Ceftazidime

Manufactured by Merck Group

Sourced in United States, United Kingdom, Germany, Sao Tome and Principe, Canada, China, Australia, Spain

Ceftazidime is a broad-spectrum cephalosporin antibiotic that belongs to the beta-lactam class of antibiotics. It is used in the treatment of a variety of bacterial infections. Ceftazidime functions by inhibiting the synthesis of the bacterial cell wall, thereby causing cell lysis and death.

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Close spelling variants of this product

Ceftazidime hydrate (13 citations) Ceftazidime (CAZ) (9 citations) Ceftazidime-avibactam (2 citations)

141 protocols using ceftazidime

Antibiotic Susceptibility of Acinetobacter baumannii

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The antibiotic susceptibility of Acinetobacter baumannii isolates are based on the results of disc diffusion and minimum inhibitory concentration (MIC). The disk diffusion method is according to CLSI guidelines [16 (link)]. Eleven different antibiotics were used to assess the susceptibility test including imipenem (10 µg), cefepime, (30 µg), ceftazidime (30 µg), amikacin (30 µg), gentamicin (10 µg), tetracycline (30 µg), ticarcillin (75 µg), piperacillin (100 mg), sulfamethoxazole/trimethoprim (25 µg), carbenicillin (100 µg) and streptomycin (10 µg) (Sigma-Aldrich, St. Louis, MI, USA).
Broth dilution method was used to determine the minimum inhibitory concentration according to CLSI guidelines [16 (link)]. The antibiotics imipenem, cefepime, ceftazidime, amikacin, gentamicin, tetracycline, ticarcillin, piperacillin, sulfamethoxazole/trimethoprim, carbenicillin and streptomycin (Sigma-Aldrich) were used for MIC determination. Multidrug resistance was defined in this analysis as resistance following five drug classes: Extended-spectrum cephalosporins (ceftazidime and cefepime), beta lactamase inhibitor penicillin (ticarcillin, piperacillin and carbenicillin), aminoglycosides (amikacin, gentamicin and streptomycin), Folate pathway inhibitors (sulfamethoxazole/trimethoprim) and carbapenems (imipenem).

Yang C.H., Su P.W., Moi S.H, & Chuang L.Y. (2019). Biofilm Formation in Acinetobacter Baumannii: Genotype-Phenotype Correlation. Molecules, 24(10), 1849.

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Screening for 3GCs-R Enterobacteriaceae

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The inoculated Tryptone Soy Broth (Oxoid) medium was transferred into 5 mL of MacConkey Broth (Oxoid) containing 8 mg/L of ceftazidime (Sigma-Aldrich, Merck, St. Louis, MO, USA) and incubated at 37 °C for 24 h under agitation. Then, a loopful (10 μL) of the mixture was plated onto MacConkey Agar (BioCen, BioCubaFarma, Bejucal, Cuba) supplemented with 8 mg/L of ceftazidime (Sigma-Aldrich) for the screening of 3GCs-R Enterobacteriaceae and reincubated overnight. Lactose-positive (pink colonies) were selected and streaked three times on selective MacConkey Agar plates to obtain pure culture. Single pink colonies from each selective plate were streaked onto Tryptone Soy Agar plates containing 5% sheep blood (TSA-SB; Becton Dickinson, Franklin Lakes, NJ, USA) and incubated overnight at 37 °C. The colonies were identified using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS, Microflex LT; Bruker Daltonics, Billerica, MA, USA) and frozen at −80 °C in glycerol stocks.

Baez M., Espinosa I., Collaud A., Miranda I., Montano D.D., Feria A.L., Hernández-Fillor R.E., Obregón D., Alfonso P, & Perreten V. (2021). Genetic Features of Extended-Spectrum β-Lactamase-Producing Escherichia coli from Poultry in Mayabeque Province, Cuba. Antibiotics, 10(2), 107.

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Solubility Enhancement and Combinatorial Antibiotic Studies

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TP0586532 was synthesized by Taisho Pharmaceutical Co, Ltd., (Saitama, Japan). The drug was dissolved in dimethyl sulfoxide (for the in vitro studies) or 11 w/v% sulfobutylether-β-cyclodextrin sodium salt (11 v/w% SBE-β-CD, for the in vivo studies). Ceftazidime was purchased from Sigma-Aldrich (St. Louis, MO). Ciprofloxacin was purchased from FUJIFILM Wako Pure Chemical Corporation (Osaka, Japan). Meropenem was purchased from Sumitomo Dainippon Pharma Co., Ltd. (Osaka, Japan) and U.S. Pharmacopeial Convention (Rockville, MD). Cilastatin was purchased from Sigma-Aldrich and AvaChem Scientific (San Antonio, TX). Meropenem was combined with Cilastatin at ratio of 1:1 for the in vivo study. Ceftazidime was dissolved in distilled water. Ciprofloxacin and meropenem were dissolved in distilled water (for in vitro studies) or saline (for the in vivo studies). Cilastatin was dissolved in saline.

Fujita K., Takata I., Yoshida I., Takashima H, & Sugiyama H. (2022). TP0586532, a non-hydroxamate LpxC inhibitor, reduces LPS release and IL-6 production both in vitro and in vivo. The Journal of Antibiotics, 75(3), 136-145.

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Antibacterial Efficacy Evaluation of P. aeruginosa

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The studies were performed on a standard strain of P. aeruginosa (ATCC 9027) and a clinical isolate of this bacterium (kindly supplied by Faculty of Veterinary Medicine, Ferdowsi University of Mashhad). Ceftazidime, tobramycin, and ciprofloxacin were purchased from Sigma.

Bayroodi E, & Jalal R. (2016). Modulation of antibiotic resistance in Pseudomonas aeruginosa by ZnO nanoparticles. Iranian Journal of Microbiology, 8(2), 85-92.

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Antimicrobial Susceptibility of A. baumannii

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Antimicrobial susceptibility of the A. baumannii isolates were determined using the broth microdilution protocols of Clinical Laboratory Standards Institute [30 ] against a total of 14 known antibiotics according to methods described previously [14 (link)]. Cefotaxime, ceftazidime, ceftriaxone, gentamicin, levofloxacin, ciprofloxacin, piperacillin and polymyxin B were purchased from Sigma-Aldrich (St. Louis, MO). Meropenem was from US Pharmacopeia (Rockville, MD). Amikacin, cefepime, gatifloxacin, imipenem and tobramycin were purchased from Fisher Scientific (Tustin, CA).

Warner W.A., Kuang S.N., Hernandez R., Chong M.C., Ewing P.J., Fleischer J., Meng J., Chu S., Terashita D., English L., Chen W, & Xu H.H. (2016). Molecular characterization and antimicrobial susceptibility of Acinetobacter baumannii isolates obtained from two hospital outbreaks in Los Angeles County, California, USA. BMC Infectious Diseases, 16, 194.

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Antibiotic Susceptibility Profiling of βLR16 Clones

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The antibiotic susceptibility of βLR16 and subclones was tested in minimum inhibitory concentration assays according to CLSI guidelines except for lower incubation temperatures (24–28°C) [20 (link)]. Briefly, serial two-fold dilutions (from 512 μg ml^-1 to 0.5 μg ml^-1, no antibiotic in the last well) of antibiotics were made in Mueller-Hinton (MH) broth (Becton, Dickinson and Company, Sparks, MD, USA) in 96-well plates. The following antibiotics were tested: ampicillin, rifampin (both from Research Products International Corp., Mt. Prospect, IL, USA), carbenicillin (Fisher Scientific, Fair Lawn, NJ, USA), ciprofloxacin (Wako Chemicals USA, Inc., Richmond, VA), erythromycin (Fluka BioChemika, Buchs, Switzerland), amoxicillin, cefamandole, cefoxitin, ceftazidime, cephalexin, piperacillin, chloramphenicol, nalidixic acid, fusidic acid, and gentamicin (all from Sigma, St. Louis, MO, USA). Each well was inoculated with 10 μl containing 10⁵ colony forming units of each clone being tested. The assay was performed in duplicate at least three times, and E. coli strains EPI300, BL21(DE3), or BW25113 (Table 1) containing empty vector always served as the negative controls. The minimum inhibitory concentration (MIC) corresponded to the antibiotic concentration of the first well in which no growth was visible.

Allen H.K., An R., Handelsman J, & Moe L.A. (2015). A Response Regulator from a Soil Metagenome Enhances Resistance to the β-Lactam Antibiotic Carbenicillin in Escherichia coli. PLoS ONE, 10(3), e0120094.

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Antimicrobial Susceptibility Testing of S. algae and E. coli

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Antimicrobial susceptibility testing was performed for the S. algae clade isolates and E. coli DH5α isolates carrying bla_OXA-55-like cloned from S. algae isolates by the broth microdilution method using BBL Mueller-Hinton II broth, which was cation adjusted (Becton Dickinson and Co., USA) according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (19 ). The following antimicrobial agents were used for antibiotic susceptibility testing: ampicillin, piperacillin, cefazolin, cefotaxime, ceftazidime (Sigma-Aldrich, St. Louis, MO, USA), aztreonam (Tokyo Chemical Industry Co., Ltd., Tokyo, Japan), imipenem (Banyu Pharmaceutical, Tokyo, Japan), clavulanic acid, and meropenem (Wako Pure Chemical Industry, Ltd., Tokyo, Japan). E. coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853 were used as quality control strains. The results were interpreted according to CLSI guidelines (20 ).

Ohama Y., Aoki K., Harada S., Nagasawa T., Sawabe T., Nonaka L., Moriya K., Ishii Y, & Tateda K. (2021). Genetic Environment Surrounding blaOXA-55-like in Clinical Isolates of Shewanella algae Clade and Enhanced Expression of blaOXA-55-like in a Carbapenem-Resistant Isolate. mSphere, 6(5), e00593-21.

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Preparation and Quality Control of Antimicrobial Solutions

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Stock solutions were prepared following the guidelines of the Clinical and Laboratory Standards Institute (CLSI) (CLSI, 2018 ) by mixing the following antimicrobial agents in powder form with deionized distilled water: cefepime, cefpodoxime (TOKU-E, Bellingham, WA, United States), ceftazidime, potassium clavulanate (Sigma-Aldrich, Saint Louis, MO, United States), cefotaxime, cloxacillin (Tokyo Chemical Industry Co., LTD, Tokyo, Japan). Quality controls of the solutions were carried out in accordance with the specifications of the CLSI (2018) and EUCAST (2018) .

Correa-Martínez C.L., Idelevich E.A., Sparbier K., Kostrzewa M, & Becker K. (2019). Rapid Detection of Extended-Spectrum β-Lactamases (ESBL) and AmpC β-Lactamases in Enterobacterales: Development of a Screening Panel Using the MALDI-TOF MS-Based Direct-on-Target Microdroplet Growth Assay. Frontiers in Microbiology, 10, 13.

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Microbial Susceptibility Testing Agents

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Ampicillin (catalog no. A9518), piperacillin (catalog no. P8396), ceftriaxone (catalog no. C5793), cephalothin (catalog no. C4520), potassium clavulanate (catalog no. 33454), cefotaxime (catalog no. C7912), and chloramphenicol (catalog no. R4405) were purchased from Sigma-Aldrich. Ceftazidime was procured from Sigma (catalog no. C3809) and Research Products International (catalog no. 33527), and the products from the two sources were used interchangeably throughout the experimentation. Imipenem was obtained from USP (catalog no. 1337809) and from the commercial source (pharmacy). Sulbactam was bought from Astatech. Tazobactam (catalog no. 15141) and aztreonam (catalog no. 15151) were purchased from Chem-Impex International. Ceftolozane-Tazobactam, cefepime, meropenem, ertapenem, and doripenem were obtained from their commercial sources. Ceftaroline was provided by Allergan. Nitrocefin (catalog no. BR0063G) was purchased from Oxoid. Avibactam was purchased from Advanced ChemBlocks (catalog no. R16073).

Barnes M.D., Winkler M.L., Taracila M.A., Page M.G., Desarbre E., Kreiswirth B.N., Shields R.K., Nguyen M.H., Clancy C., Spellberg B., Papp-Wallace K.M, & Bonomo R.A. (2017). Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering. mBio, 8(5), e00528-17.

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Antimicrobial Agents and Novel Inhibitors

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Antimicrobial agents used in this study were: ampicillin, Imipenem, meropenem, cefoxitin, ceftazidime, were purchased from sigma, USA. Whereas, novel scaffold inhibitors (M1, M17, M21, M61 and M75) used in this study were purchased from Scitech Scientifics.

Khan A.U., Ali A., D.a.n.i.s.h.u.d.d.i.n., Srivastava G, & Sharma A. (2017). Potential inhibitors designed against NDM-1 type metallo-β-lactamases: an attempt to enhance efficacies of antibiotics against multi-drug-resistant bacteria. Scientific Reports, 7, 9207.

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