Cell wall synthesis; β-lactam

Cefotaxime's minimum inhibitory concentration (MIC) for Vibrio vulnificus CMCP6 is 0.0625 mg/L [4].

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- The minimum inhibitory concentration (MIC) of cefotaxime against V. vulnificus CMCP6 was determined to be 0.0625 mg/L using the microdilution method according to CLSI guidelines [1].
The MIC of cefotaxime against V. vulnificus MO6-24/O was also 0.0625 mg/L [1].
- In time-kill assays using 3/4 MIC concentrations, cefotaxime alone showed moderate bactericidal activity against V. vulnificus CMCP6 [1].
The combination of cefotaxime with ciprofloxacin demonstrated synergistic bactericidal activity, with bacterial colony counts after 24 h of in vitro treatment being lower for the combination than for cefotaxime, ciprofloxacin, minocycline, or cefotaxime-plus-minocycline [1].
- At sub-inhibitory concentrations (1/4 MIC), cefotaxime had a modest inhibitory effect on V. vulnificus cytotoxicity for HeLa cells and on rtxA1 transcription, but was significantly less effective than ciprofloxacin (P < 0.05 for both comparisons) [1].

Compared to earlier regimens, the combination of ciprofloxacin and cefotaxime is more successful in removing V. vulnificus from the body [4].

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- In a mouse model of V. vulnificus sepsis using an initial inoculum of 1×10⁸ cfu, treatment with cefotaxime alone (30 mg/kg i.p. every 6 h for 42 h) resulted in a 96-h survival rate of 0% (0/20), which was significantly lower than the 85% (17/20) survival rate observed with the cefotaxime-plus-ciprofloxacin combination (P < 0.001) [1].
The survival rate in the cefotaxime-plus-minocycline group was 35% (7/20) [1].
- Using a lower initial inoculum of 1×10⁷ cfu, all mice treated with cefotaxime alone (n=12) survived for 96 h, similar to other treatment groups [1].
However, bacterial counts in the liver and spleen at 24 and 48 h after treatment initiation were significantly higher in the cefotaxime monotherapy group compared to the cefotaxime-plus-ciprofloxacin group: liver at 24 h (19,544 ± 12,097 vs. 473 ± 309 CFU/g, P < 0.001), liver at 48 h (9,216 ± 101 vs. 162 ± 35 CFU/g, P < 0.001), spleen at 24 h (13,180 ± 5,558 vs. 1,813 ± 6,514 CFU/g, P < 0.001), and spleen at 48 h (1,304 ± 565 vs. 217 ± 87 CFU/g, P < 0.001) [1].

- Cytotoxicity assay (LDH release): HeLa cells were seeded in 48-well plates and cultured for 24 h [1].
Overnight-cultured V. vulnificus (MO6-24/O) were re-suspended in PBS after logarithmic growth [1].
HeLa cells (2×10⁵ cells/mL) were infected with V. vulnificus (5×10⁵ cfu/mL) in the presence or absence of 1/4 MIC of cefotaxime, minocycline, or ciprofloxacin for 120 min [1].
Cytotoxicity was measured by assaying lactate dehydrogenase (LDH) released into the supernatant using a commercial kit [1].
The impaired cytotoxicity of the rtxA1 deletion mutant (CMM770) compared to the wild-type strain confirmed that cytotoxicity at 120 min was mainly due to RtxA1 [1].
At 1/4 MIC, cefotaxime inhibited V. vulnificus-induced cytotoxicity less effectively than ciprofloxacin (P < 0.05) [1].
- Transcriptional reporter assay (β-galactosidase): A chromosomal PrtxA1:lacZ transcriptional reporter strain of V. vulnificus MO6-24/O was constructed [1].
An overnight culture of the reporter strain was inoculated into HI broth at 5×10⁵ cfu/mL with or without 1/4 MICs of antibiotics for 120 min [1].
The culture was lysed, and β-galactosidase activity was measured using a substrate containing O-nitrophenyl-β-D-galactopyranoside [1].
At 1/4 MIC, cefotaxime inhibited rtxA1 transcription less effectively than ciprofloxacin (P < 0.05) [1].

Animal/Disease Models: Female, specific pathogen-free, 8weeks old balb/c (Bagg ALBino) mouse [4].
Doses: 30 mg/kg. Management: IP every 6 hrs (hrs (hours)).
Experimental Results: The number of viable bacteria in the liver of mice in the cefotaxime + ciprofloxacin treatment group was lower than that in the cefotaxime alone group (P<0.001 at 24 hrs (hrs (hours)) and 48 hrs (hrs (hours))).

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- Female, 8-week-old BALB/c mice (average weight 20 g) were used [1].
To induce iron overload, 900 μg ferric ammonium citrate was administered intraperitoneally 30 min before V. vulnificus inoculation [1].
Mice were inoculated subcutaneously over the right thigh with either 1×10⁷ or 1×10⁸ cfu of V. vulnificus CMCP6 [1].
Antibiotic therapy was initiated 2 h after inoculation [1].
Cefotaxime was administered intraperitoneally at 30 mg/kg body weight every 6 h [1].
All antibiotics were given for a total of 42 h [1].
Control mice received 0.1 mL sterile saline every 6 h [1].
For survival studies, animals were monitored every 6 h, and humane endpoints were used based on a clinical scoring system (combined score ≥8) according to KFDA guidelines [1].
For bacterial clearance studies, mice were euthanized at 24 and 48 h after treatment initiation; livers and spleens were homogenized, serially diluted, and plated onto Brain-Heart infusion agar for CFU quantification [1].

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For the survival efficacy study, female BALB/c mice (8-week-old, ~20g) were used. To increase susceptibility, mice received an intraperitoneal injection of 900 µg ferric ammonium citrate 30 minutes before bacterial inoculation. Mice were then infected by subcutaneous injection of *Vibrio vulnificus* CMCP6 (1 x 10^8 CFU) over the right thigh. [1]
**Cefotaxime** treatment was initiated 2 hours post-infection via intraperitoneal injection at a dose of 30 mg/kg body weight, administered every 6 hours. The treatment continued for a total of 42 hours. Control mice received sterile saline. [1]
For the bacterial clearance study, a similar protocol was followed, but mice were infected with a lower inoculum (1 x 10^7 CFU). Mice were humanely euthanized at 24 and 48 hours after the initiation of antibiotic treatment. The liver and spleen were harvested, homogenized, serially diluted, and plated on agar to enumerate viable bacterial counts. [1]

Absorption, Distribution and Excretion
Absorbed rapidly after intramuscular injection. Approximately 20-36% of intravenously administered 14C-cefotaxime is excreted unchanged via the kidneys, and 15-25% is excreted as a deacetylated derivative (the main metabolite). Metabolites/Metabolites Approximately 20-36% of intravenously administered 14C-cefotaxime is excreted unchanged via the kidneys, and 15-25% is excreted as a deacetylated derivative (the main metabolite). The deacetylated metabolite has been shown to have bactericidal activity. Two other urinary metabolites (M2 and M3) account for approximately 20-25%. They lack bactericidal activity. Biological Half-Life Approximately 1 hour.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Cefotaxime has been discontinued in the United States. Limited information suggests that cefotaxime concentrations in breast milk are low and are not expected to have adverse effects on breastfed infants. There have been reports that cephalosporins occasionally disrupt the infant's gut microbiota, leading to diarrhea or thrush, but these effects have not been fully assessed. Cefotaxime is safe for use by breastfeeding women.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

[1]. In vivo efficacy of the combination of ciprofloxacin and cefotaxime against Vibrio vulnificus sepsis. PLoS One. 2014 Jun 30;9(6):e101118.

[2]. A comparison of the prophylactic efficacy of ceftriaxone and cefotaxime in abdominal surgery. Am J Surg. 2003 Jan;185(1):45-9.

[3]. Prospective comparison of ceftriaxone and cefotaxime for the short-term treatment of bacterial meningitis in children. Chemotherapy. 1998 Mar-Apr;44(2):142-7.

[4]. Differences between ceftriaxone and cefotaxime: microbiological inconsistencies. Ann Pharmacother. 2008 Jan;42(1):71-9.

[5]. Use of cefotaxime, a beta-lactamase stable cephalosporin, in the therapy of serious infections, including those due to multiresistant organisms. Am J Med. 1981 Sep;71(3):435-42.

Cefotaxime is a cephalosporin compound with an acetoxymethyl and a [2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino side group. It is both a drug allergen and an antibacterial agent. It belongs to the 1,3-thiazole, oxime ether, and cephalosporin classes. It is the conjugate acid of cefotaxime (1-). Cefotaxime is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. In most cases, its safety and efficacy are comparable to ceftriaxone. Cefotaxime sodium is marketed under several brand names, including Clavulania (Sanofi-Aventis).
Cefotaxime is a cephalosporin antibacterial drug.
Cefotaxime has been reported to exist in the American giant beetle (Melodinus cochinchinensis), and relevant data are available.
Cefotaxime is a third-generation semi-synthetic cephalosporin antibiotic with bactericidal activity. Cefotaxime inhibits peptidoglycan synthesis by binding to and inactivating penicillin-binding proteins, thereby interfering with the final transpeptidation step required for peptidoglycan unit cross-linking, and peptidoglycan is a component of the bacterial cell wall. This leads to decreased cell wall stability and cell lysis.
Semi-synthetic broad-spectrum cephalosporin.
See also: Cefotaxime sodium (in salt form).
Drug Indications
For the treatment of gonorrhea, meningitis, and serious infections, including pyelonephritis and urinary tract infections. Also used for preoperative prophylaxis of postoperative infections.
FDA Label

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Mechanism of Action
The bactericidal activity of cefotaxime derives from its affinity for penicillin-binding proteins (PBPs), thereby inhibiting cell wall synthesis. Cefotaxime has a high affinity for penicillin-binding proteins (including PBP Ib and PBP III) in the cell wall.

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Pharmacodynamics
Cefotaxime is a third-generation intravenous cephalosporin antibiotic. It has broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria, but is ineffective against Pseudomonas aeruginosa. Cefotaxime exerts its effect by inhibiting bacterial cell wall biosynthesis. One advantage of cefotaxime is its resistance to penicillinase, thus it can be used to treat penicillin-resistant infections.

455.056

C, 42.19; H, 3.76; N, 15.38; O, 24.59; S, 14.08

63527-52-6

Cefotaxime sodium;64485-93-4; 63527-52-6 (free); 66340-28-1

5742673

White to off-white solid powder

1.8±0.1 g/cm3

162-163℃

1.779

1.2

3

12

8

30

833

2

CC(OCC1=C(N2C([C@@H](NC(/C(/C3=CSC(N3)=N)=N\OC)=O)[C@H]2SC1)=O)C(O)=O)=O

GPRBEKHLDVQUJE-QSWIMTSFSA-N

InChI=1S/C16H17N5O7S2/c1-6(22)28-3-7-4-29-14-10(13(24)21(14)11(7)15(25)26)19-12(23)9(20-27-2)8-5-30-16(17)18-8/h5,10,14H,3-4H2,1-2H3,(H2,17,18)(H,19,23)(H,25,26)/b20-9-/t10-,14-/m1/s1

(6R,7R)-3-(acetyloxymethyl)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Cephotaxime RU-24662 RU24662

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~250 mg/mL (~548.88 mM)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.57 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)