Penicillin

About: Penicillin is a research topic. Over the lifetime, 17916 publications have been published within this topic receiving 368480 citations. The topic is also known as: penicillin antibiotic & PCN.

Use of Enzymes in the Production of Semi-Synthetic Penicillins and Cephalosporins: Drawbacks and Perspectives

Abstract: Semi-synthetic β-lactamic antibiotics are the most used anti-bacteria agents, produced in hundreds tons/year scale. It may be assumed that this situation will even increase during the next years, with new β-lactamic antibiotics under development. They are usually produced by the hydrolysis of natural antibiotics (penicillin G or cephalosporin C) and the further amidation of natural or modified antibiotic nuclei with different carboxylic acyl donor chains. Due to the contaminant reagents used in conventional chemical route, as well as the high energetic consumption, biocatalytic approaches have been studied for both steps in the production of these very interesting medicaments during the last decades. Recent successes in some of these methodologies may produce some significant advances in the antibiotics industry. In fact, the hydrolysis of penicillin G to produce 6-APA catalyzed by penicillin G acylase is one of the most successful historical examples of the enzymatic biocatalysis, and much effort has been devoted to find enzymatic routes to hydrolyze cephalosporin C. Initially this could be accomplished in a quite complex system, using a two enzyme system (D-amino acid oxidase plus glutaryl acylase), but very recently an efficient cephalosporin acylase has been designed by genetic tools. Other strategies, including metabolic engineering to produce other antibiotic nuclei, have been also reported. Regarding the amidation step, much effort has been devoted to the improvement of penicillin acylases for these reactions since 1960. New reaction strategies, continuous product extraction or new penicillin acylases with better properties have proven to be the key to have competitive biocatalytic processes. In this review, a critical discussion of these very interesting advances in the application of enzymes for the industrial synthesis of semi-synthetic antibiotics will be presented.

Genetics of high level penicillin resistance in clinical isolates of Streptococcus pneumoniae

Abstract: Mosaic penicillin-binding proteins (PBP) 1A, 2X and 2B genes were cloned from four clinical isolates of Streptococcus pneumoniae with levels of susceptibility to penicillin ranging from 1.5 to 16 micrograms benzylpenicillin ml-1. In each instance it was possible to transform either the penicillin-sensitive laboratory strain R6 or a sensitive clinical isolate 110K/70 to the full level of penicillin resistance with these three penicillin-binding proteins alone. Until now it has not been possible to clearly determine whether alterations to PBP1A, 2X and 2B alone were sufficient to attain high level penicillin resistance.

Short-term therapy for streptococcal infective endocarditis. Combined intramuscular administration of penicillin and streptomycin.

Abstract: In a prospective study, 91 patients with penicillin-sensitive infective endocarditis (IE) were treated for two weeks with intramuscular (IM) penicillin G procaine, 1.2 million units every six hours, plus streptomycin sulfate, 500 mg IM every 12 hours. Viridans streptococci were isolated from 70 patients (77%); 21 patients (23%) had Streptococcus bovis infections. Eighteen patients (20%) had had symptoms of IE for three months or longer. Follow-up ranged from two months to 6.6 years. There were no relapses; mild vestibular toxic reactions occurred in two patients (2%). Two patients (2%) died—one of sudden-onset severe heart failure and one of cardiac arrest after aortic valve replacement. Twenty-six patients (19%) required cardiac valve replacement after completion of antimicrobial therapy. This therapy seems as efficacious as four weeks of parenteral antimicrobial therapy and is more cost-effective. ( JAMA 1981;245:360-363)

Carriage of respiratory tract pathogens and molecular epidemiology of Streptococcus pneumoniae colonization in healthy children attending day care centers in Lisbon, Portugal.

Abstract: In an effort to establish the rate of carriage of antibiotic resistant respiratory pathogens in children attending urban day care centers (DCC) in Portugal, seven DCC in Lisbon were selected for determining the rate of nasopharyngeal colonization of children between the ages of 6 months to 6 years by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Of the 586 children studied between January and March 1996, 47% carried S. pneumoniae, 72% H. influenzae, and 54% M. catarrhalis. Twenty-four percent of the pneumococci had reduced susceptibility to penicillin, and most of these belonged to serogroups 19, 23, 14, and 6. An additional 19% were fully susceptible to penicillin but showed decreased susceptibility to other antimicrobials. These isolates expressed serogroups 6, 11, 14, 18, 19, and 34. The majority (96%) of M. catarrhalis and 20% of H. influenzae were penicillin resistant due to the production of β-lactamases. Recent antimicrobial use was associated with carriage o...

Attenuation of penicillin resistance in a peptidoglycan O-acetyl transferase mutant of Streptococcus pneumoniae.

Abstract: Summary The level of penicillin resistance in clinical isolates of Streptococcus pneumoniae depends not only on the reduced affinity of penicillin binding proteins (PBPs) but also on the functioning of enzymes that modify the stem peptide structure of cell wall precursors. We used mariner mutagenesis in search of additional genetic determinants that may further attenuate the level of penicillin resistance in the bacteria. A mariner mutant of the highly penicillin-resistant S. pneumoniae strain Pen6 showed reduction of the penicillin minimum inhibitory concentration (MIC) from 6 to 0.75 μg ml−1. Decrease in penicillin MIC was also observed upon introduction of the mutation (named provisionally adr, for attenuator of drug resistance) into representatives of major epidemic clones of penicillin-resistant pneumococci. Attenuation of resistance levels was specific for β-lactams. The adr mutant has retained unchanged (low affinity) PBPs, unaltered murM gene and unchanged cell wall stem peptide composition, but the mutant became hypersensitive to exogenous lysozyme and complementation experiments showed that both phenotypes – reduced resistance and lysozyme sensitivity – were linked to the defective adr gene. DNA sequence comparison and chemical analysis of the cell wall identified adr as the structural gene of the pneumococcal peptidoglycan O-acetylase.