Patient disposition and baseline characteristics
After screening 2250 patients for entry into the study, 144 patients were selected to receive ceftriaxone/sulbactam, and 141 received cefoperazone/sulbactam (Figure 1). Between the two groups, there were no differences in age, gender, weight, course of disease, condition of infection, temperature before enrolment, presence of underlying diseases or type of infection (Table 1).
Although the overall clinical efficacy was higher in the ceftriaxone/sulbactam group than in the cefoperazone/sulbactam group, the difference was not statistically significant. There was a total cure rate of 39.55% (53/134) in the ceftriaxone/sulbactam group, compared with 36.43% (47/129) of those receiving cefoperazone/sulbactam. The efficacy rate of each group was 85.07 and 79.84%, respectively. The cure and efficacy rates for respiratory and urinary tract infections in the ceftriaxone/sulbactam group were also not significantly different. Both of the antimicrobials were equally efficient against the infections caused by Gram-negative bacteria (p > 0.05). However, the efficacy rate for the diseases caused by gram-positive bacteria in the cefoperazone/sulbactam group was significantly higher than that in the ceftriaxone/sulbactam group (p < 0.05), although the sample size was less than 10 cases (Table 2).
In total, 263 strains were evaluated, with 134 in the ceftriaxone/sulbactam group and 129 in the cefoperazone/sulbactam group. The overall eradication rate was 83.58% in the ceftriaxone/sulbactam group and 83.72% in the cefoperazone/sulbactam group. The bacteriological success rates for the overall and for the gram-negative or gram-positive pathogens were comparable between the treatment groups at the 7-day follow-up visit (Table 3).
In the ceftriaxone/sulbactam group, there were 129 ceftriaxone-resistant Gram-negative strains isolated. The eradication rate was 84.50% (109/129). Five ceftriaxone-resistant gram-positive strains were isolated, including 3 Staphylococcus haemolyticus (methicillin-sensitive) and 2 Staphylococcus aureus (methicillin-sensitive). The eradication rate was 60% (3/5).
In the cefoperazone/sulbactam group, there were 120 cefoperazone-resistant Gram-negative strains isolated. The eradication rate was 83.33% (100/120). Nine cefoperazone-resistant gram-positive strains were isolated, including 6 Staphylococcus haemolyticus (methicillin-sensitive) and 3 Staphylococcus aureus (methicillin-sensitive). The eradication rate was 88.89% (8/9).
For the respiratory tract diseases, there were 65 strains isolated from the ceftriaxone/sulbactam group, with a total eradication rate of 80.00% (52/65). The eradication rate was 75% (3/4) for the Gram-positive strains and 80.32% (49/61) for the gram-negative strains. There were 65 isolates from the cefoperazone/sulbactam group, with a total eradication rate of 81.53% (53/65). The eradication rate was 85.71% (6/7) for the gram-positive strains and 81.03% (47/58) for the gram-negative strains.
For the urinary tract diseases, there were 69 and 64 strains isolated from the ceftriaxone/sulbactam and cefoperazone/sulbactam groups, with total eradication rates of 86.96% (60/69) and 85.94% (55/64), respectively. The eradication rate for the gram-negative organisms was 88.24% (60/68) in the ceftriaxone/sulbactam group and 85.48% (53/62) in the cefoperazone/sulbactam group. Only one gram-positive strain was isolated from the ceftriaxone/sulbactam group, and it was not cleared. Two gram-positive strains were isolated and cleared in the cefoperazone/sulbactam group.
No significant difference was detected between the groups in the above eradication rates (p > 0.05).
The post-therapy (day 7 follow-up visit) bacteriological evaluation of the patients from the cured or marked improvement groups revealed no differences compared with the results at the end of therapy.
In-vitro drug susceptibility assay
The K-B disc diffusion test results showed that the sensitivity rates of the isolates given ceftriaxone/sulbactam and cefoperazone/sulbactam were 84.88 and 86.73%, respectively. The difference was not statistically significant.
Minimum inhibitory concentration assays were conducted on all of the isolates. The results, which are expressed as the range of minimum inhibitory concentrations and the concentrations required to inhibit 50% and 90% of the isolates (the latter only for isolates with more than 10 strains), are shown in Table 4. These findings suggested that ceftriaxone/sulbactam was as active as or slightly superior to cefoperazone/sulbactam against the Enterobacteriaceae; however, for P. aeruginosa and A. baumannii, ceftriaxone/sulbactam was twofold less active than cefoperazone/sulbactam.
Overall, both agents were well-tolerated by the patients in this study. Eighteen adverse events were observed in the patients receiving ceftriaxone/sulbactam (n = 18, 7.48%), and 11 were noted in the patients receiving cefoperazone/sulbactam (n = 11, 7.80%). Fifteen drug-related events were identified in the ceftriaxone/sulbactam group (15/144, 10.42%), and 10 were identified in the cefoperazone/sulbactam group (10/141, 7.09%). In the ceftriaxone/sulbactam group, the potentially drug-related clinical adverse reactions were as follows: rashes (1), headache (1), chest distress (1), nausea (2), and diarrhoea (1). The laboratory abnormalities included leucopenia (2) and hepatic dysfunction, which was characterised by a mild increase in the level of alanine transferase (7). In the cefoperazone/sulbactam group, 2 patients complained of rashes and 1 reported a headache. The laboratory abnormalities were leucopenia (3) and a slightly increased serum level of alanine transferase (4). The majority of the adverse events were mild to intermediate and spontaneously alleviated or recovered. There were 5 patients who discontinued the treatments due to adverse events, among whom two were in the ceftriaxone/sulbactam group (headache and severe renal haemorrhage) and three were in the cefoperazone/sulbactam group (headache, leucopenia and rashes). One serious adverse event was reported in the ceftriaxone/sulbactam group due to nephrorrhagia, which was confirmed to be unrelated to the study medication. The frequency of adverse events did not differ significantly between the two groups (p > 0.05).