Array ( [0] => {{Distinguish|cyclosporin}}{{Short description|Class of pharmaceutical drugs}} [1] => {{Use dmy dates|date=July 2022}} [2] => {{Infobox drug class [3] => | Name = Cephalosporin [4] => | Image = Cephalosporin core structure.svg [5] => | Alt = [6] => | Caption = Core structure of the cephalosporins [7] => | Use = Bacterial infection [8] => | Biological_target = [[Penicillin binding proteins]] [9] => | ATC_prefix = J01D [10] => | MeshID = D002511 [11] => | Drugs.com = {{Drugs.com|drug-class|cephalosporins}} [12] => | Consumer_Reports = [13] => | medicinenet = [14] => | rxlist = [15] => }} [16] => [17] => [[File:Cephalosporins Generation1.svg|thumb|Structure of the classical cephalosporins]] [18] => The '''cephalosporins''' (sg. {{IPAc-en|ˌ|s|ɛ|f|ə|l|ə|ˈ|s|p|ɔːr|ᵻ|n|,_|ˌ|k|ɛ|-|,_|-|l|oʊ|-}}{{refn|{{MerriamWebsterDictionary|cephalosporin}}}}{{refn|{{cite web |url=https://www.oxforddictionaries.com/definition/english/cephalosporin |archive-url=https://web.archive.org/web/20120707015035/http://oxforddictionaries.com/definition/english/cephalosporin |url-status=dead |archive-date=7 July 2012 |title=cephalosporin – definition of cephalosporin in English from the Oxford dictionary |publisher=[[OxfordDictionaries.com]] |access-date=2016-01-20 }} }}) are a class of [[β-lactam antibiotic]]s originally derived from the [[fungus]] ''[[Acremonium]]'', which was previously known as ''Cephalosporium''.{{DorlandsDict|two/000019430|cephalosporin}} [19] => [20] => Together with [[cephamycin]]s, they constitute a subgroup of β-lactam antibiotics called [[cephem]]s. Cephalosporins were discovered in 1945, and first sold in 1964.{{cite book|title=Oxford Handbook of Infectious Diseases and Microbiology|date=2009|publisher=OUP Oxford|isbn=9780191039621|page=56|url=https://books.google.com/books?id=5W-WBQAAQBAJ&pg=PT56}} [21] => [22] => == Discovery == [23] => The [[aerobic organism|aerobic]] [[mold]] which [[wikt:yield|yield]]ed [[cephalosporin C]] was found in the sea near a [[sewage outfall]] in [[Su Siccu]], by [[Cagliari]] [[harbour]] in [[Sardinia]], by the [[Italians|Italian]] [[pharmacologist]] [[Giuseppe Brotzu]] in July 1945.{{cite Q|Q29581637}} [24] => [25] => ==Structure== [26] => Cephalosporin contains a 6-membered dihydrothiazine ring. Substitutions at position 3 generally affect pharmacology; substitutions at position 7 affect antibacterial activity, but these cases are not always true.{{cite web |last1=Prince |first1=A |title=Cephalosporins and vancomycin |url=http://www.columbia.edu/itc/hs/medical/pathophys/id/2004/lecture/notes/CephaloVanco_Prince.pdf |publisher=Columbia University |access-date=15 October 2022 |archive-url=https://web.archive.org/web/20190819132837if_/http://www.columbia.edu:80/itc/hs/medical/pathophys/id/2004/lecture/notes/CephaloVanco_Prince.pdf |archive-date=19 August 2019}} [27] => [28] => ==Medical uses== [29] => Cephalosporins can be indicated for the [[prophylaxis]] and treatment of infections caused by [[bacteria]] susceptible to this particular form of antibiotic. First-generation cephalosporins are active predominantly against [[Gram-positive]] bacteria, such as ''[[Staphylococcus]]'' and ''[[Streptococcus]]''.{{Cite web|url=https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/cephalosporins|title=Cephalosporins – Infectious Diseases|website=Merck Manuals Professional Edition|language=en-US|access-date=2019-05-15}} They are therefore used mostly for skin and soft tissue infections and the prevention of hospital-acquired surgical infections.{{cite book |chapter=Beta Lactam Antibiotics |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK545311/ |title=StatPearls |year=2020 |pmid=31424895 |last1=Pandey |first1=Neelanjana |last2=Cascella |first2=Marco |publisher=StatPearls }} Successive generations of cephalosporins have increased activity against [[Gram-negative]] bacteria, albeit often with reduced activity against Gram-positive organisms.{{cn|date=December 2022}} [30] => [31] => The antibiotic may be used for patients who are allergic to penicillin due to the different [[β-lactam antibiotic]] structure. The drug is able to be excreted in the urine. [32] => [33] => ==Side effects== [34] => Common [[adverse drug reaction]]s (ADRs) (≥ 1% of patients) associated with the cephalosporin therapy include: diarrhea, nausea, rash, electrolyte disturbances, and 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]], [[nephrotoxicity]], [[neutropenia]], [[thrombocytopenia]], and [[fever]].{{cn|date=December 2022}} [35] => [36] => === Allergic hypersensitivity === [37] => The commonly quoted figure of 10% of patients with allergic hypersensitivity to [[penicillin]]s and/or [[carbapenem]]s also having cross-reactivity with cephalosporins originated from a 1975 study looking at the original cephalosporins,{{cite journal |last1=Dash |first1=C. H. |title=Penicillin allergy and the cephalosporins |journal=Journal of Antimicrobial Chemotherapy |date=1 September 1975 |volume=1 |issue=suppl 3 |pages=107–118 |doi=10.1093/jac/1.suppl_3.107 |pmid=1201975 }} and subsequent "safety first" policy meant this was widely quoted and assumed to apply to all members of the group.{{cite journal |last1=Pegler |first1=Scott |last2=Healy |first2=Brendan |title=In patients allergic to penicillin, consider second and third generation cephalosporins for life threatening infections |journal=The BMJ |date=10 November 2007 |volume=335 |issue=7627 |pages=991 |doi=10.1136/bmj.39372.829676.47 |pmid=17991982 |pmc=2072043 }} 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 or carbapenems.Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.{{page needed|date=June 2020}} [38] => [39] => The contraindication, however, should be viewed in the light of recent epidemiological work suggesting, for many second-generation (or later) cephalosporins, the cross-reactivity rate with penicillin is much lower, having no significantly increased risk of reactivity over the first generation based on the studies examined.{{Cite journal |last1=Pichichero |first1=Michael E |title=Cephalosporins can be prescribed safely for penicillin-allergic patients |journal=The Journal of Family Practice |volume=55 |issue=2 |pages=106–12 |year=2006 |pmid=16451776 |url=http://www.jfponline.com/Pages.asp?AID=3850 }} 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, oral [[cefixime]] or cefuroxime and injectable cefotaxime, [[ceftazidime]], and ceftriaxone can be used with caution, but the use of [[cefaclor]], [[cefadroxil]], [[cefalexin]], and [[cefradine]] should be avoided.{{Cite book |title=British National Formulary |publisher=[[BMJ Publishing Group Ltd]] and [[Royal Pharmaceutical Society of Great Britain|Royal Pharmaceutical Society Publishing]] |location=London |date=September 2008 |edition=56 |chapter=5.1.2 Cephalosporins and other beta-lactams |pages=[https://archive.org/details/britishnationalf0000unse_k4e9/page/295 295] |isbn=978-0-85369-778-7 |chapter-url=https://archive.org/details/britishnationalf0000unse_k4e9/page/295 }} A 2012 literature review similarly finds that the risk is negligible with third- and fourth-generation cephalosporins. The risk with first-generation cephalosporins having similar R1 sidechains was also found to be overestimated, with the real value closer to 1%.{{cite journal |last1=Campagna |first1=JD |last2=Bond |first2=MC |last3=Schabelman |first3=E |last4=Hayes |first4=BD |title=The use of cephalosporins in penicillin-allergic patients: a literature review. |journal=The Journal of Emergency Medicine |date=May 2012 |volume=42 |issue=5 |pages=612–20 |doi=10.1016/j.jemermed.2011.05.035 |pmid=21742459}} [40] => [41] => === MTT side chain === [42] => {{See also|Disulfiram-like drug}} [43] => {{Multiple images [44] => |title=MTT and MTDT sidechains [45] => |total_width=220 [46] => |image1=N-methylthiotetrazole.svg [47] => |caption1=Methyl­thio­tetrazole [48] => |image2=N-methylthiodioxotriazine.svg [49] => |caption2=Methyl­thio­dioxo­triazine [50] => }} [51] => [52] => Several cephalosporins are associated with [[hypoprothrombinemia]] and a [[disulfiram]]-like reaction with ethanol.{{cite journal |last1=Kitson |first1=Trevor M. |title=The effect of cephalosporin antibiotics on alcohol metabolism: A review |journal=Alcohol |date=May 1987 |volume=4 |issue=3 |pages=143–148 |doi=10.1016/0741-8329(87)90035-8 |pmid=3593530 }}{{cite journal |last1=Shearer |first1=M. J. |last2=Bechtold |first2=H. |last3=Andrassy |first3=K. |last4=Koderisch |first4=J. |last5=McCarthy |first5=P. T. |last6=Trenk |first6=D. |last7=Jähnchen |first7=E. |last8=Ritz |first8=E. |title=Mechanism of Cephalosporin-induced Hypoprothrombinemia: Relation to Cephalosporin Side Chain, Vitamin K Metabolism, and Vitamin K Status |journal=The Journal of Clinical Pharmacology |date=January 1988 |volume=28 |issue=1 |pages=88–95 |doi=10.1002/j.1552-4604.1988.tb03106.x |pmid=3350995 |s2cid=30591177 }} These include [[latamoxef]] ([[moxalactam]]), [[cefmenoxime]], [[cefoperazone]], [[cefamandole]], [[cefmetazole]], and [[cefotetan]]. This is thought to be due to the [[methylthiotetrazole]] side-chain of these cephalosporins, which blocks the enzyme [[vitamin K epoxide reductase]] (likely causing hypothrombinemia) and [[aldehyde dehydrogenase]] (causing alcohol intolerance).{{Cite book|author=Stork CM |veditors=Nelson LH, Flomenbaum N, Goldfrank LR, Hoffman RL, Howland MD, Lewin NA |title=Goldfrank's toxicologic emergencies |chapter=Antibiotics, antifungals, and antivirals |chapter-url=https://books.google.com/books?id=cvJuLqBxGUcC&pg=PA847 |publisher=McGraw-Hill |location=New York |year=2006 |pages=847 |isbn=978-0-07-143763-9 }} Thus, consumption of alcohol after taking these cephalosporin orally or intravenously is contraindicated, and in severe cases can lead to death.{{Cite journal|last1=Ren|first1=Shiyan|last2=Cao|first2=Yuxia|last3=Zhang|first3=Xiuwei|last4=Jiao|first4=Shichen|last5=Qian|first5=Songyi|last6=Liu|first6=Peng|date=2014|title=Cephalosporin Induced Disulfiram-Like Reaction: A Retrospective Review of 78 Cases|journal=International Surgery|volume=99|issue=2|pages=142–146|doi=10.9738/INTSURG-D-13-00086.1|issn=0020-8868|pmc=3968840|pmid=24670024}} The methylthiodioxotriazine sidechain found in [[ceftriaxone]] has a similar effect. Cephalosporins without these structural elements are believed to be safe with alcohol.{{cite journal |last1=Mergenhagen |first1=Kari A. |last2=Wattengel |first2=Bethany A. |last3=Skelly |first3=Megan K. |last4=Clark |first4=Collin M. |last5=Russo |first5=Thomas A. |title=Fact versus Fiction: a Review of the Evidence behind Alcohol and Antibiotic Interactions |journal=Antimicrobial Agents and Chemotherapy |date=21 February 2020 |volume=64 |issue=3 |pages=e02167-19 |doi=10.1128/aac.02167-19|pmid=31871085 |pmc=7038249 }} [53] => [54] => ==Mechanism of action== [55] => Cephalosporins are [[bactericidal]] and, like other β-lactam antibiotics, disrupt the synthesis of the [[peptidoglycan]] layer forming the bacterial [[cell wall]]. The peptidoglycan layer is important for cell wall structural integrity. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by [[penicillin-binding protein]]s (PBPs). PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptidoglycan. Beta-lactam antibiotics mimic the D-Ala-D-Ala site, thereby irreversibly inhibiting PBP crosslinking of peptidoglycan.{{Cite journal|last1=Tipper|first1=D J|last2=Strominger|first2=J L|date=October 1965|title=Mechanism of action of penicillins: a proposal based on their structural similarity to acyl-D-alanyl-D-alanine.|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=54|issue=4|pages=1133–1141|doi=10.1073/pnas.54.4.1133|issn=0027-8424|pmid=5219821|pmc=219812|bibcode=1965PNAS...54.1133T|doi-access=free}} [56] => [57] => ==Resistance== [58] => [[Antimicrobial resistance|Resistance]] to cephalosporin antibiotics can involve either reduced affinity of existing PBP components or the acquisition of a supplementary β-lactam-insensitive PBP. Compared to other β-lactam antibiotics (such as penicillins), they are less susceptible to [[β-lactamase]]s. Currently, some ''[[Citrobacter freundii]], [[Enterobacter cloacae]]'', ''[[Neisseria gonorrhoeae]]'', and ''[[Escherichia coli]]'' strains are resistant to cephalosporins. Some ''[[Morganella morganii]]'', ''[[Proteus vulgaris]], [[Providencia rettgeri]], [[Pseudomonas aeruginosa]]'', ''[[Serratia marcescens]]'' and ''[[Klebsiella pneumoniae]]'' strains have also developed resistance to cephalosporins to varying degrees.{{cite web|title=Cephalosporin spectrum of resistance|url=http://antibiotics.toku-e.com/m/?w=cephalosporin|access-date= 1 July 2012}}{{cite journal |last1=Sutaria |first1=Dhruvitkumar S. |last2=Moya |first2=Bartolome |last3=Green |first3=Kari B. |last4=Kim |first4=Tae Hwan |last5=Tao |first5=Xun |last6=Jiao |first6=Yuanyuan |last7=Louie |first7=Arnold |last8=Drusano |first8=George L. |last9=Bulitta |first9=Jürgen B. |title=First Penicillin-Binding Protein Occupancy Patterns of β-Lactams and β-Lactamase Inhibitors in Klebsiella pneumoniae |journal=Antimicrobial Agents and Chemotherapy |date=25 May 2018 |volume=62 |issue=6 |pages=e00282-18 |doi=10.1128/AAC.00282-18 |pmid=29712652 |pmc=5971569 }} [59] => [60] => ==Classification== [61] => The cephalosporin nucleus can be modified to gain different properties. Cephalosporins are sometimes grouped into "generations" by their [[antimicrobial]] properties.{{cn|date=March 2023}} [62] => [63] => The first cephalosporins were designated first-generation cephalosporins, whereas, later, more extended-[[Spectrum#Biological science|spectrum]] cephalosporins were classified as second-generation cephalosporins. Each newer generation 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.{{Cite news|url=https://www.merckmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/cephalosporins|title=Cephalosporins – Infectious Diseases – Merck Manuals Professional Edition|work=Merck Manuals Professional Edition|access-date=2018-06-14|language=en-US}} [64] => [65] => The classification of cephalosporins into "generations" is commonly practised, although the exact categorization is often imprecise. For example, the fourth generation of cephalosporins is not recognized as such in Japan.{{Citation needed|date=September 2010}} In Japan, cefaclor is classed as a first-generation cephalosporin, though in the United States it is a second-generation one; and cefbuperazone, cefminox, and cefotetan are classed as second-generation cephalosporins. [66] => [67] => === First generation === [68] => [[Cefalotin]], [[cefazolin]], [[cefalexin]], [[cefapirin]], [[cefradine]], and [[cefadroxil]] are drugs belonging to this group. [69] => [70] => === Second generation === [71] => [[Cefoxitin]], [[cefuroxime]], [[cefaclor]], [[cefprozil]], and [[cefmetazole]] are classed as second-generation cephems. [72] => [73] => === Third generation === [74] => [75] => [[Ceftazidime]], [[ceftriaxone]], and [[cefotaxime]] are classed as third-generation cephalosporins. Flomoxef and latamoxef are in a new, related class called [[oxacephem]]s.{{cite book |doi=10.1007/978-3-642-75617-7_19 |chapter=1-Oxacephem Antibiotics |title=Recent Progress in the Chemical Synthesis of Antibiotics |year=1990 |last1=Narisada |first1=Masayuki |last2=Tsuji |first2=Teruji |pages=705–725 |isbn=978-3-642-75619-1 }} [76] => [77] => === Fourth generation === [78] => [79] => Drugs included in this group are [[cefepime]] and [[cefpirome]]. [80] => [81] => === Further generations === [82] => Some state that cephalosporins can be divided into five or even six generations, although the usefulness of this organization system is of limited clinical relevance.{{Cite web|url=http://www.hawaii.edu/medicine/pediatrics/pedtext/s06c05.html |title=Case Based Pediatrics Chapter }} [83] => [84] => === Naming === [85] => [86] => Most first-generation cephalosporins were originally spelled "ceph-" in English-speaking countries. This continues to be the preferred spelling in the United States, Australia, and New Zealand, while European countries (including the United Kingdom) have adopted the [[International Nonproprietary Name]]s, which are always spelled "cef-". Newer first-generation cephalosporins and all cephalosporins of later generations are spelled "cef-", even in the United States.{{citation needed|date=April 2018}} [87] => [88] => === Activity === [89] => There exist bacteria which cannot be treated with cephalosporins of generations first through fourth:{{Citation |last1=Bui |first1=Toai |title=Cephalosporins |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK551517/ |work=StatPearls |access-date=2023-06-02 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31855361 |last2=Preuss |first2=Charles V.}} [90] => * ''[[Listeria|Listeria spp.]]'' [91] => * [[Atypical pneumonia|Atypicals]] (including ''[[Mycoplasma]]'' and ''[[Chlamydia]]'') [92] => * [[Methicillin-resistant Staphylococcus aureus|MRSA]] [93] => * [[Enterococci]] [94] => [95] => Fifth-generation cephalosporins (e.g. ceftaroline) are effective against MRSA, ''Listeria'' ''spp.'', and ''Enterococcus faecalis''.{{cite journal | pmc=3140339 | year=2011 | last1=Duplessis | first1=C. | last2=Crum-Cianflone | first2=N. F. | title=Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) | journal=Clinical Medicine Reviews in Therapeutics | volume=3 | pages=a2466 | doi=10.4137/CMRT.S1637 | pmid=21785568 }} [96] => [97] => === Overview table === [98] => {{anchor|generations}} [99] => {| class="wikitable" [100] => |- [101] => ! rowspan=2 {{vert header|stp=1|Generation}} [102] => ! colspan=3 | Name [103] => ! rowspan=2 {{vert header|stp=1|Approval status}} [104] => ! rowspan=2 {{vert header|stp=1|Coverage}} [105] => ! rowspan=2 | Description [106] => |- [107] => ! [[International nonproprietary name|Common]] [108] => ! Alternate name or spelling [109] => ! Brand [110] => |- [111] => | colspan = "4" style='border-style: none none none none; padding: 0em 0.5em;' | (#) = noncephalosporins similar to generation # [112] => | colspan = "3" style='border-style: none none none none; padding: 0em 0.5em;'|H, [[medicine|human]]; V, [[veterinary]]; W, [[List of withdrawn drugs|withdrawn]]; P, ''[[Pseudomonas]]''; MR, [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']]; An, [[anaerobe]] [113] => |- style = "border-top: 4px solid darkgray;" [114] => | rowspan="15" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;" | 1 [115] => |[[Cefalexin]] || cephalexin ||Keflex|| [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=cephalexin H] [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=animal&query=cephalexin V]|| [116] => | rowspan="15" | '''Gram-positive:''' Activity against penicillinase-producing, methicillin-susceptible [[Staphylococcus|staphylococci]] and [[Streptococcus|streptococci]] (though they are not the drugs of choice for such infections). No activity against methicillin-resistant staphylococci or [[Enterococcus|enterococci]].{{citation needed|date=April 2018}} [117] => [118] => '''Gram-negative:''' Activity against ''[[Proteus (bacterium)|Proteus mirabilis]]'', some ''[[Escherichia coli]]'', and ''[[Klebsiella pneumoniae]]'' ("PEcK"), but have no activity against ''[[Bacteroides fragilis]]'', ''[[Pseudomonas]]'', ''[[Acinetobacter]]'', ''[[Enterobacter]]'', indole-positive ''[[Proteus (bacterium)|Proteus]]'', or ''[[Serratia]]''.{{citation needed|date=April 2018}} [119] => |- [120] => |[[Cefadroxil]] || cefadroxyl ||Duricef|| [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefadroxil H] || [121] => |- [122] => |[[Cefazolin]] ||cephazolin||Ancef, Kefzol|| [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefazolin H] || [123] => |- [124] => |[[Cefapirin]] ||cephapirin||Cefadryl|| [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=animal&query=cephapirin V]|| [125] => |- [126] => | [[Cefacetrile]] || cephacetrile || || || [127] => |- [128] => |[[Cefaloglycin]] || cephaloglycin|| || || [129] => |- [130] => |[[Cefalonium]] || cephalonium|| || || [131] => |- [132] => |[[Cefaloridine]] || cephaloradine|| || || [133] => |- [134] => |[[Cefalotin]] || cephalothin ||Keflin|| || [135] => |- [136] => |[[Cefatrizine]] || || || || [137] => |- [138] => |[[Cefazaflur]] || || || || [139] => |- [140] => |[[Cefazedone]] || || || || [141] => |- [142] => |[[Cefradine]] ||cephradine||Velosef|| || [143] => |- [144] => |[[Cefroxadine]]|| || || || [145] => |- [146] => |[[Ceftezole]]|| || || || [147] => |- style = "border-top: 4px solid darkgray;" [148] => | rowspan="6" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;"| 2 [149] => |[[Cefuroxime]] || || Altacef, Zefu, Zinnat, Zinacef, Ceftin, Biofuroksym,{{Cite web | last =Jędrzejczyk | first =Tadeusz | title =Internetowa Encyklopedia Leków | publisher =leki.med.pl | url =http://www.leki.med.pl/lek.phtml?id=428&idnlek=2682&menu=4 | access-date =2007-03-03 | archive-url =https://web.archive.org/web/20071007165458/http://www.leki.med.pl/lek.phtml?id=428&idnlek=2682&menu=4 | archive-date =7 October 2007 | url-status =dead }} Xorimax || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=cefuroxime H] || [150] => | rowspan = "6" |'''Gram-positive:''' Less than first-generation.{{citation needed|date=April 2018}} [151] => '''Gram-negative:''' Greater than first-generation: HEN ''[[Haemophilus influenzae]]'', ''[[Enterobacter aerogenes]]'' and some ''[[Neisseria]]'' + the PEcK described above.{{citation needed|date=April 2018}} [152] => |- [153] => |[[Cefprozil]] ||cefproxil|| Cefzil || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefprozil H]|| [154] => |- [155] => | [[Cefaclor]] || || Ceclor, Distaclor, Keflor, Raniclor || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefaclor H] || [156] => |- [157] => |[[Cefonicid]] || || Monocid || || [158] => |- [159] => |[[Cefuzonam]] || || || || [160] => |- [161] => |[[Cefamandole]] || || || W || [162] => |- [163] => | rowspan="7" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;" | (2) [164] => |[[Cefoxitin]] || || Mefoxin || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefoxitin H]|| An [165] => | rowspan="6"| [[Cephamycin]]s sometimes grouped with second-generation cephalosporins [166] => |- [167] => |[[Cefotetan]] || || Cefotan || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefotetan H]|| An [168] => |- [169] => |[[Cefmetazole]] || || Zefazone || || An [170] => |- [171] => |[[Cefminox]] || || || || [172] => |- [173] => |[[Cefbuperazone]] || || || || [174] => |- [175] => |[[Cefotiam]] || || Pansporin || [176] => | [177] => |- [178] => | [[Loracarbef]] || ||Lorabid || || || The [[carbacephem]] analog of cefaclor [179] => |- style = "border-top: 4px solid darkgray;" [180] => | rowspan="20" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;"| 3 [181] => |[[Cefdinir]] || ||Sefdin, Zinir, Omnicef, Kefnir || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefdinir H]|| [182] => |rowspan="20"|'''Gram-positive:''' Some members of this group (in particular, those available in an oral formulation, and those with antipseudomonal activity) have decreased activity against gram-positive organisms. [183] => Activity against staphylococci and streptococci is less with the third-generation compounds than with the first- and second-generation compounds.{{cite book |last1=Scholar |first1=Eric M. |last2=Scholar |first2=Eric Michael |last3=Pratt |first3=William B. |title=The Antimicrobial Drugs |date=2000 |publisher=Oxford University Press |isbn=978-0-19-512528-3 |page=108 |url=https://books.google.com/books?id=ZQ6KNRLWHLQC&pg=PA108 }} [184] => [185] => '''Gram-negative:''' Third-generation cephalosporins have a broad spectrum of activity and further increased activity against gram-negative organisms. They may be particularly useful in treating [[nosocomial infection|hospital-acquired infection]]s, 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 [[central nervous system]], making them useful against meningitis caused by pneumococci, meningococci, ''H. influenzae'', and susceptible ''E. coli'', ''Klebsiella'', and penicillin-resistant ''N. gonorrhoeae''. Since August 2012, the third-generation cephalosporin, ceftriaxone, is the only recommended treatment for gonorrhea in the United States (in addition to azithromycin or doxycycline for concurrent ''Chlamydia'' treatment). Cefixime is no longer recommended as a first-line treatment due to evidence of decreasing susceptibility.{{cite journal |author1=Centers for Disease Control and Prevention |title=Update to CDC's Sexually transmitted diseases treatment guidelines, 2010: oral cephalosporins no longer a recommended treatment for gonococcal infections |journal=Morbidity and Mortality Weekly Report |date=10 August 2012 |volume=61 |issue=31 |pages=590–594 |pmid=22874837 |url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6131a3.htm }} [186] => |- [187] => |[[Ceftriaxone]] || ||Rocephin || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Ceftriaxone H]|| [188] => |- [189] => |[[Ceftazidime]] || ||Meezat, Fortum, Fortaz || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=all&query=Ceftazidime H]|| P [190] => |- [191] => |[[Cefixime]] || ||Fixx, Zifi, Suprax || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefixime H] || [192] => |- [193] => |[[Cefpodoxime]] || ||Vantin, PECEF, Simplicef || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefpodoxime H] [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=animal&query=Cefpodoxime V]|| [194] => |- [195] => |[[Ceftiofur]] || ||Naxcel, Excenel || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Ceftiofur H] [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=animal&query=Ceftiofur V] || [196] => |- [197] => |[[Cefotaxime]] || ||Claforan || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefotaxime H]|| [198] => |- [199] => |[[Ceftizoxime]] || ||Cefizox || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Ceftizoxime H] || [200] => |- [201] => |[[Cefditoren]] || ||Zostom-O || [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefditoren H]|| [202] => |- [203] => |[[Ceftibuten]] || ||Cedax || [https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2dd58c88-142f-41ad-bc31-0a4fff074970 H] || [204] => |- [205] => |[[Cefovecin]] || ||Convenia || [https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2daeaf25-f98f-49d3-943c-f604a844d93c V]|| [206] => |- [207] => |[[Cefdaloxime]] || || || || [208] => |- [209] => | [[Cefcapene]]|| || || || [210] => |- [211] => |[[Cefetamet]] || || || || [212] => |- [213] => |[[Cefmenoxime]] || || || || [214] => |- [215] => |[[Cefodizime]] || || || || [216] => |- [217] => |[[Cefpimizole]] || || || || [218] => |- [219] => |[[Cefteram]] || || || || [220] => |- [221] => |[[Ceftiolene]] || || || || [222] => |- [223] => |[[Cefoperazone]] || || Cefobid || W{{cite journal |last1=Arumugham |first1=VB |last2=Gujarathi |first2=R |last3=Cascella |first3=M |title=Third Generation Cephalosporins |date=January 2021 |pmid=31751071 }} || P [224] => |- [225] => | style="text-align: center;" |(3) [226] => | [[Latamoxef]] [227] => | moxalactam || || W || || An [[oxacephem]] sometimes grouped with third-generation cephalosporins [228] => |- style = "border-top: 4px solid darkgray;" [229] => | rowspan = "8" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;"| 4 [230] => | [[Cefepime]] || ||Maxipime|| [https://dailymed.nlm.nih.gov/dailymed/search.cfm?labeltype=human&query=Cefepime H] || P [231] => | rowspan = "8"|'''Gram-positive:''' They are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation cephalosporins.{{citation needed|date=April 2018}} [232] => [233] => '''Gram-negative:''' Fourth-generation cephalosporins are [[zwitterion]]s that can penetrate the [[bacterial outer membrane|outer membrane]] of Gram-negative bacteria.{{Cite book|author1=Richard L Sweet|author2=Ronald S. Gibbs|title=Infectious Diseases of the Female Genital Tract|url=https://books.google.com/books?id=wuR_ngItU5oC&pg=PA403|access-date=8 September 2010|date=1 March 2009|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-7815-2|pages=403–}} They also have a greater resistance to β-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]]''.{{citation needed|date=April 2018}} [234] => [235] => Cefiderocol has been called a fourth-generation cephalosporin by only one source as of November 2019.{{cite web |title=CHEBI:140376 – cefiderocol |url=https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:140376 |website=ebi.ac.uk |publisher=EMBL-EBI |access-date=22 November 2019}} [236] => |- [237] => | [[Cefiderocol]] || ||Fetroja || [https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=75c0c785-38e0-4049-a6fb-b77581f5b35c H] || [238] => |- [239] => | [[Cefquinome]] || || || V [240] => |- [241] => | [[Cefclidine]] || || || || [242] => |- [243] => | [[Cefluprenam]] || || || || [244] => |- [245] => |[[Cefoselis]] || || || || [246] => |- [247] => | [[Cefozopran]] || || || || [248] => |- [249] => | [[Cefpirome]] || ||Cefrom || || [250] => |- [251] => |style="text-align: center;"| (4) || [[Flomoxef]] || || || || || An [[oxacephem]] sometimes grouped with fourth-generation cephalosporins [252] => |- style = "border-top: 4px solid darkgray;" [253] => |rowspan = "3" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;"| 5 [254] => | [[Ceftaroline]] || || || [https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3ecde48b-75a2-4beb-9999-369f3f61bb8a H]|| MR [255] => |rowspan = "3"| [[Ceftobiprole]] has been described as "fifth-generation" cephalosporin,{{Cite journal|author=Widmer AF |title=Ceftobiprole: a new option for treatment of skin and soft-tissue infections due to methicillin-resistant ''Staphylococcus aureus'' |journal=Clin. Infect. Dis. |volume=46 |issue=5 |pages=656–658 |date=March 2008 |pmid=18225983 |doi=10.1086/526528 |doi-access=free |url=http://doc.rero.ch/record/295834/files/46-5-656.pdf }}{{cite journal |last1=Kosinski |first1=Mark A. |last2=Joseph |first2=Warren S. |title=Update on the Treatment of Diabetic Foot Infections |journal=Clinics in Podiatric Medicine and Surgery |date=July 2007 |volume=24 |issue=3 |pages=383–396 |doi=10.1016/j.cpm.2007.03.009 |pmid=17613382 }} though acceptance for this terminology is not universal. Ceftobiprole has anti-[[pseudomonal]] activity and ''appears'' to be less susceptible to development of resistance. [[Ceftaroline]] has also been described as "fifth-generation" cephalosporin, but does not have the activity against ''Pseudomonas aeruginosa'' or vancomycin-resistant enterococci that ceftobiprole has.{{Cite journal|author=Kollef MH |title=New antimicrobial agents for methicillin-resistant ''Staphylococcus aureus'' |journal=Crit Care Resusc |volume=11 |issue=4 |pages=282–6 |date=December 2009 |pmid=20001879 }} [[Ceftolozane]] is an option for the treatment of complicated intra-abdominal infections and complicated urinary tract infections. It is combined with the [[beta-lactamase|β-lactamase]] inhibitor [[tazobactam]], as multi-drug resistant bacterial infections will generally show resistance to all [[beta-lactam antibiotic|β-lactam antibiotics]] unless this enzyme is inhibited.{{Cite journal | pmid = 17145788| pmc = 1803152| year = 2007| last1 = Takeda| first1 = S| title = In vitro and in vivo activities of a new cephalosporin, FR264205, against Pseudomonas aeruginosa| journal = Antimicrobial Agents and Chemotherapy| volume = 51| issue = 3| pages = 826–30| last2 = Nakai| first2 = T| last3 = Wakai| first3 = Y| last4 = Ikeda| first4 = F| last5 = Hatano| first5 = K| doi = 10.1128/AAC.00860-06}}{{Cite journal | pmid = 18701284| year = 2008| last1 = Toda| first1 = A| title = Synthesis and SAR of novel parenteral anti-pseudomonal cephalosporins: Discovery of FR264205| journal = Bioorganic & Medicinal Chemistry Letters| volume = 18| issue = 17| pages = 4849–52| last2 = Ohki| first2 = H| last3 = Yamanaka| first3 = T| last4 = Murano| first4 = K| last5 = Okuda| first5 = S| last6 = Kawabata| first6 = K| last7 = Hatano| first7 = K| last8 = Matsuda| first8 = K| last9 = Misumi| first9 = K| last10 = Itoh| first10 = K| last11 = Satoh| first11 = K| last12 = Inoue| first12 = S| doi = 10.1016/j.bmcl.2008.07.085| doi-access = free}}{{Cite journal | pmid = 21321149| pmc = 3088243| year = 2011| last1 = Sader| first1 = H. S.| title = Antimicrobial activity of CXA-101, a novel cephalosporin tested in combination with tazobactam against Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides fragilis strains having various resistance phenotypes| journal = Antimicrobial Agents and Chemotherapy| volume = 55| issue = 5| pages = 2390–4| last2 = Rhomberg| first2 = P. R.| last3 = Farrell| first3 = D. J.| last4 = Jones| first4 = R. N.| doi = 10.1128/AAC.01737-10}}{{Cite journal | pmid = 23274659| pmc = 3623364| year = 2013| last1 = Craig| first1 = W. A.| title = In vivo activities of ceftolozane, a new cephalosporin, with and without tazobactam against Pseudomonas aeruginosa and Enterobacteriaceae, including strains with extended-spectrum β-lactamases, in the thighs of neutropenic mice| journal = Antimicrobial Agents and Chemotherapy| volume = 57| issue = 4| pages = 1577–82| last2 = Andes| first2 = D. R.| doi = 10.1128/AAC.01590-12}}{{Cite journal | pmid = 24352909| year = 2014| last1 = Zhanel| first1 = G. G.| title = Ceftolozane/tazobactam: A novel cephalosporin/β-lactamase inhibitor combination with activity against multidrug-resistant gram-negative bacilli| journal = Drugs| volume = 74| issue = 1| pages = 31–51| last2 = Chung| first2 = P| last3 = Adam| first3 = H| last4 = Zelenitsky| first4 = S| last5 = Denisuik| first5 = A| last6 = Schweizer| first6 = F| last7 = Lagacé-Wiens| first7 = P. R.| last8 = Rubinstein| first8 = E| last9 = Gin| first9 = A. S.| last10 = Walkty| first10 = A| last11 = Hoban| first11 = D. J.| last12 = Lynch Jp| first12 = 3rd| last13 = Karlowsky| first13 = J. A.| s2cid = 44694926| doi = 10.1007/s40265-013-0168-2| doi-access = free}} [256] => |- [257] => | [[Ceftolozane]] || || Zerbaxa || [https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70ac1d90-eff3-4f0b-9f46-5846c571b32f H] || [258] => |- [259] => | [[Ceftobiprole]] || || || || MR [260] => |- style = "border-top: 4px solid darkgray;" [261] => | rowspan ="15" "3" style="vertical-align: top; text-align: center; padding: 2.25em 0.5em;" | ? || [[Cefaloram]] || || || || [262] => | rowspan ="15" |These cephems have progressed far enough to be named, but have not been assigned to a particular generation. [[Nitrocefin]] is a chromogenic cephalosporin substrate, and is used for detection of β-lactamases.{{citation needed|date=April 2018}} [263] => |- [264] => |[[Cefaparole]] || || || || [265] => |- [266] => |[[Cefcanel]] || || || || [267] => |- [268] => |[[Cefedrolor]] || || || || [269] => |- [270] => |[[Cefempidone]] || || || || [271] => |- [272] => |[[Cefetrizole]] || || || || [273] => |- [274] => |[[Cefivitril]] || || || || [275] => |- [276] => |[[Cefmatilen]] || || || || [277] => |- [278] => |[[Cefmepidium]] || || || || [279] => |- [280] => |[[Cefoxazole]] || || || || [281] => |- [282] => |[[Cefrotil]] || || || || [283] => |- [284] => |[[Cefsumide]] || || || || [285] => |- [286] => |[[Ceftioxide]] || || || || [287] => |- [288] => |[[Cefuracetime]] || || || || [289] => |- [290] => |[[Nitrocefin]] || || || || [291] => |} [292] => [293] => ==History== [294] => {{see also|Discovery and development of cephalosporins}} [295] => Cephalosporin compounds were first isolated from cultures of ''[[Acremonium strictum]]'' from a sewer in [[Sardinia]] in 1948 by Italian scientist [[Giuseppe Brotzu]].{{cite book |last1=Podolsky |first1=Daniel K. |title=Cures out of Chaos |date=1998 |publisher=CRC Press |isbn=978-1-4822-2973-8 }}{{page needed|date=June 2020}} He noticed these cultures produced substances that were effective against ''[[Salmonella typhi]]'', the cause of [[typhoid fever]], which had β-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-ACA|7-aminocephalosporanic acid]] (7-ACA), was derived from cephalosporin C and proved to be analogous to the penicillin nucleus [[6-APA|6-aminopenicillanic acid]] (6-APA), 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, [[cefalotin]] (cephalothin), was launched by [[Eli Lilly and Company]] in 1964.{{citation needed|date=June 2020}} [296] => [297] => ==References== [298] => {{Reflist}} [299] => [300] => ==External links== [301] => * [https://web.archive.org/web/20150921163439/http://www.courses.ahc.umn.edu/pharmacy/6124/remmel_notes/cephalosporins.pdf Cephalosporins] [302] => [303] => {{CephalosporinAntiBiotics}} [304] => {{Authority control}} [305] => [306] => [[Category:Acetaldehyde dehydrogenase inhibitors]] [307] => [[Category:Cephalosporin antibiotics| ]] [308] => [[Category:Medical mnemonics]] [] => )
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Cephalosporin

Cephalosporin is a type of antibiotic that is commonly used to treat bacterial infections. It belongs to the broader class of β-lactam antibiotics, which also includes penicillin.

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It belongs to the broader class of β-lactam antibiotics, which also includes penicillin. Cephalosporin was first discovered in 1945 by Italian scientist Giuseppe Brotzu, and its commercial production began in the 1960s. Cephalosporin is effective against a wide range of bacteria, including both gram-positive and gram-negative strains. It works by inhibiting the synthesis of the bacterial cell wall, leading to the destruction of the bacteria. This mechanism of action makes cephalosporin particularly useful in treating skin and soft tissue infections, urinary tract infections, respiratory tract infections, and certain sexually transmitted diseases. There are several generations of cephalosporin, each with its own spectrum of activity and unique characteristics. The first-generation drugs are effective against many gram-positive bacteria but have limited activity against gram-negative bacteria. As the generations progress, cephalosporins become more effective against gram-negative bacteria and gain broader coverage against a wider range of organisms. While generally safe and well-tolerated, cephalosporin can cause side effects, the most common being gastrointestinal problems and allergic reactions. Cross-reactivity with penicillin allergy is also a concern, although studies have shown that the risk is often overestimated. Cephalosporin has played a crucial role in the treatment of bacterial infections for decades and continues to be an important class of antibiotics. Ongoing research and development efforts aim to improve efficacy, reduce resistance, and minimize side effects associated with this valuable therapeutic agent.

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