greater, even for organisms
resistant to first- and second-generation agents. Notable
is increased action against: Enterobacter, Haemophilus
influenzae, Escherichia coli, Klebsiella pneumoniae,
Neisseria gonorrhoeae, Citrobacter, Morganella,
Proteus, Providencia, Serratia, Moraxella
catarrhalis, Borrelia burgdorferi. Some agents have
activity against N. meningitidis (cefotaxime, ceftazidime,
ceftriaxone). Some agents have enhanced activity
against Pseudomonas aeruginosa (ceftazidime). Not
active against methicillin-resistance staphylococci or
enterococci. Some agents have activity against anaerobes,
including Bacteroides fragilis (cefotaxime, ceftriaxone).
Pharmacokinetics
Absorption: Cefotaxime, ceftazidime, and ceftriaxone
are well absorbed after IM administration.
Cefixime 40–50% absorbed after oral administration
(oral suspension); cefdinir 16–25% absorbed after
oral administration. Cefditoren pivoxil and cefpodoxime
proxetil are prodrugs that are converted to their
active components in GI tract during absorption (cefditoren—
14% absorbed [qby high-fat meal] cefpodoxime—
50% absorbed).
Distribution: Widely distributed. Cross the placenta;
enter breast milk in low concentrations. CSF penetration
better than with first- and second-generation
agents.
Protein Binding: Ceftriaxone 90%.
Metabolism and Excretion: Cefdinir, ceftazidime,
and cefditoren—85% excreted in urine. Cefpodoxime—
30% excreted in urine. Ceftriaxone and
cefotaxime—partly metabolized and partly excreted
in the urine. Cefixime—50% excreted unchanged in
urine, 10% in bile.
Half-life: Cefdinir—1.7 hr; cefditoren—1.6 hr;
cefixime—3–4 hr; cefotaxime—1–1.5 hr; cefpodoxime—
2–3 hr; ceftazidime—2 hr; ceftriaxone—
6–9 hr (all except ceftriaxone areqin renal
impairment).
TIME/ACTION PROFILE
ROUTE ONSET PEAK DURATION
Cefdinir PO rapid 2–4 hr 12–24 hr
Cefditoren PO rapid 1.5–3 hr 12 hr
Cefixime PO rapid 2–6 hr 24 hr
Cefotaxime
IM
rapid 0.5 hr 4–12 hr
Cefotaxime IV rapid end of infusion
4–12 hr
Cefpodoxime
PO
unknown 2–3 hr 12 hr
Ceftazidime
IM
rapid 1 hr 6–12 hr
Ceftazidime IV rapid end of infusion
6–12 hr
Ceftriaxone
IM
rapid 1–2 hr 12–24 hr
Ceftriaxone IV rapid end of infusion
12–24 hr
Contraindications/Precautions
Contraindicated in: Hypersensitivity to cephalosporins;
Serious hypersensitivity to penicillins; Pedi:
Premature neonates up to a postmenstrual age of 41 wk
(ceftriaxone only); Pedi: Hyperbilirubinemic neonates
(may lead to bilirubin encephalopathy); Pedi: Neonates
28 days requiring calcium-containing IV solutions (q
risk of precipitation formation); Carnitine deficiency or
inborn errors of metabolism (cefditoren only); Hypersensitivity
to milk protein (ceftidoren only; contains sodium
caseinate).
Use Cautiously in: Renal impairment (pdosing/q
dosing interval recommended for: cefdinir if CCr 30
mL/min, cefixime if CCr 60 mL/min, cefotaxime if
CCr 20 mL/min, cefpodoxime if CCr 30 mL/min,
ceftazidime if CCr 50 mL/min, cefditoren if CCr 50
mL/min); Combined severe hepatic and renal impairment
(dosep/qdosing interval recommended for ceftriaxone);
Diabetes (cefdinir suspension contain sucrose);
History of GI disease, especially colitis; Geri:
Dose adjustment due to age-relatedpin renal function
may be necessary; Pedi:qrisk of urolithiasis and acute
renal failure (ceftriaxone only); OB, Lactation: Have
been used safely.
Adverse Reactions/Side Effects
CNS: SEIZURES (high doses), headache. GI: Clostridium
difficile-ASSOCIATED DIARRHEA, diarrhea, nausea,
vomiting, cholelithiasis (ceftriaxone), cramps, pancreatitis
(ceftriaxone). Derm: STEVENS-JOHNSON SYNDROME,
rash, urticaria. GU: acute renal failure (ceftriaxone),
urolithiasis (ceftriaxone). Hemat:
agranulocytosis, bleeding, eosinophilia, hemolytic anemia,
lymphocytosis, neutropenia, thrombocytopenia,
thrombocytosis. GU: hematuria, vaginal moniliasis.
Local: pain at IM site, phlebitis at IV site. Misc: allergic
reactions including ANAPHYLAXIS and SERUM SICKNESS,
superinfection.
Interactions
Drug-Drug: Probenecidpexcretion andqserum
levels (cefdinir, cefditoren, cefixime, cefotaxime, cefpodoxime,
ceftriaxone). Concurrent use of loop diuretics,
aminoglycosides, or NSAIDs mayqrisk of
nephrotoxicity. Antacidspabsorption of cefdinir, cefditoren,
and cefpodoxime. Iron supplementspabsorption
of cefdinir. H2-receptor antagonistspabsorption
of cefditoren and cefpodoxime. Cefixime may
qcarbamazepine levels. Ceftriaxone should not be
administered concomitantly with any calcium-containing
solutions. Ceftriaxone mayqrisk of bleeding with
warfarin.
Route/Dosage
Cefdinir
PO (Adults 13 yr): 300 mg every 12 hr or 600 mg
every 24 hr (use every 12 hr dosing only for community-
acquired pneumonia or skin and skin structure infections).
PO (Children 6 mo–12 yr): 7 mg/kg every 12 hr
(use only for skin/skin structure infections) or 14 mg/
kg every 24 hr; dose should not exceed 600 mg/day.
Renal Impairment
PO (Adults and Children 13 yr): CCr 30 mL/
min—300 mg every 24 hr.
Renal Impairment
PO (Children 6 mo–12 yr): CCr 30 mL/min—7
mg/kg every 24 hr.
Cefditoren
PO (Adults and Children 12 yr): Pharyngitis/tonsillitis,
skin/skin structure infections—200 mg
twice daily; Acute bacterial exacerbation of chronic
bronchitis or community acquired pneumonia—
400 mg twice daily.
Renal Impairment
PO (Adults): CCr 30–49 mL/min—dose should not
exceed 200 mg twice daily; CCr 30 mL/min—dose
should not exceed 200 mg once daily.
Cefixime
PO (Adults and Children 12 yr or 50 kg): Most
infections—400 mg once daily; Gonorrhea—400
mg single dose.
PO (Children): 8 mg/kg once daily or 4 mg/kg every
12 h.
Renal Impairment
PO (Adults): CCr 21–60 mL/min—75% of standard
dose once daily; CCr 20 mL/min—50% of standard
dose once daily.
Cefotaxime
IM, IV (Adults and Children 12 yr): Most uncomplicated
infections—1 g every 12 hr. Moderate or severe
infections—1–2 g every 6–8 hr. Life-threatening
infections—2 g every 4 hr (maximum dose12 g/day). Gonococcal urethritis/cervicitis or rectal
gonorrhea in females—500 mg IM (single dose).
Rectal gonorrhea in males—1 g IM (single dose).
Perioperative prophylaxis—1 g 30–90 min before
initial incision (one-time dose).
IM, IV (Children 1 mo–12 yr): 50 kg —100–
200 mg/kg/day divided every 6–8 hr. Meningitis—
200 mg/kg/day divided every 6 hr. Invasive pneumococcal
meningitis—225–300 mg/kg/day divided
every 6–8 hr. 50 kg—see adult dosing.
IV (Neonates 1–4 wk): 50 mg/kg every 6–8 hr.
IV (Neonates 1 wk): 50 mg/kg every 8–12 hr.
Renal Impairment
(Adults): CCr 20 mL/min—pdose by 50%.
Cefpodoxime
PO (Adults): Most infections—200 mg every 12 hr.
Skin and skin structure infections—400 mg every
12 hr. Urinary tract infections/pharyngitis—100 mg
every 12 hr. Gonorrhea—200 mg single dose.
PO (Children 2 mo–12 yr): Pharyngitis/tonsillitis/
otitis media/acute maxillary sinusitis—5 mg/kg
every 12 hr (not to exceed 200 mg/dose).
Renal Impairment
PO (Adults): CCr 30 mL/min—qdosing interval to
every 24 hr.
Ceftazidime
IM, IV (Adults and Children 12 yr): Pneumonia
and skin/skin structure infections—500 mg–1 g
every 8 hr. Bone and joint infections—2 g every 12
hr. Severe and life-threatening infections—2 g every
8 hr. Complicated urinary tract infections—500 mg
every 8–12 hr. Uncomplicated urinary tract infections—
250 mg every 12 hr. Cystic fibrosis lung infection
caused by P. aeruginosa—30–50 mg/kg
every 8 hr (maximum dose6 g/day).
IM, IV (Children 1 mo–12 yr): 33.3–50 mg/kg
every 8 hr (maximum dose6 g/day).
IM, IV (Neonates 4 wk): 50 mg/kg every 8–12 hr.
Renal Impairment
IM, IV (Adults): CCr 31–50 mL/min—1 g every 12
hr; CCr 16–30 mL/min—1 g every 24 hr; CCr 6–15
mL/min—500 mg every 24 hr; CCr 5 mL/min—
500 mg every 48 hr.
Ceftriaxone
IM, IV (Adults): Most infections—1–2 g every 12–
24 hr. Gonorrhea—250 mg IM (single dose). Meningitis—
2 g every 12 hr. Perioperative prophylaxis—
1 g 30–120 min before initial incision (single dose).
IM, IV (Children): Most infections—25–37.5 mg/
kg every 12 hr or 50–75 mg/kg every 24 hr; dose
should not exceed 2 g/day. Meningitis—100 mg/kg
every 24 hr or 50 mg/kg every 12 hr; dose should not
exceed 4 g/day. Acute otitis media—50 mg/kg IM
single dose; dose should not exceed 1 g. Uncomplicated
gonorrhea—125 mg IM (single dose).
Availability
Cefdinir (generic available)
Oral suspension (strawberry): 125 mg/5 mL, 250
mg/5 mL. Cost: Generic—125 mg/5 mL $51.00/60
mL, 250 mg/5 mL $99.48/60 mL. Capsules: 300 mg.
Cefditoren (generic available)
Tablets: 200 mg, 400 mg. Cost: Generic—All
strengths $294.81/20.
Cefixime (generic available)
Capsules: 400 mg. Oral suspension (strawberry):
100 mg/5 mL, 200 mg/5 mL, 500 mg/5 mL. Cost: 100
mg/5 mL $170.77/50 mL, 200 mg/5 mL $341.55/50
mL, 500 mg/5 mL $170.77/10 mL. Tablets: 400 mg.
Cost: $1008.49/50. Chewable tablets: 100 mg, 150
mg, 200 mg. Cost: 100 mg $170.77/10, 200 mg
$341.51/10.
Cefotaxime (generic available)
Powder for injection: 500 mg/vial, 1 g/vial, 2 g/vial,
10 g/vial.
Cefpodoxime (generic available)
Tablets: 100 mg, 200 mg. Cost: Generic—100 mg
$134.74/20, 200 mg $169.14/20. Oral suspension
(lemon creme): 50 mg/5 mL, 100 mg/5 mL. Cost:
Generic—50 mg/5 mL $35.28/50 mL, 100 mg/5 mL
$86.17/50 mL.
Ceftazidime (generic available)
Powder for injection: 500 mg/vial, 1 g/vial, 2 g/vial,
6 g/vial. Premixed containers: 1 g/50 mL, 2 g/50 mL.
Ceftriaxone (generic available)
Powder for injection: 250 mg/vial, 500 mg/vial, 1 g/
vial, 2 g/vial, 10 g/vial. Premixed containers: 1 g/50
mL, 2 g/50 mL.
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