Evaluation of Efficiency and Safety of Various Dose Regimens of Sulperazon (Cefoperazon/Sulbactam) and Serious Infections in Intensive Care

Overview

Objective:
Clinical evaluation of efficacy and safety of different types of dosage of cefoperazon/sulbactam (Sulperazon) insevere 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 mentionedcenters 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 thebeginning 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 applicationsduring 24 hours, length of Sulperazon therapy, reason for cessation of Sulperazon therapy, adverse effects and theirconnection with the therapy, leucocytes, CRP, INR at the beginning and at the end Sulperazon therapy, type of pathogenand its elimination, persistence or superinfection. Efficacy and safety of Sulperazon therapy was evaluated in all types ofinfections 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. Themean 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 SOFAscore median 7, TISS score median 34, leukocytes median 14.1, CRP median 141, INR median 1.29. The most commonreason for hospital admission was illness of gastrointestinal tract (n=148, 74,7%), vascular disease (n=75, 37.9%) andrespiratory 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 mostcommon risk factors were invasive vascular access (n=142, 71.7%), mechanical ventilation (n=111, 56.1%) and diabetesmellitus (n=52, 26.3%). As a drug of the 1st choice Sulperazon was administered in 63 patients (31.8%), as a drug of the 2ndchoice 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 givento 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 Sulperazontherapy 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 toanother antimicrobial therapy, 14 (7%) patients died due to principal illness and 6 (3%) died because of infection. Adverseeffects (dyspepsia and nausea) were observed in 16 (9.1%) patients, but the Sulperazon therapy had to be stopped only inone patient. Microbiological examinations were carried out in 136 (68.7%) patients. Elimination of pathogen was achievedin 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 otherorigin 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 considerablylower (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 ofinfections 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 mostsuccessful therapy was found in pancreatic and biliary infections (84.2%), the lowest effectiveness of treatment wasdemonstrated in peritonitis with sepsis (61.4%). Higher dosage of Sulperazon (>4 g/day) was not associated with betteroutcome. Insignificant improvement of outcome was apparent in patients with lung infections who received higher dosageof 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