Problematic Beta-Lactamases: An Update
Robert C. Owens, Lautenbach Ebbing in Antimicrobial Resistance, 2007
Beta-lactam antibiotics arguably remain the safest and most effective antimicrobial agents used today. Unfortunately, beta-lactamases are, and will continue to be, formidable adversaries in the clinical arena when beta-lactams are used. Detailed knowledge of the epidemiology, microbiology, kinetic, and mechanistic details of their functioning, and genetic aspects of their dissemination, have already led to changes in clinical detection and treatment and infection control practices. In the future, as newer and more challenging enzymes emerge, this knowledge will be critical in the design of new beta-lactam antibiotics and beta-lactamase inhibitors, particularly for the Class B, C, and D enzymes. Rapid detection of resistance determinants in the clinical setting will allow for appropriate initial antibiotic use, thereby limiting the number of instances where potent broad-spectrum agents, such as carbapenems or colisitin, need to be administered. This will improve patient outcomes and limit the emergence of new resistance in the healthcare setting.
Unexplained Fever In Hematologic Disorders
Benedict Isaac, Serge Kernbaum, Michael Burke in Unexplained Fever, 2019
Concomitantly, an empiric antibiotic regimen is initiated. Various combinations of aminoglycosides and beta lactams have been studies to combat bacterial infections.93-97 Others tried the combination of two beta-lactam antibiotics.98-101 Some have approached the problem of avoiding various toxicities, such as the ototoxicity and nephrotoxicity of aminoglycosides, by attempting to exploit the broad spectrum of some of the “third generation” cephalosporins, such as moxalactam, ceftazidine, and cefoperazone as monotherapy.102,104 Currently, the combination of an aminoglycoside and beta-lactam antibiotic remains the standard treatment for infections in leukemia patients. Persistence of the pyrexia and granulocytopenia beyond 7 days requires the addition of amphotericin B. Documented skin infections should prompt antibiotic coverage for staphylococcus, namely, cloxacillin or vancomycin.
Allergic Diseases
Stephan Strobel, Lewis Spitz, Stephen D. Marks in Great Ormond Street Handbook of Paediatrics, 2019
It is the large group of beta-lactam antibiotics that are commonly used to treat bacterial infections and are most commonly associated with allergic reactions. In 80–90% adverse drug reactions affect the skin. Cutaneus presentations classically occur at the time of viral infections and so it can be very difficult to determine whether associated rashes (drug allergies usually present with cutaneous manifestations) arise due to the index infection for which the antibiotic was administrated or due to the antibiotic itself. If such a diagnosis is not taken forward this may cause unnecessary patient anxiety and compromise health care in the future.
A 2018–2019 patent review of metallo beta-lactamase inhibitors
Published in Expert Opinion on Therapeutic Patents, 2020
Nakita Reddy, Mbongeni Shungube, Per I Arvidsson, Sooraj Baijnath, Hendrik G Kruger, Thavendran Govender, Tricia Naicker
Beta-lactam antibiotics are the most widely prescribed class of antimicrobial drugs around the world [1]. The therapeutic benefits offered by this class of antimicrobials include accessibility, safety, and a unique mechanism of action against specific prokaryotic cell structures [2], making it the ideal antimicrobial drug of choice. However, with increased consumption, inappropriate prescribing practices, and misuse of beta-lactams to treat minor infections, beta-lactam resistance has escalated to uncontrollable rates [3]. Gram-negative bacteria are the main protagonists responsible for the rise in resistance, facilitated by genes carried on plasmids or other mobile genetic elements, which confer resistance to beta-lactam drugs [4]. Carbapenems are beta-lactam drugs that are often referred to as the last line of defense in the treatment of bacterial infections [4]. However, the emergence of carbapenem-resistant Enterobacteriaceae (CRE), along with carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) have emerged as urgent threats, requiring immediate intervention, as stated by the World Health Organization [5].
The role of PK/PD–based strategies to preserve new molecules against multi-drug resistant gram-negative strains
Published in Journal of Chemotherapy, 2020
Chiara Adembri, Iacopo Cappellini, Andrea Novelli
All 5 molecules belong to the beta-lactam antibiotic class and share some characteristics. Being hydrophilic molecules, there is the risk that if prescribed according to the manufacturer’s dose they are under-dosed in critically ill septic patients, in whom permeability and volume of distribution are increased.44 The risk of underexposure (which affects clinical cure and favors resistances) must be considered in ICU patients in whom renal function is altered. Renal function can be not only reduced, but also increased in a certain subset of ICU patients; moreover, kidney function is not static, and changes (both increasing and decreasing) can occur very rapidly.15 Therefore, increased doses during increased renal clearances should be proposed, while even in the case of reduced renal function some authors suggest not reducing doses, at least for the first 48 hrs of treatment.15 A keen revision of dosing according to CrCl formulas validated for ICU patients must also be applied. Finally, data on the probability of reaching PK/PD targets in ICU patients undergoing RRT are also necessary.
Investigation of the effects of various antibiotics against Klebsiella pneumoniae biofilms on in vitro catheter model
Published in Journal of Chemotherapy, 2018
Emel Mataraci Kara, Berna Ozbek Celik
Beta-lactam antibiotics rapidly kill bacteria during logarithmic growth but fail to kill non-growing cells. On the contrary, Eng et al.31, showed that during slow growth, with the growth rate controlled by the amount of the carbon source added, meropenem had substantial bactericidal activities against non-growing cultures. According to our results, doripenem (a beta-lactam antibiotic) alone could have a rapid in vitro bactericidal effect against tested biofilm-embedded K. pneumoniae strains and we also observed that the use of doripenem as a lock solution prevented bactericidal regrowth at least 24 h. On the other hand, clarithromycin or esomeprazole were included, antimicrobial activity of doripenem found less effective than when doripenem was used alone in ALT for K. pneumoniae biofilms, as compared with each antibiotic used alone (p < 0.001).
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