number Done by Corrected by Doctor Dr.Malik

Transcription

1 number 27 Done by Fatimah Farhan Corrected by Basil Al-Bakri Doctor Dr.Malik

2 Note: anything in red is just extra info and you will not be asked about it in the exam. In this sheet we will continue talking about antibiotics, here s a quick revision of what we took last time: We talked about three types of penicillins (natural penicillins, β-lactamase resistant penicillins and broad spectrum penicillins). Natural penicillins: Penicillin V and penicillin G which have narrow spectrums; therefore they only have a few clinical applications like the empirical treatment of strep throat which is mainly caused by streptococcus pyogenes (beta hemolytic streptococcus). Penicillin G is via injection (IM OR IV) while penicillin V is given orally. Benzathine benzylpenicillin, also known as benzathine penicillin G, is also used in the treatment of rheumatic fever المفاصل( )التهاب once every month or 28 days. (Once every 3-4 weeks) Penicillin v is usually our drug of choice in oral infections (odontogenic infections) because it s active on the anaerobic organisms which occupy the mouth. β-lactamase-resistant penicillins (Cloxacillin, Flucloxacilin, Oxacillin and methicillin): the only difference (spectrum-wise) between these four antibiotics and the two previously mentioned natural penicillins is that these are active against staphs in addition to the spectrum of penicillin G and V (strep). This causes them to be generally active against the skin flora so they are used to treat cellulitis and other skin infections. However due to the appearance of MRSA, methicillin is no longer in use and has been withdrawn from the market. Broad Spectrum Penicillins: amoxicillin and ampicillin (amoxicillin is a prodrug* of ampicillin). They cover both Gram positive bacteria and Gram negative bacteria (H.influenze, E.coli, M. catarrhalis, salmonella, serratia and shigella). This means that ampicillin and amoxicillin cover all causes of upper respiratory tract infections (refer to the slides for the table). Therefore the drug of choice to empirically treat upper respiratory tract infections (sinusitis, otitis media, tonsillitis, pharyngitis and laryngitis) is augmentin (amoxicillin +clavulanic acid) unless the infection is strep throat in which we give penicillin v or g (narrower spectrum). *Prodrug: an inactive medication which is metabolized into its active form inside the body.

3 We do not use amoxicillin alone in upper respiratory tract infections because staphylococci and even H.influenzas have become capable of producing β-lactamase, therefore we need to add a β-lactamase inhibitor (clavulanic acid) to the drug so we prescribe amoxicillin/clavulanic acid. *we give amoxicillin orally but ampicillin as an injection -Why do we find amoxicillin alone or amoxydar دار الدواء) (اسم in pharmacies? Answer: In Jordan we don t have penicillin V or G so if a patient has strep throat or an anaerobic oral infection amoxicillin is used as a replacement. الدكتور قال ال تهتم بهاي القصه بس لمعرفتك * The spectrum of amoxicillin and ampicillin also covers enterococci which causes endocarditis (a life threatening disease in the heart s endocardium especially in the valves). Endocarditis is caused by three types of organisms (staph, streptococcus pyogenes and enterococcus) which are all covered by amoxicillin and ampicillin. Because endocarditis is a life threating situation we have to give the treatment via injection, therefore ampicillin+ tazocillin (or tazobactam) is our drug of choice (amoxicillin is administered orally so we do NOT use it in life threatening situations). Tazocillin and tazobactam are β-lactamase inhibitors that are given with ampicillin (IV) In the past, it was thought that gentamicin* had a synergistic** effect with ampicillin, so when treating endocarditis a combination called amp-gent (ampicillin and gentamicin) was given to the patient, however this was later proven to be ineffective and gentamicin is no longer used in the treatment of endocarditis. *Gentamicin: a gram negative antibiotic. **Synergism: interaction of two or more antibiotics to produce an effect greater than the sum of their separate effects (1+1>2). Dentists usually ask if their patients have a history of rheumatic fever, endocarditis or (for older patients) if they have recently gotten a heart valve implant or replacement before dental surgery. This is because the oral cavity is filled with streptococci that can enter the blood stream and cause the postsurgery infective endocarditis. To prevent this from happening, a prophylactic measure must be taken so the dentist gives 2 grams (a loading dose*) of

4 augmentin** as a prophylactic against all causes of endocarditis 1.5 hours before surgery (so that it reaches its peak at the time of surgery). *loading dose: an initial high dose of a drug used to get its concentration in the body to the peak activity level without waiting for 5 half-lives. **Do not use amoxicillin without clavulanic acid because it won t cover staphilococci which is the main risk factor of endocarditis in oral surgery Otitis media is a disease common in children that is mainly caused by streptococcus pneumonia. Streptococcus pneumonia is usually found in the oral cavity and may cause otitis if it reaches the ear. Augmentin is the favored drug for the treatment of acute otitis. In children the dose is (80-90 mg/kg/day), the original dose was (40-45 mg/kg/day) but because of the selection of the more resistant types of S.pneumonia over time we had to double the dose because of the increase in the MIC*. *MIC: minimum inhibitory dose. *in adults the dose for otitis media is 675 mg instead of 365 mg. The approximate percentage of streptococcus pneumonia that is resistant to augmentin has risen from 10% when it was discovered to 20% today. Antibiotics are considered effective if less than 25% of their target population is resistant to them. In doctor Malik s opinion augmentin will probably lose its effectiveness by the time we graduate. *In Jordan the preferred dose for all infections is the high dose (675mg) because most of the staph in Jordan is intermediately resistant to amoxicillin. Extended Spectrum Penicillins (antipseudomonal penicillins): (Carbenicillin, Ticarcillin, and Piperacillin*) *piperacillin is the only one still used. Spectrum activity: most G +ve bacteria (staph: only if tazobactam is added), some anaerobes and G ve bacteria (e.coli, β-lactamase -ve H.influenza, salmonella, serratia, klebsiella, enterobacter and most importantly pseudomonas aeruginosa). -These drugs can t be taken orally they are taken via injection. -These drugs are susceptible to beta lactamses so we must add a beta lactamase inhibitor (piperacillin/tazobactam*) this combination is called tazocin. *We don t use clavunic acid because it s not compatible with these drugs.

5 Tazocin is mainly used in hospitals in the ICU* and CCU** because if a patient gets an infection in the ICU or CCU the infection is probably G ve bacteria and could be pseudomonas (green pus bacteria) which is a very dangerous bacteria only found in hospitals***. *ICU: intensive care unit **CCU: coronary care unit **Community pseudomoni are usually non infective. Normal antibiotics are used on a daily basis in hospitals eliminating the weaker types of bacteria and leaving the more resistant types alive. Hospital acquired infections are usually caused by very resistant types of bacteria such as: pseudomonas aeruginosa, Serratia marcescens, enterobacter, klebsiella pneumonia (all of which are G ve) and MRSA (G+ve). If a patient enters a hospital and gets infected after 3 days then the infection is probably hospital acquired. In case of a hospital infection we use two antibiotics: tazocin (piperacillin/tazobactam) to cover the previously mentioned G-ve bacteria and vancomycin (which we will talk about later) to work against MRSA. And with this we have finished the four main types of penicillins penicillins. A quick summary of penicillins Penicillin G and V: strep throat. Penicillin G: rheumatic fever. Penicillin V: oral infections. Β-lactamase resistant penicillins (Cloxacillin, Flucloxacilin, Oxacillin and methicillin): skin infections (strep and staph). Augmentin: for all upper respiratory tract infections Has enterococci coverage therefore ampicillin (iv) is used to treat endocarditis. Prophylaxis from endocarditis before dental surgeries using 2 grams of augmentin. Extended spectrum penicillins (antipseudomonal penicillins): Tazocin (piperacillin/tazobactam): Effective against G ve and most G +ve. Used against hospital infections (pseudomonas aeruginosa, Serratia marcescens, enterobacter, klebsiella pneumonia (all of which are G ve) and MRSA (G+ve).).

6 Side effects of penicillins: -Penicillins are free of direct toxic effects because they bind to receptors on the bacterial cell walls and we as humans have no cell walls surrounding our cells. -The main unwanted side-effect caused by penicillins is hypersensitivity reaction which is due to the combination of a penicillin metabolite (degradation product) with a certain host protein producing a compound that some bodies consider as antigenic. (The hypersensitivity varies from person to person; some people get a simple rash while others suffer anaphylaxis which can be life threatening, this is why we usually try not to prescribe penicillins for children. Around 10% of any population has an allergy to penicillin. To know whether a person is allergic to penicillin or not we conduct a skin test and injecting a small amount of penicillin under the skin, if the skin becomes swollen (elevation with redness) this indicates that the patient is allergic to penicillin. If an allergic person takes a dose of penicillin for the first time, the reaction might not be very strong because his body still hasn t produced the antibodies but if taken for a second time the allergic reaction might be life threatening. Never prescribe penicillins to patients unless you know for sure if they are allergic. (If you don t know their allergy status refer them to the skin test.) -Antibiotics cause alteration of the bacterial flora in the gut; this can be associated with GI disturbances such as Diarrhea. This happens to a greater extent with antibiotics that have a greater antibacterial spectrum. Meaning that the chance of being infected by clostridium difficile or developing pseudomembranous colitis increases when using wider spectrum antibiotics like tazocin (the lowest chance is with penicillin V and G). -Diarrhea caused by antibiotics is a serious issue in children. -All penicillins, particularly methicillin, may cause acute nephritis; thus methicillin is no longer available. -Antipseudomonal penicillins (Carbenicillin and Ticarcillin), to some extent penicillin G, may decrease agglutination. -All penicillins are best given on an empty stomach to avoid the absorption delay caused by food. Exception being amoxicillin ( don t worry about augmentin).