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Antibiotics

Antibiotics are drugs which are designed to have specific anti-bacterial properties. Some have a relatively “narrow spectrum” in other words they have lethal effects against a relatively small number of bacteria, others have a much “broader spectrum” and so cause the death of a wide range of bacterial species. Each have advantages and disadvantages. Often physicians treat infections with broad spectrum antibiotics when they are uncertain of the exact organism that is causing a particular disease, tis enables all of the potential bacteria that cause infection and sepsis to be effectively treated, however it has the disadvantage of impacting a broad range of bacteria within the normal microbiome (bugs that are meant to live in our bodies). Using broad spectrum antibiotics increases the risk of side-effects such as antibiotic associated diarrhoea and the development of bacteria that are resistant to treatment with antibiotics, bt they do afford a broad range of infections to be treated. Narrow spectrum antibiotics are often used when the healthcare team understand which organisms are causing an infection and to which antibiotics such infection is sensitive to. In general when patients present to an emergency department patients are often commenced on broad spectrum antibiotics and as the organisms likely to be causing infection are elucidated the antibiotics are changed to reflect activity against the specific organisms causing infection.

In terms of side-effects the commonest manifestations are nausea and diarrhoea, perhaps reflecting their impact on bacteria living as normal commensals within the GI tract. Allergy is also a concern with many antibiotics including penecillins.

 

Amoxicillin, Flucloxacillin and Ampicillin, Pippericillin

All of these antibiotics are penicillin’s, the first group of antibiotics discovered and part of a broader class of antibiotics known as beta-lactams. They have a broad range of activity against a rane of organisms. Theses include, staphloccoci a common cause of wound infection, streptococci (some form of pneumonia), Neisserria (meningitis) and listeria (GI infection and meiningitis). Penecillins work by inhibiting the production of bacterial cell walls, thus rendering the organism unable to survive. Originally discovered by Alexander Fleming in 1928 and derived from moulds (a kind of fungus) a number of organisms across the world have now developed resistance to this class of antibiotics. The commonest mechanism for resistance is the production of a beta lactamase by the bacteria, this protein breaks down the antibiotic making it ineffective.. For this reason a number of penecillins are now marketed in combination with a beta-lactamase inhibitor. Such drugs include augmentin (amoxicillin and clavulanic acid) and tazocin (piperacillin and tazobactam), which enables them to have greater activity against a broad range of organisms that would otherwise be penicillin resistant.

Meropenem/Imipenem

These drugs are known as carbopenems a further class of beta lactam antibiotics, as their name might imply they are related to penicillin and have a similar mechanism of action, inhibiting the production of bacterial cell walls. At the time of their discovery they were believed to be resistant to B-lacatmases, however it has now become clear that whilst they are resistant to many forms of this enzyme a number of organisms do produce proteins that can break down these antibiotics (New Dehli-beta-lactamase), thus conferring resistance to this group of antibiotics.

Cephalosporins

Cephalosporins are a further class of beta-lactams whose mechanism of action is similar to that of penicillin. They work by interfering with the production of peptidoglycan component of bacterial cell walls. Whilst having greater resistance to beta-lactamase, the protein that breaks down many antibiotics, than penicillins many organisms have now developed varying degrees of resistance to cephalosporins.

 

Ciprofloxacin/Levofloxacin; Quinolones

These antibiotics belong to a group of chemicals known as quinolones. They have a broad range of activity against a wide spectrum of organisms. Ciprofloxacin is particularly effective in the setting of biliary sepsis since it is actively secreted by the liver even in the setting of biliary obstruction (unlike many penecillins). Levofloxacin is thought to have better penetration into respiratory secretions and is therefore sometimes preferred in the setting of respiratory infections. Quinolones also tend to have excellent penetration of bone tissue and therefore are often chosen for patients with osteomyelitis (bone infection). Quinolones work by preventing the proper unwinding of bacterial DNA, by inhibiting bacterial gyrase and type II and type IV topoisomerases, as a consequence bacterial DNA becomes fragmented and bacteria are unable to survive. Resistance to these drugs is conferred either by changes in the bacterial topoisomerases, rendering them unsusceptible to the effects of quinolones or by production of proteins that prevent the quinolones from binding to their normal site of action (Qnr protein).

Gentamicin; Aminoglycosides

Gentamicin is another antibiotic derived from other organisms (A bacteria, micromonospora purpurea). It is able to kill bacteria by interfering with the RNA ribosomal interactions, leading to the inability of bacteria to produce the proteins they require to survive. It is active against a broad range of largely gram negative organisms, such as Pseudomonas, E.coli Klebsiella and on occasion the gram positive Staphylococci. Resistance is emerging even to this antibiotic. Gentamicin should be avoided in pregnancy and used with caution in the elderly and in children since it confers, even in normally well adults significant risks of renal impairment and ototoxicity (damage to hearing manifest through it’s effects on the inner ear). For this reason dosing and monitoring requires careful diligence in patients on this drug.

Tetracyclines; Oxytetracycline

Tetracyclines are a class of antibiotics derived from a bacterial class known as Streptomyces. They have activity against both gram positive and gram negative organisms, but in recent decades have become less effective because of increasing bacterial resistance. They can be used in syphilis, Lymes Disease and rickettsial disease. Historically they have been used to treat bacterial overgrowth but because they remain in the gut a number of bacterial organisms have become resistant to them.

Side-effects include nausea and diarrhoea. They should be avoided in pregnant women and young children since they appear to persist in bones and teeth if they are given during development of these tissues.

 

Rifaximin

Is an antibiotic that was developed relatively recently (2004) and has been shown to be largely unabsorbed by the gut. As such it may have particular benefits for treating infection within the gut or the gut wall since it does not appear to cause much in the way of systemic side effects. There is evidence for its use in Small intestinal bacterial overgrowth, hepatic encephalopathy and non-constipation predominant irritable bowel syndrome, however in Western Europe and North America the price of Rifaximin is a bar to it’s wider use.

Fidaxomicin

Fidaxomicin is an antibiotic which has a relatively narrow spectrum of activity, against a number of gram positive bacteria, particularly clostridia. It is there used almost exclusively as a treatment for C. difficle related diarrhoea. C. difficle related diarrhoea tends to occur when the diversity of the colonic microbiome has already been dramatically reduced by the use of broad spectrum antibiotics and evidence suggests that rates of relapse may correlate inversely with the recovery of a more diverse bacterial flora. Because of its narrow spectrum fidaxomicin may allow the background colonic flora to recover, whilst inhibiting the proliferation of C. difficle by preventing the initiation of RNA transcription.

For specfic treatments please click on the links below;

 C. difficle related diarrhoea

Antibiotics for H.pylori,

Antibiotics for IBS?

Antibiotic for GI Infection?

Antifungals

Fungi are normal skin and gut organisms. Fungi, including yeasts constitute approximately 5% of the normal colonic microbiome, however they may cause infection in susceptible individuals. The commonest fungal infections are athletes foot, intertrigo and vaginal candidiasis, which are usually due to organism called candid a albicans. These infections are usually treated with topical creams and treatments. Antibiotics, pregnancy and poorly controlled diabetes all contribute the the risk of developing such infections. On occasion fungal infections may be more invasive and cause systemic (symptoms throughout the body systems). Fungi which cause systemic disease include candida, aspergillus (aspergillosis) and cryptococcus (cryptococcal meningitis). Such infections are usually seen in the immunocompromised and require systemic anti-fungal therapy, such as fluconazole (which may cause liver upset) which an be given orally or amphotericin B (Ambisome) which can on occasion cause allergic reactions. Amphotericin may cause nausea, vomiting, gi upset and headaches and is given as an intra-venous injection.

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