General dosing:
Gestational age-directed dosing (Ref):
Preterm and term neonates: IV, IM:
Gestational Age |
Postnatal Age |
Dose |
---|---|---|
<32 weeks |
<7 days |
50 mg/kg/dose every 12 hours |
7 to 28 days |
50 mg/kg/dose every 8 hours | |
≥32 weeks |
≤7 days |
50 mg/kg/dose every 12 hours |
8 to 28 days |
50 mg/kg/dose every 8 hours |
Weight-directed dosing (Ref):
Preterm and term neonates: IV, IM:
Body Weight |
Postnatal Age |
Dose |
---|---|---|
≤2 kg |
≤7 days |
50 mg/kg/dose every 12 hours |
8 to 28 days |
50 mg/kg/dose every 8 hours | |
29 to 60 days |
50 mg/kg/dose every 6 hours | |
>2 kg |
≤7 days |
50 mg/kg/dose every 12 hours |
8 to 28 days |
37.5 mg/kg/dose every 6 hours | |
29 to 60 days |
50 mg/kg/dose every 6 hours |
Gonococcal infections, treatment:
Scalp abscess or disseminated gonococcal infection (including sepsis and arthritis): Neonates: IV, IM: 25 mg/kg/dose every 12 hours for 7 days (Ref). Note: Dosing is significantly lower than other contemporary dosages; use clinical judgment to determine if appropriate for patient scenario. See “Meningitis” section for gonococcal meningitis recommendations.
Ophthalmia neonatorum: Note: Only recommended for patients who cannot receive ceftriaxone (eg, due to simultaneous IV calcium administration).
Neonates: IV, IM: 100 mg/kg as a single dose (Ref).
Meningitis: Note: Duration of therapy is dependent on pathogen and clinical response; for gram-negative meningitis, typically treat for ≥21 days and ≥14 days after the first negative cerebrospinal fluid culture; for gonococcal meningitis, treat for 10 to 14 days (Ref).
Preterm and term neonates (Ref):
PNA ≤7 days: IV: 100 to 150 mg/kg/day divided every 8 to 12 hours.
PNA >7 days: IV: 150 to 200 mg/kg/day divided every 6 to 8 hours.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
General dosing:
Traditional intermittent infusion method: Infants, Children, and Adolescents: IV, IM: 150 to 180 mg/kg/day in divided doses every 4 to 8 hours; maximum dose: 2,000 mg/dose; higher daily doses are recommended for some indications (eg, meningitis) (Ref). Note: Based on pharmacokinetic modeling, dosing intervals of at least every 6 hours may be required to reach pharmacodynamic targets (Ref).
Continuous infusion dosing: Limited data available: Infants, Children, and Adolescents: IV: 100 to 200 mg/kg/day infused continuously over 24 hours; maximum daily dose: 12 g/day (Ref).
Endocarditis, treatment: Children and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours; maximum daily dose: 12 g/day; treat for ≥4 weeks depending on pathogen and valve type; longer durations may be necessary; use in combination with other antibiotics depending on pathogen (Ref).
Gonococcal infection, disseminated (arthritis and arthritis-dermatitis syndrome) (alternative agent):
Adolescents: IV: 1,000 mg every 8 hours. Total duration of therapy is at least 7 days (including oral step-down therapy); can usually switch to susceptibility-guided oral therapy after 24 to 48 hours. Give in combination with treatment for chlamydia if it has not been excluded (Ref).
Lyme disease (Borrelia spp. infection) (alternative agent): Infants, Children, and Adolescents: IV: 150 to 200 mg/kg/day in divided doses every 6 to 8 hours; maximum daily dose: 6,000 mg/day. Duration of therapy depends on clinical syndrome; treat meningitis or radiculopathy for 14 to 21 days (Ref).
Meningitis: Infants, Children, and Adolescents: IV: 225 to 300 mg/kg/day in divided doses every 6 to 8 hours; maximum dose: 2,000 mg/dose; use in combination with vancomycin for empiric coverage (Ref); some experts recommend 300 mg/kg/day divided every 4 to 6 hours with a maximum daily dose of 12 g/day (Ref).
Peritonitis (peritoneal dialysis) (Ref): Infants, Children, and Adolescents: Intraperitoneal:
Intermittent: 30 mg/kg/dose every 24 hours in the long dwell.
Continuous: Loading dose: 500 mg per liter of dialysate; maintenance dose: 250 mg per liter; Note: 125 mg/liter has also been recommended as a maintenance dose (Ref).
Pneumonia, community-acquired (CAP): Infants, Children, and Adolescents: IV: 150 to 200 mg/kg/day in divided doses every 6 to 8 hours; maximum dose: 2,000 mg/dose (Ref). Note: Use as part of an appropriate combination regimen if methicillin-resistant Staphylococcus aureus or atypical pathogens are of concern (Ref).
Salmonellosis: Adolescents with HIV: IV: 1,000 mg every 8 hours (Ref).
Skin and soft tissue infection, necrotizing: Infants, Children, and Adolescents: IV: 200 mg/kg/day in divided doses every 6 hours in combination with metronidazole or clindamycin; maximum dose: 2,000 mg/dose. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Surgical prophylaxis: Children and Adolescents: IV: 50 mg/kg within 60 minutes prior to surgical incision; may repeat in 3 hours if procedure is lengthy or if there is excessive blood loss; maximum dose: 1,000 mg; a larger maximum dose (2,000 mg) is recommended for patients weighing ≥120 kg or with BMI >30 kg/m2 (Ref).
Urinary tract infection: Infants, Children, and Adolescents: IM, IV: 150 mg/kg/day in divided doses every 6 to 8 hours; maximum dose: 2,000 mg/dose. Treatment duration dependent on age of patient, response to therapy, and extent of involvement (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents: The following adjustments have been recommended (Ref). Note: Renally adjusted dose recommendations are based on doses of 100 to 200 mg/kg/day divided every 8 hours.
GFR 30 to 50 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 8 to 12 hours.
GFR 10 to 29 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 12 hours.
GFR <10 mL/minute/1.73 m2: 35 to 70 mg/kg/dose every 24 hours.
Intermittent hemodialysis: 35 to 70 mg/kg/dose every 24 hours.
Peritoneal dialysis (PD): 35 to 70 mg/kg/dose every 24 hours.
CRRT: 35 to 70 mg/kg/dose every 12 hours.
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Cefotaxime (United States: Limited availability): Drug information")
Usual dosage range: IV: 1 to 2 g every 6 to 8 hours; 2 g every 4 hours may be needed for severe infections; maximum dose: 12 g/day.
Bloodstream infection: IV: 2 g every 6 to 8 hours (Ref). Usual duration of therapy is 7 to 14 days; individualize depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Ref).
Brain abscess (empiric treatment): IV: 2 g every 4 to 6 hours as part of an appropriate combination regimen (eg, metronidazole) (Ref).
Chronic obstructive pulmonary disease, acute exacerbation (patients who are hospitalized without risk factors for P. aeruginosa) (off-label use): IV: 1 g every 8 hours for 5 to 7 days; may switch to oral therapy following clinical improvement (Ref).
Gonococcal infection, disseminated (arthritis and arthritis-dermatitis syndrome) (alternative agent) (off-label use): IV: 1 g every 8 hours. Total duration of therapy is at least 7 days (including oral step-down therapy); can usually switch to susceptibility-guided oral therapy after 24 to 48 hours. Give in combination with treatment for chlamydia if it has not been excluded (Ref).
Gonococcal infection, uncomplicated (infection of the cervix, rectum, or urethra) (alternative agent):
Note: Use cefotaxime only if ceftriaxone is unavailable given a lack of contemporary efficacy data (Ref).
IM: 500 mg as a single dose (Ref); give in combination with treatment for chlamydia if it has not been excluded. Note: When treatment failure is suspected (eg, detection of N. gonorrhoeae after treatment without additional sexual exposure), consult an infectious diseases specialist. Report failures to the CDC through state and local health departments (Ref).
Intra-abdominal infection, mild to moderate (community-acquired infection in patients without risk factors for resistance or treatment failure):
Cholecystitis, acute: IV: 2 g every 8 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Ref). Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (Ref).
Other intra-abdominal infections (eg, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 2 g every 8 hours in combination with metronidazole (Ref). Total duration of therapy (which may include transition to oral antibiotics) is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref).
Lyme disease (Borrelia spp. infection) (alternative agent) (off-label use):
Carditis, patients requiring hospitalization: IV: 2 g every 8 hours for 14 to 21 days (including oral step-down therapy) (Ref).
Acute neurologic disease (eg, meningitis, radiculopathy), patients requiring hospitalization: IV: 2 g every 8 hours for 14 to 21 days (Ref).
Late neurologic disease: IV: 2 g every 8 hours for 14 to 28 days (Ref).
Recurrent arthritis after adequate oral treatment: IV: 2 g every 8 hours for 14 days; may extend to 28 days if inflammation is not resolving (Ref).
Meningitis, bacterial: As a component of empiric therapy (community-acquired infections) or pathogen-specific therapy (eg, Cutibacterium acnes, H. influenzae, N. meningitidis, S. agalactiae, S. pneumoniae, and susceptible gram-negative bacilli; alternative agent for certain pathogens):
IV: 2 g every 4 to 6 hours; for empiric therapy, use in combination with other appropriate agents. Treatment duration is 7 to 21 days, depending on causative pathogen(s) and clinical response (Ref).
Peritonitis, treatment (peritoneal dialysis) (off-label route):
Note: Intraperitoneal administration is preferred to IV administration unless the patient has sepsis (Ref).
Intermittent: Intraperitoneal: 500 mg to 1 g added to the dialysate solution once daily; allow to dwell ≥6 hours (Ref). For patients with adequate clinical response, duration of therapy is ≥2 to 3 weeks depending on organism (Ref). For patients with no improvement after 5 days, remove catheter and treat with appropriate systemic antibiotics for 14 days after catheter removal (Ref).
Pneumonia, community-acquired: Inpatients without risk factors for Pseudomonas aeruginosa:
IV: 1 to 2 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; patients should be clinically stable with normal vital signs before therapy is discontinued (Ref).
Salmonella species infection (alternative agent) (off-label use):
Enteric fever (Salmonella typhi and paratyphi): Empiric therapy for severe disease or an alternative directed therapy for quinolone-nonsusceptible infection: IV: 1 to 2 g every 6 to 8 hours for 10 to 14 days. Note: May be switched to an oral regimen based on susceptibility testing, if available. Geographic location at time of acquisition impacts risk of resistance; cefotaxime is not recommended if there is concern for extensively drug-resistant Salmonella spp. (Ref).
Nontyphoidal Salmonella GI infection: IV: 1 to 2 g every 8 hours for 3 to 14 days (7 to 14 days in patients with HIV with a CD4 count ≥200 cells/mm3 or 2 to 6 weeks in patients with a CD4 count <200 cells/mm3). Note: Reserve antibiotic treatment for patients with severe illness or at high risk of invasive disease (eg, extremes of age, immunosuppression); reserve parenteral therapy for those who cannot tolerate oral agents (Ref).
Nontyphoidal Salmonella bloodstream infection: IV: 1 to 2 g every 8 hours for 10 to 14 days for patients who are immunocompetent; 14 days for patients with HIV and a CD4 count ≥200 cells/mm3. Patients who are immunosuppressed (eg, patients with HIV with a CD4 count <200 cells/mm3) and those with an extraintestinal focus of infection require a longer duration of treatment (eg, weeks to months) (Ref).
Septic arthritis (as a component of empiric therapy for traumatic bacterial arthritis without risk factors for P. aeruginosa; pathogen-directed therapy for gram-negative bacilli): IV: 2 g every 8 hours. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy. For empiric therapy, give as part of an appropriate combination regimen (Ref).
Skin and soft tissue infection, necrotizing (off-label use):
Polymicrobial infection: IV: 2 g every 6 hours, in combination with metronidazole or clindamycin for empiric therapy of polymicrobial infections. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Necrotizing infection due to Vibrio vulnificus: IV: 2 g every 8 hours, in combination with doxycycline. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Surgical prophylaxis: IV: 1 g within 60 minutes prior to surgical incision. Doses may be repeated in 3 hours if procedure is lengthy or if there is excessive blood loss (Ref).
Obesity: The ASHP/IDSA/SIS/SHEA guidelines recommend that for patients weighing ≥120 kg (or alternatively defined as BMI >30 kg/m2), a dose of 2 g within 60 minutes prior to surgical incision should be administered (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: IV:
CrCl |
If the usual indication-specific dose is 1 to 2 g every 8 hoursa |
If the usual indication-specific dose is 1 to 2 g every 6 hoursa |
If the usual indication-specific dose is 2 g every 4 hoursb |
---|---|---|---|
a Expert opinion derived from Bouchet 1991; Matzke 1985; Seguin 2009. | |||
b Expert opinion only. | |||
c Dialyzable (~40%) (Ings 1982): When scheduled dose falls on a dialysis day, administer after hemodialysis. | |||
>50 mL/minute |
No dosage adjustment necessary |
No dosage adjustment necessary |
No dosage adjustment necessary |
>10 to 50 mL/minute |
1 to 2 g every 12 hours |
1 to 2 g every 8 hours |
2 g every 6 to 8 hours |
≤10 mL/minute |
1 to 2 g every 24 hours |
1 to 2 g every 12 hours |
2 g every 12 hours |
Hemodialysis, intermittent (thrice weekly)c |
1 to 2 g every 24 hours |
1 to 2 g every 12 hours |
2 g every 12 hours |
Peritoneal dialysisa |
1 to 2 g every 24 hours |
1 to 2 g every 12 hours |
2 g every 12 hours |
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.
IV: Dose as for CrCl >10 to 50 mL/minute (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.
IV:
PIRRT days: Dose as for CrCl >10 to 50 mL/minute (on PIRRT days, when feasible administer one of the scheduled doses after the PIRRT session) (Ref).
Non-PIRRT days: Dose as for CrCl ≤10 mL/minute (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Dermatologic: Pruritus (≤2%), skin rash (≤2%)
Gastrointestinal: Colitis (≤1%), diarrhea (≤1%), nausea (≤1%), vomiting (≤1%)
Hematologic & oncologic: Eosinophilia (≤2%)
Local: Induration at injection site (IM ≤4%), inflammation at injection site (IV ≤4%), pain at injection site (IM ≤4%), tenderness at injection site (IM ≤4%)
Miscellaneous: Fever (≤2%)
<1%, postmarketing and/or case reports: Acute generalized exanthematous pustulosis, acute renal failure, agranulocytosis, anaphylaxis, bone marrow failure, brain disease, candidiasis, cardiac arrhythmia (after rapid IV injection via central catheter), cholestasis, Clostridioides difficile-associated diarrhea, dizziness, erythema multiforme, granulocytopenia, headache, hemolytic anemia, hepatitis, increased blood urea nitrogen, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, increased serum creatinine, injection site phlebitis, interstitial nephritis, jaundice, leukopenia, local irritation, neutropenia, pancytopenia, positive direct Coombs test, pseudomembranous colitis, Stevens-Johnson syndrome, thrombocytopenia, toxic epidermal necrolysis, urticaria, vaginitis
Hypersensitivity to cefotaxime, other cephalosporins, or any component of the formulation.
Concerns related to adverse effects:
• Arrhythmia: A potentially life-threatening arrhythmia has been reported in patients who received a rapid (<1 minute) bolus injection via central venous catheter.
• Hematologic effects: Granulocytopenia, leukopenia, neutropenia, and more rarely agranulocytosis, bone marrow failure, and pancytopenia may develop during prolonged treatment (>10 days).
• Penicillin allergy: Use with caution in patients with a history of penicillin allergy, especially IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
• Tissue inflammation: Minimize tissue inflammation by changing infusion sites when needed.
Disease-related concerns:
• Colitis: Use with caution in patients with a history of colitis.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be required.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection [preservative free]:
Generic: 1 g (1 ea); 2 g (1 ea)
Yes
Solution (reconstituted) (Cefotaxime Sodium Injection)
1 g (per each): $11.76
2 g (per each): $23.56
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 1 g (1 ea); 2 g (1 ea)
Parenteral:
IM: Administer by deep IM injection into a large muscle mass such as the upper outer quadrant of the gluteus maximus. Doses of 2,000 mg should be divided and administered at two different sites.
IV:
IV push: May be administered over 3 to 5 minutes; avoid rapid injection (<1 minute) due to association with arrhythmias.
Intermittent infusion: Infuse over 15 to 30 minutes.
IM: Inject deep IM into large muscle mass. Individual doses of 2 g may be given if the dose is divided and administered in different IM sites.
IV: Can be administered IV bolus over at least 3 to 5 minutes or as an IV intermittent infusion over 15 to 30 minutes.
Intraperitoneal (off-label route): May administer intermittently (1 exchange daily); allow to dwell ≥6 hours (Ref).
Store intact vials below 30°C (86°F). Protect from light. Reconstituted solution is stable for 12 to 24 hours at room temperature, 7 to 10 days when refrigerated, for 13 weeks when frozen. For IV infusion in NS or D5W, solution is stable for 24 hours at room temperature, 5 days when refrigerated, or 13 weeks when frozen in Viaflex plastic containers. Thawed solutions of frozen premixed bags are stable for 24 hours at room temperature or 10 days when refrigerated.
Treatment of susceptible lower respiratory tract, skin and soft tissue, bone and joint, intra-abdominal, GU tract, CNS, bacteremic, and gynecologic infections (FDA approved in all ages); prevention of postoperative surgical-site infection in contaminated or potentially contaminated surgical procedures (eg, GI and GU tract surgeries and hysterectomy [abdominal or vaginal]) and caesarian section (FDA approved in all ages); has also been used for the treatment of endocarditis, Lyme disease, and peritonitis in patients with peritoneal catheters.
Cefotaxime may be confused with cefOXitin, cefuroxime
Spectrocef [Italy] may be confused with Spectracef brand name for cefditoren [US, Great Britain, Mexico, Portugal, Spain]
Substrate of OAT1/3
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Risk C: Monitor therapy
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination
Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination
Furosemide: May enhance the nephrotoxic effect of Cephalosporins. Risk C: Monitor therapy
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Mycophenolate: Antibiotics may decrease serum concentrations of the active metabolite(s) of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Cefotaxime. Management: Avoid cefotaxime doses greater than 6 grams per day with concurrent probenecid. Any patients receiving this combination should be monitored for evidence of cefotaxime toxicity. Risk D: Consider therapy modification
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain sodium.
Cefotaxime crosses the human placenta.
Cefotaxime is approved for use in women undergoing cesarean section (consult current guidelines for appropriate use).
Observe for signs and symptoms of anaphylaxis during first dose; monitor infusion site for extravasation; with prolonged therapy, monitor renal, hepatic, and hematologic function periodically; number and type of stools/day for diarrhea.
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested. Cefotaxime has activity in the presence of some beta-lactamases, both penicillinases and cephalosporinases, of gram-negative and gram-positive bacteria. Enterococcus species may be intrinsically resistant to cefotaxime. Most extended-spectrum beta-lactamase (ESBL)-producing and carbapenemase-producing isolates are resistant to cefotaxime.
Distribution: Widely to body tissues and fluids, including aqueous humor, ascitic and prostatic fluids, bone; penetrates cerebrospinal fluid (CSF) best when meninges are inflamed.
Vd:
Preterm and term neonates (GA: 23 to 42 weeks; PNA: 0 to 69 days): Median: 0.64 L/kg (Leroux 2016).
Infants, Children, and Adolescents: Median: 0.3 L/kg (range: 0.2 to 0.41 L/kg) (Béranger 2018).
CSF concentrations:
Preterm and term neonates (GA: 23 to 40 weeks; PNA: 3 to 88 days): Median: 28% (range: 6% to 76%) (Chen 2018).
Infants ≥2 months and Children: 10.1% (range: 0% to 20%) (Trang 1985).
Protein binding: 31% to 50%.
Metabolism: Partially hepatic to active metabolite, desacetylcefotaxime.
Half-life elimination:
Cefotaxime: Prolonged with renal and/or hepatic impairment.
Preterm neonates: PNA <7 days: 5.7 ± 0.8 hours; PNA 7 to 28 days: 3.5 ± 0.5 hours (Kafetzis 1982).
Term neonates: PNA <7 days: 3.4 ± 0.3 hours; PNA 7 to 28 days: 2 ± 0.4 hours (Kafetzis 1982).
Infants ≥2 months, Children, and Adolescents ≤16 years: ~0.7 to 0.8 hours (Paap 1991; Trang 1985).
Adults: 1 to 1.5 hours.
Desacetylcefotaxime: Prolonged with renal impairment (Ings 1982; Paap 1991).
Children ≥7 years and Adolescents ≤16 years: 2.04 ± 0.39 hours (Paap 1991).
Adults: 1.3 to 1.9 hours (Ings 1982).
Time to peak, serum: IM: Within 30 minutes.
Excretion: Urine (~60% as unchanged drug and metabolites).
Anti-infective considerations:
Parameters associated with efficacy: Time dependent; associated with time free drug concentration (fT) > minimum inhibitory concentration (MIC): Goal: ≥40% to 50% (fT) > MIC (bacteriostatic), ≥60% to 70% (fT) > MIC (bactericidal) (Craig 1996; Craig 1998; Turnidge 1998).
Expected drug exposure in normal renal function:
Pediatric patients, Cmax (peak):
Steady state:
Infants ≥2 months of age and children: IV: 50 mg/kg/dose every 6 hours: ~142 mg/L (Kearns 1992).
Single dose:
Preterm and term neonates (GA: 27 to 40 weeks, PNA 0 to 3 days): IV: 50 mg/kg: ~120 to 200 mg/L (Baird-Lambert 1984).
Children ≥7 years of age and adolescents ≤16 years of age: 50 mg/kg (maximum dose: 2,000 mg) IV: ~175 to 180 mg/L (Paap 1991).
Adults, Cmax (peak), single dose:
500 mg IM: 11.7 mcg/mL.
500 mg IV: 38.9 mcg/mL.
1 g IM: 20.5 mcg/mL.
1 g IV: 101.7 mcg/mL.
2 g IV: 214.4 mcg/mL.
Postantibiotic effect: Generally <1 hour; varies based on organism (Craig 1991; Craig 1998; Hanberger 1991).
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