CLAFORAN (Brand for CEFOTAXIME SODIUM)

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

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Reconstitution
-Conventional vials: Reconstitute 500 mg, 1 g, or 2 g vial with 10 ml of sterile water for injection to give concentrations of 50, 95, or 180 mg/ml, respectively.
-Storage: Reconstituted solutions are stable for 12 hours (2 g vial) or 24 hours (500 mg or 1 g vial) at room temperature or 7 days under refrigeration.
-Pharmacy bulk vials: Reconstitute 10 gram vial with 47 or 97 ml of a compatible solution (e.g., NS, D5W) to give concentrations of 200 mg/ml or 100 mg/ml, respectively. Withdraw appropriate dose and dilute in a compatible IV solution.
-Storage: Reconstituted pharmacy bulk vials must be used within 4 hours after initial entry into the vial.
-ADD-Vantage vials: For IV infusion only. Reconstitute only with NS or D5W in the appropriate 50 or 100 ml flexible diluent container.
-Storage: Reconstituted ADD-Vantage solutions are stable for 24 hours at room temperature.
-Infusion bottles: Reconstitute bottles containing 1 or 2 g with 50-100 ml of NS or D5W.
-Storage: Reconstituted infusion bottles are stable for 24 hours at room temperature or 10 days under refrigeration.

Dilution
-IV push: For neonates, a 100 mg/ml concentration is recommended. For other populations, concentrations of 50-200 mg/ml may be used.

-Intermittent IV infusion: May further dilute in compatible IV solution; concentrations of 10-60 mg/ml are commonly used in clinical practice. -ISMP recommended concentration for intermittent infusion in neonates is 100 mg/ml.

-Storage: Diluted solutions are stable for 24 hours at room temperature or 5 days under refrigeration.

Thawing Frozen Pre-mixed Bags
-Frozen GALAXY bags: Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation
-Storage: The thawed solution remains stable for 10 days under refrigeration or for 24 hours at room temperature. Do not refreeze.

IV Push
-Inject directly into a vein over 3-5 minutes or slowly into the tubing of a freely-flowing compatible IV solution. Cefotaxime can be administered by slow IV push to neonates; however, infusion over 30 minutes is preferred.
-Do not inject over a period of less than 3 minutes; rapid bolus injections (< 60 seconds) have been associated with potentially life-threatening arrhythmias in post-marketing surveillance.

Intermittent IV Infusion
-Infusion over 30 minutes is recommended for neonates; a range of 10-30 minutes has also been recommended for pediatric patients in general.

Intramuscular Administration
Reconstitution
-Reconstitute each vial with the following volumes of Sterile Water for Injection (SWI) or Bacteriostatic Water for Injection (for neonates, use SWI to avoid the administration of benzyl alcohol):-500 mg vial - reconstitute with 2 mL (final concentration = 230 mg/mL)
-1 g vial - reconstitute with 3 mL (final concentration = 300 mg/mL)
-2 g vial - reconstitute with 5 mL (final concentration = 330 mg/mL)

-Storage: Reconstituted solutions are stable for 12 hours at room temperature or 7 days under refrigeration.

Intramuscular Injection
-Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]). When multiple IM injections are necessary, rotate administration sites.
-In general, IM administration of antibiotics in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.
-For children and adolescents, when a 2 gram dose is given IM, each dose should be divided and administered in different sites.

Rapid administration (< 60 seconds) of cefotaxime through a central venous catheter can result in potentially life-threatening arrhythmias. Avoid rapid bolus intravenous administration of cefotaxime.

A local injection site reaction has been reported in 4.3% of patients receiving cefotaxime. Reactions include injection site inflammation after intravenous administration and pain, induration and tenderness after intramuscular administration.

Hematologic adverse reactions that have been reported with cefotaxime include agranulocytosis, eosinophilia (2.4%), transient leukopenia (< 1%), neutropenia (< 1%), thrombocytopenia, pancytopenia, and bone marrow failure. Rare cases of hemolytic anemia have also been reported. Positive direct Coombs' test has been reported in some patients receiving cefotaxime and other cephalosporins. If hematological testing is done in patients receiving cephalosporins, a positive Coombs' test should be considered as being possibly due to the antibiotic. Aplastic anemia and bleeding (hemorrhage) have been reported with cephalosporin antibiotics in general.

Interstitial nephritis, a hypersensitivity reaction, has been reported with many of the cephalosporins including cefotaxime. Transient elevations in BUN (< 1%) and creatinine (azotemia) have also been occasionally reported. Renal failure (unspecified) has been reported in post-marketing surveillance. Other hypersensitivity reactions reported with cefotaxime, as well as with other cephalosporins, include anaphylactoid reactions (anaphylaxis), erythema multiforme, fever (2.4%), maculopapular rash (2.4%), pruritus (2.4%), Stevens-Johnson syndrome, toxic epidermal necrolysis, and urticaria. Angioedema has also been reported with cephalosporin use.

Seizures are rare, but a serious complication of cephalosporin therapy. More commonly associated with penicillins, the epileptogenic properties of both penicillins and cephalosporins are thought to be related to their beta-lactam ring. High doses and renal impairment are associated with an increased risk of seizures. Encephalopathy may occur, especially in patients with renal impairment given high doses. Headache (< 1%) and dizziness have also been reported with cefotaxime.

Common gastrointestinal adverse effects reported with cefotaxime include nausea/vomiting, colitis, and diarrhea, all occurring in 1.4% of patients. Other reported adverse effects include elevated hepatic enzymes (less than 1%), elevated LDH (less than 1%), and malaise. Hepatic impairment, including cholestasis, jaundice, and hepatitis, has also been reported with cefotaxime.

Cefotaxime has been associated with acute generalized exanthematous pustulosis (AGEP). The non-follicular, pustular, erythematous rash starts suddenly and is associated with fever above 38 degrees C. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days.

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

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

The administration of cefotaxime may result in a false-positive reaction for glucose in the urine in patients with diabetes mellitus using Clinitest tablets, Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix) be used.

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

Cefotaxime should be used with caution in patients with renal disease or renal impairment since the drug is eliminated via renal mechanisms. Dosages may need to be reduced in these patients. Cephalosporin-class antibiotics have been associated with seizures, especially in patients with renal impairment given unadjusted doses.

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

All cephalosporins, including cefotaxime, may rarely cause hypothrombinemia and have the potential to cause bleeding. Cephalosporins which contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency) since these patients are at a higher risk for developing bleeding complications.

Rapid administration (< 60 seconds) of cefotaxime through a central venous catheter can result in infusion-related reactions that include potentially life-threatening arrhythmias. Avoid rapid bolus intravenous administration of cefotaxime.

Use cefotaxime with caution in patients with hematological disease. Hematological abnormalities, such as leukopenia, neutropenia, thrombocytopenia, granulocytopenia, and more rarely, bone marrow failure, pancytopenia, or agranulocytosis, may occur during treatment with cefotaxime. Monitor blood counts for courses of therapy lasting longer than 10 days. Treatment discontinuation should be considered in cases of abnormal results.

Description: Cefotaxime is a parenteral third-generation cephalosporin. As with other agents in this group, cefotaxime is more active and has a broader spectrum against gram-negative species than earlier generations of cephalosporins. Although it is less active against gram-positive bacteria than first-generation agents, cefotaxime is often an effective agent for the treatment of infections due to methicillin-sensitive S. aureus and susceptible strains of nonenterococcal streptococci. The spectrum of activity of cefotaxime is similar to that of ceftizoxime and ceftriaxone; none of these cephalosporins is effective for the treatment of infections due to Pseudomonas aeruginosa. A disadvantage of cefotaxime is that it must be dosed multiple times daily compared with the usual once daily administration of ceftriaxone. Cefotaxime is commonly used in neonates for enteric gram-negative meningitis and sepsis. Cefotaxime is also used in the treatment of serious bacteremia, pneumonia, intra-abdominal infections, bone and joint infections, urinary tract infections, and skin and skin structure infections. Cefotaxime is FDA-approved for use in pediatric patients as young as neonates.

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

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

For the treatment of bacteremia and sepsis:
-for the treatment of bacteremia:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day (Max: 8 g/day) IV or IM divided every 6 to 8 hours.
Children and Adolescents weighing 50 kg or more: 2 g IV every 6 to 8 hours for severe infections and 2 g IV every 4 hours for life-threatening infections.
-for the treatment of sepsis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.
Children and Adolescents weighing 50 kg or more: 2 g IV every 4 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the treatment of meningitis and ventriculitis:
NOTE: For gonococcal meningitis, see gonococcal infections. For neurologic Lyme infections, see Lyme borreliosis.
-for the treatment of meningococcal meningitis or ventriculitis as well as meningitis or ventriculitis due to H. influenzae:
Intravenous dosage:
Neonates 0 to 7 days: 50 mg/kg/dose IV every 8 to 12 hours for 7 days.
Neonates older than 7 days: 50 mg/kg/dose IV every 6 to 8 hours for 7 days.
Infants, Children, and Adolescents weighing less than 50 kg: 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 7 days.
Children and Adolescents weighing 50 kg or more: 2 g IV every 4 to 6 hours for 7 days.
-for the treatment of pneumococcal meningitis or ventriculitis:
Intravenous dosage:
Neonates 0 to 7 days: 50 mg/kg/dose IV every 8 to 12 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL.
Neonates older than 7 days: 50 mg/kg/dose IV every 6 to 8 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL.
Infants, Children, and Adolescents weighing less than 50 kg: 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL.
Children and Adolescents weighing 50 kg or more: 2 g IV every 4 to 6 hours for 10 to 14 days; consider the addition of rifampin if dexamethasone is also given or ceftriaxone MIC is more than 2 mcg/mL.
-for the treatment of meningitis or ventriculitis due to aerobic gram-negative rods:
Intravenous dosage:
Neonates 0 to 7 days: 50 mg/kg/dose IV every 8 to 12 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Neonates older than 7 days: 50 mg/kg/dose IV every 6 to 8 hours for 2 weeks beyond the first sterile CSF culture or at least 21 days, whichever is longer.
Infants, Children, and Adolescents weighing less than 50 kg: 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 10 to 21 days.
Children and Adolescents weighing 50 kg or more: 2 g IV every 4 to 6 hours for 10 to 21 days.
-for the treatment of meningitis or ventriculitis due to C. acnes*:
Intravenous dosage:
Infants, Children, and Adolescents: 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 10 to 14 days.
-for the treatment of meningitis due to S. agalactiae*:
Intravenous dosage:
Neonates 0 to 7 days: 50 mg/kg/dose IV every 8 to 12 hours for 14 to 21 days.
Neonates older than 7 days: 50 mg/kg/dose IV every 6 to 8 hours for 14 to 21 days.
Infants, Children, and Adolescents: 200 to 300 mg/kg/day (Max: 12 g/day) IV divided every 4 to 6 hours for 14 to 21 days.

For the treatment of neurologic Lyme disease*, including Lyme meningitis*, cranial neuropathy*, and radiculoneuropathy/radiculoneuritis*:
-for the treatment of neurologic Lyme disease* without parenchymal involvement, including Lyme meningitis*, cranial neuropathy*, and radiculoneuropathy/radiculoneuritis*:
Intravenous dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 6 g/day) IV divided every 6 to 8 hours until clinical improvement, then switch to oral stepdown therapy for a total of 14 to 21 days. For acutely ill patients or prior to confirmation of Lyme neuroborreliosis, IV therapy is preferred with appropriate stepdown to oral treatment.
-for the treatment of neurologic Lyme disease* with parenchymal involvement of the brain or spinal cord:
Intravenous dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 6 g/day) IV divided every 6 to 8 hours for 14 to 28 days. IV therapy is preferred.

For the treatment of gonorrhea, including ophthalmia neonatorum*:
-for the treatment of uncomplicated gonorrhea, including rectal infection in females, cervicitis, and urethritis:
Intramuscular dosage:
Children and Adolescents weighing 50 kg or more: Not recommended by guidelines. The FDA-approved dosage is 500 mg IM as a single dose.
-for the treatment of gonococcal proctitis:
Intramuscular dosage:
Children and Adolescents weighing 50 kg or more: Not recommended by guidelines. The FDA-approved dosage is 1 g IM as a single dose.
-for the treatment of gonococcal arthritis* and arthritis-dermatitis syndrome*:
Intravenous dosage:
Adolescents: 1 g IV every 8 hours for 7 days as an alternative. If treating for arthritis-dermatitis syndrome, may switch to an oral agent 24 to 48 hours after clinical improvement for a total of at least 7 days.
-for the treatment of gonococcal scalp abscesses and disseminated gonococcal infections in neonates*:
Intravenous or Intramuscular dosage:
Neonates: 25 mg/kg/dose IV or IM every 12 hours for 7 days as an alternative.
-for the treatment of neonatal gonococcal meningitis*:
Intravenous dosage:
Neonates: 25 mg/kg/dose IV or IM every 12 hours for 10 to 14 days as an alternative.
-for the treatment of ophthalmia neonatorum* due to N. gonorrhoeae:
Intravenous or Intramuscular dosage:
Neonates: 100 mg/kg/dose IV or IM as a single dose for neonates unable to receive ceftriaxone.

For the treatment of multidrug-resistant severe typhoid fever* and quinolone-resistant severe typhoid fever*:
Intravenous dosage:
Infants, Children, and Adolescents: 40 to 80 mg/kg/day (Max: 4 g/day) IV divided every 8 to 12 hours for 10 to 14 days.

For the treatment of leptospirosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 150 to 180 mg/kg/day (Max: 4 g/day) IV divided every 8 hours for 7 days as alternative therapy for severe disease.

For the treatment of lower respiratory tract infections (LRTIs), including pneumonia and community-acquired pneumonia (CAP):
-for the treatment of nonspecific lower respiratory tract infections (LRTIs) and pneumonia:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose).
Children and Adolescents weighing 50 kg or more: 1 g IV or IM every 12 hours for uncomplicated infections, 1 to 2 g IV or IM every 8 hours for moderate to severe infections, 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. Max: 12 g/day.
-for the treatment of community-acquired pneumonia (CAP):
Intravenous dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 5 to 7 days. Guidelines recommend empiric therapy with cefotaxime for hospitalized patients who are not fully immunized, in regions where local epidemiology of invasive pneumococcal strains documents high-level penicillin resistance, and for life-threatening infection. Consider combination therapy with a macrolide for suspected atypical pneumonia or with clindamycin or vancomycin for suspected infection due to S. aureus.

For the treatment of acute bacterial sinusitis* in patients with severe infection requiring hospitalization:
Intravenous dosage:
Infants, Children, and Adolescents: 100 to 200 mg/kg/day IV divided every 6 hours (Max: 8 g/day) for 10 to 14 days.

For surgical infection prophylaxis* in patients undergoing liver transplantation:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 50 mg/kg IV or IM as a single dose (Max: 1 g/dose; 2 g/dose in obese patients) within 60 minutes prior to the surgical incision, in combination with ampicillin. Repeat dose intraoperatively 3 hours after preoperative dose if surgery still in progress. The duration should not exceed 24 hours.

For the treatment of infectious diarrhea and gastroenteritis, including salmonellosis*:
-for the empiric treatment of enteric bacterial infections* in persons living with HIV:
Intravenous dosage:
Adolescents: 1 g IV every 8 hours for 5 days. Routine use is not recommended.
-for the treatment of salmonellosis* in persons living with HIV:
Intravenous dosage:
Adolescents: 1 g IV every 8 hours for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, neonatal necrotizing enterocolitis, and peritoneal dialysis-related peritonitis*:
-for the general treatment of intraabdominal infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 50 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose).
Children and Adolescents weighing 50 kg or more: 1 to 2 g IV or IM every 8 hours for moderate to severe infections; 2 g IV every 6 to 8 hours for severe infections, and 2 g IV every 4 hours for life-threatening infections. The maximum dosage is 12 g/day.
-for the treatment of complicated community-acquired intraabdominal infections with adequate source control:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Cefotaxime is an option for necrotizing enterocolitis.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Cefotaxime is an option for necrotizing enterocolitis.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Cefotaxime is an option for necrotizing enterocolitis.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Cefotaxime is an option for necrotizing enterocolitis.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 200 mg/kg/day IV divided every 6 to 8 hours (Max: 2 g/dose) as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
Children and Adolescents weighing 50 kg or more: 1 to 2 g IV every 6 to 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of uncomplicated intraabdominal infections:
Intravenous dosage:
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 200 mg/kg/day IV divided every 6 to 8 hours (Max: 2 g/dose) as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
Children and Adolescents weighing 50 kg or more: 1 to 2 g IV every 6 to 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Infants, Children, and Adolescents: 30 mg/kg/dose (Max: 1 g/dose) intraperitoneally every 24 hours for 14 to 21 days.
Continuous Intraperitoneal dosage*:
Infants, Children, and Adolescents: 500 mg/L intraperitoneal loading dose, followed by 250 mg/L in each dialysate exchange. Treat for 14 to 21 days.

For the treatment of urinary tract infection (UTI), including pyelonephritis:
-for the treatment of nonspecific uncomplicated UTI:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants 1 month: 150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose).
-for the treatment of moderate to severe UTI, including pyelonephritis:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants 1 month: 150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 150 to 180 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 2 g/dose). Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

For the treatment of skin and skin structure infections, including necrotizing infections:
-for the treatment of unspecified uncomplicated skin infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 1 g/dose). The FDA-approved dose is 50 to 180 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose).
Children and Adolescents weighing 50 kg or more: 1 g IV or IM every 8 to 12 hours.
-for the treatment of unspecified moderate to severe skin infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day IV or IM divided every 8 hours (Max: 2 g/dose). The FDA-approved dose is 50 to 180 mg/kg/day IV or IM divided every 4 to 6 hours (Max: 2 g/dose); use the higher doses for more severe infections.
Children and Adolescents weighing 50 kg or more: 1 to 2 g IV or IM every 8 hours.
-for the treatment of unspecified life-threatening skin infections:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours.
Infants, Children, and Adolescents weighing less than 50 kg: 150 to 180 mg/kg/day IV divided every 8 hours (Max: 12 g/day). The FDA-approved dose is 50 to 180 mg/kg/day IV divided every 4 to 6 hours (Max: 2 g/dose); use the higher doses for more severe infections.
Children and Adolescents weighing more than 50 kg: 2 g IV every 4 hours.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Cefotaxime is recommended for mixed infections plus metronidazole or clindamycin.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Cefotaxime is recommended as for mixed infections plus metronidazole or clindamycin.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Cefotaxime is recommended for mixed infections plus metronidazole or clindamycin.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Cefotaxime is recommended as for mixed infections plus metronidazole or clindamycin.
Infants, Children, and Adolescents: 50 mg/kg/dose (Max: 2 g/dose) IV divided every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours. Cefotaxime is recommended for mixed infections plus metronidazole or clindamycin.

For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis:
-for the treatment of osteomyelitis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 150 to 200 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 3 to 11 months: 150 to 200 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents weighing less than 50 kg: 150 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Children and Adolescents weighing 50 kg or more: 2 g IV every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 7 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 150 to 200 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 3 to 11 months: 150 to 200 mg/kg/day IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents weighing less than 50 kg: 150 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Children and Adolescents weighing 50 kg or more: 2 g IV every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.

For the treatment of gynecologic infections, including endometritis, pelvic cellulitis, pelvic inflammatory disease (PID), and tubo-ovarian abscess*:
Intravenous or Intramuscular dosage:
Children and Adolescents weighing 50 kg or more: 1 to 2 g IV or IM every 8 hours for moderate to severe infections and 2 g IV every 6 to 8 hours for severe infections. Cefotaxime in combination with doxycycline may be effective for inpatient, intravenous treatment of PID; however, there is decreased anaerobic activity and the addition of metronidazole should be considered. Cefotaxime should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral doxycycline and metronidazole for a total of 14 days of therapy. Additionally, for outpatient PID therapy, cefotaxime may be administered IM with oral doxycycline and metronidazole for 14 days.

For the treatment of infective endocarditis*:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 13 days: 50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates younger than 32 weeks gestation and 14 days and older: 50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates 32 weeks gestation and older and 0 to 7 days: 50 mg/kg/dose IV every 12 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Infants: 150 to 180 mg/kg/day IV divided every 8 hours is the general dosage recommended by the American Academy of Pediatrics (AAP).
Children and Adolescents: 200 mg/kg/day IV divided every 6 hours (Max: 12 g/day). Guidelines recommend cefotaxime as a preferred therapy for 4 weeks for endocarditis caused by HACEK group organisms or for at least 6 weeks in combination with an aminoglycoside for other gram-negative microorganisms.

For gonorrhea prophylaxis* in high-risk neonates:
Intravenous or Intramuscular dosage:
Neonates: 100 mg/kg/dose IV or IM as a single dose for neonates unable to receive ceftriaxone and are at high risk for exposure (i.e., infants born to mothers at risk for gonococcal infection or with no prenatal care).

For the treatment of invasive vibriosis*:
Intravenous dosage:
Infants, Children, and Adolescents: 50 to 60 mg/kg/dose (Max: 2 g/dose) IV every 8 hours in combination with doxycycline for 7 to 14 days.

For the treatment of epiglottitis*:
Intravenous dosage:
Infants, Children, and Adolescents: 150 to 200 mg/kg/day (Max: 8 g/day) IV divided every 6 to 8 hours for 5 to 10 days.

Maximum Dosage Limits:
-Neonates
0 to 7 days: 100 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 150 mg/kg/day have been used off-label for meningitis.
8 days and older: 150 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 200 mg/kg/day have been used off-label for meningitis.
-Infants
180 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 300 mg/kg/day have been used off-label for meningitis.
-Children
Weighing less than 50 kg: 180 mg/kg/day IV/IM is FDA-approved maximum; however, doses up to 300 mg/kg/day (Max: 12 g/day) have been used off-label for meningitis.
Weighing 50 kg or more: 12 g/day IV/IM.
-Adolescents
12 g/day IV/IM.

Patients with Hepatic Impairment Dosing
Cefotaxime is metabolized by the liver to an active metabolite, desacetylcefotaxime. Dosage adjustments in patients with hepatic impairment without concomitant renal insufficiency are usually not necessary since cefotaxime has a high therapeutic index. However, specific guidelines for dosage adjustment in patients with hepatic impairment are not available.

Patients with Renal Impairment Dosing
The following dose adjustments are based on a usual recommended dose in children of 100 to 200 mg/kg/day divided every 8 hours.
CrCl more than 50 mL/minute/1.73 m2: no dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 8 to 12 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 24 hours.

Intermittent hemodialysis
35 to 70 mg/kg/dose IV every 24 hours, given after hemodialysis on dialysis days. Approximately 50% of the serum concentration of cefotaxime is removed during a standard hemodialysis session.

Peritoneal hemodialysis
35 to 70 mg/kg/dose IV every 24 hours.

Continuous renal replacement therapy (CRRT)
35 to 70 mg/kg/dose IV every 12 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Cefotaxime, like other beta-lactam antibiotics, is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cefotaxime as well as other cephalosporins and penicillins against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefotaxime's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor. Prevention of the autolysin response to beta-lactam antibiotic exposure through loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity. Resistance to beta-lactam antibiotics develops if there are changes in the PBPs, if cell wall permeability decreases, or if certain beta-lactamases are present. Cefotaxime retains activity against some beta-lactamase-producing isolates, including penicillinase and cephalosporinase; however, most extended spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to the drug.

Beta-lactams, including cefotaxime, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T more than MIC).34145 This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.

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

Pharmacokinetics: Cefotaxime is administered intravenously and intramuscularly. Approximately 30-50% of the circulating drug is protein-bound. It is widely distributed into most body tissues and fluids including gallbladder, liver, kidney, bone, uterus, ovary, sputum, bile, and peritoneal, pleural, and synovial fluids. Cefotaxime penetrates inflamed meninges (mean 10-20%) and reaches therapeutic levels within the CSF (mean, 6.2 mcg/ml). Cefotaxime is metabolized primarily by the liver to desacetylcefotaxime, an active metabolite that displays 10% of the parent drug's antibacterial activity. Cefotaxime and its metabolites are excreted into the urine primarily via tubular secretion. Approximately 20-36% of a dose is excreted in the urine as unchanged drug and 15-25% as the desacetyl metabolite. In patients with normal renal function, the elimination half-lives of cefotaxime and desacetylcefotaxime are approximately 1-1.5 hours and 1.5-2 hours, respectively.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
Peak concentrations of the active metabolite, desacetylcefotaxime, are reached approximately 1.5-3 hours after administration.

Intramuscular Route
Peak concentrations of cefotaxime are reached approximately 30 minutes after IM administration.


-Special Populations
Pediatrics
Neonates
The volume of distribution (Vd) and elimination half-life of cefotaxime are significantly greater in neonates compared with infants and children. In premature neonates (< 37 weeks gestational age), the Vd is approximately 0.5-0.7 L/kg, the clearance is approximately 1-1.5 ml/kg/min, and the elimination half-life is approximately 3-6 hours. The elimination half-life of the desacetyl metabolite is approximately 8.4-9.4 hours, which is significantly longer compared to that reported in infants and children (about 2 hours). In term neonates, the Vd is similar to premature neonates, and values for clearance and elimination half-life are approximately 2-2.5 ml/kg/min and 2-3 hours, respectively.

Infants and Children
Pharmacokinetics of cefotaxime are similar between children and adults. The Vd and clearance of cefotaxime in infants and children is approximately 0.36 L/kg and 4.8 ml/kg/min, respectively. The mean elimination half-lives of cefotaxime and desacetylcefotaxime in infants and children are 0.8-1.2 hours and 2 hours, respectively.

Hepatic Impairment
Pharmacokinetic data in children with hepatic impairment are unavailable. However, cefotaxime is predominantly excreted by the kidneys and hepatic impairment would not be expected to alter the pharmacokinetics of cefotaxime.

Renal Impairment
Pharmacokinetic data in children with renal impairment are unavailable. Cefotaxime is significantly excreted in the kidneys and elimination half-life is prolonged in patients with renal impairment. An elimination half-life of 15 hours has been reported in adults with end-stage renal disease.