Iclaprim, a novel diaminopyrimidine for the treatment of resistant gram-positive infections

Annals of Pharmacotherapy

Volumn 43, Issue 6, 2009, Pages 1107-1114

  Sincak, Carrie A ^a   Schmidt, Justin M ^a  

^a MIDWESTERN UNIVERSITY   (United States)

Author keywords

AR 100; Dihydrofolate reductase; Gram positive; Iclaprim

Indexed keywords

BETA LACTAM ANTIBIOTIC; CLINDAMYCIN; COTRIMOXAZOLE; DALFOPRISTIN PLUS QUINUPRISTIN; DIHYDROFOLATE REDUCTASE; ERYTHROMYCIN; ICLAPRIM; LINEZOLID; MACROLIDE; POLYPEPTIDE ANTIBIOTIC AGENT; QUINOLINE DERIVED ANTIINFECTIVE AGENT; TRIMETHOPRIM; VANCOMYCIN;

ANTIBACTERIAL ACTIVITY; AREA UNDER THE CURVE; BACTERIAL SKIN DISEASE; BACTERICIDAL ACTIVITY; CLINICAL TRIAL; DIARRHEA; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG FEVER; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG SENSITIVITY; DRUG STRUCTURE; DRUG TOLERABILITY; GRAM NEGATIVE BACTERIUM; GRAM NEGATIVE INFECTION; GRAM POSITIVE BACTERIUM; GRAM POSITIVE INFECTION; HEALTHCARE ASSOCIATED PNEUMONIA; HUMAN; INFECTION RESISTANCE; LOWER RESPIRATORY TRACT INFECTION; NAUSEA; PNEUMONIA; PRIORITY JOURNAL; QT PROLONGATION; REVIEW; SIDE EFFECT; STAPHYLOCOCCAL SKIN INFECTION; STAPHYLOCOCCUS AUREUS; THROMBOCYTE COUNT; TIME TO MAXIMUM PLASMA CONCENTRATION; UNSPECIFIED SIDE EFFECT; VENTILATOR ASSOCIATED PNEUMONIA;

ANTI-BACTERIAL AGENTS; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, BACTERIAL; FOLIC ACID ANTAGONISTS; GRAM-POSITIVE BACTERIA; GRAM-POSITIVE BACTERIAL INFECTIONS; HUMANS; MICROBIAL SENSITIVITY TESTS; PYRIMIDINES; TETRAHYDROFOLATE DEHYDROGENASE;

EID: 67249100705     PISSN: 10600280     EISSN: None     Source Type: Journal    
DOI: 10.1345/aph.1L167     Document Type: Review

References (42)

1. Arpida Ltd. Press releases. www.arpida.ch/index.php?MenuID=30&UserID= 1&ContentID=20 (accessed 2008 Jan 28).
2. Hawser S, Lociuro S, Islam K. Dihydrofolate reductase inhibitors as antibacterial agents. Biochem Pharmacol 2006;71:941-948 (Pubitemid 43306786)
3. Peppard WJ, Johnston CJ, Urmanski A. Pharmacologic options for CNS infections caused by resistant gram-positive organisms. Expert Rev Anti Infect Ther 2008;6:83-99.
4. Huovinen P. Resistance to trimethoprim-sulfamethoxazole. Clin Infect Dis 2001;32:1608-1614 (Pubitemid 32458729)
5. Adrian PV, DuPlessis M, Klugman KP, Amyes SG. New trimethoprimresistant dihydrofolate reductase cassette, dfrXV, inserted in a class 1 integron. Antimicrob Agents Chemother 1998;42:2221-2224 (Pubitemid 28420353)
6. Schneider P, Hawser S, Islam K. Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria. Bioorg Med Chem Lett 2003;13:4217-4221 (Pubitemid 37410316)
7. Kohlhoff SA, Sharma R. Iclaprim. Expert Opin Investig Drugs 2007;16:1441-1448
8. Peppard WJ, Schuenke CD. Iclaprim, a diaminopyrimidine dihydrofolate reductase inhibitor for the potential treatment of antibiotic-resistant staphylococcal infections. Curr Opin Investig Drugs 2008;9:210-225 (Pubitemid 351206380)
9. Hartman PG, Kompis I, Jaeger J, Mukhija S, Islam K. AR-100, a novel diaminopyrimidine, can overcome TMP-resistance in staphylococci and streptococci (F-2020). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
10. Bajaksouzian S, Windau A, Appelbaum PC, Jacobs MR. AR-100, a novel diaminopyrimidine compound: activity against staphylococci and enterococci (F-2024). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
11. Gemmell CG, Middlemas G. AR-100, a novel diaminopyrimidine: activity against various clinical isolates of gram-positive and gram-negative bacteria (F-2022). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
12. Good CE, Windau A, Bajaksouzian S, Jacobs MR, Appelbaum PC. AR-100, a novel diaminopyrimidine compound: activity against streptococci (F-2023). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
13. Hawser S, Weiss L, Fischer M, Gillessen D, Kompis I, Islam K. AR-100, a novel diaminopyrimidine compound: activity against selected grampositive and gram-negative bacterial pathogens and synergy with other antibiotics (F-2019). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
14. Hawser S, Weiss L, Fischer M, et al. AR-100, a novel diaminopyrimidine compound: bactericidal activity and post-antibiotic effect on gram-positive pathogens (F-2029). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
15. Jones RN, Fritsche TR, Hawser S, Islam K, Sader HS. In vitro activity of iclaprim, a novel diaminopyrimidine, tested against b-haemolytic streptococci from the U.S. and Europe: results from the international study of iclaprim susceptibility (ISIS) (E-911). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
16. Sader HS, Fritsche T, Islam K, Hawser S, Jones RN. Antimicrobial activity of iclaprim tested against recent S. aureus clinical isolates: results from the international study of iclaprim susceptibility (ISIS) (E-902). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
17. Sader HS, Jones RN, Rhomberg PR, Islam K, Hawser S, Fritsche TR. Comparative evaluation of iclaprim potency and bactericidal activity tested against enterococci: results from the international study of iclaprim susceptibility (ISIS) (E-910). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
18. Mason E, Lamberth L, Hawser S. In vitro activity of iclaprim against community-acquired and nosocomial clinical isolates of Staphylococcus aureus (E-904). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
19. Zhanel GG, Palatnick LP, Hisanaga TL, et al. Activity of iclaprim against penicillin, erythromycin, trimethoprim/sulfamethoxazole or ciprofloxacin resistant Streptococcus pneumoniae from Canada (E-2002). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
20. Then RL, Hartman PG, Locher HH. AR-100, a novel diaminopyrimidine compound: in vitro activity against pneumococci (F-2021). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
21. Jacobs MR, Windau A, Bajaksouzian S, Appelbaum PC. AR-100, a novel diaminopyrimidine compound: activity against Haemophilus species and Moraxella catarrhalis (F-2026). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
22. Milatovic D, Verhoef J, Fluit AC. In vitro activity of iclaprim (AR-100) against gram-positive and gram-negative bacteria (E-2006). In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003.
23. Windau A, Bajaksouzian S, Appelbaum PC, Jacobs MR. AR-100, a novel diaminopyrimidine compound: activity against Enterobacteriaceae (F-2025). In: Abstracts of the 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, 2002.
24. Biedenbach DJ, Sader HS, Fritsche TR, Hawser S, Lociuro S, Jones RN. In vitro activity of iclaprim and comparison agents tested against Neisseria gonorrhoeae including growth stimulating effects (E-908). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
25. Donati M, Pignanelli S, Shurdhi A, Hawser S, Lociuro S, Cevenini R. In vitro activity of iclaprim and comparators against Chlamydia trachomatis (E-903). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
26. Hammerschlag MR, Kohlhoff S, Roblin PM, Reznik T, Hawser S, Islam K. In vitro activity of iclaprim, a novel diaminopyrimidine compound, against Chlamydia trachomatis and C. pneumoniae (E-2001). In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003.
27. Morrissey I, Hawser S, Islam K, Williams L, Leakey A, Shackcloth J. Activity of iclaprim and comparators against atypical bacterial respiratory pathogens (E-2003). In: Abstracts of the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2003.
28. Jones ME, Hawser S, Islam K, Torres MK, Draghi DC, Sahm DF. Iclaprim (ICL): defined quality control (QC) limits for MIC and disk diffusion (DD) susceptibility testing according to CLSI M23-A2 procedures (D -243). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
29. Engelhardt A, Yusof A, Bylund L, Ho P. Comparative evaluation of iclaprim (ICL) MIC testing with Etest and CLSI reference methods (D - 244). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
30. Brandt R, John BA, Henderson SJ, Harris SE, Islam K. Absorption, pharmacokinetics, metabolism, and excretion of iclaprim in healthy humans (A-805). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
31. Brandt R, Matthews A, Hall M, Islam K. Interactions of iclaprim with human cytochrome P450 enzymes (A-807). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, 2007.
32. Brandt R, Neuenhofer D, Thomsen T, Hadvary P, Islam K. Pharmacokinetics and bioavailability of iclaprim oral and intravenous formulations in humans (A-806). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
33. Brandt R, Warrington S, McBurney A, Islam K. Tolerability and pharmacokinetics of single and repeat ascending doses of iclaprim in healthy adults (A-804). In: Abstracts of the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 2007.
34. Andrews J, Honeybourne D, Ashby J, et al. Concentrations in plasma, epithelial lining fluid, alveolar macrophages and bronchial mucosa after a single intravenous dose of 1.6 mg/kg of iclaprim (AR-100) in healthy men. J Antimicrob Chemother 2007;60:677-680 (Pubitemid 47299890)
35. Zhanel GG, Goolia M, Rusen J, et al. Pharmacodynamic activity of iclaprim vs. resistant Streptococcus pneumoniae using an in vitro model. In: 14th European Congress of Clinical Microbiology and Infectious Diseases, Prague, Czech Republic, 2004.
36. Krievens D, Leighton A, Brandt R, et al. Efficacy and safety of intravenous iclaprim in complicated skin and skin structure infections: results of a phase 2 study (L-1579). In: Proceedings of the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 2005.
37. Stevens D, Leighton A, Dankner W, Islam K, Hadvary P. Efficacy of iclaprim in complicated skin and skin structure infections: preliminary results of ASSIST-1 (1079). In: Abstracts of the 45th Annual Meeting of Infectious Diseases Society of America, San Diego, CA, 2007.
38. Hadvary P, de la Motte S, Klinger J, Islam K. Pharmacokinetics of iclaprim in subjects with varying degrees of hepatic or renal insufficiency or obesity (448). In: Abstracts of the 45th Annual Meeting of Infectious Diseases Society of America, San Diego, CA, 2007.
39. Leighton A, Dankner W, Stevens D, Islam K, Hadvary P. Safety of iclaprim in complicated skin and skin structure infections: ASSIST-1 results (1104). In: Abstracts of the 45th Annual Meeting of Infectious Disease Society of America, San Diego, CA, 2007.
40. Hadvary P, Leighton A, Wargenau M, Thomsen T, Islam K. Evaluation of the effect of iclaprim on the QT interval in healthy volunteers (432). In: Abstracts of the 45th Annual Meeting of Infectious Diseases Society of America, San Diego, CA, 2007.
41. Hadvary P, Dankner W, Leighton A, Stevens D, Islam K. Effect of iclaprim on the QT interval based on results of ASSIST-1 (1083). In: Abstracts of the 45th Annual Meeting of Infectious Diseases Society of America, San Diego, CA, 2007.
42. FDA briefing document for anti-infective drugs advisory committee meeting. Iclaprim for the treatment of complicated skin structure infections. November 20, 2008. www.fda.gov/ohrms/dockets/ac/briefing/2008-4394b3-01-FDA.pdf (accessed 2009 Apr 23)