Journal of Chemotherapy
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections S. Esposito, C. Sardaro, G.B. Gaeta, D. Galante, G. Giusti & F. Basani To cite this article: S. Esposito, C. Sardaro, G.B. Gaeta, D. Galante, G. Giusti & F. Basani (1991) Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections, Journal of Chemotherapy, 3:1, 42-44, DOI: 10.1080/1120009X.1991.11739062 To link to this article: http://dx.doi.org/10.1080/1120009X.1991.11739062
Published online: 15 Jul 2016.
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Citing articles: 2 View citing articles
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Date: 05 October 2017, At: 03:35
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Journal of Chemotherapy
Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections S. ESPOS ITO - C. SARDARO G .B. GAE TA - D . GALANTE G. GIUSTI - F. BASAN I ,.,
Summmy Cefodi zime is a stable new beta -lac tamase cephalosporin chemi cally related to cefotaxime and with a long half-life. Its clinical efficacy and tolerability were compared with those of norfloxacin in patients with intercurrent urinary tract infec tions plus chronic liver diseases. Cefodizime (2 g, once a day, i. v. ) and norfloxacin (400 mg, twice a day , p.o.) were randoml y given to two groups of 20 patients each with urinary tract infections caused by orga nisms sensitive in vitro to these drugs. Cultures of midstrea m bladder urine, urinalysis and blood biochemi cal tes ts were perform ed before ami aft er each antibiotic treatment. Clinical resolution was observed in 100 % of the patients at the end of the treatm ents, but bacteriological eradication was obtained in 90% of the patients trea ted with cefodizime and 85 % of those treated with norfl oxacin, because of the development in fi ve patients of asymptomatic bacteriuria (superinfection s). Key words: cefodizine, norfloxacin , urinary tract infection, UTI, liver disease.
Depar tment of I nfec tious Diseases , First Med ical School, Universit y of Na ples, Italy. * Marketing Department , H oechst Itali a, Mil an, It al y. Address correspondence to : Espos ito Si lva no, M .D ., Department of Infec ti ous Diseases, Uni versity of Nap les, O spedale G esu e Maria , Vi a D. Cotugno 1, 8013 5 N aples , I taly. © Edizioni Ri viste Scien tifiche - Fi renze
Vol. 3 - n. 1 (42 -44) - 199 1
INTRO D UC TION
Cefodizime is a new antibacterial agent whose chemical structure is very close to th at of cefotaxime. It h as high serum protein binding (8 1% ) which lead s to low clearance (5 9 ml/min) and , consequently, a long half-life, 4 .2 h 1 • After a single intravenous administra tion of 1 g th e serum level of the drug is much higher th an the minimal 90 % inhibitory concentrations for Enterobac teria, Streptococci (excluding enterococci) , Staphylococci, N eisseria and H ae mophilus strains 2 • 3 . It is also highly stable to plasmid mediated beta-lac tamases and h as a hi gh affinity for PBP1 , which provides rapid bac tericid al action 4 • Cefodizime also see ms to have a positive influence on th e immune sys tem by stimulating lymphocy te proliferatio n , as demonstrated in vitro s' 6 ' 7 • U rinary trac t infec tions (UTis) are very freq uent b ac terial co mplica tion s in pa tients affec ted by liver cirrh osis, especially when poor ge neral health accompanies the liver disease. These patients frequently require paren teral therapies for their underlying co nditions and , because of the concomitant gas tric lesions, do no t tolera te well the oral administration of drugs. The aim of the prese nt study was to compare th e clinical efficacy and tolerability of cefodizime, given intravenously, with those of norfloxacin give n orally, in 40 randomized patients affec ted by intercurrent urin ary trac t infec tion s and live r cirrhosis. The reasons given above justify, in o ur opinion , a comparative stud y of a new intravenous antibiotic with one of the most effec tive oral agents for trea tment of UTis. ISSN 11 20-099X
43
CEFODIZINE (HR22 1) VERSUS NORFLOXACIN FOR TREATMENT OF URINARY TRACT INFECTIONS
MATERIAL AND METHODS
A total of 41 patients entered the study. The only significant demographic characteristic of the two groups, as reported in Table 1, was that females were prevalent (34 out of 41 = 83%), but th ere were no significant differences in the two groups. The mean age was 61 years (range 18-92).
Downloaded by [Australian Catholic University] at 03:35 05 October 2017
TABLE
.
Anribiot ics --
Demographic characteristics of the patients. N. of pts
--
Sex
Age (years)
--
RESULTS
Gram-negative bacteria were much more frequently isolated from urine culture th an grampositive as reported in Table 2. Escherichia coli was detec ted in 30 of 41 patients and a mixed culture was found only in one patient (E. coli +
Mo rganella mmganii).
-
Mean Range
mical tests performed before and after treatments were looked for in the two groups of patients using Student's t test and the Pearson test.
M ale
Female
~
Cefod izime Nor fl oxac in
2 1 ,., 20
60 62
18-8 1 42-92
3 (14 % ) 4 (20 % )
18 (86 % ) 16 (80 % )
T oral
41
61
18-92
7 (17 %)
34 (83%)
'' One drop-out .
Patients younger th an 18 years were excluded from the study as well as pregnant women, patients with impaired renal function and/or patients with allergy to cephalosporins or quinolones. All patients h ad mild or mod era te UTI which was defin ed by clinical signs and symptoms and by a midstrea m bladder urine wit h more th an 100,000 CFU/ml of urine. Minimu m inhibitory co ncentrations (MICs) of cefodizime and norfloxacin against all the responsible bacteria were de termin ed . They were always se nsitive to both antibiotics under examin ation . 70% of the patients were affec ted by liver cirrhosis and the remaining 30 % by other liver diseases. Cefodizime, supplied by Hoechst Italia Spa, Milan, Italy, was give n intraveno usly once a day at the dosage of 2 grams and norfloxacin (Merck, Sharp & D ohme) was given orally bid at 400 mg per dose. Both drugs were given for 5-10 days. Bacteriological checks of urine were done before, 3 d ays after th e beginning of the therapy, 3 days after the end and 3 weeks later (follow-up) . Urinalysis and routine blood biochemical tests were performed before and after th e end of each treatme nt . The significance of difference in the demographic distribution of patients, in the clinical and bacteriological responses and blood bioche-
Data concerning the clinical and bac teriological results observed at the end of treatment are summarized in Table 3. Three days af ter the end of the therapy we observed clinical resolu tion in 100 % of patients and bac teriological eradication in 90 % of patients trea ted with cefodizime and 85% of those trea ted with norfloxacin . This difference is not sta tistically signifi cant (P > 0.05). Super-
TABLE 2 - Bacteria responsible for UTTs treated with ce/odi:r.ime and 1101jloxacin.
N. of st rain s Orga ni sms
E. coli Staphylococcus aureus Proteus mirabilis Proteus vulgaris 5en'l1tia lique/acicns Klebsiella pncumoniae Klebsiella oxytoca Morganella morganii
TABLE
Cefodi zime group
Norfloxac in group
19
11
3
2
3 · Clinical and bacteriological results. Cefodiz ime
Norfloxacin
N. of patients
20
20
C li nical re solutions
20 (100 %)
20 (100 %)
Bacteriolog ica l eradicat ion
18 (90%)
17 (85%)
Bacteriologica l superinfec ti ons
2 (10%) ,,
,., S. au reus (2). "" S. aureus (2), Candida albicans (1).
3 (15%) '"'
Downloaded by [Australian Catholic University] at 03:35 05 October 2017
44
S. ESPOSITO - C . SARDARO - G.B. GAETA - D. GALANTE - G. GIUSTI - F. BASAN I
infections occurred in two patients after cefodizime treatment and in three patients following norfloxacin treatment. When bacteriological eradication occurred at the end of the therapy, it was always confirmed by a sterile urine culture at the follow-up check 3 weeks later. Side effects were mild and infrequent for both cefodizime and norfloxacin, necessitating interruption of treatment for only one patient who had a cutaneous rash soon after the first administration of cefodizime. This patient was, of course, not included in the evaluation of the clinical and bacteriological responses. The remaining side-effects were : two glossitis + diarrhea after cefodizime therapy and one glossitis and two nausea after norfloxacin therapy . No statistically significant differences in urinalysis and blood biochemical tests before and after treatments were seen.
which means that bac teria responsible for the first infections were always eradicated . In conclusion, the results of the present study, even if limited to a small number of patients, sugges t that cefodizime given intravenously once a day is as effective as norfloxacin in curing urinary tract infections and eradicating the responsible bacteria and its therapeutic use is advisable when the parenteral route is preferred. It efficacy, tolerability and incidence of side-effec ts is comparable with that of norflo xacin, which is a well known and widely utilized antimicrobial agent for treatment of urinary tract infections.
DISCUSSION
REFERENCES
The in-vitro sensitivity test showed good antibacterial activity for cefodizime and norfloxacin against all the bacteria isolated from the urine cultures . In fact, the MICs of both drugs were always within a range whereby all bacteria could be considered highly sensitive to their antibacterial activity, so that no patien t h ad to be excluded from the study because of in-vitro bacterial resistance of the responsible pathogen . In agreement with the favorable in-vitro results, we observed in this study therapeutic efficacy against mild and moderate urinary tract infections caused by a wide range of mostly gram-negative bacteria. Subjective symptoms of UTI soon disappeared from all patients under treatment and urine was sterile in 90% of patients treated with cefodizim~ and 85% of those treated with norfloxacin. We never observed persistence of the original responsible bacteria, only superinfections (in five patients)
' Shafer-Kortig M , Kortig M , Maas L, K iesel N, Gr igolei t HG , Mutshl er E. Cefod izime penet ration in to skin suction bli ster fluid followin g a single intravenous dose . Eur J C lin Pharm 1986; 30: 295 -298. 2 Limbe rt M, K iesel N, Seeger K, Seibert G, W in kler I , Schri nner E. Cefod izime: an aminoth iazolyl cephalosorin : in vitro act ivity. J Antibiot 198 4; 37 : 892-900. ' Jones RN , Barry AL, Thornsberry C, Wi lso n HW. In vitro ant ibacterial ac tivity of cefodizime (HR22 1), a new se mi sy nthetic cephalosporin . Antimicrob Agents C h emo ther 198 1; 20: 760-768. 4 Scull y BE, Jules K , Neu HC. In vitro activity and betalactamase stability of Cefod izime, an aminothi azolyl-iminomethoxy ceph alospor in. Ant imicrob Agents C hemother 1983; 23: 907-913. ' Limbert M, Bar tl ett RR, Dickniete G, et al. Cefod izime: am in othiazolyl cephalosporin: Influence on the immun e system. J Antib iot 1984; 37: 171 9- 1726. 6 Labro MT, Amit N, Babin -C heva ye C, Hakim J . Cefodi zime (HR221) pote ntiation of human neu troph il oxyge nindependent bactericidal act ivity . J Antimicrob Chemother 1987; 19: 331-341. ' Leyhausen M, Seibert G , Maidhof A, Muller EG. Differen ti al stimulation o f lymphocyte cell grow th in vitro by cephalospor ins. Ant imicrob Agents C hemother 1984; 26: 752-756.
ACKNOW LEDGMENTS: We wish to th ank Mr. Giacomo Buonocore and Mrs. Raffaell a Cartell a for their laboratory and clinical ass istance. The present stud y was partly su pported by CNR, Roma, It aly.
ISSN: 1120-009X (Print) 1973-9478 (Online) Journal homepage: http://www.tandfonline.com/loi/yjoc20
Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections S. Esposito, C. Sardaro, G.B. Gaeta, D. Galante, G. Giusti & F. Basani To cite this article: S. Esposito, C. Sardaro, G.B. Gaeta, D. Galante, G. Giusti & F. Basani (1991) Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections, Journal of Chemotherapy, 3:1, 42-44, DOI: 10.1080/1120009X.1991.11739062 To link to this article: http://dx.doi.org/10.1080/1120009X.1991.11739062
Published online: 15 Jul 2016.
Submit your article to this journal
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yjoc20 Download by: [Australian Catholic University]
Date: 05 October 2017, At: 03:35
Downloaded by [Australian Catholic University] at 03:35 05 October 2017
Journal of Chemotherapy
Cefodizine (HR221) Versus Norfloxacin for Treatment of Urinary Tract Infections S. ESPOS ITO - C. SARDARO G .B. GAE TA - D . GALANTE G. GIUSTI - F. BASAN I ,.,
Summmy Cefodi zime is a stable new beta -lac tamase cephalosporin chemi cally related to cefotaxime and with a long half-life. Its clinical efficacy and tolerability were compared with those of norfloxacin in patients with intercurrent urinary tract infec tions plus chronic liver diseases. Cefodizime (2 g, once a day, i. v. ) and norfloxacin (400 mg, twice a day , p.o.) were randoml y given to two groups of 20 patients each with urinary tract infections caused by orga nisms sensitive in vitro to these drugs. Cultures of midstrea m bladder urine, urinalysis and blood biochemi cal tes ts were perform ed before ami aft er each antibiotic treatment. Clinical resolution was observed in 100 % of the patients at the end of the treatm ents, but bacteriological eradication was obtained in 90% of the patients trea ted with cefodizime and 85 % of those treated with norfl oxacin, because of the development in fi ve patients of asymptomatic bacteriuria (superinfection s). Key words: cefodizine, norfloxacin , urinary tract infection, UTI, liver disease.
Depar tment of I nfec tious Diseases , First Med ical School, Universit y of Na ples, Italy. * Marketing Department , H oechst Itali a, Mil an, It al y. Address correspondence to : Espos ito Si lva no, M .D ., Department of Infec ti ous Diseases, Uni versity of Nap les, O spedale G esu e Maria , Vi a D. Cotugno 1, 8013 5 N aples , I taly. © Edizioni Ri viste Scien tifiche - Fi renze
Vol. 3 - n. 1 (42 -44) - 199 1
INTRO D UC TION
Cefodizime is a new antibacterial agent whose chemical structure is very close to th at of cefotaxime. It h as high serum protein binding (8 1% ) which lead s to low clearance (5 9 ml/min) and , consequently, a long half-life, 4 .2 h 1 • After a single intravenous administra tion of 1 g th e serum level of the drug is much higher th an the minimal 90 % inhibitory concentrations for Enterobac teria, Streptococci (excluding enterococci) , Staphylococci, N eisseria and H ae mophilus strains 2 • 3 . It is also highly stable to plasmid mediated beta-lac tamases and h as a hi gh affinity for PBP1 , which provides rapid bac tericid al action 4 • Cefodizime also see ms to have a positive influence on th e immune sys tem by stimulating lymphocy te proliferatio n , as demonstrated in vitro s' 6 ' 7 • U rinary trac t infec tions (UTis) are very freq uent b ac terial co mplica tion s in pa tients affec ted by liver cirrh osis, especially when poor ge neral health accompanies the liver disease. These patients frequently require paren teral therapies for their underlying co nditions and , because of the concomitant gas tric lesions, do no t tolera te well the oral administration of drugs. The aim of the prese nt study was to compare th e clinical efficacy and tolerability of cefodizime, given intravenously, with those of norfloxacin give n orally, in 40 randomized patients affec ted by intercurrent urin ary trac t infec tion s and live r cirrhosis. The reasons given above justify, in o ur opinion , a comparative stud y of a new intravenous antibiotic with one of the most effec tive oral agents for trea tment of UTis. ISSN 11 20-099X
43
CEFODIZINE (HR22 1) VERSUS NORFLOXACIN FOR TREATMENT OF URINARY TRACT INFECTIONS
MATERIAL AND METHODS
A total of 41 patients entered the study. The only significant demographic characteristic of the two groups, as reported in Table 1, was that females were prevalent (34 out of 41 = 83%), but th ere were no significant differences in the two groups. The mean age was 61 years (range 18-92).
Downloaded by [Australian Catholic University] at 03:35 05 October 2017
TABLE
.
Anribiot ics --
Demographic characteristics of the patients. N. of pts
--
Sex
Age (years)
--
RESULTS
Gram-negative bacteria were much more frequently isolated from urine culture th an grampositive as reported in Table 2. Escherichia coli was detec ted in 30 of 41 patients and a mixed culture was found only in one patient (E. coli +
Mo rganella mmganii).
-
Mean Range
mical tests performed before and after treatments were looked for in the two groups of patients using Student's t test and the Pearson test.
M ale
Female
~
Cefod izime Nor fl oxac in
2 1 ,., 20
60 62
18-8 1 42-92
3 (14 % ) 4 (20 % )
18 (86 % ) 16 (80 % )
T oral
41
61
18-92
7 (17 %)
34 (83%)
'' One drop-out .
Patients younger th an 18 years were excluded from the study as well as pregnant women, patients with impaired renal function and/or patients with allergy to cephalosporins or quinolones. All patients h ad mild or mod era te UTI which was defin ed by clinical signs and symptoms and by a midstrea m bladder urine wit h more th an 100,000 CFU/ml of urine. Minimu m inhibitory co ncentrations (MICs) of cefodizime and norfloxacin against all the responsible bacteria were de termin ed . They were always se nsitive to both antibiotics under examin ation . 70% of the patients were affec ted by liver cirrhosis and the remaining 30 % by other liver diseases. Cefodizime, supplied by Hoechst Italia Spa, Milan, Italy, was give n intraveno usly once a day at the dosage of 2 grams and norfloxacin (Merck, Sharp & D ohme) was given orally bid at 400 mg per dose. Both drugs were given for 5-10 days. Bacteriological checks of urine were done before, 3 d ays after th e beginning of the therapy, 3 days after the end and 3 weeks later (follow-up) . Urinalysis and routine blood biochemical tests were performed before and after th e end of each treatme nt . The significance of difference in the demographic distribution of patients, in the clinical and bacteriological responses and blood bioche-
Data concerning the clinical and bac teriological results observed at the end of treatment are summarized in Table 3. Three days af ter the end of the therapy we observed clinical resolu tion in 100 % of patients and bac teriological eradication in 90 % of patients trea ted with cefodizime and 85% of those trea ted with norfloxacin . This difference is not sta tistically signifi cant (P > 0.05). Super-
TABLE 2 - Bacteria responsible for UTTs treated with ce/odi:r.ime and 1101jloxacin.
N. of st rain s Orga ni sms
E. coli Staphylococcus aureus Proteus mirabilis Proteus vulgaris 5en'l1tia lique/acicns Klebsiella pncumoniae Klebsiella oxytoca Morganella morganii
TABLE
Cefodi zime group
Norfloxac in group
19
11
3
2
3 · Clinical and bacteriological results. Cefodiz ime
Norfloxacin
N. of patients
20
20
C li nical re solutions
20 (100 %)
20 (100 %)
Bacteriolog ica l eradicat ion
18 (90%)
17 (85%)
Bacteriologica l superinfec ti ons
2 (10%) ,,
,., S. au reus (2). "" S. aureus (2), Candida albicans (1).
3 (15%) '"'
Downloaded by [Australian Catholic University] at 03:35 05 October 2017
44
S. ESPOSITO - C . SARDARO - G.B. GAETA - D. GALANTE - G. GIUSTI - F. BASAN I
infections occurred in two patients after cefodizime treatment and in three patients following norfloxacin treatment. When bacteriological eradication occurred at the end of the therapy, it was always confirmed by a sterile urine culture at the follow-up check 3 weeks later. Side effects were mild and infrequent for both cefodizime and norfloxacin, necessitating interruption of treatment for only one patient who had a cutaneous rash soon after the first administration of cefodizime. This patient was, of course, not included in the evaluation of the clinical and bacteriological responses. The remaining side-effects were : two glossitis + diarrhea after cefodizime therapy and one glossitis and two nausea after norfloxacin therapy . No statistically significant differences in urinalysis and blood biochemical tests before and after treatments were seen.
which means that bac teria responsible for the first infections were always eradicated . In conclusion, the results of the present study, even if limited to a small number of patients, sugges t that cefodizime given intravenously once a day is as effective as norfloxacin in curing urinary tract infections and eradicating the responsible bacteria and its therapeutic use is advisable when the parenteral route is preferred. It efficacy, tolerability and incidence of side-effec ts is comparable with that of norflo xacin, which is a well known and widely utilized antimicrobial agent for treatment of urinary tract infections.
DISCUSSION
REFERENCES
The in-vitro sensitivity test showed good antibacterial activity for cefodizime and norfloxacin against all the bacteria isolated from the urine cultures . In fact, the MICs of both drugs were always within a range whereby all bacteria could be considered highly sensitive to their antibacterial activity, so that no patien t h ad to be excluded from the study because of in-vitro bacterial resistance of the responsible pathogen . In agreement with the favorable in-vitro results, we observed in this study therapeutic efficacy against mild and moderate urinary tract infections caused by a wide range of mostly gram-negative bacteria. Subjective symptoms of UTI soon disappeared from all patients under treatment and urine was sterile in 90% of patients treated with cefodizim~ and 85% of those treated with norfloxacin. We never observed persistence of the original responsible bacteria, only superinfections (in five patients)
' Shafer-Kortig M , Kortig M , Maas L, K iesel N, Gr igolei t HG , Mutshl er E. Cefod izime penet ration in to skin suction bli ster fluid followin g a single intravenous dose . Eur J C lin Pharm 1986; 30: 295 -298. 2 Limbe rt M, K iesel N, Seeger K, Seibert G, W in kler I , Schri nner E. Cefod izime: an aminoth iazolyl cephalosorin : in vitro act ivity. J Antibiot 198 4; 37 : 892-900. ' Jones RN , Barry AL, Thornsberry C, Wi lso n HW. In vitro ant ibacterial ac tivity of cefodizime (HR22 1), a new se mi sy nthetic cephalosporin . Antimicrob Agents C h emo ther 198 1; 20: 760-768. 4 Scull y BE, Jules K , Neu HC. In vitro activity and betalactamase stability of Cefod izime, an aminothi azolyl-iminomethoxy ceph alospor in. Ant imicrob Agents C hemother 1983; 23: 907-913. ' Limbert M, Bar tl ett RR, Dickniete G, et al. Cefod izime: am in othiazolyl cephalosporin: Influence on the immun e system. J Antib iot 1984; 37: 171 9- 1726. 6 Labro MT, Amit N, Babin -C heva ye C, Hakim J . Cefodi zime (HR221) pote ntiation of human neu troph il oxyge nindependent bactericidal act ivity . J Antimicrob Chemother 1987; 19: 331-341. ' Leyhausen M, Seibert G , Maidhof A, Muller EG. Differen ti al stimulation o f lymphocyte cell grow th in vitro by cephalospor ins. Ant imicrob Agents C hemother 1984; 26: 752-756.
ACKNOW LEDGMENTS: We wish to th ank Mr. Giacomo Buonocore and Mrs. Raffaell a Cartell a for their laboratory and clinical ass istance. The present stud y was partly su pported by CNR, Roma, It aly.
