Ceftobiprole (Ro 63-9141) has MIC90 values of 0.25, 2, and 2 mcg/mL, respectively, making it effective against major Gram-positive bacteria such as Enterococcus faecalis, methicillin-resistant Staphylococcus aureus, and Streptococcus pneumoniae (PRSP). The antibiotic cefbiproro, which has a minimum inhibitory concentration (MIC) of 2 μg/ml, also showed strong in vitro action against a number of clinical isolates of methicillin-resistant Staphylococcus aureus (CA-MRSA), Staphylococcus aureus (VISA), and Staphylococcus aureus (VRSA) [1]. With MICs ranging from 0.12 to 4 mg/L (just one resistant strain exhibited a MIC of 4 mg/L), cefbiproro exhibits strong levels of activity against Staphylococcus aureus. Furthermore, ceftobiprole has a MIC50 and MIC90 of 0.5 mg/L against methicillin-susceptible Staphylococcus aureus (MSSA) strains, which is two times higher than that of MRSA strains (1 mg/L). Moreover, cefbiproro had a slightly higher MIC50 and MIC90 of 0.5 mg/L and 1 mg/L for Panton-Valentine leukocidin (PVL) + MRSA compared to PVL-MRSA (MIC50 and MIC90 of 1 mg/L) [2].

[1]. Kisgen J, et al. Ceftobiprole, a Broad-Spectrum Cephalosporin With Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). P T. 2008 Nov;33(11):631-41.
[2]. Hodille E, et al. In vitro activity of ceftobiprole on 440 Staphylococcus aureus strains isolated from bronchopulmonary infections. Med Mal Infect. 2017 Mar;47(2):152-157.
[3]. E Azoulay-Dupuis, et al. Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob Agents Chemother. 2004 Apr;48(4):1105-11.

Ceftobiprole is a fifth-generation cephalosporin antibiotic having (E)-[(3'R)-2-oxo[1,3'-bipyrrolidin]-3-ylidene]methyl and [(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyimino)acetyl]amino side groups located at positions 3 and 7 respectively; developed for the treatment of hospital-acquired pneumonia (HAP, excluding ventilator-associated pneumonia, VAP) and community-acquired pneumonia (CAP). It has a role as an antimicrobial agent. It is a cephalosporin and a member of thiadiazoles.
Ceftobiprole is a cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus. It was discovered by Basilea Pharmaceutica and is being developed by Johnson & Johnson Pharmaceutical Research and Development. Ceftobiprole is the first cephalosporin to demonstrate clinical efficacy in patients with infections due to methicillin-resistant staphylococci and, if approved by regulatory authorities, is expected to be a useful addition to the armamentarium of agents for the treatment of complicated skin infections and pneumonia.
Ceftobiprole is a broad-spectrum, fifth-generation, pyrrolidinone cephalosporin with antibacterial activity. Ceftobiprole binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.

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Drug Indication
For the treatment of serious bacterial infections in hospitalised patients.

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Mechanism of Action
Cephalosporins, such as ceftobiprole, are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic this site and competitively inhibit PBP crosslinking of peptidoglycan.

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Pharmacodynamics
Ceftobiprole, a cephalosporin antibiotic, is active against methicillin-resistant Staphylococcus aureus.

C20H22N8O6S2

534.56900

534.11

209467-52-7

252188-71-9 (medocaril);209467-52-7;376653-43-9;

135413542

Light yellow to yellow solid powder

2.0±0.1 g/cm3

1.942

-2.69

5

13

6

36

1100

3

O=C(C(N12)=C(/C=C3C(N([C@H]4CNCC4)CC/3)=O)CS[C@]2([H])[C@H](NC(/C(C5=NSC(N)=N5)=N\O)=O)C1=O)O

VOAZJEPQLGBXGO-SDAWRPRTSA-N

InChI=1S/C20H22N8O6S2/c21-20-24-14(26-36-20)11(25-34)15(29)23-12-17(31)28-13(19(32)33)9(7-35-18(12)28)5-8-2-4-27(16(8)30)10-1-3-22-6-10/h5,10,12,18,22,34H,1-4,6-7H2,(H,23,29)(H,32,33)(H2,21,24,26)/b8-5+,25-11-/t10-,12-,18-/m1/s1

(6R,7R)-7-((Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(hydroxyimino)acetamido)-8-oxo-3-((E)-((R)-2-oxo-[1,3'-bipyrrolidin]-3-ylidene)methyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Ro 63-9141 Ro-63-9141 Ro63-9141 BAL 9141 AC1OCFF8 Zeftera UNII-5T97333YZK BAL-9141 BAL9141.

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product is not stable in solution, please use freshly prepared working solution for optimal results.

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

DMSO : ~4.95 mg/mL (~9.26 mM)

Solubility in Formulation 1: ≥ 0.5 mg/mL (0.94 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 5.0 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: ≥ 0.5 mg/mL (0.94 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 5.0 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: ≥ 0.5 mg/mL (0.94 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 5.0 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.)