Monobactam
{{Short description|Monocyclic β-lactam antibiotics}}
{{Infobox drug class
| Name = Aztreonam
| Image = Aztreonam structure.svg
| ImageClass = skin-invert-image
| Alt =
| Caption = Aztreonam. (The four-membered ring at the bottom is the β-lactam. There is a second thiazole ring, but it is not fused to the β-lactam ring.)
| Use = Bacterial infection
| Biological_target =
| ATC_prefix = J01DF
| MeshID = D008997
| Drugs.com =
| Consumer_Reports =
| medicinenet =
| rxlist =
}}
Monobactams are bacterially-produced monocyclic β-lactam antibiotics. The β-lactam ring is not fused to another ring, in contrast to most other β-lactams.{{cite journal|title=Monobactams|author1=Klaus R. Lindner|author2=Daniel P. Bonner|author3=William H. Koster|journal=Kirk-Othmer Encyclopedia of Chemical Technology|publisher=Wiley-VCH|doi=10.1002/0471238961.1315141512091404.a01|year=2000|isbn=0471238961}}
Monobactams are narrow-spectrum antibiotics{{Cite book |last=Murray |first=Patrick R. |title=Medical microbiology |last2=Rosenthal |first2=Ken S. |last3=Pfaller |first3=Michael A. |date=2021 |publisher=Elsevier |isbn=978-0-323-67450-8 |edition=9th |location= |pages=172}} effective only against (strictly or facultatively{{Cite book |title=Sherris Medical Microbiology - 7th Edition |pages=437}}) aerobic Gram-negative bacilli,{{Cite book |last=Ritter |first=James |title=Rang & Dale's Pharmacology |last2=Flower |first2=Rod |last3=Henderson |first3=Graeme |last4=Loke |first4=Yoon Kong |last5=MacEwan |first5=David |last6=Rang |first6=H. P. |date=2020 |publisher=Elsevier |isbn=978-0-7020-7448-6 |edition=9th |location= |pages=665}}{{Cite web |title=Dictionnaire médical de l'Académie de Médecine |url=https://www.academie-medecine.fr/le-dictionnaire/index.php?q=monobactame |access-date=2024-01-13 |website=www.academie-medecine.fr}} exhibiting a high level of resistance to beta-lactamases of these organisms. Due to their narrow spectrum, monobactams can be used to treat infections by susceptible bacteria without disrupting the patient's microbiota. Monobactams are nevertheless seldom used.
Aztreonam is the archetypal monobactam.{{Cite web |title=Monobactams - Infectious Diseases |url=https://www.msdmanuals.com/professional/infectious-diseases/bacteria-and-antibacterial-drugs/monobactams |access-date=2024-01-13 |website=MSD Manual Professional Edition |language=en}} Other monobactams include tigemonam,{{cite journal |vauthors=Fuchs PC, Jones RN, Barry AL |date=March 1988 |title=In vitro antimicrobial activity of tigemonam, a new orally administered monobactam |journal=Antimicrob. Agents Chemother. |volume=32 |issue=3 |pages=346–9 |doi=10.1128/aac.32.3.346 |pmc=172173 |pmid=3259122}} nocardicin A, carumonam and tabtoxin. An example of a monobactam that lacks antibiotic activity, but is used clinically for other purposes, is the cholesterol absorption inhibitor ezetimibe which is used to treat hypercholesterolemia.{{cite web |title=Ezetimibe Monograph for Professionals |url=https://www.drugs.com/monograph/ezetimibe.html |website=Drugs.com |publisher=American Society of Health-System Pharmacists |access-date=13 April 2019 |archive-date=17 June 2019 |archive-url=https://web.archive.org/web/20190617034725/https://www.drugs.com/monograph/ezetimibe.html |url-status=live }}
Pharmacology
Monobactams exert their antibacterial effects by binding to penicillin-binding proteins (PBPs), thereby inhibiting bacterial wall synthesis. Monobactams exhibit poor affinity for PBPs of Gram-positive bacteria as well as of strictly anaerobic bacteria, resulting in a lack of significant antimicrobial activity against these kinds of organisms. Monobactams are synergetic with aminoglycosides, and piperacillin.
Bacterial resistance to monobactams have been observed, and is mediated by bacterial beta-lactamases.
Adverse effects
Adverse effects to monobactams can include skin rash and occasional abnormal liver functions.{{cn|date=January 2023}}
Monobactam antibiotics exhibit no IgE cross-reactivity reactions with penicillin but have shown some cross reactivity with cephalosporins, most notably ceftazidime, which contains an identical side chain as aztreonam.{{Cite book|title=Applied therapeutics : the clinical use of drugs.|others=Alldredge, Brian K.,, Revision of: Koda-Kimble, Mary Anne., Revision of: Young, Lloyd Y.|isbn=9781609137137|edition=Tenth|location=Philadelphia|oclc=759179443|last1 = Alldredge|first1 = Brian K.|last2 = Corelli|first2 = Robin L.|last3 = Ernst|first3 = Michael E.|date = February 2012}} Monobactams can trigger seizures in patients with history of seizures, although the risk is lower than with penicillins.{{cn|date=January 2023}}
Research
Siderophore-conjugated monobactams show promise for the treatment of multi drug-resistant pathogens.{{cite book |last1=Gumienna-Kontecka |first1=Elzbieta |title=Essential Metals in Medicine:Therapeutic Use and Toxicity of Metal Ions in the Clinic |last2=Carver |first2=Peggy L. |date=2019 |journal=Metal Ions in Life Sciences |publisher=de Gruyter GmbH |isbn=978-3-11-052691-2 |editor1-last=Sigel |editor1-first=Astrid |volume=19 |location=Berlin |pages=181–202 |chapter=Chapter 7. Building a Trojan Horse: Siderophore-Drug Conjugates for the Treatment of Infectious Diseases |doi=10.1515/9783110527872-013 |pmid=30855108 |editor2-last=Freisinger |editor2-first=Eva |editor3-last=Sigel |editor3-first=Roland K. O. |editor4-last=Carver |editor4-first=Peggy L. (Guest editor) |s2cid=73727689}}
References
{{reflist}}