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Cefepime

A Review of its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Use

Abstract

Synopsis

Cefepime is a ‘fourth’ generation Cephalosporin that has a broader spectrum of antibacterial activity than the third generation Cephalosporins and is more active in vitro against Gram-positive aerobic bacteria. The fact that cefepime is stable to hydrolysis by many of the common plasmid and chromosomally-mediated β-lactamases, and that it is a poor inducer of type I β-lactamases, indicates that cefepime may be useful for treatment of infections resistant to earlier Cephalosporins.

In comparative trials, cefepime 1 to 2g, usually administered intravenously twice daily, was as effective as ceftazidime 1 to 2g, usually administered 3 times daily, for treatment ofbacteraemia and infections of the lower respiratory tract, urinary tract, pelvis and skin and skin structures. Furthermore, cefepime was as effective as ceftazidime and piperacillin or mezlocillin in combination with gentamicin when administered as empirical treatment for fever in patients with neutropenia. A limited number of trials have found cefepime to be as effective as cefotaxime for the treatment of gynaecological and lower respiratory tract infections. Similarly, cefepime 2g twice daily intravenously (alone or in combination with metronidazole) was as effective as gentamicin in combination with mezlocillin or Clindamycin, respectively, for the treatment of intra-abdominal infection.

Cefepime has a linear pharmacokinetic profile, an elimination half-life of approximately 2 hours and is primarily excreted by renal mechanisms as unchanged drug. Cefepime has a tolerability profile similar to that of other parenteral Cephalosporins; adverse events are primarily gastrointestinal in nature. A total of 1.4 and 2.9% of patients receiving cefepime ≤2 g/day and =2 g/day, respectively, required treatment withdrawal as a result of any adverse event.

Thus, cefepime has the advantage of an improved spectrum of antibacterial activity, and is less susceptible to hydrolysis by some β-lactamases, compared with third generation Cephalosporins. Despite these advantages, cefepime has not been found to be more effective than ceftazidime and cefotaxime in clinical trials, although most trials selected patients with organisms sensitive in vitro to both comparator agents. Further trials, particularly in areas of widespread bacterial resistance, are required to confirm the positioning of cefepime for treatment of serious infection, and in particular to further explore whether its potential advantages result in clinical benefits.

Antibacterial Activity

Cefepime is a Cephalosporin with activity against both Gram-positive and Gram-negative aerobic bacteria. In common with other β-lactam agents, cefepime exerts its antibacterial effects by binding to penicillin-binding proteins.

Cefepime has greater inhibitory activity than ceftazidime against Streptococcus pneumoniae and most other streptococcal species, and against staphylococcal species. Although cefepime is active against methicillin-sensitive strains, it is not active against methicillin-resistant Staphylococcus aureus or S. epidermidis. Cefepime demonstrates useful inhibitory activity against all common pathogens from the family Enterobacteriaceae, including those that commonly produce chromosomally-mediated β-lactamases. Cefepime also has excellent inhibitory activity against Haemophilus influenzae, regardless of the α-lactamase-producing ability of the organism. In common with most other Cephalosporins, cefepime has limited inhibitory activity against non-fermentative bacteria, although the majority of tested isolates of Pseudomonas aeruginosa were susceptible or moderately susceptible to cefepime, Cefepime has minimal inhibitory activity against enterococci, Bacteroides fragilis and Clostridium difficile.

Type I β-lactamases have a low affinity for cefepime, and therefore cefepime retains its inhibitory activity against de-repressed bacteria. In addition, cefepime is not susceptible to hydrolysis by plasmid-mediated β-lactamases expressed by Gram-negative bacteria, particularly Enterobacter species. Furthermore, unlike imipenem and some second generation Cephalosporins, cefepime is a poor inducer of type I β-lactamases.

Experimental models of infection have generally found cefepime to have activity superior to that of ceftazidime and cefotaxime against most clinically important Gram-positive and Gram-negative organisms. However, against infections caused by P. aeruginosa, cefepime had activity similar to that of ceftazidime.

Pharmacokinetic Properties

In healthy volunteers, cefepime reaches maximum serum concentrations (Cmax) of approximately 57.5 mg/L after administration of a 2g dose by intramuscular injection. The same dose of cefepime administered intravenously over a period of 30 minutes achieves higher serum concentrations than intramuscular administration, with Cmax values ranging from 126 to 193 mg/L. The drug has linear pharmacokinetics and an elimination half-life (t1/2β) of approximately 2 hours. Plasma protein binding is low, and the drug distributes widely into body tissues and fluids. Cefepime is primarily excreted by renal mechanisms as unchanged drug. The t1/2β of cefepime increases and clearance decreases progressively as renal function declines, necessitating dosage reduction in patients with renal impairment. Haemodialysis and haemofiltration remove cefepime from the systemic circulation with a t1/2β approximating that observed in individuals with normal renal function. Cefepime is removed to a lesser extent by continuous peritoneal dialysis.

Differences observed in the pharmacokinetic profile of cefepime in patients with lower respiratory tract infections, sepsis, or cystic fibrosis were not sufficient enough to require modified dosage recommendations for these patients.

Therapeutic Efficacy

Although the results of few comparative trials have been published to date, cefepime, administered intravenously or intramuscularly, has demonstrated efficacy in the treatment of bacteraemia, upper and lower respiratory tract infections, urinary tract infections, skin, skin structure and bone infections and gynaecological infections. Trials have been undertaken in US, European and Japanese patients.

The majority of comparative trials have compared the efficacy of cefepime with that of a third generation Cephalosporin ceftazidime. In most trials, equigravimetric doses were given; however, generally cefepime was administered intravenously twice daily and ceftazidime was administered intravenously 3 times daily. As treatment for nosocomial and community-acquired lower respiratory tract infections, cefepime is as effective as ceftazidime; both clinical (62 to 90% vs 64 to 94%) and bacteriological (69 to 97 vs 63 to 100%) efficacy rates were comparable in all studies. Although S. aureus and P. aeruginosa persisted most frequently, the numbers of pathogens were insufficient to differentiate between the comparator agents. Similarly, the efficacy of cefepime and ceftazidime could not be differentiated on the basis of recurrence of infection, which was rare. Cefepime also has efficacy comparable to that of ceftazidime in the treatment of bacteraemia, urinary tract infection and skin and skin structure infection. For example, clinical cure rates in patients with complicated urinary tract infection were 72 to 89% for patients receiving cefepime and 60 to 88% for ceftazidime-treated patients.

Cefepime 2g twice daily has been compared with cefotaxime 2g three times daily in patients with nosocomial lower respiratory tract infections and in patients with gynaecological infection. In these trials, the clinical and microbiological efficacy of cefepime and cefotaxime were comparable. Similarly, as treatment of intra-abdominal infection, the clinical efficacy of intravenous cefepime 2g twice daily (alone or in combination with metronidazole) was similar to that of a standard dosage of gentamicin in combination with either mezlocillin 3 to 4g every 4 to 6 hours or Clindamycin 0.9g every 8 hours, respectively.

Importantly, cefepime 2g three times daily was as effective as ceftazidime 2g three times daily, or a standard dosage regimen of piperacillin or mezlocillin in combination with gentamicin, as empirical treatment for fever in patients with neutropenia.

Tolerability

Cefepime has been well tolerated by adults in clinical trials conducted worldwide. Tolerability data pooled from clinical trials undertaken in North America and Europe indicate that cefepime has a tolerability profile similar to that of ceftazidime. The incidence of treatment withdrawal appeared to be dosage-related; therapy was discontinued because of an adverse event in 1.4% of patients receiving cefepime ≤2 g/day and in 2.9% of patients receiving cefepime =2 g/day.

A total of 20.3% of patients receiving cefepime in comparative trials experienced an adverse event, an incidence comparable to that observed in patients receiving ceftazidime. Gastrointestinal symptoms, including nausea (1.8%), diarrhoea (1.7%), vomiting (1.5%) and constipation (1.2%), and headache (3.2%) and rash (1.8%) were the most commonly occurring adverse events experienced by cefepime-treated patients.

Clinically relevant laboratory abnormalities were observed infrequently. Abnormal liver function tests were reported in ≤2.4% of patients receiving cefepime. A positive Coombs’ test was the most commonly occurring laboratory abnormality, but the clinical significance of this is unclear as no episodes of haemolysis were reported.

Intravenous and intramuscular administration of cefepime appeared to be well tolerated locally.

Dosage and Administration

Cefepime is generally administered by short intravenous infusion, but may also be administered by intramuscular injection. The most common dosage of cefepime in clinical trials was 2 or 4g daily administered in 2 divided doses; however, daily dosages as low as 1g and as high as 6g have been administered to adult patients.

The daily dosage of cefepime should be modified in patients with renal impairment. Depending on the severity of infection, the dosage and/or frequency of administration should be reduced in patients with Creatinine clearance (CLCR) values below 1.8 L/h (30 ml/min). For patients with a CLCR of between 0.66 and 1.8 L/h (11 and 30 ml/min) a dose of 1g once or twice daily or 0.5g twice daily is recommended, while 0.25 to 1g daily is recommended for patients with a CLCR of <0.6 L/h (10 ml/min). Patients undergoing haemodialysis or haemofiltration should be given a supplementary dose of cefepime 0.25g following every dialysis period. Patients undergoing peritoneal dialysis should receive cefepime 0.25 to 1g every 48 hours to maintain therapeutic cefepime concentrations.

Insufficient data are available to make any recommendations concerning the optimal dosage of cefepime in children; however, cefepime 50 mg/kg every 8 hours (to a maximum dose of 2g) has been administered to children with cystic fibrosis.

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References

  1. Akiyama H, Kanzaki H, Kanamoto A, Abe Y, Yamada T, et al. Cefepime in the field of dermatology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 332–337, 1991

    Google Scholar 

  2. Arguedas AG, Stutman HR, Zaleska M, Knupp CA, Marks MI, et al. Cefepime pharmacokinetics and clinical response in patients with cystic fibrosis. American Journal of Diseases of Children 146: 797–802, 1992

    PubMed  CAS  Google Scholar 

  3. Arkell D, Ashrap M, Andrews JM, Wise R. An evaluation of the penetration of cefepime into prostate tissue in patients undergoing elective prostatectomy. Correspondence. Journal of Antimicrobial Chemotherapy 29: 473–474, 1992

    PubMed  CAS  Article  Google Scholar 

  4. Bächer K, Schaeffer M, Lode H, Nord CE, Borner K, et al. Multiple dose pharmacokinetics, safety, and effects on faecal microflora, of cefepime in healthy volunteers. Journal of Antimicrobial Chemotherapy 30: 365–375, 1992

    PubMed  Article  Google Scholar 

  5. Barbhaiya RH, Forgue ST, Shyu WC, Papp EA, Pittman KA. High-pressure liquid Chromatographic analysis of BMY-28142 in plasma and urine. Antimicrobial Agents and Chemotherapy. 31: 55–59, 1987

    PubMed  CAS  Article  Google Scholar 

  6. Barbhaiya RH, Forgue ST, Gleason CR, Knupp CA, Pittman KA, et al. Safety, tolerance and pharmacokinetic evaluation of cefepime after administration of single intravenous doses. Antimicrobial Agents and Chemotherapy 34: 1118–1122, 1990a

    PubMed  CAS  Article  Google Scholar 

  7. Barbhaiya RH, Forgue ST, Gleason CR, Knupp CA, Pittman KA, et al. Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects. Antimicrobial Agents and Chemotherapy 36: 552–557, 1992a

    PubMed  CAS  Article  Google Scholar 

  8. Barbhaiya RH, Knupp CA, Pittman KA. Effects of age and gender on pharmacokinetics of cefepime. Antimicrobial Agents and Chemotherapy 36: 1181–1185, 1992b

    PubMed  CAS  Article  Google Scholar 

  9. Barbhaiya RH, Knupp CA, Pfeffer M, Zaccardelli D, Dukes GM, et al. Pharmacokinetics of cefepime in patients undergoing continuous ambulatory peritoneal dialysis. Antimicrobial Agents and Chemotherapy 36: 1387–1391, 1992c

    PubMed  CAS  Article  Google Scholar 

  10. Barbhaiya RH, Knupp CA, Pfeffer M, Pittman KA. Lack of pharmacokinetic interaction between cefepime and amikacin in humans. Antimicrobial Agents and Chemotherapy 36: 1382–1386, 1992d

    PubMed  CAS  Article  Google Scholar 

  11. Barbhaiya RH, Knupp CA, Forgue ST, Matzke GR, Halstenson CE, et al. Disposition of the Cephalosporin cefepime in normal and renally impaired subjects. Drug Metabolism and Disposition 19: 68–73, 1991

    PubMed  CAS  Google Scholar 

  12. Barbhaiya RH, Knupp CA, Tenney J, Martin RR, Weidler DJ, et al. Safety, tolerance and pharmacokinetics of cefepime administered intramuscularly to healthy subjects. Journal of Clinical Pharmacology 30: 900–910, 1990b

    PubMed  CAS  Google Scholar 

  13. Barbhaiya RH, Knupp CA, Forgue ST, Matzke GR, Guay DRP, et al. Pharmacokinetics of cefepime in subjects with renal insufficiency. Clinical Pharmacology and Therapeutics 48: 268–276, 1990c

    PubMed  CAS  Article  Google Scholar 

  14. Barckow D, Schwigon C-D. Cefepime versus cefotaxime in the treatment of lower respiratory tract infections. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 187–193, 1993

    PubMed  Google Scholar 

  15. Barriere SL. The pharmacokinetic profile of cefepime. American Journal of Medicine, in press, 1994

  16. Bauemfeind A, Schweighart S, Eberlein E, Jungwith R. In Vitro activity and stability against novel beta-lactamases of investigational beta-lactams (cefepime, cefpirome, flomoxef, SCE 2787 and piperacillin plus tazobactam) in comparison with established compounds (cefotaxime, latamoxef and piperacillin). Infection 19 (Suppl. 5): S264–S269, 1991

    Article  Google Scholar 

  17. Bellido F, Pechère J-C, Hancock REW. Reevaluation of the factors involved in the efficacy of new β-lactams against Enterobacter cloacae. Antimicrobial Agents and Chemotherapy 35: 73–78, 1991a

    PubMed  CAS  Article  Google Scholar 

  18. Bellido F, Pechère J-C, Hancock REW. Novel method for measurement of outer membrane permeability to new β-lactams in intact Enterobacter cloacae cells. Antimicrobial Agents and Chemotherapy 35: 68–72, 1991b

    PubMed  CAS  Article  Google Scholar 

  19. Berne TV, Yellin AE, Appleman MD, Heseltine PNR, Gill MA. A clinical comparison of cefepime and metronidazole versus gentamicin and Clindamycin in the antibiotic management of surgically treated advanced appendicitis. Surgery Gynecology and Obstetrics 177 (Suppl.): 18–22, 1993

    Google Scholar 

  20. Bhakta DR, Leader I, Jacobson R, Robinson-Dunn B, Honicky RE, et al. Antibacterial properties of investigational, new, and commonly used antibiotics against isolates of Pseudomonas cepacia in Michigan. Chemotherapy 38: 319–323, 1992

    PubMed  CAS  Article  Google Scholar 

  21. Bodey GP, Ho DH, LeBlanc B. In vitro studies of BMY-28412, a new broad-spectrum Cephalosporin. Antimicrobial Agents and Chemotherapy 27: 265–269, 1985

    PubMed  CAS  Article  Google Scholar 

  22. Bosso JA, Saxon BA, Matsen JM. Comparative activity of cefepime, alone and in combination, against clinical isolates of Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients. Antimicrobial Agents and Chemotherapy 35: 783–784, 1991

    PubMed  CAS  Article  Google Scholar 

  23. Chadha D, Wise R, Baldwin DR, Andrews JM, Ashby JP, et al. Cefepime concentrations in bronchial mucosa and serum following a single 2 gram intravenous dose. Journal of Antimicrobial Chemotherapy 25: 959–963, 1990

    PubMed  CAS  Article  Google Scholar 

  24. Chen HY, Livermore DM. Activity of cefepime and other β-lactam antibiotics against permeability mutants of Escherichia coli and Klebsiella pneumoniae. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 63–74, 1993a

    PubMed  Google Scholar 

  25. Chen HY, Livermore D.M. Effects of β-lactamase inducibility and derepression on the activity of cefepime and cefpirome against Gram-negative bacteria. Correspondence. Journal of Antimicrobial Chemotherapy 32: 651–652, 1993b

    PubMed  CAS  Article  Google Scholar 

  26. Chin N-X, Gu J-W, Fang W, Neu HC. In vitro activity of cefquinome, a new Cephalosporin, compared with other Cephalosporin antibiotics. Diagnostic Microbiology and Infectious Disease 15: 331–337, 1992

    PubMed  CAS  Article  Google Scholar 

  27. Chin NX, Gu JW, Fang W, Neu HC. In vitro activity of Ro 09–1428 compared to other Cephalosporins. European Journal of Clinical Microbiology and Infectious Diseases 10: 669–675, 1991

    CAS  Article  Google Scholar 

  28. Cho N, Fukunaga K, Kunii K, Deguchi K. Bacteriological, pharmacokinetic and clinical studies on cefepime in obstetrics and gynecology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 342–349, 1991

    Google Scholar 

  29. Clarke AM, Zemcov SJV, Wright JM. HR 810 and BMY-28412, two new Cephalosporins with broad-spectrum activity: an in-vitro comparison with other β-lactam antibiotics. Journal of Antimicrobial Chemotherapy 15: 305–310, 1985

    PubMed  CAS  Article  Google Scholar 

  30. Conrad DA, Scribner RK, Weber AH, Marks MI. In vitro activity of BMY-28412 against pediatric pathogens, including isolates from cystic fibrosis sputum. Antimicrobial Agents and Chemotherapy 28: 58–63, 1985

    PubMed  CAS  Article  Google Scholar 

  31. Cronqvist J, Nilsson-Ehle I, Öqvist B, Norrby SR. Pharmacokinetics of cefepime dihydrochloride arginine in subjects with renal impairment. Antimicrobial Agents and Chemotherapy 36: 2676–2680, 1992

    PubMed  CAS  Article  Google Scholar 

  32. Cynamon MH, Palmer GS, Sorg TB. Comparative in vitro activities of ampicillin, BMY 28412, and imipenem against Mycobacterium avium complex. Diagnostic Microbiology and Infectious Disease 6: 151–155, 1987

    PubMed  CAS  Article  Google Scholar 

  33. Dalet F, Segovia T. In vitro activity of cefepime (BMY-28412) against uropathogens. In Spanish. Revista Espanola de Quimioterapia 5: 255–262, 1992

    Google Scholar 

  34. Darveau RP, Cunningham MD. Influence of subinhibitory concentrations of Cephalosporins on the serum sensitivity of Pseudomonas aeruginosa. Journal of Infectious Diseases 162: 914–921, 1990

    PubMed  CAS  Article  Google Scholar 

  35. Di Marco R, Carrabba I, Cavallaro V, Zaccone P, Stazzone C, et al. The effect of cefepime on some immune parameters in vitro: lack of interference with mitogen-induced lymphoproliferation, immunoglobulin synthesis, IFN-Gamma and IL-2 secretion and IL-2 receptor expression. Journal of Chemotherapy 5: 297–301, 1993

    PubMed  Google Scholar 

  36. Doern GV, Vautour R. In vitro activity of cefrozil (BMY 28100) and cefepime (BMY 28142) against Streptococcus pneumoniae, Branhamella catarrhalis, and Haemophilus influenzae, and provisional interpretative criteria for disk diffusion and dilution susceptibility tests with Haemophilus influenzae. Diagnostic Microbiology and Infectious Disease 15: 633–640, 1992

    PubMed  CAS  Article  Google Scholar 

  37. Dornbusch K, Mörtsell E, Göransson E. In vitro activity of cefepime, a new parenteral Cephalosporin, against recent European blood isolates and in comparison with piperacillin/tazobactam. Chemotherapy 36: 259–267, 1990

    PubMed  CAS  Article  Google Scholar 

  38. Edelstein H, Chirurgi V, Oster S, Karp R, Cassano K, et al. A randomized trial of cefepime (BMY-28142) and ceftazidime for the treatment of pneumonia. Journal of Antimicrobial Chemotherapy 28: 569–575, 1991

    PubMed  CAS  Article  Google Scholar 

  39. Eggimann P, Glauser MP, Aoun M, Meunier F, Calandra T. Cefepime monotherapy for the empirical treatment of fever in granulocytopenic cancer patients. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 151–163, 1993

    PubMed  Google Scholar 

  40. Ehrhardt AF, Sanders CC. β-Lactam resistance amongst Enterobacter species. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 1–11, 1993

    PubMed  CAS  Google Scholar 

  41. Fuchimoto S, Orita K, Ueda Y, Kuwata Y, Kimura H, et al. Bacteriological and clinical studies of cefepime in the field of surgery. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 306–311, 1991

    Google Scholar 

  42. Fuchs PC, Jones RN, Barry AL, Thornsberry C. Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum Cephalosporin. Antimicrobial Agents and Chemotherapy 27: 679–682, 1985

    PubMed  CAS  Article  Google Scholar 

  43. Fung-Tomc J, Dougherty TJ, DeOrio FJ, Simich-Jacobson V, Kessler RE. Activity of cefepime against ceftazidime- and cefotaxime-resistant Gram-negative bacteria and its relationship to β-lactamase levels. Antimicrobial Agents and Chemotherapy 33: 498–502, 1989

    PubMed  CAS  Article  Google Scholar 

  44. Fung-Tomc J, Huczko E, Pearce M, Kessler RE. Frequency of in vitro resistance of Pseudomonas aeruginosa to cefepime, ceftazidime, and cefotaxime. Antimicrobial Agents and Chemotherapy 32: 1443–1445, 1988

    PubMed  CAS  Article  Google Scholar 

  45. Furuhata H, Iwai S, Sato T, Kunimatsu M, Nishikawa T, et al. Cefepime in the surgical field. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 265–275, 1991

    Google Scholar 

  46. Gentry LO, Rodriguez-Gomez. Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects. Antimicrobial Agents and Chemotherapy 35: 2371–2374, 1991

    PubMed  CAS  Article  Google Scholar 

  47. Giamarellou H. Low-dosage cefepime treatment for serious bacterial infections. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 123–132, 1993

    PubMed  Google Scholar 

  48. Goto Y, Yamazaki T, Nagai H, Shigeno H, Goto J, et al. Antimicrobial activity and sputum levels of a new cephem antibiotic cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 175–179, 1991

    CAS  Google Scholar 

  49. Gouin F, Papazian L, Martin C, Albanese J, Durbec O, et al. A non-comparative study of the efficacy and tolerance of cefepime in combination with amikacin in the treatment of severe infections in patients in intensive care. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 205–214, 1993

    PubMed  Google Scholar 

  50. Gradelski E, Fung-Tome J, Huczko E, Kessler RE. Development of resistance in Pseudomonas aeruginosa to broad-spectrum Cephalosporins via step-wise mutations. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 75–80, 1993

    PubMed  CAS  Google Scholar 

  51. Gubbelmans HLL, Materman ES, Maesen FPV. Cefepime versus ceftriaxone: a tolerance study by intramuscular injection. Journal for Drugtherapy and Research 15: 124–126, 1990

    Google Scholar 

  52. Hamelin BA, Moore N, Knupp CA, Ruel M, Vallée F, et al. Cefepime pharmacokinetics in cystic fibrosis. Pharmacotherapy 13: 465–470, 1993

    PubMed  CAS  Google Scholar 

  53. Hancock REW, Bellido F. Factors involved in the enhanced efficacy against Gram-negative bacteria of fourth generation Cephalosporins. Journal of Antimicrobial Chemotherapy 29 (Suppl. A): 1–6, 1992

    PubMed  CAS  Google Scholar 

  54. Harada Y, Yajin K, Suzuki M, Hirakawa K, Tada W, et al. Cefepime in otorhinolaryngology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 319–325, 1991

    Google Scholar 

  55. Hino J, Kimura M, Tatara O, Sumi M, Okimoto N, et al. Laboratory and clinical studies on cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl 2): 164–168, 1991

    Google Scholar 

  56. Hiraoka M, Masuyoshi S, Mitsuhashi S, Tomatsu K, Inoue M. Cephalosporinase interactions and antimicrobial activity of BMY-28412, ceftazidime and cefotaxime. Journal of Antibiotics 41: 86–93, 1988a

    PubMed  CAS  Article  Google Scholar 

  57. Hiraoka M, Inoue M, Mitsuhashi S. Hydrolytic rate at low drug concentration as a limiting factor in resistance to newer Cephalosporins. Reviews of Infectious Diseases 10: 746–751, 1988b

    PubMed  CAS  Article  Google Scholar 

  58. Hiraoka M, Masuyoshi S, Inoue M, Mitsuhashi S. Antibacterial activity of cefepime against cephalosporinase-producing bacteria and interactions with cephalosporinases. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 15–19, 1991

    CAS  Google Scholar 

  59. Hoepelman AIM, Kieft H, Aoun M, Kosmidis J, Strand T, et al. International comparative study of cefepime and ceftazidime in the treatment of serious bacterial infections Journal of Antimicrobial Chemotherapy, in press 1993

  60. Holloway WJ, Levine D, Schwartz R, Palmer D. Cefepime versus ceftazidime in the treatment of patients with serious infections. American Journal of Medicine, in press, 1994

  61. Huls CE, Prince RA, Seilheimer DK, Bosso JA. Pharmacokinetics of cefepime in cystic fibrosis patients. Antimicrobial Agents and Chemotherapy 37: 1414–1416, 1993

    PubMed  CAS  Article  Google Scholar 

  62. Imagawa A, Tsutsui N, Furukawa A, Numata A, Uema K, et al. Pharmacokinetics of cefepime in uremic patients. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 253–258, 1991

    Google Scholar 

  63. Immunocompromised Host Society. The design, analysis, and reporting of clinical trials on the empirical antibiotic management of the neutropenic patient. Journal of Infectious Diseases 161: 397–401, 1990

    Article  Google Scholar 

  64. Irifune M, Ogino H, Matsunaga T, Taya N, Kim S, et al. Cefepime in otorhinolaryngological infections. Practica Otologica (Kyoto) 84: 853–861, 1991

    Article  Google Scholar 

  65. Ishag AJ, Durgham SM, Shibl AM. In vitro susceptibility of methicillin-resistant Staphylococcus aureus to imipenem and other antimicrobial agents. Chemioterapia 6: 261–263, 1987

    PubMed  CAS  Google Scholar 

  66. Ito K, Tamaya T, Yamada Y, Hayasaki M, Ota T. Pharmacokinetic and clinical studies of cefepime in the field of obstetrics and gynecology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 354–365, 1991

    Google Scholar 

  67. Jacoby GA, Sutton L. β-Lactamases and β-lactam resistance in Escherichia coli. Antimicrobial Agents and Chemotherapy 28: 703–705, 1985

    PubMed  CAS  Article  Google Scholar 

  68. Jacoby GA, Carreras I. Activities of β-lactam antibiotics against Escherichia coli strains producing extended spectrum β-lactamases. Antimicrobial Agents and Chemotherapy 34: 858–862, 1990

    PubMed  CAS  Article  Google Scholar 

  69. Jarlier V, Nicolas MH, Fournier G, Philippon A. Extended broad-spectrum β-lactamases conferring transferable resistance to newer β-lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns. Reviews of Infectious Diseases 10: 867–878, 1988

    PubMed  CAS  Article  Google Scholar 

  70. Jauregui L, Matzke D, Scott M, Minns P, Hageage G. Cefepime as treatment for osteomyelitis and other severe bacterial infections. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 141–149, 1993

    PubMed  Google Scholar 

  71. Jin C, Miyazaki S, Kaneko Y, Tsuji A, Goto S. In vitro and in vivo antibacterial activity of cefepime, a new parenteral Cephalosporin. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 28–42, 1991

    CAS  Google Scholar 

  72. Jin C. Affinities of PBPs of Enterococci to cefepime and ampicillin. Nippon Saikingaku Zasshi 47: 373–385, 1992

    PubMed  CAS  Article  Google Scholar 

  73. Kaiman D, Barriere SL, Johnson Jr BL. Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoper-azone in serum and blister fluid. Antimicrobial Agents and Chemotherapy 36: 453–457, 1992

    Article  Google Scholar 

  74. Kato N, Bando K, Muto Y, Watanabe K, Ueno K. In vitro activity of cefepime, a new parenteral Cephalosporin, against anaerobic bacteria. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 43–51, 1991

    CAS  Google Scholar 

  75. Kessler RE, Bies M, Buck RE, Chisholm DR, Pursiano TA, et al. Comparison of a new Cephalosporin, BMY 28142, with other broad-spectrum β-lactam antibiotics. Antimicrobial Agents and Chemotherapy 27: 207–216, 1985

    PubMed  CAS  Article  Google Scholar 

  76. Kessler RE, Fung-Tomc J. Susceptibility of recent bacterial isolates from the cefepime clinical trials in the United States. American Journal of Medicine, in press, 1994

  77. Khan NJ, Bihl JA, Schell RF, LeFrock JL, Weber SJ. Antimicrobial activity of BMY-28412, cefbuperazone and cefpiramide compared with those of other Cephalosporins. Antimicrobial Agents and Chemotherapy 26: 585–590, 1984

    PubMed  CAS  Article  Google Scholar 

  78. Kieft H, Hoepelman AIM, Knupp CA, van Dijk A, Branger JM, et al. Pharmacokinetics of cefepime in patients with the sepsis syndrome. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 117–122, 1993

    PubMed  Google Scholar 

  79. Kim KW, Bayer AS. Efficacy of BMY-28142 in experimental bacteremia and meningitis caused by Escherichia coli and group B streptococci. Antimicrobial Agents and Chemotherapy 28: 51–54, 1985

    PubMed  CAS  Article  Google Scholar 

  80. King A, Boothman C, Phillips I. Comparative in vitro activity of cefpirome and cefepime, two new Cephalosporins. European Journal of Clinical Microbiology and Infectious Diseases 9: 677–685, 1990

    CAS  Article  Google Scholar 

  81. Klugman KP, Saunders J, Khoosal M. In-vitro activity of cefepime against bacterial pathogens from hospitalized patients. Correspondence. Journal of Antimicrobial Chemotherapy 32: 164–166, 1993

    PubMed  CAS  Article  Google Scholar 

  82. Kovarik JM, ter Maaten JC, Rademaker CMA, Deenstra M, Hoepelman IM, et al. Pharmacokinetics of cefepime in patients with respiratory tract infections. Antimicrobial Agents and Chemotherapy 34: 1885–1888, 1990

    PubMed  CAS  Article  Google Scholar 

  83. Kuga K, Inoue T, Nakamura H, Ishii M, Amagai R, et al. Bacteriological and clinical studies on cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 138–146, 1991

    Google Scholar 

  84. Kumazawa J, Matsumoto T, Ohkoshi M, Kawamura N, Nagata Y, et al. Comparative study of cefepime vs ceftazidime for the treatment of complicated urinary tract infections. Nishinihon Journal of Urology 54: 970–985, 1992a

    Google Scholar 

  85. Kumazawa J, Matsumoto T, Tanaka M, Kamidono S, Arakawa S, et al. Dose-finding study of cefepime for the treatment of complicated urinary tract infections. Nishinihon Journal of Urology 54: 285–298, 1992b

    Google Scholar 

  86. Labro MT. Immunomodulation by antibacterial agents: is it clinically relevant?. Drugs 45: 319–328, 1993

    PubMed  CAS  Article  Google Scholar 

  87. Léophonte P, Bertrand A, Nouvet G, Muir JF, Lucht F, et al. A comparative study of cefepime and ceftazidime in the treatment of community-acquired lower respiratory tract infections. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 165–173, 1993

    PubMed  Google Scholar 

  88. Levine D, Schwartz R, Palmer D. Cefepime versus ceftazidime for the treatment of serious bacterial infections: double-blind, randomized, comparative trial. American Journal of Medicine, in press, 1994

  89. Lindh E, Dornbusch K, Jalakas K, Forsgren A. Antibiotic susceptibility and β-lactamase production in clinical isolates of Enterobacter spp. APMIS 98: 462–470, 1992

    Article  Google Scholar 

  90. Marchou B, Michea-Hamzehpour M, Lucain C, Pechère J-C. Development of β-lactam resistant Enterobacter cloacae in mice. Journal of Infectious Diseases 156: 369–373, 1987

    PubMed  CAS  Article  Google Scholar 

  91. Masuyoshi S, Hirano M, Fujimura H, Shinoda M, Ohta A, et al. In vitro and in vivo antibacterial activity of cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 75–83, 1991

    CAS  Google Scholar 

  92. Masuyoshi S, Hiraoka M, Inoue M, Tomatsu K, Hirano M, et al. Comparison of the in vitro and in vivo antibacterial activities of cefepime (BMY-28142) with ceftazidime, cefuzonam, cefotaxime and cefmenoxime. Drugs Under Experimental and Clinical Research 15: 1–10, 1989

    PubMed  CAS  Google Scholar 

  93. Matsuda S, Suzuki M, Oh K. Pharmacokinetic and clinical studies of cefepime in the field of obstetrics and gynecology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 350–353, 1991

    Google Scholar 

  94. Matsumoto F, Sakurai I, Imai T, Takahashi T, Morita M. Bacteriological, pharmacokinetic and clinical studies on cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 157–163, 1991

    Google Scholar 

  95. McCabe R, Chirugi V, Farkas SA, Haddow A, Heinz G, et al. Cefepime versus ceftazidime in the treatment of lower respiratory tract infections. American Journal of Medicine, in press, 1994

  96. Mitsutake K, Higashiyama Y, Matsuda H, Miyazaki Y, Yoshitomi Y, et al. Laboratory and clinical studies with cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 180–187, 1991

    Google Scholar 

  97. Miyamoto N, Baba S, Kobayashi T, Yamamoto S, Tsuge I, et al. Fundamental and clinical investigation using cefepime (BMY-28142) in otorhinolaryngology. In Japanese. Jibi to Rinsho 37: 649–665, 1991

    Google Scholar 

  98. Mizutani S, Kameoka H, Miyoshi S, Iwao N, Higashimoto J, et al. Clinical experience with cefepime in complicated urinary tract infection. In Japanese. Chemotherapy (Tokyo) 30 (Suppl 2): 227–231, 1991

    Google Scholar 

  99. Moody JA, Peterson LR, Gerding DN. Comparative in vitro activity of BMY-28142 alone and in combination with amikacin against clinical strains of Pseudomonas aeruginosa, Staphylococcus aureus and Enterobacteriaceae. Current Therapeutic Research 39: 230–238, 1986

    CAS  Google Scholar 

  100. Mouton Y, Chidiac C, Humbert G, Leroy J, Veyssier P, et al. A non-comparative, multicentre study of cefepime in the treatment of serious bacterial infections. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 133–140, 1993

    PubMed  Google Scholar 

  101. Nagatani Y, Harada Y, Kanematsu M, Ban Y, Kawada Y, et al. Studies on the antibacterial activities and clinical efficacy of cefepime in urinary tract infection. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 221–226, 1991

    Google Scholar 

  102. Nakashimo M, Uematsu T, Kanamaru M, Nakanomyo H, Kidono M, et al. Clinical phase I study of cefepime (BMY-28142). In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 104–116, 1991

    Google Scholar 

  103. National Committee for Clinical Laboratory Standards, Jorgensen JH et al. (Eds). Performance standards for antimicrobial susceptibility testing. National Committee for Clinical Laboratory Standards Publication M100–S4, Villanova, Pennsylvania, 1992

    Google Scholar 

  104. National Committee for Clinical Laboratory Standards. Performance standards for antimicrobial susceptibility testing. National Committee for Clinical Laboratory Standards Publication Villanova, Pennsylvania, in press, 1993

  105. Neu HC. Mechanisms of bacterial resistance to antimicrobial agents, with particular reference to cefotaxime and other β-lactam compounds. Reviews of Infections Diseases 4 (Suppl.): S288–S299, 1982

    Article  Google Scholar 

  106. Neu HC. Safety of cefepime: a new extended-spectrum Cephalosporin antibiotic. American Journal of Medicine, in press, 1994

  107. Neu HC, Chin N-X, Huang H-B. In vitro activity and β-lactamase stability of FK-037, a parenteral Cephalosporin. Antimicrobial Agents and Chemotherapy 37: 566–573, 1993

    PubMed  CAS  Article  Google Scholar 

  108. Neu HC, Chin N-X, Jules K, Labthavikul P. The activity of BMY 28142 a new broad spectrum β-lactamase stable Cephalosporin. Journal of Antimicrobial Chemotherapy 17: 441–452, 1986

    PubMed  CAS  Article  Google Scholar 

  109. Neu HC, Chin N-X, Novelli A. In vitro activity of E-1040, a novel Cephalosporin with potent activity against Pseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 32: 1666–1675, 1988

    PubMed  CAS  Article  Google Scholar 

  110. Newton ER, Yoemans ER, Pastorek JG, Soper DE, Hemsell DL. Randomized comparative study of cefepime and cefotaxime in the treatment of acute obstetric and gynecological infection. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 195–204, 1993

    PubMed  Google Scholar 

  111. Nikaido H. Outer membrane barrier as a mechanism of antimicrobial resistance. Antimicrobial Agents and Chemotherapy 33: 1831–1836, 1989

    PubMed  CAS  Article  Google Scholar 

  112. Nikaido H, Liu W, Rosenberg EY. Outer membrane permeability and β-lactamase stability of dipolar ionic Cephalosporins containing methoxyimino substituents. Antimicrobial Agents and Chemotherapy 34: 337–342, 1990

    PubMed  CAS  Article  Google Scholar 

  113. Nishino T, Otsuki M, Masuyoshi S, Mitsuno H, Hiraoka H. In vitro and in vivo antibacterial activities of cefepime (BMY-28412). In Japanese. Chemotherapy (Tokyo) 39 (Suppl 2): 59–67, 1991

    Google Scholar 

  114. Nishitani Y, Uno S, Yamada D, Hayata S, Tsugawa M, et al. Bacteriological, pharmacokinetic and clinical studies on cefepime in urology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 242–252,1991

    Google Scholar 

  115. Norden CW, Gill EA. Cefepime for treatment of experimental chronic osteomyelitis due to Staphylococcus aureus. Correspondence. Journal of Infectious Diseases 162: 1218–1219, 1990

    CAS  Article  Google Scholar 

  116. Norden CW, Neiderriter K. In vitro activity of BMY-28412, a new Cephalosporin. Chemotherapy 33: 15–17, 1987

    PubMed  CAS  Article  Google Scholar 

  117. Nye KJ, Shi YG, Andrews JM, Wise R. Pharmacokinetics and tissue penetration of cefepime. Journal of Antimicrobial Chemotherapy 24: 23–28, 1989

    PubMed  CAS  Article  Google Scholar 

  118. Oishi K, Matsumoto K, Rikitomi N, Sonoda F, Takasugi M, et al. Clinical usefulness of cefepime, a new semi-synthetic Cephalosporin, in the treatment of bacterial respiratory infection. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 188–197, 1991

    Google Scholar 

  119. Okamoto MP, Chin A, Gill MA, Yellin AE, Berne TV, et al. Analysis of cefepime tissue penetration into human appendix. Pharmacotherapy 11: 353–358, 1991

    PubMed  CAS  Google Scholar 

  120. Okamoto MP, Nakahiro RK, Chin A, Bedikian A. Cefepime clinical pharmacokinetics. Clinical Pharmacokinetics 25: 88–102, 1993

    PubMed  CAS  Article  Google Scholar 

  121. Oster S, Edelstein H, Cassano K, McCabe R. Open trial of cefepime (BMY 28142) for infections in hospitalized patients. Antimicrobial Agents and Chemotherapy 34: 954–957, 1990

    PubMed  CAS  Article  Google Scholar 

  122. Paladino JA. Pharmacoeconomic comparison of cefepime and ceftazidime using decision analysis. Abstract 58. Pharmacotherapy 13: 682, 1993

    Google Scholar 

  123. Pechère J-C. Emergence of resistance during β-lactam therapy of Gram-negative infections. Bacterial mechanisms and medical responses. Drugs 35 (Suppl. 2): 22–28, 1988

    Google Scholar 

  124. Pechère J-C Vladoianu IR. Development of resistance during ceftazidime and cefepime therapy in a murine peritonitis model. Journal of Antimicrobial Chemotherapy 29: 563–573, 1992

    PubMed  Article  Google Scholar 

  125. Phillips I, King A, Gransden WR, Eykyn SJ. The antibiotic sensitivity of bacteria isolated from the blood of patients in St Thomas’ Hospital, 1969–1988. Journal of Antimicrobial Chemotherapy 25 (Suppl. C): 59–80, 1990

    PubMed  CAS  Google Scholar 

  126. Piddock LJV, Griggs DJ. Selection and characterization of cefepime-resistant Gram-negative bacteria. Journal of Antimicrobial Chemotherapy 28: 669–676, 1991

    PubMed  CAS  Article  Google Scholar 

  127. Pucci MJ, Boice-Sowek J, Kessler RE, Dougherty TJ. Comparison of cefepime, cefpirome, and cefaclidine binding affinities for penicillin-binding proteins in Escherichia coli K-12 and Pseudomonas aeruginosa SC8329. Antimicrobial Agents and Chemotherapy 35: 2312–2317, 1991

    PubMed  CAS  Article  Google Scholar 

  128. Qadri SMH, Ueno Y, Almodovar E, Tullo D, Al-Ahdal MN. Comparative in vitro evaluation of cefepime, an aminothiazolyl methoxyamino cephem. Drug Investigation 5: 127–134, 1993

    CAS  Google Scholar 

  129. Ramirez-Ronda C, May R, Doyle C, Tenney J. Cefepime (FEP) vs ceftazidime in moderately severe and severe skin infections requiring hospitalisation — an efficacy meta-analysis. Abstract 929. Clinical Infectious Diseases 17: 289, 1993

    Google Scholar 

  130. Ramphal R, Lew M, Glauser M. Worldwide experience with cefepime in the treatment of febrile episodes in neutropenic patients. Clinical Infectious Diseases, in press, 1994

  131. Raponi G, Keller N, Rozenberg-Arska M, Hoepelman IM, Verhoef J. The influence of cefepime on opsonophagocytosis of bacteria. Drugs Under Experimental and Clinical Research 15: 141–144, 1989

    PubMed  CAS  Google Scholar 

  132. Raponi G, Keller N, Overbeek BP, Rozenberg-Arska M, van Kessel KPM, et al. Enhanced phagocytosis of encapsulated Escherichia coli strains after exposure to sub-MICs of antibiotics is correlated to changes of the bacterial cell surface. Antimicrobial Agents and Chemotherapy 34: 332–336, 1990

    PubMed  CAS  Article  Google Scholar 

  133. Rolston KVI, Anaissie EA, Bodey GP. In-vitro susceptibility of Pseudomonas species to fifteen antimicrobial agents. Journal of Antimicrobial Chemotherapy 19: 193–196, 1987

    PubMed  CAS  Article  Google Scholar 

  134. Rolston KVI, Alvarez ME, Hsu K-C, Bodey GP. In-vitro activity of cefpirome (HR-810), WIN-49375, BMY-28412 and other antibiotics against nosocomially important isolates from cancer patients. Journal of Antimicrobial Chemotherapy 17: 453–457, 1986a

    PubMed  CAS  Article  Google Scholar 

  135. Rolston KVI, Ho DH, LeBlanc B, Bodey GP. Activity of newer antimicrobial agents against Aeromonas hydrophila. European Journal of Clinical Microbiology 5: 454–456, 1986b

    PubMed  CAS  Article  Google Scholar 

  136. Rolston KVI, Bodey GP. In vitro susceptibility of Acinetobacter species to various antimicrobial agents. Antimicrobial Agents and Chemotherapy 30: 769–770, 1986

    PubMed  CAS  Article  Google Scholar 

  137. Rolston KVI, Thirolf P, Ho DS, Bodey GP. Species dependent variability in the susceptibility of coagulase-negative staphylococci to various antimicrobial agents. Journal of Antimicrobial Chemotherapy 16: 659–662, 1985

    PubMed  CAS  Article  Google Scholar 

  138. Rolston KVI. Susceptibility of group B and group C streptococci to newer antimicrobial agents. European Journal of Clinical Microbiology 5: 534–536, 1986

    PubMed  CAS  Article  Google Scholar 

  139. Sáez-Llorens X, Castañno E, Garcia R, Villalaz F, Baez C, et al. Cefepime (CFP) versus cefotaxime (CTX) for the treatment of bacterial meningitis (BM) in children. Abstract 930. Clinical Infectious Diseases 17: 289, 1993

    Google Scholar 

  140. Saito A, Shigeno Y, Irabu Y, Fukuhara H, Saito A, et al. Dose finding study of cefepime for chronic respiratory infections. In Japanese. Kakenshogako Zasshi 66: 837–858, 1992a

    CAS  Google Scholar 

  141. Saito A, Shigeno Y, Irabu Y, Fukuhara H, Ohshiro H, et al. A comparative study of cefepime for chronic respiratory tract infections. In Japanese. Kakenshogaku Zasshi 66: 886–908, 1992b

    CAS  Google Scholar 

  142. Saito A, Shigeno Y, Irabu Y, Fukuhara H, Onodera S, et al. A comparative study of cefepime for bacterial pneumonia. In Japanese. Kakenshogaku Zasshi 66: 859–885, 1992c

    CAS  Google Scholar 

  143. Sanders CC. Cefepime: the next generation. Clinical Infectious Diseases 17: 369–379, 1993

    PubMed  CAS  Google Scholar 

  144. Sanders CC, Sanders Jr WE. Microbial Resistance to newer generation β-lactam antibiotics: clinical and laboratory implications. Journal of Infectious Diseases 151: 399–406, 1985

    PubMed  CAS  Article  Google Scholar 

  145. Sanders CC, Sanders Jr WE. Type I β-lactamases of Gram-negative bacteria: interactions with β-lactam antibiotics. Journal of Infectious Diseases 154: 792–800, 1986

    PubMed  CAS  Article  Google Scholar 

  146. Sato R, Nishioka K, Ogiwara H, Sato Y, Miura Y, et al. Sputum concentrations of cefepime and its therapeutic efficacy in respiratory tract infections. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 127–131, 1991

    Google Scholar 

  147. Schaeffer M, Bãcher K, Lode H, Borner K, Priesnitz M. Prospective randomized clinical study: cefepime (CEP) vs. mezlocillin (MEZ) plus sulbactam (SUL) in severe LRTI. Abstract. Presented at the 1990 International Congress on Antimicrobial Agents and Chemotherapy, 1990

  148. Schwartz R, Young LRD, Ramirez-Ronda C, Frank E. Intravenous cefepime versus intravenous ceftazidime for the treatment of serious skin and skin-structure infections. American Journal of Medicine, in press, 1994

  149. Sharifi R, Geckler R, Childs S. A comparative study of cefepime versus ceftazidime in the treatment of urinary tract infections. American Journal of Medicine, in press, 1994

  150. Sirot D, Chanal C, Labia R, Sirot J. Susceptibility of new β-lactams to the extended-spectrum β-lactamase CTX-1. Infection 17 28–30, 1989

    PubMed  CAS  Article  Google Scholar 

  151. Spangler SK, Applebaum PC, Kitch T, Jacobs MR. Activity of FK 037, cefpirome, cefepime, ceftriaxone, cefotaxime, ceftazidime, imipenem, biapenem and vancomycin against 90 penicillin-susceptible and -resistant pneumococci. Abstract 872. Clinical Infectious Diseases 17: 279, 1993

    Google Scholar 

  152. Steele Jr JCH, Edwards BH, Rissing JP. In-vitro activity of BMY 28142, a new aminothiazolyl Cephalosporin. Journal of Antimicrobial Chemotherapy 16: 463–468, 1985

    PubMed  CAS  Article  Google Scholar 

  153. Takebe K, Tamura T, Kasai F, Kudo K, Yanada A, et al. Clinical study on cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 385–388, 1991

    Google Scholar 

  154. Tanaka M, Inatsuchi H, Matsushita K, Kawamura N, Ohkoshi M, et al. Experimental and clinical investigation of cefepime in urology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 214–220, 1991

    Google Scholar 

  155. Tanaka M, Otsuki M, Nishino T. In vitro and in vivo activities of DQ-2556 and its mode of action. Antimicrobial Agents and Chemotherapy 36: 2595–2601, 1992

    PubMed  CAS  Article  Google Scholar 

  156. Taüber MG, Hackbarth CJ, Scott KG, Rusnak MG, Sande MA. New Cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits. Antimicrobial Agents and Chemotherapy 27: 340–342, 1985

    PubMed  Article  Google Scholar 

  157. Thompson JE, Bennion RS, Roettger R, Lally KP, Hopkins JA, et al. Cefepime for infections of the biliary tract. Surgery Gynecology and Obstetrics 177 (Suppl.): 30–34, 1993

    Google Scholar 

  158. Thornsberry C, Brown SD, Yee YC, Bouchillon SK, Marler JK, et al. In-vitro activity of cefepime and other antimicrobials: survey of European isolates. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 31–53, 1993

    PubMed  CAS  Google Scholar 

  159. Tomatsu K, Ando S, Masuyoshi S, Hirano M, Miyaki T, et al. Antibacterial activity of BMY-28142, a novel broad-spectrum Cephalosporin. Journal of Antibiotics 39: 1584–1591, 1986

    PubMed  CAS  Article  Google Scholar 

  160. Toye BW, Scriver SR, Low DE and the Canadian Antimicrobial Resistance Study Group. Canadian survey of antimicrobial resistance in Klebsiella spp. and Enterobacter spp. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 81–86, 1993

    PubMed  CAS  Google Scholar 

  161. Tsai YH, Bies M, Leitner F, Kessler RE. Therapeutic studies of cefepime (BMY 28412) in murine meningitis and pharmacokinetics in neonatal rats. Antimicrobial Agents and Chemotherapy 34: 733–738, 1990

    PubMed  CAS  Article  Google Scholar 

  162. Tsuji A, Maniatis A, Bertram MA, Young LS. In vitro activity of BMY-28412 in comparison with those of other β-lactam antimicrobial agents. Antimicrobial Agents and Chemotherapy 27: 515–519, 1985

    PubMed  CAS  Article  Google Scholar 

  163. Tsurumaru H, Yano H, Kiyota R, Uchizono A, Matsuzaki T, et al. Cefepime in otorhinolaryngological infection. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 326–331, 1991

    Google Scholar 

  164. Van der Auwera P, Santella PJ. Pharmacokinetics of cefepime: a review. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 103–115, 1993

    PubMed  Google Scholar 

  165. van Ogtrop ML, Mattie H, Guiot HFL, van Strijen E, Hazekamp A-M, et al. Comparative study of the effects of four Cephalosporins against Escherichia coli in vitro and in vivo. Antimicrobial Agents and Chemotherapy 34: 1932–1937, 1990

    PubMed  Article  Google Scholar 

  166. Van Landuyt HW, Lambert A, Boelaert J, Gordts B. In vitro activity of BRL 36650, a new penicillin. Antimicrobial Agents and Chemotherapy 29: 362–366, 1986

    PubMed  Article  Google Scholar 

  167. Visser MR, Hoepelman IM, Beumer H, Rozenberg-Arska M, Verhoef J. Comparative in vitro antibacterial activity of the new carbapenem meropenem (SM-7338). European Journal of Clinical Microbiology and Infectious Diseases 8: 1061–1064, 1989

    CAS  Article  Google Scholar 

  168. Vuye A, Pijck J. In vitro antibacterial activity of BMY-28412, a new extended-spectrum Cephalosporin. Antimicrobial Agents and Chemotherapy 27: 574–577, 1985

    PubMed  CAS  Article  Google Scholar 

  169. Washington JA, Jones RN, Gerlach EH, Murray PR, Allen SD, et al. Multicenter comparison of in vitro activities of FK-037, cefepime, ceftriaxone, ceftazidime, and cefuroxime. Antimicrobial Agents and Chemotherapy 37: 1696–1700, 1993

    PubMed  CAS  Article  Google Scholar 

  170. Watanabe N, Katsu K. Bactericidal activity of cefclidin (E1040) against Pseudomonas aeruginosa under conditions simulating plasma pharmacokinetics: lack of development of chromosomally-mediated resistance to β-lactams. Journal of Antimicrobial Chemotherapy 30: 475–487, 1992

    PubMed  CAS  Article  Google Scholar 

  171. Watanabe A, Aonuma S, Oizumi K, Honda Y, Tokue Y, et al. In vitro antimicrobial activity of cefepime and its therapeutic efficacy in respiratory infection. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 132–137, 1991

    Google Scholar 

  172. Yamamoto T, Yasuda J, Iwasaku K, Kanao M, Okado H. Bacteriological, pharmacokinetic and clinical studies on cefepime in the field of obstetrics and gynecology. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 366–372, 1991

    Google Scholar 

  173. Yamashita M, Takagi S, Maeda H, Kuwayama M, Arakawa S, et al. Antibacterial activity, pharmacokinetics and clinical study of cefepime. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 232–241, 1991

    Google Scholar 

  174. Yee YC, Thornsberry C, Brown SD, Bouchillon SK, Marler JK, et al. A comparative study of the in-vitro activity of cefepime and other antimicrobial agents against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. Journal of Antimicrobial Chemotherapy 32 (Suppl. B): 13–19, 1993

    PubMed  CAS  Google Scholar 

  175. Yellin AE, Berne TV, Appleman MD, Heseltine PNR, Gill MA, et al. A randomised study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis. Surgery Gynecology and Obstetrics 177 (Suppl.): 23–29, 1993

    Google Scholar 

  176. Yokota T, Jin C, Arai K. Cefepime, its in vitro antibacterial activity affinity to penicillin binding proteins (PBPs), synergy with complement or mouse cultured macrophages (Mø) in producing its bactericidal effect. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 20–27, 1991

    CAS  Google Scholar 

  177. Yokoyama T, Kodama T, Takesue Y, Okita M, Hiyama E, et al. Bacteriological and clinical studies on cefepime in the field of surgery. In Japanese. Chemotherapy (Tokyo) 39 (Suppl. 2): 312–318, 1991

    Google Scholar 

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Correspondence to Lee B. Barradell.

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Various sections of the manuscript reviewed by: R.B. Ellis-Pegler, Infectious Disease Unit, Auckland Hospital, Auckland, New Zealand; F. Fraschini, Dipartimento di Farmacologia, Chemioterapia E Tossicologia Medica, Milano, Italy; G. Gialdroni Grassi, Facolta di Medicina e Chirurgia, Università di Privia, Milano, Italy; A.M. Hoepelman, Department of Internal Medicine, Section of Clinical Immunology and Infectious Diseases, University Hospital Utrecht, Utrecht, The Netherlands; J.E. Hoppe, University Children’s Hospital, Tübingen, Germany; J. Kumazawa, Department of Urology, Faculty of Medicine, Kyushu University, Fukuoka, Japan; D.R Levine, Department of Medicine, Division of Infectious Diseases, Detroit Receiving Hospital and University Health Center, Detroit, Michigan, USA; M.P. Okamoto, Clinical Research Division, Kaiser Permanente, Southern California Region, Downey, California, USA; A. Saito, The First Department of Internal Medicine, Faculty of Medicine, University Ryukyus, Okinawa, Japan; C.C. Sanders, Department of Medical Microbiology, Creighton University School of Medicine, Omaha, Nebraska, USA.

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Barradell, L.B., Bryson, H.M. Cefepime. Drugs 47, 471–505 (1994). https://doi.org/10.2165/00003495-199447030-00007

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Keywords

  • Cystic Fibrosis
  • Cephalosporin
  • Cefotaxime
  • Ceftazidime
  • Lower Respiratory Tract Infection