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==Role in disease== [[File:Diagnostic algorithm of possible bacterial infection.png|thumb|Example of a workup algorithm of possible bacterial infection in cases with no specifically requested targets (non-bacteria, mycobacteria etc.), with most common situations and agents seen in a New England setting. Clinically significant gram-negative bacteria are usually rods, as shown near bottom right. Although some gram-negative bacteria can be recognized by "bench tests", diagnosis in the modern microbiology lab usually involves [[MALDI-TOF]] and/or multitarget assay.]] One of the several unique characteristics of gram-negative bacteria is the structure of the [[bacterial outer membrane]]. The outer leaflet of this membrane contains [[lipopolysaccharide]] (LPS), whose [[lipid A]] portion acts as an [[Lipopolysaccharide|endotoxin]].<ref name=Baron/> If gram-negative bacteria enter the [[circulatory system]], LPS can trigger an [[innate immune response]], activating the [[immune system]] and producing [[cytokine]]s (hormonal regulators). This leads to [[inflammation]] and can cause a toxic reaction, resulting in fever, an increased respiratory rate, and [[Hypotension|low blood pressure]]. That is why some infections with gram-negative bacteria can lead to life-threatening [[septic shock]].<ref name="ww.ncbi.nlm.nih.gov"/> The outer membrane protects the bacteria from several [[antibiotic]]s, [[dye]]s, and [[detergent]]s that would normally damage either the inner membrane or the cell wall (made of [[peptidoglycan]]). The outer membrane provides these bacteria with resistance to [[lysozyme]] and [[penicillin]]. The [[Periplasm|periplasmic space]] (space between the two cell membranes) also contains [[enzyme]]s which break down or modify antibiotics. Drugs commonly used to treat gram negative infections include amino, carboxy and ureido penicillins ([[ampicillin]], [[amoxicillin]], [[Piperacillin|pipercillin]], [[ticarcillin]]). These drugs may be combined with [[beta-lactamase inhibitor]]s to combat the presence of enzymes that can digest these drugs (known as [[beta-lactamase]]s) in the peri-plasmic space. Other classes of drugs that have gram negative spectrum include [[cephalosporin]]s, [[monobactam]]s ([[aztreonam]]), [[Aminoglycoside|aminoglycosides]], [[quinolone antibiotic|quinolones]], [[macrolide]]s, [[chloramphenicol]], [[Antifolate|folate antagonists]], and [[carbapenem]]s.<ref>{{cite web|last=Glück|first=Thomas|url=https://www.jwatch.org/id200312120000007/2003/12/12/gram-negative-bacteria-and-broad-spectrum|title=Gram-Negative Bacteria and Broad-Spectrum Antibiotics: Good News Except for Fluoroquinolones|publisher=NEJM Journal Watch|website=www.jwatch.org|date=12 December 2003|access-date=10 March 2018|archive-date=10 March 2018|archive-url=https://web.archive.org/web/20180310074653/https://www.jwatch.org/id200312120000007/2003/12/12/gram-negative-bacteria-and-broad-spectrum|url-status=live}}</ref>
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