Pediatric Infectious Disease Journal:
Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin
GUAY, DAVID R. P. PHARMD, FCP, FCCP, FASCP, CGP
From the Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota and HealthPartners, Inc., Minneapolis, MN.
Reprints not available.
Background. Oral second and third generation cephalosporins are undergoing continuing research and development in the arena of pediatric infectious disease in an attempt to fill voids created by existing agents in the quest for the “ideal” antimicrobial. This paper reviews the in vitro antimicrobial activity (pharmacodynamics) and pharmacokinetics of cefdinir, an extended spectrum oral cephalosporin, with an emphasis on those aspects relevant to the pediatric patient population.
Methods. A MEDLINE literature search was conducted for the years 1985 through 2000, identifying all English language papers examining the in vitro antimicrobial activity and human pharmacokinetics of cefdinir. Bibliographies of these papers were reviewed, as were relevant data on file with the manufacturer.
Cefdinir exhibits broad range in vitro activity against Gram-positive and Gram-negative aerobes. It exhibits superior activity against Gram-positive aerobes, compared with drugs like cefixime, ceftibuten, cefuroxime and cefpodoxime. In addition it is stable to hydrolysis by many of the common beta-lactamases. The pharmacokinetic parameters of cefdinir in children are similar to those obtained in adults using similar milligram per m2 doses (300, 600 mg in adults = 7, 14 mg/kg in children, respectively).
Conclusions. The pharmacodynamic and pharmacokinetic characteristics of cefdinir as described in this paper, as well as the results of the clinical trials program, support the use of this agent in the treatment of a wide variety of pediatric infectious diseases.
The “ideal” antimicrobial for ambulatory pediatric patients would encompass the following characteristics: clinical efficacy; bactericidal activity; appropriate antimicrobial spectrum, including activity against Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes; optimal pharmacokinetic properties, including excellent oral absorption, good penetration to infection sites, long terminal disposition half-life and stability in serum; low adverse event potential, including low impact on colonic microflora; patient convenience, including once or twice daily dosing and a palatable, pleasant-tasting suspension formulation. Unfortunately no oral antimicrobial fulfills all of these characteristics, thus prompting continuing research and development in this field.
The oral second and third generation cephalosporins have been developed in an attempt to fill this void. Although drugs such as penicillin for streptococcal pharyngotonsillitis or amoxicillin or trimethoprim-sulfamethoxazole for acute otitis media are generally considered first line therapy, 1–3 cephalosporins may be useful agents in areas where local susceptibility patterns reveal a high prevalence of organisms resistant to traditional first line agents 1, 4, 5 or in patients with sulfonamide or nonimmediate penicillin allergies. 1, 2, 6 In addition cephalosporins may be useful when less frequent dosing or shorter duration of therapy may be viewed as significant benefits, from the patient’s or family’s perspective. 7
Available cephalosporins and carbacephems have certain liabilities. Cefprozil has modest in vitro activity against M. catarrhalis and H. influenzae and lesser clinical performance than comparators in some studies. 8–10 Cefuroxime is limited by poor palatability. 8–10 Loracarbef exhibits marginal activity against H. influenzae, and its bioavailability is reduced by food. 9, 10 Cefixime has marginal to modest activity against S. pneumoniae and no activity against Staphylococcus aureus as well as a high risk of antibiotic-associated diarrhea. 8–10 Ceftibuten has liabilities similar to those of cefixime with the exception of diarrhea. 8, 9 Cefpodoxime has only modest activity against Staphylococcus aureus when standard doses are utilized; in addition palatability of the suspension formulation is inferior to that of many other agents. 8–10
The purpose of this paper is to review the in vitro antimicrobial activity (pharmacodynamics) and pharmacokinetics of cefdinir, an oral expanded spectrum cephalosporin (Omnicef; Abbott Laboratories, Chicago, IL), with an emphasis on application to pediatric patients.
IN VITRO ANTIMICROBIAL ACTIVITY
As with the older beta-lactam compounds, cefdinir binds to penicillin-binding proteins, thereby causing cell death by impairing cell wall formation. 11 Cefdinir binds to penicillin-binding proteins 1, 2, 3 and 4 of Staphylococcus aureus (strain 123-1-2) and 1A, 1B, 2, 3 and 4 of Escherichia coli (strains NIHJ JC-2 and K12). 12, 13
Table 1 illustrates the in vitro antibacterial activity of cefdinir and comparator cephalosporins against a wide variety of Gram-positive and Gram-negative aerobes and anaerobes. 12–42 Unlike several extended spectrum oral beta-lactams, cefdinir retains excellent activity against gram-positive aerobes, including staphylococci (except methicillin-resistant strains) and group A, B, C and G streptococci. It also exhibits excellent activity against Neisseriaceae, Haemophilus and Moraxella spp. and variable species-specific activity against the Enterobacteriaceae. In general cefdinir is inactive against Enterococcus and Listeria spp. and exhibits variable activity against S. pneumoniae, with increased MICs for penicillin-intermediate and -resistant vs. penicillin-susceptible strains. Cefdinir is generally inactive against Legionella spp. and anaerobes. 14, 15, 18, 26, 43
The minimum bactericidal concentration of cefdinir is usually <4 times the MIC. 14, 18 The presence of human serum or urine does not affect cefdinir MIC or minimum bactericidal concentration. 14, 15, 25, 44 The presence of CO2, magnesium ions and pH alterations (over a range of pH 5.5 to 8) similarly have no significant effect on cefdinir MIC. 13, 14, 18, 44 Cefdinir MIC increases with increasing inoculum size, but this increase is modest for most species. 14, 15, 18, 41, 44 Brief (up to 2 h) in vitro postantibiotic effect periods have been reported for S. pneumoniae, S. pyogenes, Staphylococcus aureus, Staphylococcus epidermidis, other coagulase-negative staphylococci, H. influenzae, M. catarrhalis and E. coli. 44–46 Cefdinir is stable to hydrolysis by numerous beta-lactamases, including TEM-1, TEM-2, TEM-6, TEM-7, TEM-9, TEM-10, CAZ-2, SHV-1, HMS-1, OXA-1, OXA-2, OXA-3 and P99 type 1a. 14, 15, 18, 40, 47–49 Cefdinir exhibits no deleterious effects on human immune system function ex vivo. 50–52
Cefdinir appears to exert little effect on normal human fecal flora. In a study involving seven pediatric patients (0.5 to 12.5 years old) treated with doses ranging from 9 to 11 mg/kg/day for 4 to 14 days, only modest effects on fecal flora were observed. Aerobic and anaerobic counts, except those of enterococci, varied little over time and in no case did glucose nonfermenters or fungi become predominant species for any length of time. 53
Interpretive criteria and quality control parameters have been published for broth microdilution and disk diffusion methods for cefdinir susceptibility testing of pneumococci, Neisseria gonorrhoeae, H. influenzae, E. coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. 17, 39, 54–60 The MIC breakpoint is 1 mg/l (sensitive, ≤1 mg/l; intermediate, 2 mg/l; resistant, ≥4 mg/l) and the zone size breakpoint for disk diffusion testing with a 5-mg disk is 20 mm (resistant, ≤16 mm; intermediate, 17 to 19 mm; sensitive, ≥20 mm) for organisms other than streptococci. 53, 61 MIC and disk diffusion breakpoints have been established for S. pneumoniae and streptococci other than S. pneumoniae. 53
Pharmacokinetic parameters for cefdinir in adults and children are illustrated in Table 2. Absorption appears to be reasonably rapid in children, with a time to peak plasma concentration (Tmax) of ∼2 h.
Bioavailability of the capsule formulation ranges from 16 to 21%; bioavailability of the suspension formulation is 20% greater than that of the capsule formulation. 53 Food exerts no clinically significant effect on cefdinir bioavailability. 53
Few published data are available regarding tissue and body fluid penetration of cefdinir. In studies utilizing healthy adult volunteers, significant penetration was noted into suction-induced blister fluid (84 to 108%), bronchial mucosal tissue (31 to 41%), bronchial epithelial lining fluid (12 to 15%), tonsillar tissue (24%) and maxillary/ethmoid sinus mucosal tissue (16%). 53, 62, 63 In pediatric patients with acute bacterial otitis media, the mean middle ear fluid concentration 3 h after single 7- and 14-mg/kg doses of cefdinir was 15% that of the corresponding plasma concentration. 53
In adults cefdinir is primarily eliminated as unchanged drug via the renal route. 53, 62 This may not, however, be the case in children based on the low fractional elimination of unchanged drug in children (mean range, 2.7 to 12.7%) compared with that in adults (mean range, 12.7 to 23%). 53, 62 Terminal disposition half-life (t1/2) is ∼1.5 h in healthy adult and pediatric volunteers. 53, 62 Apparent total body clearance appears to be higher in younger (0- to 3-year-old) than in older (3- to 12-year-old) children, consistent with data obtained with other beta-lactam antimicrobials. 53 In adults with normal renal function, drug accumulation does not occur with multiple once or twice daily administration, and pharmacokinetic parameters are similar for multiple dose as compared with single dose administration. 53
Studies have been conducted in adults evaluating the effect of renal dysfunction and dialysis on cefdinir pharmacokinetics. 53 Decreases in apparent total body clearance and renal clearance of cefdinir were approximately proportional to the reduction in creatinine clearance (CrCl). For example in subjects with CrCl between 30 and 60 ml/min, peak plasma concentration (Cmax), t1/2 and area under the plasma concentration-vs.-time curve (AUC) increased ∼2-, 2- and 3-fold, respectively, compared with subjects who had normal renal function. Corresponding increases in subjects with CrCl <30 ml/min were 2-, 5- and 6-fold, respectively.
In hemodialysis patients studied on a nondialysis day, cefdinir Cmax, Tmax, AUC and t1/2 were elevated 3-, 2-, 17- and 11-fold, respectively, compared with healthy volunteers. Cefdinir appears to be hemodialyzable based on a comparison of inter-vs. intradialytic t1/2 and AUC. Fractional elimination in dialysate was 61%. 64 In continuous ambulatory peritoneal dialysis patients, cefdinir Cmax, t1/2 and AUC were elevated 6-, 11- and 24-fold, respectively, compared with healthy volunteers. In contrast to hemodialysis, continuous ambulatory peritoneal dialysis removal of the drug was minimal (<5 mg/24 h). 20
Simultaneous administration of magnesium-aluminum hydroxide antacid reduced cefdinir bioavailability by 38% (based on Cmax data) and 44% (based on AUC data). Separating the dose administrations by 2 h eliminated the interaction. 53
The effect of iron on cefdinir bioavailability is controversial. One study described a significant reduction in bioavailability when 1050 mg of ferrous sulfate were coadministered with or 3 h after cefdinir capsule administration. 65 Another study found that concomitant administration of ferrous sulfate (60 mg elemental iron) and multiple vitamins supplemented with iron (10 mg elemental iron) reduced cefdinir bioavailability by 79 and 38%, respectively (based on Cmax data) and 80 and 31%, respectively (based on AUC data). In contrast iron-fortified infant formula was not found to significantly affect cefdinir bioavailability from the suspension formulation in healthy infants. 53
Cefdinir is an extended spectrum oral cephalosporin with a broad range of activity against Gram-positive and Gram-negative aerobes. It exhibits superior activity against Gram-positive aerobes such as staphylococci and streptococci compared with drugs such as cefixime, cefpodoxime, cefuroxime and ceftibuten. The pharmacokinetic parameters of cefdinir in children are similar to those obtained in adults using similar milligram per m 2 doses (300 mg in adults = 7 mg/kg in children and 600 mg in adults = 14 mg/kg in children). Pharmacokinetic data have thus validated the use of 7 mg/kg twice daily and 14 mg/kg once daily dosing in the pediatric efficacy studies described in the literature 53, 66–68 and in this supplement.
I thank Kari Bunjer for administrative assistance in the preparation of the manuscript.
1. Stohlmeyer LA, Kraus DM. Oral cephalosporins: focus on new agents. J Pediatr Health Care 1996; 10: 289–94.
2. Barnett ED, Klein JO. Use of oral cephalosporins in infants and children. Curr Clin Top Infect Dis 1997; 17: 316–33.
3. Holm SE. Reasons for failures in penicillin treatment of streptococcal tonsillitis and possible alternatives. Pediatr Infect Dis J 1994; 13 (Suppl): S66–9.
4. Baquero F, Loza E. Antibiotic resistance of microorganisms involved in ear, nose and throat infections. Pediatr Infect Dis J 1994; 13 (Suppl): S9–14.
5. Pichichero ME. Empiric antibiotic selection criteria for respiratory infections in pediatric practice. Pediatr Infect Dis J 1997; 16 (Suppl): S60–4.
6. Liston TE. Management of otitis media. Clin Pediatr 1995; 34: 542–8.
7. Guay DRP. Short-course antimicrobial therapy for upper respiratory infections. Clin Ther 2000; 22: 673–84.
8. Mason WH. The management of common infections in ambulatory children. Pediatr Annu 1996; 25: 620–30.
9. Rodriguez WJ, Wiederman BL. The role of newer oral cephalosporins, fluoroquinolones, and macrolides in the treatment of pediatric infections. Adv Pediatr Infect Dis 1994; 9: 125–59.
10. Harrison CJ. Perspectives on newer oral antimicrobials: what do they add? Pediatr Infect Dis J 1995; 14: 436–44.
11. Hatano K, Nishino T. Morphological alterations of Staphylococcus aureus
and Streptococcus pyogenes
exposed to cefdinir, a new oral broad-spectrum cephalosporin. Chemotherapy 1994; 40: 73–9.
12. Fukuoka T, Ohya S, Utsui Y, et al. In vitro
and in vivo
antibacterial activities of CS-834, a novel oral carbapenem. Antimicrob Agents Chemother 1997; 41: 2652–63.
13. Sakagawa E, Otsuki M, Ou T, Nishino T. In-vitro
antibacterial activities of CS-834, a new oral carbapenem. J Antimicrob Chemother 1998; 42: 427–37.
14. Neu HC, Saha G, Chin NX. Comparative in vitro
activity and beta-lactamase stability of FK482, a new oral cephalosporin. Antimicrob Agents Chemother 1989; 33: 1795–800.
15. Wise R, Andrews JM, Thornber D. The in-vitro
activity of cefdinir (FK482), a new oral cephalosporin. J Antimicrob Chemother 1991; 28: 239–48.
16. Qadri SMH, Ueno Y, Saldin J, Cunha BA. In vitro
activity of cefdinir (FK482, PD134393, CI-983): a new orally active cephalosporin. Chemotherapy 1993; 39: 112–19.
17. Gerlach EH, Jones RN, Allen SD, et al. Cefdinir (FK482), an orally administered cephalosporin in vitro
activity comparison against recent clinical isolates from five medical centers and determination of MIC quality control guidelines. Diagn Microbiol Infect Dis 1992; 15: 537–43.
18. Briggs BM, Jones RN, Erwin ME, Barrett MS, Johnson DM. In vitro
activity evaluations of cefdinir (FK482, CI-983, and PD 134393). a novel orally administered cephalosporin. Diagn Microbiol Infect Dis 1991; 14: 425–34.
19. Sultan T, Baltch AL, Smith RP, Ritz W. In vitro
activity of cefdinir (FK482) and ten other antibiotics against Gram-positive and Gram-negative bacteria isolated from adult and pediatric patients. Chemotherapy 1994; 40: 80–91.
20. Tomino Y, Fukui M, Hamada C, Inoue S, Osada S. Pharmacokinetics of cefdinir and its transfer to dialysate in patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis. Arzneim Forsch 1998; 48: 862–7.
21. Inamoto Y, Chiba T, Kamimura T, Takaya T. FK482, a new orally active cephalosporin. synthesis and biological properties. J Antibiot 1988; 41: 828–30.
22. Fung-Tomc JC, Huczko E, Stickle T, et al. Antibacterial activities of cefprozil compared with those of 13 oral cephems and 3 macrolides. Antimicrob Agents Chemother 1995; 39: 533–8.
23. Bauernfeind A, Jungwirth R, Eberlein E, et al. RU29246, the active compound of the cephalosporin-prodrug-ester HR916: I. antibacterial activity in vitro
. J Antibiot 1992; 45: 505–20.
24. Scriver SR, Willey BM, Low DE, Simor AE. Comparative in vitro
activity of cefdinir (CI-983; FK-482) against staphylococci, Gram-negative bacilli and respiratory tract pathogens. Eur J Clin Microbiol Infect Dis 1992; 11: 646–52.
25. Garcia-Rodriguez JA, Trujillano-Martin I, Garcia-Sanchez JE. Cefdinir:in vitro
activity study and effect of human serum. Drugs Exp Clin Res 1993; 19: 51–8.
26. Mine Y, Kamimura R, Watanabe Y, et al. In vitro
antibacterial activity of FK482, a new orally active cephalosporin. J Antibiot 1988; 41: 1873–87.
27. Cohen MA, Joannides ET, Roland GE, et al. In vitro
evaluation of cefdinir (FK482), a new oral cephalosporin with enhanced antistaphylococcal activity and beta-lactamase stability. Diagn Microbiol Infect Dis 1994; 8: 31–9.
28. Yamaguchi K, Domon H, Miyazaki S, et al. In vitro
and in vivo
antibacterial activities of CS-834, a new oral carbapenem. Antimicrob Agents Chemother 1998; 42: 555–63.
29. Tamura S, Miyazaki S, Tateda K, et al. In vivo
antibacterial activities of sanfetrinem cilexetil, a new oral tricyclic antibiotic. Antimicrob Agents Chemother 1998; 42: 1858–61.
30. Bauernfeind A, Jungwirth R. Antibacterial activity of cefpodoxime in comparison with cefixime, cefdinir, cefetamet, ceftibuten, loracarbef, cefprozil, BAY 3522, cefuroxime, cefaclor, and cefadroxil. Infection 1991; 19: 353–62.
31. Choi KI, Cha JH, Pae AN, et al. Studies on novel 3-isoxazolylvinyl-cephalosporins: II. synthesis and biological activity of 7-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido] derivatives. J Antibiot 1998; 51: 1122–5.
32. Blandino G, Aleo G, Caccamo F, Nicolosi BM, Siracusa V, Speciale A. In vitro
activity of cefdinir against respiratory pathogens isolated in Sicily with reference to beta-lactamase production. J Chemother 1996; 8: 193–9.
33. Mikamo H, Kawazoe K, Sato Y, Izumi K, Tamaya T. In vitro
and in vivo
antibacterial activities of S-1090, a new oral cephalosporin, in the fields of obstetrics and gynecology. Chemotherapy 1998; 44: 153–6.
34. Spangler SK, Jacobs MR, Appelbaum PC. In vitro
susceptibilities of 185 penicillin-susceptible and -resistant pneumococci to WY-49605 (SUN/SY 5555), a new oral penem, compared with those to penicillin G, amoxicillin, amoxicillin-clavulanate, cefixime, cefaclor, cefpodoxime, cefuroxime, and cefdinir. Antimicrob Agents Chemother 1994; 38: 2902–4.
35. Spangler SK, Jacobs MR, Appelbaum PC. Activities of RPR 106972 (a new oral streptogramin), cefditoren (a new oral cephalosporin), two new oxazolidinones (U-100592 and U-100766), and other oral and parenteral agents against 203 penicillin-susceptible and -resistant pneumococci. Antimicrob Agents Chemother 1996; 40: 481–4.
36. Linares J, Alonso T, Perez JL, et al. Decreased susceptibility of penicillin-resistant pneumococci to twenty-four beta-lactam antibiotics. J Antimicrob Chemother 1992; 30: 279–88.
37. Spangler SK, Jacobs MR, Pankuch GA, Appelbaum PC. Susceptibility of 170 penicillin-susceptible and penicillin-resistant pneumococci to six oral cephalosporins, four quinolones, desacetylcefotaxime, Ro 23-9424 and RP 67829. J Antimicrob Chemother 1993; 31: 273–80.
38. Yamashiro T, Nakasone N, Higa N, et al. Etiological study of diarrheal patients in Vientiane, Lao People’s Democratic Republic. J Clin Microbiol 1998; 36: 2195–9.
39. Barrett MS, Jones RN. Susceptibility testing interpretive criteria and drug stability for cefdinir, cefetamet, and cefpodoxime against Neisseria gonorrhoeae
. Diagn Microbiol Infect Dis 1992; 15: 685–91.
40. Payne DJ, Amyes SGB. The sensitivity of clinical bacteria isolated in Scotland to the oral cephalosporin, cefdinir. Drugs Exp Clin Res 1992; 18: 225–31.
41. Perea EJ, Garcia Iglesias MC. Comparative in-vitro
activity of cefdinir against multiresistant Haemophilus influenzae
. J Antimicrob Chemother 1994; 34: 161–4.
42. Seki H, Kasahara Y, Ohta K, et al. Increasing prevalence of ampicillin-resistant, non-beta-lactamase-producing strains of Haemophilus influenzae
in children in Japan. Chemotherapy 1999; 45: 15–21.
43. Jones RN, Erwin ME, Barrett MS. Antimicrobial activity of three investigational cephalosporins (BK-218, cefdinir, and RU29246) against Legionella.
Diagn Microbiol Infect Dis 1991; 14: 519–21.
44. Saverino D, Debbia EA, Pesce A, Schito GC. Antistaphylococcal activity of cefdinir, a new oral third-generation cephalosporin, alone and in combination with other antibiotics, at supra- and sub-MIC levels. J Antimicrob Chemother 1995; 35: 53–66.
45. Howard BMA, Pinney RJ, Smith JT. Post-antibiotic effects of cefdinir on Escherichia coli
, Klebsiella pneumoniae
, Staphylococcus aureus
, and Streptococcus pyogenes
. Chemotherapy 1994; 40: 232–8.
46. Blandino G, Caccamo F, DiMarco R, Nicoletti A, Speciale A, Nicoletti G. Bactericidal activity and postantibiotic effect of cefdinir (CI983, FK482) against selected pathogens. Drugs Exp Clin Res 1992; 18: 319–27.
47. Payne DJ, Amyes SGB. Stability of cefdinir (CI-983, FK482) to extended-spectrum plasmid-mediated beta-lactamases. J Med Microbiol 1993; 38: 114–7.
48. Jacoby GA, Carreras I. Activities of other beta-lactam antibiotics against Escherichia coli
strains producing extended-spectrum beta-lactamases. Antimicrob Agents Chemother 1990; 34: 858–62.
49. Labia R, Morand A. Interaction of cefdinir with beta-lactamases. Drugs Exp Clin Res 1994; 20: 43–8.
50. Labro MT, El Benna J, Charlier N, Abdelghaffar H, Hakim J. Cefdinir (CI-983), a new oral amino-2-thiazolyl cephalosporin, inhibits human neutrophil myeloperoxidase in the extracellular medium but not the phagolysosome. J Immunol 1994; 152: 2447–55.
51. Fietta A, Merlini C, Gialdroni Grassi G. In vitro
activity of two new oral cephalosporins, cefixime and cefdinir (CI983), on human peripheral mononuclear and polymorphonuclear neutrophil functions. Chemotherapy 1994; 40: 317–23.
52. Pruul H, McDonald PJ. Cefdinir-mediated modification of the susceptibility of bacteria to the antibacterial activity of human serum and polymorphonuclear neutrophils. Eur J Clin Microbiol Infect Dis 1993; 12: 170–6.
53. Omnicef (cefdinir) package insert and data on file. Abbott Park, IL: Abbott Laboratories, 2000.
54. Fuchs PC, Barry AL, Tenover FC, Allen SD, Jorgensen JH, Murray PR. Tests for susceptibility of Streptococcus pneumoniae
to cefdinir: proposed interpretive criteria and quality control parameters for broth microdilution and disc diffusion methods. J Antimicrob Chemother 1995; 36: 781–6.
55. Bale MJ, Jones RN, The Quality Control Study Group. Quality control guidelines for cefdinir, cefepime, cefetamet, cefmetazole, cefpodoxime, cefprozil, and clinafloxacin (CI-960) for various National Committee for Clinical Laboratory Standards susceptibility testing methods. J Clin Microbiol 1993; 31: 2538–40.
56. Erwin ME, Jones RN, Koontz FP, Gerlach EH, Murray PR, Washington JA. MIC and disk diffusion quality control guidelines for Neisseria gonorrhoeae
susceptibility tests of cefdinir, cefetamet, CI-960, fleroxacin, lomefloxacin, and temafloxacin. J Clin Microbiol 1992; 30: 1317–9.
57. Bale MJ, Jones RN, Erwin ME, et al. Disk diffusion quality control guidelines for Haemophilus
susceptibility tests using cefdinir, CI-960, fleroxacin, temafloxacin, and trospectomycin. J Clin Microbiol 1992; 30: 744–5.
58. Bale MJ, Jones RN, Erwin ME, et al. MIC quality control guidelines for Haemophilus
susceptibility tests using cefdinir (FK482), cefepime, cefetamet, cefpirome, ceftibuten, fleroxacin, temafloxacin, clarithromycin, RP59500, and trospectomycin. J Clin Microbiol 1992; 30: 225–6.
59. Jones RN, Erwin ME. Haemophilus
test medium interpretive criteria for disk diffusion susceptibility tests with cefdinir, cefetamet, cefmetazole, cefpodoxime, cefdaloxime (RU 29246, HR-916 metabolite), and trospectomycin. Diagn Microbiol Infect Dis 1992; 15: 693–701.
60. Fuchs PC, Barry AL, Brown SD, et al. Reproducibility of broth microdilution and disk diffusion susceptibility tests of nine antimicrobial agents against Streptococcus pneumoniae
ATCC 49619. Diagn Microbiol Infect Dis 1997; 28: 27–9.
61. Jones RN, Erwin ME, Gooding BB. Interpretive criteria for disk diffusion tests using 5-microgram cefdinir disks with rapidly growing clinical isolates. J Clin Microbiol 1992; 30: 1022–3.
62. Richer M, Allard S, Manseau L, Vallee F, Pak R, LeBel M. Suction-induced blister fluid penetration of cefdinir in healthy volunteers following ascending oral doses. Antimicrob Agents Chemother 1995; 39: 1082–6.
63. Cook PJ, Andrews JM, Wise R, Honeybourne D. Distribution of cefdinir, a third generation cephalosporin antibiotic, in serum and pulmonary compartments. J Antimicrob Chemother 1996; 37: 331–9.
64. Hishida A, Ohishi K, Nagashima S, Kanamaru M, Obara M, Kitada A. Pharmacokinetic study of an oral cephalosporin, cefdinir, in hemodialysis patients. Antimicrob Agents Chemother 1998; 42: 1718–21.
65. Ueno K, Tanaka K, Tsujimura K, Morishima Y, Iwashige H, Yamazaki K, Nakata I. Impairment of cefdinir absorption by iron ion. Clin Pharmacol Ther 1993; 54: 473–5.
66. Tack KJ, Hedrick JA, Rothstein E, et al. A study of 5-day cefdinir treatment for streptococcal pharyngitis in children. Arch Pediatr Adolesc Med 1997; 151: 45–9.
67. Tack KJ, Keyserling CH, McCarty J, Hedrick JA, Cefdinir Pediatric Skin Infection Study Group. Study of the use of cefdinir versus
cephalexin for treatment of skin infections in pediatric patients. Antimicrob Agents Chemother 1997; 41: 739–42.
68. Adler M, McDonald PJ, Trostmann U, Keyserling C, Tack K. Cefdinir versus
amoxicillin/clavulanic acid in the treatment of suppurative acute otitis media in children. Eur J Clin Microbiol Infect Dis 1997; 16: 214–9.
Cefdinir; cephalosporins; pharmacokinetics; pharmacodynamics
© 2000 Lippincott Williams & Wilkins, Inc.
What does "Remember me" mean?
By checking this box, you'll stay logged in until you logout. You'll get easier access to your articles, collections,
media, and all your other content, even if you close your browser or shut down your
To protect your most sensitive data and activities (like changing your password),
we'll ask you to re-enter your password when you access these services.
What if I'm on a computer that I share with others?
If you're using a public computer or you share this computer with others, we recommend
that you uncheck the "Remember me" box.
Highlight selected keywords in the article text.
- Articles in PubMed by DAVID R. P. GUAY, PHARMD, FCP, FCCP, FASCP, CGP
- Articles in Google Scholar by DAVID R. P. GUAY, PHARMD, FCP, FCCP, FASCP, CGP
- Other articles in this journal by DAVID R. P. GUAY, PHARMD, FCP, FCCP, FASCP, CGP
Data is temporarily unavailable. Please try again soon.
Readers Of this Article Also Read