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    Cephalosporin

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    Cephalosporins are a class of β-lactam antibiotics derived from the fungus Acremonium. They work by inhibiting the synthesis of bacterial cell walls. Generations of cephalosporins have been developed with increasing spectrum of activity against gram-negative bacteria but sometimes decreased activity against gram-positive bacteria. Common side effects include diarrhea and rash while some can cause disulfiram-like reactions with alcohol or bleeding issues due to interactions with vitamin K.

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    Cephalosporin

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    Cephalosporins are a class of β-lactam antibiotics derived from the fungus Acremonium. They work by inhibiting the synthesis of bacterial cell walls. Generations of cephalosporins have been developed with increasing spectrum of activity against gram-negative bacteria but sometimes decreased activity against gram-positive bacteria. Common side effects include diarrhea and rash while some can cause disulfiram-like reactions with alcohol or bleeding issues due to interactions with vitamin K.

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    Cephalosporins are a class of β-lactam antibiotics derived from the fungus Acremonium. They work by inhibiting the synthesis of bacterial cell walls. Generations of cephalosporins have been developed with increasing spectrum of activity against gram-negative bacteria but sometimes decreased activity against gram-positive bacteria. Common side effects include diarrhea and rash while some can cause disulfiram-like reactions with alcohol or bleeding issues due to interactions with vitamin K.

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    239 views8 pages

    Cephalosporin

    Uploaded by

    vidagurl
    Cephalosporins are a class of β-lactam antibiotics derived from the fungus Acremonium. They work by inhibiting the synthesis of bacterial cell walls. Generations of cephalosporins have been developed with increasing spectrum of activity against gram-negative bacteria but sometimes decreased activity against gram-positive bacteria. Common side effects include diarrhea and rash while some can cause disulfiram-like reactions with alcohol or bleeding issues due to interactions with vitamin K.

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    of 8

    Cephalosporin

    From Wikipedia, the free encyclopedia

    Jump to: navigation, search

    Core structure of the cephalosporins

    The cephalosporins (sg. pronounced /ˌsɛfəlɵˈspɔrɨn/) are a class of β-lactam antibiotics


    originally derived from Acremonium, which was previously known as "Cephalosporium".
    [1]

    Together with cephamycins they constitute a subgroup of β-lactam antibiotics called


    cephems.

    Contents
    [hide]

    • 1 History
    • 2 Mode of action
    • 3 Clinical use
    o 3.1 Indications
    o 3.2 Adverse effects
    • 4 Classification
    o 4.1 First generation
    o 4.2 Second generation
    o 4.3 Third generation
    o 4.4 Fourth generation
    o 4.5 Fifth generation
    o 4.6 Yet to be classified
    • 5 See also
    • 6 References
    • 7 Further reading

    • 8 External links
    [edit] History
    Cephalosporin compounds were first isolated from cultures of Cephalosporium
    acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu [2]. He
    noticed that these cultures produced substances that were effective against Salmonella
    typhi, the cause of typhoid fever, which had beta-lactamase. Guy Newton and Edward
    Abraham at the Sir William Dunn School of Pathology at the University of Oxford
    isolated cephalosporin C. The cephalosporin nucleus, 7-aminocephalosporanic acid (7-
    ACA), was derived from cephalosporin C and proved to be analogous to the penicillin
    nucleus 6-aminopenicillanic acid, but it was not sufficiently potent for clinical use.
    Modification of the 7-ACA side-chains resulted in the development of useful antibiotic
    agents, and the first agent cephalothin (cefalotin) was launched by Eli Lilly in 1964.

    [edit] Mode of action


    Cephalosporins are bactericidal and have the same mode of action as other beta-lactam
    antibiotics (such as penicillins) but are less susceptible to penicillinases. Cephalosporins
    disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan
    layer is important for cell wall structural integrity. The final transpeptidation step in the
    synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin
    binding proteins (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides
    (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic
    this site and competitively inhibit PBP crosslinking of peptidoglycan.

    [edit] Clinical use


    [edit] Indications

    Cephalosporins are indicated for the prophylaxis and treatment of infections caused by
    bacteria susceptible to this particular form of antibiotic. First-generation cephalosporins
    are predominantly active against Gram-positive bacteria, and successive generations have
    increased activity against Gram-negative bacteria (albeit often with reduced activity
    against Gram-positive organisms).

    [edit] Adverse effects

    Common adverse drug reactions (ADRs) (≥1% of patients) associated with the
    cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and/or
    pain and inflammation at injection site. Infrequent ADRs (0.1–1% of patients) include:
    vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis,
    superinfection, eosinophilia, and/or fever.

    The commonly quoted figure of 10% of patients with allergic hypersensitivity to


    penicillins and/or carbapenems also having cross-reactivity with cephalosporins
    originated from a 1975 study looking at the original cephalosporins,[3] and subsequent
    "safety first" policy meant this was widely quoted and assumed to apply to all members
    of the group.[4] Hence it was commonly stated that they are contraindicated in patients
    with a history of severe, immediate allergic reactions (urticaria, anaphylaxis, interstitial
    nephritis, etc) to penicillins, carbapenems or cephalosporins.[5] This however should be
    viewed in the light of recent epidemiological work suggesting that for many 2nd
    generation (or later) cephalosporins that the cross-reactivity rate with penicillin is much
    lower, having no significantly increased risk of reactivity in the studies examined.[4][6] The
    British National Formulary previously issued blanket warnings of 10% cross reactivity;
    but since the September 2008 edition suggests in the absence of suitable alternatives that
    oral cefixime or cefuroxime and injectable cefotaxime, ceftazidine and ceftriaxone can be
    used with caution, but to avoid cefaclor, cefadrocil, cefalexin and cefradine.[7]

    Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like


    reaction with ethanol.[8][9] These include latamoxef, cefmenoxime, moxalactam,
    cefoperazone, cefamandole, cefmetazole, and cefotetan. This is thought to be due to the
    N-methylthiotetrazole (NMTT) side chain of these cephalosporins, which blocks the
    enzyme vitamin K epoxide reductase (likely causing hypothrombinemia) and aldehyde
    dehydrogenase (causing alcohol intolerance).[10]

    [edit] Classification
    The cephalosporin nucleus can be modified to gain different properties. Cephalosporins
    are sometimes grouped into "generations" by their antimicrobial properties. The first
    cephalosporins were designated first generation, whereas later, more extended spectrum
    cephalosporins were classified as second-generation cephalosporins. Each newer
    generation of cephalosporins has significantly greater Gram-negative antimicrobial
    properties than the preceding generation, in most cases with decreased activity against
    Gram-positive organisms. Fourth-generation cephalosporins, however, have true broad
    spectrum activity.

    The classification of cephalosporins into "generations" is commonly practised, although


    the exact categorisation of cephalosporins is often imprecise. For example, the fourth
    generation of cephalosporins is not yet recognized in Japan. In Japan, cefaclor is classed
    as a first-generation cephalosporin, even though in the United States it is a 2nd
    generation; and cefbuperazone, cefminox, and cefotetan are classed as second-generation
    cephalosporins. Cefmetazole and cefoxitin are classed as third-generation cephems.
    Flomoxef, latamoxef are in a new class called oxacephems.

    Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking


    countries. This continues to be the preferred spelling in the US and Australia, while
    European countries have adopted International Nonproprietary Names, which are usually
    spelled "cef-". Newer first-generation cephalosporins and all cephalosporins of later
    generations are spelled "cef-".

    Some state that although cephalosporins can be divided into five or even six generations,
    the usefulness of this organization system is of limited clinical relevance.[11]
    [edit] First generation
    Structure of the classical cephalosporins

    Although first-generation cephalosporins are moderate spectrum agents, with a spectrum


    of activity of bacteria that includes penicillinase-producing, methicillin-susceptible
    staphylococci and streptococci, they are not the drugs of choice for such infections. They
    also have activity against some Escherichia coli, Klebsiella pneumoniae and Proteus
    mirabilis, but have no activity against Bacteroides fragilis, enterococci, methicillin-
    resistant staphylococci, Pseudomonas, Acinetobacter, Enterobacter, indole-positive
    Proteus, or Serratia.

    • Cefacetrile (cephacetrile)
    • Cefadroxil (cefadroxyl; Duricef)
    • Cephalexin (cephalexin; Keflex)
    • Cefaloglycin (cephaloglycin)
    • Cefalonium (cephalonium)
    • Cefaloridine (cephaloradine)
    • Cefalotin (cephalothin; Keflin)
    • Cefapirin (cephapirin; Cefadryl)
    • Cefatrizine
    • Cefazaflur
    • Cefazedone
    • Cefazolin (cephazolin; Ancef, Kefzol)
    • Cefradine (cephradine; Velosef)
    • Cefroxadine
    • Ceftezole

    [edit] Second generation

    The second-generation cephalosporins have a greater Gram-negative spectrum while


    retaining some activity against Gram-positive cocci. They are also more resistant to beta-
    lactamase.

    • Cefaclor (Ceclor, Distaclor, Keflor, Raniclor)


    • Cefonicid (Monocid)
    • Cefprozil (cefproxil; Cefzil)
    • Cefuroxime (Zinnat, Zinacef, Ceftin, Biofuroksym[12])
    • Cefuzonam

    Second generation cephalosporins with antianaerobe activity

    • Cefmetazole
    • Cefotetan
    • Cefoxitin

    The following cephems are also sometimes grouped with second-generation


    cephalosporins:
    • Carbacephems: loracarbef (Lorabid)
    • Cephamycins: cefbuperazone, cefmetazole (Zefazone), cefminox, cefotetan
    (Cefotan), cefoxitin (Mefoxin)

    [edit] Third generation

    Third-generation cephalosporins have a broad spectrum of activity and further increased


    activity against Gram-negative organisms. Some members of this group (in particular,
    those available in an oral formulation, and those with anti-pseudomonal activity) have
    decreased activity against Gram-positive organisms. They may be particularly useful in
    treating hospital-acquired infections, although increasing levels of extended-spectrum
    beta-lactamases are reducing the clinical utility of this class of antibiotics. They are also
    able to penetrate the CNS, making them useful against meningitis caused by
    pneumococci, meningococci, H. influenzae, and susceptible E. coli, Klebsiella, and
    penicillin-resistant N. gonorrhoeae. Since 2007, third-generation cephalosporins
    (ceftriaxone or cefixime) have been the only recommended treatment for gonorrhea in the
    United States.[13]

    • Cefcapene
    • Cefdaloxime
    • Cefdinir (Omnicef, Kefnir)
    • Cefditoren
    • Cefetamet
    • Cefixime (Suprax)
    • Cefmenoxime
    • Cefodizime
    • Cefotaxime (Claforan)
    • Cefovecin (Convenia)
    • Cefpimizole
    • Cefpodoxime (Vantin, PECEF)
    • Cefteram
    • Ceftibuten (Cedax)
    • Ceftiofur
    • Ceftiolene
    • Ceftizoxime (Cefizox)
    • Ceftriaxone (Rocephin)

    Third-generation cephalosporins with antipseudomonal activity

    • Cefoperazone (Cefobid)
    • Ceftazidime (Fortum, Fortaz)

    The following cephems are also sometimes grouped with third-generation


    cephalosporins:

    • Oxacephems: latamoxef (moxalactam)


    [edit] Fourth generation

    Fourth-generation cephalosporins are extended-spectrum agents with similar activity


    against Gram-positive organisms as first-generation cephalosporins. They also have a
    greater resistance to beta-lactamases than the third-generation cephalosporins. Many can
    cross the blood-brain barrier and are effective in meningitis. They are also used against
    Pseudomonas aeruginosa.

    • Cefclidine
    • Cefepime (Maxipime)
    • Cefluprenam
    • Cefoselis
    • Cefozopran
    • Cefpirome(Cefrom)
    • Cefquinome

    The following cephems are also sometimes grouped with fourth-generation


    cephalosporins:

    • Oxacephems: flomoxef

    [edit] Fifth generation

    Ceftobiprole has been described as "fifth generation",[14][15] though acceptance for this
    terminology is not universal.

    Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole
    has powerful antipseudomonal characteristics and appears to be less susceptible to
    development of resistance.

    [edit] Yet to be classified

    These cephems have progressed far enough to be named, but have not been assigned to a
    particular generation.

    • Cefaloram
    • Cefaparole
    • Cefcanel
    • Cefedrolor
    • Cefempidone
    • Cefetrizole
    • Cefivitril
    • Cefmatilen
    • Cefmepidium
    • Cefoxazole
    • Cefrotil
    • Cefsumide
    • Ceftaroline
    • Ceftioxide
    • Cefuracetime

    [edit] See also


    • Beta-lactam antibiotic
    • Medicinal mushrooms

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