Beta lactam tshuaj tua kab mob (β-lactams) hais txog pab pawg loj ntawm cov tshuaj tua kab mob nrog beta lactam nplhaib hauv cov qauv tshuaj, suav nrog penicillins thiab cephalosporins uas feem ntau siv hauv tsev kho mob, nrog rau cov tshuaj tua kab mob atypical lact -lactam tshiab xws li cephamycin, chav kawm tshuaj sulfur thiab ib lub nplhaib -lactam.
Xws li cov tshuaj tua kab mob muaj qhov ua tau zoo ntawm cov tshuaj tua kab mob muaj zog, tsis muaj tshuaj lom, nthuav qhia dav thiab ua tau zoo hauv chaw kho mob. Cov txheej txheem tshuaj lom neeg ntawm cov tshuaj no, tshwj xeeb tshaj yog kev hloov pauv ntawm cov saw sab, tau tsim ntau yam tshuaj tua kab mob nrog cov tshuaj tua kab mob sib txawv thiab cov tshuaj tua kab mob thiab ntau yam tshuaj kho mob.
Beta lactam tshuaj tua kab mob yog ntau yam tshuaj tua kab mob, suav nrog penicillin thiab nws cov txiaj ntsig, cephalosporins, monoamide rings, carbapenems thiab penicillene enzyme inhibitors thiab lwm yam. Beta lactam tshuaj tua kab mob (β-lactams) hais txog chav kawm tshuaj tua kab mob loj nrog ring-lactam ntiv nplhaib hauv cov qauv tshuaj. Yeej yog txhua yam tshuaj tua kab mob uas suav nrog core-lactam core hauv lawv cov txheej txheem molecular koom nrog beta lactam tshuaj tua kab mob.
Cov txheej txheem ntawm kev ua ntawm ntau yam tshuaj tua kab mob β-lactam zoo sib xws, thiab lawv tuaj yeem tiv thaiv cell phab ntsa mucopeptide synthase, uas yog, penicillin khi cov protein, yog li ua rau cuam tshuam rau kev sib txuas ntawm cell phab ntsa mucopeptide, ua rau cov kab mob ntawm phab ntsa ntawm tes tsis zoo, cov kab mob nthuav dav ntawm tes thiab lysis. Ib qho ntxiv, qhov ua rau tuag ntawm cov kab mob yuav tsum suav nrog ua rau muaj kev ua haujlwm autolysin ntawm cov kab mob, thiab cov kab mob hloov pauv yam tsis muaj autolysin qhia ua haujlwm. Cov tsiaj tsis muaj phab ntsa ntawm tes thiab tsis cuam tshuam los ntawm cov tshuaj β-lactam. Yog li, chav kawm ntawm cov tshuaj no tau xaiv cov kab mob tua kab mob ntawm cov kab mob thiab muaj tshuaj lom tsawg rau tus tswv tsev.
Hauv kaum xyoo dhau los, nws tau lees paub tias cov protein tshwj xeeb PBPs ntawm cov kab mob cytoplasmic membrane yog lub hom phiaj ntawm cov tshuaj β-lactam. Tus lej, qhov hnyav ntawm lub cev, thiab kev nkag siab ntawm PBPs ntawm cov xovtooj ntawm tes ntawm ntau cov kab mob sib txawv, tab sis cov kab mob uas muaj cov lej sib thooj muaj hom zoo sib xws thiab lub cev ua haujlwm ntawm PBPs.
Piv txwv li, E. coli muaj 7 yam PBPs. PBP1A thiab PBP1B muaj feem cuam tshuam rau kev tua cov kab mob. Penicillin, tshuaj ampicillin, cephalothin, thiab lwm yam muaj kev sib raug zoo nrog PBP1A thiab PBP1B, uas tuaj yeem tiv thaiv kev loj hlob, kev tsim dua tshiab thiab txuas ntxiv ntawm cov kab mob, thiab cov kab mob yuav yaj thiab tuag. PBP2 cuam tshuam nrog cov duab ntawm cov raj. Mecillin, clavulanic acid thiab thiomycin (imipenem) tuaj yeem xaiv ua ke nrog lawv los ua cov kab mob ua cov kab mob loj loj, uas ruaj khov rau osmotic siab, thiab tuaj yeem txuas ntxiv mus rau ntau tiam neeg ua ntej kev ploj tuag thiab tuag.
Kev ua haujlwm ntawm PBP3 zoo ib yam li PBP1A, tab sis tus nqi me dua, uas cuam tshuam nrog septum tsim thiab faib cov kab mob. Feem ntau tshuaj penicillin or cephalosporin tshuaj tua kab mob feem ntau ua ke nrog PBP1 thiab (lossis) PBP3 txhawm rau tsim cov kab xev thiab spheroids, uas ua rau cov kab mob deforms, ntsws, maj mam ua kom tuag. PBP1, 2, 3 yog qhov tsim nyog rau kev muaj sia nyob, kev loj hlob thiab tsim cov kab mob. PBP4, 5, thiab 6 cuam tshuam nrog kev ua haujlwm ntawm carboxypeptidase thiab tsis muaj qhov tseem ceeb rau kev muaj sia nyob thiab rov tsim dua ntawm cov kab mob. Tom qab tshuaj tua kab mob ua ke nrog lawv, lawv tsis muaj kev cuam tshuam rau cov kab mob.
A. Txhais
Penicillin (penicillin G), tseem hu ua benzyl penicillin, yog ntuj tsim penicillin nrog cov saw benzyl sab. Nws cov sodium lossis potassium ntsev feem ntau siv. Nws cov hmoov siv lead ua ruaj khov ntawm chav sov thiab yooj yim soluble hauv dej. Nws cov kua dej tsis ruaj tsis khov ntawm chav sov. Thaum nws tau muab tso rau ntawm 20 ° C rau 24 teev, cov tshuaj tua kab mob tau ua kom nrawm dua, thiab cov tshuaj tiv thaiv kab mob tuaj yeem tsim tawm. Yog li penicillin yuav tsum tau npaj ua cov kua dej ua ntej siv.
B. Cov kab mob tua kab mob
Penicillin feem ntau yog ua rau cov kab mob Gram-positive, Gram-negative cocci, Haemophilus, thiab ntau yam kab mob tshwm sim.
Penicillin muaj kev cuam tshuam zoo rau hemolytic streptococcus, viridis streptococcus, pneumococcus, thiab lwm yam, tab sis kev nkag siab ntawm enterococcus tsis zoo. Staphylococcus aureus uas tsis tsim tawm penicillinase thiab feem ntau Staphylococcus epidermidis rhiab rau penicillin, tab sis Staphylococcus aureus uas ua rau penicillinase yog heev resistant rau nws.
Gram-positive bacilli, Bacillus diphtheria, Bacillus anthracis, thiab gram-positive anaerobic bacilli xws li Perfringens, Tetanus, Clostridium difficile, Propionibacterium, Eubacterium, Lactobacillus, thiab lwm yam yog txhua yam rhiab rau penicillin. Ntawm cov kab mob gram-negative, meningococci muaj kev nkag siab zoo rau penicillin, thiab tshuaj tiv thaiv tsis tshua muaj. Neisseria gonorrhoeae, uas rhiab rau penicillin, yog qhov nce zuj zus. Bacillus pertussis rhiab rau penicillin. Cov kab mob pathogenic spirochetes xws li Treponema pallidum thiab Leptospira tau nkag siab zoo rau nws.
A. Lus txhais
Cephalosporin tshuaj tua kab mob yog semi-hluavtaws tshuaj tua kab mob ua los ntawm nucleus 7-aminocephalosporanic acid (7-ACA) ntawm cephalosporins txuas nrog rau sab sib txawv saw. Cov tshuaj tua kab mob hauv chav kawm no muaj qhov zoo ntawm cov tshuaj tua kab mob dav, muaj zog tua cov kab mob, ruaj khov rau cov kua qaub thiab beta lactamase cov, tsis tshua muaj kev fab tshuaj tiv thaiv, (tsuas yog ib nrab ntawm qhov tsis sib xws tshwm sim nrog penicillin), thiab lwm yam.
B. Cov kab mob tua kab mob
Cov kab mob tua kab mob yog dav, feem ntau cov kab mob gram-positive ua rau nws mob, tab sis enterococci feem ntau tiv taus nws; feem ntau cov kab mob gram-tsis zoo yog qhov rhiab heev, tsuas yog qee qhov cephalosporins, Pseudomonas aeruginosa thiab cov kab mob anaerobic. Cov chav kawm ntawm cov tshuaj no muaj cov tshuaj tiv thaiv kab mob sib xyaw nrog penicillins thiab tshuaj tua kab mob aminoglycoside.
Cephalosporins yog cov tshuaj tua kab mob, thiab lawv cov tshuaj tua kab mob zoo ib yam li penicillins, thiab lawv tseem tuaj yeem khi rau sib txawv penicillin khi cov protein (PBPs) ntawm phab ntsa ntawm tes.
Cov kab mob muaj ib nrab hla kev tiv thaiv rau cephalosporins thiab penicillins.
A. Cephamycin
Cephamycin yog ib qho beta lawm tshuaj tua kab mob tau txais los ntawm Streptomyces. Muaj peb hom: A, B, thiab C, nrog hom C yog qhov muaj zog tshaj plaws. Nws muaj cov tshuaj tua kab mob dav, muaj zog tiv thaiv kab mob gram-negative, ruaj khov rau ntau yam beta lactamases. Cov qauv tshuaj lom neeg ntawm cephamycin zoo ib yam li cephalosporin, tab sis muaj cov pab pawg methoxy ntawm 7th carbon ntawm cephalosporin nucleus.
Tam sim no, cefoxitin yog siv dav Nws cov kab mob tua kab mob thiab ua haujlwm tiv thaiv kab mob yog tib yam li cov cephalosporins tiam thib ob. Nws muaj cov txiaj ntsig zoo ntawm cov kab mob anaerobic suav nrog Bacteroides fragilis. Nws yog qhov tsim nyog rau kab mob pelvic, kis kab mob gynecological thiab sib xyaw ua ke nrog cov kab mob anaerobic.
C. Latamoxef
Latamoxef, tseem hu ua moxalactam, muaj cov qauv tshuaj ntawm oxycephalosporin. Nws cov leej faj ntawm txoj haujlwm 1 yog hloov los ntawm cov pa, thiab cov pa ntawm txoj haujlwm 7 kuj tseem muaj cov pab pawg methoxy. Nws muaj ib tug dav antibacterial spectrum thiab muaj cov tshuaj tua kab mob zoo ib yam li cefotaxime. Nws muaj qhov ua tau zoo ntawm cov kab mob Gram-positive thiab tsis zoo thiab cov kab mob anaerobic, tshwj xeeb tshaj yog Bacteroides fragilis. Nws ruaj khov heev rau beta lactamase cov thiab tswj cov ntshav ntshav kom ntev.
C. Beta lactamases inhibitor
D. Monocyclic beta lactams
Aztreonam yog thawj monocyclic beta lawm tshuaj tua kab mob uas tau ua tiav siv hauv kev kho mob. Nws muaj cov kab mob tua kab mob muaj zog ntawm cov kab mob aerobic gram-negative, nrog kev tiv thaiv enzyme, tsis muaj tshuaj lom, thiab tsis muaj kev tsis haum tshuaj rau penicillin. Nws tuaj yeem siv rau cov neeg mob ua xua rau tshuaj penicillin thiab feem ntau siv los hloov pauv rau aminoglycosides.
E. Carbapenems
Cov tshuaj tua kab mob Carbapenem yog atypical beta lawm tshuaj tua kab mob nrog rau qhov dav tshaj plaws ntawm cov kab mob tua kab mob thiab muaj zog tiv thaiv kab mob tshaj plaws. Vim lawv stability beta lactamase cov thiab muaj tshuaj lom tsawg, lawv tau dhau los ua ib qho tshuaj tua kab mob kho cov kab mob loj.
Thienamycin cov qauv tshuaj lom neeg yog rau carbapenems, thiab lub nplhaib thiazole muaj cov saw khov, thiab 1-txoj hauj lwm leej faj tau hloov los ntawm cov pa roj carbon. Nws muaj cov tshuaj tua kab mob dav dav nrog cov tshuaj tua kab mob muaj zog thiab muaj tshuaj lom tsawg, tab sis nws muaj kev ruaj ntseg tsis zoo thiab tsis muaj txiaj ntsig zoo. Mipenem (imipenem, imithiamycin) muaj cov yam ntxwv ntawm kev ua haujlwm siab, nthuav dav cov kab mob tua kab mob thiab tiv thaiv enzyme. Nws tau yooj yim tsis ua haujlwm los ntawm dehydropeptidase hauv lub cev. Kev sib xyaw siv yog kev sib xyaw ua ke ntawm cov khoom no thiab peptidase inhibitor cilasTATin, hu ua tienam, uas muaj kev ruaj ntseg zoo thiab yog rau kev tso ntshav tawm.
Tshuaj tua kab mob Carbapenem yog hom tshiab beta lactam tshuaj tua kab mob hloov los ntawm tshuaj penicillin, uas tau tawm hauv xyoo 1980s. Nws cov qauv zoo ib yam li lub nplhaib penicillium ntawm penicillins, tshwj tsis yog tias cov tshuaj sulfur atom ntawm lub nplhaib thiazole tau hloov los ntawm cov pa roj carbon, thiab muaj qhov sib npaug tsis sib xws ntawm C2 thiab C3; ntxiv rau, 6-txoj haujlwm hydroxyethyl sab saw tau thim rov qab hloov pauv.
Cov kev tshawb fawb tau qhia tias nws yog pab pawg tshwj xeeb no uas ua rau cis-kev hloov pauv ntawm hom kev sib xyaw no sib txawv los ntawm qhov niaj zaus penicillene. Nws muaj qhov pom dav heev, muaj zog tiv thaiv kab mob, muaj qib siab tiv taus thiab ruaj khov rau beta lactamase. Tam sim no, Taineng (imipenem thiab cilastatin) thiab meropenem feem ntau siv.
Beta lactam muaj kev faib tawm nplua nuj heev thiab nthuav dav cov kab mob tua kab mob. Tab sis nws kuj muaj qee cov kev mob tshwm sim zoo ib yam li lwm cov tshuaj tua kab mob, yog li cov tib neeg yuav tsum tau hais txog kev ceev faj tshwj xeeb thaum siv cov tshuaj tua kab mob zoo li no.
BALLYA muab a betalactam xeem los qhia koj yog tias muaj cov beta lactams seem hauv cov khoom siv mis uas koj noj txhua hnub.
References