Objective: Clinical evaluation of efficacy and safety of different types of dosage of cefoperazon/sulbactam (Sulperazon) in severe infections in intensive care. Design: Multicenter prospective observation clinical study. Setting: 31 centers in the Czech Republic (interdisciplinary, surgical and medical ICUs, Departments of surgery). Material and methods: Patients with severe infection treated with Sulperazon who were hospitalized in above mentioned centers from March to September 2002. Evaluated parameters: basic demographic parameters, type of illness, principal diagnosis for admission to the hospital, diagnosis for hospitalization in intensive care, kind of infection thatwas the reason for antibiotic therapy, presence of sepsis, risk factors of infectious complications, APACHE II score at the beginning of treatment, SOFA score and TISS score at the beginning and at the end of Sulperazon therapy, kind of indication of Sulperazon therapy (drug of the 1st or the 2nd choice), antibiotic therapy before, during and after administration of Sulperazon, daily dose of Sulperazon, number of applications during 24 hours, length of Sulperazon therapy, reason for cessation of Sulperazon therapy, adverse effects and their connection with the therapy, leucocytes, CRP, INR at the beginning and at the end Sulperazon therapy, type of pathogen and its elimination, persistence or superinfection. Efficacy and safety of Sulperazon therapy was evaluated in all types of infections together and in individual kinds of infections with regard to different types of dose regimens of Sulperazon. Results: 198 patients – 133 (67%) males, 65 (33 %) females, from whom 195 (98.5%) were treated with intensive care. The mean age was 62 ± 15.2 years, weight 79.2 ± 18.0 kg, height 172.8 ± 9 cm, APACHE II score median 20, input values of SOFA score median 7, TISS score median 34, leukocytes median 14.1, CRP median 141, INR median 1.29. The most common reason for hospital admission was illness of gastrointestinal tract (n=148, 74,7%), vascular disease (n=75, 37.9%) and respiratory tract disease (n=51, 25.8%). The most frequent reasons for antibiotic therapy were abdominal (60.1%) and lung (53.1%) infections. Sepsis was diagnosed in 102 (52%) patients, risk factors were present in 178 (89.9%) patients. The most common risk factors were invasive vascular access (n=142, 71.7%), mechanical ventilation (n=111, 56.1%) and diabetes mellitus (n=52, 26.3%). As a drug of the 1st choice Sulperazon was administered in 63 patients (31.8%), as a drug of the 2nd choice it was given after the failure of previous antibiotic therapy (n=77, 38.9%), or in accordance with microbiology results (n=58, 29.3%). The mean length of the Sulperazon therapy was 8.4 ± 3.1 days (median 8 days), the dose 4 g/24 hrs was given to 102 (51.2%) patients, the dose 8 g/24 hrs to 66 (33.3%) patients. Sulperazon was most often administered two-times daily (n=155, 78.3%), it was given four-times to 28 (14.2%) patients. Organ dysfunction was improved during the Sulperazon therapy and initial values of leucocytes, CRP, TISS and INR decreased significantly. Treatment was clinically evaluated as successful in 141 (71.2%) patients, in 36 (18.3%) patients the therapy was changed to another antimicrobial therapy, 14 (7%) patients died due to principal illness and 6 (3%) died because of infection. Adverse effects (dyspepsia and nausea) were observed in 16 (9.1%) patients, but the Sulperazon therapy had to be stopped only in one patient. Microbiological examinations were carried out in 136 (68.7%) patients. Elimination of pathogen was achieved in 77 (56%) cases, persistence or superinfection was found in 37 (27%) respectively in 22 (16%) cases. Clinical success of the treatment of ventilator pneumonia was observed in 70.2% of events, in case of pneumonia of other origin in 66.6% of events. Clinical efficacy of the treatment of pancreatic and biliary infections was significantly better (84.2%, P=0,02) than the treatment of peritonitis (61.4%). Clinical success of treatment in the mixed origin of illness was considerably lower (51.6%, P=0,02) than in medical (73.2%) and in surgical (75.4%) kinds of illness. No influence of dosage of Sulperazon (neither dose/24 hrs nor number of administration/24 hrs) on the efficacy and safety of therapy was found in all kinds of infections together and also in individual types of infections. Conclusion: Clinical efficacy of Sulperazon therapy in the treatment of severe infections was higher than 70%. The most successful therapy was found in pancreatic and biliary infections (84.2%), the lowest effectiveness of treatment was demonstrated in peritonitis with sepsis (61.4%). Higher dosage of Sulperazon (>4 g/day) was not associated with better outcome. Insignificant improvement of outcome was apparent in patients with lung infections who received higher dosage of Sulperazon. Higher dose of Sulperazon (8 g/day) was safe and did not lead to the deterioration of organ functions. Sulperazon administration was well-tolerated and was associated with low frequency of adverse effects.

        Key words: Sulperazon – severe infections – efficacy of treatment