Citizendia
Your Ad Here

Cephalosporin nucleus
Cephalosporin nucleus

The cephalosporins (pronounced /ˌsɛfələˈspɔrən/, /ˌkɛfə-/) are a class of β-lactam antibiotics. β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems Together with cephamycins they belong to a sub-group called cephems. Cephamycins are a group of Beta-lactam antibiotics very similar to Cephalosporins Together with cephalosporins they form a sub-group of antibiotics called Cephems Cephems are a sub-group of Beta-lactam antibiotics including Cephalosporins and Cephamycins

Contents

History

Cephalosporin compounds were first isolated from cultures of Cephalosporium acremonium from a sewer in Sardinia in 1948 by Italian scientist Giuseppe Brotzu [1]. Acremonium strictum is a plant animal and human Pathogen. The genus Acremonium contains around 100 species most of which are saprophytic Sardinia (sɑrˈdɪnɪə Sardegna Sardigna or Sardinnya is the second-largest island in the Mediterranean Sea (after Sicily) Year 1948 ( MCMXLVIII) was a Leap year starting on Thursday (link will display the 1948 calendar of the Gregorian calendar. He noticed that these cultures produced substances that were effective against Salmonella typhi, the cause of typhoid fever. Salmonella enterica is a rod shaped Flagellated Gram-negative Bacterium, and a member of the Genus Salmonella Typhoid fever, also known as enteric fever, bilious fever, Yellow Jack or commonly just typhoid, is an illness caused by the Bacterium Researchers at the Sir William Dunn School of Pathology at the University of Oxford isolated cephalosporin C, which had resistance to β-lactamases but was not sufficiently potent for clinical use. The Sir William Dunn School of Pathology is a Department within the University of Oxford. The University of Oxford (informally "Oxford University" or simply "Oxford" located in the city of Oxford, Oxfordshire, England is the Beta-lactamases are Enzymes ( produced by some bacteria and are responsible for their resistance to Beta-lactam antibiotics like Penicillins 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. Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections 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. Cefalotin ( INN) (sɛfəˈlotən/ /kɛfə- or cephalothin ( USAN) (/sɛfəˈloθən/ /kɛfə-/ is a first-generation Cephalosporin Antibiotic Eli Lilly and Company ( is a global Pharmaceutical company and one of the world's largest corporations Year 1964 ( MCMLXIV) was a Leap year starting on Wednesday (link will display full calendar of the 1964 Gregorian calendar.

Mode of action

Cephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). A bactericide or bacteriocide is a substance that kills bacteria and preferably nothing else β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. Not to be confused with Glycoprotein. Peptidoglycan, also known as murein, is a Polymer consisting of sugars and amino A cell wall is a tough flexible and sometimes fairly rigid layer surrounding a cell, located external to the Cell membrane, which provides the cell with structural 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). Penicillin-binding proteins (PBPs are a group of Proteins that are characterized by their affinity for and binding of Penicillin. 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. β-lactam antibiotics are a broad class of Antibiotics that include Penicillin derivatives Cephalosporins Monobactams Carbapenems

Clinical use

Indications

Cephalosporins are indicated for the prophylaxis and treatment of infections caused by bacteria susceptible to this particular form of antibiotic. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose 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). Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol

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. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Infrequent ADRs (0. 1–1% of patients) include: vomiting, headache, dizziness, oral and vaginal candidiasis, pseudomembranous colitis, superinfection, eosinophilia, and/or fever. Candidiasis, commonly called yeast infection or thrush, is a Fungal infection (mycosis of any of the Candida species of which Clostridium difficile Pseudomembranous colitis is an infection of the colon often but not always caused by the Bacterium Clostridium difficile In Virology, superinfection is the process by which a cell that has previously been infected by one Virus gets coinfected with another virus Eosinophilia is the state of having a high concentration of eosinophils ( Eosinophil granulocytes in the Blood.

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,[2] and subsequent "safety first" policy meant this was widely quoted and assumed to apply to all members of the group. Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Carbapenems are a class of Beta-lactam antibiotics with a broad spectrum of antibacterial activity and have a structure which renders them highly resistant to Beta-lactamases [3] 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. Anaphylaxis is an acute systemic (multi-system and severe Type I Hypersensitivity allergic reaction in humans and other Mammals Interstitial nephritis (or Tubulo-interstitial nephritis) is a form of Nephritis affecting the Interstitium of the Kidneys surrounding the [4] 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. [5][3]

Several cephalosporins are associated with hypoprothrombinemia and a disulfiram-like reaction. Hypoprothrombinemia is a blood disorder in which a deficiency of prothrombin ( Factor II) results in impaired blood clotting, leading to an increased physiological Disulfiram is a drug used [6][7] These include latamoxef, cefmenoxime, moxalactam, cefoperazone, cefamandole, cefmetazole, and cefotetan. Latamoxef (or moxalactam) is an oxacephem Antibiotic usually grouped with the Cephalosporins In oxacephems such as latamoxef the Sulfur atom Cefmenoxime is a third-generation Cephalosporin Antibiotic. Cefoperazone is a third generation Cephalosporin Antibiotic, marketed by Pfizer under the name Cefobid. Cefamandole ( INN, also known as cephamandole) is a broad-spectrum Cephalosporin Antibiotic. Cefmetazole is a Cephalosporin. Side Effects - The N-methyl-thiotetrazole side chain causes many bleeding problems and disulfaram-like reactions with substances such Cefotetan is an injectable Antibiotic of the Cephamycin type for prophylaxis and treatment of Bacterial infections It is often grouped together with second-generation This is thought to be due to the N-methylthiotetrazole (NMTT) side chain of these cephalosporins, which blocks the enzyme vitamin K epoxide reductase. Vitamin K epoxide reductase (VKOR is an Enzyme ( that reduces Vitamin K after it has been oxidised in the carboxylation of Glutamic acid.

Classification

The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their antimicrobial properties. An antimicrobial is a substance that kills or inhibits the growth of Microbes such as Bacteria, Fungi, or Viruses. The first cephalosporins were designated first generation, whereas later, more extended spectrum cephalosporins were classified as second-generation cephalosporins. A spectrum (plural spectra or spectrums) is a condition that is not limited to a specific set of values but can vary infinitely within a continuum. 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. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. 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 spelt "cef-". An International Nonproprietary Name ( INN; also known as rINN, for recommended International Nonproprietary Name or pINN for proposed Newer first-generation cephalosporins and all cephalosporins of later generations are spelled "cef-".

Structure of the classical cephalosporins
Structure of the classical cephalosporins

First generation

Although first-generation cephalosporins are moderate spectrum agents, with a spectrum of activity or treatable range of bacteria that includes penicillinase-producing, methicillin-susceptible staphylococci and streptococci, they are not the drugs of choice for such infections. Staphylococcus (in Greek σταφυλη staphyle means bunch of grapes and κοκκος coccos means granule is a genus of Gram-positive Streptococcus is a Genus of spherical Gram-positive bacteria belonging to the phylum Firmicutes and the 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. Klebsiella pneumoniae is a Gram-negative, non- Motile, Encapsulated, Lactose fermenting, Facultative anaerobic Proteus is a genus of Gram-negative Proteobacteria, which includes Pathogens responsible for many Human Urinary tract infections Bacteroides is a Genus of Gram-negative, bacillis bacteria. Bacteroides species are non- Endospore -forming anaerobes Enterococcus is a Genus of Lactic acid bacteria of the phylum Firmicutes. Pseudomonas is a Genus of gamma Proteobacteria, belonging to the larger family of Pseudomonads Recently 16S rRNA sequence Acinetobacter is a Gram-negative Genus of bacteria belonging to the Phylum Proteobacteria. Enterobacter is a genus of common Gram-negative, facultatively-anaerobic, rod-shaped Bacteria of the family Enterobacteriaceae Proteus is a genus of Gram-negative Proteobacteria, which includes Pathogens responsible for many Human Urinary tract infections Serratia is a Genus of Gram-negative, facultatively anaerobic, rod-shaped Bacteria of the Enterobacteriaceae

Second generation

The second-generation cephalosporins have a greater Gram-negative spectrum while retaining some activity against Gram-positive cocci. Cefacetrile ( INN, also spelled cephacetrile is a broad-spectrum first generation Cephalosporin Antibiotic effective in Gram-positive Cefadroxil is a Broad-spectrum antibiotic effective in Gram-positive and Gram-negative bacterial infections Cefalexin ( INN) (sɛfəˈlɛksɨn/ /kɛfə- or cephalexin ( USAN) is a first-generation Cephalosporin Antibiotic. Cefaloglycin INN (also spelled cephaloglycin) is a first generation Cephalosporin Antibiotic. Cefaloridine (or cephaloridine) is a Cephalosporin. It is unique among cephalosporins in that it exists as a Zwitterion. Cefalotin ( INN) (sɛfəˈlotən/ /kɛfə- or cephalothin ( USAN) (/sɛfəˈloθən/ /kɛfə-/ is a first-generation Cephalosporin Antibiotic Cefapirin ( INN, also spelled cephapirin) is a first-generation Cephalosporin Antibiotic. Cefatrizine is a broad-spectrum Cephalosporin Antibiotic. Cefazedone is a Cephalosporin Antibiotic. Cefazolin ( INN) also known as cefazoline or cephazolin, is a first generation Cephalosporin Antibiotic. Cefradine ( INN) or cephradine (former BAN) is a first generation Cephalosporin Antibiotic. Cefroxadine is a Cephalosporin antibiotic Ceftezole (or ceftezol) is a Cephalosporin Antibiotic. Gram-negative bacteria are those Bacteria that do not retain Crystal violet dye in the Gram staining protocol Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. They are also more resistant to beta-lactamase. Beta-lactamases are Enzymes ( produced by some bacteria and are responsible for their resistance to Beta-lactam antibiotics like Penicillins

Second generation cephalosporins with antianaerobe activity

The following cephems are also sometimes grouped with second-generation cephalosporins:

Third generation

Third-generation cephalosporins have a broad spectrum of activity and further increased activity against Gram-negative organisms. Cefaclor, also known as cefachlor or cefaclorum (brand names Ceclor, Distaclor, Keflor, Raniclor) is a second-generation Cefonicide (or cefonicid) is a Cephalosporin. It's also an antibiotic Cefprozil, sometimes spelled cefproxil and sold under the brand name Cefzil, is a Cephalosporin type Antibiotic. Cefuroxime is a second-generation Cephalosporin Antibiotic that has been widely available in the USA as Ceftin since 1977 Cefmetazole is a Cephalosporin. Side Effects - The N-methyl-thiotetrazole side chain causes many bleeding problems and disulfaram-like reactions with substances such Cefotetan is an injectable Antibiotic of the Cephamycin type for prophylaxis and treatment of Bacterial infections It is often grouped together with second-generation Cefoxitin is a Cephamycin Antibiotic developed by Merck & Co Inc Carbacephem is a class of Antibiotic medication specifically modified forms of Cephalosporin. Loracarbef is a Carbacephem Antibiotic sometimes grouped together with the second-generation Cephalosporin antibiotics Cephamycins are a group of Beta-lactam antibiotics very similar to Cephalosporins Together with cephalosporins they form a sub-group of antibiotics called Cephems Cefmetazole is a Cephalosporin. Side Effects - The N-methyl-thiotetrazole side chain causes many bleeding problems and disulfaram-like reactions with substances such Cefotetan is an injectable Antibiotic of the Cephamycin type for prophylaxis and treatment of Bacterial infections It is often grouped together with second-generation Cefoxitin is a Cephamycin Antibiotic developed by Merck & Co Inc 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. Nosocomial infections are Infections which are a result of treatment in a Hospital or a healthcare service unit but secondary to the patient's original condition They are also able to penetrate the CNS, making them useful against meningitis caused by pneumococci, meningococci, H. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. influenzae, and susceptible E. coli, Klebsiella, and penicillin-resistant N. gonorrhoeae.

Cephalosporins with antipseudomonal activity

The following cephems are also sometimes grouped with third-generation cephalosporins:

Fourth generation

Fourth-generation cephalosporins are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation cephalosporins. Cefdinir (marketed by Abbott Laboratories under the Brand name Omnicef) is a semi-synthetic Broad-spectrum antibiotic in the third generation Cefditoren is a third-generation Cephalosporin Antibiotic for oral use Cefixime is an oral third generation Cephalosporin Antibiotic. Cefmenoxime is a third-generation Cephalosporin Antibiotic. Cefodizime is a Cephalosporin. Cefotaxime ( INN) (sɛfəˈtæksiːm/ /kɛfə- is a third-generation Cephalosporin Antibiotic. Cefpodoxime (marketed as the Prodrug cefpodoxime proxetil by Pharmacia & Upjohn under the trade name Vantin, is an oral third generation Ceftibuten is a third-generation Cephalosporin Antibiotic. It is an orally-administered agent with 2 dosage forms capsule or oral suspension Ceftiofur is an Antibiotic of the Cephalosporin type ( third generation) licensed for use in Veterinary medicine. Ceftriaxone ( INN) (ˌsɛftraɪˈæksoʊn/ /ˌkɛf- is a third-generation Cephalosporin Antibiotic. Cefoperazone is a third generation Cephalosporin Antibiotic, marketed by Pfizer under the name Cefobid. Ceftazidime ( INN) (sɛfˈtæzɨdiːm/ /kɛf- is a third-generation Cephalosporin Antibiotic. Latamoxef (or moxalactam) is an oxacephem Antibiotic usually grouped with the Cephalosporins In oxacephems such as latamoxef the Sulfur atom They also have a greater resistance to beta-lactamases than the third-generation cephalosporins. Many can cross blood-brain barrier and are effective in meningitis. The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic Meningitis is Inflammation of the protective membranes covering the Brain and Spinal cord, known collectively as the Meninges. They are also used against Pseudomonas aeruginosa. Pseudomonas aeruginosa is a Gram-negative, aerobic, rod-shaped Bacterium with unipolar motility.

The following cephems are also sometimes grouped with third-generation cephalosporins:

Yet to be classified

These cephems have progressed far enough to be named, but have not been assigned to a particular generation. Cefepime ( INN) (ˈsɛfəpiːm/ /ˈkɛfəpiːm is a fourth-generation Cephalosporin Antibiotic developed in 1994. Cefozopran ( INN) is a fourth-generation Cephalosporin. Cefpirome is a fourth-generation Cephalosporin. Trade name Cefrom Cefquinome (4GC is a fourth generation Cephalosporin with pharmacological and antibacterial properties valuable in the treatment of coliform mastitis and other infections Flomoxef ( INN) is a Cephalosporin antibiotic Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole (brand name Zeftera) is a next generation Cephalosporin Antibiotic with activity against methicillin-resistant ''Staphylococcus aureus'' Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance. Ceftobiprole (brand name Zeftera) is a next generation Cephalosporin Antibiotic with activity against methicillin-resistant ''Staphylococcus aureus''

References

  1. ^ Podolsky, M. Ceftobiprole (brand name Zeftera) is a next generation Cephalosporin Antibiotic with activity against methicillin-resistant ''Staphylococcus aureus'' Lawrence (1998) Cures Out of Chaos: How Unexpected Discoveries Led to Breakthroughs in Medicine and Health, Harwood Academic Publishers
  2. ^ Dash CH (1975). "Penicillin allergy and the cephalosporins". J. Antimicrob. Chemother. 1 (3 Suppl): 107–18. PMID 1201975.  
  3. ^ a b Pegler S, Healy B (10 November 2007). "In patients allergic to penicillin, consider second and third generation cephalosporins for life threatening infections". BMJ 335 (7627): 991. doi:10.1136/bmj.39372.829676.47. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
  4. ^ Rossi S, editor. Australian Medicines Handbook 2006. The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly General practitioners Adelaide: Australian Medicines Handbook; 2006.
  5. ^ Pichichero ME (2006). "Cephalosporins can be prescribed safely for penicillin-allergic patients" (PDF). The Journal of family practice 55 (2): 106–12. PMID 16451776.  
  6. ^ Kitson TM (1987). "The effect of cephalosporin antibiotics on alcohol metabolism: a review". Alcohol 4 (3): 143–8. doi:10.1016/0741-8329(87)90035-8. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 3593530.  
  7. ^ Shearer MJ, Bechtold H, Andrassy K, et al (1988). "Mechanism of cephalosporin-induced hypoprothrombinemia: relation to cephalosporin side chain, vitamin K metabolism, and vitamin K status". Journal of clinical pharmacology 28 (1): 88–95. PMID 3350995.  
  8. ^ Jędrzejczyk, Tadeusz. Internetowa Encyklopedia Leków. leki. med. pl. Retrieved on 2007-03-03. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 1284 - Statute of Rhuddlan incorporated the Principality of Wales into England 1575 - Indian

See also

External links

Dictionary

cephalosporin

-noun

  1. Any of a class of natural and synthetic antibiotics developed from Cephalosporium fungi, having a cepham structure.
© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
 Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic