Klebsiella spp. as Pathogens: Epidemiology, Pathogenesis, Identification, Treatment, and Prevention
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Treatment for Klebsiella infection is site dependent. Local susceptibility patterns determine the choice of antimicrobial agents. Once the bacteremia in patients is confirmed, treatment may be enhanced with highly intrinsic antimicrobials against Klebsiella. Examples of such antimicrobial agents include third-generation cephalosporins (e.g., cefotaxime and ceftriaxone), carbapenems (e.g., imipenem/cilastatin), aminoglycosides (e.g., gentamicin and amikacin), and quinolones. These antimicrobials may be used as monotherapy or combination therapy. The combination therapy using aminoglycoside and third-generation cephalosporin is used to treat the non-ESBL-producing Klebsiella strains.29,30 In 2015, the U.S. Food and Drug Administration approved ceftazidime-avibactam, novel antibacterial agents to treat adults with severe intraabdominal infections and UTIs. The combination of ceftolozane/tazobactam and ceftazidime/avibactam may also be used to treat Klebsiella. Additionally, infection by carbapenem-resistant Klebsiella is treated with ceftazidime/avibactam.59 Aztreonam is used to treat the patients who are allergic to ß-lactam antibiotics. Likely, quinolones are used for patients allergic to carbapenems and ß-lactam. The antibiotics used to treat susceptible Klebsiella infection include ticarcillin/clavulanate, ampicillin/sulbactam, piperacillin/tazobactam, ceftazidime, cefepime, norfloxacin, levofloxacin, moxifloxacin, ertapenem, and meropenem.
Cystic fibrosis infection and biofilm busters
Anthony J. Hickey, Heidi M. Mansour in Inhalation Aerosols, 2019
Current treatment strategies against established pulmonary bacterial infections effectively slow down the progression of infections and improve the quality of life for CF patients (3). Chronic airway infections are treated using suppressive antibiotic therapy in order to maintain lung function. Approved antibiotics for the inhalation treatment of respiratory infections in CF patients, including tobramycin, aztreonam, and colistimethate sodium. Tobramycin inhalation solutions (such as TOBI®, TIS®, Kitabis Pak®, and Bethkis®) and tobramycin inhalation powder (TOBI Podhaler™), are currently available for management of chronic P. aeruginosa infections (28). Nebulized monobactam aztreonam lysine inhalation solution (Cayston®) is a safe and efficacious formulation against chronic P. aeruginosa infections in CF patients (28). Clinical studies carried out to compare the efficacies of Cayston and TIS in CF patients demonstrated superiority of Cayston over TIS in improving lung function, reducing pulmonary exacerbations, and aiding patient weight gain (32–34). An open-label study of aztreonam lysine inhalation solution showed similar success rates in eradicating P. aeruginosa as those reported for other antibiotic regimens (35). Cayston is available in the United States, Canada, Switzerland, and the European Union (28). Typically patients age 7 and over alternate between 28-day treatments of tobramycin and aztreonam.
Aztreonam and Aztreonam-Avibactam
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Aztreonam is a monocyclic beta-lactam antibiotic. Studies in humans and animals have demonstrated only a low level of immunologic cross-reactivity between aztreonam and IgG antibodies to penicillin G and cephalothin (Adkinson et al., 1984; Adkinson et al., 1985). Cross-reactivity with penicillins and cephalosporins seems to be rare. When skin tests were performed on 41 penicillin-allergic subjects with positive reactions for IgE antibody to penicillin, there was no cross-reactivity with aztreonam reagents (Saxon et al., 1984). In a retrospective clinical study of hypersensitivity reactions to aztreonam and other beta-lactam antibiotics in cystic fibrosis patients receiving multiple treatment courses, 50.9% of patients receiving piperacillin, 13% of patients receiving ceftazidime, but only 6.5% of patients receiving aztreonam, developed reactions (Koch et al., 1991). In two prospective studies, 15 and 18 cystic fibrosis patients who had previously experienced severe penicillin or cephalosporin allergic reactions, and whose allergy was confirmed by skin tests, were treated by aztreonam. They had negative aztreonam skin tests. In the first study 13 patients tolerated aztreonam well, but 2 developed drug fever. In the second study all 18 patients tolerated aztreonam. However, 2 of these patients had anaphylaxis on reexposure to aztreonam (Jensen et al., 1991; Moss et al., 1991). Therefore, despite the reduced immunogenicity and cross-reactivity, aztreonam should be administered with caution to patients who are allergic to other beta-lactam antibiotics.
Current and future pharmacotherapy options for non-cystic fibrosis bronchiectasis
Published in Expert Review of Respiratory Medicine, 2018
Rodrigo Athanazio, Joao Cordeiro da Costa, David de la Rosa Carrillo, Miguel Ángel Martínez-García
The intravenous formulation of gentamicin has also been tested in bronchiectasis patients colonized by various pathogenic microorganisms, with not only some clinical improvements but also bronchospasm in 21% of these patients [55]. The administration of aztreonam lysine failed to demonstrate any efficacy with respect to the primary end point of quality of life, apart from a reduction in the sputum bacterial load; furthermore, many patients suffered frequent adverse events that led them to withdraw from the study [56]. We can therefore conclude that the favorable results obtained in CF patients have not all been validated yet for bronchiectasis. There may be several reasons for these disappointing findings, including scarcity of studies, short-term design, small and heterogeneous samples and inadequate primary outcomes.
Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents
Published in Postgraduate Medicine, 2020
Mazen S. Bader, Mark Loeb, Daniela Leto, Annie A. Brooks
Aztreonam is a β-lactam antibiotic and the only clinically available member of its monobactam class. Aztreonam remains an option for treating infections due to MBLs) producing gram-negative organisms that test susceptible to this agent. However, these carbapenemase-producing bacteria are often coupled with additional resistance mechanisms, such as ESBLs and AmpC-type enzymes, which confer resistance to aztreonam (Table 2) [104]. Therefore, aztreonam should not be used as empiric monotherapy for cUTIs or acute pyelonephritis due to high resistance and failure rate [114]. Combing aztreonam with other antibiotics (ceftazidime-avibactam, amoxicillin-clavulanic acid) or β -lactam inhibitors (avibactam, zidebactam, nacubactam, and WCK 5153) enhances activity against these resistant organisms [37,115–118].
Investigational inhaled therapies for non-CF bronchiectasis
Published in Expert Opinion on Investigational Drugs, 2018
Inhaled aztreonam was associated with a notable reduction in respiratory symptom burden compared to placebo at day 28 (p = 0.0005), with a significant improvement in lung function at day 28 (p < 0.0001), with a considerable reduction in sputum PA load (−1.38 log 10 CFU/mL compared to 0.069 log 10 CFU/mL, p < 0.0001). However, it did not display a significant therapeutic effect on the number of patients requiring systemic antibiotic therapy or on the number of patients requiring at least one hospital admission over 42 days including 28 days of active treatment. In terms of serious adverse events, intestinal obstruction, nausea, pyrexia, and peripheral edema had each an incidence of 1.25% in the aztreonam group.
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