Abstract: Background: Offlabel drug use is common in neonates. Appropriate and effective administration of antibiotics for Carbapenemresistant Enterobacteriaceae （CRE） infection in neonates is challenging. Sulfamethoxazole compound (SMZco) can be taken orally with high bioavailability, however, it is not recommended to be used in infants under 2 months. Objective: To summarize the experience and therapeutic effect of oral SMZco for the CRE septicemia in newborns. Design: Case series report. Methods: Through the hospital drug management system, SMZco medical records that meet the following criteria were collected: a. Patients were hospitalized in NICU of Beijing Children's Hospital, Capital Medical University from January 2018 to June 2021; b. The age on admission was ≤ 28 d or the corrected age was ≤ 44 weeks; c. The CRE septicemia was confirmed by positive blood culture results and clinical manifestations. The oral SMZco as a combined use of medications was administered when the pros and cons were thoroughly discussed by neonatal physicians and clinical pharmacists, and formal written consents were signed by parents. The dose of SMZco was referred to that for children above 2 months old. Signs of allergy and manifestations of bilirubin encephalopathy had been closely watched during the treatment. Complete blood counting and renohepatofunction were monitored weekly. The following information was collected: demographic characteristics, history of surgical intervention or long line catheterization, ventilation time, time interval between blood drawing and culture positive, species of the positive culture results together with the drug sensitivity test, age of starting SMZco administration, dosage of SMZco, WBC, PLT and CRP before and after SMZco treatment, adverse reactions and clinical outcomes. Main outcome measures: Discharge after improvement. Results: A total of 9 newborns with CRE septicemia were enrolled, among which 5 were males, 6 received surgery intervention before CRE septicemia was confirmed, and 8 had history of long line catheterization. The average gestational age was (31.0 ± 4.4) weeks, ventilation time was (793±381）h . Specimens for the positive CRE cultures were blood (2 cases), tracheal bronchial secretion (3 cases), tip of PICC (1 case), surgical wound swab (1 case), blood and tracheal bronchial secretion (1 case) and blood+cerebrospinal fluid (1 case). Before the administration of SMZco, all cases were treated with broadspectrum antibiotics for more than 2 weeks. There were 2 cases of CRE meningitis. The medium time of positive CRE culture was 39 (23.5,49) d of hospitalization before or after being transferred to our center. Among the 9 cases, 8 were Klebsiella pneumoniae and 1 was Escherichia coli, all of which produced extendedspectrum βlactamases. Analysis of antimicrobial susceptibility assay revealed resistance to Amikacin (3 cases), Gentamicin (6 cases), Ciprofloxacin (7 cases), and Tetracycline (3 cases). All were sensitive to SMZco and Tegacyclin. SMZco treatment was initiated at 49(38,70.5) days of life for patients, and the dose of SMZ was 4060 mg·kg-1·d-1. There were 6 cases treated with oral SMZco in combination of intravenous carbapenems or thirdgeneration cephalosporins, while 3 cases were with oral SMZco only. Six out of nine patients completed the SMZco course of (24.3 ± 11.6) days, while three out of nine patients did not complete the required SMZco course due to their discharge against medical advice. Among the 6 patients with complete SMZco course, 1 was treated for 10 d (tracheal bronchial secretion positive), and the other 5 were treated for more than 2 weeks. All patients presented improved clinical symptoms and inflammatory markers after the starting of SMZco. All patients had normalization of WBC and PLT, 7 patients had normalization of CRP and other 2 patients had dramatically improved CRP before discharge against medical advice. No allergy was found, nor signs of bilirubin encephalopathy or hemolytic anemia or thrombocytopenia. There were 3 patients (33.3%) with an ALT elevation 2.23.5 times of normal value, which was normalized after symptomatic intervention. All patients had normal renal function during SMZco treatment. Conclusion: For neonates who had culture confirmed CRE septicemia, under the instruction of drug sensitivity results, a combined use of oral SMZco is a choice to treat the CRE infection when the treatment response of strong broad spectrum antibiotics is negative. However, it is necessary to strictly follow the procedures of offlabel drug use, parent consenting, and close monitoring of side effects.

Key words: SMZco, Infant, Newborn, Drug-resistant Enterobacteriaceae, Septicemia, Antibiotics