Cephalosporins in clinical development

Expert Opinion on Investigational Drugs

Volumn 13, Issue 8, 2004, Pages 973-985

  Page, Malcolm G P ^a  

^a BASILEA PHARMACEUTICA INTERNATIONAL LTD   (Switzerland)

Author keywords

lactam; Anti MRSA; BAL 5788; BAL 9141; Cephalosporin; PPI 0903; RWJ 442831; RWJ 54428; S 3578; TAK 599

Indexed keywords

7 [[(2 AMINO 5 CHLORO 4 THIAZOLYL)(HYDROXYIMINO)ACETYL]AMINO] 3 [[3 [[(2 AMINOETHYL)THIO]METHYL] 4 PYRIDINYL]THIO] 8 OXO 5 THIA 1 AZABICYCLO[4.2.0]OCT 2 ENE 2 CARBOXYLIC ACID; 7BETA [2 (5 AMINO 1,2,4 THIADIAZOL 3 YL) 2 ETHOXYIMINOACETAMIDO] 3 [(1 METHYLAMINOPROPYL 1H IMIDAZO[4,5 B]PYRIDINIUM 4 YL)METHYL] 3 CEPHEM 4 CARBOXYLIC ACID; AMOXICILLIN PLUS CLAVULANIC ACID; ANTIBIOTIC AGENT; BETA LACTAMASE; CAB 175; CB 181963; CEFADROXIL; CEFALEXIN; CEFAPIRIN; CEFAZOLIN; CEFEPIME; CEFOTAXIME; CEFRADINE; CEFTAZIDIME; CEFTIZOXIME; CEFTIZOXIME ALAPIVOXIL; CEFTOBIPROLE; CEFTOBIPROLE MEDOCARIL; CEFTRIAXONE; CEPHALOSPORIN DERIVATIVE; CILASTATIN PLUS IMIPENEM; DURICEL; METICILLIN; PENICILLIN G; PPI 0903; RO 639141; RWJ 442831; T 91825; TAK 599; UNCLASSIFIED DRUG; UNINDEXED DRUG; VANCOMYCIN;

ANAEROBIC BACTERIUM; ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; AREA UNDER THE CURVE; BACTERIAL INFECTION; CLINICAL TRIAL; DIARRHEA; DRUG CLASSIFICATION; DRUG ERUPTION; DRUG MECHANISM; DRUG METABOLISM; DRUG STABILITY; DRUG STRUCTURE; DRUG SYNTHESIS; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; HOSPITAL INFECTION; HUMAN; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; MULTIDRUG RESISTANCE; NAUSEA AND VOMITING; NONHUMAN; PENICILLIN RESISTANCE; REVIEW; STAPHYLOCOCCUS; STREPTOCOCCUS PNEUMONIAE;

ANTI-BACTERIAL AGENTS; CEPHALOSPORINS; DRUG RESISTANCE, MULTIPLE; GRAM-POSITIVE BACTERIA; MOLECULAR STRUCTURE;

EID: 4344660156     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.13.8.973     Document Type: Review

References (147)

1. BROTZU G: Richerche su di un nuovo antibiotico. Lavori Dell'Istituto D'Igiene di Cagliari (1948):1-11.
2. ABRAHAM EP, NEWTON GGF: Structure of cephalosporin C. Biochem. J. (1961) 79:377-393.
3. HODGKIN DC, MASLEN EN: The X-ray analysis of the structure of cephalosporin C. Biochem J. (1961) 79:393-402
4. HEINZE-KRAUSS I, ANGEHRN P, GUERRY P et al.: Synthesis and structure-activity relationship of (lactamylvinyl)cephalosporins exhibiting activity against staphylococci, pneumococci, and enterococci. J. Med. Chem. (1996) 39:1864-1871.
5. HARDMAN JC, LIMBIRD LE, GILMAN AG: Goodman and Gilman's The Pharmacological Basis of Therapeutics (9th Edition) McGraw-Hill Professional, NY, USA (1996).
6. SHETTY N, SHULMAN RI, SCOTT GM: An audit of first generation cephalsoporin usage. J. Hosp. Infect. (1999) 41:229-232.
7. HILL DA, HERFORD T, PARRATT D: Antibiotic usage and methicillin-resistant Staphylococcus aureus: an analysis of causality. J. Antimicrob. Chemother. (1998) 42:676-677.
8. SCHENTAG JJ, HYATT JM, CARR JR et al.: Genesis of methicillin-resistant Staphylococcus aureus (MRSA), how treatment of MRSA infections has selected for vancomycin-resistant Enterococcus faecium, and the importance of antibiotic management and infection control. Clin. Infect. Dis. (1998) 26:1204-1214.
9. RICE L: Evolution and clinical importance of extended-spectrum β-lactamases. Chest (2001) 11(Suppl. 2):S391-S396.
10. PATTERSON JE. Antibiotic utilization. Is there an effect on antimicrobial resistance? Chest (2001) 119(Suppl. 2):S426-S430.
11. DU B, CHEN D, LIU D et al.: Restriction of third-generation cephalosporin use decreases infection-related mortality. Crit. Care Med. (2003) 31:1088-93.
12. GHUYSEN JM: Molecular structures of penicillin-binding proteins and β-lactamases. Trends Microbiol. (1994) 2:372-380.
13. GOFFIN C; GHUYSEN JM: Multimodular penicillin-binding proteins: an enigmatic family of orthologs and paralogs. Microbiol. Mol. Biol. Rev. (1998) 62:1079-93.
14. BRAMHILL D: Cell Division. Ann. Rev. Cell Dev. Biol. (1997) 13:395-424.
15. VOLLMER W, VON RECHENBERG M, HÖLTE J-V: Demonstration of molecular interactions between the murein polymerase PBP1B, the Lytic transglycosylase MltA, and the scaffolding protein MipA of Escherichia coli. J. Biol. Chem. (1999) 274:6726-6734.
16. KITANO K, TOMASZ A. Triggering of autolytic cell wall degradation in Escherichia coli by β-lactam antibiotics. Antimicrob. Agents Chemother. (1979) 16: 838-848.
17. SHOCKMAN G D, DANEO-MOORE L, KARIYAMA R, MASSIDDA O: Bacterial walls, peptidoglycan hydrolases, autolysins, and autolysis. Microbial Drug Res. (1996) 2:95-98.
18. GIESBRECHT P, KERSTEN T, MAIDHOF H, WECKE J: Staphylococcal cell wall: Morphogenesis and fatal variations in the presence of penicillin. Microbiol. Mol. Biol. Rev. (1998) 62:1371-1414.
19. SUGINAKA H: Roles of autolysins produced from Staphylococcus aureus. Hifu (1998) 40(Suppl. 20):13-18.
20. LEWIS K: Programmed death in bacteria. Microbiol. Mol. Biol Rev. (2000) 64:503-514.
21. SABATH LD, WHEELER N, LAVERDIERE M, BLAZEVIC D, WILKINSON BJ: A new type of penicillin resistance of Staphylococcus aureus. Lancet (1977) 1(8009):443-447.
22. FERNEBRO J, ANDERSSON I, SUBLETT J et al.: Capsular expression in Streptococcus pneumoniae negatively affects spontaneous and antibiotic-induced lysis and contributes to antibiotic tolerance. J. Infect. Dis. (2004) 189:328-338.
23. TUOMANEN E, TOMASZ A: Mechanism of phenotypic tolerance of nongrowing pneumococci to β-lactam antibiotics. Scandinavian J. Infect.Dis. Supplementum (1990) 74:102-112.
24. GUSTAFSON JE, WILKINSON BJ: Lower autolytic activity in a homogeneous methicillin-resistant Staphylococcus aureus strain compared to derived heterogeneous-resistant and susceptible strains. FEMS Microbiol. Lett. (1989) 50:107-111.
25. JACKSON JJ, KROPP H: Differences in mode of action of β-lactam antibiotics influence morphology, LPS release and in vivo antibiotic efficacy. J. Endotoxin Res. (1996) 3:201-218.
26. JACKSON JJ, KROPP H: Antibiotic-induced endotoxin release: important parameters dictating responses. Endotoxin in Health & Disease (1999): 67-75.
27. SJOLIN J, GOSCINSKI G, LUNDHOLIN M, BRING J, ODENHOLT I: Endotoxin release from Escherichia coli after exposure to tobramycin: dose-dependency and reduction in cefuroxime-induced endotoxin release. Clin. Microbiol. Infection (2000) 6:74-81.
28. SIMPSON AJH, OPAL SM, ANGUS BJ et al.: Differential antibiotic-induced endotoxin release in severe melioidosis. J. Infect. Dis. (2000) 181:1014-1019.
29. BONOMO RA, PAGE MGP: Penicillin-binding proteins and β-lactam resistance. In: Enzyme-mediated resistance to antibiotics: mechanisms and prospects for inhibition. RA Bonomo, M Tolmalsky (Eds), ASM Press, Washington DC, USA. (Awaiting publication).
30. MASUDA N, GOTOH N, ISHII C, SAKAGAWA E, OHYA S, NISHINO, T: Interplay between chromosomal β-lactamase and the MexAB-OprM efflux system in intrinsic resistance to β-lactams in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. (1999) 43:400-402.
31. ZHANG F-K, PAGE MGP, JIN S-H: Factors determining the resistance of Pseudomonas aeruginosa to β-lactam antibiotics. Zhongguo Kangshengsu Zazhi (2000) 25:362-367.
32. DUBOIS V, ARPIN C, MELON M et al.: Nosocomial outbreak due to a multiresistant strain of Pseudomonas aeruginosa P12: efficacy of cefepime-amikacin therapy and analysis of β-lactam resistance. J. Clin. Microbiol. (2001) 39:2072-2078.
33. OKAMOTO K, GOTOH N, NISHINO T: Pseudomonas aeruginosa reveals high intrinsic resistance to penem antibiotics: penem resistance mechanisms and their interplay. Antimicrob. Agents Chemother. (2001) 45:1964-1971.
34. NIKAIDO H: Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science (1994) 264:382-388.
35. HANCOCK RE: The bacterial outer membrane as a drug barrier. Trends Microbiol. (1997) 5:37-42.
36. GILL MJ, SIMJEE S, AL-HATTAWI K, ROBERTSON BD, EASMON CSF, ISON CA: Gonococcal resistance to β-lactams and tetracycline involves mutation in loop 3 of the porin encoded at the penB locus. Antimicrob. Agents Chemother. (1998) 42: 2799-2803.
37. DÉ E, BASLÉ A, JAQUINOD M et al.: A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin. Mol. Microbiol. (2001) 41:189-198.
38. AGGELER R, THEN RL, GHOSH R: Reduced expression of outer-membrane proteins in β-lactam-resistant mutants of Enterobacter cloacae. J. Gen. Microbiol. (1987) 133:3383-3392.
39. MEDEIROS AA, O'BRIEN TF, ROSENBERG EY, NIKAIDO H: Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy. J. Infect. Dis. (1987) 156:751-757.
40. DOMÉNEcH-SÁNCHEZ A, HERNÁNDEZ-ALLÉS S, MARTÍNEZ-MARTÍNEZ L, BENEDÍ VJ, ALBERTÍ S: Identification and characterization of a new porin gene of Klebsiella pneumoniae, its role in β-lactam antibiotic resistance. J. Bacteriol. (1999) 181:2726-2732.
41. CHARREL RN, PAGÈS J-M, DE MICCO P, MALLÉA M: Prevalence of outer membrane porin alteration in β-lactam antibiotic-resistant Enterobacter aerogenes. Antimicrob. Agents Chemother. (1996) 40:2854-2858.
42. CHEVALIER J, PAGÈS J-M, MALLÉA M: In vivo modification of porin activity conferring antibiotic resistance to Enterobacter aerogenes. Biochem Biophys. Res. Commun (1999) 266:248-251.
43. LI XZ, MA D, LIVERMORE DM, NIKAIDO H: Role of efflux pump(s) in intrinsic resistance of Pseudomonas aeruginosa: active efflux as a contributing factor to β-lactam resistance. Antimicrob. Agents Chemother. (1994) 38:1742-1752.
44. SRIKUMAR R, TSANG E, POOLE K: Contribution of the MexAB-OprM multidrug efflux system to the β-lactam resistance of penicillin-binding protein and β-lactamase-derepressed mutants of Pseudomonas aeruginosa. J. Antimicrob. Chemother. (1999) 44:537-540.
45. OKAMOTO K, GOTOH N, NISHINO T:Extrusion of penem antibiotics by multicomponent efflux systems MexAB-OprM, MexCD-OprJ, and MexXY-OprM of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. (2002) 46:2696-2699.
46. LI X-Z, ZHANG L, POOLE K: SmeC, an outer membrane multidrug efflux protein of Stenotrophomonas maltophilia. Antimicrob. Agents Chemother. (2002) 46:333-343.
47. NIKAIDO H, BASINA M, NGUYEN VY, ROSENBERG EY: Multidrug efflux pump AcrAB of Salmonella typhimurium excretes only those β -lactam antibiotics containing lipophilic side chains. J. Bacteriol. (1998) 180:4686-4692.
48. MAZZARIOL A, CORNAGLIA G, NIKAIDO H: Contributions of the AmpC β-lactamase and the acrAB multidrug efflux system in intrinsic resistance of Escherichia coli K-12 to β-lactams. Antimicrob. Agents Chemother. (2000) 44:1387-1390.
49. BUSH K, JACOBY GA, MEDEIROS AA: functional classification scheme for β-lactamases and its correlation with molecular structure. Antimicrob. Agents Chemother. (1995) 39:1211-1233
50. AMBLER RP: The structure of β-lactamases. Philos. Trans. R. Soc. Lond. B Biol. Sci. (1980) 289:321-331.
51. AMBLER RP, COULSON AFW, FRERE J-M et al.: A standard numbering scheme for the class A β-lactamases. Biochem. J. (1991) 276:269-272.
52. JORIS B, LEDENT P, DIDEBERG O et al.: Comparison of the sequences of class A β-lactamases and of the secondary structure elements of penicillin-recognizing proteins. Antimicrob. Agents Chemother. (1991) 35:2294-301.
53. MEDEIROS AA. Evolution and dissemination of β-lactamases accelerated by generations of β-lactam antibiotics. Clin. Infect. Dis. (1997) 24 (Suppl.1):S19-S45.
54. PATTERSON JE, ZERVOS MJ: Susceptibility and bactericidal activity studies of four β-lactamase-producing enterococci. Antimicrob. Agents Chemother. (1989) 33:251-253.
55. PATTERSON JE, WANGER A, ZSCHECK KK, ZERVOS MJ, MURRAY BE: Molecular epidemiology of β-lactamase-producing enterococci. Antimicrob. Agents Chemother. (1990) 34:302-305.
56. OKHUYSEN PC, SINGH KV, MURRAY BE: Susceptibility of β-lactamase-producing enterococci to piperacillin with tazobactam. Diagnostic Microbial Infect. Dis. (1993) 17:219-224.
57. TANG L, CHEN Q: Detection of β-lactamase and analysis of drug resistance in enterococci spp. Zhongguo Kangshengsu Zazhi (2003) 28:354-356.
58. UBUKATA K, CHIBA N, NAKAYAMA N, KONNO M: Drug-resistance mechanism of β-lactamase nonproducing ampicillin-resistant strains of Haemophilus influenzae. Nippon Rinsho Biseibutsugaku Zasshi (1999) 9:22-29.
59. MENDELMAN PM, CHAFFIN DO, KALAITZOGLOU G: Penicillin-binding proteins and ampicillin resistance in Haemophilus influenzae. J. Antimicrob. Chemother. (1990) 25:525-34.
60. VILLAR HE, DANEL F, LIVERMORE DM: Permeability to carbapenems of Proteus mirabilis mutants selected for resistance to imipenem or other β-lactams. J. Antimicrob. Chemother. (1997),40:365-370.
61. NEUWIRTH C, SIEBOR E, DUEZ J-M, PECHINOT A, KAZMIERCZAK A: Imipenem resistance in clinical isolates of Proteus mirabilis associated with alterations in penicillin-binding proteins. J. Antimicrob. Chemother. (1995) 36:335-342.
62. GODFREY AJ, BRYAN LE, RABIN HR: β-Lactam-resistant Pseudomonas aeruginosa with modified penicillin-binding proteins emerging during cystic fibrosis treatment. Antimicrob. Agents Chemother. (1981) 19:705-711.
63. MIRELMAN D, NUCHAMOWITZ Y, RUBINSTEIN E: Insensitivity of peptidoglycan biosynthetic reactions to β-lactam antibiotics in a clinical isolate of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. (1981) 19:687-695.
64. GOTOH N, NUNOMURA K, NISHINO T: Resistance of Pseudomonas aeruginosa to cefsulodin: modification of penicillin-binding protein 3 and mapping of its chromosomal gene. J. Antimicrob. Chemother. (1990) 25:513-23.
65. PAGANI L, DEBIAGGI M, TENNI R, CEREDA PM, LANDINI P. ROMERO E: β-Lactam-resistant Pseudomonas aeruginosa strains emerging during therapy: synergistic resistance mechanisms. Microbialogica (1988) 11:47-53
66. RODRIGUEZ-TEBAR A, ROJO F, DAMASO D, VAZQUEZ D. Carbenicillin resistance of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. (1982) 22:255-261
67. GEHRLEIN M, LEYING H, CULLMANN W, WENDT S, OPFERKUCH W,: Imipenem resistance in Acinetobacter baumanii is due to altered penicillin-binding proteins. Chemotherapy (1991) 37:405-412.
68. FERNANDEZ-CUENCA F, MARTINEZ-MARTINEZ L, CONEJO MC, AYALA JA, PEREA EJ, PASCUAL A: Relationship between β-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J. Antimicrob. Chemother. (2003) 51:565-574.
69. FONTANA R, GROSSATO A, ROSSI L, CHENG YR, SATTA G: Transition from resistance to hypersusceptibility to β-lactam antibiotics associated with loss of a low-affinity penicillin-binding protein in a Streptococcus faecium mutant highly resistant to penicillin. Antimicrob. Agents Chemotherapy (1985) 28:678-683.
70. CHEN HY, WILLIAMS JD: Penicillin-binding proteins in Streptococcus faecalis and S. faecium. J. Med. Microbiol. (1987) 23:141-7.
71. LIGOZZI M, PITTALUGA F, FONTANA R: Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium. Antimicrob. Agents Chemother. (1996) 40:354-357.
72. RYBKINE T, MAINARDI J-L, SOUGAKOFF W, COLLATZ E, GUTMANN L: Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of β-lactam resistance. J. Infect. Dis. (1998) 178:159-163.
73. SIFAOUI F, ARTHUR M, RICE L, GUTMANN L: Role of penicillin-binding protein 5 in expression of ampicillin resistance and peptidoglycan structure in Enterococcus faecium. Antimicrob. Agents Chemother. (2001) 45:2594-2597.
74. DOUGHERTY TJ, KOLLER AE, TOMASZ A; Penicillin-binding proteins of penicillin-susceptible and intrinsically resistant Neisseria gonorrhoeae. Antimicrob. Agents Chemother. (1980) 18:730-737.
75. DOUGHERTY TJ: Genetic analysis and penicillin-binding protein alterations in Neisseria gonorrhoeae with chromosomally mediated resistance. Antimicrob. Agents Chemother. (1986) 30:649-652.
76. SPRATT BG: Hybrid penicillin-binding proteins in penicillin-resistant strains of Neisseria gonorrhoeae. Nature (1988) 332:173-176.
77. MENDELMAN PM, CAMPOS J, CHAFFIN DO, SERFASS DA, SMITH AL, SAEZ-NIETO JA: Relative penicillin G resistance in Neisseria meningitidis and reduced affinity of penicillin-binding protein 3. Antimicrob. Agents Chemother. (1988) 32:706-709.
78. SPRATT BG, ZHANG QY, JONES DM, HUTCHISON A, BRANNIGAN JA, DOWSON CG: Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis. Proc. Nat. Acad. Sci. USA (1989) 86:8988-8992.
79. ZHANG QY, JONES DM, NIETO JAS, TRALLERO EP, SPRATT BG: Genetic diversity of penicillin-binding protein 2 genes of penicillin-resistant strains of Neisseria meningitidis, revealed by fingerprinting of amplified DNA. Antimicrob. Agents Chemother. (1990) 34:1523-1528.
80. JABES D, NACHMAN S, TOMASZ A: Penicillin-binding protein families: evidence for the clonal nature of penicillin resistance in clinical isolates of pneumococci. J. Infect. Dis. (1989) 159:16-25.
81. HAKENBECK R, KONIG A, KERN I et al.: Acquisition of five high-Mr penicillin-binding protein variants during transfer of high-level β-lactam resistance from Streptococcus mitis to Streptococcus pneumoniae. J. Bacteriol. (1998) 180:1831-1840.
82. BRANNIGAN JA, TIRODIMOS IA, ZHANG QY, DOWSON CG, SPRATT BG: Insertion of an extra amino acid is the main cause of the low affinity of penicillin-binding protein 2 in penicillin-resistant strains of Neisseria gonorrhoeae. Mol. Microbiol. (1990) 4:913-919.
83. GREBE T, HAKENBECK R: Penicillin-binding proteins 2b and 2x of Streptococcus pneumoniae are primary resistance determinants for different classes of β-lactam antibiotics. Antimicrob. Agents Chemother. (1996) 40:829-834.
84. NAGAI K, DAVIES TA, JACOBS MR, APPELBAUM PC: Effects of amino acid alterations in penicillin-binding proteins (PBPs) 1a, 2b, and 2x on PBP affinities of penicillin, ampicillin, amoxicillin, cefditoren, cefuroxime, cefprozil, and cefaclor in 18 clinical isolates of penicillin-susceptible, -intermediate, and -resistant pneumococci. Antimicrob. Agents Chemother (2002) 46:1273-1280.
85. ASAHI Y, UBUKATA K: Association of a Thr-371 substitution in a conserved amino acid motif of penicillin-binding protein 1A with penicillin resistance of Streptococcus pneumoniae. Antimicrob. Agents Chemother. (1998) 42:2267-2273.
86. HENZE UU, BERGER-BAECHI B: Penicillin-binding protein 4 overproduction increases β-lactam resistance in Staphylococcus aureus. Antimicrob. Agents Chemother (1996) 40:2121-2125.
87. CHAMBERS HF, SACHDEVA MJ, HACKBARTH CJ: Kinetics of penicillin binding to penicillin-binding proteins of Staphylococcus aureus. Biochem. J. (1994) 301:139-44.
88. UTSUI Y, TAJIMA M, SEKIGUCHI R, SUZUKI E, YOKOTA T: Role of an altered penicillin-binding protein (PBP) and membrane-bound penicillinase in cephem-resistant Staphylococcus aureus. Proceedings of the 13th International Congress on Chemotherapy Vienna, Austria (1983).
89. HARTMAN BJ, TOMASZ A; Low-affinity penicillin-binding protein associated with β-lactam resistance in Staphylococcus aureus. J. Bacteriol. (1984) 158:513-516.
90. BERGER-BACHI B, ROHRER S: Factors influencing methicillin resistance in staphylococci. Arch. Microbiol. (2002) 178:165-171.
91. STAPLETON PD, TAYLOR PW: Methicillin resistance in Staphylococcus aureus: mechanisms and modulation. Science Progress (2002) 85:57-72.
92. TSUJI A TI, NAKANISHI M, TERASAKI T, HAMANO S: Intestinal brush-border transport of the oral cephalosporin antibiotic, cefdinir, mediated by dipeptide and monocarboxylic acid transport systems in rabbits. J. Pharmacy Pharmacol. (1993) 45:996-998.
93. DECROIX MO, CHAUMEIL JC: Simulated absorption of oral cephalosporins: diffusion through artificial lipid barriers. Drug Devel. Industrial Pharmacy (1989) 15:2515-2529.
94. KOHDA-SHIMIZU R, LI Y-H, SHITARA Y, ITO K, TSUDA Y, YAMADA H, ITOH T: Oral absorption of cephalosporins; is quantitatively predicted from in vitro uptake into intestinal brush border membrane vesicles. Internat. J. Pharmaceutics (2001) 220:119-128.
95. MIYAUCHI M, HIROTA T, FUJIMOTO K, IDE J: Studies on orally active cephalosporin esters. IV. Effect of the C-3 substituent of cephalosporin on the gastrointestinal absorption in mice. Chem. Pharm. Bull. (1989) 37:3272-3276.
96. YOKOO C, GOI M, ONODERA A, MURATA M, NAGATE T, WATANABE Y: Studies on cephalosporin antibiotics. III. Synthesis, antibacterial activity and oral absorption of new 3-(substituted-alkylthio)-7 β-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino acetamido]cephalosporins. J. Antibiotics (1991) 44:498-506.
97. YOKOO C, GOI M, ONODERA A, FUKUSHIMA H, NAGATE T: Studies on cephalosporin antibiotics. IV. Synthesis, antibacterial activity and oral absorption of new 3-(2-substituted-vinylthio)-7 β-[(Z)-2-(2-aminothiazol-4-yl)-2-(carboxymedioxyimino acetamido]cephalosporins. J. Antibiotics (1991) 44:1422-1431.
98. YOKOO C, ONODERA A, FUKUSHIMA H, NUMATA K, NAGATE T: Studies on cephalosporin antibiotics. V. Synthesis, antibacterial activity and oral absorption of new 3-[(Z)-2-methoxycarbonylvinylthiol-7 β-[(Z)-2-(2-aminothiazol-4-yl)-2-(oxyimino acetamido]cephalosporins. J. Antibiotics (1992) 45:932-939.
99. YAMAMOTO H, TERASAWA T, NAKAMURA A et al.: Orally active cephalosporins. Part 3: synthesis, structure-activity relationships and oral absorption of novel C-3 heteroarylmethylthio cephalosporins. Bioorganic Med. Chem. (2001) 9:465-475.
100. MORI N, KODAMA T, SAKAI A et al.: AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity. Internat. J Antimicrob. Agents (2001) 18:451-461
101. SUNKAWA K, NISHIMURA T, MOTOHIRO T, FUJIl R: A multicenter, controlled open trial of a novel prodrug, ceftizoxime-alapivoxil (CZX-AP), in pediatrics: efficacy, safety and palatability of its granular formulation. Poster G-1467. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy San Diego, CA, USA (2002).
102. IWATA S, TOYONAGA Y, SATO Y, AKITA H, SUNAKAWA K: The influence of ceftizoxime-alapivoxil (CZX-AP) on intestinal bacterial flora in pediatrics. Poster G-1468. 42nd Interscience Conference an Antimicrobial Agents and Chemotherapy San Diego, CA, USA (2002).
103. HANAKI H, AKAGI H, MASARU Y, OTANI T, HYODO A, HIRAMATSU K: TOC-39, a novel parenteral broad-spectrum cephalosporin with excellent activity against methicillin-resistant Staphylococcus aureus. Antimicrob. Agents Chemother. (1995) 39:1120-6.
104. KIM OK, HUDYMA TW, MATISKELLA JD, UEDA Y BRONSON JJ, MANSURI MM: Synthesis and structure-activity relationship of C-3 quaternary ammonium cephalosporins exhibiting anti-MRSA activities. Bioorganic Med. Chem. Lett. (1997) 7:2753-2758.
105. TSUSHIMA M, IWAMATSU K, UMEMURA E et al.: CP6679, a new injectable cephalosporin. Part 1: Synthesis and structure-activity relationships. Bioorganic Med. Chem. (2000) 8:2781-2789.
106. ISHIKAWA T, KAMIYAMA K, NAKAYAMA Y, IIZAWA Y, OKONOGI K, MIYAKE A: Studies on anti-MRSA parenteral cephalosporins. III. Synthesis and antibacterial activity of 7β-[2-(5-amino-1,2,4-thiadiazol-3-yl -2(Z) -alkoxyiminoacetamido]-3-[(E -2-(1-alkylimidazo[1,2-b]pyridazinium-6-yl) thiovinyl] -3-cephem-4-carboxylates and related compounds. J. Antibiotics (2001) 54:257-277.
107. HEBEISEN P, HEINZE-KRAUSS I, ANGEHRN P, HOHL P, PAGE MGP, THEN RL: In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob. Agents Chemother. (2001) 45:825-836.
108. JOHNSON AP, WARNER M, CARTER M, LIVERMORE DM: In vitro activity of cephalosporin RWJ-54428 (MC-02479) against multidrug-resistant Gram-positive cocci. Antimicrob Agents Chemother. (2002) 46:321-326.
109. JOHNSON AP: Anti-MRSA cephalosporins of Bristol-Myers Squibb. Curr. Opin. Investig. Drugs (2001) 2:205-208.
110. YOSHIZAWA H, ITANI H, ISHIKURA K et al.: S-3578, a new broad spectrum parenteral cephalosporin exhibiting potent activity against both methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Synthesis and structure-activity relationships. J. Antibiotics (2002) 55:975-992
111. ISHIKAWA T, MATSUNAGA N, TAWADA H et al.: TAK-599, a novel N-Phosphono type prodrug of anti-MRSA cephalosporin T-91825: synthesis, physicochemical and pharmacological properties. Bioorg. Med. Chem. (2003) 11:2427-2437.
112. ABBANAT D, MACIELAG M, BUSH K: Novel antibacterial agents for the treatment of serious Gram-positive infections. Expert Opin. Investig. Drugs (2003) 12:379-399.
113. PAGE M, BUR D, DANEL F et al.: Inhibition of the penicillin-binding proteins of methicillin-resistant staphylococci by parrolidinone-3-ytidenemethyl cephems. Poster F-022. 38th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Diego, CA, USA (1998).
114. DESHPANDE LM, JONES RN: Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci. Clin. Microbiol. Infection (2003) 9:1120-1124.
115. JONES RN, DESHPANDE LM, MUTNICK AH, BIEDENBACH DJ: In vitro evaluation of BAL9141, a novel parenteral cephalosporin active against oxacillin-resistant staphylococci. J. Antimicrob. Chemother. (2002) 50:915-932.
116. BOZDOGAN B, ESEL D, WHITENER C, BROWNE FA, APPELBAUM PC: Antibacterial susceptibility of a vancomycin-resistant Staphylococcus aureus strain isolated at the Hershey Medical Center. J. Antimicrob. Chemother. (2003) 52:864-868.
117. HOELLMANN DB, JACOBS MR, APPELBAUM PC: MIC determination of the antipneumococcal activity of BAL9141, the active component of the prodrug BAL5788, compared to other agents. Poster P537. 14th European Congress of Clinical Microbiology and Infectious Diseases. Prague, Czech Republic (2004).
118. FUJIMURA T, YAMANO Y, YOSHIDA I, SHIMADA J, KUWAHARA S: In vitro activity of S-3578, a new broad-spectrum cephalosporin active against methicillin-resistant staphylococci. Antimicrob. Agents Chemother. (2003) 47:923-931.
119. SWENSON JM, TENOVER FC: In vitro activity of a new cephalosporin, RWJ-54428, against streptococci, enterococci, and staphylococci, including glycopeptide-intermediate Staphylococcus aureus. J. Antimicrob. Chemother (2002) 49:845-850.
120. JOHNSON AP, WARNER M, CARTER M, LIVERMORE DM: In vitro activity of cephalosporin RWJ-54428 (MC-02479) against multidrug-resistant Gram-positive cocci. Antimicrob. Agents Chemother. (2002) 46:321-326.
121. CHAMBERLAND S, BLAIS J, HOANG M et al.: In vitro activities of RWJ-54428 (MC-02,479) against multiresistant Gram-positive bacteria. Antimicrob. Agents Chemother. (2001) 45:1422-1430.
122. KATAYAMA Y, ZHANG H-Z, CHAMBERS HF: PBP 2a mutations producing very-high-level resistance to β-lactams. Antimicrob. Agents Chemother. (2004) 48:453-459.
123. HELLER S, MARRER E, PAGE MGP, SHAPIRO S, THENOZ L: Development of endogenous resistance by staphylococci to BAL9141 and comparators. Poster 536. 14th European Congress of Clinical Microbiology and Infectious Diseases. Prague, Czech Republic (2004).
124. MALOUIN F, BLAIS J, CHAMBERLAND S et al.: RWJ-54428 (MC-02,479), a new cephalosporin with high affinity for penicillin-binding proteins, Including PBP 2a, and stability to staphylococcal β-lactamases. Antimicrob. Agents Chemother. (2003) 47:658-664.
125. ISSA NC, ROUSE MS, PIPER KE, WILSON WR, STECKELBERG JM, PATEL R: In vitro activity of BAL9141 against clinical isolates of Gram-negative bacteria. Diagn. Microbiol. Infect. Dis. (2004) 48:73-75.
126. ZBINDEN R, PUNTER V, VON GRAEVENITZ A. In vitro activities of BAL9141, a novel broad-spectrum pyrrolidinone cephalosporin, against Gram-negative nonfermenters. Antimicrob. Agents Chemother. (2002) 46:871-874.
127. KRESKEN M, HEEP M: In vitro activities of BAL9141 and seven other β-lactam antimicrobial agents towards clinical isolates of 12 members of the Enterobacteriaceae family. Poster 1209. 14th European Congress of Clinical Microbiology and Infectious Diseases. Prague, Czech Republic (2004).
128. HUJER AM, BETHEL CR, SHAPIRO S, PATERSON DL, PAGE MGP BONOMO RA: In vitro activity of BAL9141, a broad-spectrum pyrrolidinone cephalosporin, against Klebsiella pneumoniae isolates possessing extended spectrum β-lactamases. Poster F-542. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, Il, USA (2003).
129. SHV mutants conferring ceftazidime (TAZ) resistance. Poster C1-685. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, Il, USA (2003).
130. KRESKEN M, HEEP M, WIEGAND I: Gram-negative bacteria producing characterized β-lactamases: in vitro activities of BAL9141 and comparators. Paoster P536, 14th European Congress of Clinical Microbiology and Infectious Diseases. Prague, Czech Republic (2004).
131. WOOTTON M, BOWKER KE, HOLT HA, MACGOWAN AP: BAL 9141, a new broad-spectrum pyrrolidinone cephalosporin: activity against clinically significant anaerobes in comparison with 10 other antimicrobials. J. Antimicrob. Chemother. (2002) 49:535-539.
132. HOELLMAN DB, KELLY LM, JACOBS MR, APPELBAUM PC: In vitro anti-anaerobic activity of the cephalosporin derivative RWJ 54428, compared to seven other compounds. Clin. Microbiol. Infect. (2002) 8:814-822.
133. ANDES DR, Craig W: In vivo pharmaocdynamics of RO 63-9141 against multiple bacterial pathogens. Poster 1079. 40th Interscience Conference on Antimicrobial Agents and Chemotherapy. Toronto, Canada (2000).
134. SCHMITT-HOFFMANN A, ROOS B, SCHLEIMER M et al.: Single dose pharmacokinetics and safety of a broad spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob. Agents Chemother. (2004) 48(7):2570-2575.
135. SCHMITT-HOFFMANN A, NYMAN L, ROOS B et al.: Multiple dose pharmacokinetics and safety of a novel broad spectrum cephalosporin (BAL5788) in healthy volunteers. Antimicrob. Agents Chemother. (In press).
136. MOUTON JW, SCHMITT-HOFFMANN A, SHAPIRO S, NASHED N, PUNT NC: Use of Monte Carlo simulations to select therapeutic doses and provisional breakpoints of BAL914. Antimicrob. Agents Chemother (2004) 48:1713-1718.
137. SCHMITT-HOFFMANN A, HARSCH M, HEEP M et al.: BAL5788 in patients with complicated skin and skin structure infections caused by Gram-positive pathogens including methicillin-resistant Staphlococcus species (MRSS). Pharmacokinetic results from 27 patients. Poster P-1031, 14th ECCMID (2004).
138. SCHMITT-HOFFMANN A, ROOS B, HEEP M et al.: Influence of gender on the pharmacokinetics of BAL9141 after intravenous infusion of pro-drug BAL5788. Poster P-1030. 14th European Congress of Clinical Microbiology and Infectious Diseases Prague, Czech Republic (2004).
139. SCHMITT-HOFFMANN A, ROOS B, SCHLEIMER M et al.: Dose adjustment in subjects with normal and impaired renal function based on the pharmacokinetics of BAL5788. Poster P 1032. 14th European Congress of Clinical Microbiology and Infectious Diseases. Prague, Czech Republic (2004).
140. MIYAZAKI S, OKAZAKI K, TSUJI M, YAMAGUCHI K: Pharmacodynamics of S-3578, a novel cephem, in murine lung and systemic infection models. Antimicrob. Agents Chemother. (2004) 48:378-383.
141. AZOULAY-DUPUIS E, BEDOS JP, MOHLER J, SCHMITT-HOFFMANN A, SCHLEIMER M, SHAPIRO S: Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia. Antimicrob. Agents Chemother. (2004) 48:1105-1111.
142. ROUSE M, AGUITA-ALONSO P, STECKELBERG J, PATEL R: BAL9141/BAL5788 Treatment of β-lactamase positive Haemophilus influenzae type b experimental pneumonia in immunocompetent mice: Poster F-539.43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, II, USA (2003).
143. ENTENZA JM, HOHL P, HEINZE-KRAUSS I, GLAUSER MP, MOREILLON P: BAL9141, a novel extended-spectrum cephalosporin active against methicillin-resistant Staphylococcus aureus in treatment of experimental endocarditis. Antimicrob. Agents Chemother. (2002) 46:171-177.
144. BASUINO L, MADRIGAL AG, CHAMBERS HF: Evaluation of BAL9141 in a rabbit model of aortic valve endocarditis due to methicillin resistant Staphylococcus aureus (MRSA) or vancomycin-intermediate Staphylococcus (VISA). Poster B-1090. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL, USA (2003).
145. TSUJI M, TAKEMA M, MIWA H, SHIMADA J, KUWAHARA S: In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models. Antimicrob. Agents Chemother. (2003) 47:2507-2512.
146. DUDLEY MN, HUIE K, GRIFFITH D, GLINKA T, HECKER S, MILLER G: In vitro cleavage of RWJ-442831, a soluble prodrug of the anti-MRSA cephalosporin RWJ-54428, in serum anf liver homogenates from animals and humans. Poster F-549. 43rd Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, II, USA (2003).
147. GRIFFITH DC, HARFORD L, WILLIAMS R, LEE VJ, DUDLEY MN: In vivo antibacterial activity of RWJ-54428, a new cephalosporin with activity against Gram-positive bacteria. Antimicrob. Agents Chemother. (2003) 47:43-47.