number 28 Done by Dina Yaseen Corrected by حسام أبو عوض Doctor مالك الزحلف
Cephalosporins -Cephalosporins are β-lactam antibiotics isolated from a strain of Streptomyces. -They are bactericidal and work in the same way as the penicillins. -Resistance is due to β-lactamases, permeability mutants and mutations to the target proteins. -Bicyclic ring structure: β-lactam ring and 6 membered sulfur containing dihidrothiaizine ring -Cephalosporins come in many generations, and these generations were named according to the time in which they were introduced to the market and there is no relationship between the name and the spectrum (i.e. it's not necessarily true that a third or fourth generation member is active against organisms that a second generation member is active on). First generation: (cefazolin, cephalexin, cefadroxil, cephalothin) -active against most gram positive aerobes (except enterococci, MRSA, s.epidermis) with modest activity against gram negatives (clinically we don t use drugs that have moderate activity, we don t put the patient at risk. First generation cephalosporins are important drugs for 2 reasons: -They can't be deactivated by β-lactamase (penicillinase) (active on staphylococcus aureus). -They are the drugs of choice when the patient has a staph or a streptococcus infection (skin infections) Matching to memorize : first generation cephalosporins= β-lactamase resistant penicillins (cloxacillin, flucloxacillin, oxacillin), they are the same in the spectrum and the uses. -If a patient with a staph infection has an allergy toward penicillins or there are no penicillins available (you can't give him cloxa, flucloxa, oxacillins), you give him the first generation of cephalosporins.
-Cephalexin (or cefadroxil or cephalothin) is administered orally for the treatment of skin (. خياطة الجرح ( suturing infections, and as a post-treatment prophylactic drug after -Cefazolin is injected before surgery (1 gram - 1 hour before the surgery) as a prophylactic agent against skin flora (strept, staph). Second generation: (cefuroxime, cefoxitin, cefotetan, cefaclor) -Weaker activity against gram positive, and more active against gram negative Enterbactor erogenes -There are 2 components: 1- Respiratory component: cefuroxime (zinnat): covers all the causes for upper respiratory tract infections (Strep.pneumoniae, H.influenzae, M.catarrhalis, Strep.pyogenes) Cefuroxime= Augmentin in the spectrum with an exception (enterococcci) *note: 1 st, 2 nd,3 rd, 4 th generations of cephalosporins are not active against enterococci, (don't use them empirically to treat endocarditis) -If a patient with an upper respiratory tract infection has an allergy toward penicillins, give him cefuroxime. -Cefuroxime is better than augmentin since streptococcus pneumoniae is intermediately resistant toward augmentin so we have to increase the dose from 40-45mg/kg/day to 80-90mg/kg/day given to children with otitis media (Strep.pneumoniae not resistant at all to cefuroxime) 2-Fragilis component: cefoxitin and cefotetan -The cephamycins (cefoxitin and cefotetan) are the only 2 nd generation cephalosporins that have activity against anaerobes: (Bacteroides fragilis)
Used for the treatment of intra abdominal infections (peritonitis and diverticulitis) caused by intra abdominal flora (anearobic fragilis: Bacteroides fragilis,...) -2 nd g. Drugs cefoxitin and cefotetan (not cefuroxime) are given before abdominal surgeries (colectomy,...) where prophylaxis for intestinal anaerobes is desired. Third generation: (cefdinir, cefixime, cefotaxime, ceftazidime, ceftriaxone, ceftibuten) -Have 3 components: 1- (cefdinir, cefixime): same as cefuroxime(2 nd g. Drug) Given for upper respiratory tract infections -Same as cefuroxime's spectrum: causes of upper respiratory tract infection: -Gram positive: s.pneumoniae, s.pyogenes, staph. -Gram negative: H.influenzae, and more active against E.coli than cefuroxime -Administered orally (only oral 3 rd generation cephalosporins). - If a patient has otitis media and has allergy/resistance towards penicillins (can't give him augmentin), give him cefuroxime, cefnidir or cefixime. However, cefnidir and cefixime(3 rd g.) are better (stronger) than cefuroxime (2 nd g.). -Patients with UTI (common in children and ladies, especially post-partum) (mainly caused by E.coli (90%) or staphylococcus saprophyticus(9%), in western world a third cause is present) are given ciprofloxacin (from quinolones group, not a cephalosporin) because it covers the causes of it, and it can keep its concentration at high levels in urinary tract ducts. However, ciprofloxacin is contraindicated in children below 18 years because it causes orthopathy (a problem related to bones and cartilage), so we give them cefnidir or cefixime (you can give an injection, but no need). 2- Ceftazidime (also cefoperazone, but not included in the exam) -Active against pseudomonas and other gram negative bacteria -Not active against gram positive (purely gram negative drug) so it can't be used in patients with upper respiratory tract infection empirically -A patient allergic towards anti-pseudomonas penicillin (piperacillin): we give him ceftazidime ) ملبس المستشفيات, rocephin ) 3- ceftriaxone -It is not active against pseudomonas (a common misconception among doctors is giving this drug for pseudomonal infections). -Given via injection -The drug of choice in:
1- gonorrhea (caused by neisseria gonorrhoeae) and lyme disease 2- meningitis [caused by neisseria meningitidis, s.pneumoniae, H.influenzae, E.coli, group B strep(strep.pyogenes)]. -We give the patient ceftriaxone because it covers all the causes and it has high penetration to the CSF (we need to reach to the brain in the case of meningitis. Since this drug is injectable it can be used in emergencies). -We don't treat patients with meningitis empirically using penicillin G (can be used as a definite therapy) although it covers N.meningitidis, because it doesn't cover H.influenzae nor E.coli -We don't use ceftriaxone with patients who suffer from hyperbilirubinemia, instead, we use cefotaxime **Cefotaxime : is a 3 rd g. Drug. It can cross the blood brain barrier, same as ceftriaxone's spectrum, used instead of ceftriaxone with patients who suffer from hyperbilirubinemia like neonates- (42 weeks or less, pregnancy-time included, must reach 42 weeks regardless of pregnancy duration) (physiological hyperbilirubinemia-yellowish skin) and patients with jaundice (pathological hyperbilirubinemia) (ceftriaxone is not used because it binds to bilirubin and precipitates in the blood, lungs, kidneys and the liver and can be lethal to neonates). [Extra note: ceprafloxain cannot be used for upper respiratory tract infections because it lost its activity against streptococcus pneumoniae]. Fourth generation: (cefepime) (known as CefaMAX) - Maximum coverage of all generations of cephalosporins (except 5 th g.) - Cefepime spectrum= ceftriaxone+ ceftazidime - All cephalosporins, when given against bacteria, trigger a reaction by the bacteria which induces the production of extended spectrum β-lactamases, especially the 3 rd generation guys like ceftriaxone and ceftazidime, so this is a major problem as with time bacteria are becoming resistant to the cephalosporins. However, cefepime does not induce this action so the bacteria DO NOT produce these extended spectrum β- lactamases with cefepime which means that it is difficult for them to become resistant to it. This drug is one of the reserved drugs (so the Doctor is preferred not to talk much about it as we are not supposed to use it and are supposed to keep it aside, ONLY use it if your patient is resitant to the 3 rd generation guys, DO NOT begin your therapy with cefepime, always begin with a narrower spectrum drug). [This last point was just for your info. It won t be tested in the exam].