Ciclacillin Explained

Ciclacillin (INN) or cyclacillin (USAN), trade names Cyclapen, Cyclapen-W, Vastcillin, and others, is an aminopenicillin antibiotic. Its spectrum of activity is similar to that of ampicillin, although it is less susceptible to beta-lactamases than ampicillin and has much higher bioavailability.^[1] A large randomized, double-blind clinical trial published in 1978 also showed that ciclacillin is associated with significantly fewer and milder adverse effects than ampicillin;^[2] later studies seemed to confirm this improved tolerability, at least in children.^{[3] [4]}

Ciclacillin has been superseded by newer antibiotics and is no longer in clinical use, at least in the United States.^[5] __TOC__

Synthesis

In an attempt to form orally active penicillins unrelated to ampicillin, use was made of the fact that certain spiro α-amino acids, such as Cycloleucine, are well absorbed orally and transported like normal amino acids.Reaction of cyclohexanone with ammonium carbonate and KCN under the conditions of the Bucherer-Bergs reaction led to hydantoin 1. On acid hydrolysis, α-amino acid 2 resulted. Treatment with phosgene both protected the amino group and activated the carboxyl group toward amide formation (as 3) and reaction with 6-aminopenicillanic acid (6-APA) gave cyclacillin (4).

This artifice seems to have worked, since cyclacillin is more active in vivo than its in vitro spectrum suggests.

Further reading

• Scheld WM, Sydnor A, Farr B, Gratz JC, Gwaltney JM . Comparison of cyclacillin and amoxicillin for therapy for acute maxillary sinusitis . Antimicrobial Agents and Chemotherapy . 30 . 3 . 350–353 . September 1986 . 3535660 . 180557 . 10.1128/aac.30.3.350 .

Notes and References

1. Warren GH . Cyclacillin: microbiological and pharmacological properties and use in chemotherapy of infection - a critical appraisal . Chemotherapy . 22 . 3–4 . 154–182 . 1976 . 773605 . 10.1159/000221924 .
2. Gold JA, Hegarty CP, Deitch MW, Walker BR . Double-blind clinical trials of oral cyclacillin and ampicillin . Antimicrobial Agents and Chemotherapy . 15 . 1 . 55–58 . January 1979 . 371540 . 352600 . 10.1128/aac.15.1.55 .
3. McLinn SE, Goldberg F, Kramer R, Saltstein E, Bomze JP, Deitch MW . Double-blind multicenter comparison of cyclacillin and amoxicillin for the treatment of acute otitis media . The Journal of Pediatrics . 101 . 4 . 617–621 . October 1982 . 6750067 . 10.1016/S0022-3476(82)80724-5 .
4. McLinn SE, Kaplan J, West N . Multicenter comparison of cyclacillin and amoxicillin in the treatment of acute streptococcal pharyngitis . Clinical Therapeutics . 5 . 3 . 299–304 . 1983 . 6342785 .
5. Book: Gorbach SL, Bartlett JG, Blacklow NR . Infectious diseases . 3rd . . Hagerstown, MD . 2004 . 186 . 0-7817-3371-5 . Retrieved on September 7, 2008 through Google Book Search.