internal medicine sheet # 1 - Abdulhameed 3a8rabawe

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internal medicine sheet # 1 - Abdulhameed 3a8rabawe

Post by Shadi Jarrar on 15/10/2011, 1:30 am

Antibiotic therapy

· First of all , we will talk about principles of antibiotics therapy as :

How can I choose the appropriate antibiotic, side effects of antibiotics, effects of patient age , kidney function , immunity , type and sit of infection on antibiotics working .

· History of antibiotics :

Knowing of antibiotics started after discovering of penicillin by Sir A. Fleming who got Nobel Prize 1945

· Antibiotics divided into groups : the most imp. Groups are :

· PCNs (penicillin)

· Cephalosporins

· Carbapenem

· Monobactams

· Glycopeptide

· Aminoglycoside

· Fluroquinolone

And each group has many types and special properties for example:

PCNs : there are several types of PCNs such as :



l Amoxicillin

l Cloxacillin

l Oxacillin

l Ampicillin

l Piperacillin

l Methicillin

· How to choose the proper agent of antibiotics :

1) The first step when you treat the patient is to know the type of organism (Identification of the organism) , how can we identify the organism ??

Through several methods as:

1- Culture : for example : we send the pus to the lap for culture

2- Bacteriological statistics (statistical guess ) : there are many of cases that we cannot identify the name of the causative organism so in these cases we depend on the publish researches about that ill for ex. : cellulitis : if you have 100 patient with cellulitis maybe only one of them has positive blood culture or 2% of them have positive results depending on biopsy, so we depend on the researches about cellulitis that say the most common causes of cellulitis is staph. Aurous or the most common cause of UTI is E. coli ….etc so Bacteriological statistics : the application of knowledge of the organisms most likely to cause infection in a given clinical sitting

3- PCR(POLYMARASE CHAIN REACTION) : may identify the organisms that don’t appear in culture test

These are the three methods that the doctor talked about …(other methods written in slides)

2) Antimicrobial susceptibility ( Does the pathogen kill through the prescribed antibiotic??) : there are three imp. Methods that done in clinical lap such as :

1- Disk diffusion method : we bring antibiotic in the form of disc and we put this disc on plate that is filled with organism then we wait for 24 – 48 hours after that , we will see zone of inhibition then we measure the diameter of this zone and we decide if the organism is sensitive or resistant to antibiotic but we must have organism to take place this method \

2- Epsilometer (E-test) : we will talk about it later

3- Minimum inhibitory conc. (MIC) : it is the least concentration of antibiotic that prohibits the growth(does not kill) of bacteria which is fine for clinical practice

4- Minimum bactericidal conc. (MBC) : it is the least concentration of antibiotic that kills the bacteria ,,, usually MBC higher than MIC because we need higher con. To kill the bacteria than to stop the growth of bacteria

In our hospital , they use disc diffusion method. In some hospitals, they use automated method : they put the plate of bacteria(in some cases they don’t the type of bacteria) in automated machine called Voitek that gives us the type of organisms and their sensitivity and resistant

3) Pharmacodynamic profile : you should know three imp. Terms :

· Area under the curve / time curve to MIC (AUC / MIC)

· Maximal serum conc. / MIC (C max / MIC)

· Time during dosing interval that plasma conc. exceed the MIC (t / MIC)

The following picture will explain these terms ….

The dotted lines explain the MIC of the organisms (A , B , C ) ….

We give antibiotic to patient , its level rises abruptly , then it will decline this occur normally in most of antibiotics ….

· For organism A : the area from MIC of organism A to the peak con. Of antibiotic to called ( C max or Maximal serum conc.)

· the least level of antibiotic in human serum called (truf … I don’t sure about spelling)

· the area under the curve of antibiotic called (area under the curve)

· The area between MIC and the curve called (area under the curve to MIC).. area under the curve to MIC of the organism C is the largest one

· The time of antibiotic level that remains above MIC is also imp. And this time differs from organism to other depending on type and dose of antibiotic

Ø Conc. Dependent killing : this mean that the killing activity of antibiotic depends on con. Of the antibiotic but the time of antibiotic above MIC is not important factor ….increase in conc. leads to a more rapid rate of bacterial death (i.e. large dose at long intervals) ex. Of this case(floroquinon FQ,aminoglycosine AG) so, usually these drugs given once or twice times a day

Ø Time dependent killing : this mean that if con. Of antibiotic above MIC , this does not affect killing activity but the time the con. Above MIC is very imp. ….reduction in bacterial density is proportional to the time that the conc. exceeds MIC (i.e. sufficient dose at appropriate intervals to keep conc. above MIC) … ex. Of this case(b-lactams(as penicillin) , vancomycin) so, , usually these drugs given three or four times a day ,,, in the past , they gave the penicillin infusion then they started to give it four times a day

· Resistance selection : Do we create the resistant ?? or the resistant already presents in bacteria ??

· The resistant genes present in bacteria since thousands years but what we do is : select these resistant organisms …. So the resistant presents in organisms since long periods of time but it is present in very small amount of organisms …. What happens in hospital or in endemic place is the following : these people will have low immunity and when they become infected by certain organisms , they take antibiotic for treatment… suppose that the patient has a million of bacteria, one of them will become resistant to this antibiotic then the remaining bacteria will kill by this antibiotic and only the resistant one will remain

· This resistant bacteria maybe transfer to other person and cause infection and the patient will take antibiotic and what happen is encourage of resistant and in next population the resistant organisms will increase but almost this patient will not affected by these resistant organisms because of generation of huge normal flora but if the immunity is low the patient will affected…… the following picture will explain what I talked about

· There is imp. Manual for antibiotics which is Sanford’s

· Medical letter on drugs and therapeutics

4) Host factors : Dose the patient has sensitivity to certain drugs , adverse reactions to certain drugs , immunity problems or cancer ….??

· Previous history of adverse reactions

· Neutrophil function à neutropenic are treated aggressively

· CLL(chronic lymphocytic leukemia), MM(multiple myeloma), asplenia à treated empirically (Empirical treatment is a medical treatment not derived from the scientific method, but derived from observation, survey or common use,,,,, from Wikipedia)

Ø there is four types of antibiotic prescription :

therapeutic , empirical , prophylactic , preemptive

1- therapeutic : you know the type of organism , so we give the appropriate antibiotic for this organism ( ex. UTI caused by E.coli , so give cebro. Drug for treatment )

2- empirical : treatment the patient from the infection without knowing the type of organism … as we said before

3- prophylactic : treatment the patient who is at high risk for certain ill .( ex. AIDS patient , when the level of CD4 of these patient less than 200 , they become at high risk for pneumocystic pneumonia )

4- Preemptive : the patient has diagnostic marker for certain disease but still not affected but this disease ( ex. Bow marrow transplant patient at high risk for cytomegalo virus(CMV) infection so either I give prophylactic drug for this patient or we use several PCR tests at several intervals until the level of diagnostic marker become at high risk )

5) age of patient : is very important factor for prescription of drugs because of :

1- Renal function (impaired physiologic function) which it is the most imp. Affect of age … decrease with age .. so maybe we need to give the patient less dose

2- Absorption : decrease with age

3- Tetracyclines and Doxycyclin : they are not given for children less than 8 years and also not given for pregnant women

4- INH (isonicotinylhydrazine)hepatotoxicity: will become higher for older people

5- Nephrotoxicity : higher in older people

6- Ag (aminoglycosides)and cochlear toxicity

6) Genetic / metabolic :

Ø Hemolysis in G6PD deficiency patients when they take some antibiotics such as balkatrin

Ø DM : sulfa drugs can potentiate the sulfonylurea hypoglycemic agents ( the patient that takes balkatrin with hypoglycemic agents maybe suffer from hypoglycemia)

- Dextrose load: some drugs may given with dextrose load and that may leads to high sugar level in blood

- Poor IM absorption (use IV route)

7) Pregnancy : you should before prescribing antibiotics, know if the patient pregnant or not because some drugs contraindicated with pregnant ladies …

· Safe with pregnancy : PCN, cephalosporin, erythromycin

· Dangerous with pregnancy(so not given): tetracyclines (hepatic toxicity, dental discoloration)

· FQ à Contraindicated with pregnancy

· metronidazole : dangerous for class C pregnancy (less dangerous on fetus) but in the past , according to animal studies , they said that it is dangerous on pregnant but it is not approved on humans (so better to avoided)

· in general , it is better to avoid drugs for the first trimester of the pregnancy , to avoid teratogenic

· some drugs almost it is safe for pregnancy but there is no researches about their affect on pregnancy such as : rifampin, Ag(aminoglycosides), azithromyccin, clindamycin, imipenem,vancomycin, TMP

· The problem with pregnancy that it is difficult to make researches on them …. So , usually the researchers use what we called registries : they monitor the affect of certain antibiotic on pregnant women and register it effect…. Also, animal studies may help also

· Do you we need to increase antibiotic dose in pregnant women ? ….. until now , we don’t increase the dose although the volume distribution in pregnant is higher

8) Renal and liver function : mainly with Vancomycin & Aminoglycosides

9) Site of infection :

· You should know before prescribing antibiotic , know the site that you want to cover with antibiotics such as :

· Meningitis

· Endocarditis

· Osteomylitis

· Chronic prostatitis

· Intraocular infections

· Abscesses

· Foreign body


· Because some antibiotics will not work on CNS or abcesses….

10) Immune system :

· Abx can cause immune suppression esp. in the immunosuppressed patients

· Suppress monocyte transformation, phagocytosis, chemotaxis, antibody production

Ø Combinations: use more than one antibiotic in the same time , sometimes it is justified and sometimes not ….

· The main example on combination is TB infection and staph endocarditis to prevent the emergence of resistant bacteria

· Sometimes, this practice(combination) is overuse

· So, the combination therapy should be careful because of drug – drug interaction , emergence of resistant , may cause increase of allergy and increase the cost on the patient , antagonism ( the drugs work against each other … common example on antagonism, in the past thy use penicillin for treat. Of meningitis then when they started to use tetracycline in addition to PNC the patients die because the penicillin and tetracycline antagonize each other )

Ø Adverse effects :

· 5% of patients will have a side effect

· Combinations à more cost, more adverse effects

· The most imp. Adverse effects are :

· Anaphylaxis , hepatotoxicity , nephrotoxicity , cochlear toxicity and resistant

· Do you think that the antibiotic may cause cancer ??

· Yes, some antibiotics are carcinogenic …. Some new researches say that the patients who take much antibiotics , they are at high risk to have cancer (antibiotics are not benign drugs)

· Anaphylaxis :

· it is hypersensitive condition that affect the lungs of the patients , and the results are bronchoconstriction , wheezing and difficulty in breathing and low blood tension and these occur immediately after taking antibiotics \

· Beta lactams (penecillins)are the most common ABx to cause anaphylaxis

· PCN risk of anaphylaxis: 0.01%

· Death occurs in 1 / 100,000 courses

· 10 - 20% of pts who claim to have an allergy to PCN are truly allergic

· 50% of pts with a positive skin test (allergy test): reaction

· PCN cross reaction with Cephalosporins

· Minimum cross reaction with carbapenem » 1%

· No cross reaction with Aztreonam (except ceftazidime)

Ø Route:

· Oral à stable patients , mild infection (reliable pts)

· IV à serious infections (sepsis) + DM ( as we said before)

Ø Cost :

· If all other factors are equal, the least expensive drug should be chosen



Shadi Jarrar
مشرف عام

عدد المساهمات : 997
النشاط : 12
تاريخ التسجيل : 2009-08-28
العمر : 27
الموقع : Amman-Jordan

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