Hypotheses for Synthesis of Novel Chiral beta-amino-beta-lactams Through Amidines

The problem of the uncontrolled use of antibiotics currently remains unresolved. Step-by-step monitoring of meat using modern methods will reduce the risk of using contaminated meat raw materials for food production. Qualitative monitoring will identify samples containing residual antimicrobial substances. The use of methods for identifying groups of antibiotics will help narrow the search for antibiotics by expensive chromatographic methods. A study was carried out of beef, pork and poultry meat, which is used in meat processing plants in the production of raw smoked sausages, using two methods. At the first stage, using a qualitative microbiological method, the raw meat was evaluated for the presence of antimicrobial substances, then their group was determined using a NovoCyte flow cytometer. According to the results of a study on a flow cytometer, it was found that out of 10 groups of antibiotics that can be determined by the tested method, the group of lincosamides was not found in all meat samples. The most common groups of chemotherapy drugs in pork were sulfonamides – 29.6 %, tetracycline group – 18.5 % and beta-lactams – 14.8 %, and in beef aminoglycosides – 36.7 %, phenicols – 30 % and beta-lactams – 13.3 %. In poultry meat samples, the most common were sulfonamides – 23.2 %, fenicols – 23.2 %, and beta-lactams – 16 %. Five groups of antibiotics were found in all studied types of meat: fenicols, β-lactams, macrolides, polypeptide antibiotics, and quinolones. This indicates their widespread use in animal husbandry and poultry farming.

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2.8-A Structure of penicillin-sensitive D-alanyl carboxypeptidase-transpeptidase from Streptomyces R61 and complexes with beta-lactams.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(18)88993-1 ◽

1985 ◽

Vol 260 (10) ◽

pp. 6449-6458

Author(s):

J A Kelly ◽

J R Knox ◽

P C Moews ◽

G J Hite ◽

J B Bartolone ◽

...

Keyword(s):

Beta Lactams

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Wastewaters, with or without Hospital Contribution, Harbour MDR, Carbapenemase-Producing, but Not Hypervirulent Klebsiella pneumoniae

Antibiotics ◽

10.3390/antibiotics10040361 ◽

2021 ◽

Vol 10 (4) ◽

pp. 361

Author(s):

Adela Teban-Man ◽

Anca Farkas ◽

Andreea Baricz ◽

Adriana Hegedus ◽

Edina Szekeres ◽

...

Keyword(s):

Principal Component Analysis ◽

Klebsiella Pneumoniae ◽

Wastewater Treatment Plants ◽

Principal Component ◽

Drug Resistant ◽

Beta Lactams ◽

Carbapenemase Gene ◽

Antibiotic Susceptibility Patterns ◽

Sequence Types ◽

Susceptibility Patterns

Carbapenemase-producing Klebsiella pneumoniae (CPKP) isolated from influent (I) and effluent (E) of two wastewater treatment plants, with (S1) or without (S2) hospital contribution, were investigated. The strains belonged to the Kp1 phylogroup, their highest frequency being observed in S1, followed by S2. The phenotypic and genotypic hypervirulence tests were negative for all the strains tested. At least one carbapenemase gene (CRG), belonging to the blaKPC, blaOXA-48, blaNDM and blaVIM families, was observed in 63% of CPKP, and more than half co-harboured two to four CRGs, in different combinations. Only five CRG variants were observed, regardless of wastewater type: blaKPC-2, blaNDM-1, blaNDM-6, blaVIM-2, and blaOXA-48. Sequence types ST258, ST101 and ST744 were common for both S1 and S2, while ST147, ST525 and ST2502 were found only in S1 and ST418 only in S2. The strains tested were multi-drug resistant (MDR), all being resistant to beta-lactams, cephalosporins, carbapenems, monobactams and fluoroquinolones, followed by various resistance profiles to aminoglycosides, trimethoprim-sulphamethoxazole, tigecycline, chloramphenicol and tetracycline. After principal component analysis, the isolates in S1 and S2 groups did not cluster independently, confirming that the antibiotic susceptibility patterns and gene-type profiles were both similar in the K. pneumoniae investigated, regardless of hospital contribution to the wastewater type.

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Beta-Lactams Toxicity in the Intensive Care Unit: An Underestimated Collateral Damage?

Microorganisms ◽

10.3390/microorganisms9071505 ◽

2021 ◽

Vol 9 (7) ◽

pp. 1505

Author(s):

Claire Roger ◽

Benjamin Louart

Keyword(s):

Risk Factors ◽

Intensive Care Unit ◽

Intensive Care ◽

Clinical Manifestations ◽

Acute Interstitial Nephritis ◽

Convulsive Status Epilepticus ◽

Beta Lactam ◽

Beta Lactams ◽

Drug Induced ◽

Icu Patients

Beta-lactams are the most commonly prescribed antimicrobials in intensive care unit (ICU) settings and remain one of the safest antimicrobials prescribed. However, the misdiagnosis of beta-lactam-related adverse events may alter ICU patient management and impact clinical outcomes. To describe the clinical manifestations, risk factors and beta-lactam-induced neurological and renal adverse effects in the ICU setting, we performed a comprehensive literature review via an electronic search on PubMed up to April 2021 to provide updated clinical data. Beta-lactam neurotoxicity occurs in 10–15% of ICU patients and may be responsible for a large panel of clinical manifestations, ranging from confusion, encephalopathy and hallucinations to myoclonus, convulsions and non-convulsive status epilepticus. Renal impairment, underlying brain abnormalities and advanced age have been recognized as the main risk factors for neurotoxicity. In ICU patients, trough concentrations above 22 mg/L for cefepime, 64 mg/L for meropenem, 125 mg/L for flucloxacillin and 360 mg/L for piperacillin (used without tazobactam) are associated with neurotoxicity in 50% of patients. Even though renal complications (especially severe complications, such as acute interstitial nephritis, renal damage associated with drug induced hemolytic anemia and renal obstruction by crystallization) remain rare, there is compelling evidence of increased nephrotoxicity using well-known nephrotoxic drugs such as vancomycin combined with beta-lactams. Treatment mainly relies on the discontinuation of the offending drug but in the near future, antimicrobial optimal dosing regimens should be defined, not only based on pharmacokinetics/pharmacodynamic (PK/PD) targets associated with clinical and microbiological efficacy, but also on PK/toxicodynamic targets. The use of dosing software may help to achieve these goals.

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An EAACI Task Force Report on Allergy to Beta‐Lactams in Children: Clinical Entities and Diagnostic Procedures

Pediatric Allergy and Immunology ◽

10.1111/pai.13529 ◽

2021 ◽

Author(s):

N Blanca‐Lopez ◽

M Atanaskovic‐Markovic ◽

ER Gomes ◽

M Kidon ◽

S Kuyucu ◽

...

Keyword(s):

Task Force ◽

Diagnostic Procedures ◽

Beta Lactams ◽

Task Force Report

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An Application of Imipenem Discs or P. aeruginosa ATCC 27853 Reference Strain Increases Sensitivity of Carbapenem Inactivation Method for Non-Fermenting Gram-Negative Bacteria

Antibiotics ◽

10.3390/antibiotics10070875 ◽

2021 ◽

Vol 10 (7) ◽

pp. 875

Author(s):

Tomasz Bogiel ◽

Mateusz Rzepka ◽

Eugenia Gospodarek-Komkowska

Keyword(s):

Human Population ◽

Reference Strain ◽

Resistance Mechanisms ◽

Gram Negative Bacteria ◽

Opportunistic Pathogens ◽

Beta Lactams ◽

Gram Negative ◽

E Coli ◽

Human Infections ◽

Reliable Diagnostic Method

Non-fermenting Gram-negative rods are one of the most commonly isolated bacteria from human infections. These microorganisms are typically opportunistic pathogens that pose a serious threat to public health due to possibility of transmission in the human population. Resistance to beta-lactams, due to carbapenemases synthesis, is one of the most important antimicrobial resistance mechanisms amongst them. The aim of this study was to evaluate the usefulness of the Carbapenem Inactivation Method (CIM), and its modifications, for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. This research involved 81 strains of Gram-negative rods. Of the tested strains, 55 (67.9%) synthesized carbapenemases. For non-fermenting rods, 100% sensitivity and specificity was obtained in the version of the CIM test using imipenem discs and E. coli ATCC 25922 strain. The CIM test allows for differentiation of carbapenems resistance mechanisms resulting from carbapenemase synthesis from other resistance types. It is a reliable diagnostic method for the detection of carbapenemase activity amongst non-fermenting Gram-negative rods. Application of imipenem discs and P. aeruginosa ATCC 27853 reference strain increases CIM results sensitivity, while imipenem discs and E. coli ATCC 25922 strain use maintains full precision of the test for non-fermenting rods.

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Cumulative Effect of an Antimicrobial Stewardship and Rapid Diagnostic Testing Bundle on Early Streamlining of Antimicrobial Therapy in Gram-Negative Bloodstream Infections

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00189-17 ◽

2017 ◽

Vol 61 (9) ◽

Cited By ~ 31

Author(s):

P. B. Bookstaver ◽

E. B. Nimmich ◽

T. J. Smith ◽

J. A. Justo ◽

J. Kohn ◽

...

Keyword(s):

Antimicrobial Stewardship ◽

Antimicrobial Therapy ◽

Phase 1 ◽

Bloodstream Infections ◽

Antimicrobial Stewardship Program ◽

Phase 2 ◽

Beta Lactams ◽

Gram Negative ◽

Stewardship Program ◽

Tof Ms

ABSTRACT The use of rapid diagnostic tests (RDTs) enhances antimicrobial stewardship program (ASP) interventions in optimization of antimicrobial therapy. This quasi-experimental cohort study evaluated the combined impact of an ASP/RDT bundle on the appropriateness of empirical antimicrobial therapy (EAT) and time to de-escalation of broad-spectrum antimicrobial agents (BSAA) in Gram-negative bloodstream infections (GNBSI). The ASP/RDT bundle consisted of system-wide GNBSI treatment guidelines, prospective stewardship monitoring, and sequential introduction of two RDTs, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and the FilmArray blood culture identification (BCID) panel. The preintervention period was January 2010 through December 2013, and the postintervention period followed from January 2014 through June 2015. The postintervention period was conducted in two phases; phase 1 followed the introduction of MALDI-TOF MS, and phase 2 followed the introduction of the FilmArray BCID panel. The interventions resulted in significantly improved appropriateness of EAT (95% versus 91%; P = 0.02). Significant reductions in median time to de-escalation from combination antimicrobial therapy (2.8 versus 1.5 days), antipseudomonal beta-lactams (4.0 versus 2.5 days), and carbapenems (4.0 versus 2.5 days) were observed in the postintervention compared to the preintervention period (P < 0.001 for all). The reduction in median time to de-escalation from combination therapy (1.0 versus 2.0 days; P = 0.03) and antipseudomonal beta-lactams (2.2 versus 2.7 days; P = 0.04) was further augmented during phase 2 compared to phase 1 of the postintervention period. Implementation of an antimicrobial stewardship program and RDT intervention bundle in a multihospital health care system is associated with improved appropriateness of EAT for GNBSI and decreased utilization of BSAA through early de-escalation.

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