Bacterial resistance to aminoglycosides and beta-lactams: the Tn1331 transposon paradigm

1999 ◽  
Vol 5 (1) ◽  
pp. d20 ◽  
Author(s):  
Marcelo, E. Tolmasky
1990 ◽  
Vol 3 (1) ◽  
pp. 13-31 ◽  
Author(s):  
T D Gootz

The unprecedented growth in the number of new antibiotics over the past two decades has been the result of extensive research efforts that have exploited the growing body of knowledge describing the interactions of antibiotics with their targets in bacterial cells. Information gained from one class of antimicrobial agents has often been used to advance the development of other classes. In the case of beta-lactams, information on structure-activity relationships gleaned from penicillins and cephalosporins was rapidly applied to the cephamycins, monobactams, penems, and carbapenems in order to discover broad-spectrum agents with markedly improved potency. These efforts have led to the introduction of many new antibiotics that demonstrate outstanding clinical efficacy and improved pharmacokinetics in humans. The current review discusses those factors that have influenced the rapid proliferation of new antimicrobial agents, including the discovery of new lead structures from natural products and the impact of bacterial resistance development in the clinical setting. The development process for a new antibiotic is discussed in detail, from the stage of early safety testing in animals through phase I, II, and III clinical trials.


2021 ◽  
Vol 45 ◽  
pp. 1
Author(s):  
Silvia Boni ◽  
Gustavo H. Marin ◽  
Laura Campaña ◽  
Lupe Marin ◽  
Alejandra Corso ◽  
...  

Objective. To describe bacterial resistance and antimicrobial consumption ratio at the subnational level in Argentina during 2018, considering beta-lactams group as a case-study. Methods. Antimicrobial consumption was expressed as defined daily doses (DDD)/1000 inhabitants. Resistance of Escherichia coli, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus to beta-lactams was recorded. Resistance/consumption ratio was estimated calculating “R” for each region of Argentina, and this data was compared with other countries. Results. The most widely consumed beta-lactams in Argentina were amoxicillin (3.64) for the penicillin sub-group, cephalexin (0.786) for first generation cephalosporins, cefuroxime (0.022) for second generation; cefixime (0.043) for third generation and cefepime (0.0001) for the fourth generation group. Comparison between beta-lactams consumption and bacterial resistance demonstrated great disparities between the six regions of the country. Conclusions. The case-study of Argentina shows that antimicrobial consumption and resistance of the most common pathogens differed among regions, reflecting different realities within the same country. Because this situation might also be occurring in other countries, this data should be taken into account to target local efforts towards better antimicrobial use, to improve antimicrobial stewardship programs and to propose more suitable sales strategies in order to prevent and control antimicrobial resistance.


1995 ◽  
Vol 8 (4) ◽  
pp. 557-584 ◽  
Author(s):  
D M Livermore

beta-Lactamases are the commonest single cause of bacterial resistance to beta-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are known and may be classified by their sequences or phenotypic properties. The ability of a beta-lactamase to cause resistance varies with its activity, quantity, and cellular location and, for gram-negative organisms, the permeability of the producer strain. beta-Lactamases sometimes cause obvious resistance to substrate drugs in routine tests; often, however, these enzymes reduce susceptibility without causing resistance at current, pharmacologically chosen breakpoints. This review considers the ability of the prevalent beta-lactamases to cause resistance to widely used beta-lactams, whether resistance is accurately reflected in routine tests, and the extent to which the antibiogram for an organism can be used to predict the type of beta-lactamase that it produces.


Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 14
Author(s):  
Anna Różańska ◽  
Agnieszka Pac ◽  
Estera Jachowicz ◽  
Dorota Jaślan ◽  
Małgorzata Siewierska ◽  
...  

Background: excessive and incorrect use of antibiotics is a common event that contributes to increased bacterial resistance to antibiotics. Based on the European Centre for Disease Control and Prevention (ECDC) European Surveillance of Antimicrobial Consumption (ESAC)-Net reports, outpatient antibiotics prescribing in Poland, is higher than the European average rate. However, ECDC reports do not provide data on consumption in specific patient groups. Additional studies focused on selected patient groups are needed for a more detailed analysis. The use of antibiotics during pregnancy is inevitable due to the proven risk of complications in this period, perinatal infections, and infections in newborns, in the situation of frequent infections of the genital tract, urinary tract, and asymptomatic bacteriuria in pregnant women. The aim of this study was to analyze the use of antibiotics/the implementation of antibiotic prescriptions ordered by gynecologists during pregnancy in pregnant women in Małopolska Voivodeship, with particular emphasis on demographic data and drug groups. Material and methods: the analysis used data on the reimbursement of antibiotics from the Małopolska Health Fund for 2013–2014. The database contained information of a demographic nature: age, place of residence, date of birth, as well as information on the type of drug, and the number of packages purchased by the patients. Results: the study included 67,917 women. During pregnancy, 23.6% filled their prescriptions for antibiotics. In the first trimester, the percentage of women filling their prescriptions for antibiotics was the lowest and amounted to 7.8%, in the second and third trimesters, these were 9.0% and 11.2%, respectively. The inhabitants of rural areas bought antibiotics more often (23.5%). Most frequently, antibiotics were purchased by women under 18 years of age (32.1%), but the use of antibiotics in women aged 18–34 and over 35 was similar, amounting to 23.8% and 22.7%, respectively. Most often (94.78% of cases) monotherapy was used, including beta-lactams and beta-lactams with an inhibitor (67.3%), then second-generation cephalosporins (13.5%), macrolides (14.73%), and others. Prescription of two different preparations was found in 5.06% of cases, three (0.19%), and four or more (0.03%). Conclusions: due to the fact that studies on antibiotic therapy in pregnant women in Poland are rare, it is impossible to assess the situation thoroughly. Additionally, in Poland, the prevalence of gestational infections is unknown, and their diagnostics is important, especially in relation to microbiological diagnostics and targeted treatment. However, the present results indicate the need to implement broad health promotion programs, accessible to all women, also those living outside large cities, particularly promoting the prevention of urinary tract infections and reproductive health in general.


2020 ◽  
pp. 53-69
Author(s):  
D. Kryukova ◽  
A. Sokolov ◽  
Maksim Maksimov

Beta-lactam antibiotics are the most widely used class of antibacterial drugs, both for outpatient and hospital infections. Their further improvement in relation to overcoming the resistance of microorganisms to this group of antibiotics has given new opportunities in the treatment of severe infectious diseases. Due to the obtained high efficiency of β-lactam antibiotics and their low toxicity, they form the basis of antimicrobial chemotherapy at present. Antibiotic resistance is the phenomenon of resistance of a stain of infectious agents to the action of one or more antibacterial drugs. It is a reduced sensitivity (resistance, immunity) of a culture of microorganisms to the action of an antibacterial substance. One of the main mechanisms for the formation of bacterial resistance to them is the production of beta-lactams. To overcome the acquired resistance widespread among microorganisms, compounds have been developed that can irreversibly suppress the activity of these enzymes, the so-called beta-lactam inhibitors - clavulanic acid (clavulanate), sulbactam and tazobactam. They are used to create combined (inhibitor-protected) beta-lactams. Currently, there are several fixed combinations of beta-lactams and beta-lactam inhibitors on the pharmaceutical market. The review article presents the key issues of pharmacology of inhibitor-protected beta-lactam antibacterial drugs.


2021 ◽  
Vol 4 (1) ◽  
pp. 63-73
Author(s):  
Dewi Puspita Apsari ◽  
◽  
Ni Made Krisna Dwiyanti ◽  
I.B.N. Maharjana I.B.N. Maharjana ◽  

Hospitalized community-acquired pneumonia (CAP) patients are always prescribed intravenous (IV) antibiotics. Inappropriate and unnecessary IV antibiotics usage leads to an increase in healthcare costs and bacterial resistance. IV to per oral (PO) conversion therapy can overcome these problems. The aim of the study was to evaluate the practice of switching from intravenous to oral antibiotics of inpatients with community-acquired pneumonia (CAP). This retrospective observational study was conducted by taking patient medical record from january until december 2019. Outcomes of the study are patient characteristics, pattern use, antibiotic and type conversion therapy. Adult inpatients on conversion therapy were eligible for study enrollment. Data were analyzed descriptively using SPSS 17.0. The study showed that among 78 patients who were eligible for conversion therapy. Most of the patient has mean duration conversion therapy 48-72 hours as much as 55 (70,5%). Beta-lactams were the most commonly converted antibiotics. However, the step-down therapy was the major type of conversion practiced in this study as much as 48 (61,5) followed by sequential and switch over with numbers 21 (27%) and 9 (11,5%) respectively. Based on the study findings wangaya hospital should improve the practice of sequential therapy in order to reduce the burden of CAP.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Anna V. Kuzmina ◽  
Irina L. Asetskaya ◽  
Sergey K. Zyryanov ◽  
Vitaliy A. Polivanov

Abstract Background Comprehensive analysis of all available data in spontaneous reports (SRs) can reveal previously unidentified medication errors (MEs). Methods To detect MEs, we performed a retrospective analysis of SRs submitted to the Russian pharmacovigilance database in the period from January 01, 2012, to August 01, 2014. This study evaluated SRs of cases where beta-lactam antibiotics were the suspected drug. Results A total of 3608 SRs were analyzed. MEswere detected in 1043 reports (28.9% of all cases). The total number of detected errors was 1214. Reporters themselves indicated MEs in 29 SRs. A term denoting an ME was selected in the “Adverse Reactions” section in 18 of these SRs, whereas in the other 11 reports information on the ME was found only in the “Case narrative” section. MEs were associated with wrong indications in 32.5% of the cases; 61.0% of these cases were viral infections. Various dosing regimen violations constituted 29.7% of MEs. A contraindicated drug was administered in 17.3% of all detected MEs, most commonly to a patient with a history of allergy to the suspected drug or severe hypersensitivity reactions to other drugs of the same group. Conclusion Automatic identification of MEs in the pharmacovigilance database is sometimes precluded by the absence of a code for the respective episode in the “Adverse Reactions” section, even when the error was detected by the reporter. The most frequent types of MEs associated with the use of beta-lactams in Russia are the leading risk factors of growing bacterial resistance.


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