number Done by Corrected by Doctor مالك الزحلف

Transcription

1 number 30 Done by حسام أبو عوض Corrected by Shahd Alqudah Doctor مالك الزحلف

2 Vancomycin As mentioned in the previous lecture, vancomycin is a pure gram-positive drug (has no effect on gram-negative bacteria), so it is used against MRSA, enterococci and Clostridium difficile. In general, in staph or strep infections, we avoid using vancomycin and prefer penicillins and cephalosporins. However, if resistance/allergy are noted in the patient then we choose vancomycin (NOT carbapenems, vancomycin has a narrower spectrum compared to carbapenems and we must always choose the drug with the narrowest spectrum). In enterococci, it was noted that some bacteria developed resistance to ampicillin (penicillin family), in such cases vancomycin is the drug of choice (if also resistant to vancomycin then use ceftaroline (5 th gen. cephalosporin). Side effects: As mentioned in the previous sheet, vancomycin is administered intra-venously (except with Clostridium difficile where it is administered orally) [ remember that vancomycin deals with life threatening situations ]. When vancomycin is administered as a single shot (single bolus )(which is a very high dose that gets us to the steady-state immediately) it will cause thrombophelebitis, pain and red man syndrome**.. If you ever meet a doctor that does such a thing you probably do not want to come back to them again.. ** When vancomycin is given as a bolus dose an allergic reaction is noted in 30-40% of the patients (that s tooooo high) and this may lead to anaphylaxis, the first sign of anaphylaxis appears on the neck which obtains a red color red- This allergic reaction is given the name.(حسب حكي الدكتور زي البندورة بتصير ( neck syndrome, you might also hear people calling it red-man syndrome. To avoid this problem, vancomycin is given as drips in a highly diluted solution.(زي الصورة) hours over a time period of one to two This allergic reaction can occur in some patients even though they're receiving the drug in a dilute solution as infusion, so if you notice phlebitis or red neck syndrome stop the drug immediately because anphlyaxis is likely to happen. The allergic reaction to vancomycin is noted equally in males and females.

3 In ALL pharmacology books you ll find the following written: Side effects of vancomycin; it can cause ototoxicity and nephrotoxicity (and hypersensitivity). In reality (according to Dr. Malik), ototoxicity and nephrotoxicity are the side effects of gentamycin (aminoglycosides) which is often given with vancomycin, however, if you give only vancomycin such incidences are extremely rare in monotherapy. This occurs in patients who are already very susceptible [e.g. those who have renal impairment (so there will be a problem in the drug clearance), in prolonged therapy, high doses, high serum concentrations, or other toxic medications]. However, we are supposed to follow the agreed-on guidelines which say that we should trough the drug. [Explanatory note: do you remember the drug concentration curve at the steady state? There was a certain maximum level that we reach after administering the drug and a minimum level just before giving the next dose; that maximum is called the peak and the minimum is called the trough. So, what we actually do is that we give a certain dose to the patient and just before the time for the next dose we take a blood sample and measure vancomycin s concentration in it, if it is too high we either stop giving vancomycin or we simply lower the dose]. Dealing with neonates who have hospital acquired meningitis, consideration should be given to MRSA. In meningitis we use ceftriaxone ( for G-ve & Niessria), in this case Vancomycin should be added to cover MRSA. - You have to monitor the vancomycin level in neonates (because their kidneys have not yet developed completely) and it is more preferred to use Teicoplanin; a drug very similar to vancomycin, since allergic incidences are very rare here. [ this is applied also with adults who have renal impairment ] If you are too lazy (or want to make your patient pay a lot), use teicoplanin for it does not require troughing", however, teicoplanin is waaaay more expensive than vancomycin. Monobactams

4 These are β-lactam antibiotics with a limited activity on aerobic gram-negative rods ( including pseudomonas). The main drug we are concerned with in this family is Aztreonam. We need it in patients allergic to Penicillins and Cephalosporins who have G-ve infections (sepsis or hospital acquired infections). This drug is good to be used against pseudomonads, E.coli, H.influenza, proteus, serriata, enterobacter, shigella, salmonella (All G-ve bacteria). Despite being β-lactam antibiotics (Aztreonam is a monocyclic β-lactam) just like penicillins, it is noted that people allergic to penicillins are rarely allergic to monobactams. It is note-worthy that aztreonam is resistant to β-lactamases (no need for clavulanic acid). Protein Synthesis Inhibitors Now let s move on to protein synthesis inhibitors (in case you got lost, all the previous antibiotic families were under cell-wall inhibitors group). The protein synthesis inhibitors we will be discussing in this course are: Tetracyclines (only one in this sheet), mycolides, aminoglycosides and clindamycin. The mechanisms of action of these drugs were discussed in microbiology and Dr. Malik said he is not concerned much with those details and that we can read them from microbiology lectures. (I have no idea whether questions related to these mechanisms will be asked in the exam, the details are found in microbiology (bacteriology) lecture 8). Tetracyclines They were first introduced to markets in They are five drugs, the most important one is doxycycline( which is the only one available in Jordan). They are bacteriostatic drugs with a quite wide spectrum without activity on pseudomonas, however, bacteria managed to develop resistance to these drugs, but in quite a special way. Bacteria began producing plasmid-encoded proteins that bind to the cell wall (so bacteria without a cell wall, will be

5 suscpetible to tetracyclines) forming pumps(atp-dependent pumps) that pump the drug molecules out-side the cell so they lost their broad spectrum! However,the production of Tigecycline is considered as a revival of tetracyclins. Tigeycyclin which is a new member of tetracyclins (introduced to markets in 2013) has a broad spectrum(including MRSA) because bacteria is not resistant to it since it is not a substrate of the ATP-dependent pump. These drugs are still used for certain atypical bacteria which have no cell wall or a cell wall with an abnormal structure, e.g. mycoplasma and chlamydia. The diagram above shows all the bacteria against which tetracyclines are still used and following are some short notes to ADD to what is above in the diagram: Brucella seems to be coming back to Jordan and some infections were seen. The lyme disease is caused by Borrelia. It is seen mostly in Nigeria and no such cases were recorded in Jordan, it won t be discussed (it is not included in the exam) Ricketssia is also not common in Jordan, cases are more common in USA, again it won t be discussed. (it is not included in the exam)

6 Chlamydia causes atypical community acquired pneumonia (lungs) and urethritis (90% of urethritis cases are caused by Chlamydia trachomatis). To treat chlamydia give a 250mg tetracycline twice daily for one week (Dr. Malik said he won t ask about the numbers in the exam.i'm not sure!). Mycoplasma pneumonia causes pneumonia in young adults and in close confines الضيقة والمغلقة زي الجامعة) (األماكن [used to be called military disease, because it was first extracted from military camps]. You can use tetracyclines here ONLY as a definitive therapy as they do not cover the other causes of pneumonia ( Strep. Pneumonia, H. Influenza, klebsiella) to be used empirically. Cholera is a disease caused by Vibrio cholera which results in a very severe diarrhea. It has a special treatment that uses no drugs: simply give the patient fluids, normal saline and electrolytes to avoid dehydration. Of course this treatment does not get rid of the bacteria, but it makes things easier. To eliminate the bacteria you need to give a single shot ( 3 grams one shot) of a tetracycline. Brucella الحم ى المالطية) /بتسبب Brucellosis)is a special bacteria as it enters INTO the cell (intracellular infection) so its treatment needs to be quite aggressive: give 250mg of a tetracycline twice daily for one month with an aminoglycoside(gentamycin) given IM or IV for the first week (for the exam, you will not be asked about these numbers). Some other diseases can be treated with tetracyclines like acne الشباب) (حب (this is controversial though, some people say acne is caused by bacteria and others tend to disagree, however, 20-30% of patients do respond to antibiotics) and syphilis (use tetracylines if the patient does not respond to penicillin G or is allergic to it). Side effects Tetracyclines are known to be chelating agents to Ca²+, Mg²+ and Al³+, so when taking tetracyclines any drugs/dietary elements that contain these di- and trivalent metal ions must be avoided in order to avoid the binding between tetracyclines and these ions which decreases the absorption of the drug (e.g. anti-acids, they all contain Mg(OH)₂ or Al(OH)₃, and milk, contains Ca²+, and iron preparations).

7 Tetracyclines are very lipophilic that will penetrate through the bones and the teeth. If the bones are yet to be completely formed and tetracyclines are taken bone deformity can occur(ca²+ is needed for bone-building and it is being trapped and not allowed to be used), same goes for teeth (teeth will be small in the future, this condition is called teeth hypoplasia). Therefore, tetracyclines are contraindicated for kids under the age of 8, nursing ladies (breastfeeding ladies) (as tetracylines are very lipophilic, they would enter into the milk and then the kids would drink a tetracycline-rich milk and same bone and teeth problems can occur) and for pregnant ladies (as tetracyclines are lipophilic, they can reach the fetus and cause, again, the same problems).staining of teeth can also occur in adults. Another side effect, hepato-toxicity (liver will be damaged), can occur to the pregnant lady (to the mother this time) and its reason is unknown. Phototoxicity is another side effect of tetracyclines. If the patient taking a tetracycline goes to a place that is very sunny like Melbourne (where the damaged part of the ozone Iocated ) a severe sun burn might occur. Also, GI disturbance is the most common side effect. Never take doxacycline (or other tetracyclines) before eating as they cause GI disturbances due to direct irritations (initially) and later due to altering the gut normal flora.