Version October 2024
Dosage guidance:
Safety: Use alternative therapy if patient is receiving IV calcium in any form (including parenteral nutrition); administer cautiously to hyperbilirubinemic neonates, especially those born prematurely (Ref).
General dosing (Ref): Preterm and term neonates: IM, IV: 50 mg/kg/dose every 24 hours.
Gonococcal infections (Ref): Note: Administer cautiously to hyperbilirubinemic neonates, especially those born prematurely; alternative agent may be necessary.
Prophylaxis, asymptomatic neonates born to mothers with gonococcal infection: IM, IV: 25 to 50 mg/kg as a single dose; maximum dose: 250 mg/dose.
Treatment:
Disseminated infection (including sepsis, arthritis, and meningitis) or scalp abscess: IM, IV: 25 to 50 mg/kg/dose every 24 hours. For sepsis, arthritis, or scalp abscess, treat for 7 days; for documented meningitis treat for 10 to 14 days.
Ophthalmia neonatorum: IM, IV: 25 to 50 mg/kg as a single dose; maximum dose: 250 mg/dose. Note: May also be used for prophylaxis if erythromycin ointment is not available.
Meningitis, nongonococcal: Limited data available; optimal dose not established: Note: IDSA guidelines do not provide ceftriaxone dosing for neonates (Ref). Dosing based on an open-label prospective trial of 71 patients (age range: PNA 14 days to 15 years) which included 26 patients diagnosed with meningitis and a pharmacokinetic analysis of 20 neonates and infants (n=12 neonates; including 6 with PNA <14 days) with sepsis or meningitis; both trials reported adequate cerebrospinal fluid penetration and favorable response (Ref).
PNA <14 days: IV: 50 mg/kg/dose every 24 hours.
PNA ≥14 days: IV: 100 mg/kg for one dose, followed by 80 to 100 mg/kg/dose every 24 hours.
Syphilis, congenital (alternative agent for confirmed or highly probable congenital syphilis): Note: Only for use when aqueous and procaine penicillin are unavailable (eg, shortage) due to insufficient data for use; if used, close monitoring and follow-up in consultation with an expert are required (Ref).
IV: 50 to 75 mg/kg/dose every 24 hours; duration dependent on close clinical and serological follow-up (Ref).
General dosing: Infants, Children, and Adolescents: IM, IV: 50 to 75 mg/kg/day in divided doses every 12 to 24 hours; maximum daily dose: 2,000 mg/day; higher doses are recommended in certain infections (eg, endocarditis, meningitis) (Ref).
Chancroid: Infants, Children, and Adolescents: IM: 50 mg/kg as a single dose; maximum dose: 250 mg/dose (Ref).
Endocarditis, prophylaxis before invasive dental procedures (alternative agent): Limited data available:
Note: Alternative agent for use in patients who are unable to take oral medication and who have penicillin or ampicillin allergy (excluding those with a history of anaphylaxis, angioedema, or urticaria) (Ref). Recommended only in patients who are at highest risk for infective endocarditis (IE) or adverse outcomes (eg, history of IE, cardiac valve repair using prosthetic valves or material, unrepaired cyanotic congenital heart disease [CHD], left ventricular assist device or implantable heart, repaired CHD with prosthetic material or device during first 6 months after procedure, pulmonary artery valve or conduit placement [eg, Melody valve, Contegra conduit], repaired CHD with residual defects at the site or adjacent to site of prosthetic patch or device, heart transplant recipients with cardiac valvulopathy) (Ref).
Infants, Children, and Adolescents: IV, IM: 50 mg/kg as a single dose administered 30 to 60 minutes prior to dental procedure; maximum dose: 1,000 mg/dose (Ref).
Endocarditis, treatment: Children and Adolescents: IV: 50 mg/kg/dose every 12 hours or 80 mg/kg/dose every 24 hours; maximum daily dose: 4,000 mg/day; daily doses over 2,000 mg should be divided into 2 doses. Treat for ≥4 weeks depending on pathogen and valve type; longer durations may be necessary; use in combination with other antibiotics depending on pathogen (Ref).
Epididymitis, acute; empiric treatment: Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended for patients weighing ≥150 kg. Use as part of an appropriate combination regimen (Ref).
Gonococcal infections, treatment:
Uncomplicated gonococcal infection (cervicitis, pharyngitis, proctitis, and urethritis): Note: For pharyngeal gonorrhea, a test-of-cure is recommended 7 to 14 days following treatment (Ref).
Infants and Children weighing ≤45 kg: IM, IV: 25 to 50 mg/kg as a single dose; maximum dose: 250 mg/dose (Ref).
Children weighing >45 kg and Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended for patients weighing ≥150 kg. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (Ref).
Disseminated gonococcal infection (arthritis or arthritis-dermatitis syndrome):
Infants and Children: IM, IV: 50 mg/kg/dose every 24 hours for 7 days; maximum dose: 2,000 mg/dose (Ref).
Adolescents: IM, IV: 1,000 mg every 24 hours; may switch to an oral agent (per susceptibility testing) 24 to 48 hours after clinical improvement and treat for a total of ≥7 days. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (Ref).
Gonococcal bacteremia:
Infants and Children weighing ≤45 kg: IM, IV: 50 mg/kg/dose every 24 hours for 7 days; maximum dose: 2,000 mg/dose (Ref).
Children weighing >45 kg and Adolescents: IM, IV: 1,000 mg every 24 hours for 7 days (Ref).
Gonococcal conjunctivitis: Adolescents: IM: 1,000 mg in a single dose. If chlamydial infection has not been excluded, give as part of an appropriate combination regimen (Ref).
Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 50 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 2,000 mg/day (Ref).
Lyme disease (Borrelia spp. infection): Limited data available: Infants, Children, and Adolescents: IV: 50 to 75 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose. Duration of therapy depends on clinical syndrome; treat meningitis, radiculopathy, or carditis for 14 to 21 days, and recurrent or refractory arthritis for 14 to 28 days depending on clinical response (Ref).
Meningitis, bacterial: Note: Per the manufacturer's labeling, doses may be administered IM.
Community-acquired meningitis: Infants, Children, and Adolescents: IV: 80 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 4,000 mg/day (Ref).
Health care-associated meningitis/ventriculitis: Infants, Children, and Adolescents: IV: 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 4,000 mg/day (Ref).
Otitis media, acute:
Infants, Children, and Adolescents:
Initial treatment (alternative agent for patients who cannot tolerate oral therapy): IM, IV: 50 mg/kg/dose every 24 hours for 1 to 3 days; maximum dose: 1,000 mg/dose (Ref).
Failure of initial treatment or suspected/proven penicillin-resistant Streptococcus pneumoniae: IM, IV: 50 mg/kg/dose every 24 hours for 3 days; maximum dose: 1,000 mg/dose (Ref).
Peritonitis (peritoneal dialysis), prophylaxis for patients receiving peritoneal dialysis who require dental procedures: Infants, Children, and Adolescents: IM, IV: 50 mg/kg administered 30 to 60 minutes before dental procedure; maximum dose: 1,000 mg/dose (Ref).
Pneumonia, community-acquired (CAP): Infants >3 months, Children, and Adolescents: IV: 50 to 100 mg/kg/day divided every 12 to 24 hours; maximum daily dose: 2,000 mg/day (Ref); higher maximum daily doses of 4,000 mg/day are recommended for HIV-exposed/-infected patients (Ref). Note: Use as part of appropriate combination therapy if methicillin-resistant Staphylococcus aureus (MRSA) or atypical pathogens are of concern. Use doses on the higher end of the range for penicillin-resistant S. pneumoniae (Ref).
Rhinosinusitis, acute bacterial:
Ambulatory patients (alternative agent): Children and Adolescents: IM, IV: 50 mg/kg as a single dose; maximum dose: 1,000 mg/dose; use for patients who are unable to tolerate oral medication, or unlikely to be adherent to the initial doses of antibiotic (Ref).
Severe infection requiring hospitalization: Infants, Children, and Adolescents: IV: 25 mg/kg/dose every 12 hours for 10 to 14 days; maximum dose: 2,000 mg/dose (Ref).
Salmonella species infection, treatment:
Nontyphoidal Salmonella infection (alternative agent): Note: Antibiotic treatment is typically not needed for uncomplicated nontyphoidal Salmonella infection; consider treating infants <3 months of age and persons with immunosuppression, chronic GI tract disease, and significant cardiac or joint disease (Ref).
Non-HIV-infected: Infants, Children, and Adolescents: IM, IV: 75 to 100 mg/kg/day divided every 12 to 24 hours; treat GI infections for 5 to 14 days (Ref); maximum dose: 2,000 mg/dose.
HIV-infected: Adolescents: IV: 1,000 mg every 24 hours for ≥7 to 14 days; bacteremia should be treated for ≥14 days (longer if bacteremia persists or infection is complicated); treat patients with CD4 counts <200 cells/mm3 for 2 to 6 weeks (Ref).
Typhoid fever (Salmonella typhi): Note: Reserve for patients who have failed oral therapy or who have severe disease, intestinal complications, or obtundation and cannot take oral medications (Ref).
Infants, Children, and Adolescents: IV: 75 to 80 mg/kg/dose every 24 hours for 5 to 14 days (Ref); maximum dose: 2,000 mg/dose (Ref).
Sexually transmitted infections, prophylaxis following sexual assault: Adolescents: IM: 500 mg as a single dose; 1,000 mg is recommended in patients weighing ≥150 kg. Use as part of an appropriate combination regimen (Ref).
Shigellosis: Infants, Children, and Adolescents: IM, IV: 50 to 100 mg/kg/dose every 24 hours for 2 to 5 days; maximum dose: 2,000 mg/dose (Ref). Note: Mild infections typically do not require antibiotic treatment; antibiotics are recommended for patients with severe disease or immunosuppression (Ref).
Skin and soft tissue infection: Infants, Children, and Adolescents: IM, IV: 50 to 75 mg/kg/day in divided doses every 12 to 24 hours; maximum daily dose: 2,000 mg/day.
Surgical prophylaxis: Children and Adolescents: IV: 50 to 75 mg/kg within 60 minutes prior to the procedure; maximum dose: 2,000 mg/dose (Ref).
Syphilis (alternative agent): Note: Not considered first-line therapy; use should be reserved for special circumstances with close monitoring and follow-up.
Congenital syphilis (Ref): Note: Only for use when aqueous and procaine penicillin are unavailable (eg, shortage) due to insufficient data for use; if used, close monitoring and follow-up in consultation with an expert are required (Ref).
Infants: IM, IV: 75 mg/kg/dose every 24 hours for 10 to 14 days; maximum dose: 2,000 mg/dose.
Children: IM, IV: 100 mg/kg/dose every 24 hours for 10 to 14 days; maximum dose: 2,000 mg/dose.
Acquired syphilis (nonpregnant patients with penicillin allergy):
Early syphilis (primary, secondary, and early-latent): Adolescents: IM, IV: 1,000 mg every 24 hours for 10 to 14 days; optimal dose and duration have not been defined (Ref). Note: If adherence or follow-up cannot be ensured, patients with penicillin allergy should be desensitized to penicillin (Ref).
Neurosyphilis: Adolescents: IM, IV: 1,000 to 2,000 mg every 24 hours for 10 to 14 days; patients infected with HIV should receive 2,000 mg once daily. Note: Patients with penicillin allergy should be desensitized to penicillin whenever possible (Ref).
Urinary tract infection: Infants, Children, and Adolescents: IM, IV: 50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose. Treatment duration dependent on age of patient, response to therapy, and extent of involvement (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment is generally necessary in renal impairment; Note: If concurrent renal and hepatic dysfunction, a reduced maximum daily dose should be considered; in adults a maximum daily dose ≤2,000 mg/day is suggested.
Not dialyzable; no supplemental dose is necessary following hemodialysis or peritoneal dialysis; patients with concomitant hepatic dysfunction must be monitored closely for safety and efficacy.
No adjustment is generally necessary in hepatic impairment; Note: If concurrent renal and hepatic dysfunction, a reduced maximum daily dose should be considered; in adults a maximum daily dose ≤2,000 mg/day is suggested.
(For additional information see "Ceftriaxone: Drug information")
Actinomycosis, severe or extensive (alternative agent) (off-label use):
IV: 1 to 2 g once daily for 4 to 6 weeks, followed by appropriate long-term oral therapy (Ref).
Bite wound infection, treatment (animal or human bite) (off-label use):
IV: 2 g once daily or 1 g every 12 hours in combination with an agent appropriate for anaerobes. Duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days (Ref).
Bloodstream infection: For pathogen-directed therapy of susceptible organisms in the absence of CNS infection:
IV: 2 g once daily (Ref). For patients with pneumococcal bacteremia, administer 2 g every 12 hours in combination with vancomycin until meningitis is ruled out (Ref). May also be given as empiric therapy for gram-negative bloodstream infection in hemodynamically stable, immunocompetent patients without health care exposures (Ref).
Duration of therapy: Usual duration is 7 to 14 days; individualize depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Ref).
Chronic obstructive pulmonary disease, acute exacerbation (hospitalized patients without risk factors for Pseudomonas aeruginosa) (off-label use):
IV: 1 g once daily for 5 to 7 days; may switch to oral therapy following clinical improvement (Ref).
Diabetic foot infection, moderate to severe (off-label use):
IV: 1 to 2 g once daily in combination with other appropriate agents. Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (Ref). Note: Do not use for empiric therapy of patients at risk for Pseudomonas (eg, significant water exposure, macerated wound) (Ref).
Endocarditis, prophylaxis (dental or invasive respiratory tract procedures) (alternative agent for patients with nonsevere, non-IgE-mediated allergy to penicillin who cannot take oral therapy) (off-label use):
IM, IV: 1 g 30 to 60 minutes before procedure; if inadvertently not given prior to the procedure, may be administered up to 2 hours after the procedure. Note: Reserve for select situations (cardiac condition with the highest risk of adverse endocarditis outcomes and procedure likely to result in bacteremia with an organism that can cause endocarditis) (Ref).
Endocarditis, treatment (off-label use):
Enterococcus faecalis, native or prosthetic valve (penicillin-susceptible): Note: Recommended regimen in patients with or at risk of renal insufficiency (eg, older age, concomitant nephrotoxins) or with aminoglycoside resistance (Ref); some experts prefer this regimen for all patients with susceptible enterococcal native valve endocarditis (Ref).
IV: 2 g every 12 hours for 6 weeks in combination with ampicillin (Ref).
HACEK organisms, native or prosthetic valve: IV, IM: 2 g once daily for 4 weeks (native valve) or 6 weeks (prosthetic valve) (Ref).
Viridans group streptococci (VGS) and Streptococcus gallolyticus (Streptococcus bovis): IV, IM:
Native valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g once daily alone for 4 weeks or in combination with gentamicin for 2 weeks for patients with uncomplicated infection, rapid response to therapy, and no underlying renal disease (Ref).
Native valve: Relatively penicillin-resistant (MIC >0.12 to <0.5 mcg/mL), ceftriaxone-susceptible (alternative agent): 2 g once daily for 4 weeks (Ref).
Native valve: Penicillin-resistant (MIC ≥0.5 mcg/mL), ceftriaxone-susceptible (alternative agent): 2 g once daily in combination with gentamicin. The duration of this regimen is not well established; infectious diseases consultation recommended (Ref).
Prosthetic valve: Highly penicillin-susceptible (MIC ≤0.12 mcg/mL): 2 g once daily for 6 weeks (with or without concomitant gentamicin for the first 2 weeks) (Ref).
Prosthetic valve: Relatively or fully penicillin-resistant (MIC >0.12 mcg/mL), ceftriaxone-susceptible: 2 g once daily in combination with gentamicin for 6 weeks (Ref).
Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure:
Cholecystitis, acute:
IV: 1 to 2 g once daily; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Ref). Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (Ref).
Other intra-abdominal infections (eg, appendicitis, diverticulitis, intra-abdominal abscess):
IV: 1 to 2 g once daily in combination with metronidazole. Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref).
Intracranial abscess (brain abscess or intracranial epidural abscess) or spinal epidural abscess (off-label use):
IV: 2 g every 12 hours; for empiric therapy, use in combination with other appropriate agents. Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Ref). Note: For postoperative neurosurgical patients and those at risk for P. aeruginosa, other regimens with expanded gram-negative coverage are preferred (Ref).
Lyme disease (Borrelia spp. infection) (off-label use):
Carditis, severe disease (patients who are symptomatic, have second or third-degree AV block, or have first degree AV block with PR interval ≥300 msec):
IV: 2 g once daily until high-grade AV block resolved and PR interval <300 msec; may switch to oral therapy to complete a total of 14 to 21 days (Ref).
Acute neurologic disease (eg, meningitis or radiculopathy), patients requiring hospitalization:
IV: 2 g once daily for 14 to 21 days (Ref).
Late disease, neurologic disease:
IV: 2 g once daily for 14 to 28 days (Ref); some experts favor a duration of 28 days (Ref).
Recurrent arthritis after adequate oral regimen:
IV: 2 g once daily for 14 days; may extend to 28 days if inflammation is not resolving (Ref).
Meningitis, bacterial: As a component of empiric therapy (community-acquired infections in immunocompetent patients) or pathogen-specific therapy (eg, Streptococcus pneumoniae [ceftriaxone MIC <1 mcg/mL], Neisseria meningitidis, Haemophilus influenzae, Cutibacterium acnes, and susceptible gram-negative bacilli; alternative agent for certain pathogens):
IV: 2 g every 12 hours; for empiric therapy, use in combination with other appropriate agents. Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (Ref).
Meningococcal disease, chemoprophylaxis after close contact with high-risk patient (off-label use):
IM: 250 mg as a single dose. Note: Prophylaxis should be initiated as soon as possible following exposure (ideally <24 hours after identification of index patient) (Ref). Close contacts include persons with prolonged exposure (≥8 hours) in close proximity (<3 feet) to index patient or direct exposure to oral secretions (eg, household contacts, childcare center contacts) (Ref).
Neurobrucellosis (off-label use): IV: 2 g every 12 hours for 4 to 6 weeks as part of an appropriate combination regimen (Ref).
Odontogenic soft tissue infection, pyogenic (alternative agent) (off-label use):
Note: For patients unable to take penicillin (Ref).
IV: 2 g once daily in combination with metronidazole; following clinical improvement, transition to oral step-down therapy and continue antibiotics until resolution, typically for a total of 7 to 14 days. Use in addition to appropriate surgical management (eg, drainage and/or extraction) (Ref).
Osteomyelitis and/or discitis:
Treatment: As a component of empiric therapy or pathogen-specific therapy (eg, Streptococci [beta-hemolytic], C. acnes, susceptible gram-negative bacilli):
IV: 2 g every 24 hours, generally for ≥6 weeks depending on patient-specific factors such as organism, extent of infection, debridement, and clinical response. Shorter courses are appropriate if the affected bone is completely resected (eg, by amputation). For empiric therapy, use as part of an appropriate combination regimen (Ref).
Prevention, following open fractures (type III [severe contamination or comminution]): IV: 2 g every 24 hours as part of an appropriate combination regimen; ideally, administer within 6 hours of injury. Duration is 72 hours after injury or up to 24 hours after wound closure (Ref). Note: For patients with risk for methicillin-resistant S. aureus (MRSA), potential water exposure, or fecal or clostridial contamination, alternative or additional antibiotics are recommended (Ref).
Otitis media, acute (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy):
IM, IV: 1 to 2 g once daily for 3 days (Ref).
Peritonitis, treatment (peritoneal dialysis) (off-label route):
Note: Intraperitoneal administration is preferred to IV administration unless the patient has sepsis (Ref).
Intermittent: Intraperitoneal: 1 g added to the dialysate solution once daily; allow to dwell ≥6 hours (Ref). For patients with adequate clinical response, duration of therapy is ≥2 to 3 weeks depending on organism (Ref). For patients with no improvement after 5 days, remove catheter and treat with appropriate systemic antibiotics for 14 days after catheter removal (Ref).
Pneumonia, community-acquired: Inpatients without risk factors for P. aeruginosa:
IV: 1 to 2 g once daily in combination with other appropriate agent(s) (Ref); 1 g once daily is sufficient for most hemodynamically stable hospitalized patients with community-acquired pneumonia (Ref); for critically ill patients, some experts favor the 2 g dose (Ref). Total duration (which may include oral step-down therapy) is for a minimum of 5 days; patients should be clinically stable with normal vital signs prior to discontinuation (Ref).
Prosthetic joint infection: As a component of empiric therapy or pathogen-specific therapy (eg, Streptococci [beta-hemolytic], C. acnes, susceptible gram-negative bacilli):
IV: 2 g every 24 hours for 4 to 6 weeks; for empiric therapy, use as part of an appropriate combination regimen (Ref).
Rat bite fever (off-label use):
Uncomplicated infection: IV: 1 g once daily; if patient clinically improves, may switch to an oral antibiotic after 5 to 7 days to complete a 14-day course (Ref).
Serious invasive infection (including bacteremia, meningitis, endocarditis, and other focal organ involvement): IV: 2 g once daily; for patients with meningitis, increase dose to 2 g twice daily. Duration depends on the site of infection and extent of disease (eg, 4 weeks for endocarditis) (Ref).
Salmonella species infection (alternative agent) (off-label use):
Enteric fever (Salmonella typhi and paratyphi): Empiric therapy for severe disease or an alternative directed therapy for quinolone-nonsusceptible infection:
IV: 2 g every 12 to 24 hours for 10 to 14 days. Note: May be switched to an oral regimen based on susceptibility testing, if available. Geographic location at time of acquisition impacts risk of resistance; ceftriaxone is not recommended if there is concern for extensively drug-resistant Salmonella spp. (Ref).
Nontyphoidal Salmonella GI infection:
IV: 1 to 2 g every 24 hours for 3 to 14 days (7 to 14 days in patients with HIV with a CD4 count ≥200 cells/mm3 or 2 to 6 weeks in patients with a CD4 count <200 cells/mm3). Note: Reserve antibiotic treatment for patients with severe illness or at high risk of invasive disease (eg, extremes of age, immunosuppression); reserve parenteral therapy for those who cannot tolerate oral agents (Ref).
Nontyphoidal Salmonella bloodstream infection:
IV: 1 to 2 g every 24 hours for 10 to 14 days for patients who are immunocompetent; 14 days for patients with HIV and a CD4 count ≥200 cells/mm3. Patients who are immunosuppressed (eg, patients with HIV with a CD4 count <200 cells/mm3) and those with an extraintestinal focus of infection require a longer duration of treatment (eg, weeks to months) (Ref).
Septic arthritis (as a component of empiric therapy for traumatic bacterial arthritis without risk factors for P. aeruginosa; pathogen-directed therapy for gram-negative bacilli):
IV: 2 g once daily. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy. For empiric therapy, give as part of an appropriate combination regimen (Ref).
Sexually transmitted infections:
Chancroid (due to Haemophilus ducreyi) (off-label use):
IM: 250 mg as a single dose. Note: Efficacy data in patients with HIV are limited (Ref).
Empiric treatment following sexual assault (off-label use):
IM: 500 mg (1 g in patients ≥150 kg) as a single dose, as part of an appropriate combination regimen (Ref).
Epididymitis (off-label use):
Inpatients: IV: 1 g once daily; use in combination with doxycycline for patients at risk for sexually transmitted infection. May switch to an appropriate oral regimen after patient is afebrile for 24 hours; total duration (including oral step-down therapy) is 10 to 14 days (Ref).
Outpatients: IM: 500 mg (1 g in patients ≥150 kg) as a single dose in combination with doxycycline, or for patients who practice insertive anal sex, levofloxacin (Ref).
Gonococcal infection:
Uncomplicated gonorrhea (infection of the cervix, pharynx, rectum, urethra): Note: Coverage for gonococcal infection should be included in empiric regimens for cervicitis or urethritis in patients at high risk for gonorrhea or if the community prevalence of gonorrhea is high (eg, >5%) (Ref), and in empiric regimens for proctitis in individuals who practice anal receptive sex (Ref).
IM: 500 mg as a single dose; 1 g is recommended for patients weighing ≥150 kg. Give in combination with treatment for chlamydia if it has not been excluded. A test-of-cure (culture or nucleic acid amplification test) is recommended 7 to 14 days after initial treatment of pharyngeal gonorrhea. When treatment failure is suspected (eg, detection of N. gonorrhoeae after treatment without additional sexual exposure), consult an infectious diseases specialist. Report failures to the CDC through state and local health departments (Ref).
Uncomplicated gonorrhea (conjunctivitis) (off-label use):
IM: 1 g as a single dose. Give in combination with treatment for chlamydia if it has not been excluded (Ref).
Disseminated gonococcal infection (tenosynovitis, dermatitis, polyarthralgia; purulent arthritis) (off-label use):
IV (preferred), IM: 1 g once daily. For patients with triad of tenosynovitis, dermatitis, and arthralgia or synovitis, may switch to IM ceftriaxone 500 mg (1 g in patients ≥150 kg) once daily 24 to 48 hours after clinical improvement to complete a total of ≥7 days of therapy. Patients with purulent arthritis often require ≥7 to 14 days of parenteral therapy; duration depends on clinical status and response to therapy. Note: Give in combination with treatment for chlamydia if it has not been excluded (Ref).
Pelvic inflammatory disease:
Mild to moderate: IM: 500 mg (1 g in patients ≥150 kg) as a single dose in combination with doxycycline and metronidazole (Ref).
Severe (including tubo-ovarian abscess): IV: 1 g once daily in combination with doxycycline and metronidazole; after 24 to 48 hours of sustained clinical improvement, transition to oral therapy to complete 14 days of treatment (Ref).
Syphilis (alternative agent for nonpregnant patients with nonsevere, non-IgE-mediated penicillin allergy) (off-label use):
Note: Optimal dose/duration not established; use in consultation with an expert in syphilis management (Ref). Some experts prefer the IV formulation (Ref).
Early syphilis (primary, secondary, and early latent [<1-year duration]): IM, IV: 1 g once daily for 10 to 14 days (Ref).
Late syphilis (late latent [>1-year duration] or tertiary syphilis with normal CSF examination): IM, IV: 1 to 2 g once daily for 10 to 14 days (Ref).
Neurosyphilis (including ocular and otosyphilis): Note: Penicillin is preferred; reserve ceftriaxone for when penicillin desensitization or challenge is not feasible (Ref).
IM, IV: 1 to 2 g once daily for 10 to 14 days (Ref); some experts prefer the 2 g once daily dose (Ref).
Skin and soft tissue infection (eg, select surgical site or necrotizing infections):
IV: 1 to 2 g once daily, usually as part of an appropriate combination regimen. Duration varies by extent of infection, clinical response, and other patient factors; for necrotizing infection, continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (Ref).
Spontaneous bacterial peritonitis (off-label use):
Primary prophylaxis: Note: For patients with advanced cirrhosis and active GI bleeding (Ref).
IV: 1 g once daily; may transition to oral antibiotic prophylaxis when bleeding is controlled and oral intake is resumed. Total duration (including oral agents) is 7 days (Ref).
Treatment (alternative agent): Note: For patients without sepsis or risk for multidrug resistance (Ref).
IV: 2 g once daily; duration is for 5 to 7 days, as long as fever and pain have resolved (Ref).
Surgical prophylaxis, colorectal (alternative agent):
IV: 2 g within 60 minutes prior to surgical incision in combination with metronidazole. Note: Reserved for locations where gram-negative resistance to first- and second-generation cephalosporins is high (Ref). Postoperative prophylaxis is not recommended in clean and clean-contaminated surgeries (Ref).
Toxic shock syndrome, streptococcal (alternative agent for patients with nonsevere, non-IgE-mediated penicillin allergy) (off-label use):
IV: 1 to 2 g every 12 hours in combination with clindamycin. Duration of therapy depends on extent and severity of infection and response to treatment; treat patients who are bacteremic for ≥14 days (Ref).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms):
Note: Use empirically only in patients who do not have risk factors for multidrug-resistant organisms, critical illness, or suspected urinary tract obstruction (Ref).
Inpatients: IV: 1 g once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Ref).
Outpatients: IV, IM: 1 g once, followed by 5 to 14 days of appropriate oral therapy (Ref). Note: For patients who are systemically ill or at risk for more severe illness, some experts continue daily parenteral therapy pending culture and susceptibility testing results (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney impairment: IM, IV:
CrCl >15 mL/minute: No dosage adjustment necessary.
CrCl <15 mL/minute: No dosage adjustment necessary (Ref). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Ref).
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): IV: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine levels. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematological malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref). Note: Dosing based on Monte Carlo simulation.
CrCl ≥150 mL/minute (empiric therapy or organism with minimum inhibitory concentration [MIC] = 2): 2 g twice daily (Ref).
Hemodialysis, intermittent (thrice weekly): IM, IV: Poorly dialyzed; no dosage adjustment necessary (Ref). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Ref). Alternatively, 2 g thrice weekly post dialysis achieves pharmacodynamic goals when the MIC ≤1 mcg/mL (Ref).
Peritoneal dialysis: IM, IV: Poorly dialyzed; no dosage adjustment necessary (Ref). Use of >2 g/day has not been studied and should be done with close monitoring, especially in patients with concurrent hepatic dysfunction (decreased biliary excretion) (Ref).
CRRT: IM, IV: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency hemodiafiltration): IM, IV: No dosage adjustment necessary (Ref).
The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Child-Turcotte-Pugh class A through C: No dosage adjustment necessary (Ref).
Ceftriaxone-calcium precipitation has occurred, leading to fatal lung and kidney damage in premature and term neonates. Urinary sludge (hypercalciuria), nephrolithiasis, urolithiasis, and acute renal failure have been reported (Ref). Gallbladder sludge, cholelithiasis, and pseudolithiasis, as well as subsequent pancreatitis, have also occurred. Most reports have occurred in pediatric patients; however, there are reports in adults (Ref).
Mechanism : Incompatibility with calcium, resulting in ceftriaxone-calcium precipitates; pancreatitis occurs subsequent to biliary obstruction.
Onset: Varied; 2 to 18 days after last dose for detection via ultrasound of gallbladder sludge, cholelithiasis, or pseudolithiasis in pediatric patients (Ref).
Risk factors:
• Pediatric patients (Ref); age ≥12 to 24 months (for biliary precipitation) (Ref)
• High doses (>40 mg/kg/day or ≥2 g) (Ref)
• Longer durations of treatment (>5 days) (Ref)
• Impaired gallbladder emptying (Ref)
• Biliary stasis risk factors (eg, major surgery, severe illness, TPN)
Clostridioides difficile infection has occurred, including Clostridioides difficile-associated diarrhea and Clostridioides difficile colitis.
Onset: Variable; may start on the first day of antibiotic therapy or up to 3 months post antibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor) (Ref)
• Type of antibiotic (third-/fourth-generation cephalosporins among the highest risk) (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older adults (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)
• Chemotherapy (Ref)
Immune hemolytic anemia has occurred in patients receiving cephalosporins, including ceftriaxone (Ref).
Mechanism: Non–dose-related; immunologic (ie, induces complement activating drug-dependent antibodies [mainly IgM-type] resulting in immune complexes) (Ref).
Onset: Varied; occurs several minutes to 7 days after the first dose (Ref).
Risk factors:
• Pediatric patients (Ref)
• Sickle cell disease (Ref)
• Cross-reactivity with other cephalosporins (Ref)
Hypersensitivity reactions (immediate and delayed) range from maculopapular skin rash to rare cases of anaphylaxis and anaphylactic shock. Severe cutaneous adverse reactions (SCARs), including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) have been reported (Ref). Urticaria and serum sickness-like reaction have also occurred (Ref).
Mechanism: Non–dose-related; immunologic. Immediate hypersensitivity reactions (eg, anaphylaxis, urticaria) are IgE mediated. Delayed hypersensitivity reactions, including maculopapular rash and SCARs, are T-cell mediated (Ref).
Onset: Immediate hypersensitivity reactions: rapid; occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Delayed hypersensitivity reactions: Maculopapular reactions: intermediate; occur 7 to 10 days after initiation. Other reactions (including SCARs): varied; occur after 7 to 14 days up to 3 months (Ref).
Risk factors:
• Cross-reactivity between penicillins and cephalosporins and among cephalosporins is mostly related to side chain similarity (Ref). A meta-analysis showed negligible cross-reactivity between penicillins and third-generation cephalosporins, such as ceftriaxone (Ref).
Kernicterus has been reported in neonates, resulting from hyperbilirubinemia (increased serum bilirubin).
Mechanism: Displaces bilirubin from albumin, resulting in higher concentrations of free unconjugated bilirubin, leading to kernicterus (Ref).
Risk factors:
• Neonates, especially premature infants
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Skin tightness (IM; local)
Local: Induration at injection site (incidence higher with IM), warm sensation at injection site (IM)
1% to 10%:
Dermatologic: Skin rash (2%)
Gastrointestinal: Diarrhea (3%)
Hematologic & oncologic: Eosinophilia (6%), leukopenia (2%), thrombocytosis (5%)
Hepatic: Increased serum alanine aminotransferase (3%), increased serum aspartate aminotransferase (3%)
Local: Pain at injection site (≤1%), tenderness at injection site (≤1%)
Renal: Increased blood urea nitrogen (1%)
<1%:
Cardiovascular: Flushing, palpitations, phlebitis
Dermatologic: Diaphoresis, pruritus
Gastrointestinal: Abdominal pain, cholelithiasis, Clostridioides difficile colitis, dysgeusia, dyspepsia, flatulence, gallbladder sludge, nausea, vomiting
Genitourinary: Glycosuria, hematuria, vaginitis
Hematologic & oncologic: Agranulocytosis, anemia, basophilia, decreased prothrombin time, granulocytopenia, hemolytic anemia, lymphocytopenia, lymphocytosis, monocytosis, neutropenia, prolonged prothrombin time, thrombocytopenia
Hepatic: Increased serum alkaline phosphatase, increased serum bilirubin, jaundice
Hypersensitivity: Anaphylaxis, serum sickness
Infection: Candidiasis
Local: Injection-site phlebitis
Nervous system: Chills, dizziness, headache, seizure
Renal: Casts in urine, increased serum creatinine, nephrolithiasis
Respiratory: Bronchospasm, epistaxis, hypersensitivity pneumonitis
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Salman 2019), allergic dermatitis, erythema multiforme, Stevens-Johnson syndrome (Liberopoulos 2003), toxic epidermal necrolysis (Atanaskovic-Markovic 2013; Lam 2008), urticaria (Baniasadi 2007)
Gastrointestinal: Clostridioides difficile-associated diarrhea, glossitis, pancreatitis, stomatitis
Genitourinary: Hypercalciuria (Zeng 2020), oliguria (Shen 2014), ureteral obstruction (Lu 2012), urolithiasis (Shen 2014)
Hepatic: Hepatitis (Peker 2009)
Hypersensitivity: Anaphylactic shock (Calapai 2016)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Hansel 2017)
Nervous system: Encephalopathy (Roncon-Albuquerque 2009), kernicterus, neurotoxicity (including myoclonus [Hagiya 2017] and nonconvulsive status epilepticus [Kim 2012])
Renal: Acute kidney injury (post renal) (Li 2014; Shen 2014)
Hypersensitivity to ceftriaxone, any component of the formulation, or other cephalosporins; do not use in hyperbilirubinemic neonates, particularly those who are premature since ceftriaxone is reported to displace bilirubin from albumin binding sites; concomitant use with intravenous calcium-containing solutions/products in neonates (≤28 days); IV use of ceftriaxone solutions containing lidocaine.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Elevated INR: May be associated with increased INR (rarely), especially in nutritionally deficient patients, prolonged treatment, hepatic or renal disease. Monitor INR during treatment if patient has impaired synthesis or low stores of vitamin K; supplementation may be needed if clinically indicated.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Renal/hepatic impairment (concurrent): Use with caution in patients with concurrent hepatic dysfunction (impaired biliary excretion) and severe kidney disease; dosing adjustments may be recommended.
Special populations:
• Neonates: Use extreme caution in neonates due to risk of hyperbilirubinemia, particularly in premature infants (contraindicated in hyperbilirubinemic neonates and neonates <41 weeks postmenstrual age).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Generic: 20 mg/mL (50 mL); 40 mg/mL (50 mL)
Solution Reconstituted, Injection [preservative free]:
Generic: 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea); 100 g (1 ea)
Solution Reconstituted, Intravenous [preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea); 10 g (1 ea)
Yes
Solution (cefTRIAXone Sodium in Dextrose Intravenous)
20 mg/mL (per mL): $0.34
40 mg/mL (per mL): $0.81
Solution (reconstituted) (cefTRIAXone Sodium Injection)
1 g (per each): $1.22 - $46.75
2 g (per each): $2.30 - $91.72
100 g (per each): $270.00
250 mg (per each): $0.91 - $15.94
500 mg (per each): $1.16 - $27.99
Solution (reconstituted) (cefTRIAXone Sodium Intravenous)
1 g (per each): $4.97 - $46.75
2 g (per each): $9.56 - $91.72
10 g (per each): $20.78 - $448.43
Solution (reconstituted) (cefTRIAXone Sodium-Dextrose Intravenous)
1GM 3.74%(50ML) (per each): $23.62
2GM 2.22%(50ML) (per each): $31.49
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 20 mg/mL (50 mL); 40 mg/mL (50 mL)
Solution Reconstituted, Injection:
Generic: 250 mg (1 ea); 500 mg (1 ea); 1 g (1 ea); 2 g (1 ea); 100 g (1 ea)
Solution Reconstituted, Intravenous:
Generic: 10 g (1 ea)
Rocephin contains 3.6 mEq sodium per gram of ceftriaxone.
Parenteral: Do not coadminister with calcium-containing solutions.
IM: Administer IM injections deep into a large muscle mass.
Intermittent IV infusion:
Neonates: Administer over 60 minutes to decrease risk of bilirubin encephalopathy.
Infants, Children, and Adolescents: Administer over 30 minutes; shorter infusion times (15 minutes) have been reported (Ref).
Due to reports of precipitation reaction in neonates, do not reconstitute, admix, or coadminister with calcium-containing solutions (eg, LR, Hartmann's solution, parenteral nutrition), even via separate infusion lines/sites or at different times in any neonate. Ceftriaxone should not be diluted or administered simultaneously with any calcium-containing solution via a Y-site in any patient. However, ceftriaxone and calcium-containing solutions may be administered sequentially of one another for use in patients other than neonates if infusion lines are thoroughly flushed (with a compatible fluid) between infusions.
IV Push: Administration over 2 to 4 minutes has been reported in pediatric patients >11 years and adults primarily in the outpatient setting (Ref) and over 5 minutes in pediatric patients ages newborn to 15 years with meningitis (Ref). Rapid IVP injection over 5 minutes of a 2,000 mg dose resulted in tachycardia, restlessness, diaphoresis, and palpitations in an adult patient (Ref). IV push administration in young infants may also have been a contributing factor in risk of cardiopulmonary events occurring from interactions between ceftriaxone and calcium (Ref).
IM: Inject deep IM into large muscle mass; a concentration of 250 mg/mL or 350 mg/mL is recommended for all vial sizes except the 250 mg size (250 mg/mL is suggested); can be diluted with 1:1 water or 1% lidocaine for IM administration only.
IV: Infuse as an intermittent infusion over 30 minutes. IV push administration over 1 to 4 minutes has been reported (concentration: 100 mg/mL), primarily in patients outside the hospital setting (Ref), although a 2 g dose administered IV push over 5 minutes resulted in tachycardia, restlessness, diaphoresis, and palpitations in one patient (Ref). Do not coadminister with calcium-containing solutions.
Intraperitoneal (off-label route): May administer intermittently (1 exchange daily); allow to dwell ≥6 hours (Ref).
Powder for injection: Prior to reconstitution, store at 20°C to 25°C (68°F to 77°F). Protect from light.
Premixed solution (manufacturer premixed):
Duplex container: Store the unactivated container at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze.
Galaxy container: Store at −20°C (−4°F); once thawed, solutions are stable for 48 hours at 25°C (77°F) or for 21 days at 5°C (41°F). Do not refreeze.
Frozen premixed solutions: Store at −20°C or below. Once thawed, solutions are stable for 48 hours at 25°C (77°F) or for 21 days at 5°C (41°F). Do not refreeze.
Stability of reconstituted solutions:
10 to 40 mg/mL: Reconstituted in D5W, D10W, NS, or SWFI: Stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F). Stable for 26 weeks when frozen at −20°C when reconstituted with D5W or NS. Once thawed (at room temperature), solutions are stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F); does not apply to manufacturer's premixed bags. Do not refreeze. If D5NS or D51/2NS are used, solutions are only stable for 2 days at of 25°C (77°F).
100 mg/mL:
Reconstituted in D5W, SWFI, or NS: Stable for 2 days at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F).
Reconstituted in lidocaine 1% solution or bacteriostatic water: Stable for 24 hours at room temperature of 25°C (77°F) or for 10 days when refrigerated at 4°C (39°F).
250 to 350 mg/mL: Reconstituted in D5W, NS, lidocaine 1% solution, bacteriostatic water, or SWFI: Stable for 24 hours at room temperature of 25°C (77°F) or for 3 days when refrigerated at 4°C (39°F).
Treatment of sepsis, meningitis, infections of the lower respiratory tract, acute bacterial otitis media, skin and skin structure, bone and joint, intra-abdominal and urinary tract due to susceptible organisms (FDA approved in infants, children, adolescents, and adults); surgical prophylaxis (FDA approved in adults); documented or suspected uncomplicated gonococcal infection or pelvic inflammatory disease (FDA approved for adults); has also been used for the treatment of endocarditis, Lyme disease, acute bacterial rhinosinusitis, salmonellosis, shigellosis, syphilis, and typhoid fever and prophylaxis of peritonitis in patients undergoing invasive dental procedures.
CefTRIAXone may be confused with ceFAZolin, cefoTEtan, cefOXitin, cefTAZidime, Cetraxal
Rocephin may be confused with Roferon
Ceftriaxone is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) for use in asymptomatic bacteriuria (O’Mahony 2023).
KIDs List: Ceftriaxone, when used in neonates, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be used with caution due to risk of kernicterus (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Calcium Salts (Intravenous): May enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium forming an insoluble precipitate. Management: Use of ceftriaxone is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions. In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Furosemide: May enhance the nephrotoxic effect of Cephalosporins. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy
Ringer's Injection (Lactated): May enhance the adverse/toxic effect of CefTRIAXone. Ceftriaxone binds to calcium in the Lactated Ringer's forming an insoluble precipitate. Management: Use of ceftriaxone is contraindicated in neonates (28 days of age or younger) who require (or are expected to require) treatment with IV calcium-containing solutions (ie, LR). In older patients, flush lines with compatible fluid between administration. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain sodium.
Ceftriaxone crosses the placenta.
Based on available data, cephalosporin antibiotics are generally considered compatible for use during pregnancy.
Pregnancy was found to influence the single dose pharmacokinetics of ceftriaxone when administered prior to delivery (Popović 2007). The pharmacokinetics of ceftriaxone following multiple doses in the third trimester are similar to those of nonpregnant patients (Bourget 1993a).
Ceftriaxone is recommended for use in pregnant patients for the treatment of gonococcal infections, Lyme disease, and may be used in certain situations prior to vaginal delivery in patients at high risk for endocarditis (consult current guidelines) (ACOG 2018; CDC [Workowski 2021]; IDSA/AAN/ACR [Lantos 2021]; Lambert 2020). Ceftriaxone should not be used as an alternative agent in penicillin-allergic pregnant patients for the treatment of maternal syphilis or the prevention of congenital syphilis (CDC [Workowski 2021]).
CBC with differential, platelet count, PT, renal and hepatic function tests periodically; number and type of stools/day for diarrhea; observe for signs and symptoms of anaphylaxis.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Absorption: IM: Well absorbed.
Distribution: Widely throughout the body including gallbladder, lungs, bone, bile, CSF (higher concentrations achieved when meninges are inflamed).
Vd:
Neonates: 0.34 to 0.55 L/kg (Richards 1984).
Infants and Children: 0.32 to 0.4 L/kg (Richards 1984).
Adults: ~6 to 14 L.
CSF:blood ratio: ~14% (range: 6% to 66%) (Grégoire 2019).
Pleural fluid:serum ratio: ~27% to 29% (range: 1% to 63%) (Goonetilleke 1996).
Protein binding: 85% to 95%.
Half-life elimination:
Neonates: 1 to 4 days: 16 hours; 9 to 30 days: 9 hours (Martin 1984).
Infants and Children: 4 to 6.6 hours (Richards 1984).
Adults: Normal renal and hepatic function: ~5 to 9 hours.
Adults: Renal impairment (mild to severe): ~12 to 16 hours.
Time to peak, serum: IM: 2 to 3 hours.
Excretion: Urine (33% to 67% as unchanged drug); feces (as inactive drug).
Anti-infective considerations:
Parameters associated with efficacy:
Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC):
Organism specific:
Enterobacterales: Goal: ≥ ~38% fT > MIC (bacteriostatic); ≥ ~60% to 70% fT > MIC (bactericidal) (Craig 1995; Turnidge 1998).
S. pneumoniae: ≥ ~40% fT > MIC (bacteriostatic) (Craig 1995; Craig 1998; Turnidge 1998).
Population specific:
Critically ill patients in the ICU: Minimum goal: ≥50% fT > MIC; preferred goal: ≥100% fT > MIC (Roberts 2014); some experts favor ≥100% fT >4 times the MIC (Guilhaumou 2019).
Expected drug exposure in normal renal function:
Neonates and Infants: Cmax (peak): IV: 50 mg/kg, single dose: ~136 to 184 mg/L (Chadwick 1983; McCracken 1983).
Infants and Children ≤3 years of age: Cmax (peak): IV:
50 mg/kg, single dose: 207 mg/L (range: 120 to 375 mg/L) (Del Rio 1982).
50 mg/kg every 12 hours, steady state: 263 mg/L (range: 150 to 410 mg/L) (Del Rio 1982).
Adults: Cmax (peak): IV:
1 g once daily, steady state: ~136.4 ± 21.2 mg/L (Chiu 2002).
1 g every 12 hours, steady state: 168 ± 25 mg/L (Pollock 1982).
2 g every 12 hours, steady state: 280 ± 39 mg/L (Pollock 1982).
Postantibiotic effect: Generally <1 hour; varies based on organism (Aldridge 2002; Buxbaum 1996; Craig 1993).
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