Cefotaxime is a third generation semisynthetic cephalosporin antibiotic with bactericidal activity. Cefotaxime inhibits mucopeptide synthesis by binding to and inactivating penicillin-binding proteins thereby interfering with the final transpeptidation step required for cross-linking of peptidoglycan units which are a component of bacterial cell walls. This results in a reduction of cell wall stability and causes cell lysis.
Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad-spectrum activity against Gram positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to ceftriaxone in terms of safety and efficacy.
Mechanism of action of Cefotaxime
Cefotaxime is a β-lactam antibiotic (which refers to the structural components of the drug molecule itself). As a class, β-lactams inhibit bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs). This 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) in the absence of cell wall assembly. Due to the mechanism of their attack on bacterial cell wall synthesis, β-lactams are considered to be bactericidal.
Unlike β-lactams such as penicillin and amoxicillin, which are highly susceptible to degradation by β-lactamase enzymes (produced, for example, nearly universally by S. aureus), cefotaxime boasts the added benefit of resistance to β-lactamase degradation due to the structural configuration of the cefotaxime molecule. The syn-configuration of the methoxyimino moiety confers stability against β-lactamases. Consequently, the spectrum of activity is broadened to include several β-lactamase-producing organisms (which would otherwise be resistant to β-lactam antibiotics), as outlined below. Cefotaxime, like other β-lactam antibiotics, does not only block the division of bacteria, including cyanobacteria, but also the division of cyanelles, the photosynthetic organelles of the glaucophytes, and the division of chloroplasts of bryophytes. In contrast, it has no effect on the plastids of the highly developed vascular plants. This supports the endosymbiotic theory and indicates an evolution of plastid division in land plants.
Indications of Cefotaxime
- Lower respiratory tract infections – e.g. pneumonia (most commonly caused by S. pneumonia)
- Genitourinary system infections – urinary tract infections (e.g. E. coli, S. epidermidis, P. mirabilis) and cervical/urethral gonorrhea
- Bacteremia/septicemia – secondary to Streptococcus spp., S. aureus, E. coli, and Klebsiella spp.
- Intra-abdominal infections – e.g. peritonitis
- Bone and joint infections – S. aureus, Streptococcus spp.
- CNS infections – e.g. meningitis/ventriculitis secondary to N. meningitidis, H. influenzae, S. pneumoniae
- Acute maxillary sinusitis caused by M. catarrhalis
- Bacteremia
- Bacterial Infections
- Bacterial Sepsis
- Bacterial Urinary Tract Infections
- Bone and Joint Infections
- CNS ventriculitis
- Central Nervous System Infections
- Community Acquired Pneumonia (CAP)
- Endometritis
- Osteomyelitis
- Peritonitis
- Pneumonia
- Skin or Soft Tissue Infection
- Surgical Prophylaxis
- Urinary Tract Infection
- Gonococcal Infection – Disseminated
- Lyme Disease – Neurologic
- Sinusitis
- Rhinitis
- Also used to treat gonorrhoea, meningitis, and severe infections including infections of the kidney (pyelonephritis) and urinary system. Also used before an operation to prevent infection after surgery.
Gyanocological infection
- Gonococcal arthritis
- Gonorrhea
- Infected animal bite
- Intra-abdominal infections
- Lower respiratory tract infection bacterial
- Lyme neuroborreliosis
- Meningitis bacterial
- Pelvic inflammatory disease
- Pelvic cellulitis
- Peritonitis bacterial
- Pneumonia, bacterial
- Postoperative infections
- Skin and subcutaneous tissue bacterial infections
Contra Indications of Cefotaxime
- Clostridium difficile infection
- Carnitine Deficiency
- Decrease in the Blood-Clotting Protein Prothrombin
- Moderate to Severe Kidney Impairment
- Antimicrobial resistance, viral infection. …
- Cephalosporin hypersensitivity, penicillin hypersensitivity. …
- Dialysis, renal failure, renal impairment. …
- Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis.
Allergies
- Cephalosporins
- Beta-lactams
Dosages of Cefotaxime
Strengths: 500 mg; 1 g; 2 g; 10 g; 1 g/50 mL; 2 g/50 mL; 20 g
Bacteremia
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Septicemia
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Sepsis
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Cesarean Section
- 1 g IV as soon as the umbilical cord is clamped, then additional 1 g IM or IV doses at 6 and 12 hours after the initial dose
Meningitis
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
CNS Infection
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Pelvic Inflammatory Disease
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Endometritis
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Gonococcal Infection – Uncomplicated
- Urethritis/cervicitis: 0.5 g IM once
Rectal gonorrhea
- Females: 0.5 g IM once
- Males: 1 g IM once
US Centers for Disease Control and Prevention (CDC) Recommendations
- Urogenital and anorectal infections: 500 mg IM once
Intraabdominal Infection
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/daySurgical Infection Society (SIS) and IDSA Recommendations: 1 to 2 g IV every 6 to 8 hours PLUS metronidazole
Joint Infection
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Osteomyelitis
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Peritonitis
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Pneumonia
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Skin or Soft Tissue Infection
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Urinary Tract Infection
- Uncomplicated infections: 1 g IM or IV every 12 hours
- Moderate to severe infections: 1 to 2 g IM or IV every 8 hours
- Infections needing higher-doses: 2 g IV every 6 to 8 hours
- Life-threatening infections: 2 g IV every 4 hours
- Maximum dose: 12 g/day
Pediatric Dose for Bacteremia
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
IDSA Recommendations
- Neonates 0 to 4 weeks and less than 1200 g: 100 mg/kg IV per day, given in divided doses every 12 hours
- Postnatal age 7 days or less and 1200 to 2000 g: 100 mg/kg IV per day, given in divided doses every 12 hours
- Postnatal age 7 days or less and greater than 2000 g: 100 to 150 mg/kg IV per day, given in divided doses every 8 to 12 hours
- Postnatal age over 7 days and 1200 to 2000 g: 150 mg/kg IV per day, given in divided doses every 8 hours
- Postnatal age over 7 days and over 2000 g: 150 to 200 mg/kg IV per day, given in divided doses every 6 to 8 hours
- Infants and children 12 years and younger: 100 to 150 mg/kg per day, given in divided doses every 8 hours
Septicemia
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
IDSA Recommendations
- Neonates 0 to 4 weeks and less than 1200 g: 100 mg/kg IV per day, given in divided doses every 12 hours
- Postnatal age 7 days or less and 1200 to 2000 g: 100 mg/kg IV per day, given in divided doses every 12 hours
- Postnatal age 7 days or less and greater than 2000 g: 100 to 150 mg/kg IV per day, given in divided doses every 8 to 12 hours
- Postnatal age over 7 days and 1200 to 2000 g: 150 mg/kg IV per day, given in divided doses every 8 hours
- Postnatal age over 7 days and over 2000 g: 150 to 200 mg/kg IV per day, given in divided doses every 6 to 8 hours
- Infants and children 12 years and younger: 100 to 150 mg/kg per day, given in divided doses every 8 hours
Sepsis
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
Meningitis
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
CNS Infection
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
Intraabdominal Infection
- 0 to 1 week: 50 mg/kg IV every 12 hours
- 1 to 4 weeks: 50 mg/kg IV every 8 hours
Side Effects of Cefotaxime
The most common
- allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
- leukopenia/leukemia
- hemolytic anemia
- serum sickness
- agranulocytosis
- pain, swelling, irritation where injected
- stomach upset
- sweating
- skin color change, mild diarrhea
- mild nausea
- loss of appetite
- vaginal discharge and itching
- swelling of feet or legs
- chest pain
- constipation
- cough
- diarrhea or loose stools
- difficulty with breathing
- dizziness
- heartburn
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in chest
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- seizures
- abnormal or fast heart rate
- weight loss
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- hallucinations
- headache
- irritability
- muscle pain or cramps
- pale or yellowed skin, dark colored urine, fever, confusion or weakness;
- jaundice (yellowing of the skin or eyes);
- sore throat, and headache with a severe blistering, peeling, and red skin rash;
- swelling, rapid weight gain, feeling short of breath (even with mild exertion); or
- increased thirst, loss of appetite, urinating less than usual or not at all.
Drug Interactions of Cefotaxime
Cefotaxime may interacts with following drugs, suppliments & change the efficacy of drugs
- methotrexate ;
- antiviral medicines such as adefovir, cidofovir or foscarnet ;
- cancer medicine such as , carmustine, cisplatin , ifosfamide, streptozocin , or tretinoin ;
- a diuretic such as bumetanide , furosemide , indapamide hydrochlorothiazide , metolazone , spironolactone , torsemide , and others;
- a medication that reduces stomach acid, such as an antacid, or cimetidine , famotidine ,omeprazole , ranitidine and others;
- IV antibiotics such as amphotericin B , amikacin , bacitracin , capreomycin gentamicin , kanamycin , streptomycin, or vancomycin ;
- medicines used to prevent organ transplant rejection, such as sirolimus or tacrolimus
- medicines used to treat ulcerative colitis, such as or sulfasalazine ; or
- pain or arthritis medicines such as aspirin acetaminophen diclofenac , etodolac ,ibuprofen , indomethacin , naproxen , and others.
- aminoglycosides such as amikacin , gentamicin , and tobramycin
- birth control pills
This is not a complete list of cefotaxime drug interactions. Ask your doctor or pharmacist for more information.
Pregnancy & Lactation of Cefotaxime
FDA Pregnancy category B
Pregnancy
The safety of cefotaxime has not been established in human pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. There are, however, no adequate and well-controlled studies in pregnant women.
Lactation
Cefotaxime passes into human breast milk in small amounts and is usually compatible with breastfeeding, but careful monitoring of the infant is recommended. Effects on the physiological intestinal flora of the breastfed infant leading to diarrhea, colonization by yeast-like fungi, and sensitization of the infant cannot be excluded.
References
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