β-lactam; cell wall synthesis

Isolated microspore culture is a promising option to rapidly fix the product of meiotic recombination of F1 hybrids, in the process of varietal development. Clean culture and high embryogenesis rate are essential to commercial triticale and wheat microspore cultures. So, this study investigated (1) contaminants from isolated microspores cultures, (2) two antibiotics to control bacterial growth, and (3) the contribution of antibiotics to increased microspore-derived embryo-like structures (ELS), green and albino plants. Five species of bacteria were identified in contaminated cultures (Erwinia aphidicola, Pantoea agglomerans, Pseudomonas sp., Staphylococcus epidermis and Staphylococcus warneri) using fatty acid analysis and 16S ribosomal RNA sequences analysis, and yeast. Antibacterial susceptibility test using Cefotaxime and Vancomycin resulted in strong inhibition of 24 bacterial isolates, using Cefotaxime at 100 mg/l, but not Pseudomonas sp. Other antibiotic treatments inhibited bacterial growth at least partially. Microspore induction medium supplemented with the same antibiotics treatments resulted in successful microspore embryogenesis and green plant production. Antibiotic treatments were first tested in triticale and then validated in wheat cultivars AC Carberry and AC Andrew. Induction medium supplemented with Cefotaxime at 50 and 100 mg/l substantially increased the formation of ELS and green plants in triticale and wheat, respectively. Incidentally, it also affected the occurrence of albinism in all genotypes. Our results demonstrated dual purpose of Cefotaxime for isolated microspore culture, most importantly it increases cell growth and success of microspore cultures in triticale and wheat genotypes, but would also prevent accidental loss of cultures with most common bacterial contaminants[3].

In rats infected with neutropenic Pseudomonas, carbenicillin (100–400 mg/kg; intramuscularly every 8 hours for 72 hours) dramatically lowers mortality [1].

The isolates were grown for 48–72 h at 27 °C on LB medium in individual Petri dishes that were supplemented with different antibiotics (Table 1) to evaluate colony sensitivity towards antibiotics. The following antibiotics treatments were applied into the antibiotic assay on isolates and in isolated microspores cultures of triticale and wheat genotypes: T1: Control (no antibiotic); T2: Vancomycin at 100 mg/l; T3: Vancomycin 500 mg/l; T4: Cefotaxime at 50 mg/l; T5: Cefotaxime 100 mg/l; T6: Vancomycin 100 mg/l and Cefotaxime 50 mg/l; and T7: Vancomycin 500 mg/l and Cefotaxime 100 mg/l. The isolates’ growth was noted as no inhibition (+++), weak inhibition (++), strong inhibition (+) and no growth (−) relative to control, where no antibiotic was applied[3].

Rats made neutropenic with cyclophosphamide were infected intraperitoneally with Pseudomonas aeruginosa. The challenge organism was killed synergistically in vitro by the combination of gentamicin and carbenicillin. Untreated neutropenic rats infected with 3 x 10(6)Pseudomonas died between days 2 and 7, and the overall mortality was 70%. Groups of infected neutropenic rats were treated intramuscularly with 1.5 or 6 mg of gentamicin per kg per dose, 100 or 400 mg of carbenicillin per kg per dose, or 1.5 mg of gentamicin and 100 mg of carbenicillin per kg per dose. Treatment was begun at 2 h postinfection and was continued every 8 h for about 72 h. Cultures of blood and peritoneal washings were performed in control and treated rats at 1, 4, 24, 48, and 72 h postinfection. Gentamicin at either dose level was ineffective in preventing death, but mortality was significantly reduced by high-dose carbenicillin and low-dose combination therapy. In addition, the latter regimens sterilized the peritoneal fluid and blood. Carbenicillin and gentamicin showed in vivo synergy in the treatment of neutropenic Pseudomonas-infected rats[1].

Absorption, Distribution and Excretion
Rapidly absorbed from the small intestine following oral administration. Oral bioavailability is 30 to 40%.
CARBENICILLIN IS NOT ABSORBED FROM GI TRACT &, THEREFORE MUST BE GIVEN PARENTERALLY. ... IM INJECTION OF 1 G PRODUCES PEAK PLASMA CONCN OF 15-20 UG/ML IN 1/2-2 HR... MAX PLASMA CONCN ARE ABOUT 4 TIMES HIGHER AFTER IV THAN AFTER IM ADMIN... IV INFUSION...1 G/HR RESULTS IN AVG PLASMA CONCN OF APPROX 150 UG/ML.
ABOUT 50% OF ANTIBIOTIC IN PLASMA IS PROTEIN BOUND. ...CARBENICILLIN IS EXCRETED PRIMARILY BY RENAL TUBULES. ABOUT 75-80%...IS RECOVERABLE IN ACTIVE FORM IN URINE IN 9 HR.
Carbenicillin is not stable in acids nor does it resist penicillinases; thus it is administered parenterally because of poor absorption following oral administration. A parenteral dose of 50-200 mg/kg is divided for administration every 4-6 hr.
Although carbenicillin is eliminated from the bovine mammary gland within 72 hr posttreatment, mastitis produced by P. aeruginosa is not effectively treated; resistant organisms are recovered 24-48 hr postinfusion.
For more Absorption, Distribution and Excretion (Complete) data for CARBENICILLIN (11 total), please visit the HSDB record page.

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Metabolism / Metabolites
Minimal.

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Biological Half-Life
1 hour
...T 1/2...IN INDIVIDUALS WITH NORMAL RENAL FUNCTION IS ABOUT 1 HR...PROLONGED TO ABOUT 2 HR IN PRESENCE OF HEPATIC DYSFUNCTION.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Limited information indicates that carbenicillin produces low levels in milk that are not expected to cause adverse effects in breastfed infants. Occasionally disruption of the infant's gastrointestinal flora, resulting in diarrhea or thrush have been reported with penicillins, but these effects have not been adequately evaluated. Carbenicillin indanyl disodium is acceptable in nursing mothers.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
30 to 60%

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Interactions
Extended-spectrum penicillins are physically and/or chemically incompatible with aminoglycosides and can inactivate the drugs in vitro. The extent of in vitro inactivation of aminoglycosides by penicillins depends on the specific drugs involved and appears to be directly proportional to the penicillin concn, length of exposure, and temp ... Most in vitro studies indicate that carbenicillin ... inactivates aminoglycosides at a faster rate than mazlocillin, piperacillin, or ticarcillin.
Extended-spectrum penicillins can also inactivate aminoglycosides in vivo. In patients with impaired renal function, concomitant admin of carbenicillin ... and gentamicin has resulted in decreased serum aminoglycoside concn and serum half-lives compared with admin of the aminoglycoside alone.
Some in vitro studies indicate that the antibacterial activity of extended-spectrum penicillins may be additive or partially synergistic with other beta-lactam antibiotics ... . /Extended-spectrum penicillins/
In vitro studies indicate that the combination of carbenicillin ... with clavulanic acid, a beta-lactamase inhibitor, results in a synergistic bactericidal effect against many strains of beta-lactamase-producing bacteria.
For more Interactions (Complete) data for CARBENICILLIN (7 total), please visit the HSDB record page.

[1]. Scott RE, et, al. Synergistic activity of carbenicillin and gentamicin in experimental Pseudomonas bacteremia in neutropenic rats. Antimicrob Agents Chemother. 1976 Oct;10(4):646-51.
[2]. Neu HC, et, al. Carbenicillin and ticarcillin. Med Clin North Am. 1982 Jan;66(1):61-77.
[3]. Cefotaxime prevents microbial contamination and improves microspore embryogenesis in wheat and triticale. Plant Cell Rep . 2013 Oct;32(10):1637-46.

Carbenicillin is a penicillin antibiotic having a 6beta-2-carboxy-2-phenylacetamido side-chain. It has a role as an antibacterial drug. It is a penicillin and a penicillin allergen. It is a conjugate acid of a carbenicillin(2-).
Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.
Carbenicillin is a Penicillin-class Antibacterial.
Carbenicillin has been reported in Solanum lycopersicum with data available.
Carbenicillin is a broad-spectrum, semi-synthetic penicillin antibiotic with bactericidal and beta-lactamase resistant activity. Carbenicillin acylates the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation prevents the cross-linkage of peptidoglycan strands, thereby inhibiting the third and last stage of bacterial cell wall synthesis. This leads to incomplete bacterial cell wall synthesis and eventually causes cell lysis.
Broad-spectrum semisynthetic penicillin derivative used parenterally. It is susceptible to gastric juice and penicillinase and may damage platelet function.

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Drug Indication
For the treatment of acute and chronic infections of the upper and lower urinary tract and in asymptomatic bacteriuria due to susceptible strains of bacteria.

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Mechanism of Action
Free carbenicillin is the predominant pharmacologically active fraction of the salt. Carbenicillin exerts its antibacterial activity by interference with final cell wall synthesis of susceptible bacteria. Penicillins acylate the penicillin-sensitive transpeptidase C-terminal domain by opening the lactam ring. This inactivation of the enzyme prevents the formation of a cross-link of two linear peptidoglycan strands, inhibiting the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that carbenicillin interferes with an autolysin inhibitor.
The penicillins and their metabolites are potent immunogens because of their ability to combine with proteins and act as haptens for acute antibody-mediated reactions. The most frequent (about 95 percent) or "major" determinant of penicillin allergy is the penicilloyl determinant produced by opening the beta-lactam ring of the penicillin. This allows linkage of the penicillin to protein at the amide group. "Minor" determinants (less frequent) are the other metabolites formed, including native penicillin and penicilloic acids. /Penicillins/
Bactericidal; inhibit bacterial cell wall synthesis. Action is dependent on the ability of penicillins to reach and bind penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. Penicillin-binding proteins (which include transpeptidases, carboxypeptidases, and endopeptidases) are enzymes that are involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Penicillins bind to, and inactivate, penicillin-binding proteins, resulting in the weakening of the bacterial cell wall and lysis. /Penicillins/

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Therapeutic Uses
Penicillins
MAJOR ADVANTAGE OF THIS AGENT IS THAT IT OFTEN CURES SERIOUS INFECTIONS CAUSED BY PSEUDOMONAS SPECIES /PRC: ESP PSEUDOMONAS AEROGINOSA/, PROTEUS STRAINS RESISTANT TO AMPICILLIN, & CERTAIN OTHER GRAM-NEGATIVE MICROORGANISMS.
Carbenicillin (parenteral) /is/ indicated in the treatment of bacterial pneumonia caused by susceptible organisms. /Included in US product labeling/
Carbenicillin (parenteral) /is/ indicated in the treatment of bone and joint infections caused by susceptible organisms. /Included in US product labeling/
For more Therapeutic Uses (Complete) data for CARBENICILLIN (14 total), please visit the HSDB record page.

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Drug Warnings
IN FEW INSTANCES, IT IS NECESSARY TO INTERDICT FUTURE USE OF PENICILLIN BECAUSE OF RISK OF DEATH, & PT SHOULD BE SO WARNED. IT MUST AGAIN BE STRESSED THAT FATAL EPISODES OF ANAPHYLAXIS HAVE FOLLOWED THE INGESTION OF VERY SMALL DOSES OF THIS ANTIBIOTIC. /PENICILLINS/
THESE AGENTS ARE...LESS EFFECTIVE AGAINST MICROORGANISMS SUSCEPTIBLE TO PENICILLIN G, & THEY ARE NOT USEFUL AGAINST GRAM-NEGATIVE BACTERIA, MICROORGANISMS CAN BECOME RESISTANT TO THESE DRUGS IN STEPWISE FASHION, & CROSS-RESISTANCE TO ALL PENICILLINS IS USUALLY COMPLETE /PENICILLINS/
Because of the risk of therapeutic failure from subtherapeutic drug concn, carbenicillin indanyl sodium should not be used when rapid high blood and/or urine concn are necessary or in patients with severe renal impairment (i.e., creatinine clearances less than 10 ml/min). /Carbenicillin indanyl sodium/
Penicillins are distributed into breast milk, some in low concentrations. Although significant problems in humans have not been documented, the use of penicillins by nursing mothers may lead to sensitization, diarrhea, candidiasis, and skin rash in the infant. /Penicillins/
For more Drug Warnings (Complete) data for CARBENICILLIN (24 total), please visit the HSDB record page.

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Pharmacodynamics
Carbenicillin is a semisynthetic penicillin. Though carbenicillin provides substantial in vitro activity against a variety of both gram-positive and gram-negative microorganisms, the most important aspect of its profile is in its antipseudomonal and antiproteal activity. Because of the high urine levels obtained following administration, carbenicillin has demonstrated clinical efficacy in urinary infections due to susceptible strains of: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Pseudomonas species, Providencia rettgeri, Enterobacter species, and Enterococci (S. faecalis).

C17H18N2O6S

378.399623394012

378.089

C, 53.96; H, 4.79; N, 7.40; O, 25.37; S, 8.47

4697-36-3

Carbenicillin disodium;4800-94-6

20824

Typically exists as solid at room temperature

1.53g/cm3

737.8ºC at 760mmHg

400ºC

1.675

0.815

3

7

5

26

645

3

O=C([C@@H](C(C)(C)S[C@]1([H])[C@@H]2NC(C(C(O)=O)C3=CC=CC=C3)=O)N1C2=O)O

FPPNZSSZRUTDAP-UWFZAAFLSA-N

InChI=1S/C17H18N2O6S/c1-17(2)11(16(24)25)19-13(21)10(14(19)26-17)18-12(20)9(15(22)23)8-6-4-3-5-7-8/h3-7,9-11,14H,1-2H3,(H,18,20)(H,22,23)(H,24,25)/t9?,10-,11+,14-/m1/s1

(2S,5R,6R)-6-[(2-carboxy-2-phenylacetyl)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Carboxybenzylpenicillin; 4697-36-3; alpha-Carboxybenzylpencillin; Carbenicilina; Carbenicilline; Carbenicillinum; Carboxybenzylpenicillin acid;

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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