Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & ISI's SCI  
Users online: 707  
Home | Subscribe | Feedback | Login 
About Latest Articles Back-Issues Articlesmenu-bullet Search Instructions Online Submission Subscribe Etcetera Contact
 
  NAVIGATE Here 
  Search
 
 :: Next article
 :: Previous article 
 :: Table of Contents
  
 RESOURCE Links
 ::  Similar in PUBMED
 ::  Search Pubmed for
 ::  Search in Google Scholar for
 ::  [PDF Not available] *
 ::  Citation Manager
 ::  Access Statistics
 ::  Reader Comments
 ::  Email Alert *
 ::  Add to My List *
* Registration required (free) 

  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Material and Methods
 ::  Results
 ::  Discussion
 ::  Acknowledgements
 ::  References
 ::  Article Figures
 ::  Article Tables

 Article Access Statistics
    Viewed2944    
    Printed103    
    Emailed2    
    PDF Downloaded0    
    Comments [Add]    

Recommend this journal


 


 
ARTICLE
Year : 1977  |  Volume : 23  |  Issue : 4  |  Page : 161-167

Cephradine-a new cephalosporin in recurrent urinary tract infection


Artificial Kidney Division Department of Medicine, Seth G. S. Medical College & K.E.M. Hospital, Parel, Bombay-400 012., India

Correspondence Address:
Vidya N Acharya
Artificial Kidney Division Department of Medicine, Seth G. S. Medical College & K.E.M. Hospital, Parel, Bombay-400 012.
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


PMID: 615262

Rights and PermissionsRights and Permissions


 :: Abstract 

Out of 866 bacterial isolates grown in significant colony counts from 3 consecutive mid-stream urine samples or from a single sample of urine obtained by suprapubic bladder puncture, 305 isolates (35.22%) were found to be sensitive to Cephradine. It was noted that Gram positive organisms (63.44%) manifested highest sensitivity to this antibiotic. Next in order was E. coli with a sensitivity of 60.54%. The clinical trial revealed a good response in 59.37% and 81.81; of patients with oral and injectable group re­spectively. The maximum response was seen in E. coli infections (89.47%) and Gram positive organisms coming next with 80% re­sponse. No major untoward reactions were noted in patients with or without azotaemia and the antibiotic could be used safely even in presence of renal failure.



How to cite this article:
Acharya VN, Shroff KJ, Mehta NH, Patel K C, Jadav SK. Cephradine-a new cephalosporin in recurrent urinary tract infection. J Postgrad Med 1977;23:161-7

How to cite this URL:
Acharya VN, Shroff KJ, Mehta NH, Patel K C, Jadav SK. Cephradine-a new cephalosporin in recurrent urinary tract infection. J Postgrad Med [serial online] 1977 [cited 2020 Dec 3];23:161-7. Available from: https://www.jpgmonline.com/text.asp?1977/23/4/161/42744



 :: Introduction Top


Cephradine is a new, acid stable, unique, broad spectrum, semisynthetic derivative of cephalosporine. It was syn­thesized in 1969 at the Squibb Institute for Medical Research . [4] The structure of Cephradine is shown in [Figure 1].

The previous bacteriological studies have demonstrated its antibacterial acti­vity against a wide range of micro-organ­isms including both Gram positive and Gram negative bacteria. It has been re­ported that cephradine is not acted upon by staphylococcal penicillinase. [5],[6],[18] It has also been proved by several investi­gators that cephalosporins are important agents for antimicrobial therapy of uri­nary tract infection. [14],[19] Cephradine has an advantage over other cephalosporins in that it is the only one of this group effective by both oral and injectable route. Various reports on the evaluation of cephradine in clinical situations have been published and these have confirmed that orally and parenterally it is highly effective in the treatment of infections of urinary tract. [3],[9],[12],[13],[16],[17],[18],[22]

It has been shown that most of the cephradine is excreted unchanged in the urine within 6 hours. [18],[23] However, in studies of mice, rats, dogs and monkeys, cephradine has been shown to possess a low order of acute, sub-acute and chronic toxicity after its administration by either route and does not induce any teratogenic changes in the offsprings of mice and rats. [8]

The study reported here was initiated to determine the effectiveness of cephra­dine by oral as well as parenteral route ix: treating recurrent urinary tract infec­tion with micro-organisms susceptible to cephradine and to record the incidences of side effects if any.


 :: Material and Methods Top


Urine cultures were done from 829 suspected cases of recurrent urinary tract infection by 3 consecutive mid-stream urine samples or by a single urine sample drawn by suprapubic bladder aspiration technique. The mid-stream samples were studied for significant bacteriuria (colony count of more than 10 5 organisms/ml.) by Dip Slide Inoculum Method as reported earlier. [10] The sensitivity test was perform­ed by impregnated disc method as de­scribed by Bauer and Kirby [1] by using 30 meg. sensitivity discs of cephradine. De­pending upon the zone of inhibition that developed round the disc, the organisms were labelled as highly sensitive (10-20 mm diameter), mildly sensitive (5-10 mm diameter) and resistant (less than 5 mm diameter).

Patient Selection: Patients taken up for the study were found to be suffering from an infection of urinary tract confirmed by the presence of micro-organism's in the urine in a concentration of >10 5 organ­isms/ml. as described above. Cephradine was administered to a total of 54 patients having recurrent urinary tract infection due to various causes. The underlying etiological factors for recurrent urinary tract infections were diabetes mellitus, calculus disease, prostatic enlargement, chronic pyelonephritis with varying grades of renal failure and congenital ab­normalities of urinary tract.

Trial Design: The treatment was start­ed on receipt of positive urine culture. Out of 54 patients, 32 were treated with oral cephradine in a dose of 1 gm. (2 capsules of 500 mgs. each) 4 times a day for 14 days. The remaining 22 patients were administered cephradine parente­rally in the dosage of 500 mgs. twice a day by intramuscular route for 14 days. Urine was cultured at the beginning of the trial and after 2, 7 and 14 days of the treatment. The same was repeated one month after stopping the treatment. The laboratory investigations including complete blood count with a differential smear, BUN, Creatinine and liver func­tion tests were carried out before and after starting the treatment.

Criteria for assessing efficacy: The re­sponse as obtained was graded as follows:

Good response: Symptomatic im­provement plus urine becoming sterile at 2 days after starting therapy and remaining sterile thereafter.

Partial response: Symptomatic im­provement plus urine becoming ste­rile at 2 days and remaining sterile at 7 days and/or 14 days, but not one month after stopping therapy.

Poor response: No symptomatic improvement, urine not becoming sterile at 2, 7 or 14 days.


 :: Results Top


A total of 866 bacterial isolates were obtained from 829 patients. Out of these, 305 isolates (35.22%) were found to be sensitive to cephradine. Bacteriological data on these 305 cultures is presented in [Table 1]. It can be seen that E. colt and Gram positive organisms showed higher sensitivity to cephradine while Pseudornonas aeruginosa and Proteus group were highly resistant to cephradine.

The results of oral and parenteral therapy have been evaluated separately as shown in [Table 2].

Although 59.37% and 81.81; 0 of the patients in oral and parenteral group re­spectively showed a good response, there is no statistically significant difference in the response in relation to the type of therapy (x 2 = 3.148, df = 2, N.S.). It was noted that 8 of these 54 patients had recurrent urinary tract infection due to other microorganisms after 14 days of therapy or one month after stopping treatment. These patients were consider­ed to have partial response, though the original infection cleared.

It can be noted from [Table 3] that maximum response was seen in E. colt infections (89.47%), in Gram positive organisms (80%) and in infections with other Gram negative organisms (77.77%) which include Providence group, Entero­bacter group and Alcaligenes f aecalis.

Out of 54 cases on trial, 11 showed azotaemia of varying degree with serum creatinine of 4.5 mg% to 15.3 mg%. There were 7 subjects with azotaemia in oral group and 4 in injectable group. Out of the patients in oral group group, 3 sub­jects became non-azotaemic with the con­trol of infection at the end of trial, 2 died due to septicaemia and had exhibited poor response and-2 showed good response, but still remained azotaemic. Out of 4 azotaemic patients in the injectable group, 2 responded with good outcome, 1 had partial response and 1 died due to end stage renal failure.

There was no significant difference in the renal function tests and liver function tests in both the azotaemic and non-azo­taemic groups except that there was a significant reduction in BUN (p<0.01) and Creatinine (p<0.05) in patients with azotaemia [Table 4] at the end of the therapy. [Table 4] shows the laboratory in­vestigations to include renal function tests and liver function tests before and after the trial in azotaemic and non-azo­taemic trial patients.

Side effects: No gastro-intestinal symp­toms were noted in both azotaemic and non-azotaemic patients. Transient skin rash was noted in one azotaemic patient which disappeared with anti-histaminics inspite of continuing the antibiotic with good outcome.


 :: Discussion Top


Many reports are available on the clini­cal trials of cephradine in acute urinary tract infection. However, there are only two such reports available in literature for its utility in recurrent urinary tract infection. [2],[13] The studies reported here were initiated to determine the effective­ness of a new antibiotic- cephradine by oral and parenteral route in treating re­current urinary tract infection with organisms susceptible to cephradine and to record the incidence of side effects.

The previous bacteriological studies of cephradine have demonstrated its bacteri­cidal activity, against a wide range of pathogens like staphylococcus, strepto­coccus,  Neisseria More Detailse,  Escherichia More Details, klebsiella, aerobacter and proteus group specially indole positive strains. [5],[19] The present study has shown that E. coli and Gram positive organisms were more sensitive to cephradine. Clinical trials at various centres have confirmed that orally and parenterally, cephradine is effective in the treatment of infections of the urinary tract caused by susceptible organ­isms. [2],[3],[9],[15],[16],[22] Published data of multicentric trials of cephradine in uri­nary tract infections has indicated that an average of 76% of patients showed satisfactory outcome. [21] Klastersky et al, [11] in their trials of cephradine in urinary tract infection, observed excellent re­sponse in 42% whereas the response was graded as only favourable in 21% cases. In the present study, good response was noted in 59.37% and 81.815 of the pa­tients treated by oral and parenteral route respectively. A maximum and satisfactory bacteriological response was noted in E. coli and in infections with other Gram negative organisms like Enterobacter group, Providence group and Alcaligenes faecalis. Gulati et al [7] have also reported a satisfactory bacte­riological suppression in majority of E. coli and Klebsiella infection.

The side effects noted were hardly any except in one azotaemic patient who developed a hypersensitivity rash. There appeared to be no deterioration in renal functions as well as in liver functions at the end of the study period. It has been stated that some of the patients of renal failure by the nature of their illness some­times have some degree of renal damage, however, cephradine does not lead to any deterioration. [2],[20] The same was confirm­ed by the present work too. Thus the study confirms the efficacy of cephradine in both azotaemic and non-azotaemic pa­tients with recurrent urinary tract infec­tion.


 :: Acknowledgements Top


This clinical trial was made possible by the financial support given by Messrs. Sarabhai Chemicals Ltd. We sincerely thank them for their supply of oral and parenteral cephradine for this work. Our thanks are also due to Dr. C. K. Desh­pande-President, K. E. M. Hospital and Seth G. S. Medical College Research Society for having given us facilities to carry out the project. For statistical analysis of the results we are grateful to Mrs. K. D. Lotlikar. The Laboratory Staff of No. 44-Department of Medicine carried out the biochemical and haemato­logical data for this project-our sincere gratitude to them.

 
 :: References Top

1.Bauer, A. W . , Kirby, W. H . , Sherris, J. C. and Turk, 1VI.: Antibiotic suscep­tibility testing by a standardised single disc method. Amer. J. Clin. Path., 45: 493-496, 1966.  Back to cited text no. 1    
2.Brillenburg, W. and Clarke, T. K.: Ce­phradine in the treatment of chronic re­current infections of the urinary tract. Curr. Med. Res. Opin., 4: 139-143, 1976.  Back to cited text no. 2    
3.Butler, M.: Clinical Trial. Cephradine in the treatment of urinary tract infec­tion. J. Irish Med. Assoc., 66: Suppl. 13, 1973.  Back to cited text no. 3    
4.DolFini, J. H., Applegate, G. Bach, Bernstein, B. J., Schwartz, S. and Wei­senborn, F.: A new class of semisynthetic penicillins and cephalosporins derived from D-2 (1, 4, cyclohaxadiencyl) glycine. J. Med. Chem., 14: 117-119, 1971.  Back to cited text no. 4    
5.Gadebusen, H. H., Miraglia, G. J., Basch, H. I., Goodwin, C., Pan, S. and Renz Kathleen, J.: A new orally absorb­ed cephalospcrin antibiotic. Adv. Anti­microb. Antineoplast. Chemotherapy, 2: 1059-1063, 1972.  Back to cited text no. 5    
6.Garrod, L. P., Lambert, H. P. and O'Grady, F.: In "Antibiotics and Chemo­therapy", 4th ed. Churchill, Livingstone, Edinburgh and London, 1973, p. 400.  Back to cited text no. 6    
7.Gulati, P. D., Agarwal, D. S., Baweja, U., Sethi, Kusum, Geeta V., Rizvi, S. N. A. and Vaishnava, H.: A newer cepha­losporin (cephradine) in the treatment of urinary tract infections. J. Assoc. Phys. Ind., 25: 2;49-254, 1977.  Back to cited text no. 7    
8.Hassert, G. L., Debaecke, P. J., Kulesza, J. S., Traina, V. M., Sinha, D. P. and Bernal, E.: Toxicological, Pathological and teratological studies in animals with cephradine, Antimicrobial Agents and Chemotherapy, 3: 682-685, 1973.  Back to cited text no. 8    
9.Hubsher, J. A., Zaki, A., Semar, R. W. and Bernfeld, G. E.: A multi-centre clini­cal trial with oral cephradine. In "8th International Congress of Chemotherapy, Athens Sept. 8-14" P. 23, Excerpta Medica, Amsterdam, 1973.  Back to cited text no. 9    
10.Jadhav, S. K . , Patel, K. C . , Jain, U . , Dastur, F. D. and Acharya, V. N.: Dip Slide Method in the diagnosis of Urinary tract infection. J. Assoc. Phys. India, 22: 255-259, 1974.  Back to cited text no. 10    
11.Klastersky, J., Dancan, D. and Weerts Daniele: Cephradine antibacterial activity and clinical effectiveness. Chemotherapy, 18: 191-204, 1973.  Back to cited text no. 11    
12.Landa, L.: Cephradine in the treatment of intestinal infections caused by Shigella or Salmonella organisms. Curr. Ther. Res. Clin. Exp., 14: 496-502, 1972.  Back to cited text no. 12    
13.Limson, B. M., Siasoeo, R. E. and Dial, F. P.: A new cephalosporin derivative cephridine, in the treatment of acute in­fective disease. Curr. Ther. Res. Clin. Exp., 14: 101-106, 1972.  Back to cited text no. 13    
14.Low, R. A. L. and Clarke, T. K.: Ce­phradine in urinary tract infections-a double blind comparison with Ampicil­lin Curr. Med. Res. Opin., 3: 211-217, 1975.  Back to cited text no. 14    
15.Martin, R. R.: Clinical experience with oral Cephradine, J. Irish. Med. Ass., 66: Suppl. 25, 1973.  Back to cited text no. 15    
16.Mclean, P.: Cephradine in the treatment of Urinary tract infection. J. Irish. Med. Ass., 66(6): Suppl. 16, 1973.  Back to cited text no. 16    
17.Mitelman, A.: Cephradine-A new syn­thetic cephalosporin, Clinical and bacter­iological evaluation. Dia. Med., 44: 152­153, 1972.  Back to cited text no. 17    
18.Neiss, E. S.: Cephradine-a summary of pre-clinical studies and clinical pharmacology. J. Irish. Med. Ass., 66(6): Suppl. 1, 1973.  Back to cited text no. 18    
19.Poutsiaki, J. W., Gadebusch, H. H., Keysser, C. H. and Schreiber, E. C.: Preclinical studies with Cephradine. Pro­ceedings of 8th International Congress of Chemotherapy. Athens 8-14 Sept. P-6, Excerpta Medica, Amsterdam, 1973.  Back to cited text no. 19    
20.Solomon, Anne E., Briggs, J. D., Me. Geachy, R. and Sleigh, J. D.: The ad­ministration of Cephradine to patients In renal failure. Brit. J. Clin. Pharmacol., 2: 443-448, 1975.  Back to cited text no. 20    
21.Squibb, E. R. and Sons, Inc. Lawrence­wille. Clinical summary cephradine (SQ 11-436) Worldwide clinical experience. International regulaticns affairs, N.J. U.S.A. 1971.  Back to cited text no. 21    
22.Whitworth, Judith A., Fairley, K. F. and Mclvor Margaret M.: Cephradine in re , current urinary tract infection. Med. J Aust., 2: 742-747, 1973.  Back to cited text no. 22    
23.Zaki , A., Schreiber, E. C., Weliky, J., Knill, J. R. and Hubsher, J. A.: Clinical Pharmacology cf oral cephradine. J. Clin. Pharmaccl., 14: 118-126, 1974.  Back to cited text no. 23    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
Print this article  Email this article
Previous article Next article
Online since 12th February '04
© 2004 - Journal of Postgraduate Medicine
Official Publication of the Staff Society of the Seth GS Medical College and KEM Hospital, Mumbai, India
Published by Wolters Kluwer - Medknow