Beta-lactam Ring Research Articles

Pre-Operative Management of the Penicillin Allergic Patient: A Narrative Review

Penicillin is a frequently reported medication allergy. The beta-lactam ring shared between cephalosporins and penicillin often leads to the use of alternative antibiotics for surgical prophylaxis due to concern for cross-reactivity, despite a true IgE-mediated hypersensitivity being very rare. This misconception leads to the use of less effective second line antibiotics, such as clindamycin or vancomycin, for penicillin-allergic patients which has been shown to increase odds of postoperative infection in elective knee arthroplasty, shoulder arthroplasty and spine surgery. Preoperative penicillin allergy testing has been demonstrated to be a cost-effective measure in the prevention of prosthetic joint infection and is suggested for all penicillin-allergic patients in the peri-operative setting. This review highlights and summaries the outcomes of orthopaedic procedures in patients with reported penicillin allergies and discusses potential solutions to the perioperative challenges of patients with reported penicillin allergies.

Bacteroides fragilis бактериясының карбапенемге төзімділіктің молекулалық механизмдер

Carbapenems are generally the most successful group of antibacterial drugs due to the combination of a wide spectrum of activity, rapid bactericidal effect, greater potential for the selection of resistant strains and resistance compared to other classes of antibacterial drugs. Carbapenems are potent antimicrobial agents that effective against a wide range of bacteria, including both gram-positive and gram-negative types. Bacteroides fragilis is one of the important and frequently isolated bacteria in clinical laboratories for mono- and polymicrobial infections. Bacteroides fragilis is also resistant to macrolides, beta-lactams, metronidazole, and some newer fluoroquinolones. Carbapenem resistance is considered a rapidly growing problem due to overuse of the drug in therapy. Molecular mechanisms of carbapenem resistance in bacteria involve several factors. The first mechanism is associated with the development of multidrug resistance in microorganisms through the export of drugs via efflux systems. This process enables bacteria to avoid the negative effects of antibiotics. The second mechanism involves the synthesis of beta-lactamases, which is a key factor in the resistance of Bacteroides fragilis to beta-lactam compounds, including carbapenems. These enzymes are capable of hydrolyzing the beta-lactam ring of antibiotics, rendering them inactive. The third mechanism involves changes in the structure of penicillin-binding proteins (PBPs), which are the target sites for carbapenems. Mutations in genes encoding PBPs can lead to decreased affinity of carbapenems to these proteins, making them less sensitive to the antibiotic. The cfiA gene plays an important role in carbapenem resistance, especially in B. fragilis. It encodes a protein that confers resistance to carbapenems and other beta-lactam antibiotics. This gene can be horizontally transferred between different bacteria, increasing the risk of resistance spreading. Understanding the mechanism of antimicrobial resistance is important to avoid pitfalls when selecting alternative antimicrobials for the treatment and prevention of severe infections. This article examines several mechanisms that influence the resistance of B. fragilis strains to carbapenems.

DOCKING, SYNTHESIS AND β-LACTAMASE INHIBITORY ACTIVITY EVALUATION FOR NEW AMIDE COMPOUNDS

The beta-lactams are recognized as effective antibiotics for treating infections, yet bacterial production of β-lactamase, which hydrolyzes the beta-lactam ring, can render these drugs inactive. Combining these antibiotics with a β-lactamase inhibitor, such as clavulanic acid, mitigates this resistance. In a docking study involving Temoniera-1 (TEM-1), 1pzp, we induced the synthesis of eight amide compounds by reacting acid chloride derivatives with sulphathiazol or oxadiazol amine, forming an amide bond. The newly synthesized compounds were differentiated using physical and spectroscopic methods and verified biologically by estimating their minimum inhibitory concentration (MIC) against four strains of βlactamase G(+)ve and G(-)ve bacteria. Their anti β-lactamase behaviors were then compared with that of clavulanic acid as a co-inhibitor with amoxicillin against the same four strains of bacteria. The results indicate that four of the new amides exhibit excellent anti-β-lactamase activity and contain one or more hydrophobic residues in their structures. Halogen atoms enhance the selectivity of tower β-lactamases. Derivatives of both oxadiazole and sulfathiazole scaffolds show promising anti-β-lactamase activity as nonβ-lactam inhibitors.

A rare case of oxacillin-induced leukocytoclastic vasculitis

Leukocytoclastic vasculitis is a pathology whose mechanisms are associated with the process of vascular inflammation. It is estimated that up to 24% of the cases of vasculitis are drug-related, with beta-lactam antimicrobials being one of the pharmacological groups commonly associated with this adverse outcome. Oxacillin, a semisyntheticpenicillin, has a beta-lactam ring that confers biological activity and is most frequently associated with reports of leukocytoclastic vasculitis. However, similar cases related to this antimicrobial are rare, with only three cases identified in the literature. Against this background, we report a fourth case of leukocytoclastic vasculitis in a 56-yearold man, on oxacillin treatment, who developed the vasculitis on the 3rd day of antimicrobial use. In addition to oxacillin suspension, he was treated with 125 mg/day of intravenous methylprednisolone for seven days, followed by 20 mg/day of oral prednisone for four days, resulting in satisfactory remission of the skin lesions and no new adverse outcomes. This case provides further evidence supporting the potential causal relationship between the use of oxacillin and the development of leukocytoclastic vasculitis, albeit a rare occurrence. The positive response to therapeutic interventions, such as oxacillin suspension and corticosteroid treatment, underscores the effectiveness of these approaches in addressing this complication.

Carbapenemase Detection and Identification: Which method should be Chosen?

Carbapenemase production constitutes the key mechanism of resistance to carbapenems. Rapid detection or confirmation of the involvement of carbapenemase-producing bacteria (CPB) in infections is crucial for adequate antibiotic therapy and infection control, particularly during epidemics or for surveillance purposes. The Ambler classification proposes four classes of carbapenemases: classes A, B, C, and D. Carbapenemases A, C, and D are called serine carbapenemases because they use serine in their active site to catalyze the hydrolysis of carbapenems. Class B carbapenemases are metallo-beta-lactamases (MBLs) that use a cation (Zn2+) to hydrolyze the beta-lactam ring. Biochemical, chromogenic, immunochromatographic, mass spectrometric, and molecular methods have both advantages and limitations for carbapenemase detection. Although there is no single method that meets all specifications of an ideal test, it is important to explore methods to identify the most suitable ones. Thus, according to the research articles reported in this review and the criteria (cost, turnaround time, sensitivity, specificity, expertise needs, target carbapenemases), chromogenic tests such as ChromID CARBA SMART and CHROMagar™ mSuperCARBA™ would be the best candidates for the rapid and effective detection of carbapenemase-producing bacteria in developing countries. Moreover, Carba NP, SUPERCARBA and Carbapenem Inactivation Method (CIM) could also be considered good carbapenemase-detecting methods. WGS may be reserved for large-scale funded studies of carbapenemase-producing bacteria.

Exploiting the aggregation propensity of beta-lactamases to design inhibitors that induce enzyme misfolding

There is an arms race between beta-lactam antibiotics development and co-evolving beta-lactamases, which provide resistance by breaking down beta-lactam rings. We have observed that certain beta-lactamases tend to aggregate, which persists throughout their evolution under the selective pressure of antibiotics on their active sites. Interestingly, we find that existing beta-lactamase active site inhibitors can act as molecular chaperones, promoting the proper folding of these resistance factors. Therefore, we have created Pept-Ins, synthetic peptides designed to exploit the structural weaknesses of beta-lactamases by causing them to misfold into intracellular inclusion bodies. This approach restores sensitivity to a wide range of beta-lactam antibiotics in resistant clinical isolates, including those with Extended Spectrum variants that pose significant challenges in medical practice. Our findings suggest that targeted aggregation of resistance factors could offer a strategy for identifying molecules that aid in addressing the global antibiotic resistance crisis.

The Activity of Some Antibiotics Depend on Stereochemistry of Them (Its Structure)

The chiral carbon in biological compounds lead to its activity, for example, the beta lactam ring contains two carbon centers carbon number three and carbon number four both are chiral carbon. This chirality plays important role in the activity and bind with structures activity relationship. Also the ofloxacin act on topoisomerase which required for protein Synthesis of microorganism, the ofloxacin when become Levo isomer not only racemic mixture the activity is more than the racemic or Dextro isomer. Also, the old Antibiotics Chloramphenicol the RR’ isomers only active not the other isomers of Chloramphenicol.

A Review on Benzothiazole Derivatives and Their Biological Significances

Benzothiazole is a molecule that has a wide range of pharmacological activities. The addition of a fluorine atom into the structure of benzothiazole enhances the various activities of the drug as the alteration of hydrogen or oxygen atom from a carbon bond by a fluorine atom improves desirable pharmacological properties such as greater biological half-life, higher ability to bind with the targeted receptor, and also enhances the lipophilic character of the drug. The special property that makes fluorine a very important molecule in the drug discovery includes a very small radius of the fluorine atom, a higher attacking power towards electrons, and a very low polarizability of the fluorine atom. Literature reveals that strong electron-attacking groups like fluorine in the structure of benzothiazole can exhibit anticancer activity of the drug, benzothiazole with Sulphonamide or with beta-lactam ring enhances the anti-inflammatory and antioxidant activity. Benzothiazole with oxadiazole shows potent anthelmintic activity [1-5].

Theoretical insights into the reaction mechanism and kinetics of ampicillin degradation with hydroxyl radical.

Ampicillin (AMP) is a penicillin-class beta-lactam antibiotic widely used to treat infections caused by bacteria. Therefore, due to its widespread use, this antibiotic is found in wastewater, and it contains long-term risks such as toxicity to all living organisms. In this study, the degradation reaction of ampicillin with hydroxyl radical was investigated by the density functional theory (DFT) method. All the calculations were performed with B3LYP functional at 6-31G(d,p) basis set. The thermodynamic energy values and reaction rates of all possible reaction paths were calculated. The addition of the hydroxyl radical to the carbonyl group of the beta-lactam ring is thermodynamically the most probable reaction path. The calculated overall reaction rate constant is 1.36 × 1011M-1s-1. To determine the effect of temperature on the reaction rate, rate constants were calculated for all reaction paths at five different temperatures. The subsequent reaction kinetics of the most preferred primary route was also examined, and the toxicity values of the intermediates were estimated. The acute toxicity of AMP and its degradation product were calculated using the Ecological Structure Activity Relationships (ECOSAR) software. The degradation product was found to be more toxic than AMP.

Comparative Evaluation of Three Phenotypic Tests-Carba NP, Modified Carba NP and Rapidec Carba NP Test for Rapid Detection of Carbapenem Resistance in Blood Culture Isolates of Escherichia coli in an ICU Setting.

To determine the antibiotic resistance pattern, the prevalence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance in blood culture isolates of E. coli. Further, we evaluated and compared Carba NP, Modified Carba NP and a kit-based Rapidec Carba NP test to detect carbapenem resistance rapidly. Twenty-six carbapenem-resistant strains and four susceptible strains were selected. The three methods mentioned above were evaluated as per Clinical Laboratory Standards Institute (CLSI). These tests are based on biochemical detection of the hydrolysis of the beta-lactam ring of a carbapenem-imipenem, followed by the colour change of a pH indicator. Carba NP test was positive in 24 out of 26 isolates; the Modified Carba NP and Rapidec Carba NP tests were positive for all the isolates (26/26). All the carbapenemase non-producers (100%, 04/04) were negative. Modified Carba NP is a more effortless and inexpensive alternative to the Carba NP test, allowing the detection of carbapenemase activity directly from bacterial cultures of Enterobacteriaceae. The test could be used in low-income countries with large reservoirs for carbapenemase producers and can be implemented in any laboratory worldwide.

891. Challenging the Dogma of Beta-Lactam Allergies: Impact of an Antimicrobial Stewardship Program

Abstract Background Penicillin allergies are reported in approximately 10% of patients in the US but ∼90% of these allergies can be de-labeled. Consequences of inappropriate allergy labeling leads to use of alternative agents associated with increased adverse events and resistance rates, leading to worse outcomes. Though all beta-lactam agents share the core beta-lactam ring, the R1 side chain has been identified as the focus of cross-reactivity. Agents that do not share the same or similar R1 side chain are likely to have negligible risk of hypersensitivity reactions. The purpose of this study was to assess the incidence of hypersensitivity reactions in patients with a documented beta-lactam allergy that received a beta-lactam agent with a different side chain based on recommendation by an antimicrobial stewardship clinical pharmacist. Methods This was a retrospective, single-center, observational study of patients admitted to NYU Langone Hospital – Long Island from October 2019 to February 2022. Data was collected by review of the electronic medical record and descriptive statistics were generated as appropriate. The primary outcome was the proportion of patients that experienced a hypersensitivity reaction to a beta-lactam agent with a different side chain. Secondary outcomes included impact of antimicrobial stewardship intervention by clinical pharmacists, avoidance of alternative antibiotics, and cost comparison between agents requested and recommended. Results A total of 181 patients were included in the final analysis, including 37 patients with a history of anaphylaxis. No patients with a documented beta-lactam allergy experienced a hypersensitivity reaction upon receiving a beta-lactam agent with a different side chain. Within the cost comparison, meropenem accounted for 45.6% and 75.9% of the total minimum and maximum wholesale costs of requested agents, respectively. Conclusion The results of this study suggest that receipt of a beta-lactam agent with a different side chain is safe in patients with a history of beta-lactam allergy, including anaphylaxis history, and supports 'in the moment' antimicrobial stewardship intervention to ensure patients receive optimal therapy when access to in-depth allergy history or detailed patient interview is not feasible. Disclosures All Authors: No reported disclosures.

Molecular docking analysis of beta-lactamase from Salmonella species with eicosane.

beta-lactamases of Salmonella Sp. belongs to a group of enzymes produced by bacteria which break the beta-lactam ring to inactivate the beta-lactam antibiotic. Therefore, it is of interest to document the molecular docking analysis of beta-lactamase from Salmonella species with eicosane. Hence, we document the molecular docking analysis data of beta-lactamase from Salmonella species with eicosane.

Synthesizes, characterization, molecular docking and in vitro bioactivity study of new compounds containing triple beta lactam rings

Penicillin bioactivity is continuously decreased due to the misuses by people which resulted in an antibiotics resistance. However, B-lactam ring is still an effect group the attack bacterial infection. In this study, we aimed to synthesize compounds with triple B-lactam rings and study in vitro their bioactivity. Schiff bases were followed to form two effective ligands involving triple B-lactam rings that were also docked against Penicillin binding protein to show their abilities through computational simulation studies. The synthesis of the compounds was mainly performed in two major steps: the first step was to form three Schiff bases of the compound named as BTTP compound and the second step to perform a cyclisation to produce triple B-lactam rings named as BTTCDP compounds. The prepared compounds were then confirmed using various routinely spectroscopic methods such as FTIR, NMR and CHN techniques. In vitro study showed (MIC in µg ml−1) ranged from (0.254 and 0.568), respectively for both ligands. However, no inhibition was shown against fungus which could be considered as specific antibacterial. The molecular docking study showed the pockets of the binding with minimum free energy about -8.9 and -9.0 kcal/mol. All to gather, the two novel compounds containing triple B-lactam rings showed an effective bioactivity that are promising for in vivo studies in future.

Design, Molecular Docking, Synthesis of Aromatic Amino Acids Linked to Cephalexin.

Infections caused by bacteria have a significant impact on public health. Chemical synthesis of new derivatives of cephalexin inked to amino acid (tryptophan or histidine) through an amide bond at the acyl side chain is achieved. This is a new
 approach of incorporating, tryptophan and histidine into the the primary amino group of cephalexin, in order to provide a bulky group very close to the β-lactam ring. This chemical addition act as isosteric group to the alkoximino that protect beta lactam ring from bacterial beta lactamase enzyme. The new derivatives may show resistance to β-lactamases, improve activity and pharmacokinetic properties and may give new life for old drugs that are susceptible to hydrolysis by most β-lactamases. The chemical structures of these derivatives were confirmed by: FTIR, 1H-NMR spectroscopy, elemental micro analysis and some physical properties. Molecular docking on serine beta lactamase and prediction of ADME parameters were recorded using GOLD suite and Swiss ADME software respectively. Docking scores of the new derivatives of Cephalexin on β-lactamases were higher than those of Cephalexin, which may indicate better activity

Machine learning for functional dynamics in TEM beta-lactamase predicts inhibitor binding sites

The most common class of antibiotics, Beta Lactams, are most often resisted by an enzyme called Beta-Lactamase (BL) which hydrolyses the antibiotic's beta lactam ring, rendering it useless. Extended Spectrum BL (ESBL) expands substrate specificity to include third generation cephalosporins. A machine learning method called Supervised Projective Learning with Orthogonal Completeness (SPLOC) is applied to discriminate the functional dynamics in BL associated with substrate specificity while exploring potential binding targets for inhibitors.

Docking and Molecular Dynamic of Microalgae Compounds as Potential Inhibitors of Beta-Lactamase.

Bacterial resistance is responsible for a wide variety of health problems, both in children and adults. The persistence of symptoms and infections are mainly treated with β-lactam antibiotics. The increasing resistance to those antibiotics by bacterial pathogens generated the emergence of extended-spectrum β-lactamases (ESBLs), an actual public health problem. This is due to rapid mutations of bacteria when exposed to antibiotics. In this case, β-lactamases are enzymes used by bacteria to hydrolyze the beta-lactam rings present in the antibiotics. Therefore, it was necessary to explore novel molecules as potential β-lactamases inhibitors to find antibacterial compounds against infection caused by ESBLs. A computational methodology based on molecular docking and molecular dynamic simulations was used to find new microalgae metabolites inhibitors of β-lactamase. Six 3D β-lactamase proteins were selected, and the molecular docking revealed that the metabolites belonging to the same structural families, such as phenylacridine (4-Ph), quercetin (Qn), and cryptophycin (Cryp), exhibit a better binding score and binding energy than commercial clinical medicine β-lactamase inhibitors, such as clavulanic acid, sulbactam, and tazobactam. These results indicate that 4-Ph, Qn, and Cryp molecules, homologous from microalgae metabolites, could be used, likely as novel β-lactamase inhibitors or as structural templates for new in-silico pharmaceutical designs, with the possibility of combatting β-lactam resistance

Beta-lactam antibiotics and extended spectrum beta-lactamases

Extended spectrum beta-lactamases (ESBLs) are enzymes produced by bacteria, mostly members of the family Enterobacteriaceae commonly Escherichia coli and Klebsiella pneumoniae. ESBLs hydrolyze the beta-lactam ring of beta-lactam antibiotics making these antibiotics ineffective therefore rendering the bacteria resistance against beta-lactam antibiotics. The global upsurge of ESBLs producing bacteria causing both hospital and community acquired infections mostly urinary tract infections, pneumonia and bloodstream infections, threatens the effectiveness of infectious diseases treatment. ESBL families; TEM, SHV and CTX-M are globally disseminated and frequently detected in clinical isolates as well as colonization and contamination isolates. Various laboratory detection methods of ESBLs producing Gram negative bacteria are available. These methods; phenotypic methods, automated methods and molecular-based methods are varying in sensitivity and specificity, need of technical expertise, and rapidness. Therefore, they should be clearly understood before being employed for routine or research use for detection of ESBLs production among Enterobacteriaceae. In addition, understanding the mode of action and mechanisms of resistance to beta-lactam antibiotics, and the epidemiology of ESBLs producing bacteria is of paramount.

Nanoparticles engineered from endophytic fungi (Botryosphaeria rhodina) against ESBL-producing pathogenic multidrug-resistant E. coli

BackgroundESBLs hydrolyze the beta-lactam ring of antibiotics and are not affected by 1st, 2nd, 3rd, and 4th generation antibiotics. There are over 400 ESBL enzymes that have already been investigated globally are present in Enterobacteriaceae species such as Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca strains. Prevalence of ESBLs is slowly increased, from 10 to 40% in E. coli and K. pneumonia strains. Microorganisms producing ESBLs are challenging to physicians, clinical microbiologists, and antibiotic researchers.ResultsIn this study, ESBL-producing strains of E. coli were subjected to antibiotic sensitivity screening. The efficacy of myco BR-AgNPs on growth in E. coli ATCC (25922) and clinical isolates of E. coli was determined by well diffusion method. Myco BR-AgNPs reduced the growth as well as inhibited the biofilm formation in ESBL-producing strains of E. coli. MIC and MBC were determined by using serial microdilution and surface drop method. The MICs were 0.078–0.625 µg/ml and MBCs were 0.312–1.25 µg/ml. The biofilm formation was effectively inhibited by myco BR-AgNPs when compared with control. The expression of CTX-M-15 gene was studied in clinical isolates of E. coli treated with antibiotic (positive control), mycosilver nanoparticles (test) and compared with the other positive control (untreated strains). Interestingly, the expression of CTX-M-15 was downregulated in the samples treated with myco BR-AgNPs.ConclusionThe use of myco BR-AgNPs and their growth inhibitory effect on ESBL-positive strains were the main focus of this research. ATCC and ESBL strains used in this study were effectively inhibited by myco BR-AgNPs. The effect of myco BR-AgNPs on the expression of a gene encoding CTX-M-15 was tested on a molecular level, and the observed results showed that the gene expression was reduced when compared with control and antibiotic treatment. According to the current research, myco BR-AgNPs synthesized with the aid of endophytic fungal extract could be used to suppress the growth of ESBL-positive strains of E. coli. Myco BR-AgNPs may be an important alternative to various antibiotics in preventing bacterial resistance if optimized and tested for toxicity.

Pengolahan Air Limbah Betalaktam Menggunakan Reagen Kaporit, PAC, dan Alum Sulfat

Beta lactam antibiotics are pollutant in water bodies such as lakes and rivers. Beta lactam rings may have a negative impact on living beings in lakes and rivers. Beta lactam rings also cause resistance or bacterial resistance to antibiotics. If human beings are exposed to beta lactam ring, this could negatively impact on their health. This study attempted to break down the beta lactam rings with several chemical reagents. These reagents hydrolyze the beta lactam ring and are then analyzed using the HPLC (High Performance Liquid Chromatography) instrument. This study aims to determine the how effective the reagent for breaking the beta lactam ring. The research was conducted in three stages: preliminary research, research on reagent effectiveness , and research on β-lactamase degradation using reagents. The results showed that calcium hypochlorite was able to break the beta lactam cycle with 100% efficiency.

ANTIBIOTIC RESISTANCE OF BACTERIA OF THE FAMILY PASTEURELLACEAE, PATHOGENS OF RESPIRATORY INFECTIONS OF CATTLE AND PIGS

In the article a literature review of scientific papers on the topic of antimicrobial resistance of bacteria of the family Pasteurellaceae, pathogens of respiratory diseases in pigs and cattle, is presented. The main mechanisms of the development of Pasteurellaceae resistance to β-lactam antibiotics are the synthesis of β-lactamases by bacteria, what are able to break the beta-lactam ring, thereby inactivating β-lactams, or alteration of the penicillin-binding proteins structure. Other mechanisms, such as reduced permeability of the outer membrane or the process of active removal of antibiotics from the bacterial cell (efflux), are very rare. Resistance among Pasteurellaceae to β-lactams is often associated with plasmids. Eflux and ribosomal protection are the main mechanisms for the development of resistance of Pasteurellaceae to tetracyclines. At least nine tetracycline resistance genes (tet genes) have been identified in bacteria of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus, what encode these processes. Resistance to aminoglycosides and aminocyclitols is mainly caused by enzymatic inactivation of antibiotics, as well as through mutations in chromosomal genes. Many plasmids carry genes of resistance to aminoglycosides, causing resistance to antibiotics of other groups. Chemical modification of a ribosomal target by rRNA methylases and mutations in ribosomal proteins are the main resistance mechanisms of bacteria of the family Pasteurellaceae to macrolides. Many gram-negative bacteria have a natural resistance to macrolide antibiotics. The development of lincosamide resistance is influenced by methyltransferase 23S rRNA, active efflux proteins, enzymatic inactivation and chromosomal mutations. Resistance of bacteria of the family Pasteurellaceae to chloramphenicol is caused mainly by enzymatic inactivation, while the emergence of resistance to fluorophenicol is associated with the efflux of an antibiotic from a bacterial cell. Plasmids carrying phenicol resistance genes were detected in isolates of P. multocida, M. haemolytica, A. pleuropneumoniae and H. parasuis. Usually the level of bacteria sensitivity of the genus Pasteurella, Mannheimia, Actinobacillus and Haemophilus to quinolones is quite high. Resistance to quinolones mainly occurs due to mutational alterations in chromosomal genes, and may also be in consequence of the export antibiotics from the cell by membrane proteins or thanks to qnr genes of plasmids. The main mechanism of resistance to sulfonamides and trimethoprim is both plasmid-mediated and mutation-induced production of altered dihydropteroate synthetase and dihydrofolate reductase with reduced affinity with these antimicrobials. Monitoring of antibiotic resistance with the determination of its mechanism phenomenon will facilitate the choice of an effective agent of etiotropic therapy of respiratory diseases of cattle and pigs caused by bacteria of the family Pasteurellaceae.