cefTRIAXone (Monograph)

Drug class: Third Generation Cephalosporins

Medically reviewed by Drugs.com on May 10, 2025. Written by ASHP.

Introduction

Antibacterial; β-lactam antibiotic; third generation cephalosporin.¹ ¹⁶ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁶⁵ ¹⁷¹

Uses for cefTRIAXone

Acute Otitis Media (AOM)

Treatment of AOM caused by Streptococcus pneumoniae, Haemophilus influenzae (including β-lactamase-producing strains), or Moraxella catarrhalis (including β-lactamase-producing strains).¹ ³¹⁰ ³¹¹ ³¹² ³¹³ ⁴²⁷ ⁴²⁸ ⁴²⁹ ⁴⁵⁸ ⁶¹⁴ ⁶⁸³ ⁷⁵⁰ ⁷⁵¹

When anti-infectives indicated, American Academy of Pediatrics (AAP) recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of choice for initial treatment of AOM; certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) are recommended as alternatives for initial treatment in penicillin-allergic patients.⁶⁸³ ⁷⁵⁰ ⁷⁵¹

Has been effective for initial or repeat treatment of AOM;⁶⁸³ good choice when patient has persistent vomiting or cannot otherwise tolerate an oral regimen.⁶⁸³

A single-dose regimen can be used, but manufacturer cautions that potentially lower cure rate should be balanced against the advantages of a single-dose regimen.¹ AAP states a 1- or 3-day regimen^{† [off-label]} can be used for initial treatment of AOM, but cautions that more than a single dose may be required to prevent recurrence.⁶⁸³

AAP recommends a 3-day regimen^{† [off-label]} for retreatment of AOM in patients who failed to respond to an initial anti-infective regimen.⁶⁸³

Bone and Joint Infections

Treatment of bone and joint infections (e.g., osteomyelitis, septic arthritis) caused by susceptible Staphylococcus aureus, S. pneumoniae, Enterobacter, Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis.¹ ³ ¹⁸ ³⁰ ³² ⁸⁷ ¹⁰⁴ ¹²¹ ¹²⁴ ¹²⁷ ¹³¹ ¹³² ¹⁵⁰ ²⁴⁶ ⁵⁹⁰ ⁵⁹¹

The Infectious Diseases Society of America (IDSA) recommends nafcillin (or oxacillin), cefazolin, or ceftriaxone as drugs of choice for treatment of native vertebral osteomyelitis or prosthetic joint infections caused by oxacillin-susceptible staphylococci.⁵⁹⁰ ⁵⁹¹ If caused by β-hemolytic streptococci, IDSA recommends penicillin G or ceftriaxone.⁵⁹⁰ ⁵⁹¹ If caused by Cutibacterium acnes^{† [off-label]} (formerly Propionibacterium acnes), IDSA recommends penicillin G or ceftriaxone.⁵⁹⁰ ⁵⁹¹

Ceftriaxone recommended as an alternative to ciprofloxacin for treatment of native vertebral osteomyelitis caused by susceptibleSalmonella^{† [off-label]}.⁵⁹⁰

Endocarditis

Treatment of endocarditis^{† [off-label]} caused by viridans group streptococci (e.g., S. milleri group, S. mutans, S. salivarius, S. sanguis) or nonenterococcal group D streptococci (e.g., S. gallolyticus [formerly S. bovis]) involving native valves or prosthetic valves or other prosthetic material.⁴¹⁵ ⁴¹⁷ ⁴⁵⁰ ⁴⁵² ⁴⁹¹

Treatment of endocarditis^† caused by S. pneumoniae, S. pyogenes (group A β-hemolytic streptococci; GAS), S. agalactiae (group B streptococci; GBS), or streptococci groups C, F, or G involving native valves or prosthetic valves or other prosthetic material.⁴⁵⁰ ⁴⁵²

Treatment of endocarditis^† caused by enterococci (e.g., Enterococcus faecalis, E. faecium) involving native valves or prosthetic valves or other prosthetic material.⁴⁵⁰ ⁴⁵²

Treatment of endocarditis^† caused by fastidious gram-negative bacilli of the HACEK group (i.e., Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella).⁴⁵⁰ ⁴⁵²

The American Heart Association (AHA) recommends that treatment of endocarditis be managed in consultation with an infectious disease expert, especially when endocarditis is caused by S. pneumoniae, β-hemolytic streptococci, staphylococci, or enterococci.⁴⁵⁰ ⁴⁵²

GI Infections

Treatment ofSalmonella gastroenteritis^†.¹⁹⁷ ²¹⁷ ⁴⁴⁰ ⁷⁵² Anti-infectives not generally used in otherwise healthy individuals with uncomplicated (noninvasive) gastroenteritis caused by nontyphoidal Salmonella (e.g., Salmonella serovars Enteritidis or Typhimurium); anti-infective treatment recommended in those with severe Salmonella gastroenteritis and those at increased risk for invasive disease.²¹⁷ ²⁹⁹ ⁴⁴⁰ When considered necessary, select anti-infective based on in vitro susceptibility.¹⁹⁷ ²¹⁷ ²⁹⁹ ⁴⁴⁰ ⁷⁵²

Treatment of shigellosis^† caused by susceptible Shigella sonnei or S. flexneri.¹⁹⁷ ⁴⁰¹ ⁴⁰² ⁷⁵³ Anti-infectives generally indicated in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression.⁴⁴⁰ ⁷⁵³ Empiric treatment regimen can be used initially, but in vitro susceptibility testing recommended since resistance is common.⁴⁴⁰ ⁷⁵³ Ceftriaxone is a drug of choice for shigellosis.²¹⁷ ⁴⁰³

Empiric treatment of infectious diarrhea^†.⁴⁴⁰ Alternative for empiric treatment of severe bacterial diarrhea in HIV-infected adults and adolescents pending results of diagnostic studies; ciprofloxacin is drug of choice.⁴⁴⁰

Intra-abdominal Infections

Treatment of intra-abdominal infections caused by susceptible E. coli, K. pneumoniae, Bacteroides fragilis, Clostridium, or Peptostreptococcus.¹ ³ ¹⁸ ³⁰ ³² ¹⁰⁴ ¹⁰⁵ ¹²⁹ ¹³² ¹⁴⁹

May be used alone for initial empiric treatment of mild to moderate community-acquired biliary tract infections (acute cholecystitis or cholangitis), but should be used in conjunction with metronidazole for initial empiric treatment of mild to moderate extrabiliary community-acquired intra-abdominal infections.⁷⁰⁸

Meningitis and Other CNS Infections

Treatment of meningitis caused by susceptible H. influenzae, Neisseria meningitidis, or S. pneumoniae.¹ ³ ¹⁸ ³⁰ ³² ⁸⁰ ⁸⁷ ¹⁰⁴ ¹³⁰ ¹³⁸ ¹³⁹ ¹⁴⁰ ¹⁴¹ ¹⁴² ¹⁴³ ¹⁴⁴ ¹⁸⁷ ¹⁹⁷ ²⁴³ ²⁴⁵ ²⁴⁶ ²⁴⁹ ²⁵⁰ ²⁵⁷ ²⁵⁸ ²⁵⁹ ²⁷⁰ ²⁷¹ ²⁷² ⁷⁵⁰ ⁷⁵¹ ⁷⁵⁴ ⁷⁵⁵ A drug of choice for meningitis caused by these bacteria.¹⁴¹ ¹⁶⁶ ¹⁹⁷ ³²⁴ ³³¹ ³³² ³³⁴ ³⁴⁶ ³⁴⁷ ³⁴⁹ ⁴¹⁸ ⁴¹⁹ ⁴⁷⁵ ⁷⁵⁰ ⁷⁵¹ ⁷⁵⁴ ⁷⁵⁵ Consider that S. pneumoniae with reduced susceptibility to cephalosporins have been reported with increasing frequency¹⁰⁹ ¹¹¹ ⁴⁷⁰ ⁴⁷¹ and susceptibility can no longer be assumed.²⁴³ ³²³ ³³⁰ ³²⁴ ⁴¹⁹ ⁷⁵⁰ ⁷⁵¹

Treatment of meningitis and other CNS infections caused by susceptible Enterobacteriaceae^† (e.g., E. coli, Klebsiella^†).¹ ¹⁸ ³⁰ ³² ¹⁰⁴ ¹³³ ¹⁵⁶

Used with or without other anti-infectives (e.g., ampicillin, gentamicin, vancomycin) for empiric treatment of meningitis^† pending results of CSF culture and in vitro susceptibility testing.²⁹² ³⁴³ ⁴¹⁸ ⁴¹⁹ ⁴⁶⁸ ⁴⁷¹ ⁴⁷⁵ ⁷⁵⁰ ⁷⁵¹ Do not use alone for empiric treatment of meningitis when Listeria monocytogenes, enterococci, staphylococci, or Pseudomonas aeruginosa may be involved.⁹ ⁸⁷ ¹³⁷ ¹⁹⁷ ²⁹² ⁴⁶⁸ ⁴⁷⁵ AAP recommends treatment with vancomycin in addition to ceftriaxone in children with bacterial meningitis presumed to be caused byS. pneumoniae.⁷⁵⁰ ⁷⁵¹ AAP recommends cefotaxime over ceftriaxone in neonates with bacterial meningitis known or suspected to be caused by S. pneumoniae; if cefotaxime is not available, may use ceftazidime or cefepime in addition to vancomycin.⁷⁵¹ Consider consultation with infectious diseases specialist for all pediatric patients with bacterial meningitis.⁷⁵¹

A drug of choice for treatment of healthcare-associated ventriculitis and meningitis caused by susceptible β-lactamase-producing H. influenzae, S. pneumoniae, or Enterobacteriaceae^†.⁴¹⁶ Alternative to penicillin G for treatment of healthcare-associated ventriculitis and meningitis caused by susceptibleC. acnes^† (formerly P. acnes).⁴¹⁶

Respiratory Tract Infections

Treatment of respiratory tract infections (including pneumonia) caused by susceptible S. aureus, S. pneumoniae, H. influenzae, H. parainfluenzae, E. aerogenes, E. coli, K. pneumoniae, P. mirabilis, or Serratia marcescens.¹ ³ ¹⁸ ³⁰ ³² ⁸⁷ ⁸⁸ ¹⁰⁴ ¹⁰⁵ ¹¹⁹ ¹²⁰ ¹²¹ ¹²⁴ ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³¹ ¹⁹⁷ ²⁴⁶ ³¹³ ⁴²³ ⁴⁹³ ⁵¹² ⁵¹³ ⁷²⁸

Treatment of community-acquired pneumonia (CAP).⁵¹² Recommended by American Thoracic Society (ATS) and IDSA in certain combination regimens used for empiric treatment of CAP in hospitalized patients.⁵¹² Select regimen for empiric treatment of CAP based on most likely pathogens, local susceptibility patterns, and individual patient characteristics.⁵¹²

Recommended by AAP for empiric treatment of CAP in hospitalized pediatric patients in regions with high levels of penicillin-resistant pneumococcus.⁷⁵⁰ Also recommended by AAP for treatment of hospitalized pediatric patients with CAP caused by pneumococci suspected or proven to be penicillin-nonsusceptible, in patients with serious infections including empyema, or in those not fully immunized with pneumococcal conjugate vaccines PCV13, PCV15, or PCV20.⁷⁵¹

Alternative for treatment of acute bacterial sinusitis^†.⁷²⁸ ⁷²⁹ Oral amoxicillin or fixed combination of amoxicillin and clavulanate usually recommended for empiric treatment.⁷²⁸ ⁷²⁹ In children who are vomiting, unable to tolerate, or unlikely to adhere to initial oral therapy, treatment can be initiated with ceftriaxone and then switched to an oral regimen if clinical improvement observed at 24 hours.⁷²⁸ ⁷²⁹ Also an alternative for severe sinusitis requiring hospitalization.⁷²⁸ ⁷²⁹

Septicemia

Treatment of septicemia caused by susceptible S. aureus, S. pneumoniae, E. coli, H. influenzae, or K. pneumoniae.¹ ³ ¹⁸ ³⁰ ³² ⁸⁷ ¹⁰⁴ ¹⁰⁵ ¹²⁰ ¹²¹ ¹²⁴ ¹²⁵ ¹³¹ ²⁴⁶

Skin and Skin Structure Infections

Treatment of skin and skin structure infections caused by susceptible S. aureus, S. epidermidis, S. pyogenes, viridans group streptococci, E. cloacae, E. coli, K. oxytoca, K. pneumoniae, P. mirabilis, Morganella morganii, S. marcescens, Acinetobacter calcoaceticus, B. fragilis, or Peptostreptococcus.¹ ³ ¹⁸ ³⁰ ³² ⁸⁷ ⁸⁹ ¹⁰⁴ ¹⁰⁵ ¹²⁰ ¹²¹ ¹²⁴ ¹²⁸ ¹²⁹ ¹³¹ ¹³²

Has been used for treatment of some skin and skin structure infections caused by Ps. aeruginosa.¹ ³ ¹⁸ ³⁰ ³² Consider that many strains of Ps. aeruginosa are only susceptible to high ceftriaxone concentrations in vitro and resistant strains have developed during therapy with the drug.¹²⁰ ¹²¹ ¹²⁴ ¹²⁷ ¹³² ¹⁵⁰ Do not use alone in any infection where Ps. aeruginosa may be present.¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹²⁴ ¹²⁵ ¹²⁸ ¹⁷⁰ ²⁵⁰

Used in multiple-drug anti-infective regimens for empiric treatment of necrotizing infections of the skin, fascia, and muscle^†.⁵⁴³ Broad-spectrum coverage important since necrotizing fasciitis (including Fornier gangrene) may be polymicrobial (e.g., mixed aerobic-anaerobic infections) or monomicrobial (e.g., S. pyogenes, S. aureus, Vibrio vulnificus, Aeromonas hydrophila, Peptostreptococcus).⁵⁴³

Empiric treatment of certain surgical site infections.⁵⁴³ Used in conjunction with metronidazole for infections following GI or GU surgery;⁵⁴³ used alone or in conjunction with vancomycin for infections following procedures involving axilla or peritoneum.⁵⁴³

Empiric treatment of infected animal bite wounds⁵⁴³ or empiric treatment of moderate or severe diabetic foot infections.⁵⁴⁴

Urinary Tract Infections (UTIs)

Treatment of complicated and uncomplicated UTIs caused by susceptible E. coli, K. pneumoniae, M. morganii, P. mirabilis, or P. vulgaris.¹ ³ ¹⁸ ³⁰ ³² ⁸² ⁹¹ ¹⁰⁴ ¹¹⁹ ¹²⁰ ¹²¹ ¹²⁴ ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³¹ ²⁴⁶ ⁴⁵⁵ ⁷⁴³

May be a drug of choice for treatment of complicated UTIs caused by susceptible Enterobacteriaceae, including susceptible strains of E. coli, K. pneumoniae, P. rettgeri, M. morganii, P. vulgaris, or P. stuartii; an aminoglycoside usually used concomitantly in severe infections.¹⁹⁷

Ceftriaxone (like other third generation cephalosporins) generally should not be used for treatment of uncomplicated UTIs when other anti-infectives with a narrower spectrum of activity could be used.¹⁰⁵ ¹⁰⁶ ¹²⁸ ¹⁷⁹ ⁴⁴⁶

Actinomycosis

Has been used for treatment of infections caused byActinomyces^†.²⁷⁸ ³⁸⁰ ³⁸¹ Penicillin G generally drug of choice for initial treatment of all forms of actinomycosis, including thoracic, abdominal, genitourinary, CNS, and cervicofacial infections.¹⁹⁷ ²⁶³ ²⁷⁸ ²⁹² ³⁸²

Bartonella Infections

Treatment of bacteremia caused by Bartonella quintana ^† (in conjunction with oral erythromycin or oral azithromycin).³⁹⁶ Optimum anti-infective regimens for treatment of infections caused by B. quintana not identified;³⁹⁶ ⁴⁶⁴ ⁴⁶⁵ various drugs have been used or are recommended.¹⁹⁷ ²⁹² ⁴⁴⁰ ⁴⁶⁴ ⁴⁶⁵ Infections tend to persist or recur and prolonged therapy (several months or longer) usually necessary.³⁹⁶ ⁴⁴⁰ ⁴⁶⁵

Capnocytophaga Infections

Treatment of infections caused by Capnocytophaga canimorsus^†.¹⁹⁷

Optimum regimens for treatment of Capnocytophaga infections not identified; some clinicians recommend penicillin G¹⁹⁷ ⁴⁶³ or, alternatively, a third generation cephalosporin (ceftriaxone), a carbapenem (imipenem, meropenem), vancomycin, a fluoroquinolone, or clindamycin.¹⁹⁷

Chancroid

Has been used in the treatment of chancroid^† (genital ulcers caused by H. ducreyi).²¹⁰ ²¹¹ ²²⁹ ²⁴¹ ²⁷⁴ ³⁴⁴ ⁷⁴⁷ ⁷⁴⁸

CDC and other experts recommend azithromycin, ceftriaxone, ciprofloxacin, or erythromycin as drugs of choice for treatment of chancroid.³⁴⁴ ⁷⁴⁷ ⁷⁴⁸

Gonorrhea and Associated Infections

Treatment of uncomplicated cervical, urethral, rectal, or pharyngeal infections caused by susceptible Neisseria gonorrhoeae in adults, adolescents, and children.¹ ³ ¹⁸ ³⁰ ³² ¹¹⁵ ¹¹⁸ ³³⁶ ³⁴⁴ ⁷⁴⁶ ⁷⁴⁷ ⁷⁴⁸ Ceftriaxone is the drug of choice for most patients.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷

Treatment of gonococcal conjunctivitis^† in adults and adolescents; ceftriaxone is drug of choice.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷ Because only limited data available regarding treatment of gonococcal conjunctivitis, consider consultation with an infectious disease specialist.³⁴⁴ ⁷⁴⁶

Initial treatment of disseminated gonococcal infections^†.²²¹ ³⁴⁴ Drug of choice for initial parenteral treatment in adults, adolescents, and children, especially when meningitis, endocarditis, or conjunctivitis is involved.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷

Empiric treatment of acute epididymitis^†.³⁴⁴ ⁷⁴⁷ Used in conjunction with doxycycline if infection most likely caused by sexually transmitted N. gonorrhoeae and Chlamydia trachomatis;³⁴⁴ ⁷⁴⁷ ⁷⁴⁸ used in conjunction with levofloxacin if infection most likely caused by sexually transmitted chlamydia, gonorrhea, and enteric bacteria.³⁴⁴ ⁷⁴⁷ ⁷⁴⁸

Presumptive treatment of proctitis^† prior to availability of diagnostic laboratory test results; used in conjunction with doxycycline.³⁴⁴ ⁷⁴⁷ ⁷⁴⁸

Parenteral prophylaxis^† and presumptive treatment of gonorrhea^† in neonates born to mothers with gonorrhea.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷ Also recommended in other neonates if topical erythromycin prophylaxis is unavailable, especially for neonates born to women who are at risk for gonococcal infection or received no prenatal care.³⁴⁴

Treatment of ophthalmia neonatorum^† caused by N. gonorrhoeae.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷ A single-dose ceftriaxone regimen is adequate for treatment of gonococcal conjunctivitis, but infants with ophthalmia neonatorum should be hospitalized and evaluated for signs of disseminated infection (e.g., sepsis, arthritis, meningitis).³⁴⁴ ⁷⁴⁶ CDC and AAP recommend that infants with gonococcal ophthalmia be managed in consultation with an infectious disease specialist.³⁴⁴ ⁷⁴⁶

Treatment of disseminated gonococcal infections (e.g., sepsis, arthritis, meningitis) and gonococcal scalp abscesses in neonates.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷ Contraindicated in certain neonates .¹ ¹⁸ ³⁰ ³² ³⁴⁴ ⁷⁴⁶

Remain vigilant for treatment failures (evidenced by persistent symptoms or positive follow-up test despite treatment).³⁴⁴ Consider that N. gonorrhoeae with reduced susceptibility to ceftriaxone and/or cefixime or other cephalosporins reported in US and elsewhere.³⁴⁴ ⁷¹⁶ ⁷¹⁷ ⁷¹⁸ ⁷¹⁹ ⁷²⁰ ⁷²¹ ⁷²² ⁷²³ ⁷²⁴ ⁷²⁵ ⁷²⁶ ⁷²⁷

If infection persists (treatment failure) and reinfection unlikely, culture relevant clinical specimens and perform in vitro susceptibility tests.³⁴⁴ Also consult infectious disease specialist, STD/HIV Prevention Training Center ([Web]), local or state health department STD program, or CDC (800-232-4636) for advice on obtaining cultures, in vitro susceptibility testing, and treatment.³⁴⁴ Report suspected treatment failures to CDC through local or state health departments within 24 hours of diagnosis.³⁴⁴ ⁷²²

Empiric anti-infective prophylaxis in adult and adolescent sexual assault victims^†; 3-drug prophylaxis regimen of ceftriaxone, doxycycline, and metronidazole provides coverage against gonorrhea, chlamydia, and trichomoniasis.³⁴⁴ ⁷⁴⁹ In male sexual assault victims, use 2-drug regimen omitting metronidazole.³⁴⁴ ⁷⁴⁹

Leptospirosis

Treatment of severe leptospirosis^† caused by Leptospira.¹⁹⁷ ⁶⁹⁰ ⁶⁹⁴ ⁶⁹⁵ ⁷⁵⁸

Leptospirosis is a spirochete infection that may range in severity from a self-limited systemic illness to a severe, life-threatening illness that includes jaundice, renal failure, hemorrhage, myocarditis, cardiac arrhythmias, pneumonitis, and hemodynamic collapse (Weil syndrome).²⁹² ⁶⁹¹ ⁶⁹³

Penicillin G generally considered drug of choice for treatment of moderate to severe leptospirosis;¹⁹⁷ ⁶⁹⁰ ⁶⁹¹ ⁶⁹⁵ ⁷⁵⁸ doxycycline has been used in less severe infections.¹⁹⁷ ⁷⁵⁸ Cephalosporins (ceftriaxone, cefotaxime), aminopenicillins (ampicillin, amoxicillin), tetracyclines (doxycycline, tetracycline), or macrolides (azithromycin) also have been recommended for severe infections.¹⁹⁷ ⁶⁹¹ ⁶⁹³ ⁶⁹⁴ ⁶⁹⁵ ⁷⁵⁸

Lyme Disease

Ceftriaxone is a drug of choice for the treatment of acute neurologic Lyme disease^†.¹⁹⁷ ²⁷⁹ ³²⁹ ³⁵³ ³⁵⁶ ³⁵⁷ ³⁵⁸ ³⁵⁹ ³⁶¹ ³⁶² ³⁶³ ³⁶⁵ ³⁶⁶ ³⁶⁷ ⁴⁸¹ ⁷⁴⁴ ⁷⁴⁵ In patients with Lyme disease-associated meningitis, cranial neuropathy, radiculoneuropathy, or with other peripheral nervous system manifestations, recommended treatment is parenteral therapy with ceftriaxone, cefotaxime, or penicillin G, or oral therapy with doxycycline.³²⁹ Route of therapy may be changed from IV to oral during treatment in patients who have experienced clinical improvement.³²⁹ ⁷⁴⁵ Recommended treatment duration is 14–21 days.³²⁹ ⁷⁴⁴ ⁷⁴⁵

Treatment of Lyme carditis^† when a parenteral regimen indicated.³²⁹ ⁴⁹⁷ ⁷⁴⁴ ⁷⁴⁵ In outpatients with Lyme carditis, oral antibiotics (doxycycline, amoxicillin, cefuroxime axetil, or azithromycin) recommended.³²⁹ ⁷⁴⁵ In patients with or at high risk of severe cardiac complications, including those with a PR interval >0.3 seconds, other arrhythmias, or clinical manifestations of myopericarditis, hospitalization with continuous ECG monitoring and treatment with IV ceftriaxone recommended; upon clinical improvement, may switch to oral antibiotics to complete recommended 14–21 days of treatment.³²⁹ ⁷⁴⁵ For patients with symptomatic bradycardia that cannot be managed medically, temporary pacing modalities recommended over a permanent pacemaker.³²⁹

In pediatric patients with Lyme disease associated with atrioventricular heart block or carditis^†, oral treatment with doxycycline, amoxicillin, or cefuroxime for 14 days (range: 14–21 days) or IV treatment with ceftriaxone for 14 days (range: 14–21 days for a hospitalized patient) recommended.⁷⁴⁴ ⁷⁴⁵ May substitute oral antibiotics for IV treatment when patient stabilized or discharged from hospital to complete recommended 14–21 days of treatment.⁷⁴⁴ ⁷⁴⁵

Treatment of Lyme arthritis^† when a parenteral regimen indicated.³²⁹ ⁴⁹⁷ ⁴⁹⁸ ⁷⁴⁴ ⁷⁴⁵ In patients with Lyme disease-associated arthritis, recommended initial treatment is a 28-day course of oral antibiotics (doxycycline, amoxicillin, or cefuroxime).³²⁹ ⁷⁴⁴ ⁷⁴⁵ In patients who experience a partial response to an initial course of treatment, a second course of oral antibiotics for up to 1 month may be reasonable.³²⁹ In patients with minimal or no response (moderate to severe joint swelling with minimal reduction of the joint effusion) to an initial 28-day course of oral antibiotic, a 2- to 4-week course of IV ceftriaxone is recommended.³²⁹ ⁷⁴⁴ ⁷⁴⁵ In patients who have failed one course of oral antibiotics and one course of IV antibiotics, refer to rheumatologist or other trained specialist.³²⁹ Antibiotic therapy for >8 weeks (including one course of IV antibiotic) not expected to provide additional benefit to patients with persistent arthritis.³²⁹

Neisseria Meningitidis Infections

Treatment of invasive infections, including meningitis, caused by N. meningitidis;¹ ³ ¹⁸ ³⁰ ³² ¹⁶⁶ ⁷⁵⁴ a drug of choice for empiric treatment of suspected meningococcal disease.⁴¹⁸ ⁷⁵⁴

Elimination of nasopharyngeal carriage of N. meningitidis ^† in patients with invasive meningococcal disease.¹⁶⁶ ³⁷⁶ ⁷⁵⁴ Recommended regimens are ceftriaxone, rifampin, or ciprofloxacin.¹⁶⁶ ²⁹² ³⁷⁶

Chemoprophylaxis to prevent meningococcal disease in household or other close contacts of patients with invasive meningococcal disease^†.¹⁶⁶ ³⁷⁶ ⁷⁵⁴ ⁷⁵⁹ Recommended regimens are ceftriaxone, rifampin, or ciprofloxacin.¹⁶⁶ ³⁷⁶ ⁷⁵⁴

Nocardia Infections

Treatment of nocardiosis^† caused by Nocardia.¹⁹⁷ ⁶⁹⁷ ⁶⁹⁸ ⁶⁹⁹ ⁷⁰⁰ ⁷⁰¹ ⁷⁰² ⁷⁶³

Co-trimoxazole (fixed combination of sulfamethoxazole and trimethoprim) generally is drug of choice for treatment of mild nocardiosis.¹⁹⁷ ⁷⁶³ If infection does not respond to co-trimoxazole, may consider a fluoroquinolone or a carbapenem; however, most Nocardia species are resistant to ertapenem.⁷⁶³ Other agents with activity against specific Nocardia species include clarithromycin (N. nova) and amoxicillin and clavulanate (N. brasiliensis and N. abscessus complex).⁷⁶³

For serious Nocardia infections (pulmonary infection, disseminated disease, CNS involvement) or in immunocompromised patients, combination therapy is recommended.⁷⁶³ AAP recommends initial treatment with co-trimoxazole, amikacin, and either linezolid, imipenem, or meropenem until susceptibility information available.⁷⁶³ Ceftriaxone is considered an alternative agent; however, resistance reported in many strains of N. farcinica, N. transvalensis complex, and N. otitidiscaviarum complex.⁷⁶³ Treat immunocompromised patients and patients with severe disease for 6–12 months and for at least 3 months after apparent cure.⁷⁶³ Patients with HIV may need longer treatment; consider suppressive therapy.⁷⁶³

Alternative to co-trimoxazole for treatment of skin and skin structure infections caused by Nocardia ^† (e.g., N. farcinica, N. brasiliensis).⁵⁴³ Prolonged anti-infective treatment (6–24 months) and/or multiple-drug anti-infective regimen may be necessary for severe or disseminated infections or in patients with immunosuppression.⁵⁴³

Pelvic Inflammatory Disease (PID)

Treatment of PID caused by N. gonorrhoeae.¹ ³ ¹⁸ ³⁰ ³² ³⁴⁴ ³⁹⁷ ³⁹⁸ ⁴⁶⁰ ⁷⁴⁷ ⁷⁴⁸

When IV treatment indicated, regimen of ceftriaxone in conjunction with doxycycline and metronidazole or regimen of cefoxitin (or cefotetan) in conjunction with doxycycline recommended.³⁴⁴ ⁷⁴⁷ ⁷⁴⁸ CDC states cefotaxime or ceftizoxime may be effective, but are less active than cefotetan or cefoxitin against anaerobic bacteria; if used, consider adding metronidazole in addition to doxycycline.³⁴⁴

When IM and oral regimen used for treatment of mild to moderately severe acute PID, CDC and AAP recommend a single IM dose of ceftriaxone, cefoxitin (with oral probenecid), or other parenteral third generation cephalosporin (e.g., cefotaxime) given in conjunction with oral doxycycline (with or without oral metronidazole).³⁴⁴ ⁷⁴⁸

Because ceftriaxone (like other cephalosporins) not active against Chlamydia, concomitant use of a drug active against Chlamydia (e.g., doxycycline) is necessary when these organisms are suspected pathogens.¹ ³ ¹⁸ ³⁰ ³² ³⁴⁴

Relapsing Fever

Treatment of relapsing fever^† caused by Borrelia recurrentis;²⁶⁴ other drugs (e.g., tetracyclines, penicillin G) usually considered drugs of choice.¹⁹⁷ ⁷⁶² Second-line agents include erythromycin and azithromycin.⁷⁶² AAP states that treatment with IV antibiotics (e.g., penicillin, ceftriaxone) preferred for pregnant patients, when CNS involvement is present, or when oral therapy is not well tolerated.⁷⁶²

Syphilis

Alternative for treatment of primary or secondary syphilis^† in penicillin-allergic nonpregnant adults and adolescents.³⁴⁴

Alternative for treatment of latent syphilis^† in penicillin-allergic nonpregnant adults and adolescents.³⁴⁴

Alternative for treatment of neurosyphilis^† in penicillin-allergic nonpregnant adults and adolescents.³⁴⁴

CDC recommends that a specialist be consulted when making decisions regarding treatment of syphilis in penicillin-allergic patients.³⁴⁴

Optimal dosage and duration of ceftriaxone for treatment of primary, secondary, or latent syphilis or neurosyphilis not defined and close follow-up is essential.³⁴⁴ Consider possibility of cross-sensitivity between penicillin and ceftriaxone.³⁴⁴ If compliance or follow-up with alternative regimens cannot be ensured, CDC recommends desensitization and treatment with the appropriate penicillin G preparation.³⁴⁴

CDC states that ceftriaxone is a possible alternative for treatment of infants or children with clinical evidence of congenital syphilis in certain circumstances when penicillin G not available (i.e., during a penicillin shortage).³⁴⁴ Use in consultation with a specialist in treatment of infants with congenital syphilis and with close clinical, serologic, and CSF follow-up.³⁴⁴

CDC, NIH, and IDSA state that efficacy of non-penicillin alternatives not well evaluated in people with HIV; close clinical and serologic monitoring required.⁴⁴⁰

Typhoid Fever and Other Invasive Salmonella Infections

Treatment of typhoid fever^† or paratyphoid fever^† (enteric fever) or septicemia caused by Salmonella serovars Typhi or Paratyphi, respectively, including multidrug-resistant strains.¹⁶⁷ ¹⁸⁸ ²⁶⁷ ⁴⁰⁶ ⁴⁰⁷ ⁴⁰⁸ ⁴⁰⁹ ⁴¹⁰ ⁷⁵² ⁷⁶⁵ ⁷⁶⁶ A drug of choice for empiric treatment of enteric fever pending results of in vitro susceptibility tests (depending on patient travel history and regional resistance patterns).⁷⁵² ⁷⁶⁶

Treatment of invasive infections (bacteremia, osteomyelitis) caused by nontyphoidal Salmonella ^†, including Salmonella serovar Typhimurium.⁴¹⁰ ⁵⁰⁵ ⁵⁹⁰ ⁷⁵²

Whipple’s Disease

Treatment of Whipple’s disease^†, a progressive systemic infection caused by Tropheryma whipplei (formerly Tropheryma whippelii).³⁸³ ³⁸⁴ ³⁸⁵ ³⁸⁶ ⁵⁰⁶ ⁷³⁰ ⁷³¹ ⁷³² Optimal regimens not identified; some clinicians recommend initial parenteral regimen (e.g., ceftriaxone or penicillin G used with or without streptomycin) followed by long-term (1–2 years) treatment with oral co-trimoxazole.⁷³⁰ ⁷³²

For treatment of encephalitis caused by T. whipplei, IDSA recommends initial treatment with ceftriaxone for 2–4 weeks followed by co-trimoxazole or cefixime for 1–2 years.⁵⁰⁶

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients^†; used in conjunction with an aminoglycoside.³⁸⁷ ³⁸⁸ ⁴³⁷

Ceftriaxone monotherapy not usually recommended⁴³⁵ ⁴³⁶ since it may not provide adequate coverage against some potential pathogens (e.g., P. aeruginosa).³⁸⁷ ³⁸⁸ ⁴³⁷

Consult published protocols on treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of initial empiric regimen, when to change initial regimen, possible subsequent regimens, and duration of therapy in these patients.⁴⁵⁷ Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also advised.⁴⁵⁷

Prevention of Bacterial Endocarditis

Alternative for prevention of α-hemolytic (viridans group) streptococcal endocarditis^† in individuals undergoing certain dental or upper respiratory tract procedures who have cardiac conditions that put them at highest risk of adverse outcome from endocarditis.⁴⁵¹

Oral amoxicillin is usual drug of choice for such prophylaxis;⁴⁵¹ ceftriaxone (or cefazolin) is an alternative in penicillin-allergic individuals or when an oral anti-infective cannot be used.⁴⁵¹ Should not be used in those with a history of anaphylaxis, angioedema, or urticaria after receiving a penicillin.⁴⁵¹

Consult current AHA recommendations for information on which cardiac conditions are associated with highest risk of adverse outcomes from endocarditis and additional information regarding prophylaxis for prevention of bacterial endocarditis.⁴⁵¹

Perioperative Prophylaxis

Perioperative prophylaxis to reduce the incidence of infection in patients undergoing contaminated or potentially contaminated surgical procedures,¹ ¹⁸ ³⁰ ³² including biliary tract procedures (e.g., cholecystectomy),¹ ¹⁸ ³⁰ ³² ¹⁴⁷ ¹⁵² ²⁹⁴ ²⁹⁵ ²⁹⁶ ²⁹⁷ ²⁹⁸ ³⁷⁴ ⁴⁴⁹ colorectal procedures,³⁷⁴ intra-abdominal surgery,¹⁵² ⁴¹³ or vaginal or abdominal hysterectomy,¹ ¹⁸ ³⁰ ³² ¹⁵⁴ and in those undergoing clean surgical procedures in which the development of infection at the surgical site would represent a serious risk,¹ ¹⁸ ³⁰ ³² including coronary artery bypass,¹ ¹⁸ ³⁰ ³² open heart surgery,⁶⁷ ¹⁰⁵ ¹⁵¹ thoracic surgery,⁵⁰⁰ or orthopedic surgery.¹⁰⁵ ¹⁵³ Also has been used perioperatively in patients undergoing transurethral resection of the prostate^†¹⁴⁸ ¹⁵⁵ ⁵⁰⁹ or renal transplantation^†.³⁷⁴

First and second generation cephalosporins (cefazolin, cefuroxime) generally preferred when a cephalosporin used for perioperative prophylaxis.¹⁰⁴ ¹⁰⁶ ¹⁷⁵ ³⁶⁰ ³⁷⁴ Third generation cephalosporins (cefotaxime, ceftriaxone, ceftazidime) and fourth generation cephalosporins (cefepime) not usually recommended for routine perioperative prophylaxis since they are expensive, some are less active than first or second generation cephalosporins against staphylococci, they have spectrums of activity wider than necessary for organisms encountered in elective surgery, and their use for prophylaxis may promote emergence of resistant organisms.³⁶⁰ ⁴³⁵

cefTRIAXone Dosage and Administration

General

Pretreatment Screening

Prior to initiation of therapy with ceftriaxone, careful inquiry should be made concerning previous hypersensitivity reactions to ceftriaxone, cephalosporins, penicillins, other β-lactam anti-infectives, or other drugs.¹ ³ ¹⁸ ³²

Patient Monitoring

Monitor patients for possible emergence and overgrowth of nonsusceptible organisms with prolonged ceftriaxone therapy.¹ ³² If superinfection or suprainfection occurs, institute appropriate therapy.¹⁸
Monitor patients for hypersensitivity reactions.¹ If a severe hypersensitivity reaction occurs during ceftriaxone therapy, immediately discontinue the drug and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway, oxygen).¹ ³ ¹⁸ ³²
Monitor prothrombin time (PT) in patients with impaired vitamin K synthesis or low vitamin K stores (e.g., patients with chronic hepatic disease, malnutrition).¹ ³ ¹⁸ ³² Administer vitamin K when indicated.¹ ³ ¹⁸ ³²
Some clinicians recommend that serum concentrations of ceftriaxone be monitored periodically in patients with severe renal impairment (e.g., dialysis patients) or in patients with both renal and hepatic impairment; dosage should be adjusted if necessary.⁷³ ⁷⁴ ⁷⁷ ¹⁷⁰

Other General Considerations

Ensure that patients receiving ceftriaxone are adequately hydrated.¹ ¹⁸ ³²
To reduce the development of drug-resistant bacteria and maintain effectiveness of ceftriaxone and other antibacterials, use ceftriaxone only for the treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹ ¹⁸ ³²
The Institute for Safe Medication Practices (ISMP) includes cefTRIAXone on the ISMP List of Confused Drug Names, and recommends special safeguards to ensure the accuracy of prescriptions for this drug.⁷¹¹

Administration

Administer by IV infusion¹ ³ ¹⁸ ³⁰ ³² or deep IM injection.¹

Should not be administered intrathecally.⁴¹⁶

Do not use diluents containing calcium (e.g., Ringer’s/lactated Ringer’s injection, Hartmann’s injection) to reconstitute or further dilute ceftriaxone because a precipitate can form.¹ ³ ¹⁸ ³⁰ ³² ⁵⁰⁷ ⁵¹¹ ⁵²⁹

Because precipitation of ceftriaxone-calcium can occur, ceftriaxone must not be admixed with calcium-containing solutions and must not be administered simultaneously with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age).¹ ³ ¹⁸ ³⁰ ³² ⁵⁰⁷ ⁵¹⁰ ⁵¹¹ ⁵²⁹

Contraindicated in neonates (≤28 days of age) if they are receiving (or expected to require) treatment with calcium-containing IV solutions, including continuous calcium-containing infusions such as parenteral nutrition.¹ ¹⁸ ³⁰ ⁵²⁹

In adult and pediatric patients >28 days of age, ceftriaxone and calcium-containing solutions may be administered sequentially if the infusion lines are thoroughly flushed between infusions with a compatible fluid (e.g., 0.9% sodium chloride injection, 5% dextrose injection).¹ ³ ¹⁸ ³⁰ ³² ⁵²⁹

Ensure that patients receiving ceftriaxone are adequately hydrated.¹ ³ ¹⁸ ³²

IV Infusion

The recommended concentration for IV infusion is 10–40 mg of ceftriaxone/mL; lower concentrations may be used if desired.¹

Reconstitution and Dilution

Reconstitute vials containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone with 2.4, 4.8, 9.6, or 19.2 mL, respectively, of a compatible IV solution to provide solutions containing approximately 100 mg/mL.¹ Then, further dilute to desired concentration in a compatible IV solution.¹

Reconstitute ADD-Vantage vials containing 1 or 2 g of ceftriaxone with 0.9% sodium chloride or 5% dextrose injection in ADD-Vantage flexible containers according to the manufacturer’s directions.³²

Reconstitute (activate) commercially available Duplex drug delivery system containing 1 or 2 g of ceftriaxone and 50 mL of 3.74 or 2.22% dextrose injection, respectively, in separate chambers according to the manufacturer's directions.³ If refrigerated after reconstitution, allow solution to reach room temperature prior to administration.³

Reconstitute 10-g pharmacy bulk package by adding 95 mL of a compatible IV solution to provide a solution containing approximately 100 mg/mL and then further dilute in a compatible IV infusion solution.¹⁸ Dilution to a concentration of 10–40 mg/mL usually recommended; lower concentrations may be used if desired.¹⁸

Thaw commercially available premixed injection (frozen) at room temperature (25°C) or in a refrigerator (5°C); do not thaw by immersion in a water bath or by exposure to microwave radiation.³⁰ A precipitate may have formed in the frozen injection, but should dissolve with little or no agitation after reaching room temperature.³⁰ Discard thawed injection if an insoluble precipitate is present or if container seals or outlet ports are not intact or leaks are found.³⁰ Do not use in series connections with other plastic containers; such use could result in air embolism from residual air being drawn from the primary container before administration of fluid from secondary container is complete.³⁰

Rate of Administration

Give intermittent IV infusions over 30 minutes (except neonates).¹ ³ ¹⁸ ³⁰ ³²

Give intermittent IV infusions over 60 minutes in neonates.¹ ¹⁸ ³²

IM Administration

Inject IM deeply into a large muscle mass using usual techniques and precautions.¹

Do not use IM solutions reconstituted with bacteriostatic water containing benzyl alcohol in neonates.¹⁷⁶ ¹⁷⁷

Reconstitution

Prepare IM injections by adding 0.9, 1.8, 3.6, or 7.2 mL of sterile water for injection, 0.9% sodium chloride injection, 5% dextrose injection, bacteriostatic water for injection containing 0.9% benzyl alcohol, or 1% lidocaine hydrochloride (without epinephrine) to a vial containing 250 mg, 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 250 mg/mL or by adding 1, 2.1, or 4.2 mL of one of these diluents to a vial containing 500 mg, 1 g, or 2 g of ceftriaxone, respectively, to provide solutions containing approximately 350 mg/mL.¹

More dilute solutions of the drug may be used for IM injection if required.¹

Dosage

Available as ceftriaxone sodium; dosage expressed in terms of ceftriaxone.¹ ³ ¹⁸ ³⁰ ³²

Do not use ceftriaxone available in Duplex drug delivery system in patients who require less than the entire 1- or 2-g dose in the container.³

Pediatric Patients

General Pediatric Dosage

Infections in Neonates ≤28 Days of Age

IV or IM

AAP recommends 50 mg/kg once daily, regardless of weight.⁷⁵⁷

Infections Other than CNS Infections or Endocarditis in Children Beyond Neonatal Period

IV or IM

AAP recommends 50–75 mg/kg once daily (maximum 1 g/day).⁷⁵⁷

CNS Infections or Endocarditis in Children Beyond Neonatal Period

IV or IM

AAP recommends 100 mg/kg daily given in 1 or 2 divided doses (maximum 4 g/day).⁷⁵⁷

Manufacturers recommend 50–75 mg/kg daily (up to 2 g daily) given in 2 equally divided doses every 12 hours.¹ ¹⁸ ³⁰ ³²

Acute Otitis Media (AOM)

IM

Single 50-mg/kg dose (maximum 1 g) recommended by manufacturers.¹ ³²

For initial treatment, AAP recommends 50 mg/kg daily (maximum 1 g/day) given for 1 or 3 days^†.⁶⁸³ ⁷⁵⁷ More than a single dose may be required to prevent recurrence.⁶⁸³

For retreatment, AAP recommends 50 mg/kg daily given for 3 days^†.⁶⁸³

Endocarditis†

Native Valve Endocarditis Caused by Viridans Group Streptococci, S. gallolyticus, or Other Streptococci†

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): 100 mg/kg daily in divided doses every 12 hours for 4 weeks recommended by AHA.⁴⁵² Alternatively, 80 mg/kg once daily (up to 4 g daily), but give doses >2 g in divided doses every 12 hours.⁴⁵²

Strains relatively resistant to penicillin (penicillin MIC >0.1 mcg/mL but <0.5 mcg/mL): 100 mg/kg daily in divided doses every 12 hours for 4 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours during first 2 weeks of ceftriaxone treatment) recommended by AHA.⁴⁵² Alternatively, ceftriaxone dosage of 80 mg/kg once daily (up to 4 g daily) can be used in the regimen.⁴⁵²

Prosthetic Valve Endocarditis Caused by Viridans Group Streptococci, S. gallolyticus, or Other Streptococci†

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.1 mcg/mL): 100 mg/kg daily in divided doses every 12 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours during first 2 weeks of ceftriaxone treatment) recommended by AHA.⁴⁵² Alternatively, ceftriaxone dosage of 80 mg/kg once daily (up to 4 g daily) can be used in the regimen.⁴⁵²

Strains relatively or highly resistant to penicillin (penicillin MIC >0.1 mcg/mL): 100 mg/kg daily in divided doses every 12 hours for 6 weeks in conjunction with gentamicin (3–6 mg/kg daily IV in divided doses every 8 hours during entire 6 weeks of ceftriaxone treatment) recommended by AHA.⁴⁵² Alternatively, ceftriaxone dosage of 80 mg/kg once daily (up to 4 g daily) can be used in the regimen.⁴⁵²

Native or Prosthetic Valve Endocarditis Caused by the HACEK Group†

IV or IM

100 mg/kg daily in divided doses every 12 hours for 4 weeks recommended by AHA.⁴⁵² Alternatively, 80 mg/kg once daily (up to 4 g daily) for 4 weeks.⁴⁵²

GI Infections†

Salmonella Gastroenteritis†

HIV-infected adolescents: 1 g every 24 hours.⁴⁴⁰

Recommended duration is 7–14 days if CD4⁺ T-cells ≥200 cells/mm³ (≥14 days if patient is bacteremic or infection is complicated) or 2–6 weeks if CD4⁺ T-cells <200 cells/mm³.⁴⁴⁰

Shigellosis†

IV or IM

50 mg/kg once daily for 2–5 days has been used.⁴⁰¹ ⁴⁰²

Empiric Treatment of Infectious Diarrhea†

HIV-infected adolescents: 1 g every 24 hours.⁴⁴⁰ Adjust therapy based on stool microbiology results and antibiotic sensitivity testing.⁴⁴⁰ If no pathogen is identified and patient recovers quickly, 5 days of treatment is recommended.⁴⁴⁰

Intra-abdominal Infections

IV or IM

50–75 mg/kg once or twice daily has been recommended.⁷⁰⁸

May be used alone for initial empiric treatment of community-acquired biliary tract infections (cholecystitis or cholangitis); use in conjunction with metronidazole for initial empiric treatment of extrabiliary community-acquired intra-abdominal infections.⁷⁰⁸

Meningitis and Other CNS Infections

Meningitis

Initial dose of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily (up to 4 g daily) given as a single daily dose or in equally divided doses every 12 hours recommended by manufacturers and some clinicians.¹ ³ ¹⁸ ³⁰ ³² ¹²³ ¹³⁰ ¹⁴⁰ ¹⁴² ¹⁴³ ¹⁸⁷ ²⁴³ ²⁹² ⁷⁵⁷ Other clinicians recommend 80–100 mg/kg daily (up to 4 g daily) given as a single daily dose or in divided doses every 12 hours.²⁴⁵ ²⁴⁹ ²⁵⁰ ²⁵⁹ ⁴¹⁸ ⁴⁷¹ Twice-daily regimen may be preferred for S. pneumoniae.²⁹² In neonates, AAP recommends a dosage of 50 mg/kg once every 24 hours.⁷⁵⁷

Duration of 7–10 or 5–7 days may be adequate for uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis, respectively; at least 10–14 days suggested for complicated meningitis caused by S. pneumoniae; at least 21 days suggested for Enterobacteriaceae^† (e.g., E. coli, Klebsiella^†).⁴¹⁸ ⁴⁷⁵ ⁷⁵⁰ In neonates, some experts recommend continuing treatment for 2 weeks beyond first sterile CSF culture or for at least 3 weeks, whichever is longer.⁴¹⁸

Healthcare-associated Ventriculitis and Meningitis

100 mg/kg daily as a single dose or in divided doses every 12 hours recommended by IDSA.⁴¹⁶

Treatment duration depends on causative organism and patient characteristics.⁴¹⁶ Duration of 10–14 days recommended for infections caused by gram-negative bacilli (with or without significant CSF pleocytosis, CSF hypoglycorrhachia, or clinical symptoms or systemic features);⁴¹⁶ some experts recommend a duration of 21 days.⁴¹⁶

Respiratory Tract Infections

Acute Bacterial Rhinosinusitis†

Severe infections requiring hospitalization: 50 mg/kg daily in divided doses every 12 hours recommended by IDSA.⁷²⁸

Community-acquired Pneumonia

IV or IM

Pediatric patients ≥3 months of age with CAP caused by S. pneumoniae: 50–100 mg/kg daily as a single dose or in divided doses every 12 hours for penicillin-susceptible strains or 100 mg/kg daily as a single dose or in divided doses every 12 hours for penicillin-resistant strains recommended by IDSA/ATS.⁵¹³ Treatment usually continued for 10 days.⁵¹³

Pediatric patients ≥3 months of age with CAP caused by S. pyogenes or H. influenzae: 50–100 mg/kg daily as a single dose or in divided doses every 12 hours recommended by IDSA/ATS.⁵¹³ Treatment usually continued for 10 days.⁵¹³

Pediatric patients with CAP: 50–75 mg/kg once daily (maximum 1 g daily) recommended by AAP.⁷⁵⁷ Duration of treatment of 5 days recommended for uncomplicated cases with clinical improvement (i.e., resolution of fever, tachypnea, supplemental oxygen requirement); longer duration recommended for complicated cases.⁷⁵⁰

Neonates with CAP: 50 mg/kg every 24 hours recommended by AAP.⁷⁵⁷ Duration of treatment of 5 days recommended for uncomplicated cases with clinical improvement; longer duration recommended for complicated cases.⁷⁵⁰

Skin and Skin Structure Infections

IV or IM

50–75 mg/kg daily as a single dose or in divided doses every 12 hours.¹

Chancroid†

IM

Infants and children weighing <45 kg: Single 50-mg/kg dose (up to 250 mg).⁷⁴⁸

Infants and children weighing ≥45 kg; Single 250-mg dose.⁷⁴⁸

Adolescents: Single 250-mg dose.³⁴⁴

Gonorrhea and Associated Infections

Parenteral Prophylaxis or Presumptive Treatment in Neonates Born to Mothers with Gonococcal Infection†

IV or IM

Single dose of 20–50 mg/kg (up to 250 mg) recommended by CDC.³⁴⁴

Gonococcal Ophthalmia Neonatorum†

IV or IM

Single dose of 25–50 mg/kg (up to 250 mg) recommended by CDC and AAP.³⁴⁴ ⁷⁴⁶ ⁷⁴⁷

Disseminated Gonococcal Infection and Gonococcal Scalp Abscess in Neonates†

IV or IM

25–50 mg/kg once daily for 7 days recommended by CDC and AAP;³⁴⁴ ⁷⁴⁶ if meningitis documented, continue for 10–14 days.³⁴⁴ ⁷⁴⁶

Uncomplicated Urethral, Cervical, Rectal, or Pharyngeal Gonorrhea in Infants and Children

IV or IM

Children weighing ≤45 kg: CDC and AAP recommend single dose of 25–50 mg/kg IV or IM (up to 250 mg IM).³⁴⁴ ⁷⁴⁸

Children weighing >45 kg: CDC and AAP recommend single 500-mg IM dose (1 g in patients weighing ≥150 kg).³⁴⁴ ⁷⁴⁸

Disseminated or Complicated Gonorrhea in Infants and Children†

IV or IM

Children weighing ≤45 kg with gonococcal bacteremia or arthritis: CDC recommends 50 mg/kg (up to 2 g) every 24 hours for 7 days.³⁴⁴

Children weighing >45 kg with gonococcal bacteremia or arthritis: CDC recommends 1 g every 24 hours for 7 days.³⁴⁴

Uncomplicated Cervical, Urethral, Anorectal, or Pharyngeal Gonorrhea in Adolescents

Single 500-mg dose (1 g in patients weighing ≥150 kg).¹ ³⁴⁴ ³⁴⁵

Gonococcal Conjunctivitis in Adolescents†

Single 1-g dose.³⁴⁴

Disseminated Gonococcal Infections in Adolescents†

IV or IM

Gonococcal arthritis and arthritis-dermatitis syndrome: 1 g once daily.³⁴⁴ Continue ceftriaxone for 24–48 hours after substantial clinical improvement; treatment may then be switched to an oral antibacterial (selected based on in vitro susceptibility testing) to complete total treatment duration of at least 7 days.³⁴⁴

Gonococcal meningitis or endocarditis: 1–2 g IV every 24 hours.³⁴⁴ Continue ceftriaxone for 10–14 days in those with meningitis and for at least 4 weeks in those with endocarditis.³⁴⁴

Prophylaxis in Adolescent Sexual Assault Victims†

Single 500-mg dose (1 g in patients weighing ≥150 kg) in conjunction with oral doxycycline (100 mg twice daily for 7 days) and metronidazole (500 mg twice daily for 7 days) recommended by CDC and AAP.³⁴⁴ ⁷⁴⁹ Two-drug regimen omitting metronidazole recommended in male survivors of sexual assault.³⁴⁴ ⁷⁴⁹

Lyme Disease†

Acute Neurologic Lyme Disease†

50–75 mg/kg (up to 2 g) once daily for 14–21 days recommended by AAP for Lyme disease in children with acute neurologic manifestations (e.g., meningitis, radiculopathy).⁷⁴⁴ ⁷⁴⁵

Lyme Carditis†

50–75 mg/kg (up to 2 g) once daily for 14 days (range: 14–21 days for hospitalized patients) recommended by AAP for children with AV heart block and/or myopericarditis associated with Lyme disease when parenteral regimen indicated (e.g., hospitalized patients).

Parenteral regimen can be switched to an oral regimen (doxycycline, amoxicillin, or cefuroxime axetil) to complete therapy and for outpatients.⁷⁴⁴ ⁷⁴⁵

Lyme Arthritis†

50–75 mg/kg (up to 2 g) once daily for 14–28 days recommended by AAP for children when arthritis has not responded to an oral regimen.⁷⁴⁴ ⁷⁴⁵

Neisseria meningitidis Infections

Meningitis

Initial dose of 100 mg/kg (up to 4 g) followed by 100 mg/kg daily (up to 4 g daily) given as a single daily dose or in equally divided doses every 12 hours recommended by manufacturers.¹ ³ ¹⁸ ³⁰ ³²

Some clinicians recommend 80–100 mg/kg daily (up to 4 g daily) given as a single daily dose or in divided doses every 12 hours.²⁴⁵ ²⁴⁹ ²⁵⁰ ²⁵⁹ ⁴¹⁸ ⁴⁷¹

Usual duration is 7–14 days;¹ AAP states 5–7 days may be adequate for meningococcal disease.⁷⁵⁰

Elimination of Nasopharyngeal Carrier State†

Children and adolescents <15 years of age: Single 125-mg dose.³⁷⁶ ⁷⁵⁴

Adolescents ≥15 years of age: Single 250-mg dose.³⁷⁶ ⁷⁵⁴

Chemoprophylaxis in Household or Other Close Contacts†

IV or IM

Children and adolescents <15 years of age: Single 125-mg dose.³⁷⁶ ⁷⁵⁴

Adolescents ≥15 years of age: Single 250-mg dose.³⁷⁶ ⁷⁵⁴

Pelvic Inflammatory Disease

IM

Adolescents: Single 500-mg dose (1-g in patients weighing ≥150 kg) followed by 14-day regimen of doxycycline (100 mg orally twice daily) and metronidazole (500 mg orally twice daily).³⁴⁴ ⁷⁴⁷ ⁷⁴⁸

If no clinical response within 72 hours, reevaluate patient to confirm diagnosis and administer an IV regimen if indicated.³⁴⁴

IV

Adolescents: 1 g every 24 hours in conjunction with doxycycline (100 mg IV or orally every 12 hours) and metronidazole (500 mg orally or IV every 12 hours).³⁴⁴ ⁷⁴⁷ ⁷⁴⁸ Usually can transition to oral therapy within 24 to 48 hours of clinical improvement.³⁴⁴ ⁷⁶¹

Syphilis†

Congenital Syphilis When Penicillin Unavailable†

IV or IM

Infants ≥30 days of age with clinical evidence of congenital syphilis: 75 mg/kg once daily for 10–14 days recommended by CDC.³⁴⁴ Dosage adjustments may be needed based on weight.³⁴⁴

Children: 100 mg/kg once daily for 10–14 days recommended by CDC.³⁴⁴

Neonates: 50–75 mg/kg IV once daily for 10–14 days recommended by CDC.³⁴⁴

Use for treatment of congenital syphilis only when necessary (i.e., during a penicillin shortage); use in consultation with a specialist in treatment of infants with congenital syphilis and with close clinical, serologic, and CSF follow-up.³⁴⁴ ⁷⁶⁴

Consider that ceftriaxone is contraindicated in certain neonates.³⁴⁴

Syphilis in Penicillin-allergic Nonpregnant Adolescents†

IV or IM

Primary or secondary syphilis: 1 g once daily for 10–14 days suggested by CDC and others.³⁴⁴ ⁷⁴⁷ ⁷⁶⁴

Early latent syphilis: 1 g once daily for 10–14 days suggested by some clinicians.⁷⁴⁷ ⁷⁶⁴

Neurosyphilis: 1–2 g daily for 10–14 days suggested by CDC and others based on limited data.³⁴⁴ ⁷⁶⁴

Consider that optimal dosage and duration of ceftriaxone for treatment of syphilis not defined; close follow-up is essential.³⁴⁴

Typhoid Fever and Other Invasive Salmonella Infections†

IV or IM

50–75 mg/kg once daily.¹⁶⁷ ⁴⁰⁷ ⁴⁰⁸ ⁴⁰⁹

May be effective for treatment of typhoid fever when given for 3–7 days,¹⁶⁷ ⁴⁰⁶ ⁴⁰⁷ ⁴⁰⁹ ⁴¹⁰ but anti-infective treatment usually continued for ≥14 days to prevent relapse.⁴⁰⁴ ⁴⁰⁸ AAP recommends a duration of treatment of at least 7–10 days of treatment for uncomplicated disease.⁷⁵² Immunocompromised patients may require longer duration of treatment as well as retreatment.⁷⁵²

Empiric Therapy in Febrile Neutropenic Patients†

IV

80 mg/kg (up to 2 g) once daily in conjunction with IV amikacin (20 mg/kg daily) has been used.³⁸⁷ ³⁸⁸

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures

IV or IM

Single 50-mg/kg dose given 30–60 minutes prior to the procedure recommended by AHA.⁴⁵¹

Adults

General Adult Dosage

IV or IM

1–2 g once daily or in equally divided doses twice daily.¹ ³ ¹⁸ ³⁰ ³² ⁸⁷ ⁸⁹ ⁹¹ ¹⁰⁴ ¹¹⁹ ¹²⁰ ¹²⁵ ¹²⁷ ¹²⁸ ¹²⁹ ¹³¹

One manufacturer recommends 50–75 mg/kg every 12 hours (up to 2 g daily) for treatment of serious infections other than meningitis.³

Bone and Joint Infections

Native Vertebral Osteomyelitis

Infections caused by susceptible staphylococci, β-hemolytic streptococci, or C. acnes^†: 2 g once daily for 6 weeks recommended by IDSA.⁵⁹⁰

Infections caused by susceptible Salmonella^† (nalidixic acid-resistant strains): 2 g once daily for 6–8 weeks recommended by IDSA.⁵⁹⁰

Prosthetic Joint Infections

Infections caused by susceptible staphylococci: 1–2 g once daily for 2–4 weeks in conjunction with rifampin (300–450 mg orally twice daily) recommended by IDSA.⁵⁹¹ Use oral anti-infective regimen (e.g., rifampin and ciprofloxacin or levofloxacin) to complete a total treatment duration of 3 months for infections related to total hip arthroplasty or 6 months for infections related to total knee arthroplasty.⁵⁹¹

Infections caused by susceptible β-hemolytic streptococci or C. acnes^†: 2 g once daily for 4–6 weeks recommended by IDSA.⁵⁹¹

Endocarditis†

Native Valve Endocarditis Caused by Viridans Group Streptococci or S. gallolyticus†

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 4 weeks recommended by AHA for most patients.⁴⁵⁰

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 2 weeks in conjunction with gentamicin (3 mg/kg daily IV or IM as a single daily dose or as 1 mg/kg every 8 hours for 2 weeks) recommended by AHA for selected patients.⁴⁵⁰ May be considered in adults with uncomplicated endocarditis who are at low risk for gentamicin adverse effects; do not use in those with known cardiac or extracardiac abscess, Cl_cr <20 mL/minute, impaired eighth cranial nerve function, or infection caused by Abiotrophia, Granulicatella, or Gemella.⁴⁵⁰

Prosthetic Valve Endocarditis Caused by Viridans Streptococci or S. gallolyticus†

IV or IM

Highly penicillin-susceptible strains (penicillin MIC ≤0.12 mcg/mL): 2 g once daily for 6 weeks with or without gentamicin (3 mg/kg daily IV or IM as a single daily dose or as 1 mg/kg every 8 hours during first 2 weeks of ceftriaxone treatment) recommended by AHA.⁴⁵⁰

Strains relatively or highly resistant to penicillin (penicillin MIC >0.12 mcg/mL): 2 g once daily for 6 weeks in conjunction with gentamicin (3 mg/kg daily IV or IM as a single daily dose or as 1 mg/kg every 8 hours during entire 6 weeks of ceftriaxone treatment) recommended by AHA.⁴⁵⁰

Native or Prosthetic Valve Endocarditis Caused by Enterococci†

2 g every 12 hours in conjunction with ampicillin (2 g IV every 4 hours).⁴⁵⁰ Continue this double β-lactam regimen for 6 weeks.⁴⁵⁰

Native or Prosthetic Valve Endocarditis Caused by the HACEK Group†

IV or IM

2 g once daily recommended by AHA.⁴⁵⁰ Treatment duration of 4 weeks for native valve endocarditis or 6 weeks for endocarditis involving prosthetic valves or other prosthetic material.⁴⁵⁰

GI Infections†

Salmonella Gastroenteritis†

HIV-infected: 1 g every 24 hours.⁴⁴⁰

Recommended duration is 7–14 days if CD4⁺ T-cells ≥200 cells/mm³ (≥14 days if patient is bacteremic or infection is complicated) or 2–6 weeks if CD4⁺ T-cells <200 cells/mm³.⁴⁴⁰

Empiric Treatment of Infectious Diarrhea†

HIV-infected: 1 g every 24 hours.⁴⁴⁰ Adjust therapy based on stool microbiology results and antibiotic sensitivity testing.⁴⁴⁰ If no pathogen identified and patient recovers quickly, 5 days of treatment recommended.⁴⁴⁰

Intra-abdominal Infections

IV or IM

1–2 g once or twice daily.⁷⁰⁸

Meningitis and Other CNS Infections

Meningitis

2 g every 12 hours.¹⁷⁹ ⁴¹⁸ ⁴⁷⁵ Some manufacturers and clinicians suggest 50–100 mg/kg (up to 4 g) once daily or in 2 equally divided doses every 12 hours;³ ⁴⁷³ others suggest 4 g daily in 1 or 2 equally divided doses.⁴¹⁸

While 7 days may be adequate for uncomplicated meningitis caused by susceptible H. influenzae or N. meningitidis, ≥10–14 days suggested for complicated meningitis caused by S. pneumoniae and ≥21 days suggested for meningitis caused by susceptibleEnterobacteriaceae^† (e.g., E. coli, Klebsiella^†).⁴¹⁸ ⁴⁷⁵

Healthcare-associated Ventriculitis and Meningitis

4 g daily in divided doses every 12 hours recommended by IDSA.⁴¹⁶

Respiratory Tract Infections

Acute Bacterial Rhinosinusitis†

Severe infections requiring hospitalization: 1–2 g every 12–24 hours^†.⁷²⁸

Community-acquired Pneumonia

1–2 g daily.⁵¹²

Skin and Skin Structure Infections

IV or IM

50–75 mg/kg daily (up to 2 g) given as single daily dose or in 2 divided doses every 12 hours.³

Infected Animal Bite

1 g IV every 12 hours recommended by IDSA.⁵⁴³

Necrotizing Fasciitis†

Infections involving A. hydrophila: 1–2 g once daily in conjunction with doxycycline (100 mg IV every 12 hours) recommended by IDSA.⁵⁴³

Infections involving V. vulnificus: 1 g once daily in conjunction with doxycycline (100 mg IV every 12 hours) recommended by IDSA.⁵⁴³

Surgical Site Infections

IV or IM

Following GI or GU surgery: 1 g once daily in conjunction with metronidazole (500 mg IV every 8 hours) recommended by IDSA.⁵⁴³

Following procedures involving axilla or perineum: 1 g once daily recommended by IDSA;⁵⁴³ concomitant vancomycin (15 mg/kg every 12 hours) may also be needed.⁵⁴³

Urinary Tract Infections

IV

Empiric treatment of acute pyelonephritis (e.g., pending results of in vitro susceptibility testing): Single 1-g dose followed by an appropriate oral anti-infective given for 7–14 days.⁷⁴³

Chancroid†

IM

Single 250-mg dose recommended by CDC and others.³⁴⁴ ³⁴⁵ ⁷⁴⁸

Gonorrhea and Associated Infections

Uncomplicated Cervical, Urethral, Anorectal, or Pharyngeal Gonorrhea

Single 500-mg dose (1-g dose in patients weighing ≥150 kg) recommended by CDC.³⁴⁴ ⁷⁴⁷ Single 250-mg dose (maximum 1 g) recommended by manufacturers.¹ ³²

Gonococcal Conjunctivitis†

Single 1-g dose.³⁴⁴ ⁷⁴⁷

Disseminated Gonococcal Infections†

IV or IM

Gonococcal arthritis and arthritis-dermatitis syndrome: 1 g once daily and azithromycin (single 1-g oral dose).³⁴⁴ ⁷⁴⁷ Continue ceftriaxone for 24–48 hours after substantial clinical improvement; treatment may then be switched to an oral antibacterial (selected based on in vitro susceptibility testing) to complete total treatment duration of at least 7 days.³⁴⁴ ⁷⁴⁷

Gonococcal meningitis or endocarditis: 1–2 g IV every 24 hours.³⁴⁴ ⁷⁴⁷ Continue ceftriaxone for 10–14 days in those with meningitis and for at least 4 weeks in those with endocarditis.³⁴⁴ ⁷⁴⁷

Epididymitis†

Presumptive treatment when most likely caused by chlamydia and gonorrhea: Single 500-mg dose (1-g dose in patients weighing ≥150 kg) in conjunction with doxycycline (100 mg orally twice daily for 10 days).³⁴⁴ ⁷⁴⁷

Presumptive treatment when most likely caused by chlamydia, gonorrhea, and enteric bacteria (e.g., E. coli): Single 500-mg dose in conjunction with levofloxacin (500 mg orally once daily for 10 days) or ofloxacin (300 mg orally twice daily for 10 days).³⁴⁴

Proctitis†

Presumptive treatment: Single 500-mg dose (1 g in patients weighing ≥150 kg) in conjunction with doxycycline (100 mg orally twice daily for 7 days).³⁴⁴ ⁷⁴⁷

Prophylaxis in Sexual Assault Victims†

Single 500-mg dose (1-g dose in patients weighing ≥150 kg) in conjunction with doxycycline (100 mg twice daily for 7 days) and metronidazole (500 mg twice daily for 7 days) recommended by CDC.³⁴⁴ In male survivors of sexual assault, 2-drug regimen omitting metronidazole recommended.³⁴⁴

Leptospirosis†

IV

1 g once daily for 7 days has been used for treatment of severe infections.⁶⁹⁰

Lyme Disease†

Acute Neurologic Lyme Disease†

2 g once daily for 14–21 days recommended by IDSA/AAN/ACR for adults with acute neurologic manifestations (e.g., meningitis, radiculopathy).³²⁹ ⁷⁴⁵

Lyme Carditis†

2 g once daily for 14–21 days recommended by IDSA/AAN/ACR and others for adults with AV heart block and/or myopericarditis associated with Lyme disease when parenteral regimen indicated (e.g., hospitalized patients).²⁷⁹ ²⁹⁰ ³²⁹ ³⁵⁷ ³⁵⁹ ³⁶¹ ³⁶² ³⁶⁶ ⁴⁹⁷ ⁷⁴⁵

Parenteral regimen can be switched to oral regimen (doxycycline, amoxicillin, or cefuroxime axetil) to complete therapy and for outpatients.³²⁹ ⁷⁴⁵

Lyme Arthritis†

2 g once daily for 14–28 days recommended by IDSA/AAN/ACR and others for adults with evidence of neurologic disease or when arthritis has not responded to an oral regimen.²⁷⁹ ²⁹⁰ ³²⁹ ³⁵⁷ ³⁵⁹ ³⁶¹ ³⁶² ³⁶⁶ ⁴⁹⁷ ⁷⁴⁵

Neisseria meningitidis Infections

Meningitis

2 g every 12 hours.¹⁷⁹ ⁴⁷⁵ Usual duration is 7–14 days.¹

Elimination of Nasopharyngeal Carrier State†

Single 250-mg dose.³⁷⁶ ⁷⁵⁴

Postexposure Chemoprophylaxis in Household or Other Close Contacts†

Single 250-mg dose.³⁷⁶ ⁷⁵⁴

Pelvic Inflammatory Disease

IM

Single 500-mg dose (1 g if ≥150 kg) followed by 14-day regimen of doxycycline (100 mg orally twice daily) and metronidazole (500 mg orally twice daily).³⁴⁴ ⁷⁴⁷

If no clinical response within 72 hours, reevaluate patient to confirm diagnosis and administer an IV regimen if indicated.³⁴⁴

IV

1 g IV every 24 hours in conjunction with doxycycline (100 mg IV or orally every 12 hours) and metronidazole (500 mg IV or orally every 12 hours).³⁴⁴ ⁷⁴⁷

Syphilis†

Penicillin-allergic Nonpregnant Adults†

IV or IM

Primary or secondary syphilis: 1 g once daily for 10–14 days suggested by CDC and others.³⁴⁴ ⁷⁴⁷

Early latent syphilis: 1 g once daily for 10–14 days suggested by some clinicians.⁷⁴⁷

Neurosyphilis: 2 g daily for 10–14 days suggested by CDC and others based on limited data.³⁴⁴ ⁷⁴⁷

CDC cautions that optimal dosage and duration not defined; close follow-up is essential.³⁴⁴

Typhoid Fever and Other Invasive Salmonella Infections†

IV or IM

2–4 g once daily.¹⁶⁷ ⁴⁰⁷ ⁴¹⁰

May be effective for treatment of typhoid fever when given for 3–7 days,¹⁶⁷ ⁴⁰⁶ ⁴⁰⁷ ⁴⁰⁹ ⁴¹⁰ but anti-infective treatment usually continued for ≥14 days to prevent relapse.⁴⁰⁴ ⁴⁰⁸ AAP recommends a duration of treatment of at least 7–10 days of treatment for uncomplicated disease, 4 weeks for meningitis, and 4–6 weeks for osteomyelitis or other focal metastatic infections.⁷⁵² Immunocompromised patients may require longer duration of treatment as well as retreatment.⁷⁵² ,

Whipple's Disease†

IV

2 g once daily for 2–4 weeks followed by oral co-trimoxazole given for 1–2 years has been recommended.⁷³⁰ ⁷³¹ ⁷³² For treatment of encephalitis caused by T. whipplei, IDSA recommends initial treatment with ceftriaxone for 2–4 weeks followed by co-trimoxazole or cefixime for 1–2 years.⁵⁰⁶

Empiric Therapy in Febrile Neutropenic Patients†

IV

30 mg/kg (up to 2 g) once daily in conjunction with IV amikacin.³⁸⁸ ⁴³⁷

Perioperative Prophylaxis

IV

Single 1-g dose given 0.5–2 hours prior to surgery.¹ ³ ¹⁸ ³⁰ ³² ¹⁴⁸ ¹⁵¹ ¹⁵² ¹⁵⁴ ¹⁵⁵

Cholecystectomy: Single 1-g dose has been given 0.5–2 hours prior to surgery.¹⁹² ²⁹⁴ ²⁹⁵ ²⁹⁶ ²⁹⁷ ²⁹⁸

Colorectal procedures: Some experts recommend single 2-g dose in conjunction with metronidazole (single 500-mg IV dose) given within 1 hour prior to surgery.³⁷⁴

Prevention of Bacterial Endocarditis†

Patients Undergoing Certain Dental or Upper Respiratory Tract Procedures†

IV or IM

Single 1-g dose given 30–60 minutes prior to the procedure recommended by AHA.⁴⁵¹

Special Populations

Hepatic Impairment

Dosage adjustments not usually necessary in patients with impaired hepatic function receiving dosage up to 2 g daily.¹ ³ ¹⁸ ³⁰ ³² ⁸⁵ ¹⁰⁴

In those with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed dosage of 2 g daily.¹ ³ ¹⁸ ³⁰ ³²

Some clinicians recommend monitoring serum concentrations.⁷³ ⁷⁴ ⁷⁷ ¹⁷⁰

Renal Impairment

Dosage adjustments not usually necessary in patients with mild to moderate renal impairment receiving dosage up to 2 g daily.¹ ³ ¹⁸ ³⁰ ³² ⁷³ ⁷⁷ ⁸⁴ ⁸⁵ ¹⁰⁴ ¹⁷⁰

In those with clinically significant renal impairment and hepatic dysfunction, use caution and do not exceed dosage of 2 g daily.¹ ³ ¹⁸ ³⁰ ³²

Some clinicians recommend monitoring serum concentrations in patients with severe renal impairment (e.g., dialysis patients) or with both hepatic impairment and clinically important renal impairment.³ ⁷³ ⁷⁴ ⁷⁷ ¹⁷⁰

Additional supplemental doses not needed in patients undergoing dialysis.¹ ³ ¹⁸ ³⁰ ³²

Cautions for cefTRIAXone

Contraindications

Known hypersensitivity to ceftriaxone, any other cephalosporin, or any ingredient in the formulation.¹ ¹⁸ ³⁰ ³²
History of anaphylaxis to ceftriaxone, cephalosporins, penicillins, or other β-lactam anti-infectives.³
Certain neonates (e.g., premature or hyperbilirubinemic, those requiring calcium-containing IV solutions).¹ ³ ¹⁸ ³⁰ ³²
Commercially available premixed (frozen) injection in dextrose may be contraindicated in patients with known allergy to corn or corn products.³⁰

Warnings/Precautions

Hypersensitivity Reactions

Serious, occasionally fatal, hypersensitivity reactions (anaphylaxis or anaphylactoid) reported.¹ ³ ³⁰ ³²

Other hypersensitivity reactions, including rash (maculopapular or erythematous), pruritus, fever, eosinophilia, urticaria, bronchospasm, serum sickness, generalized exanthematous pustulosis, and severe cutaneous reactions (erythema multiforme, Stevens-Johnson syndrome, Lyell’s syndrome/toxic epidermal necrolysis) reported.¹ ³ ¹⁸ ³⁰ ³² ⁹² ¹²⁰

Although it has not been proven that allergic reactions to antibiotics are more frequent in atopic individuals,¹⁸² ¹⁸³ ¹⁸⁴ some manufacturers state use ceftriaxone with caution in patients with history of allergy, particularly to drugs.¹ ¹⁸ ³⁰ ³²

Hypersensitivity reactions, including anaphylaxis, reported with dextrose-containing solutions;³ usually reported in patients receiving high dextrose concentrations (i.e., 50% dextrose), but also reported when corn-derived dextrose solutions administered to patients with or without history of hypersensitivity to corn products.³

If a severe hypersensitivity reaction occurs, immediately discontinue drug and institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).¹ ³ ¹⁸ ³⁰ ³²

Cross-hypersensitivity

Partial cross-sensitivity among cephalosporins and other β-lactam antibiotics, including penicillins and cephamycins.³ ¹⁷⁰ ¹⁸⁴ ³²⁵ ⁴³² ⁴³³

Prior to initiation of therapy, make careful inquiry concerning previous hypersensitivity reactions to cephalosporins, penicillins, other β-lactam anti-infectives, or other drugs.¹ ³ ¹⁸ ³⁰ ³²

Interaction with Calcium-containing Products

Fatalities reported in some neonates receiving ceftriaxone and calcium-containing IV solutions; a crystalline material was observed in the lungs and kidneys at autopsy.¹ ¹⁸ ³⁰ ³² In some cases, the same IV infusion line had been used for both ceftriaxone and the calcium-containing fluid and, in some, a precipitate was observed in the IV infusion line.¹ ¹⁸ ³⁰ ³² At least 1 fatality occurred in a neonate who received ceftriaxone and calcium-containing fluids administered at different times and through different infusion lines; no crystalline material was observed at autopsy in this neonate.¹ ¹⁸ ³⁰ ³² ⁵¹¹

No similar reports to date in patients other than neonates treated with ceftriaxone and calcium-containing IV solutions.¹ ¹⁸ ³⁰ ³² ⁵⁰⁷

There is some evidence that neonates have an increased risk for precipitation of ceftriaxone-calcium.¹ ³ ¹⁸ ³⁰ ³² In vitro studies evaluating the combination of ceftriaxone and calcium in adult plasma and neonatal plasma from umbilical cord blood indicate that recovery of ceftriaxone from plasma was reduced with calcium concentrations ≥24 mg/dL in adult plasma or ≥16 mg/dL in neonatal plasma.¹ ³ ¹⁸ ³⁰ ³² This may reflect ceftriaxone-calcium precipitation.¹ ³ ¹⁸ ³⁰ ³²

Ceftriaxone must not be admixed with calcium-containing IV solutions and must not be administered simultaneously with calcium-containing IV solutions, including calcium-containing infusions such as parenteral nutrition, even via different infusion lines at different sites in any patient (irrespective of age).¹ ³ ¹⁸ ³⁰ ³² ⁵⁰⁷ ⁵²⁹

No reports to date of an interaction between ceftriaxone and oral calcium-containing products or between IM ceftriaxone and calcium-containing products (IV or oral).¹ ³ ¹⁸ ³⁰ ³² ⁵²⁹

Neurological Reactions

Serious adverse neurological reactions (e.g., encephalopathy [disturbance of consciousness including somnolence, lethargy, confusion], seizures, myoclonus, and nonconvulsive status epilepticus) reported.¹ ³ ¹⁸ ³⁰ ³² Reversible upon discontinuance of drug.¹ ³ ¹⁸ ³⁰ ³²

Some cases reported in patients with severe renal impairment who did not receive appropriate dosage adjustment of ceftriaxone; however, cases also reported in patients who did receive proper dosage adjustment.¹ ³ ¹⁸ ³⁰ ³²

If adverse neurological reactions associated with ceftriaxone occur, discontinue drug and initiate appropriate supportive treatment.¹ ³ ¹⁸ ³⁰ ³² Adjust ceftriaxone dosage appropriately in patients with severe renal impairment.¹ ³ ¹⁸ ³⁰ ³²

Discontinue ceftriaxone if seizures occur; administer anticonvulsant therapy if clinically indicated.¹ ³ ¹⁸ ³⁰ ³²

Superinfection/Clostridioides difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organisms with prolonged therapy,¹ ³ ¹⁸ ³⁰ ³² ¹¹⁹ ¹²¹ ¹²⁵ ¹³² ¹⁵⁰ ²⁴⁶ ²⁴⁹ ²⁵⁰ ²⁶⁵ especially Candida, enterococci, Bacteroides fragilis, or Pseudomonas aeruginosa.¹¹⁹ ¹²¹ ¹²⁵ ¹³² ¹⁵⁰ ²⁴⁶ ²⁴⁹ ²⁵⁰ ²⁶⁵ Resistant strains of Ps. aeruginosa¹²⁰ ¹²¹ ¹²⁷ ¹³¹ ¹³² ¹⁵⁰ and Enterobacter¹²⁰ ¹²¹ ¹³² ¹⁵⁰ have developed during ceftriaxone therapy. Careful observation of the patient is essential.¹ ³ ¹⁸ ³⁰ Institute appropriate therapy if superinfection occurs.¹ ³ ¹⁸ ³⁰

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridioides difficile.¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸ C. difficile infection (CDI) and C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) reported with nearly all anti-infectives, including ceftriaxone, and may range in severity from mild diarrhea to fatal colitis.¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸ C. difficile produces toxins A and B which contribute to the development of CDAD;¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸ hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹ ³ ¹⁸ ³⁰ ³²

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸ Obtain careful medical history since CDAD may occur as late as 2 months or longer after anti-infective therapy is discontinued.¹ ³ ¹⁸ ³⁰ ³²

If CDAD is suspected or confirmed, discontinue anti-infectives not directed against C. difficile as soon as possible.¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸ Initiate anti-infective therapy directed against C. difficile (e.g., vancomycin, fidaxomicin, metronidazole), appropriate supportive therapy (e.g., fluid and electrolyte management, protein supplementation), and surgical evaluation as clinically indicated.¹ ³ ¹⁸ ³⁰ ³² ³⁰² ³⁰³ ³⁰⁴ ³⁰⁵ ³²⁸

Hemolytic Anemia

Immune-mediated hemolytic anemia reported.¹ ³ ³⁰ ³² Severe cases, including fatalities, have occurred in both adults and children.¹ ³ ³⁰ ³² ³³⁸ ³³⁹ ⁶²⁶ Some cases occurred shortly after administration of a ceftriaxone dose; some reactions have consisted of severe intravascular hemolysis and anemia, decreased hemoglobin concentrations, reticulocytosis, hemoglobinuria, and cardiac arrest.³³⁸ ³³⁹ ⁶²⁶

Consider diagnosis of cephalosporin-associated anemia if anemia occurs in a patient receiving ceftriaxone.¹ ³ ¹⁸ ³⁰ ³² Discontinue ceftriaxone until etiology of the anemia determined.¹ ³ ¹⁸ ³⁰ ³²

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of ceftriaxone and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹ ³ ¹⁸ ³⁰ ³²

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ ³ ¹⁸ ³⁰ ³² In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹ ³ ¹⁸ ³⁰ ³²

Prolonged PT

Prolonged PT reported rarely.¹ ¹⁸ ³⁰ ³²

Monitor PT in patients with impaired vitamin K synthesis or low vitamin K stores (e.g., chronic hepatic disease, malnutrition).¹ ¹⁸ ³⁰ ³² Administer vitamin K when indicated.¹ ¹⁸ ³⁰ ³²

Possible increased risk of bleeding if used concomitantly with vitamin K antagonists.¹ ¹⁸ ³⁰ ³²

Gallbladder Pseudolithiasis

Ceftriaxone-calcium precipitates in the gallbladder reported rarely; symptoms of gallbladder disease (e.g., colic, nausea, vomiting, anorexia) can occur.¹ ³ ¹⁸ ³⁰ ³² ²⁰⁹ ²⁴⁷ ²⁴⁸ ²⁵⁵

The precipitates appear on sonography as an echo without acoustical shadowing (suggesting sludge) or as an echo with acoustical shadowing and may be misinterpreted as gallstones.¹ ³ ¹⁸ ³⁰ ³²

Probability of gallbladder precipitates associated with ceftriaxone therapy appears to be greatest in pediatric patients.¹ ³ ¹⁸ ³²

Discontinue ceftriaxone in patients with manifestations suggestive of gallbladder disease and/or if sonographic abnormalities characteristic of ceftriaxone-calcium precipitates are detected.¹ ³ ¹⁸ ³⁰ ³² ²⁴⁸ ²⁵⁶ ³⁰⁸ ³⁰⁹

The condition appears to be transient and generally resolves following discontinuance of the drug and conservative management.¹ ³ ¹⁸ ³⁰ ³² ²⁰⁹ ²⁴⁷ ²⁴⁸ ²⁵⁵ ³⁰⁸ The time to resolution may range from a few days to several months.²⁰⁹ ²⁴⁸ ²⁵⁵ ³⁰⁸ ³⁰⁹

Consider upper abdominal ultrasonography for patients who develop biliary colic while receiving ceftriaxone therapy; biliary precipitates of ceftriaxone may be detected by ultrasonography after only 4 days of ceftriaxone therapy.³¹⁵ The risk of precipitation may depend on the dose and rate of IV administration of ceftriaxone, occurring more frequently with relatively high dosages and rapid (e.g., over several minutes) rates of administration.²⁰⁶ ²⁴⁷ ²⁴⁸ ³¹⁶

Urolithiasis and Post-renal Acute Renal Failure

Ceftriaxone-calcium precipitates in urine reported and may be detected as sonographic abnormalities.¹ ³ ¹⁸ ³² Patients may be asymptomatic or may develop symptoms of urolithiasis, ureteral obstruction, and post-renal acute renal failure.¹ ³ ¹⁸ ³²

Probability of such precipitates appears to be greatest in pediatric patients.¹ ³ ¹⁸ ³²

The condition appears to be reversible following discontinuance of the drug and conservative management.¹ ³ ¹⁸ ³²

Ensure that patients are adequately hydrated during ceftriaxone therapy.¹ ³ ¹⁸ ³²

Discontinue ceftriaxone in patients with signs and symptoms suggestive of urolithiasis, oliguria or renal failure, and/or if sonographic abnormalities characteristic of ceftriaxone-calcium precipitates are detected.¹ ³ ¹⁸ ³²

Pancreatitis

Pancreatitis, possibly secondary to biliary obstruction, reported rarely.¹ ³ ¹⁸ ³⁰ Most had preexisting risk factors for biliary stasis and biliary sludge (e.g., preceding major therapy, severe illness, total parenteral nutrition).¹ ³ ¹⁸ ³⁰

Co-factor role of ceftriaxone-related biliary precipitation cannot be ruled out.¹ ³ ¹⁸ ³⁰

Patients with Diabetes

Like other dextrose-containing solutions, use Duplex drug delivery system containing 1 or 2 g of lyophilized ceftriaxone and 50 mL of dextrose 3.74 or 2.22% injection, respectively, with caution in patients with overt or known subclinical diabetes mellitus or in patients with carbohydrate intolerance for any reason.³

Lidocaine

Although IM injections can be prepared using 1% lidocaine hydrochloride, consider all contraindications to lidocaine before administering such injections.¹

IV administration of ceftriaxone solutions containing lidocaine is contraindicated.¹ ¹⁸ ³²

Sodium Content

Contains approximately 83 mg (3.6 mEq) of sodium per g of ceftriaxone.¹ ³ ¹⁸ ³⁰ ³²

Specific Populations

Pregnancy

Reproduction studies in mice, rats, and primates have not revealed evidence of embryotoxicity, fetotoxicity, or teratogenicity.¹ ³ ¹⁸ ³⁰ ³²

No drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes observed in data from published prospective cohort studies, case series, and case reports over several decades with use of cephalosporins, including ceftriaxone, in pregnant women.³ Ceftriaxone crosses the placenta.³

No adequate or controlled studies in pregnant women.¹ ¹⁸ ³⁰ ³² Use during pregnancy only when clearly needed.¹ ¹⁸ ³⁰ ³²

Lactation

Distributed into milk in low concentrations; use with caution.¹ ³ ¹⁸ ³⁰ ³²

Effects of ceftriaxone on nursing infants or on milk production not known.³ Consider developmental and health benefits of breast-feeding along with mother’s clinical need for ceftriaxone and any potential adverse effects on infant from drug or mother’s underlying condition.³

Pediatric Use

Contraindicated in premature neonates up to postmenstrual age 41 weeks (i.e., time elapsed since first day of the mother’s last menstrual period to birth plus time elapsed after birth).¹ ¹⁸ ³²

Contraindicated in hyperbilirubinemic neonates, particularly those who are premature.¹ ³ ¹⁸ ³⁰ ³² ²⁹² ²³⁷ ²³⁸ Ceftriaxone can displace bilirubin from serum albumin;¹ ³ ¹⁸ ³⁰ ²³⁷ ²³⁸ ²⁹² possible risk of bilirubin encephalopathy.¹ ³ ¹⁸ ³⁰ ³² ²³⁷ ²³⁸ ²⁹²

Contraindicated in neonates (≤28 days of age) who are receiving (or are expected to require) treatment with calcium-containing IV solutions, including continuous infusions of calcium-containing solutions such as parenteral nutrition; risk of precipitation of ceftriaxone-calcium salt.¹ ¹⁸ ³⁰ ³² ⁵²⁹ Fatalities reported in neonates who received ceftriaxone and calcium-containing IV solutions.¹ ¹⁸ ³² ³⁰ ⁵⁰⁷

To reduce risk of bilirubin encephalopathy, give IV infusions of ceftriaxone over 60 minutes in neonates.¹ ¹⁸ ³²

Do not use ceftriaxone IM injections prepared using bacteriostatic water for injection containing benzyl alcohol in neonates.¹⁷⁶ ¹⁷⁷ Although causal relationship not established, administration of injections preserved with benzyl alcohol has been associated with toxicity in neonates.¹⁷⁶ ¹⁷⁷ Toxicity appears to have resulted from administration of large amounts (i.e., about 100–400 mg/kg daily) of benzyl alcohol in these neonates.¹⁷⁶ ¹⁷⁷

To avoid unintentional overdosage, do not use ceftriaxone available in Duplex drug delivery system in pediatric patients who require less than entire 1- or 2-g dose in the container.³

Geriatric Use

No overall differences in safety and efficacy in those ≥60 years of age compared with younger adults, but the possibility of increased sensitivity in some geriatric individuals cannot be ruled out.¹ ³ ¹⁸ ³⁰ ³²

Pharmacokinetics only minimally altered in geriatric patients compared with healthy younger adults.¹ ³ ¹⁸ ³⁰ ³² Dosage adjustments based solely on age not needed in those receiving up to 2 g daily.¹ ³ ¹⁸ ³⁰ ³²

Substantially eliminated by the kidneys; risk of adverse effects may be greater in those with impaired renal function.³ Select dosage with caution and consider monitoring renal function because of age-related decreases in renal function.³

Hepatic Impairment

Hepatic impairment generally does not affect ceftriaxone pharmacokinetics; dosage adjustments not usually needed unless both hepatic and renal function are impaired.¹

In patients with hepatic dysfunction and clinically significant renal disease, use caution and do not exceed a dosage of 2 g daily.¹ ³ ¹⁸ ³⁰ Some manufacturers and clinicians suggest monitoring serum ceftriaxone concentrations periodically and adjusting dosage if there is evidence of accumulation.³ ⁷³ ⁷⁴ ⁷⁷ ¹⁷⁰

Renal Impairment

Since ceftriaxone is eliminated by both biliary and renal routes, dosage adjustments not usually needed in patients with mild to moderate renal impairment alone.¹ ³ ⁷³ ⁷⁴ ⁷⁷ ⁸⁴ ⁸⁵ ¹⁰⁴ ¹⁰⁵ ¹⁰⁷ ¹⁷⁰

In patients with clinically significant renal disease and hepatic impairment, use caution and do not exceed a dosage of 2 g daily.¹ ³ ¹⁸ ³⁰ Some clinicians suggest monitoring serum ceftriaxone concentrations periodically in patients with severe renal impairment (e.g., dialysis patients) or with both renal and hepatic impairment; adjust dosage if there is evidence of accumulation.³ ⁷³ ⁷⁴ ⁷⁷ ¹⁷⁰

Ceftriaxone overdosage reported in patients with severe renal impairment; manifestations included neurological outcomes (e.g., encephalopathy, seizures, myoclonus, nonconvulsive status epilepticus).¹ ³ ¹⁸ ³⁰ ³² Adjust ceftriaxone dosage appropriately in patients with severe renal impairment.¹ ³ ¹⁸ ³⁰ ³²

Common Adverse Effects

Local reactions at the administration site (warmth, tightness, induration, phlebitis); hematologic effects (eosinophilia, thrombocytosis, leukopenia); hypersensitivity reactions.¹

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test	Interaction	Comments
Aminoglycosides	Nephrotoxicity reported with concomitant use of some cephalosporins and aminoglycosides¹ In vitro evidence of additive or synergistic antibacterial activity against some Enterobacteriaceae and Pseudomonas aeruginosa³⁴ ³⁶ ¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁵⁸
Anticoagulants (warfarin)	Possible increased risk of bleeding if used concomitantly with vitamin K antagonists¹ ¹⁸ ³⁰ ³² Increased INR reported in patients receiving warfarin and ceftriaxone concomitantly⁶⁸⁸ ⁶⁸⁹	Warfarin: Monitor coagulation parameters frequently during and after ceftriaxone treatment; adjust anticoagulant dosage as needed¹ ¹⁸ ³⁰ ³²
Chloramphenicol	Antagonism reported in vitro¹ ³ ¹⁸ ³⁰ ³²
Probenecid	Concomitant use of oral probenecid (500 mg daily) does not appear to affect the pharmacokinetics of ceftriaxone,¹ ³ ¹⁸ ³⁰ ³² ¹⁰⁴ ¹⁷⁰ ¹⁷⁹ presumably because ceftriaxone is excreted principally by glomerular filtration and nonrenal mechanisms⁸⁴ ¹⁰⁴ ¹⁷⁰ ¹⁷⁹ Higher dosages of oral probenecid (1 or 2 g daily) may partially block biliary secretion of ceftriaxone as well as displace the drug from plasma proteins resulting in increased clearance and decreased half-life of ceftriaxone¹⁷⁹
Quinolones	In vitro evidence of synergistic antibacterial effect between ceftriaxone and trovafloxacin (not commercially available in the US) against penicillin-susceptible and penicillin-resistant S. pneumoniae, including some strains resistant to ceftriaxone alone⁴⁸⁵	Clinical importance unknown⁴⁸⁵
Tests for glucose	Possible false-positive reactions in nonenzymatic urine glucose tests (e.g., Clinitest, Benedict’s solution)¹ ¹⁸ ³² ¹⁰⁰ Possible falsely low estimated blood glucose with some blood glucose monitoring systems¹ ¹⁸ ³²	Use urinary glucose tests based on enzymatic glucose oxidase reactions (e.g., Clinistix, Tes-Tape)¹ ¹⁸ ³² ¹⁰⁰ Consult manufacturer's instructions for glucose monitoring systems; use alternative testing methods if needed¹ ¹⁸ ³²

cefTRIAXone Pharmacokinetics

Absorption

Bioavailability

Not appreciably absorbed from GI tract; must be given parenterally.¹⁷⁰

Appears to be completely absorbed following IM administration in healthy adults;¹ ⁵² ⁵⁷ ⁸⁴ peak serum concentrations attained 1.5–4 hours after the dose.¹ ⁴⁸ ⁵² ⁵⁷

Multiple-dose studies in healthy adults indicate serum concentrations at steady state on day 4 of therapy are 15–36% higher than serum concentrations attained with a single dose.¹ ⁵⁶ ⁸⁴ ¹⁷⁰

Distribution

Extent

Following IM or IV administration, widely distributed into body tissues and fluids, including the gallbladder,¹ ⁸⁴ ¹⁰⁴ lungs,¹⁰⁴ ¹⁵⁹ ³⁵⁵ bone,⁶⁸ ¹⁰⁴ ⁴⁸⁹ heart,³⁷⁸ bile,¹ ⁶⁹ ⁷² ⁸⁴ ¹⁰⁴ prostate adenoma tissue,¹⁵⁷ uterine tissue,⁷¹ ¹⁰⁴ atrial appendage,⁶⁸ sputum,¹⁰⁴ tears,¹⁰⁴ middle ear fluid,¹ ⁴⁸⁸ and pleural,¹⁰⁴ peritoneal,¹⁰⁴ synovial,¹⁰⁴ ascitic,¹⁰⁴ ¹⁰⁵ and blister¹⁰⁴ ¹⁷⁰ fluids.

Generally diffuses into CSF following IM or IV administration;¹ ⁶⁰ ⁶¹ ⁶² ⁶⁴ ⁶⁵ ⁸⁴ ¹⁰⁴ ¹⁰⁵ ¹⁰⁷ ¹⁴¹ ¹⁷⁰ CSF concentrations are higher in patients with inflamed meninges.⁶⁵ ⁸⁴ ¹⁰⁴

Crosses the placenta and is distributed into amniotic fluid.⁶⁶ ⁸⁴ ¹⁰⁴ Distributed into milk.⁶⁶ ⁸⁴ ¹⁰⁴

Plasma Protein Binding

Degree of protein binding is concentration dependent; decreases nonlinearly with increasing concentrations of the drug.¹ ⁴⁹ ⁵⁰ ⁵⁴ ⁵⁵ ⁵⁶ ⁵⁹ ⁸⁴ ¹⁰⁴ ¹⁰⁵ ¹⁶² ¹⁷⁰ ²⁰⁵ Principally binds to albumin.⁸⁴ ¹⁰⁴ ¹⁷⁰

93–96% bound to plasma proteins at <70 mcg/mL,¹ ⁸⁴ ¹⁰⁵ ¹⁷⁰ ²⁰⁵ 84–87% at 300 mcg/mL,¹ ⁸⁴ ¹⁰⁵ ¹⁷⁰ and ≤58% at 600 mcg/mL.¹⁷⁰

Protein binding is lower in neonates and children than in adults because of decreased plasma albumin concentrations in this age group.⁵⁹ ¹⁰⁴ ¹⁷⁸ Also less protein bound in patients with renal or hepatic impairment as the result of decreased plasma albumin concentrations or displacement from protein binding sites by bilirubin and other endogenous compounds that may accumulate.⁷⁴ ⁷⁶

Elimination

Metabolism

Metabolized to a small extent in the intestines after biliary elimination.⁸⁴

Elimination Route

Eliminated by renal and nonrenal mechanisms.¹ ⁷² ⁸⁴ ¹⁰⁴ ¹⁷⁰

33–67% eliminated in urine by glomerular filtration as unchanged drug; remainder eliminated in feces via bile as unchanged drug and microbiologically inactive metabolites.⁷² ⁸⁴ ¹⁰⁴ ¹⁷⁰

Half-life

Adults with normal renal and hepatic function: Distribution half-life 0.12–0.7 hours⁵⁵ ⁵⁷ ¹⁷² and elimination half-life 5.4–10.9 hours.¹ ⁴⁸ ⁵¹ ⁵² ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ⁵⁷ ⁵⁸ ⁸⁴ ¹⁰⁴ ¹⁰⁵ ¹⁷⁰ ¹⁷²

Neonates: 16.2 hours in those 1–4 days of age and 9.2 hours in those 9–30 days of age.⁶⁰

Children 2–42 months of age: Distribution half-life 0.25 hours and elimination half-life 4 hours.⁶¹

Special Populations

Patients with moderately impaired renal function: Elimination half-life averages 10–16 hours.⁴⁸ ⁷⁷ ⁸⁵ ¹⁰⁴ ¹⁷⁰

Elimination half-life averages 12.2–18.2 hours in patients with creatinine clearances <5 mL/min⁴⁸ ⁷³ ⁷⁴ ⁷⁵ ⁷⁷ and 15–57 hours in uremic patients.⁷³ ⁷⁴ ⁷⁷ ¹⁰⁴ ¹⁷⁰

Stability

Storage

Parenteral

Powder for IM Injection or IV Infusion

20–25°C; protect from light.¹ ¹⁸ No need to protect reconstituted solutions from normal light.¹ ¹⁸

IV solutions containing 10–40 mg/mL prepared using sterile water, 0.9% sodium chloride, or 5 or 10% dextrose are stable for 3 days at room temperature (25°C) or 10 days refrigerated at 4°C.¹ ¹⁸ Those containing 10–40 mg/mL prepared using 5% dextrose and 0.45 or 0.9% sodium chloride are stable for 2 days at 25°C; do not refrigerate.¹ ¹⁸

IM solutions containing 100 mg/mL prepared using sterile water, 0.9% sodium chloride, or 5% dextrose are stable for 2 days at room temperature (25°C) or 10 days refrigerated at 4°C;¹ those containing 250 or 350 mg/mL are stable for 24 hours at 25°C or 3 days at 4°C.¹

IM solutions containing 100 mg/mL prepared using 1% lidocaine hydrochloride (without epinephrine) or bacteriostatic water (containing 0.9% benzyl alcohol) are stable for 24 hours at 25°C or 10 days at 4°C; those containing 250 or 350 mg/mL are stable for 24 hours at 25°C or 3 days at 4°C.¹

For Injection, for IV Infusion

Pharmacy bulk package: 20–25°C; protect from light.¹⁸ Following reconstitution, further dilute in compatible IV infusion solution without delay; discard unused portions of reconstituted solution after 4 hours.¹⁸ No need to protect reconstituted solution from normal light.¹⁸

ADD-Vantage vials: 20–25°C; protect from light.³² Following reconstitution, IV solutions containing 10–40 mg/mL are stable for 2 days at room temperature (25°C) or 10 days refrigerated at 4°C.³²

Duplex drug delivery: 20–25°C (may be exposed to 15–30°C).³ Following reconstitution (activation), use within 24 hours if stored at room temperature or within 7 days if stored in refrigerator; do not freeze.³

Injection (Frozen) for IV Infusion

-20° C or lower.³⁰ Thawed solutions are stable for 48 hours at room temperature (25°C) or 21 days under refrigeration (5°C).³⁰

Do not refreeze after thawing.³⁰

Actions and Spectrum

Based on spectrum of activity, classified as a third generation cephalosporin.¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹⁶² ¹⁶⁵ ¹⁷⁰ Usually less active in vitro against susceptible staphylococci than first generation cephalosporins, but has expanded spectrum of activity against gram-negative bacteria compared with first and second generation cephalosporins.⁴ ⁷ ²³ ³⁶ ³⁷ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁷⁰
Usually bactericidal.¹ ³ ⁴ ¹⁸ ²² ³⁰ ³² ⁴¹ ¹⁰⁴
Like other β-lactam antibiotics, antibacterial activity results from inhibition of bacterial cell wall synthesis.¹ ³ ¹⁸ ³⁰ ³² ¹⁰⁴
Spectrum of activity includes many gram-positive aerobic bacteria, many gram-negative aerobic bacteria, and some anaerobic bacteria; inactive against Chlamydia, fungi, and viruses.¹
Gram-positive aerobes: Active in vitro and in clinical infections against Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci; GAS), Staphylococcus aureus (including penicillinase-producing strains), S. epidermidis, and viridans streptococci.¹ ⁷ ¹⁴ ²² ²³ ³⁶ ³⁷ ⁴⁵ ¹⁰⁴ ¹⁰⁶ ¹⁰⁸ ¹²¹ ¹²³ Also active in vitro against S. agalactiae (group B streptococci; GBS).¹ ⁷ ⁹ ¹⁴ ²² ²³ ⁴³ ⁴⁵ ¹⁰⁴ ¹⁰⁶ ¹²⁸ Methicillin-resistant (oxacillin-resistant) staphylococci and most enterococci (e.g., Enterococcus faecalis) are resistant.¹ ⁶ ⁷ ¹⁴ ¹⁶ ²² ²³ ³⁶ ³⁷ ³⁹ ⁴⁵ ⁴⁶ ¹⁰⁴ ¹⁰⁶ ¹²⁰
Strains of staphylococci resistant to penicillinase-resistant penicillins (methicillin-resistant [oxacillin-resistant] staphylococci) should be considered resistant to ceftriaxone, although results of in vitro susceptibility tests may indicate that the organisms are susceptible to the drug.¹⁶⁶
Active in vitro against some strains of Nocardia,⁵²⁶ ⁵²⁷ ⁶⁹⁸ including some strains of N. asteroides⁵²⁷ ⁶⁹⁸ and N. brasiliensis.⁵²⁶ Resistance to ceftriaxone reported in some environmental isolates of N. asteroides⁵²⁷ and clinical isolates of N. farcinica.⁷⁰¹
Gram-negative aerobes: Active in vitro and in clinical infections against Acinetobacter calcoaceticus,¹ Enterobacter (including E. aerogenes,¹ E. cloacae),¹ Escherichia coli, Haemophilus influenzae (including ampicillin-resistant and β-lactamase-producing strains),¹ H. parainfluenzae,¹ Klebsiella pneumoniae,¹ K. oxytoca,¹ Moraxella catarrhalis (including β-lactamase-producing strains),¹ Morganella morganii,¹ Neisseria gonorrhoeae,¹ N. meningitidis,¹ Proteus mirabilis,¹ P. vulgaris,¹ Pseudomonas aeruginosa¹ , and Serratia marcescens.¹ Also active in vitro against Bartonella,³⁵⁴ Capnocytophaga,⁴⁶¹ ⁴⁶² Citrobacter,¹ Providencia,¹ Salmonella,¹⁴ ¹⁷ ³⁷ ⁴⁰ and Shigella.¹ ⁴ ¹⁴ ³⁶ ³⁷ ¹⁰⁶ Less active than ceftazidime against Ps. aeruginosa.¹⁰ ¹⁰¹ ¹⁰⁶
Anaerobes: Active in vitro and in clinical infections against Clostridium (except Clostridioides difficile)¹ ¹⁶ ¹⁹ ²² ²³ ³⁶ and Peptostreptococcus.¹ ⁷ ⁸ ¹⁶ ¹⁹ ²² Also active in vitro against Prevotella¹ and Porphyromonas melaninogenicus.¹ Most strains of Bacteroides fragilis are resistant.⁶ ⁷ ⁸ ¹⁴ ¹⁶ ¹⁹ ²² ³⁶
Spirochetes: Has some activity against Treponema pallidum when tested in a rabbit model.¹⁷³ Active in vitro against Borrelia burgdorferi, causative agent of Lyme disease.²⁰⁷ ²⁸³ ²⁸⁴ ²⁸⁵ ³⁴⁰ ³⁴¹ Active in vitro against Leptospira, including L. interrogans and L. weilii.⁶⁹⁶

Advice to Patients

Advise patients that antibacterials (including ceftriaxone) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹ ³ ¹⁸ ³⁰ ³²
Importance of completing full course of therapy, even if feeling better after a few days.¹ ³ ¹⁸ ³⁰ ³²
Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with ceftriaxone or other antibacterials in the future.¹ ³ ¹⁸ ³⁰ ³²
Advise patients that allergic reactions, including serious allergic reactions, can occur and that serious reactions require immediate treatment and discontinuance of ceftriaxone.³ Importance of informing clinicians of any previous allergic reactions to ceftriaxone, cephalosporins, penicillins, or similar antibacterials.³
Inform patients that adverse neurologic reactions can occur with ceftriaxone and of the importance of immediately informing a healthcare provider of any neurologic signs and symptoms, including encephalopathy (disturbance of consciousness including confusion, somnolence, and lethargy), myoclonus, nonconvulsive status epilepticus, and seizures.¹ ³ ¹⁸ ³⁰ In such situations, immediate treatment, dosage adjustment, or discontinuance of the drug is indicated.¹ ³ ¹⁸ ³⁰
Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ ³ ³⁰ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹ ³ ³⁰
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹
Advise patients to inform their clinician if they are or plan to become pregnant or plan to breast-feed.¹
Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

cefTRIAXone Sodium
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	250 mg (of ceftriaxone)*	cefTRIAXone for Injection
		500 mg (of ceftriaxone)*	cefTRIAXone for Injection
		1 g (of ceftriaxone)*	cefTRIAXone for Injection
		2 g (of ceftriaxone)*	cefTRIAXone for Injection
	For injection, for IV infusion	1 g (of ceftriaxone)*	cefTRIAXone ADD-Vantage	Hospira
			cefTRIAXone for Injection, for IV Infusion (available in dual-chambered Duplex drug delivery system with 3.74% dextrose injection)	B Braun
			cefTRIAXone for Injection, for IV Infusion
		2 g (of ceftriaxone)*	cefTRIAXone ADD-Vantage	Hospira
			cefTRIAXone for Injection, for IV Infusion (available in dual-chambered Duplex drug delivery system with 2.22% dextrose injection)	B Braun
			cefTRIAXone for Injection, for IV Infusion
		10 g (of ceftriaxone) pharmacy bulk package*	cefTRIAXone for Injection, for IV Infusion
		100 g (of ceftriaxone) pharmacy bulk package*	cefTRIAXone for Injection, for IV Infusion

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

cefTRIAXone Sodium in Dextrose
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection (frozen), for IV infusion	20 mg (of ceftriaxone) per mL (1 g) in 3.8% Dextrose*	cefTRIAXone Iso-osmotic in Dextrose Injection (Galaxy [Baxter])
		40 mg (of ceftriaxone) per mL (2 g) in 2.4% Dextrose*	cefTRIAXone Iso-osmotic in Dextrose Injection (Galaxy [Baxter])

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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3. B Braun Medical Inc. Ceftriaxone for injection and dextrose injection in Duplex container, for intravenous use prescribing information. Bethlehem, PA; 2022 Jan.

4. Hall MJ, Westmacott D, Wong-Kai-In P. Comparative in-vitro activity and mode of action of ceftriaxone (Ro 13-9904), a new highly potent cephalosporin. J Antimicrob Chemother. 1981; 8:193-203. https://pubmed.ncbi.nlm.nih.gov/6270051

6. Pierson CL, Schaberg DR, Fekety FR et al. In-vitro activity of SCH 29482, MK 0787, ceftriaxone and seven other antimicrobials against 840 separate clinical isolates. J Antimicrob Chemother. 1982; 9(Suppl C):79-89. https://pubmed.ncbi.nlm.nih.gov/6277844

7. Shannon K, King A, Warren C et al. In vitro antibacterial activity and susceptibility of the cephalosporin Ro 13-9904 to beta-lactamases. Antimicrob Agents Chemother. 1980; 18:292-8. https://pubmed.ncbi.nlm.nih.gov/6969574

8. Rolfe RD, Finegold SM. Comparative in vitro activity of ceftriaxone against anaerobic bacteria. Antimicrob Agents Chemother. 1982; 22:338-41. https://pubmed.ncbi.nlm.nih.gov/6100430

9. Bradsher RW, Ulmer WC. Beta-lactam antibiotic susceptibility of bacteria responsible for neonatal meningitis. Chemotherapy. 1983; 29:213-7. https://pubmed.ncbi.nlm.nih.gov/6409519

10. Dibb WL, Kjellevold VA, Digranes A. Pseudomonas aeruginosa and Acinetobacter calcoaceticus: in vitro susceptibility of 150 clinical isolates to five β-lactam antibiotics and tobramycin. Chemotherapy. 1983; 29:332-6. https://pubmed.ncbi.nlm.nih.gov/6311491

14. Clarke AM, Zemcov SJV. Ro 13-9904 and GR 20263, two new cephalosporins with broad-spectrum activity: an in vitro comparison with other β-lactam antibiotics. J Antimicrob Chemother. 1981; 7:515-20. https://pubmed.ncbi.nlm.nih.gov/6790506

16. Heard ML, Bawdon RE, Hemsell DL et al. Susceptibility profiles of potential aerobic and anaerobic pathogens isolated from hysterectomy patients. Am J Obstet Gynecol. 1984; 149:133-43. https://pubmed.ncbi.nlm.nih.gov/6562855

17. Preblud SR, Gill CJ, Campos JM. Bactericidal activities of chloramphenicol and eleven other antibiotics against Salmonella spp. Antimicrob Agents Chemother. 1984; 25:327-30. https://pubmed.ncbi.nlm.nih.gov/6372681

18. Hospira, Inc. Ceftriaxone sodium for injection (pharmacy bulk package) prescribing information. Lake Forest, IL; 2022 Mar.

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40. Chau PY, Ng WS, Ling J et al. In vitro susceptibility of Salmonella to various antimicrobial agents, including a new cephalosporin, Ro 13-9904. Antimicrob Agents Chemother. 1981; 19:8-11. https://pubmed.ncbi.nlm.nih.gov/7247363

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48. Meyers BR, Srulevitch ES, Jacobson J et al. Crossover study of the pharmacokinetics of ceftriaxone administered intravenously or intramuscularly to healthy volunteers. Antimicrob Agents Chemother. 1983; 24:812-4. https://pubmed.ncbi.nlm.nih.gov/6318657

49. McNamara PJ, Gibaldi M, Stoeckel K. Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding. Part I. Theoretical considerations. Eur J Clin Pharmacol. 1983; 25:399-405. https://pubmed.ncbi.nlm.nih.gov/6313379

50. McNamara PJ, Gibaldi M, Stoeckel K. Volume of distribution terms for a drug (ceftriaxone) exhibiting concentration-dependent protein binding. Part II. Physiological significance. Eur J Clin Pharmacol. 1983; 25:407-12. https://pubmed.ncbi.nlm.nih.gov/6313380

51. McNamara PJ, Stoeckel K, Ziegler WH. Pharmacokinetics of ceftriaxone following intravenous administration of a 3 g dose. Eur J Clin Pharmacol. 1982; 22:71-5. https://pubmed.ncbi.nlm.nih.gov/6284519

52. Delsignore R, Baroni CM, Crotti G et al. Absolute bioavailability of ceftriaxone after intramuscular administration to healthy volunteers. Chemotherapy. 1983; 29:157-62. https://pubmed.ncbi.nlm.nih.gov/6307601

53. Luderer JR, Patel IH, Durkin J et al. Age and ceftriaxone kinetics. Clin Pharmacol Ther. 1984; 35:19-25. https://pubmed.ncbi.nlm.nih.gov/6317271

54. Stoeckel K, McNamara PJ, Brandt R et al. Effects of concentration-dependent plasma protein binding on ceftriaxone kinetics. Clin Pharmacol Ther. 1981; 29:650-7. https://pubmed.ncbi.nlm.nih.gov/7053242

55. Patel IH, Chen S. Parsonnet M et al. Pharmacokinetics of ceftriaxone in humans. Antimicrob Agents Chemother. 1981; 20:634-41. https://pubmed.ncbi.nlm.nih.gov/6275779

56. Pollock AA, Tee PE, Patel IH et al. Pharmacokinetic characteristics of intravenous ceftriaxone in normal adults. Antimicrob Agents Chemother. 1982; 22:816-23. https://pubmed.ncbi.nlm.nih.gov/6295268

57. Patel IH, Weinfeld RE, Konikoff J et al. Pharmacokinetics and tolerance of ceftriaxone in humans after single-dose intramuscular administration in water and lidocaine diluents. Antimicrob Agents Chemother. 1982; 21:957-62. https://pubmed.ncbi.nlm.nih.gov/6287931

58. Salvador P, Smith RG, Weinfeld RE et al. Clinical pharmacology of ceftriaxone in patients with neoplastic disease. Antimicrob Agents Chemother. 1983; 23:583-8. https://pubmed.ncbi.nlm.nih.gov/6305263

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