CEFTRIAXONE

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Ensure adequate hydration during treatment with ceftriaxone to prevent ceftriaxone-calcium precipitation in the urinary tract.
Intravenous Administration
NOTE: Do NOT use diluents containing calcium to reconstitute ceftriaxone vials or for further dilution of the reconstituted vial for IV administration due to the potential for precipitation. This precipitation can also occur when ceftriaxone is mixed with calcium-containing solutions in the same IV line; do not administer ceftriaxone simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions (i.e. parenteral nutrition) via a Y-site. In patients other than neonates, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are flushed with a compatible solution. Ceftriaxone is contraindicated in neonates that require any calcium-containing IV solutions. There have been no reports of an interaction between ceftriaxone and oral calcium-containing products.
NOTE: The IV administration of ceftriaxone solutions containing lidocaine is contraindicated.

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
-Do NOT use solutions containing calcium (i.e., Lactated Ringer's Injection or Hartmann's solution).
-Reconstitute 250 mg, 500 mg, 1 g, and 2 g vials with 2.4, 4.8, 9.6, or 19.2 mL, respectively, with a compatible IV solution to give solutions containing 100 mg/mL of ceftriaxone.
-Compatible IV solutions include Sterile Water for Injection, Bacteriostatic Water for Injection, 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and 10% Dextrose Injection. Bacteriostatic Water for Injection should NOT be used for the preparation of neonatal doses.
-Storage: Reconstituted solutions may be stored for 2 days at room temperature (25 degrees C) or for 10 days in the refrigerator (4 degrees C).

Dilution
-Do NOT use diluents containing calcium (i.e., Lactated Ringer's Injection or Hartmann's solution).
-Dilute the appropriate dose of reconstituted ceftriaxone with a compatible IV solution to a usual final concentration of 10 to 40 mg/mL (usually 50 or 100 mL for older children and adults).
-Compatible IV solutions include Sterile Water for Injection, Bacteriostatic Water for Injection, 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and 10% Dextrose Injection. Bacteriostatic Water for Injection should NOT be used for the preparation of neonatal doses.
-Storage: Diluted solutions may be stored for 2 days at room temperature or for 10 days in the refrigerator. Ceftriaxone reconstituted and diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection at concentrations of 10 to 40 mg/mL are stable frozen (-20 degrees C) in PVC or polyolefin contains for 26 weeks. Frozen solutions should be thawed at room temperature before use. Do not refreeze.

Bulk Vials for Injection
Reconstitution
-Do NOT use diluents containing calcium (i.e., Lactated Ringer's Injection or Hartmann's solution)
-Reconstitute 10 g vial with 95 mL of a compatible IV solution to result in a 100 mg/mL solution.
-For pharmacy bulk packages, the closure may be penetrated only one time after reconstitution; use a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents. Withdrawal of the contents should be completed within 4 hours from initial closure entry.
-Compatible IV solutions include Sterile Water for Injection, Bacteriostatic Water for Injection, 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and 10% Dextrose Injection.
-Further dilution is required.
-Storage: Reconstituted bulk vials should be used within 4 hours.

Dilution
-Do NOT use diluents containing calcium (i.e., Lactated Ringer's Injection or Hartmann's solution)
-Dilute the appropriate dose of reconstituted ceftriaxone with a compatible IV solution to a usual final concentration of 10 to 40 mg/mL (usually 50 or 100 mL for older children and adults).
-Compatible IV solutions include Sterile Water for Injection, Bacteriostatic Water for Injection, 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and 10% Dextrose Injection.
-For pharmacy bulk packages, the closure may be penetrated only one time after reconstitution; use a suitable sterile transfer device or dispensing set that allows measured dispensing of the contents.
-Storage: Diluted solutions may be stored for 2 days at room temperature (25 degrees C) or for 10 days in the refrigerator (4 degrees C). Ceftriaxone reconstituted and diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection at concentrations of 10 to 40 mg/mL are stable frozen (-20 degrees C) in PVC or polyolefin contains for 26 weeks. Frozen solutions should be thawed at room temperature before use. Do not refreeze.

ADD-Vantage vials
Reconstitution
-Reconstitute 1 or 2 g vial with 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the appropriate 50 or 100 mL flexible diluent container.
-Storage: Reconstituted solutions may be stored for 2 days at room temperature or for 10 days in the refrigerator.

Frozen Pre-mixed Bags
Preparation
-Thaw at room temperature; do not force thaw. No reconstitution is necessary.
-Storage: Thawed solution is stable for 48 hours at room temperature or 21 days in the refrigerator. Do not refreeze thawed antibiotics.

DUPLEX Drug Delivery System
Preparation
-Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber.
-Protect from light after removal of foil strip. If the foil strip is removed and the container will not be used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
-Once ready for activation, allow the product to reach room temperature before patient use.
-Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
-To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete
-Storage: After reconstitution (activation), use within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.

Intermittent IV Infusion
-Infuse IV over 30 minutes. In neonates, infuse IV over 60 minutes to decrease the risk of bilirubin encephalopathy (kernicterus).

Intravenous (IV) Push*
NOTE: Ceftriaxone is not approved by the FDA for IV push administration.
Powder Vials for Injection
Reconstitution
-A study included 544 adult hospitalized patients who received ceftriaxone IV push (median 3 doses).
--Doses of 1 g were reconstituted with 10 mL of 0.9% Sodium Chloride Injection and doses of 2 g were reconstituted with 20 mL of 0.9% Sodium Chloride Injection.

-A study included 1,110 adult patients who received cephalosporins, including ceftriaxone, by IV push in the emergency department.-Doses of 1 and 2 g were reconstituted with 10 mL of Sterile Water for Injection.

-A study included 63 adult and pediatric patients who received ceftriaxone by IV push at home.-Doses of 1 g were reconstituted in 10 mL of Sterile Water for Injection.

-A study included 9 adult patients who received ceftriaxone by IV push.-Doses of 1 g were reconstituted in 10 mL of Sterile Water for Injection.

-Stability:-Solutions reconstituted to a concentration of 100 mg/mL with a compatible solution are stable for 2 days at room temperature (25 degrees C) or for 10 days in the refrigerator (4 degrees C).
-In a study, ceftriaxone reconstituted in Sterile Water for Injection and stored in polypropylene syringes, was stable for 5 days at 20 degrees C, for 40 days at 4 degrees C, and for 180 days at -20 degrees C. Concentrations were at least 90% the initial concentration.


Intermittent IV Push
-Doses have been administered IVP at a rate of 2 to 4 minutes for patients 11 years and older, 5 minutes in patients as young as 5 months, and 1 to 5 minutes for adults.
-Although data are limited, there may be a higher risk of certain adverse events with IV push administration compared to intermittent IV infusion.-In one report, an adult experienced tachycardia, restlessness, diaphoresis, and palpitations after receiving a 2 gram dose via IV push over 5 minutes. Subsequent doses were administered over 30 minutes without any complications.
-Limited data suggest that in young infants, IV push administration may have contributed to the risk of cardiopulmonary adverse events associated with the interaction between ceftriaxone and IV calcium.
-A small study showed a higher rate of cholelithiasis when ceftriaxone was administered to children as IV push as compared to a 30 minute IV infusion.


Intramuscular Administration
Reconstitution
-Vials may be reconstituted with Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, Bacteriostatic Water for Injection containing 0.9% benzyl alcohol, or 1% lidocaine HCl (without epinephrine). Do NOT use diluents containing calcium (e.g., Lactated Ringer's Injection or Hartmann's solution), as particulate formation can result. Bacteriostatic Water for Injection should NOT be used for the preparation of neonatal doses.
-For a solution concentration of 250 mg/mL, reconstitute the 250 mg vial with 0.9 mL, the 500 mg vial with 1.8 mL, the 1 g vial with 3.6 mL, and the 2 g vial with 7.2 mL of diluent.
-For a solution concentration of 350 mg/mL, reconstitute the 500 mg vial with 1 mL, the 1 g vial with 2.1 mL, and the 2 g vial with 4.2 mL of diluent; do not use the 250 mg vial to reconstitute a 350 mg/mL solution.
-Storage: Reconstituted solution may be stored for 24 hours at room temperature or 3 days in the refrigerator.

Intramuscular Injection
-Inject deeply into a large muscle (e.g., anterolateral thigh or deltoid [children and adolescents only]).
-In general, the American Academy of Pediatrics suggests the following volume limits for intramuscular administration of medications :-0.5 mL per injection for small infants
-1 mL per injection for larger infants
-2 mL per injection for school-aged children
-3 mL per injection for adolescents

A local injection site reaction can occur after IM or IV administration of ceftriaxone. In clinical trials, pain, induration and tenderness occurred in 1% overall. Phlebitis was reported in < 1% after IV administration. The incidence of warmth, pain, tightness or induration was 17% after IM administration of 350 mg/ml and 5% after IM administration of 250 mg/ml. Pain with administration of IM ceftriaxone can be minimized by using lidocaine as a diluent, when appropriate. Fatal reactions related to incompatibilities during intravenous (IV) administration have resulted from ceftriaxone-calcium precipitates in lung and kidneys in both term and premature neonates. In some cases, the infusion lines and the times of administration of ceftriaxone and calcium containing solutions differed. Ceftriaxone is contraindicated in neonates (i.e., <= 28 days of age) that require any calcium-containing IV solutions, including continuous calcium-containing infusions (e.g., parenteral nutrition). In non-neonatal patients, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are flushed with a compatible solution between the administration of the infusions.

Diarrhea (2.7%) is one of the most common adverse GI effects that occurs with ceftriaxone use. Nausea, vomiting, and dysgeusia have been reported in < 1% of patients. Abdominal pain, colitis, dyspepsia, and flatulence have been rarely (< 0.1%) reported. Stomatitis and glossitis have been noted in post-marketing reports.

Eosinophilia (6%), thrombocytosis (5.1%), and leukopenia (2.1%) are the most frequent hematologic adverse effects of ceftriaxone therapy. Anemia, hemolytic anemia, neutropenia, lymphopenia, and thrombocytopenia have been reported in less than 1% of ceftriaxone-treated patients in clinical trials. An immune-mediated hemolytic anemia has been observed in patients receiving cephalosporin class antibacterials including ceftriaxone. Severe cases of hemolytic anemia, including fatalities, have been reported during treatment in both adults and children. If a patient develops anemia while receiving ceftriaxone, consider the diagnosis of a cephalosporin-associated anemia and discontinue ceftriaxone until the etiology is determined. Hypoprothrombinemia has been reported with some cephalosporins, including ceftriaxone (less than 0.1%). Although hypoprothrombinemia may be due to a methylthiotetrazole (MTT) side chain, others believe a sulfhydryl group (SH) may be responsible. Ceftriaxone does contain a sulfhydryl group and has been associated with hypoprothrombinemia; however, the degree of change in prothrombin time is of questionable significance. Coagulopathy (0.4%) has been reported in ceftriaxone-treated patients in clinical trials. Alterations in prothrombin times have occurred in patients treated with ceftriaxone. Vitamin K administration may be necessary if the prothrombin time is prolonged before or during therapy (less than 1%). Other hematologic adverse reactions have been reported in less than 0.1% of patients and include agranulocytosis, basophilia, leukocytosis, lymphocytosis, monocytosis, prothrombin time decrease, and serum sickness. Other adverse events associated with the cephalosporin class include aplastic anemia, hemorrhage/bleeding, and a positive direct Coombs' test.

Serious neurological adverse reactions have been reported during postmarketing surveillance with ceftriaxone. These reactions include encephalopathy (disturbance of consciousness including drowsiness, lethargy, and confusion), seizures, myoclonia, and non-convulsive status epilepticus. Some cases occurred in patients with severe renal impairment who did not receive appropriate dosage adjustment. However, these reactions also occurred in patients receiving an appropriate dosage adjustment. The neurological adverse reactions were reversible and resolved after ceftriaxone discontinuation. Discontinue ceftriaxone and institute appropriate supportive measures if neurological adverse reactions occur. Headache and dizziness have been reported in less than 1% of ceftriaxone-treated patients in clinical trials. Adverse reactions associated with the cephalosporin class include reversible hyperactivity and hypertonia.

Hepatic and biliary adverse events may be noted with ceftriaxone therapy. Elevated hepatic enzymes, occurring as elevations of SGOT (3.1%) or SGPT (3.3%), are the more common laboratory effects. Less frequently reported (less than 1%) were elevations of alkaline phosphatase and bilirubin (hyperbilirubinemia). Other rarely observed adverse reactions (less than 0.1%) include cholelithiasis, gallbladder sludge, and jaundice. Kernicterus has been reported in postmarketing reports. Pseudo-cholelithiasis or pseudolithiasis (also referred to as biliary 'sludge') has been known to develop, especially in children, during ceftriaxone therapy. Ceftriaxone-calcium precipitates in the gallbladder have been observed in patients receiving ceftriaxone. These precipitates appear on sonography as an echo without acoustical shadowing suggesting sludge or as an echo with acoustical shadowing which may be misinterpreted as gallstones. Patients may be asymptomatic or may develop symptoms of gallbladder disease. The condition appears to be reversible upon discontinuation of ceftriaxone and institution of conservative management. Discontinue ceftriaxone in patients who develop signs and symptoms suggestive of gallbladder disease and/or sonographic findings. Cases of pancreatitis, possibly secondary to biliary obstruction, have been reported in patients treated with ceftriaxone sodium. Most patients presented with risk factors for biliary stasis and biliary sludge (preceding major therapy, severe illness, total parenteral nutrition). A cofactor role of ceftriaxone-related biliary precipitation cannot be ruled out. Other adverse events associated with cephalosporins include elevated LDH, hepatic dysfunction, and cholestasis.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with ceftriaxone. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Candidiasis, reported as moniliasis or vaginitis, was reported occasionally (less than 1%).

Rash (unspecified) is reported in roughly 1.7% of patients receiving ceftriaxone, while pruritus occurs rarely (< 1%). Other rare adverse reactions (< 0.1%) include allergic pneumonitis and anaphylaxis/anaphylactoid reactions. Other dermatologic adverse events noted in post-marketing reports include exanthema, allergic dermatitis, urticaria, edema, acute generalized exanthematous pustulosis (AGEP), and isolated cases of severe cutaneous reactions (erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome/toxic epidermal necrolysis). Angioedema has been reported with cephalosporin use.

General adverse events reported in < 1% of patients receiving ceftriaxone include fever, chills, diaphoresis, and flushing. Palpitations have occurred in < 0.1% of patients.

Renal and urinary adverse events reported with ceftriaxone include elevated BUN/azotemia (1.2%), elevated serum creatinine (less than 1%), and urinary casts (less than 1%). Glycosuria, hematuria, nephrolithiasis, and renal precipitations were rarely reported (less than 0.1%) in clinical trials. Oliguria, ureteric urinary tract obstruction, and postrenal acute renal failure (PARF) have been noted with ceftriaxone in postmarketing reports. Ceftriaxone-calcium precipitates in the urinary tract have been reported in patients receiving ceftriaxone. The risk appears to be higher in pediatric patients. Cases of fatal reactions with ceftriaxone-calcium precipitates in kidneys in neonates have been described. In some cases the infusion lines and times of administration of ceftriaxone and calcium-containing solutions differed. These precipitates may be detected as sonographic abnormalities. Patients may be asymptomatic or present with symptoms of urolithiasis, ureteral obstruction, or PARF. The condition appears to be transient and reversible upon discontinuation of the drug and institution of appropriate management. Ensure adequate hydration in patients receiving ceftriaxone. Discontinue ceftriaxone in patients who develop signs and symptoms indicative of urolithiasis, oliguria, or renal failure, and/or sonographic findings. Cases of urolithiasis and PARF have been reported with ceftriaxone therapy in children. Other adverse events associated with the cephalosporin class include renal dysfunction, toxic nephropathy, and a false-positive test for urinary glucose.

Bronchospasm and epistaxis have been reported in < 0.1% of patients receiving ceftriaxone therapy.

The Jarisch-Herxheimer reaction is a self-limiting systemic reaction that has been reported in the setting of spirochete infections, such as Lyme disease, syphilis, relapsing fever, and leptospirosis, after the initiation of antimicrobial therapy. It is characterized by fever, chills, myalgias, headache, exacerbation of cutaneous lesions, tachycardia, hyperventilation, vasodilation with flushing, and mild hypotension. Less commonly, symptoms may include meningitis, pulmonary failure, hepatic and renal dysfunction, myocardial injury, premature uterine contractions in pregnant patients, and worsening cerebral function as well as strokes and seizures. The reaction has been noted in up to 30% of patients with early Lyme disease. The timing of the reaction varies by underlying infection but typically presents within a few hours after the initiation of antibiotics. For Lyme disease, the reaction usually begins within 1 to 2 hours after starting therapy and disappears within 12 to 24 hours. The reaction after treatment in syphilis usually starts at 4 hours, peaks at 8 hours, and subsides by 16 hours whereas it starts at about 1 to 2 hours, peaks at 4 hours, and subsides by 8 hours after treatment in relapsing fever. The pathogenesis of this reaction is unknown but may be due to the release of spirochetal heat-stable pyrogen. Fluids and antipyretics can be used to alleviate symptoms and duration of the reaction if severe.

Ceftriaxone is contraindicated in patients with cephalosporin hypersensitivity or cephamycin hypersensitivity. Use ceftriaxone cautiously in patients with hypersensitivity to penicillin. The structural similarity between ceftriaxone and penicillin means that cross-reactivity can occur. Penicillins can cause a variety of hypersensitivity reactions ranging from mild rash to fatal anaphylaxis. Patients who have experienced severe penicillin hypersensitivity should not receive ceftriaxone. Cross-reactivity to cephalosporins is approximately 3-7% with a documented history to penicillin.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including ceftriaxone, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Ceftriaxone is contraindicated in premature neonates up to a postmenstrual age of 41 weeks (gestational age plus chronological age). Ceftriaxone can displace bilirubin from serum albumin and is contraindicated for use in term neonates with hyperbilirubinemia (neonatal jaundice). Ceftriaxone is contraindicated in neonates that require or are expected to require calcium-containing IV solutions, including continuous calcium-containing infusions (e.g., parenteral nutrition) because of the risk of precipitation of ceftriaxone-calcium salts. Fatal reactions involving ceftriaxone-calcium precipitates in lung and kidneys have been reported in both term and premature neonates. Infusion lines and times of administration of ceftriaxone and calcium-containing solutions have differed.

Regardless of the patient's age, ceftriaxone must NOT be mixed or administered simultaneously with calcium-containing IV solutions or products, even via a Y-site or different infusion lines at different sites. The use of ceftriaxone is contraindicated in neonates that require or are expected to require coadministration of calcium-containing IV's, including continuous calcium-containing infusions (e.g., parenteral nutrition), because of the risk of precipitation of ceftriaxone-calcium salts. Fatal reactions involving ceftriaxone-calcium precipitates in lung and kidneys have been reported in both term and premature newborns. Infusion lines and times of administration of ceftriaxone and calcium-containing solutions have differed. There are no reports of intravascular or pulmonary precipitations in non-neonatal patients; however, the possibility exists for an interaction between ceftriaxone and IV calcium-containing solutions in patients of all ages. In non-neonatal patients, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are thoroughly flushed between the infusions with a compatible fluid. According to the manufacturer, there have been no reports of an interaction between ceftriaxone and oral calcium supplements or interaction between intramuscular ceftriaxone and calcium-containing products (IV or oral).

All cephalosporins may rarely cause hypothrombinemia and have the potential to cause bleeding. Cephalosporins which contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been associated with an increased risk for bleeding. Monitor prothrombin time during ceftriaxone treatment in patients with impaired vitamin K synthesis or vitamin K deficiency (e.g., chronic hepatic disease and malnutrition). Alterations in prothrombin times have occurred in patients treated with ceftriaxone. Vitamin K administration may be necessary if the prothrombin time is prolonged before or during therapy. Use ceftriaxone with caution and do not exceed 2 g/day in persons with hepatic dysfunction and significant renal dysfunction. Ceftriaxone dosage adjustments are not normally required in persons with hepatic dysfunction alone.

Use ceftriaxone with caution and do not exceed 2 g/day in persons with hepatic dysfunction and significant renal disease, renal impairment, or renal failure. Ceftriaxone dosage adjustments are not normally required in persons with renal failure alone.

Ceftriaxone is associated with laboratory test interference. In patients treated with ceftriaxone the Coombs test may become positive. Ceftriaxone, like other antibacterial drugs, may result in positive test results for galactosemia. A false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as ceftriaxone, and using Benedict's solution, Fehling's solution, or Clinitest tablets for urine glucose testing. However, this reaction has not been observed with glucose oxidase tests (e.g., Tes-tape, Clinistix, Diastix). Patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on ceftriaxone treatment. Ceftriaxone may also cause falsely lower blood glucose concentrations with some blood glucose monitoring systems. Refer to specific instructions for use for each system; alternative testing methods may be necessary.

Description: Ceftriaxone is a parenteral broad-spectrum third-generation cephalosporin. Similar to other third-generation cephalosporins, ceftriaxone possesses significant activity against serious gram-negative organisms; however, in general, it is not effective for the treatment of infections due to Pseudomonas aeruginosa. Although it is less active against gram-positive bacteria than first-generation agents, ceftriaxone can be effective for infections due to susceptible strains of nonenterococcal streptococci and methicillin-sensitive S. aureus. Because ceftriaxone penetrates into cerebral spinal fluid (CSF), it is often used in combination with vancomycin for the empiric treatment of meningitis in pediatric patients > 1 month of age. Ceftriaxone has a long half-life compared to other cephalosporins allowing for once-daily dosing for mild to moderate infections; however, twice daily dosing is recommended for the treatment of meningitis and other serious infections. Neonatal patients should be carefully evaluated before initiating ceftriaxone therapy. Because it can displace bilirubin from serum albumin, ceftriaxone is contraindicated in neonates with hyperbilirubinemia. In addition, ceftriaxone is contraindicated in neonates that require or are expected to require calcium-containing IV solutions, including continuous calcium-containing infusions, because of the risk of precipitation of ceftriaxone-calcium salts. Ceftriaxone is FDA-approved for use in pediatric patients as young as neonates.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Acinetobacter calcoaceticus, Bacteroides bivius, Bacteroides fragilis, Citrobacter diversus, Citrobacter freundii, Clostridium sp., Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Haemophilus parainfluenzae, Klebsiella aerogenes, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Peptostreptococcus sp., Prevotella melaninogenica, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia sp., Salmonella enterica serotype Typhi , Salmonella sp., Serratia marcescens, Shigella sp., Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Viridans streptococci
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Borrelia burgdorferi, Leptospira sp.
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of meningitis and ventriculitis*:
NOTE: For gonococcal meningitis, see disseminated gonococcal infections. For neurologic Lyme infections, see Lyme borreliosis.
-for the treatment of meningococcal meningitis as well as meningitis or ventriculitis* due to H. influenzae:
Intravenous dosage:
Neonates: 50 mg/kg/dose IV every 24 hours for 7 days. Guidelines recommend cefotaxime as the third-generation cephalosporin of choice for meningitis in neonates.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 7 days.
-for the treatment of pneumococcal meningitis and ventriculitis*:
Intravenous dosage:
Neonates: 50 mg/kg/dose IV every 24 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL. Guidelines recommend cefotaxime as the third-generation cephalosporin of choice for meningitis in neonates.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL.
-for the treatment of meningitis or ventriculitis due to aerobic gram-negative rods*:
Intravenous dosage:
Neonates: 50 mg/kg/dose IV every 24 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer. Guidelines recommend cefotaxime as the third-generation cephalosporin of choice for meningitis in neonates.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 to 21 days.
-for the treatment of meningitis or ventriculitis due to C. acnes*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 to 14 days.
-for the treatment of meningitis due to S. agalactiae*:
Intravenous dosage:
Neonates: 50 mg/kg/dose IV every 24 hours for 14 to 21 days. Guidelines recommend cefotaxime as the third-generation cephalosporin of choice for meningitis in neonates.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 14 to 21 days.

For the treatment of acute otitis media:
Intramuscular or Intravenous* dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 1 g/dose) IV/IM every 24 hours for 1 or 3 days as initial treatment for patients who cannot tolerate oral therapy and for 3 days in patients who have failed initial oral antibiotic therapy.

For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP) and pleural empyema*:
-for the treatment of nonspecific lower respiratory tract infections (LRTIs):
Intravenous or Intramuscular dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV or IM every 24 hours.
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours. Consider 100 mg/kg/day (Max: 4 g/day) IV or IM divided every 12 hours for serious infections.
-for the empiric treatment of community-acquired pneumonia (CAP):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 5 to 7 days. Guidelines recommend empiric therapy with ceftriaxone for hospitalized patients who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents high-level penicillin resistance, and for life-threatening infection. Consider combination therapy with a macrolide for suspected atypical pneumonia or with clindamycin or vancomycin for suspected infection due to S. aureus.
-for the treatment of CAP in pediatric patients due to S. pneumoniae (penicillin MIC 2 mcg/mL or less):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to S. pneumoniae, relatively resistant (penicillin MIC 4 mcg/mL or more):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to Group A Streptococcus:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 5 to 7 days.
-for the treatment of CAP in pediatric patients due to H. influenzae (beta-lactamase positive):
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 5 to 7 days.
-for the treatment of community-acquired pleural empyema*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose IV every 12 hours (Max: 2 g/day). Use in combination with metronidazole for at least 2 weeks after drainage and defervescence.

For the treatment of bacteremia and sepsis:
Intravenous dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV every 24 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours. The FDA-approved dosage is 50 to 75 mg/kg/day (Max: 2 g/day) IV divided every 12 hours; however, higher doses have been shown to be necessary to attain pharmacodynamic targets (100% free T above the MIC) in critically ill children. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the treatment of acute bacterial sinusitis*:
-for the treatment of severe acute bacterial sinusitis requiring hospitalization*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 1 g/dose) IV every 24 hours for 10 to 14 days.
-for the treatment of mild to moderate acute bacterial sinusitis in patients unable to tolerate oral antibiotics due to severe vomiting*:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM as a single dose, followed by an oral antibiotic 24 hours later.

For the treatment of uncomplicated or complicated urinary tract infection (UTI), including pyelonephritis and catheter-associated urinary tract infection:
-for the treatment of uncomplicated or complicated UTI, including pyelonephritis:
Intravenous or Intramuscular dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV or IM every 24 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants 1 month: 50 to 75 mg/kg/day IV or IM divided every 12 to 24 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours. Treat for 48 to 72 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
-for the treatment of catheter-associated UTI:
Intravenous or Intramuscular dosage:
Infants 1 month: 50 to 75 mg/kg/day IV or IM divided every 12 to 24 hours for 7 to 14 days.
Infants, Children, and Adolescents 2 months to 17 years: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for 7 to 14 days.

For the treatment of infective endocarditis*:
NOTE: For gonococcal endocarditis, see gonococcal infections.
-for the treatment of native valve endocarditis due to highly susceptible streptococci*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 4 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 4 weeks.
-for the treatment of native valve endocarditis due to relatively resistant streptococci*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 4 weeks plus gentamicin for 2 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 4 weeks plus gentamicin for 2 weeks.
-for the treatment of prosthetic valve endocarditis due to highly susceptible streptococci*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 6 weeks plus gentamicin for 2 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 6 weeks plus gentamicin for 2 weeks.
-for the treatment of prosthetic valve endocarditis due to relatively resistant streptococci*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 6 weeks plus gentamicin.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 6 weeks plus gentamicin.
-for the treatment of native or prosthetic valve endocarditis due to Enterococcus sp.*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 4 to 6 weeks plus ampicillin for aminoglycoside-resistant enterococci or aminoglycoside-intolerant patients.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 4 to 6 weeks plus ampicillin for aminoglycoside-resistant enterococci or aminoglycoside-intolerant patients.
-for the treatment of native or prosthetic valve endocarditis due to HACEK microorganisms*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 4 weeks.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 4 weeks.
-for the treatment of native or prosthetic valve endocarditis due to enteric gram-negative microorganisms*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM for at least 6 weeks plus an aminoglycoside.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for at least 6 weeks plus an aminoglycoside.
-for the treatment of suspected Bartonella endocarditis (culture negative)*:
Intravenous or Intramuscular dosage:
Neonates: 50 mg/kg/dose IV or IM every 24 hours for 6 weeks plus gentamicin for 2 weeks.
Infants: 50 mg/kg/dose IV or IM every 12 hours for 6 weeks plus gentamicin for 2 weeks.
Children and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV or IM every 12 hours for 6 weeks plus gentamicin for 2 weeks with or without doxycycline for 6 weeks.

For bacterial endocarditis prophylaxis*:
Intravenous or Intramuscular dosage:
Children and Adolescents: 50 mg/kg/dose (Max: 1 g/dose) IV or IM as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin and/or unable to take oral medications. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

For post-exposure meningococcal infection prophylaxis*:
Intramuscular dosage:
Infants, Children, and Adolescents 1 month to 14 years: 125 mg IM as a single dose. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.
Adolescents 15 to 17 years: 250 mg IM as a single dose. Initiate prophylaxis as soon as possible after exposure (ideally less than 24 hours after identification of index patient); prophylaxis initiated more than 14 days after onset of illness in the index patient has very limited or no value.

For the treatment of Lyme disease, including Lyme arthritis*, Lyme carditis*, and Lyme meningitis*, cranial neuropathy*, and radiculoneuropathy/radiculoneuritis*:
-for the treatment of recurrent or refractory Lyme arthritis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 2 g/dose) IV once daily for 14 to 28 days in patients with no or minimal response (moderate to severe joint swelling with minimal reduction of the joint effusion) to the initial course of oral antibiotics.
-for the treatment of Lyme carditis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 2 g/dose) IV once daily in hospitalized patients with severe disease (i.e., symptomatic, first degree AV block with PR interval 300 milliseconds or greater, second or third degree AV block) until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days.
-for the treatment of neurologic Lyme disease* without parenchymal involvement, including Lyme meningitis*, cranial neuropathy*, and radiculoneuropathy/radiculoneuritis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 2 g/dose) IV once daily until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.
-for the treatment of neurologic Lyme disease* with parenchymal involvement of the brain or spinal cord:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 2 g/dose) IV once daily for 14 to 28 days. IV therapy is preferred.

For the treatment of quinolone-resistant uncomplicated or severe typhoid fever* and multidrug-resistant severe typhoid fever*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/day (Max: 4 g/day) IV divided every 12 to 24 hours for 5 to 14 days; treat for at least 7 days after defervescence.

For the treatment of leptospirosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 80 to 100 mg/kg/dose (Max: 2 g/dose) IV every 24 hours for 7 days as first-line therapy for severe disease.

For the treatment of gonorrhea*, including bacterial conjunctivitis* and ophthalmia neonatorum*:
-for the treatment of uncomplicated gonorrhea*, including cervicitis*, urethritis*, pharyngitis*, and proctitis*:
Intravenous or Intramuscular dosage:
Infants and Children weighing 45 kg or less: 25 to 50 mg/kg/dose (Max: 250 mg/dose) IV or IM as a single dose.
Children weighing more than 45 kg: 500 mg IM as a single dose.
Adolescents weighing less than 150 kg: 500 mg IM as a single dose.
Adolescents weighing 150 kg or more: 1 g IM as a single dose.
-for the treatment of gonococcal scalp abscesses and disseminated gonococcal infections in neonates:
Intravenous or Intramuscular dosage:
Neonates: 25 to 50 mg/kg/dose IV or IM every 24 hours for 7 days.
-for the treatment of gonococcal arthritis* and arthritis-dermatitis syndrome*:
Intravenous or Intramuscular dosage:
Infants and Children: 50 mg/kg/dose (Max: 1 g/dose) IV or IM every 24 hours for 7 days.
Adolescents: 1 g IV or IM every 24 hours for 7 days. If treating for arthritis-dermatitis syndrome, may switch to an oral agent 24 to 48 hours after clinical improvement for a total of at least 7 days.
-for the treatment of gonococcal bacteremia*:
Intravenous or Intramuscular dosage:
Infants and Children: 50 mg/kg/dose (Max: 1 g/dose) IV or IM every 24 hours for 7 days.
-for the treatment of gonococcal meningitis*:
Intravenous dosage:
Neonates: 25 to 50 mg/kg/dose IV every 24 hours for 10 to 14 days.
Infants and Children: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours for 10 to 14 days.
Adolescents: 1 to 2 g IV every 24 hours for 10 to 14 days.
-for treatment of gonococcal endocarditis*:
Intravenous dosage:
Adolescents: 1 to 2 g IV every 24 hours for at least 4 weeks.
-for the treatment of gonococcal bacterial conjunctivitis*:
Intramuscular dosage:
Adolescents: 1 g IM as a single dose. Lavage the infected eye(s) with saline solution to remove accumulated secretions.
-for the treatment of ophthalmia neonatorum* due to N. gonorrhoeae:
Intravenous or Intramuscular dosage:
Neonates: 25 to 50 mg/kg/dose (Max: 250 mg/dose) IV or IM as a single dose.

For gonorrhea prophylaxis*, including ophthalmia neonatorum prophylaxis*:
-for gonorrhea prophylaxis in high-risk neonates*:
Intravenous or Intramuscular dosage:
Neonates: 25 to 50 mg/kg/dose (Max: 250 mg/dose) IV or IM as a single dose for infants at high risk for exposure (i.e., infants born to mothers at risk for gonococcal infection or with no prenatal care).
-for ophthalmia neonatorum prophylaxis*:
Intravenous or Intramuscular dosage:
Neonates: 25 to 50 mg/kg/dose (Max: 250 mg/dose) IV or IM as a single dose may be used if erythromycin ointment is not available and infant is at high risk for exposure (i.e., infants born to mothers at risk for gonococcal infection or with no prenatal care).
-for gonorrhea prophylaxis in victims of sexual assault*:
Intramuscular dosage:
Adolescents weighing less than 150 kg: 500 mg IM as a single dose.
Adolescents weighing 150 kg or more: 1 g IM as a single dose.

For the treatment of pelvic inflammatory disease (PID), including tubo-ovarian abscess*:
-for the treatment of mild-to-moderate PID:
Intramuscular dosage*:
Adolescents weighing less than 150 kg: 500 mg IM as a single dose in combination with oral doxycycline and metronidazole for 14 days. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.
Adolescents weighing 150 kg or more: 1 g IM as a single dose in combination with oral doxycycline and metronidazole for 14 days. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.
-for the treatment of severe PID or tubo-ovarian abscess*:
Intravenous dosage:
Adolescents: 1 g IV every 24 hours in combination with doxycycline and metronidazole. Ceftriaxone should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy.

For the treatment of syphilis*, including neurosyphilis*:
NOTE: A Jarisch-Herxheimer reaction may occur within the first 24 hours of therapy.
NOTE: While the CDC recommends non-penicillin alternatives for syphilis in HIV-infected patients, their efficacy has not been evaluated and they should only be used with close clinical and serologic monitoring.
-for primary, secondary, or early latent syphilis* in nonpregnant, penicillin-allergic patients:
Intravenous or Intramuscular dosage:
Adolescents: 1 g IV or IM once daily for 10 days may be effective for primary or secondary syphilis. Ceftriaxone may also be effective for treating latent syphilis; however, the optimal dose and duration have not been established.
-for neurosyphilis* in nonpregnant, penicillin-allergic patients:
Intravenous or Intramuscular dosage:
Adolescents: 1 to 2 g IV or IM once daily for 10 to 14 days if penicillin desensitization is not possible.
-for the treatment of congenital syphilis*:
Intravenous or Intramuscular dosage:
Neonates: 50 to 75 mg/kg/dose IV or IM every 24 hours for 10 to 14 days may be considered with careful clinical and serologic follow-up during a shortage of aqueous penicillin G and penicillin G procaine.
Infants: 75 mg/kg/dose IV or IM every 24 hours for 10 to 14 days may be considered with careful clinical and serologic follow-up during a shortage of aqueous penicillin G and penicillin G procaine.
Children: 100 mg/kg/dose (Max: 2 g/dose) IV or IM every 24 hours for 10 to 14 days may be considered with careful clinical and serologic follow-up during a shortage of aqueous penicillin G and penicillin G procaine.

For the treatment of epididymitis*:
Intramuscular dosage:
Children weighing 45 kg or more: 500 mg IM as a single dose in combination oral doxycycline when most likely due gonorrhea or chlamydia or with oral levofloxacin when most likely due to gonorrhea, chlamydia, or enteric organisms.
Adolescents weighing less than 150 kg: 500 mg IM as a single dose in combination oral doxycycline when most likely due gonorrhea or chlamydia or with oral levofloxacin when most likely due to gonorrhea, chlamydia, or enteric organisms.
Adolescents weighing 150 kg or more: 1 g IM as a single dose in combination oral doxycycline when most likely due gonorrhea or chlamydia or with oral levofloxacin when most likely due to gonorrhea, chlamydia, or enteric organisms.

For the treatment of chancroid* due to Haemophilus ducreyi:
Intramuscular dosage:
Infants and Children: 50 mg/kg/dose (Max: 250 mg/dose) IM as a single dose. A longer course may be required in HIV-infected patients and uncircumcised males.
Adolescents: 250 mg IM as a single dose. A longer course of therapy may be required in HIV-infected patients and uncircumcised males. Data for efficacy of single-dose ceftriaxone regimen are limited in patients with HIV; an erythromycin 7-day regimen or ciprofloxacin 3-day regimen may be preferred.

For the treatment of skin and skin structure infections, including cellulitis:
-for treatment of unspecified skin and skin structure infections:
Intravenous or Intramuscular dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV or IM every 24 hours.
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours.
-for the treatment of nonpurulent skin infections, such as cellulitis and erysipelas:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV divided every 12 to 24 hours for 5 to 14 days.

For surgical infection prophylaxis*:
Intravenous dosage:
Neonates: 50 to 75 mg/kg/dose IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 2 g/dose) IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. The duration of prophylaxis should not exceed 24 hours.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, and intraabdominal abscess:
-for the treatment of complicated community-acquired intraabdominal infections with adequate source control:
Intravenous or Intramuscular dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV or IM every 24 hours as part of combination therapy for 7 to 10 days. Ceftriaxone plus metronidazole is standard of care for appendicitis.
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess. Ceftriaxone plus metronidazole is standard of care for appendicitis.
-for the treatment of uncomplicated intraabdominal infections with adequate source control:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel. Ceftriaxone plus metronidazole is standard of care for appendicitis.
-for the treatment of uncomplicated intraabdominal infections without definitive source control:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV or IM divided every 12 to 24 hours for at least 48 hours, followed by oral step-down therapy for a total treatment duration of 5 to 10 days as part of combination therapy. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel. Ceftriaxone plus metronidazole is standard of care for appendicitis.

For the treatment of infectious diarrhea* and gastroenteritis*, including salmonellosis*, shigellosis*, and yersiniosis*:
-for the empiric treatment of enteric bacterial infections* in persons living with HIV:
Intravenous dosage:
Adolescents: 1 g IV every 24 hours for 5 days. Routine use is not recommended.
-for the treatment of salmonellosis* in persons without HIV:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/dose (Max: 1 g/dose) IV every 24 hours for 48 to 72 hours or until the patient becomes afebrile; treat for 7 to 14 days if concurrent bacteremia. Routine use is not recommended; reserve for patients at high risk for invasive infection.
-for the treatment of salmonellosis* in persons living with HIV:
Intravenous dosage:
Adolescents: 1 g IV every 24 hours for 7 to 14 days as alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
-for the treatment of shigellosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 100 mg/kg/dose (Max: 1 g/dose) IV every 24 hours for 2 to 5 days.
-for the treatment of yersiniosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours for 5 to 14 days; treat for 14 days if concurrent bacteremia.

For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis:
-for the treatment of osteomyelitis:
Intravenous dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 50 to 100 mg/kg/day IV divided every 12 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 50 to 100 mg/kg/day (Max: 2 g/day) IV divided every 12 to 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis:
Intravenous dosage:
Premature* and Term Neonates: 50 mg/kg/dose IV every 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 50 to 100 mg/kg/day IV divided every 12 to 24 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 50 to 100 mg/kg/day (Max: 2 g/day) IV divided every 12 to 24 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

For the treatment of bartonellosis*, including severe Oroya fever*:
NOTE: See endocarditis for treatment of endocarditis.
Intravenous dosage:
Infants, Children, and Adolescents: 70 mg/kg/dose (Max: 2 g/dose) IV every 24 hours for 7 to 14 days plus ciprofloxacin as first-line therapy.

For the treatment of invasive vibriosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/dose (Max: 1 g/dose) IV every 24 hours in combination with doxycycline for 7 to 14 days.

For the treatment of acute exacerbations of bronchiectasis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 75 mg/kg/day (Max: 2 g/day) IV divided every 12 to 24 hours for 14 days.

For the treatment of epiglottitis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours for 5 to 10 days.

Maximum Dosage Limits:
-Neonates
50 mg/kg/day IV/IM.
-Infants
100 mg/kg/day IV/IM.
-Children
100 mg/kg/day IV/IM (Max: 4 g/day).
-Adolescents
100 mg/kg/day IV/IM (Max: 4 g/day).

Patients with Hepatic Impairment Dosing
Use ceftriaxone with caution and do not exceed 2 g/day in persons with hepatic impairment and significant renal impairment. Ceftriaxone dosage adjustments are not normally required in persons with hepatic dysfunction alone.

Patients with Renal Impairment Dosing
Use ceftriaxone with caution and do not exceed 2 g/day in persons with significant renal impairment and hepatic impairment. Ceftriaxone dosage adjustments are not normally required in persons with renal failure alone.

GFR 10 mL/minute/1.73 m2 or more:* No dosage adjustment needed.
GFR less than 10 mL/minute/1.73 m2:* Administer usual dose every 24 hours.

Intermittent hemodialysis*
50 mg/kg/dose (Max: 2 g/dose) IV or IM every 24 hours. Ceftriaxone is not removed by hemodialysis. Therefore, no supplementary doses are necessary after dialysis.

Peritoneal dialysis*
50 mg/kg/dose (Max: 2 g/dose) IV or IM every 24 hours. Ceftriaxone is not removed by peritoneal dialysis. Therefore, no supplementary doses are necessary after dialysis.

Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.

50 mg/kg/dose (Max: 2 g/dose) IV or IM every 24 hours.

Plasmapheresis*
Administer usual dose after plasmapheresis or at least 15 hours before plasmapheresis.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Ceftriaxone, a beta-lactam antibiotic, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in cell wall synthesis and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of ceftriaxone and other beta-lactams against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, ceftriaxone's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.

Beta-lactams, including ceftriaxone, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T more than MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.

The susceptibility interpretive criteria for ceftriaxone are delineated by pathogen. The MICs are defined for Enterobacterales, Viridans group Streptococcus sp., Abiotrophia sp., Granulicatella sp., Aerococcus sp., Gemella sp., Corynebacterium sp., Lactococcus sp., and Aeromonas sp. as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Enterobacterales based on a dosage of 1 g IV every 24 hours. The MICs are defined for Pasteurella sp. as 0.12 mcg/mL or less. The MICs are defined for E. rhusiopathiae as susceptible at 1 mcg/mL or less. The MICs are defined for H. influenzae, H. parainfluenzae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and Moraxella catarrhalis as susceptible at 2 mcg/mL or less. The MICs are defined for N. gonorrhoeae as susceptible at 0.25 mcg/mL or less. The MICs are defined for N. meningitidis as susceptible at 0.12 mcg/mL or less. The MICs are defined for beta-hemolytic Streptococcus sp. as susceptible at 0.5 mcg/mL or less. The MICs are defined for Acinetobacter sp. as susceptible at 8 mcg/mL or less, intermediate at 16 to 32 mcg/mL, and resistant at 64 mcg/mL or more. For S. pneumoniae, MICs are based on the site of infection. For non-meningitis infections, the MICs are defined for S. pneumoniae as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. For meningitis, the MICs are defined for S. pneumoniae as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more (requires therapy with maximum doses). The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for anaerobes. The MICs are defined for anaerobes by the FDA as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more; however, the MICs are defined for anaerobes by CLSI as susceptible at 16 mcg/mL or less, intermediate at 32 mcg/mL, and resistant at 64 mcg/mL or more. Oxacillin-susceptible staphylococci may be considered susceptible to ceftriaxone.

Pharmacokinetics: Ceftriaxone is administered intravenously and intramuscularly. Protein binding ranges from 85-95%. It is widely distributed into most body tissues including the gallbladder, liver, and kidney, and fluids including urine, biliary, peritoneal, pleural, middle ear, and synovial fluids. Ceftriaxone penetrates inflamed meninges and reaches therapeutic concentrations within the cerebrospinal fluid (CSF). The drug does cross the placenta. Approximately 33-67% of ceftriaxone is excreted into the urine as unchanged drug with the remainder eliminated into the feces via bile. A small percentage is excreted in breast milk. In children with normal renal function, the plasma elimination half-life is approximately 4-7 hours. The elimination half-life increases as renal function declines. The elimination half-life in middle ear fluid is approximately 24 hours.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
Peak ceftriaxone serum concentrations occur within 30 minutes of an IV dose. In pediatric patients with meningitis who received ceftriaxone 50 mg/kg IV or 75 mg/kg IV, the mean maximum serum concentrations were 216 mcg/ml and 275 mcg/ml, respectively; the mean maximum serum concentrations in healthy adults who received 1 g or 2 g IV were 151 mcg/ml and 257 mcg/ml, respectively. One to 3 hours after a 1 g IV dose in adults, average concentrations of ceftriaxone were 581 mcg/ml in the gallbladder bile, 788 mcg/ml in the common duct bile, 898 mcg/ml in the cystic duct bile, 78.2 mcg/g in the gallbladder wall, and 62.1 mcg/ml in the concurrent plasma.

Intramuscular Route
Ceftriaxone is completely absorbed after IM administration, and peak serum concentrations occur within 2-3 hours after the dose. In pediatric patients, concentrations in the middle ear reach a peak of 35 mcg/ml approximately 24 hours after a single IM dose of 50 mg/kg; concentrations of 19 mcg/ml persist for up to 48 hours.


-Special Populations
Pediatrics
Neonates
Ceftriaxone pharmacokinetics were studied in 39 septic neonates <= 16 days postnatal age (birth weight = 1.88 +/- 0.86 kg, gestational age = 31.7 +/- 4 weeks). Mean maximum plasma concentration, volume of distribution, and elimination half-life after a single dose of ceftriaxone 50 mg/kg IV were approximately 153 +/- 39 mg/L, 326 +/- 70 ml/kg, and 15.4 +/- 5.6 hours, respectively. Clearance increased and elimination half-life decreased with increasing postnatal age. After multiple doses of 50 mg/kg IV or IM daily, the half-life decreased to 8.5 +/- 1.5 hours and accumulation of the drug did not occur. Cerebrospinal fluid (CSF) concentrations ranged from 2.1 to 3.8 mg/L in 3 neonates with uninflamed meninges.

Infants and Children
Ceftriaxone pharmacokinetics were studied in pediatric patients with bacterial meningitis (ages not specified). Mean peak plasma concentrations after a 50 mg/kg and 75 mg/kg IV dose were 216 mcg/ml and 275 mcg/ml, respectively. Mean volume of distribution and elimination half-life was 338-373 ml/kg and 4.3-4.6 hours, respectively. Ceftriaxone penetrated inflamed meninges; mean cerebrospinal fluid (CSF) concentrations after a 50 mg/kg and 75 mg/kg IV dose were 5.6 mcg/ml and 6.4 mcg/ml, respectively. In another study of infants and young children (n = 10; 7 to 70 months of age), mean elimination half-life after a 50 mg/kg dose was 6.5 hours.

Hepatic Impairment
Patients with hepatic impairment do not require ceftriaxone dosage adjustments; however, in older children and adolescents receiving the adult dosage, if concomitant significant renal impairment exists, dosage should not exceed 2 g/day without close monitoring. Specific recommendations for infants and young children with concomitant renal and hepatic impairment are not available, but caution should be exercised when using dosages in the upper end of the dosage range in this population.

Renal Impairment
Pharmacokinetic data in pediatric patients with renal impairment are not available; however, the pharmacokinetics of ceftriaxone are only minimally changed in adult patients with renal impairment. Because ceftriaxone undergoes both renal and hepatic elimination, renal impairment alone does not impact clearance enough to require a dosage adjustment when typical dosages are used. However, when both severe renal and hepatic impairment are present, clearance is reduced and the dosage should not exceed 2 g/day without close monitoring. Ceftriaxone is not removed to any significant extent by hemodialysis or peritoneal dialysis.