Antimicrobial Agents
Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple in Basic Urological Sciences, 2021
Key featuresBactericidal.Broad-spectrum.Intrinsic beta-lactamase resistance.Examples: imipenem (+ cilastatin), meropenem, ertapenem, doripenem.Urological uses: gram-positive cocci, gram-negative bacilli, and anaerobes.Considered a ‘last resort’ drug because of its significant adverse effects.Adverse effects: secondary fungal infections, can lower seizure threshold (especially imipenem), gastrointestinal (GI) upset, rash, thrombophlebitis.Best avoided during pregnancy but may be used if potential benefit outweighs the risk.
The Antimicrobial Formulary: Reevaluating Parenteral Cephalosporins in the Context of Emerging Resistance
Robert C. Owens, Paul G. Ambrose, Charles H. Nightingale in Antibiotic Optimization, 2004
General resistance mechanisms to beta-lactam antimicrobials include alteration of target binding sites (e.g., PBPs), decreased permeability into the bacterial cell (e.g., altered membrane porin channels), efflux pumps, and most commonly, the production of a heterogenous group of beta-lactamases. Beta-lactamases enzymatically cleave the amide bond in the beta-lactam ring structure, thus inactivating its activity. Similar to the earlier-described penicillin-Stap/iyfo- coccus situation, many clinically important Enterobacteria-ceae have developed resistance to beta-lactams through the elaboration of more complex chromosomal and/or plasmid-mediated beta-lactamase. The result of these increasingly common mutants has seriously limited the use of the third-generation cephalosporins (e.g., ceftazidime) in many institutions and has unfortunately led to the increased use of carbapenems (e.g., imipenem, meropenem) in some hospitals. Among the most common and challenging to treat are the chromosomally mediated AmpC beta-lactamases and the typically plasmid-mediated ESBLs.
Infections
Evelyne Jacqz-Aigrain, Imti Choonara in Paediatric Clinical Pharmacology, 2021
Production of beta-lactamases. Beta-lactamases are enzymes which catalyse the hydrolysis of the beta-lactam ring to yield microbiologically inactive products. Genes encoding these enzymes are found on the chromosome or on plasmids. In Gram-positive bacteria, beta-lactamases are released into the extra-cellular environment. In Gram-negative cells, the beta-lactamases remain within the periplasm [14,15]. There are many different beta-lactamase enzymes which have the same function, but differ in their affinity for different beta-lactam substrates. Beta-lactamase inhibitors, such as clavulanic acid, are molecules which contain a beta-lactam ring and which act as ‘suicide inhibitors’, binding to beta-lactamases and preventing them from destroying beta-lactams (Figure 11) [15].
Prediction of infection caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: development of a clinical decision-making nomogram
Published in Scandinavian Journal of Urology, 2018
Ana García-Tello, Helena Gimbernat, Cristina Redondo, Elisa Meilán, David M. Arana, Juana Cacho, Juan F. Dorado, Javier C. Angulo
Beta-lactamases are bacterial enzymes encoded in chromosomes or plasmids that protect microorganisms from the lethal effects of beta-lactam antibiotics by hydrolyzing the beta-lactam ring. In Gram-negative pathogens, their production remains one of the most important resistance mechanisms. The first plasmid-mediated beta-lactamases in Gram-negative bacteria (TEM-1, SHV-1) were described in the 1960s [1]. Extended-spectrum beta-lactamases (ESBLs) are a group of these enzymes, which are plasmid-encoded and characterized by having hydrolytic activity against beta-lactam antibiotics of the oximino group. They confer resistance to penicillins, first, second and third generation cephalosporins and monobactams, and are inhibited in vitro by beta-lactamase inhibitors such as clavulanic acid and tazobactam. They are often found in bacteria of the family Enterobacteriaceae, mainly Klebsiella sp. and Escherichia coli. ESBL-producing pathogens often show coresistance to other antimicrobials, such as fluoroquinolones, aminoglycosides and trimethoprim–sulfamethoxazole (TMP-SMX).
Genotypic validation of extended-spectrum β-lactamase and virulence factors in multidrug resistance Klebsiella pneumoniae in an Indian hospital
Published in Pathogens and Global Health, 2019
Rajesh Kumar Sahoo, Aradhana Das, Mahendra Gaur, Ankita Pattanayak, Saubhagini Sahoo, Nagen Kumar Debata, Pattanathu K.S.M. Rahman, Enketeswara Subudhi
Klebsiella pneumoniae is the most important gram-negative pathogenic bacteria of the family Enterobacteriaceae, and it is frequently associated with several nosocomial infections. This bacteria has been reported to have developed resistance globally [1]. Hence, routine testing and reporting for this bacterium have been recommended by CLSI since 2006. The intensity of their pathogenicity and virulence depends on the presence of several other factors, including adhesion, lipopolysaccharide cell wall, serotype of the capsule, iron-scavenging mechanism, and biofilm-producing ability. The beta-lactam group of antibiotics is the most common treatment option worldwide for treating diseases caused by gram-negative bacterial isolates. However, frequent exposure of this group of antibiotics to bacterial isolates (including K. pneumoniae), have induced the diversification and production of the hydrolytic enzyme beta-lactamase. Beta-lactamase enzymes are generally plasmid-encoded and can hydrolyze the beta-lactam group of antibiotics. Only few bacteria can hydrolyze third-generation penicillins and cephalosporins [2], and they are called extended-spectrum beta-lactamase (ESBL)-producing bacteria.
Addressing clinical safety of antimicrobial resistance: personal perspectives
Published in Expert Review of Anti-infective Therapy, 2019
Petros I Rafailidis, Matthew E Falagas
Bacteria have evaded the attack by humans by elaborating various mechanisms of antimicrobial resistance: production of enzymes capable of destroying antibiotics such as beta-lactamases, loss of porins that hamper the move of antibiotics into the bacterium, creation of efflux pumps that essentially eject the antibiotic, modification by gene production of antibiotic binding sites on the bacterial cell wall such as mutation of penicillin-binding proteins [22]. The production of beta-lactamases by bacteria has occurred as an epidemic on a global level and includes productions of various enzyme categories such as extended-spectrum beta-lactamases, metallo beta-lactamases, penicillinases and cephalosporinases and oxacillinases [23]. Biofilm production is another bacterial strategy that hampers further the effect of antimicrobial agents [24]. Environmental pollution of wastewater with antibiotics produced in factories producing antimicrobial agents in Asia is a significant factor that has been associated with antimicrobial resistance [25].
Related Knowledge Centers
- Antibiotic
- Bacteria
- Carbapenem
- Cephalosporin
- Cephamycin
- Enzyme
- Ertapenem
- Multiple Drug Resistance
- Beta-Lactam Antibiotics
- Beta-Lactam