Clinical experience with ceftazidime in urology in Japan

Transcription

1 Journal of Antimicrobial Chemotherapy (98), Suppl. A, 6- Clinical experience with ceftazidime in urology in Japan Noboo Kawamura Department of Urology, Tokai University, School of Medicine, Bosei-dai, Isehara, Kanagawa, Japan Ceftazidime was given in a total of 6 cases of urinary tract infections in Japan. The efficacy rate was found to be % in the assessable cases. In 6 cases of complicated urinary tract infection, the efficacy rate was 8% when it was assessed according to a unified protocol after days' treatment Bacterial eradication rate and pyuria clearance rate in these cases were 6% and %, respectively. Adverse events were noted in -% and abnormal laboratory findings in -8% or less. From thesefindings,ceftazidime was considered to be very effective in urinary tract infections, with safety comparable to that of other drugs, and t6 be particularly useful for infections caused by Pseudomonas aeruginosa and Serratia marcescens. Introduction The properties of ceftazidime, such as good urinary excretion and high anti-bacterial activity against Gram-negative bacilli, make it a suitble drug for the treatment of urinary tract infections. We have carried out an open trial in Japan on a nationwide scale in order to evaluate its effects and compare the results with those reported in other countries. Methods and results A total of 6 cases of urinary tract infection were treated with ceftazidime at institutions located in various parts of Japan. The patients were 6 males and 98 females, % of them being to 9 years and 6%, 6 to 69 years of age. Most patients received or g of ceftazidime daily, % by intravenous drip infusion and 6% by intravenous bolus injection. Clinical assessment, made by doctors in charge, subjectively and on their own criteria for each diagnosis is given in Table I. The clinical efficacy in all the cases of uncomplicated infection was assessed as 'excellent' or 'good'. In complicated infections, the efficacy rate was % in cases of pyelonephritis and % in 6 cases of cystitis. The efficacy rate in cases of male genital infections was 8%. Thus ceftazidime was shown to be effective in % of assessable cases in total. Efficacy in complicated urinary tract infections was further assessed according to the ' Criteria for Evaluation on Clinical Efficacy of Antimicrobial Agents on Urinary Tract Infection' edited by the members of the Japan UTI Assessment Committee (98), which are generally used in Japan. (Table II). The standard treatment duration was days and 6 cases complied with these criteria. The clinical efficacy was excellent in 8 cases and moderate in cases, based on these criteria, the overall efficacy rate being 8%. In the 8 cases (%) evaluated as excellent, bacteria in the urine were eliminated and the pyuria was cleared. Pyuria was cleared in cases (%) and decreased in 8 cases (8%), the efficacy rate of ceftazidime being % for pyuria. Bacteria were eliminated 6 -/8/A6 + $./ 98 The Britiah Society for Antimicrobial Chemotherapy Downloaded from at Pennsylvania State University on March, 6

2 66 N. Kawamnra Table I. Overall efficacy of ceftazidime by diagnosis Diagnosis cases Excellent Good Fair Poor Effectiveness rate Uncomplicated Pyelonephritis Cystitis Complicated Pyelonephritis Cystitis Male genital infection Others.6 cases assessed as excellent andgood no. of cases x Table II. Criteria for complicated UTI () Target infection Complicated urinary tract infection associated with underlying urinary tract diseases). () Specifications for patients (i) Age/sex: 6 years or older, regardless of sex (ii) Pyuria: WBC in the urine before treatment cells/hpf (iii) Bacterial count: viable bacteria before treatment ^ * bacteria/ml () Treatment period Five days: even when the drug is given for more than days, these criteria can be applied if the efficacy is evaluated at the end of the first days. () Overall clinical efficacy Efficacy is graded as' excellent',' moderate' or' poor' (including failure) by combining changes in parameters, pyuria and bacteriuria. For further details see UTI Committee, Japan (98). Bacteriuria Table IIL Overall efficacy of ceftazidime in complicated UTI Cleared Pyuria Decreased Unchanged Efficacy on bacteriuria Downloaded from at Pennsylvania State University on March, 6 Eliminated Decreased Replaced Unchanged Efficacy on pyuria (%) (8%) 6 (9%) (6%) (%) (%) (6%) Case total 6 Excellent Moderate Poor (or Failed) (Assessment by criteria of UTI committee.) 8(%) Overall effectiveness rate 6/6 (8%)

3 Clinkal studies of ceftazidime in urology 6 Table IV. Overall efficacy of ceftazidime by type of infection in complicated UTI Group cases (% of total) Excellent Moderate Poor Overall effectiveness rate <%> Monomicrobial infection st group (indwelling catheter) nd group (post-prostatectomy) rd group (upper Ull) th group (lower UTI) Polymicrobial infection th group (indwelling catheter) 6th group (no indwelling catheter) (9) () 8() 8(8) (6) 6() 96() () 6() (Assessment by criteria of UTI committee.) Daily dose (g) (-x) (lxl) (x) (x) Others* - Table V. Overall efficacy of ceftazidime by daily dose in complicated UTI cases Excellent Moderate Poor * - g (), g (), g (), dose changed (). (Assessment by criteria of UTI committee.) Overall effectiveness rate(%) Downloaded from at Pennsylvania State University on March, 6 in cases (6%), and decrease in cases (%); thus ceftazidime was effective in % for bacteria. The causative organisms werereplacedwith others in cases (%) (Table ). The clinical efficacy of ceftazidime classified by the type of infection is given in Table FV. This classification was also established by the Japan UTI Assessment Committee, in which infections are classified into 6 groups, viz. groups in monomicrobial infections and in polymicrobial infections. Table V shows the clinical efficacy by the daily dose, with no significant difference between the regimens. No difference in the clinical efficacy was shown between once a day and twice a day administration. -

4 68 N. Kawamnra Table VL Bacteriological response to ceftazidime in complicated UTI Isolate strains Eradicated Persisted Gram-positive bacteria Staph. aureus Staph. epidermidis Staphylococcus* Str. faecalis Other Gram-positive () () () (6) () (6) Gram-negative bacteria E. coli Klebsiella Pr. mirabilis Pr. vulgaris Pr. rettgeri Pr. morganii Proteus* Ent. cloacae Enterobacter* Serratia Acinetobacter Citrobacter Ps. aeruginosa Pseudomonas* Other Gram-negative Others Candida Yeast-like organisms (9) () 6() 9() () () () (8) (86) 98 (9) 9() (9) (6) 6(9) 8(86) (88) () () 96 (8) (Assessment by anterior of UTI committee.) * Other species or not speaatcd. Table VI gives the bacteriological response in complicated urinary tract infections. Out of 99 strains of Gram-positive organisms, strains persisted even after completion of the standard days' treatment with ceftazidime, and the bacterial eradication rate was 6%, whilst against Gram-negative bacilli, an 88% eradication rate was achieved. Adverse events and abnormal laboratory findings are tabulated in Table VII. Out of 6 cases, adverse effects suspected to be associated with ceftazidime were observed in 8 cases (-%): rash in, gastrointestinal tract disorders in 6 and headache and lightheadedness in. Elevation in serum GOT and GPT were the most frequent laboratory findings among those observed, and eosinophilia was noted in -%. Downloaded from at Pennsylvania State University on March, 6 Discussion The present study was characterized by the large proportion of aged, male patients reflecting the fact that all the subjects were in-patients.

5 Clinical studies of ceftazidime in urology 69 Table VII. Adverse events and abnormal laboratory findings Type of adverse event Adverse events No of cases with adverse events Incidence Wai Rash Diarrhoea and/or loose stool Nausea and/or vomiting Headache and lightheadedness no. of cases evaluated: 6. Item Elevation of GOT Elevation of GPT Elevation of Al-P Elevation of BUN Leukopenia Eosinophilia Neutrophilia Oligocythaemia Oligochromaemia Haematocytopenia Abnormal laboratory findings no. of cases evaluated Number of cases showing abnormal laboratory values: cases. abnormal cases (in total) Incidence (%) The overall clinical efficacy rates in patients with complicated infections was % by the doctors' assessment (Table I) and 8% in the assessment based on the criteria of the UTI Committee (Table III), with no marked difference, therefore, in the clinical efficacy between both the assessments. In evaluations by the same criteria of the UTI Committee, the overall clinical efficacy rates of cefoperazone (Nishiura, 98), ceftizoxime (Shimazu et al., 98) and cefmenoxime (Kawada & Nishiura, 98) in complicated urinary tract infections ranged between 6 and %. Analysed by type of infection, the total clinical efficacy rates were 8% in monomicrobial infections and 69% in polymicrobial infections. In the patients with indwelling catheters, the clinical efficacy rates were % in monomicrobial infections and 66% in polymicrobial infections, which were lower than those in monomicrobial infections in patients without a catheter (Table IV). Ceftazidime eradicated % of Proteus spp., 9% of Serratia, and 6% of Ps. aeruginosa in urine (Table VI). Furthermore, ceftazidime was shown to be more effective than other antibiotics in eradication of Enterobacter, Acinetobacter and Citrobacter in urine. The incidence of adverse events with ceftazidime was low. Abnormal laboratory findings seemed to be comparable to those observed with other cephem antibiotics Downloaded from at Pennsylvania State University on March, 6

6 N. Kawamura Acknowledgements I thank the medical staff of the institutions who participated in this study, for their active co-operation. It is not possible to acknowledge them individually. References Kawada, Y. & Nishiura, T. (98). Comparative studies of cefmenoxime (SCE-6) and cefazolin in complicated urinary tract infections. In Current Chemotherapy and Immunotherapy, vol., pp. 8-. Proceedings of the th International Congress of Chemotherapy. Nishiura, T. (98). Clinical comparison of cefoperazone in complicated urinary tract infections using a double-blind method. Clinical Therapeutics, Special issue. Shimazu, R., Kato, N., Doi, T., Kawada, Y., Nishiura, T., Nishino, A. & Kumamoto, Y. (98). Antimicrobial activity in urine and clinical efficacy of ceftizoxime. Current Chemotherapy and Immunotherapy, vol., pp. -. Proceedings of the th International Congress of Chemotherapy. UTI Committee, Japan (98). Criteria for the evaluation of clinical efficacy of antimicrobial agents on urinary tract infections. Chemotherapy (Tokyo) 8, -. Downloaded from at Pennsylvania State University on March, 6