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Antibiotic-Induced Endotoxin Release: Important Parameters Dictating Responses
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Jesse J. Jackson, Helmut Kropp
In addition, investigators should also consider that antibiotics not only have affinity for bacteria but may bind irreversibly to plasma proteins and other tissues. Therefore, the actual amount of bioavailable (free) drug necessary for efficacy against the infecting pathogen may be quite different from the amount administered. The percent of free β-lactam antibiotic may range from as high as 95–100% to as low as 3–5% and should be taken into account (19–21).
New Developments in Drug Treatment
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Alexander S. Pym, Camus Nimmo, James Millard
The widespread use of β-lactam antibiotics means they have relatively well-established safety profiles and can be used for pediatric MDR-TB, where drug options are far more limited than for adults. However, due to their broad spectrum of action they are at risk of affecting the host microbiome and their common use for other indications means that, as for the fluoroquinolones, there is a risk that undiagnosed patients may be exposed to them as mono-therapy, promoting the development of resistance.
Urolithiasis
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Thomas Johnston, James Armitage, Oliver Wiseman
Beta (β)-lactam antibiotics contain a β-lactam ring in their molecular structure, which act as an irreversible inhibitor of the enzyme transpeptidase, which is used by the bacteria to cross-link peptidoglycan in their cell walls. β-lactam antibiotics include penicillin derivatives (penams such as amoxicillin), cephalosporins (cephems such as cephalexin) and carbapenems (such as meropenem or itrapenem). Aminoglycosides (gentamicin) are important treatments against Gram-negative infections. They act by inhibiting protein synthesis by binding to ribosomal RNA, which disrupts the integrity of the bacterial cell wall membrane. Sulphonamides are one of the oldest groups of antibiotic compounds (trimethoprim-sulphonamide) in use. They are structurally similar to para-aminobenzoic acid (PABA) and act as a false substrate for the enzyme dihydrofolate synthase, which blocks the synthesis of folate. This results in inhibition of DNA synthesis and therefore bacterial cell growth. Fluoroquinolone (ciprofloxacin) antibiotics inhibit the enzyme DNA gyrase, which is essential for transcription bacterial DNA synthesis, and results in irreversible damage and bacterial cell death. Nitrofurantoin is reduced inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple intermediates that attack ribosomal proteins (ribosomal subunit 50 S and target 23 S ribosomal RNA, DNA and pyruvate metabolism (Table 16.2).
Therapeutic drug monitoring of carbapenem antibiotics in critically ill patients: an overview of principles, recommended dosing regimens, and clinical outcomes
Published in Expert Review of Clinical Pharmacology, 2023
Gavin Matthew Joynt, Lowell Ling, Wai Tat Wong, Jeffrey Lipman
Individualized dosing techniques for β-Lactam antibiotics may provide a partial but not complete solution to improved dosing. These techniques may improve antimicrobial target exposure attainment by accounting for major organ failures, the use of artificial organ replacement techniques, estimation of renal function, and markers of severity of illness [21–23]. However, they are limited in effectiveness and remain largely unvalidated [24]. The use of TDM to guide dosing provides a potentially more robust solution, especially if the TDM can be provided in ‘real-time,’ within several hours of sampling at a relatively low cost [2,25]. A major limitation in realizing the potential of TDM to guide carbapenem dosing is the availability of the assay and the conventionally long lag time between sampling and reporting, making meaningful adjustments difficult. The implementation of real-time TDM has already been shown to substantially alter dose and dose frequency for carbapenems such as imipenem/cliasatin and meropenem [2,26]. Precise and adaptive dosing guided by predictive software has the potential to integrate population PK (PopPK) data, individual patient parameters, and ‘real-time’ TDM [27].
Acute abdomen: a rare presentation of group a streptococcal infection
Published in Acta Chirurgica Belgica, 2023
Jelle Lubach, Marie Vannijvel, Hendrik Stragier, Yves Debaveye, Albert Wolthuis
Even though postponing surgery is controversial, taking blood, urinary and vaginal cultures and starting broad-spectrum antibiotics combined with supportive measures is essential. Of course, the choice of empirical antibiotic therapy should be conform institution guidelines with knowledge of local resistance patterns. A broad-spectrum antibiotic like a combination of piperacillin-tazobactam to treat septic patients with a likely abdominal focus should be started empirically. S. pyogenes is known to be susceptible to penicillin and is advised after cultures are positive. Clindamycin reduces streptococcus virulence factors and endotoxin production in patients with group A hemolytic streptoccus infections and most likely improves clinical outcome [12]. According to a large, retrospective multicentre cohort study from Babiker et al. [13], association to β-lactam antibiotics reduces in-hospital mortality significantly (6.5 vs 11.0%).
A review on the mechanistic details of OXA enzymes of ESKAPE pathogens
Published in Pathogens and Global Health, 2023
Fatma Gizem Avci, Ilgaz Tastekil, Amit Jaisi, Pemra Ozbek Sarica, Berna Sariyar Akbulut
β-lactam antibiotics are life-saving drugs that kill bacterial cells by irreversibly preventing the proper formation of the peptidoglycan polymers in their cell walls through the inactivation of the peptidoglycan transpeptidases. Unfortunately, bacteria evolve different resistance mechanisms to counteract the action of these wonder drugs [1–3]. The production of β-lactamases is one of the most prevalent resistance mechanisms encountered in clinical settings. Just like the peptidoglycan transpeptidases, β-lactamases form an intermediate complex with β-lactams and then render these drugs ineffective by cleaving their β-lactam rings, the chemical moiety with the amidic function [4,5]. The use of β-lactamase inhibitors in combinatorial treatments is one major strategy to restore the efficacy of β-lactam antibiotics to prevent the antibiotic from being hydrolyzed by the enzyme [3].