MicroBiology-Antibacterials

*VancoMycin and Bacitracin work by inhibiting SYNTHESIS(not just cross-linking) of Peptidoglycan>Target cell wall.*Bacitracin helps us to differ between Strep.pyogEnEs(Bacitracin sEnsitivE) and Strep.AgAlActiA(Bacitracin resistAnt) as both of them are B-hemolytic.*Vancomycin works by Binding D-Ala-D-Ala of cell wall precursors and inhibits Peptidoglycan synthesis. it is B-lactamase RESISTANT and this largely Batericidal(kills MRSA,Enterococcus,S.epidermidis) antibiotic is Bacteriostatic(only halts growth) against C.Difficle(given orally for Pseudomembranous colitis)

* Nephrotoxicity and Ototoxicity can accompany vancomycin use(So avoid Aminoglycosides and other Nephro/ototxic drugs), we could prevent Red-man syndrome(Diffuse flushing) by PRE-treatment by antihistamines(prevent Non-specific mast cell degranulation) and by Slow infusion rate of IV vancomycin.*Bugs can become resistant to this peptidoglycan synthesis inhibitor by changing D-Ala-D-Ala to D-Ala-D-LAC(So altered binding site renders vancomycin ineffective)*Look they can describe mechanism of action of Vanco as Blocking elongation by blocking transglycosylation reactions.

*Penicilin is Bactericidal(kills not just stops growth) against Gram+Bacilli and Cocci,gram-cocci and Spirochetes,(kills actinomyces israeli Gram Positive,Branching ANaerobe,Bacilli).*Penicilin G(IV,IM) and Pencilin V(Oral-More acid stable) can be used for treatment of Actinomyces,S.pyogenes,S.pneumonia), this bactericidal antibiotic can also kill Treponema pallidum(Spirochete>Syphilis) and N.Meningitidis(Gram Negative Cocci).*BENZATHINE PENICILIN(IM) is used for Tertiary syphylis, due to its long-lasting effect.*Don't forget when you treat Syphilis by penicillin(Esp.BenzathineP), you can get Jarisch-Herhxeimer(Flu-like symptoms with fever,swelling,headache,myalgia,chills)<Due to toxin release from dead bug.

*They Block Transpeptidase cross-linking of peptidoglycan in cell wall by binding Penicilin-Binding Proteins(Transpeptidases) as they are D-Ala-Ala analogs+ these prototype B-lactam antibiotics activate AUTOLYTIC ENZYMES.Bugs use the fact that this drugs have B-lactam ring and cleave this ring by PENICILINASE>Resistance.*Complications:Type 1 hypersensitivity-Even anaphylactic reacton is possible*Type 2 hypersensitivity-Direct coombs+(antibodies already adhered to rbc) AutWoimmune Hemolytic anemia.

*Aminopenicilins are B-lactamASE sensitive penicillins that are often combined with Clavulinic acid(Suicide inhibitor of B-lactamASE), Aminopeniilins are famous for causing Pseudomembranous colitis(C.Difficile overgrowth),hypersensitivity reactions and Rash(Esp. when given to patient with EBV or ALL, This rash is NON-Pruritic+Maculopapular rash, don't confuse this with Hives(Pruritic) which are possible due to type 1 hypersensitivity in response to these drugs.)*Don't forget that amOxicillin hasgreater biOavailability than Ampicillin, and is poorly absorbed(Remains in GI tract more)

*Patient was given DON(Dicloxacillin,Oxacillin,Nafcillin)which are B-lactamase RESISTANT antibiotics, which are often used for S.aureus, BUT MRSA has Altered Penicillin-Binding-protein target site, so it is RESISTANT to DON too, so not only we couldn't treat the patient we also gave him interstitial nephritis as a side effect of this drug.(Hypersensitivity is possible side effect too, but not very special one)*Note:Nafcicillin and Oxacillin are excreted in the bile so they don't require dose change in renal failure but they do need dose change in Liver failure.

* You choose B-lactamase SENSITIVE antibiotics with B-lactamase inhibitors(Tazobactam,Clavulinic acid,Sulbactam-CAST but most importantly know the antibiotics themselves: Ticearcillin,Piperacillin.(Tic loves Cillindricall pipe :P)*This drugs can also be used for proteus and other gram- rods and can cause hypersensitivity reactions as side-effects.*Ticearcillin can cause -Hypertension, hypervolemia, and bleeding as unqiue side effects..

*By altering penicilin binding proteins(transpeptidases).*Long-term cephalosporin use can cause Vitamin.K deficiency which explains symptoms of our patient.*particular drug she was on belongs to 5Th generation cephalosporin(Ceftaroline) class as they are the only ones that can kill MRSA,(They can't kill P.aeruginosa though), don't confuse this with Cefazolin(1st generation)which is used PRIOR to surgery to prevent S.Aureus wound infections.*Generally cephalosporins can't kill lame bugs(Listeria,Atypicals-Chlamydia,Mycoplasma,MRSA,Enterococci.)

*3rd generation cephalosporins esp.Ceftriaxone which is part of treatment of Meningitis,Gonorrhea,Disseminated Lyme disease.*Ceftazidine is 3rd generation cephalosporin used for Pseudomona infections.*Know that Ceftriaxone and Cefoperazone are eliminated in Bile(So adjust dose for Liver failure).*Kaplan reallllly wants you to know that Cefoperazone is associated with Disulfiram-like reaction and becker wants you to know that CEFOPERAZONE and Cefotetan as they POTENTIATE anticoagulant effects of warfarin by causing VitK deficiency(remember colonic bacteria synthesize vitK, technically any antibiotic can do it , but especially cefoperazone and cefotetan)

*Due to their SYNERGISTIC toxic effect on Kidney.(so modify doses and try to avoid combination in someone with renal problems).

*Cephalosporin use with alcohol can cause Disulfiram-like reaction(Due to too much acetaldehyde as acetaldehyde dehydrogenase is inhibted), in this case i wanted to underline the fact that cephalosporins(esp.2nd generation-CeFAclor,CeFURoxime,ceFOXitin) can kill Enterobacter,but they can't kill Enterococcus(Gram+,Yhemolytic<can be killed by Amoxicillin/Ampicillin+aminoglycosides) as students often confuse these 2.*Note Cefuroxime can cross BBB.(Theoretical use for meningitis),generally 3rd generation and above generations do this so this is the special second generation drug,*Cefotetan-Is 2nd generation cephalosporin most commonly associated with Disulfiram-like raction.

*Aztreonam(Monobactam group)binds to PBP3(only gram-,aerobic rods have this) and prevents peptidoglycan cross-linking, this drug is less susceptible to B-lactamases and has NO cross-allergenicity with penicillins.*remember that Cephalosporins are B-lactam drugs and if your patient developed Type1 hypersensitivty reaction(allergy) or Type 2 hypersenstiviity(Auotimmune hemolytic anemia) in response to penicillin, they are likely to develop similar symptoms with cephalosporins, so in a patient with renal failure(Can't tolerate aminoglycosides) who has Gram- ROD which is AEROBE(aztreonam can't kill Gram+ and anaerobes) aztreonam would be DOC.

*Well Imipenem is B-lactamase Resistant Carbapenem that can kill Gram+cocci,Gram-rods,ANaerobes.* you use Carbapenems when other drugs fail, but even here you can decrease risk of seizures by giving patient MEropenem which is stable to DehydropeptidaseI and doesn't need cilastatin.*Carbapenems are associated with Seizures,GI distress,Skin rash.*Ertapenem is new generation carbapenem which is WEAK against pseudomona so not a good choice,doripenem is also new generation carbapenem which is as effective as older carbapenems in treating Pseudomona aeruginosa(Non-lactose fermenter,Gram-) induced pneumonia.

Because it is BacteriCidal while other protein synthesis inhibitors are generally bacteriostatic(Only halt their growth/division, can't directly kill bacteria.)*Hence synergism of aminoglycoside with penicilin<Both are bactericidal.

*This trait will help us to understand why we use Neomycin in Treatment of hepatic encephalopathy, where we use this antibiotic to remove ammonia producing bacteria in intestine>Less ammonia) and why we use it in Bowel surgery to decrease risk of infection.+NOTE:**NEOMYCIN is topical Aminoglycoside and has been associated with Type 4 hypersensitivity=CONTACT DERMATITIS.