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Antimicrobial Agents
Published in Karl H. Pang, Nadir I. Osman, James W.F. Catto, Christopher R. Chapple, Basic Urological Sciences, 2021
Thomas E. Webb, Karl H. Pang, Ased Ali
Key featuresBactericidal.Broad-spectrum.Intrinsic beta-lactamase resistance.Examples: imipenem (+ cilastatin), meropenem, ertapenem, doripenem.Urological uses: gram-positive cocci, gram-negative bacilli, and anaerobes.Considered a ‘last resort’ drug because of its significant adverse effects.Adverse effects: secondary fungal infections, can lower seizure threshold (especially imipenem), gastrointestinal (GI) upset, rash, thrombophlebitis.Best avoided during pregnancy but may be used if potential benefit outweighs the risk.
Infections
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Production of beta-lactamases. Beta-lactamases are enzymes which catalyse the hydrolysis of the beta-lactam ring to yield microbiologically inactive products. Genes encoding these enzymes are found on the chromosome or on plasmids. In Gram-positive bacteria, beta-lactamases are released into the extra-cellular environment. In Gram-negative cells, the beta-lactamases remain within the periplasm [14,15]. There are many different beta-lactamase enzymes which have the same function, but differ in their affinity for different beta-lactam substrates. Beta-lactamase inhibitors, such as clavulanic acid, are molecules which contain a beta-lactam ring and which act as ‘suicide inhibitors’, binding to beta-lactamases and preventing them from destroying beta-lactams (Figure 11) [15].
Critical Care and Anaesthesia
Published in Tjun Tang, Elizabeth O'Riordan, Stewart Walsh, Cracking the Intercollegiate General Surgery FRCS Viva, 2020
Rajkumar Rajendram, Alex Joseph, John Davidson, Avinash Gobindram, Prit Anand Singh, Animesh JK Patel
What bacteria are typically responsible for VAP and how would you treat them?These are Gram-negative organisms including Pseudomonas aeruginosa, Enterobacter sp., Klebsiella and E. coli.Antimicrobial choice will depend on local patterns of resistance and should be guided by microbiology advice targeted to specific organisms.Some bacteria produce beta-lactamases, inducing resistance to several classes of antibiotic including fluoroquinolones, aminoglycosides and those containing β-lactam. These ESBL are often seen with Klebsiella, Enterobacter sp. and E. coli infections.
Carbapenem-resistant Klebsiella pneumoniae outbreak in a COVID-19 intensive care unit; a case-control study
Published in Journal of Chemotherapy, 2022
Pınar Ergen, M. Esra Koçoğlu, Müge Nural, Mert Ahmet Kuşkucu, Özlem Aydin, Ferda Y. İnal, Hande Öztürk, Ayşe C. Üçişik, Hülya Çaşkurlu, Büşra Güneysu, Büşra Yildirim, Kenan Midilli, Yasemin Çağ, Ferhat Arslan, Haluk Vahaboglu
Beta-lactamases belong to four structural classes: A, B, C and D [9]. Carbapenemases are present in all these classes, and this structural diversity restricts treatment options [10]. This study detected a blaNDM-1 gene along with a blaCTX-M-15 determinant in one K. pneumoniae isolate [11,12]. This isolate was resistant to all antibiotics, except COL, cotrimoxazole and gentamycin. The class D carbapenemase gene blaOXA-48 was first identified in a K. pneumoniae isolate from Istanbul, Turkey [13]. In this study, the isolate carrying the blaOXA-48 gene was susceptible to CAZ-AVI. The blaKPC-2 bearing isolate was sensitive to CAZ-AVI, as well. Although effective antibiotics were administered, CRKP infections were significantly associated with adverse outcomes. Overall, the current scenario suggests that CRKP can cause a healthcare crisis in our megacity, complicating COVID-19, an already severe viral respiratory infection. Moreover, the results of this study imply that carbapenem resistance in K. pneumoniae is widespread and would remain a healthcare concern after the mitigation of COVID-19 pandemic.
Hydrolytic activity of KPC-producing Klebsiella pneumoniae clinical isolates
Published in Journal of Chemotherapy, 2022
Vincent H. Tam, Cole S. Hudson, Paul R. Merlau, Ryan K. Shields
Carbapenem-resistant Enterobacterales is an urgent antibiotic resistance threat [1]. In the U.S., carbapenem resistance in Enterobacterales is primarily due to the production of serine-based carbapenemase (e.g. KPC). Clinical isolates expressing KPC could be resistant to a broad range of antimicrobial agents, limiting effective treatment options. Notably, the hydrolytic activity of these isolates varies as a function of bacterial density at the site of infection (e.g. empyema vs. uncomplicated urinary tract infection), enzyme variants (e.g. KPC-2 vs. KPC-3), presence of other beta-lactamases and their transcriptional levels, as well as substrate stability. Novel beta-lactamase inhibitors (e.g. avibactam, vaborbactam, relebactam) have been used to restore the activity of beta-lactam agents, when they are used in combination [2]. These beta-lactamase inhibitors are expected to reduce enzymatic degradation of the partnering beta-lactam agents and preserve their therapeutic effect. Theoretically, the effective concentration needed for a beta-lactamase inhibitor should match (or exceed) the hydrolytic activity of the target isolates. Where available, molecular testing in microbiology laboratories aims to detect the presence of target beta-lactamase genes, but not the functional capacity quantitatively. Accordingly, routine testing may not be very informative to guide dosing of beta-lactamase inhibitors. We examined the hydrolytic activity of several KPC-positive isolates to provide insights on the utility of this approach.
Lemierre’s syndrome with muscle necrosis and chronic osteomyelitis
Published in Baylor University Medical Center Proceedings, 2021
Azka Latif, Muhammad Junaid Ahsan, Amman Yousaf, Asim Tameezuddin, Akshat Sood, Joseph Thirumalareddy
The management of LS warrants an integrated approach from different specialties. Antibiotics are the mainstay of treatment, but there is a lack of consensus on specific agents. Ideally, antibiotic therapy should include at least one beta-lactamase inhibitor. As a combination drug, metronidazole has shown promising results in LS, but our patient had progression of myositis even on metronidazole. Different antibiotics, including beta-lactam drugs and clindamycin, can be employed as single-agent regimens. We used a combination of piperacillin/tazobactam and daptomycin to counter the infection. As an antipseudomonal drug, piperacillin/tazobactam was used for Fusobacterium. Daptomycin was added against the gram-positive bacteria, as the patient had a positive nasal swab test. The duration of antibiotic therapy is prolonged—at least 3 to 6 weeks.11