1370. Role of Clindamycin Versus Linezolid for Serious Group A Streptococcal Infections

Background Streptococcus pyogenes can cause severe illnesses such as toxic-shock syndrome and necrotizing fasciitis due to pyrogenic exotoxins. Clindamycin is added to penicillin for treatment of severe S. pyogenes infections as it is a bacterial protein synthesis inhibitor which reduces toxin production. However, clindamycin is associated with several adverse effects including C. difficile infection. Linezolid is a bacterial protein synthesis inhibitor that has been shown to provide excellent coverage of S. pyogenes including toxin inhibition in vitro, but clinical evidence is lacking. We compared outcomes of patients treated with linezolid versus clindamycin for serious S. pyogenes infections. Methods This was a retrospective study of patients with necrotizing fasciitis or toxic shock syndrome caused by S. pyogenes admitted to the Shock Trauma Center at University of Maryland Medical Center treated with at least 48 hours of either clindamycin or linezolid. Data collected included Sequential Organ Failure Assessment (SOFA) and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) severity scores, time to resolution of infection, number of surgeries, C. difficile infection, other antibiotic associated adverse effects, and mortality. Associations between patient characteristics, antibiotic groups, and outcomes were analyzed using the chi-square test, Fisher’s exact test and t-test or Wilcoxon rank-sum test as appropriate (SAS v 9.4). Results 52 patients were included, 26 treated with clindamycin and 26 with linezolid. Most patients (85% clindamycin and 96.2% linezolid) were treated for necrotizing fasciitis. Baseline characteristics, including SOFA and LRINEC scores, were similar between the groups. There was no difference in mortality between patients treated with clindamycin versus linezolid (11.5% vs. 7.7%, p = 0.22), and resolution of infection was similar between the groups (92.3% vs. 88.5%, p = 1.0). There was no difference in adverse effects between the clindamycin and linezolid groups, including C. difficile infection (3.9% vs. 0% p = 1.0) and thrombocytopenia (30.8% vs. 42.3%, p = 0.4). Conclusion Linezolid could be an alternate to clindamycin for the treatment of serious toxin producing S. pyogenes infections. Further prospective studies are needed. Disclosures Emily Heil, PharmD, MS, BCIDP, Nothing to disclose

RISE OF RIFAXIMIN IN PAEDIATRIC INFECTIOUS DIARRHOEA

The incidence and risk of morality is high under the age of five years is due to diarrhoea. In India twenty percentages of paediatric deaths is due to diarrhoeal disease. It is the second cause of leading mortality in children after acute respiratory infections. Following on from the GEMS study when we looked at the data in the management of bacterial diarrhoea the primary treatments included oral rehydration solution, oral zinc probiotics and antibiotics. Anecdotally we noted that a lot of children were treated with oral antibiotics and the majority of them were treated with fluoroquinolones like Ofloxacin and drugs like Metronidazole there are multiple side-effects associated with the usage of fluoroquinolones and a major side-effect of that is the risk to the growing cartilage. We also noticed that irrational combinations such as imidazole like metronidazole have shown more problems than solutions .usage of Ofloxacin in children should be discouraged for all the side-effects plus the infectivity in the management of bacterial diarrhoea. The duration of treatment have paved the way for usage of drugs such as new molecules in paediatric i.e. rifaximin comes under the group of oral non-absorbable GI antibiotics broad-spectrum agents with antibacterial activity against gram positive and gram negative aerobes and Anaerobes makes Rifaximin a bactericidal drug in nature. Rifaximin is particularly recommended in children above the age of two years in acute infectious diarrhoea the mechanism of action of rifaximin is by inhibition of bacterial protein synthesis by reversibly binding to bacterial DNA dependent RNA polymerase. In this review we discussed the “phrma” behind rifaximin, clinical experience of rifaximin in children and indications and dosage of rifaximin in paediatric.

Quantitative Control for Stoichiometric Protein Synthesis

Bacterial protein synthesis rates have evolved to maintain preferred stoichiometries at striking precision, from the components of protein complexes to constituents of entire pathways. Setting relative protein production rates to be well within a factor of two requires concerted tuning of transcription, RNA turnover, and translation, allowing many potential regulatory strategies to achieve the preferred output. The last decade has seen a greatly expanded capacity for precise interrogation of each step of the central dogma genome-wide. Here, we summarize how these technologies have shaped the current understanding of diverse bacterial regulatory architectures underpinning stoichiometric protein synthesis. We focus on the emerging expanded view of bacterial operons, which encode diverse primary and secondary mRNA structures for tuning protein stoichiometry. Emphasis is placed on how quantitative tuning is achieved. We discuss the challenges and open questions in the application of quantitative, genome-wide methodologies to the problem of precise protein production. Expected final online publication date for the Annual Review of Microbiology, Volume 75 is October 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Reduced Lytic Activity of Bacteriophages in Presence of Antibiotics Targeting Bacterial Protein Synthesis

Combination therapy of bacteriophage and antibiotics offers promise to treat multiple drug resistant bacterial infections through phage antibiotic synergy. However, its usage requires careful assessment as most antibiotics with mechanisms dependent upon inhibiting cell growth through interfering bacterial protein synthesis machinery were found to have an antagonistic effect on phage activity.

Impact of Azithromycin and 8-Hydroxychloroquine in 2019 Novel Coronavirus (COVID-19) Pandemic: A Systematic Review

As we know novel coronavirus is an emergent nuisance in this stipulated period. Corona virus is a group of enveloped viruses, with non-segmented, single stranded & positive sense RNA genomes. Human Corona virus is mainly subdivided into four categories such as 229E, NL63, OC43, HKU1. Epidemiologically it has a greater prevalence in the modern era. The features encountered in the clinical course of the disease are multifarious spanning from cough, sneezing, fever, breathlessness. It may take 2-14 days for a person to notice symptoms after infection. Azithromycin and 8 Hydroxychloroquine both plays an instrumental role for management of COVID-19. Azithromycin is a macrolide antibiotic and it binds with a 50s ribosome then inhibits bacterial protein synthesis. On the other hand 8-Hydroxychloroquine was approved by United State in the year of 1955 .Basically it is used as a antimalarial drugs . Briefly, in inflammatory conditions it binds with toll like receptor & blocks them. 8- hydroxychloroquine increases lysosomal pH in antigen presenting cells . In inflammatory conditions it blocks toll like receptors on plasmacytoid dendritic cells. In our review we focused on the role of Azithromycin, and 8-hydroxychloroquine in Covid-19 .

Review: Modification of Nanocellulose as Conjugate of Infection-Causing Antibacterial Hydrogel

Infection is the process of entering and reproducing microorganisms such as bacteria, viruses, fungi, and parasites that cause tissue injury. Some of the common types of bacteria that play a role in wound infection are Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, and Staphylococcus epidermis. The antibacterial able to inhibit bacterial growth by inhibiting cell wall biosynthesis, increasing the permeability of the bacterial cytoplasmic membrane, and interfering with the normal bacterial protein synthesis. The aim of this review article is to conduct a study of nanocellulose as an antibacterial hydrogel conjugate. The method used is to summarize information from various recent journals related to nanocellulose, nanocellulose modification, nanocellulose-based hydrogels, and their application as antibacterial. Some journals from primary sources such as the PMC system (PubMed Central), National Library of Medicine (NIH), Science Direct, Elsevier, Nature, ACS Chemical Society, and several other sources. Nanocellulose consists of β-1, 4-glucose, and there are three hydroxyls active at the C2, C3, and C6 positions of the pyranose attachment. Nanocellulose can respond by the reaction of oxidation, esterification, or etherification, by adding a new functional group. Nanocellulose can become nanocellulose nanocrystals (CNC), cellulose nanofibers (NFC), and nanocellulose bacteria (BNC). Nanocellulose formulated in the form of hydrogels and combined with antibiotics will increase the effectiveness in reducing the risk of infection that is resistant to antibiotics.

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

Secondary metabolites provide Bacillus subtilis with increased competitiveness towards other microorganisms. In particular, nonribosomal peptides (NRPs) have an enormous antimicrobial potential by causing cell lysis, perforation of fungal membranes, enzyme inhibition, or disruption of bacterial protein synthesis. This knowledge was primarily acquired in vitro when B. subtilis was competing with other microbial monocultures. However, our understanding of the true ecological role of these small molecules is limited. In this study, we have established soil-derived semisynthetic mock communities containing 13 main genera and supplemented them with B. subtilis P5_B1 WT, the NRP-deficient strain sfp, or single-NRP mutants incapable of producing surfactin, plipastatin, or bacillaene. Through 16S amplicon sequencing, it was revealed that the invasion of NRP-producing B. subtilis strains had no major impact on the bacterial communities. Still, the abundance of the two genera Lysinibacillus and Viridibacillus was reduced. Interestingly, this effect was diminished in communities supplemented with the NRP-deficient strain. Growth profiling of Lysinibacillus fusiformis M5 exposed to either spent media of the B. subtilis strains or pure surfactin indicated the sensitivity of this strain towards the biosurfactant surfactin. Our study provides a more in-depth insight into the influence of B. subtilis NRPs on semisynthetic bacterial communities and helps to understand their ecological role.

Characterization of Cetacean Proline-Rich Antimicrobial Peptides Displaying Activity against ESKAPE Pathogens

Proline-rich antimicrobial peptides (PrAMPs) may be a valuable weapon against multi-drug resistant pathogens, combining potent antimicrobial activity with low cytotoxicity. We have identified novel PrAMPs from five cetacean species (cePrAMPs), and characterized their potency, mechanism of action and in vitro cytotoxicity. Despite the homology between the N-terminal of cePrAMPs and the bovine PrAMP Bac7, some differences emerged in their sequence, activity spectrum and mode of action. CePrAMPs with the highest similarity with the Bac7(1-35) fragment inhibited bacterial protein synthesis without membrane permeabilization, while a second subgroup of cePrAMPs was more membrane-active but less efficient at inhibiting bacterial translation. Such differences may be ascribable to differences in presence and positioning of Trp residues and of a conserved motif seemingly required for translation inhibition. Unlike Bac7(1-35), which requires the peptide transporter SbmA for its uptake, the activity of cePrAMPs was mostly independent of SbmA, regardless of their mechanism of action. Two peptides displayed a promisingly broad spectrum of activity, with minimal inhibiting concentration MIC ≤ 4 µM against several bacteria of the ESKAPE group, including Pseudomonas aeruginosa and Enterococcus faecium. Our approach has led us to discover several new peptides; correlating their sequences and mechanism of action will provide useful insights for designing optimized future peptide-based antibiotics.

Secondary metabolites of Bacillus subtilis impact soil-derived semi-synthetic bacterial community assembly

Secondary metabolites provide Bacillus subtilis with increased competitiveness towards other microorganisms. In particular nonribosomal peptides (NRPs) have an enormous antimicrobial potential by causing cell lysis, perforation of fungal membranes, enzyme inhibition or disruption of bacterial protein synthesis. This knowledge was primarily acquired in vitro when B. subtilis was competing with other microbial monocultures. However, our understanding of the true ecological role of these small molecules is limited.In this study, we have established soil-derived semi-synthetic mock communities containing 13 main genera and supplemented them with B. subtilis P5_B1 WT, its NRP deficient strain sfp or single NRP mutants incapable of producing surfactin, plipastatin or bacillaene. 16S amplicon sequencing revealed that the invasion of NRP-producing B. subtilis strains had no major impact on the bacterial communities. Still, the abundances of the two genera Lysinibacillus and Viridibacillus were reduced. Interestingly, this effect was diminished in communities supplemented with the NRPs deficient strain. Growth profiling of Lysinibacillus fusiformis M5 exposed to either spent media of the B. subtilis strains or pure surfactin indicates the sensitivity of this strain towards the biosurfactant surfactin.Our study provides a more in-depth insight into the influence of B. subtilis NRPs on semi-synthetic bacterial communities and helps to understand their ecological role.

A Review of Newly Approved Antibiotic Treatment for Community-Acquired Bacterial Pneumonia: Lefamulin

Lefamulin is a novel systemic, semi-synthetic pleuromutilin class of antimicrobials that has been shown to be effective against common respiratory pathogens associated with community-acquired bacterial pneumonia (CABP). CABP, a common infection among older people, leads to an increase in hospitalizations and mortality. Therefore, the use of lefamulin could be beneficial for CABP treatment in patients who are 65 years of age or older.<br/> The Food and Drug Administration (FDA) approved lefamulin for the treatment of CABP, which is available in both intravenous and oral formulations. This medication offers the benefit of not having any cross-resistance to other antibiotics and is highly concentrated in lung tissues. Lefamulin is unique because it has an induced-fit mechanism of action which inhibits bacterial protein synthesis. The clinical efficacy of lefamulin has demonstrated noninferiority to current standard-of-care for CABP, and patients, generally, have tolerated it well in clinical trials.<br/> Lefamulin does not require dosage adjustment in renal impairment. However, the drug does requires dosage adjustment in severe hepatic impairment, based on Child-Pugh scores and clinical consideration in patients with severe hepatic impairment based on Child-Pugh scores. Though the benefit of adding lefamulin to a formulary is still in question; its potential to be a beneficial treatment for CABP is encouraging.