Gram-negative infections

The mass balance approach was also applied to amoxicillin data. Amoxicillin is a broad-spectrum bacterial antibiotic administered orally for the treatment of various gram-positive and gram-negative infections. The dose ranged from 250 to 3000 mg with 200 mL of water. The corresponding dose concentration varied from 1.25 to 15 mg/mL. Low solubility (6 mg/mL) and a nonpassive absorption mechanism makes estimation or prediction of absorption more diffi-... 

The introduction of streptomycin as an antibiotic in 1944 was welcomed as the long-sought solution to combat tuberculosis and other intractable gram-negative infections. The first clinical trial, however, already highlighted the side effects... 

Pharmacology The aminoglycosides are bactericidal antibiotics used primarily in the treatment of gram-negative infections. 

Netea MG, Demacker PN, Kullberg BJ, et al. Low-density lipoprotein receptor-deficient mice are protected against lethal endotoxemia and severe gram-negative infections. J Clin Invest 1996 97 1366-1372. 

Lipopolysaccharides are heat-stable complex amphiphilic macromolecules indispensable for the bacterial growth, viability and for the correct assembly of the external membrane they represent a defensive barrier which helps bacteria to resist to antimicrobial compounds and environmental stresses and are involved in many aspects of host-bacterium interactions as recognition, adhesion, colonization, and, in the case of extremophile bacteria, in the survival under harsh conditions (Alexander and Rietschel, 2001 Raetz and Whitfield, 2002 Raetz et al 2007). LPS are also called endotoxins because they are cell-bound and, once released, play a key role in the pathogenesis of Gram-negative infections, in mechanisms as... 

The horseshoe crab hemolymph contains mainly one type of blood cells called amoebocytes (Fig. 9.3), which are extremely sensitive to LPS. During a Gram negative infection, the amoebocytes release granular components into the plasma... 

Vaarala, O., Vaara, M., Palosuo, T. Effective inhibition of cardiolipin-binding antibodies in gram-negative infections by bacterial lipopolysaccharide. Scand J Immunol 28 (1988) 607-612. 

Indications Serious Gram-negative infections 100 92 2 patients were treated for Mycobacterium avium intracellularae (MAI)... 

R. B. Sykes and D. P. Bonner, "Monobactam Antibiotics History and Development," in J. D. Williams and P. Woods, Eds., Aztreonam, The Antibiotic Discovery for Gram-negative Infections, Royal Society Medicine International Congress Symposium Series No. 89, Royal Society Medicine, London, 1985, pp. 3-24. 

Giamarellou H, Yiallouros K, Petrikkos G, Moschovakis E, Vavouraki E, Voutsinas D, Sfikakis P. Comparative kinetics and efficacy of amikacin administered once or twice daily in the treatment of systemic Gram-negative infections. J Antimicrob Chemother 199127(Suppl C) 73-9. 

Mailer R, Ahrne H, Holmen C, Lausen I, Nilsson LE, Smedjegard J. Once- versus twice-daily amikacin regimen efficacy and safety in systemic Gram-negative infections. Scandinavian Amikacin Once Daily Study Group. J Antimicrob Chemother 1993 31(6) 939-48. 

Aztreonam, a monobactam, is a useful alternative for patients with aerobic gram-negative infections who are allergic to penicillins, but has no activity against anaerobes. Aztreonam appears to be the only p-lactam antibiotic that can be safely administered to penicillin-allergic patients [58]. Aztreonam has a spectrum of activity that is comparable to the aminoglycosides but it is less nephrotoxic in patients [59] and it appears to be well tolerated in infants and children [60]. 

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