Over 75% of P. aeruginosa isolates were suppressed by 12.5 μg/mL of azocellin. Azlocillin exhibits antibacterial activity against both positive and indole-negative Proteus bacteria, demonstrating 98% and 71% inhibition, respectively, at a 12.5 μg/mL concentration. All Gram-positive cocci are susceptible to azlocillin, with the exception of Staphylococcus aureus, which is resistant to penicillin G [1].

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Azlocillin inhibited over 75% of Pseudomonas aeruginosa isolates at a concentration of 12.5 μg/ml or less. Against indole-negative Proteus spp. (P. mirabilis), 75% were inhibited at 1.56 μg/ml; against indole-positive Proteus spp., 71% were inhibited at 12.5 μg/ml or less. For Escherichia coli, 63% were inhibited at 12.5 μg/ml; for Serratia spp., 46% at the same concentration; for Klebsiella spp., 21% inhibited at 12.5 μg/ml; for Enterobacter spp., 26% inhibited at 12.5 μg/ml. All Streptococcus pyogenes isolates were inhibited by ≤0.10 μg/ml. Only 4 out of 9 Streptococcus pneumoniae isolates were inhibited at 0.10 μg/ml. Most penicillin G-susceptible Staphylococcus aureus were inhibited by ≤0.20 μg/ml of azlocillin, whereas penicillin G-resistant S. aureus were also resistant to azlocillin. The minimum bactericidal concentration (MBC) was generally the same as, or one concentration higher than, the minimum inhibitory concentration (MIC).[1]
The effect of inoculum size: using an inoculum of 10⁶ CFU/ml, all E. coli isolates were completely inhibited at 6.25 μg/ml; 8 of 10 Klebsiella pneumoniae and 8 of 10 P. aeruginosa isolates were inhibited at ≤50 μg/ml. With an inoculum of 10⁷ CFU/ml, none of the isolates was inhibited at a concentration of 400 μg/ml.[1]
Effect of pH: the activity of azlocillin increased against all tested organisms (E. coli, K. pneumoniae, P. aeruginosa) as the pH became more alkaline (pH 6.4, 7.2, 8.2).[1]
Effect of medium: media variation had little effect on activity, but P. aeruginosa isolates were slightly more susceptible in nutrient broth.[1]
Comparative activity: azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against P. aeruginosa. Against most other gram-negative bacilli, azlocillin was not as active as mezlocillin. Against Klebsiella spp., mezlocillin was the most active. Against Enterobacter spp., 70% of isolates were resistant to 25 μg/ml of azlocillin. Against Serratia marcescens, azlocillin inhibited fewer isolates at 12.5 μg/ml than other penicillins, but some isolates resistant to carbenicillin and ticarcillin were inhibited by azlocillin. Against E. coli and P. mirabilis, azlocillin, carbenicillin, BLP-1654, and ticarcillin had similar activity. Against indole-positive Proteus spp., azlocillin was less active than mezlocillin but more active than BLP-1654, inhibiting 64% of isolates at 3.12 μg/ml.[1]
Activity against carbenicillin-resistant P. aeruginosa: eleven isolates resistant to carbenicillin (MIC ≥400 μg/ml) were tested. Most were also resistant to other penicillins, but a few carbenicillin-resistant isolates were susceptible to azlocillin. Azlocillin was the most active among the tested penicillins against those isolates that were only marginally susceptible to carbenicillin and ticarcillin.[1]

Treatment with azlocillin (75 mg/kg) enhances survival in neutropenic mice infected with Escherichia coli or Klebsiella pneumoniae [2].

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In a neutropenic mouse model infected with E. coli, K. pneumoniae, or S. marcescens, Azlocillin sodium salt was administered subcutaneously at subeffective doses (approximating the PD2.5, the dose protecting 2.5% of mice) 1 hour and 3–4 hours after bacterial challenge. The specific doses for each organism were: E. coli: 30 mg/kg; K. pneumoniae: 30 mg/kg; S. marcescens: 60 mg/kg (see Table 3). Treatment with azlocillin alone resulted in some survival (exact numbers not detailed), but each combination of subeffective doses (including azlocillin plus amikacin or azlocillin plus cefotaxime) was significantly more effective than each drug alone against E. coli infection. Against K. pneumoniae, azlocillin plus amikacin was more effective than azlocillin alone [2].

Susceptibility tests were conducted using a dilution technique with an automatic microtiter system. All gram-negative bacilli and Staphylococcus aureus isolates were incubated in Mueller-Hinton broth (pH 7.4) for 18 hours at 37°C. Streptococcus pyogenes and S. pneumoniae were incubated in tryptose phosphate broth. An inoculum of approximately 10⁵ CFU/ml was used for gram-negative bacilli and S. aureus; for other gram-positive cocci, an inoculum of 10⁶ CFU/ml was used. The minimum inhibitory concentration (MIC) was determined as no visible growth after 18 hours of incubation at 37°C. The minimum bactericidal concentration (MBC) was defined as the lowest concentration of drug that yielded less than 5 colonies on subculture to sheep blood agar (99% kill). A 0.01-ml calibrated pipette was used to transfer the inoculum. Comparative studies were performed simultaneously in triplicate.[1]
For inoculum size effect studies: organisms were incubated in Mueller-Hinton broth for 18 hours at 37°C, assuming approximately 10⁸ CFU/ml. Serial 10-fold dilutions were made to obtain 10⁷ and 10⁵ CFU/ml as inocula. Colony counts were performed on sheep blood agar after 14 hours of incubation at 37°C to confirm the inoculum size.[1]
For pH effect studies: Mueller-Hinton broth was adjusted to pH 6.4, 7.2, and 8.2 with phosphate buffer.[1]
For medium effect studies: activity was compared in different media (e.g., nutrient broth) with Mueller-Hinton broth as reference.[1]

Neutropenic mouse model: Female BALB/c mice (22–24 g) were rendered neutropenic by two intraperitoneal injections of cyclophosphamide (200 mg/kg) given 54–56 hours apart. On day 4 after the first injection, mice were injected intraperitoneally with bacterial inoculum (0.2 ml of Mueller-Hinton broth) at concentrations 3 to 20 times the 50% lethal dose (LD50). One hour after infection, Azlocillin sodium salt was injected subcutaneously in a volume of 0.2 ml, followed by a second injection of the same dose and volume 3–4 hours later. The doses used were subeffective (approximately PD2.5 extrapolated from protective dose curves). For E. coli: 30 mg/kg; K. pneumoniae: 30 mg/kg; S. marcescens: 60 mg/kg. Each treatment group consisted of 20–40 mice. Survival was recorded and compared using the chi-square test [2].

Absorption, Distribution and Excretion
Gastrointestinal absorption is minimal. Metabolism/Metabolites Primarily excreted via the kidneys, but also undergoes biotransformation in tissues and is degraded by intestinal bacteria, resulting in higher concentrations in bile. Biological Half-Life The average elimination half-life is 1.3 to 1.5 hours. The half-life is longer in newborns and 2 to 6 hours in patients with renal insufficiency.

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In human volunteers with normal renal and hepatic function, Azlocillin sodium salt was administered as a single intravenous infusion of 75 mg/kg in 50 ml of 5% dextrose over 30 minutes. The mean peak serum concentration (± standard deviation) was 192 ± 45 μg/ml. At 6 hours after infusion, the mean serum concentration was 30 ± 23 μg/ml [2].

Protein Binding
20% to 46% binds to plasma proteins.

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Azlocillin does not appear to cause nephrotoxicity (personal communication cited in the paper). In contrast, BLP-1654 was observed to cause renal damage in toxicology studies.[1]

[1]. D Stewart, at al. Azlocillin: in vitro studies of a new semisynthetic penicillin. Antimicrob Agents Chemother. 1977 May;11(5):865-70.

[2]. In vitro and in vivo studies of three antibiotic combinations against gram-negative bacteria and Staphylococcus aureus. Antimicrob Agents Chemother. 1981 Oct;20(4):463-9.

[3]. Searching for new antimalarial therapeutics amongst known drugs. Chem Biol Drug Des. 2006 Jun;67(6):409-16.

Azlocillin is a semi-synthetic penicillin with a 6β-{(2R)-2-[(2-oxoimidazolidine-1-carbonyl)amino]-2-phenylacetyl}amino side chain. It is an antibiotic used to treat infections caused by Pseudomonas aeruginosa, Escherichia coli, and Haemophilus influenzae. It is an antibacterial drug. It is a penicillin, a semi-synthetic derivative, and also a penicillin allergen. It is the conjugate acid of azlocillin(1-). Azlocillin is a semi-synthetic ampicillin derivative acylurea penicillin. Azlocillin has been reported in Apis cerana, and there is relevant data. Azlocillin is a semi-synthetic broad-spectrum acylchlorine penicillin with antibacterial activity. Azlocillin binds to penicillin-binding protein (PBP) located within the bacterial cell wall, thereby inhibiting the cross-linking of peptidoglycan, a key component of the bacterial cell wall. This prevents the normal synthesis of the bacterial cell wall, leading to weakening of the bacterial cell wall and ultimately cell lysis.
A semi-synthetic ampicillin derivative, belonging to the acylurea penicillin class.
See also: Aloxicillin sodium (note moved to).

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Indications
For the treatment of infections caused by Pseudomonas aeruginosa, Escherichia coli, and Haemophilus influenzae.

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Mechanism of Action
Aloxicillin inhibits the third and final stage of bacterial cell wall synthesis by binding to a specific penicillin-binding protein (PBP) located within the bacterial cell wall. Cell lysis is mediated by bacterial cell wall autolysins (such as autolysins); aloxicillin may interfere with autolysin inhibitors.

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Azlocillin is a new semisynthetic penicillin, specifically a ureido-substituted penicillin. Its chemical structure is 6-[α-2-(2-oxoimidazolidine-1-carboxamido)-2-phenylacetamido]-penicillanic acid, sodium salt. The paper notes that azlocillin is of interest because of its activity against gram-negative bacilli, especially Pseudomonas aeruginosa. A major disadvantage of BLP-1654 was renal damage, which was not observed with azlocillin. Preliminary therapeutic studies have been encouraging . The authors suggest that azlocillin deserves further investigation for clinical therapeutic studies.[1]

C20H22N5NAO6S

483.4734

483.118

37091-65-9

Azlocillin;37091-66-0

6479523

White to off-white solid powder

0.1

4

7

5

32

844

4

CC1([C@@H](N2[C@H](S1)[C@@H](C2=O)NC(=O)[C@@H](C3=CC=CC=C3)NC(=O)N4CCNC4=O)C(=O)O)C

JTWOMNBEOCYFNV-NFFDBFGFSA-N

InChI=1S/C20H23N5O6S/c1-20(2)13(17(28)29)25-15(27)12(16(25)32-20)22-14(26)11(10-6-4-3-5-7-10)23-19(31)24-9-8-21-18(24)30/h3-7,11-13,16H,8-9H2,1-2H3,(H,21,30)(H,22,26)(H,23,31)(H,28,29)/t11-,12-,13+,16-/m1/s1

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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

DMSO : ~100 mg/mL (~206.84 mM)
H2O : ~6.67 mg/mL (~13.80 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.17 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 25.0 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: ≥ 2.5 mg/mL (5.17 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 25.0 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: ≥ 2.5 mg/mL (5.17 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 4: 100 mg/mL (206.84 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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