Mechanism of antibiotics action and development of antiobiotic resistance (original) (raw)

Antibiotic resistance and extended spectrum beta-lactamases: Types, epidemiology and treatment

Antibiotic resistance is a problem of deep scientific concern both in hospital and community settings. Rapid detection in clinical laboratories is essential for the judicious recognition of antimicrobial resistant organisms. Production of extended-spectrum b-lactamases (ESBLs) is a significant resistance-mechanism that impedes the antimicrobial treatment of infections caused by Enterobacteriaceae and is a serious threat to the currently available antibiotic armory. ESBLs are classified into several groups according to their amino acid sequence homology. Proper infection control practices and barriers are essential to prevent spread and outbreaks of ESBL producing bacteria. As bacteria have developed different strategies to counter the effects of antibiotics, the identification of the resistance mechanism may help in the discovery and design of new antimicrobial agents. The carbapenems are widely regarded as the drugs of choice for the treatment of severe infections caused by ESBL-producing Enterobacteriaceae, although comparative clinical trials are scarce. Hence, more expeditious diagnostic testing of ESBL-producing bacteria and the feasible modification of guidelines for community-onset bacteremia associated with different infections are prescribed. ª 2014 Production and hosting by Elsevier B.V. on behalf of King Saud University.

What's new in antibiotic resistance? Focus on beta-lactamases

Drug Resistance Updates, 2006

In gram-negative bacteria, beta-lactamases are the most important mechanism of resistance to beta-lactam antibiotics. Currently, the beta-lactamases receiving the most attention are the extended-spectrum beta-lactamases (ESBLs), inhibitor-resistant beta-lactamases and carbapenemases. When found in Escherichia coli and Klebsiella spp., ESBLs confer resistance to extended-spectrum cephalosporins, such as ceftazidime, cefotaxime and cefepime. Hence, ESBLs limit the choice of beta-lactam therapy to carbapenems. A worrisome trend is the increasing number of pathogens found in isolates from patients in the community that possess ESBLs. It is equally distressing that carbapenemases (serine and metallo-beta-lactamases) are being found in many of the same bacteria that harbor ESBLs, for example Klebsiella pneumoniae. Despite many years studying beta-lactamases, important clinical and scientific questions still remain.

Comparison of Antibiotic-Resistant Pattern of Extended Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia Coli Isolates from Clinical and Non-Clinical Sources

Journal of Drug Delivery and Therapeutics

The increasing rate of antibiotic resistance among E. coli especially those mediated by extended spectrum beta-lactamases and carbapenem-resistant (CR) presents a major threat to public health and healthcare delivery globally. The aim of this research was to compare the antibiotic resistant pattern of extended spectrum beta-lactamase and carbapenem-resistant Escherichia coli isolates from clinical and non-clinical sources. A total of two hundred and fifteen (215) clinical and non-clinical samples were collected for the study. The collected samples were analysis using Standard Microbiological protocol for isolation and identification. Phenotypic detection of ESBL Production and carbapenem resistant was performed using Double Disk Synergy Test (DDST) and Modified Hodge Test (MHT) respectively. Antibiogram studies of ESBL producing and Carbapenem-resistant E. coli was determined using the Kirby–Bauer disk diffusion method. The result of isolation and characterization revealed higher oc...

Bench-to-bedside review: The role of β-lactamases in antibiotic-resistant Gram-negative infections

Critical Care, 2010

Multidrug resistance has been increasing among Gram-negative bacteria and is strongly associated with the production of both chromosomal-and plasmid-encoded β-lactamases, whose number now exceeds 890. Many of the newer enzymes exhibit broad-spectrum hydrolytic activity against most classes of β-lactams. The most important plasmid-encoded β-lactamases include (a) AmpC cephalosporinases produced in high quantities, (b) the expanding families of extended-spectrum β-lactamases such as the CTX-M enzymes that can hydrolyze the advancedspectrum cephalosporins and monobactams, and (c) carbapenemases from multiple molecular classes that are responsible for resistance to almost all β-lactams, including the carbapenems. Important plasmid-encoded carbapenemases include (a) the KPC β-lactamases originating in Klebsiella pneumoniae isolates and now appearing worldwide in pan-resistant Gram-negative pathogens and (b) metallo-β-lactamases that are produced in organisms with other deleterious β-lactamases, causing resistance to all β-lactams except aztreonam. β-Lactamase genes encoding these enzymes are often carried on plasmids that bear additional resistance determinants for other antibiotic classes. As a result, some infections caused by Gramnegative pathogens can now be treated with only a limited number, if any, antibiotics. Because multidrug resistance in Gram-negative bacteria is observed in both nosocomial and community isolates, eradication of these resistant strains is becoming more diffi cult.

Prevalence of Extended-Spectrum Beta-Lactamase-Producing Strains Isolated at Zinder National Hospital (ZNH) in 2021 and Their Antibiotic Susceptibility Profile

Open Journal of Medical Microbiology, 2023

Purpose: Bacterial resistance to antibiotics has become a global public health problem. Enterobacteriaceae ESBL is among the most incriminated in this emergence which reduces the therapeutic possibilities. Thus, the objective of this study is to determine the prevalence of the extended-spectrum betalactamase (ESBL) producing Enterobacteriaceae at ZNH and their antibiotic susceptibility profile. Materials and Methods: This is a prospective study carried out over 5 months in all hospitalized and non-hospitalized patients in whom a culture was taken for the diagnosis of an infection. The search for ESBL is done by the double disc diffusion method. Results: In total, 21 out of 45 of our strains are ESBL-producing, i.e. a frequency of 46.7%. The mean age is 41.62 (±22.90) with extremes of 2.6-78 years. The distribution of ESBL producing species showed a predominance of E. coli with 66.7% followed by K. pneumoniae and K. oxytoca each 9.5%. All ESBL strains were resistant to Amoxicillin, Cefalotin, Pipiracillin, Piperacillin + tazobactam, Ticarcillin, Ticarcillin + clavulanic acid. Resistance to C3G and Aztreonam was each 95.5%, to Amoxicillin/clavulanic acid 9.1%. All strains were sensitive to imipenem. E. coli strains showed resistance: 85.7% to ciprofloxacin, 50% to Amikacin, 57.1% to Gentamicin.

β-lactam and β-lactamase inhibitor combinations in the treatment of extended-spectrum β-lactamase producing Enterobacteriaceae: time for a reappraisal in the era of few antibiotic options?

The Lancet. Infectious diseases, 2015

The spread of extended-spectrum β-lactamase (ESBL) genes in Enterobacteriaceae such as Escherichia coli or Klebsiella spp is a major challenge to modern medical practice. Carbapenems are the treatment of choice for serious infections caused by ESBL producers; however, carbapenem resistance has increased globally. ESBL producers might be susceptible to β-lactam-β-lactamase inhibitor (BLBLI) combination antibiotics such piperacillin-tazobactam or amoxicillin-clavulanate. These drugs are frequently avoided in serious infections caused by ESBL producers because of the inoculum effect in-vitro (especially for piperacillin-tazobactam), animal data suggesting inferior efficacy when compared with carbapenems, concerns about pharmacokinetic-pharmacodynamic drug target attainment with standard doses, and poor outcomes shown in some observational studies. Prospective cohort data and a meta-analysis suggest that BLBLIs are non-inferior to carbapenems in the treatment of bloodstream infections c...

Prevalence of extended spectrum β-lactamases in multidrug resistant strains of Gram-negative bacteria

Extended spectrum beta-lactamases (ESBLs) are enzymes that are now becoming major sources of resistance to β-lactamase antibiotics more especially in enteric bacteria such as Klebsiella pneumoniae, P. aeruginosa and Escherichia coli. Increase in the frequency of the β-lactam resistance in bacteria has become a serious threat for treating bacterial infections caused by enterobacteriaceae. This study aims to determine the prevalence of ESBLs producers among enteric Gram negative bacteria isolated from patients in OAUTHC, Ile-Ife, Osun State. The subject used in this study involved patients presenting with evidence of hospital infections. The collected sputum specimens were processed for the isolation and identification of Gram negative bacilli. Resistance of the isolates to different antibiotics tested was determined using the standard disc diffusion method of Kirby-Bauer. Phenotypic and confirmatory test of the isolates were done for ESBL production using double disc synergy test (DDST) on Mueller Hinton agar according to CLSI 2013 guidelines. Results reveal that the highest occurrence of bacteria was recovered in Klebsiella species (35%), followed by Enterobacter sp. (13%), P. aeruginosa (10%), Escherichia coli and Salmonella sp. (7%) while the least occurs in Proteus sp. All the isolates were 100% resistance to class piperacillin, 76.6% to beta-lactamase inhibitor and 52% resistance to cephalosporins while they were susceptible to carbapenems, nitrofurans, and fluoroquinolones. The prevalence of ESBLs producing isolates was 51.1% while non-ESBL producing strains were 48.8%. Therefore, it can be concluded that extended spectrum beta lactamases are gradually increasing in Nigeria with co-resistance to some other classes of antibiotics which is very alarming. There is a limited number of drugs sensitivity for these bacteria and the drug of choice is imipenem, ciprofloxacin and ofloxacin.