In this study, the PSM method was used to compare the clinical efficacy of broad-spectrum antibiotics and broad-spectrum antibiotics combined with nitroimidazoles in the treatment of abdominal infection. The results showed that although the basic condition matching was consistent, the infection index and the surgical patients of a combination of broad-spectrum antibiotics with nitroimidazoles were higher than that in the group of broad-spectrum antibiotics. The clinical effective rate of broad-spectrum antibiotics combined with nitroimidazole in the treatment of abdominal infection was similar to that of broad-spectrum antibiotics, while the hospitalization days of patients in the combination group were longer and the cost of hospitalization was higher.
This study was the first to directly compare the efficacy of broad-spectrum antibiotics and broad-spectrum antibiotics combined with nitroimidazoles in the treatment of abdominal infection. The results showed that there was no significant difference in the clinical effective rate between the NCBSA and BSA in treatment of abdominal infection, which was mainly consistent with the recommendations of previous studies and current guidelines[2-4,11]. As some scholars have shown, NCBSA can not improve the therapeutic effect of perforated appendicitis, nor can it reduce the deterioration rate of necrotizing enterocolitis. Solomkin et al. performed a randomized trial to assess the safety and efficacy of Ceftolozane/Tazobactam plus metronidazole in intra-abdominal infections. And the results indicated that this combination regimen was non-inferior to meropenem for patients with complicated intra-abdominal infections. Similarly, another study from Qin et al. demonstrated that ceftazidime/avibactam in combination with metronidazole was not inferior to meropenem in the treatment of complicated intra-abdominal infections in Asia.
Combining our results for further analysis, there may be three reasons for the no difference in the effectiveness of the two groups. First of all, the detection rate of carbapenemase resistance genes in Enterobacteriaceae isolated from abdominal infections is increasing year by year, which increases the difficulty of treating abdominal infections. Second, in the selection of nitroimidazole drugs, the drugs used in the combination group in this study were 23 cases of metronidazole, 119 cases of ornidazole, and 7 cases of levornidazole. Among them, metronidazole is the first-generation nitroimidazole drug, ornidazole is the third-generation nitroimidazole drug, and levornidazole is the levorotatory isomer of the third-generation ornidazole. Although there was a lack of clear drug resistance data, second and third-generation nitroimidazole antibiotics (such as Levoornidazole) are significantly better than metronidazole in the treatment of abdominal anaerobic infections. Studies have shown that compared with ornidazole, levornidazole has obvious advantages in the treatment of anaerobic infections[23-24], and the clinical effect of treating abdominal infections is better than ornidazole. However, due to the small number of levornidazole used in the combination group, the efficacy of combined nitroimidazole drugs may not be reflected. Finally, the overall span of this research is 10 years, during which many treatment concepts and technologies are continuously improved. The difference in the treatment effect in different periods, in particular, the low treatment effect caused by the backward treatment technology in the early stage may be one of the reasons for the comprehensive indifference.
However, in this study, we also found that after PSM the basic clinical features, the infection indexes such as PCT and Temperature in the combination group were significantly higher than those in BSA group, and although there was no statistical difference, WBC and CRP were also higher than those in BSA group, which may suggest that the infection in the combination group was more severe. Besides, more patients (92 vs 38) in NCBSA group underwent abdominal surgery, which was also in line with the doctor's habit of an empirical combination of drugs, that is, it seems that the infection or the clinical conditions are more severe and tends to be combined with drugs. And this may be one of the reasons why the combination group had longer hospitalization days and higher costs in this study. Therefore, we could also speculate that under the premise of more severe infection and clinical conditions in the combination group, the curative effect of the two groups is the same, and on the other hand, the efficiency of the combination group may be higher. However, due to the complexity of abdominal infections, such as the source of infection, the treatment of primary infections and other clinical data complexity, we cannot fully balance the severity of all infections and clinical conditions for the time being, and we have not continuously dynamically assessed changes in infection indicators, therefore, we still can not conclude that the combination of drugs is more effective. This is also the deficiency of this study, which needs to be confirmed by more prospective studies in the future.
In addition, a subgroup analysis of abdominal surgery found that the effective rate of patients with abdominal surgery in the single-use group was higher than that in the combination group, but because we did not record the length of the operation and the amount of blood loss, we could not match the size of the surgery and the severity of the postoperative condition of the two groups. Therefore, the results may be biased. However, it is worth noting that in the subgroup analysis of the severity of the disease, we found that although there was no statistical difference in the severity of the disease for empirical treatment of abdominal infection alone or in combination, when the APACHEII score was 11-15, the effective rate of broad-spectrum antibiotics combined with nitroimidazoles was higher than that of broad-spectrum antibiotics alone (76.5% versus 65.0%), but the difference was not statistically significant. This may be because neither too severe nor too mild can reflect the advantage of the combination group, but just when the severity of the disease is moderate can reflect the advantage of the combination therapy. In future studies, as the number of cases increases, the advantages of broad-spectrum antibiotics combined with nitroimidazole drugs in the treatment of abdominal infections under this condition are likely to be revealed.
Finally, we also compared the safety of the two groups, and our results showed that there were no more obvious side effects in the combination group. More recently, a meta-analysis repotted by Che et al showed that there were no significant differences in overall adverse events, severe adverse events or mortality between β-lactam/β-lactamase inhibitors combined with metronidazole and carbapenem in the treatment of complex abdominal infection, but the risk of vomiting was higher in the combination group. This is consistent with our findings.
In this study, there are also some limitations. First, it is a retrospective single-center study with relatively small sample size. In addition, this study spans a long period of 10 years, and the difference in effect caused by the progress of treatment technology may affect the results of the study. Future prospective, multi-center, large sample research is expected to provide us with more reliable evidence.