Neonatal gastric perforation (NGP) is a life-threatening condition during the neonatal period, and its etiology remains unclear. However, there are three possible mechanisms: spontaneous perforation, trauma, and ischemia. Spontaneous perforation is caused by agenesis of the gastric musculature leading to lesions, while trauma can result from excessive gastric distension caused by non-invasive ventilators or perforation of the stomach by gastric tubes. Ischemia may be caused by septic embolism or neonatal suffering.[16, 17] The mortality rate of NGP has significantly reduced due to improvements in surgical treatment and perioperative comprehensive management, including antibiotic treatment, fluid and nutrition management, and correction of blood coagulation dysfunction. The mortality rate has decreased from 100% in the 1980s to 16.7% in the 2010s.[1]
Antibiotic treatment is essential for the postoperative management of gastric perforation. However, there is no standardized antibiotic treatment protocol. In this study, we found that most doctors in our center chose metronidazole in combination with broad-spectrum antibiotics for NGP patients with significantly increased inflammatory indicators. Nevertheless, we observed no significant difference in short-term prognosis between the children who received broad-spectrum antibiotics alone and those who received a combination of metronidazole and broad-spectrum antibiotics. Further studies are required to investigate the optimal antibiotic treatment protocol for NGP patients.
Antibiotic treatment is an important aspect of the management of NGP. Empirical use of broad-spectrum antibiotics that provide Gram-negative and anaerobic coverage is commonly used until culture results become available.[18] Once gastric perforation is identified, prompt resuscitation and treatment are initiated, including the use of triple antibiotics (cefotaxime/ceftriaxone, amikacin, and metronidazole). Some studies have suggested that both ertapenem and metronidazole plus gentamicin are safe and effective options for the treatment of diffuse peritonitis, with ertapenem showing better short-term prognosis.[12]
As shown in Tables 1 and 2, we observed no differences in baseline characteristics, clinical manifestations, and comorbidities before surgery between the two groups (with or without metronidazole). However, after matching for gestational week and birth weight (Table 2), we found that clinicians were more likely to use metronidazole in infants with significantly elevated CRP and PCT (P ༜ 0.05).
In the management of NGP, there is currently no consensus on the antibiotic protocol, and opinions vary on the choice and duration of antibiotic treatment. Prolonged daily infusion of antibiotics may lead to decreased parenteral nutrition, potentially causing postoperative malnutrition in newborns. In our study, although the use of broad-spectrum antibiotics in combination with metronidazole was associated with higher inflammatory markers, we observed no differences in antibiotic duration, comorbidities, or main laboratory results after surgery (Tables 3 and 4). Our previous study found that anaerobic antimicrobial therapy did not reduce the mortality of infants with necrotizing enterocolitis who progressed to stage III.[15] The use of broad-spectrum antibiotics plus metronidazole may further reduce intestinal probiotics, leading to decreased butyrate production.[19] Therefore, the regimen of broad-spectrum antibiotics plus metronidazole may have potentially adverse effects on recovery in newborns.
Surgical Site Infection (SSI) is a common complication after neonatal gastrointestinal surgery, and it remains a significant problem in infants operated for NGP.[20] Topical or intravenous antibiotic therapy is considered essential for the treatment of SSI, but there is no consensus on specific treatment options. As shown in Table 3, the incidence of SSI was significantly higher in group M (plus metronidazole) than in group N, but there was no significant difference after matching for gestational age and birth weight. This finding suggests that gestational age and birth weight may be important factors influencing the occurrence of SSI, which is consistent with previous reports.[21] A recent meta-analysis of topical antibiotic prophylaxis for SSI concluded that “Given the current evidence, the routine application of topical antibiotics to surgical wounds did not reduce the incidence of SSI.” While a standardized preoperative antibiotic regimen in adult patients is considered to reduce the incidence of SSI, there is still no consensus among neonatal surgeons regarding preoperative antibiotic prophylaxis.[22]
Our study has some limitations, including the inherent errors and biases of retrospective studies. Furthermore, the sample size of this study is small, and it is necessary to expand the sample size and conduct a multi-center study with a larger sample size to provide more conclusive evidence. Although our results are interesting, they must be interpreted with caution in the absence of large randomized controlled trials. A prospective randomized study may be necessary to further confirm our conclusion.