Streptococcus pneumoniae
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward in Case Studies in Infectious Disease, 2010
S. pneumoniae, once highly susceptible to penicillin, has now acquired resistance to this and many other antibiotics. Penicillin resistance results from the generation of penicillin-binding proteins (PBPs) with decreased affinity for penicillin. PBPs are involved in the assembly of the cell wall. It is likely that these altered PBP genes arose by interspecies recombination in which segments of the PBPs’ structural genes were replaced by regions derived from PBP genes of oral streptococci. These altered PBP genes of penicillin-resistant pneumococci can be spread horizontally to sensitive pneumococci by transformation. About one-third of the strains isolated in the United States are resistant to penicillin and higher rates of resistance have been observed in other countries. Although there are over 90 S. pneumoniae serotypes, over 90% of penicillin-resistant strains are found within seven serotypes (6A, 6B, 9V, 14, 19A, 19F, and 23F). Unfortunately, these are the same serotypes that cause the vast majority of infections in children. Cefotaxime, ceftriaxone, and clindamycin are effective antibiotics for treating pneumonia caused by penicillin-resistant pneumococcal isolates that are susceptible to these antibiotics. Clindamycin or vancomycin is recommended when a pneumococcal isolate is resistant to cefotaxime or ceftriaxone.
Endotoxin, Antibiotics, and Inflammation in Gram-Negative Infections
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Penicillin-binding proteins (PBPs) are the primary biochemical targets of β-lactam antibiotics in bacteria. These PBPs catalyze terminal stages in the assembly of the peptidoglycan network of the bacterial cell wall (47). Whereas the older penicillins (penicillin G) aspecifically bind to all of these PBPs, the newer β-lactams often specifically bind to only one or two of the PBPs. Treatment of Enterobacteriaceae with (β-lactam antibiotics that have a high selective affinity for PBP 1a and especially 1b causes rapid and extensive killing of the bacteria, with degradation of cell wall material and cellular lysis. Antibiotics with selective affinity for PBP 2 cause conversion of the bacilli to round-shaped cells (also called spheroplasts). Inhibitors of PBP 3 cause selective inhibition of bacterial septation, which leads to the formation of long filaments, but initially only limited bactericidal activity and lysis takes place (47).
Antibiotics
Kate McCombe, Lara Wijayasiri, Paul Hatton, David Bogod in The Primary FRCA Structured Oral Examination Study Guide 2, 2017
Inappropriate use of antibiotics and poor prescribing play a vital role in propagating antibiotic resistance. There are several mechanisms by which bacteria develop resistance to penicillins: Drug inactivation – bacterial production of β-lactamase leads to hydrolysis of the β-lactam ring.Alteration of penicillin binding proteins – this prevents the antibiotics from binding onto the bacterial cell wall.Alteration of bacterial cell wall permeability – this prevents antibiotics from penetrating the cell wall.
Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I)
Published in Postgraduate Medicine, 2021
Ofelia Loani Elvir-Lazo, Paul F White, Hillenn Cruz Eng, Firuz Yumul, Raissa Chua, Roya Yumul
Aminoglycosides inhibit bacterial protein synthesis by binding to the 16S rRNA component of the 30S ribosome subunit [56]. Beta-lactams (e.g. penicillins, cephalosporins, and carbapenems) and glycopeptides (e.g. vancomycin) interfere with specific steps in bacterial cell wall biosynthesis, resulting in cell lysis. Beta-lactams block the cross-linking of peptidoglycan units by inhibiting the peptide bond formation reaction catalyzed by penicillin-binding proteins (PBP). Vancomycin achieves the same inhibition by blocking the transglucosylase and PBP activity [56]. Fluoroquinolones inhibit DNA synthesis by targeting the enzyme DNA gyrase, which is a topoisomerase, which prevents bacteria from replicating its DNA. Cyclic lipopeptides (daptomycin) also inhibit cell wall synthesis by altering the structural integrity of bacteria by inserting themselves into the cell membrane and inducing membrane depolarization [57]. Nitroimidazoles (metronidazole) inhibits protein synthesis by forming cytotoxic nitro-radical anions that result in DNA strand breakage [58].
Proteomics approach to understand bacterial antibiotic resistance strategies
Published in Expert Review of Proteomics, 2019
Bo Peng, Hui Li, Xuanxian Peng
β-lactams are a class of broad-spectrum antibiotics that contain a beta-lactam ring, including penicillins, cephalosporins, cephamycins, carbapenems, and monobactam as well as β-lactamase inhibitors. β-Lactam antibiotics are currently the most used class of antibacterial agents in the treatment of bacterial infection [19]. β-Lactams target penicillin-binding proteins to inhibit bacterial cell wall synthesis and are one of the most commonly prescribed drugs. Thus, β-lactam-resistant bacteria are predominant in the clinic and environment. There are three common mechanisms of resistance to β-lactams: inactivating β-lactams by β-lactamases such as NDM-1 (New Delhi Metallo-beta-lactamase 1), failing to bind to penicillin-binding proteins, and altering binding affinity to penicillin-binding proteins [20,21]. Additionally, these mechanisms are always accompanied with decreased uptake and increased efflux of β-lactams by bacteria, which is the major cause of high-level resistance in clinical settings [19].
Acute bacterial skin and skin structure infections in pediatric patients: potential role of dalbavancin
Published in Expert Review of Anti-infective Therapy, 2023
Lorenzo Volpicelli, Mario Venditti, Alessandra Oliva
Ceftaroline is a new parenteral beta-lactam agent, a fifth-generation cephalosporin with activity against Gram-positive pathogens including MRSA. Being provided with a greater binding affinity to penicillin-binding proteins in comparison to other beta-lactams, it exhibits a very rapid bactericidal effect. Ceftaroline has no activity on Enterococci and Pseudomonas spp and exerts only moderate activity on other Gram-negatives [45], although these agents are rarely implicated in pediatric SSTI. Multiple daily administrations are required but, noteworthyly, the standard doses were found to achieve similar probability of target attainment against S. aureus and S. pneumoniae with infusion duration of 5 or 60 minutes [45]. A meta-analysis of three randomized controlled trials found ceftaroline to have a clinical cure rate similar to comparators with no significant differences for the risk of treating emergent adverse events in children affected by acute bacterial infection [46].
Related Knowledge Centers
- Bacteria
- Cell Wall
- Escherichia Coli
- Glutamine Synthetase
- Peptidoglycan
- Protein
- Beta-Lactam Antibiotics
- Tabtoxinine Β-Lactam
- Dd-Transpeptidase
- Filamentation