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35 Cards in this Set
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Identify the group of agent and principle site of action for penicillin, amoxicillin, flucloxacilin, cefalexin, vancomycin, gentamicin, erythromycin, chloramphenicol, tetracycline, ciproflocacin, rifampicin, trimethoprim, metronidazole.
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Penicillin, amoxicillin and flucloxacillin are all beta lactam penicillin antibitotics and work by inhibiting peptidoglycan cross linking in cell walls. Naural penicillins have been modified to have penicillinase resistance or extended antibacterial spectrum. Natural penicillins include penicillin G or penicillin V, flucloxacillin is penicillinase resistant penicillin and amoxicillin is a normal penicillin that is usually combined with beta lactamase inhibitors eg clavulanate to form co-amoxiclav.
Cefalexin is a first generation cephalosporin and has the same action as beta lactams in preventing the cross linking between peptidoglycan in the cell wall. It is not susceptible to beta lactamase. Vancomycin is a glycopeptide which also inhibits peptidoglycan cross linking. Gentamicin is an aminoglycoside which prevent translation of mRNA into protein. Erthryomycin is a macrolide which binds to the 50s ribosome, interfering with protein synthesis. Chloramphenicol does not belong to a class and binds to the 50S ribosome. Tetracyclines interfere with protein synthesis by blocking binding of aminoacyl tRNA to the mRNA ribosome complex. They do this by binding to the 30S subunit in the mRNA translation complex. Ciprofloxacin is a quinolone which inhibits bacterial DNA gyrase, thereby inhibiting DNA replication and transcription. Rifampicin is used to treat mycobacterium and binds to beta subunit of RNA polymerase to inhibit transcription. Trimethoprim are sulphonamides which inhibit the synthesis of tetrahydrofolate by being competitive inhibitors of dihydropteroate synthase. Metronidazole is active against all anaerobic organisms and acts by accepting electrons under anaerobic conditions and forming toxic metabolites that damage bacterial DNA. |
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Describe the basis on which a particular agent is selected for a particular condition.
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The choice of antibiotic depends on the site of infection, the susceptibilities of the likely infecting organisms, the severity of infection, any history of allergy, the likelihood of unwanted effects and lastly cost.
Empirical therapy follows local policy as well as looking at the individual case and going with clinical suspicion, knowledge of likely cause and known resistance/ susceptibility of likely organism. Laboratory guided therapy follows consultation with microbiologist, efficacy in clinical studies, cost benefit and susceptibility report. |
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Identify the key clinical uses for penicillin, cefalexin, vancomycin and gentamycin.
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Penilcillin – streptococcal infection, sphyillis, lyme disease
Cefalexin – gram positive infections Vancomycin – gram positive organisms, must be IV or IP except for treating pseudomonas colitis – oral. It is used for MRSA infection Gentamicin – gram negative bacteria, in combination with penicillin to treat endocarditis |
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Identify the key clinical uses for erythromycin, clindamycin, tetracycline, ciprofloxacin
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Erythromycin – used instead of penicillin if patient allergic to treat streptococcal infections. Also treats other gram positive cocci, many anaerobes, mycoplasm and Chlamydia.
Clindamycin – serious staphylococcus, streptococcus pneumonia and other strep infections in penicillin resistance, used topically to treat acne, anaerobic infections. Tetracycline – gram positive an some gram negative pathogens, chlymida,mycoplasma, rickettsia and treponemes. Doxycycline used against protozoa ( plasmodium and entamoeba histolytica). Ciprofloxacin – urinary tract infections, community acquired pneumonia |
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Identify the key clinical uses for rifampacin, metronidazole and trimethoprim.
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Rifampacin – used to treat tb, causes hepatitis
Metronidazole – anaerobic bacteria and some protozoa – giardia, entamoeba histolytica, and trichomanas vaginalis. Trimethoprim – UTI, pneumocystis jiroveci and protozoal infections |
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Briefly explain the importance of understanding the pharmacology of antimicrobials ( ADME) in achieving a therapeutic effect and in avoiding toxicity
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Most antibiotics have a wide therapeutic index, so the dose at which unwanted effects occur is very much higher than that which inhibit bacterial growth. However some antibitotcs such as gentamicin and vancomycin have their therapeutic ranges very close to their toxic range and so the serum levels. must be monitored regularly. Gentamycin at high levels can damage the kidneys and the 8th cranial nerve ( auditory nerve) causing renal failure and loss of hearing.
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Describe beta lactam antibiotics.
There are 4 classes of beta lactam antibiotics |
There are 4 classes of beta lactam antibiotics
1. Peniclilln – derive from fungus 2. Cephalosporins – derive from fungus 3. Carbapenems – synthetic 4. Monobactams - synthetic The synthetic drugs They have a ‘house’ and ‘garage’. The house being the 5 carbon ring and the garage being the 4-membered beta lactam ring which is essential for antibacterial activity. The beta lactam ring is destroyed by pathogens with beta lacatamase eg salmonella typhi and so the antibiotic is ineffective. Cepholosporins have a basement – house is 6 membered. |
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Describe penicillin and the different spectrums of all beta lactams.
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Penicillin is a beta lactam antibiotic and works by inhibiting peptidoglycan cross linking in cell walls. Natural penicillins have been modified to have penicillinase ressitance or an extended antibacterial spectrum
- Naural penicillins include penicillin G or V - Penicilinase resistance penicillins eg flucloxacillin - Aminopenicillins eg ampicillin – broad spectrum - Expanded spectrium penicillins eg piperacillin -> anti psudomonal - Penicilins and beta lactam inhibitor combinations – amoxicillin and clavulanate form co-amoxiclav Narrow spectrum beta lactam antibiotics - Benzyl penicillin used to treat streptococcal endocarditis along with gentamicin - Flucloxacillin used to treat staphylococcal infections eg skin infections Broad spectrum beta lactams - Co-amoxiclav and cefuroxime Very broad spectrum antibitotics - Impenem, meropenm, tazocin, tigecycline |
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Describe cephalosporins.
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Cephalosporins are broad spectrum beta lactam antibiotics that are closely related to penicllins. There are 5 classes:
1. Oral cephalosporins – eg cefalexin – gram positive spectrium 2. Injectable agents eg cefuroxime active against gram positive organisms such as e coli and some species of proteus. 3. New injectable cephalosporin agents eg cefotaxime or ceftriaxone, activat against most gram negative organisms end streptococcus 4. Same spectrum as 3rd but can be given orally 5. Antipseudoman eg broat spectrium that also includes pseudomonas eg ceftazidime. |
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What is co-amoxiclav?
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Co amoxiclav is a combination of amoxicillin, a penicillin, and clavulonic acid a beta lactamase inhibitor. It can therefore not be given to someone allergic to penicillin.
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Describe aminoglycosides.
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The main aminoglycoside is GENTAMICIN. They prevent translation of mRNA into protein. They are given parentarlly and are limited to the extra-cellular fluid and they are excreted in urine. They are used in combination therapy with other antibiotics to achieve synergistic killing of bacteria in infective endocarditis.
- viridians streptococcus (MOST COMMON) – benzyl penicillin and gentamicin - Staphlococcus aureus – flucloxacillin and gentamicin - Enterococcus faecalis – amoxicillin and gentamicin SIDE EFFECT – aminoglycosides are toxic to the kidney and eighth cranial nerve(auditory nerve) at amounts close to therapeutic levels so careful monitoring of serum concentration is required to prevent renal failure or loss of hearing. |
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Give examples of macrolides and their use.
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Examples of macrolides include erythromyocin and clarithromyosin. Macrolides bind to the 50s ribosome, interfering with protein synthesis. They are active against gram positive cocci, many anaerobes, mycoplasma and chlyamidia. They are absorbed orally and can cross the placenta, are concentrated in macrophages, polymorphs and the liver and are excreted in bile. Erythromycin may cause nausea. They can be used in penicillin allergic patients to treat upper respiratory tract infections and skin and soft tissue infections.
They are first line agents for ATYPICAL PNEUMONIA eg caused by mycoplasma, chlyamidia, legionella. |
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Give examples of tetracyclines and how they should be taken.
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The main tetracycline is doxycycline which is used for acne treatment. They interfere with protein synthesis by binding to 30s subunit of mRNA ribosome complex and prevent amino-acyl tRNA from binding. They are active against gram positive and some gram negative pathogens, chlyamydia, mycoplasma, ricettsia and treponemes. Doxycylcine has useful activity against some protozoa including plasmodium and entamoeba histolytica. Absorbed orally, doxyclycine has a long half life and adequate therapeutic levels may be obtained by a once a day dosage. It is distributed to many tissues including the lung, liver, kidney, brain and respiratory tract and is concentrated in bile. Tetracyclines should be taken on an empty stomach – either 1 hr before food or 2 hrs after food. This is because they bind to milk and other dairy products and so are prevented from being absorbed.
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Give examples of quinolones and their uses.
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Quinolones include ciprofloxacin and inhibits bacterial DNA gyase preventin replication and translation. Ciprofloxacin does not achieve high tissue levels and is commonly used to treat UTIs. Fluoroquinolones are more active against gram negative pathogens including pseudomonas and Chlamydia. They have been used for single dose treatment of genital infections. They are well absorbed orally and penetrate cells well. levofloxacin which is used to treat atypical pneumonia and moxifloxacin used to treat multiple resistant TB.
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Describe vancomycin.
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Vancomycin is a glycopeptides and works by inhibiting cross linking of peptidoglycan in cell wall of gram positive organisms only. It is the first line agent for serious MRSA infections such as MRSA bacteraemia. 1g/L is given slowly over an hour intravenously or intraperitoneally. If it is given quickly, it can lead to red neck syndrome, renal failure and ear disease. Oral vancomycin is used to treat pseudomembranous colitis
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List some important miscellaneous agents.
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Rifampacin – first line anti tb agent
Trimethoprim – first line anti UTI agent Metronidazole – to treat ANAEROBIC BACTERIA eg clostridium dificille and bacteroides fragillis List the first line anti tb agents and the 2nd line agents used to treat tb. First line: isoniazid, rifampacin, ethambutol and pyrazinamide Second line: streptomycin, fifabutin, prothrionamide, moxifloxacin Treating tb takes a very long time and must always be done using a combination of drugs otherwise resistance will develop very quickly to one drug. Lung tb treatment lasts 6 months, CNS tb treatment lasts over a year, bone tb treatment lasts 8months – 1 year and multiresistant tb treatment can last 2-3years. |
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Why are 1st line agents superior to 2nd line agents?
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First line agents are bactericidal whereas second line agents are mostly bacteriostatic. Also first line agents have a proven record of efficacy, success, safety and tolerability whereas second line agents can be more toxic and are less effective.
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Describe the 2 approaches to antimicrobial therapy.
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Empirical therapy is best guest therapy which is the initial antimicrobial treatments for serious infections, based on local epidemiology of common organisms and their susceptibilities.
Organism based therapy is the adjusted therapy undertaken once the culture and susceptibility results are available from the lab. |
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Describe how susceptibility to antibacterial agents is determined and explain the acronyms MIC and MBC.
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Impregnated antibiotic discs are placed onto agar plates covered by colonises of isolated bacterium. They are incubated over night and the zone of clearance away from the disc is the zone of inhibition. The more susceptible the bacteria is the antibiotic, the larger the zone.
MIC – minimum inhibitory concentration is the minimum concentration of bacteriostatic antibiotic which inhibits the visible growth of a micro-organism after overnight incubation. It is used to test new antibiotics and to look for resistance. The smaller the concentration, the more effective the drug is. MBC – Minimum bacteriocidal concentration is the minimum concentration of bacteriocidal antibitotic which kills bacteria. MBC is usually larger than MIC. |
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What are the 5 key questions to ask before commencing empirical therapy?
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1. Is it infection or just inflammation (trauma, cancer)?
2. What is the likely focus of infection ( eg brain, heart, UT) 3. What are the likely organisms? 4. What antibiotics are they sensitive to? 5. What are the adverse effects? Eg consider pregnancy Empiral therapy takes into consideration local policy as well as looking at individual case and going with clinical suspicion, knowledge of likely cause and known sensitivity/resistance of likely organisms. |
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What would be the most likely causative agent of lobar pneumonia in an elderly or an alcoholic patient? Describe the organism’s virulence factors, the investigation undertaken and the treatment.
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The most likely cause is STREPTOCOCCUS PNEUMONIAE - group A which is a gram positive diplococi.
Its major virulence factors are its polysaccharide capsule and production of pneumolysin. Investigations: sputum culture ( creamy or green), blood culture, chest x-ray (consolidation in a lobe), FBC ( elevated neutrophils) Treatment is amoxicillin ( oral if in community and IV if in hospital). |
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What would the most likely causative agent be of hospital acquired pneumonia in an elderly patient one week after hepatobiliary surgery? Describe the chest x ray appearance, the investigations undertaken and the treatment.
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Cause: pseudomonas aeruginosa (gram negative)
Chest x ray: bilateral patchy consolidation Investigations: sputum culture, blood culture, chest xray, FBC Treatment: oral ciprofloxacin or IV imipenem |
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A patient who has had a bone marrow transplant presents with severe pneumonia with extensive bilateral ground glass opacity and air space consolidation on chest x-ray. Describe the potential aetiology, investigations and treatment.
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The causative agent is probably pneumocystitis jirovecci, a yeast fungi, which doesn’t grow in lab and so biopsies are taken and PCR .
Immuno-fluorescent stain of respiratory secretions, silver stain of lung biopsy showing cysts Treatmeant – high dose IV co-trimoxazole. |
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A previously well 18 year old student is admitted into ICU with a one day history of malaise, headache and myalgia. Over the last 6 hrs he has become increasingly drowsy and is now unresponsive to pain. On examination he is found to have some dark petechial blotches on his lower legs. In the emergency department it is suggested that he should be given some antibiotic before he has a CT scan oh his brain and then a lumbar puncture. Aetiology? Investigation? Therapy?
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Aetiology – neisseria meningitis.
The CSF taken by lumbar puncture – gram negative diplococcic, red kidney bean shaped and a large number of neutrophils. Blood cultures, throat swab, EDTA blood for PCR, serum for antibodies. Therapy is IV ceftriaxone or IV cefotaxime ( cephalosporins – beta lactam) - ORAL WON’T CROSS BLOOD BRAIN BARRIER SO MUST BE IV Also notify public health and infection control. |
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Describe endocarditis including the normal presentation and the normal bacterial causes.
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In endocarditis the heart valves are infected during transcient bacteraemia. The endothelium is damaged and fibrin and platelets deposit. Bacteria may arise from the mouth, urinary tract, intravenous drug user or colonised IV lines and colonise the fibrin and platelet deposit. The pathogen multiplies on the valve, usually aortic or mitral valve and forms a vegetation (large biofilm) in which the pathogen resides and remains protected from phagocytosis. Systemic signs of infection develop and toxic emboli and immune complexes form.
The classical presentation is: malaise, fever and variable heart murmurs and arthalgia ( immune complexes). The classical stigmata is: janeway lesions, oslers nodes, splinter haemorrhages, clubbing of fingers – these are present if infection has been present a while. The most common cause is viridians streptococci, then staph aureus ( a very VIRULENT organism – rapid infection ->acute sepsis, often following IV DRUG USERS ), then enterococcus faecalis. Rare causes include gram negative bacilli, candida species. |
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Describe diagnosis of endocarditis.
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Major criteria: positive blood culture for typical organisms, persistently positive blood cultures with any organism, echocardiogram showing endocardial involvement and new valvular regurgitiation
Minor critera: predisposition, fever, immunological signs eg septic pulomonary infarcts, echocardiographic or microbiological evidence. A diagnosis is made if there is 1 major and 3 minor symptoms or if there are 2 major criteria present. |
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Describe management of endocarditis and prevention.
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Organism based therapy is preferred and if possible antibiotics are not given until lab results have come back. Therapy is planned based on sensitivity testing and MIC and MBC. The therapy is combinational usually with gentamicin and a beta lactam, but if bacteria is beta lactam resistant vancomycin is given.
- Viridians streptococcus – gentamicin and benzyl penicillin - Staph aureus – gentamicin and flucloxacilin - Penicillin resistant – vancomycin and gentamicin - Penicillin allergic – erythromycocin and gentamicin Gentamicin levels should be observed closely as patients with endocarditis are susceptible to toxic effects to kidney due to renal impairment ( caused by septic embolus -> immune complex on nephron). Prevention: antibiotic prophalaxis is given to patients with damaged valves when they undergo procedures that give rise to bacteraemia eg dental work or urogenital surgery. |
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What are the risk factors for endocarditis?
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- Iv drug user
- Congenital valve defects - Atherosclerosis - Rheumatic fever - Prosphetic metarial eg valves, central venous lines |
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What are the complications for endocarditis?
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- Abscess formation in aortic root
- Severe cardiac failure caused by destruction of valve eg if in left atria -> pulmonary hypetension -> pulmonary oedema, if in right atrium -> increased jugular venous pressure - Septic embolus – stroke, cerebral or limb infarction - Nephritis – immune complex deposition ( increased by gentamicin) |
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Describe cellulitis.
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Cellulitis is the most common skin and soft tissue infection caused mainly by staph aureus and strep pyogens ( beta haemolytic group A). It affects the lower legs most commonly and can spread to the lymph nodes and bloodstream to cause bacteraemia. If left untreated it can be life threatening.
Affected skin shows rubor, calor, dolor and tumor and fever is usually associated. Mild forms – use ORAL FLUCLOXACILLIN Severe forms – use IV FLUCLOXACILLIN Perform FBC and blood cultures. |
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Describe urinary tract infections.
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Upper urinary tract infections involve the kidneys and ureters and lower urinary tract infections involve the bladder and the urethra.
UTIs cause increased frequency and dysuria. A dipstick test can be used to identify: LEUKOCYTE ESTERASE and NITRITES which indicate UTI (in 98% of cases). Aetiology: Community acquired ( in order): E COLI, coagulase –ve staph, proteus, pseudomonas aeruginosa and other gram –ve bacteria, enterococcus faecalis. Hospital acquired ( 48hrs after admission): E COLI, pseudomonas and other gram negative bacteria, enterococcus feacalis, proteus, CANDIDA ALBICANS ( due to catheter), coagulase –ve staph. |
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What are the 6 risk factors for UTI?
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1. Female – short urethra. Only occurs in old men, due to prostate cancer blocking urethra or kidney stones, chronic STIS or catheters
2. Catheter 3. Diabetes 4. Anatomical anomalies 5. Pregnancy – at 16 weeks a urine sample is tested as a UTI could damage foetus 6. Previous history of UTI or pyelonephritis (infection of renal pelvis) |
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What are the indications of combination therapy?
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1. To prevent emergence of resistance eg in tb treatment with 1 drug, resistance will develop
2. To achieve synergistic bactericidal activity eg benzyl penicillin and gentamycin in viridians streptococcal endocardidits. 3. To achieve broad spectrum cover as in polymicrobial infections eg faecal peritonitis, billiary sepsis, necrotising fascilitis |
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Name and describe bactericidal and bacteriostatic agents.
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Bactericidal agents are the first line agents which kill micro-organisms. Examples include penicillin, ciprofloxacin, imipenem, gentamicin,vancomycin. These should be used in infection of immunocompromised patients, infections in transplant patients and life threatening infections ( bacterial meningitis, infective endocardidits, blood stream infection, faecal peritonitis, billary sepsis).
Bacteriostatic agents are the second line agents which can only inhibit bacterial growth eg tetracycline, erythromyocin. |
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Give examples of toxicity and adverse effects of antibiotics.
5-10% of patients on antibiotics develop side effects. |
- Anaphylaxis eg penicillin
- Allergic skin rashes eg amoxicillin to ebv - glandular fever - Nephrotoxcity and ototoxicity (loss of hearing and balance) eg gentamicin - Hepatotoxicity eg rifampicin - Haematological disturbances eg linezolid - C difficile associated colitis eg cephalosporins - Minor QT disturbances eg erythromyocin - Selection of multi drug resistant superbugs |
