Tracing the origin of NDM-1-producing and extensively drug-resistant Pseudomonas aeruginosa ST357 in the Netherlands.

BACKGROUND: In the hospital environment, carbapenemase-producing Pseudomonas aeruginosa (CPPA) may lead to fatal patient infections. However, the transmission routes of CPPA often remain unknown. Therefore, this case study aimed to trace the origin of CPPA ST357, which caused a hospital-acquired pneumonia in a repatriated critically ill patient suffering from Guillain-Barré Syndrome in 2023. METHODS: Antimicrobial susceptibility of the CPPA isolate for 30 single and combination therapies was determined by disk-diffusion, Etest or broth microdilution. Whole-genome sequencing was performed for three case CPPA isolates (one patient and two sinks) and four distinct CPPA ST357 patient isolates received in the Dutch CPPA surveillance program. Furthermore, 193 international P. aeruginosa ST357 assemblies were collected via three genome repositories and analyzed using whole-genome multi-locus sequence typing in combination with antimicrobial resistance gene (ARG) characterization. RESULTS: A Dutch patient who carried NDM-1-producing CPPA was transferred from Kenya to the Netherlands, with subsequent dissemination of CPPA isolates to the local sinks within a month after admission. The CPPA case isolates presented an extensively drug-resistant phenotype, with susceptibility only for colistin and cefiderocol-fosfomycin. Phylogenetic analysis showed considerable variation in allelic distances (mean = 150, max = 527 alleles) among the ST357 isolates from Asia (n = 92), Europe (n = 58), Africa (n = 21), America (n = 16), Oceania (n = 2) and unregistered regions (n = 4). However, the case isolates (n = 3) and additional Dutch patient surveillance program isolates (n = 2) were located in a sub-clade of isolates from Kenya (n = 17; varying 15-49 alleles), the United States (n = 7; 21-115 alleles) and other countries (n = 6; 14-121 alleles). This was consistent with previous hospitalization in Kenya of 2/3 Dutch patients. Additionally, over half of the isolates (20/35) in this sub-clade presented an identical resistome with 9/17 Kenyan, 5/5 Dutch, 4/7 United States and 2/6 other countries, which were characterized by the blaNDM-1, aph(3')-VI, ARR-3 and cmlA1 ARGs. CONCLUSION: This study presents an extensively-drug resistant subclone of NDM-producing P. aeruginosa ST357 with a unique resistome which was introduced to the Netherlands via repatriation of critically ill patients from Kenya. Therefore, the monitoring of repatriated patients for CPPA in conjunction with vigilance for the risk of environmental contamination is advisable to detect and prevent further dissemination.

Pulmonary levels of biomarkers for inflammation and lung injury in protective versus conventional one-lung ventilation for oesophagectomy: A randomised clinical trial.

BACKGROUND: It is uncertain whether protective ventilation reduces ventilation-induced pulmonary inflammation and injury during one-lung ventilation. OBJECTIVE: To compare intra-operative protective ventilation with conventional during oesophagectomy with respect to pulmonary levels of biomarkers for inflammation and lung injury. DESIGN: Randomised clinical trial. SETTING: Tertiary centre for oesophageal diseases. PATIENTS: Twenty-nine patients scheduled for one-lung ventilation during oesophagectomy. INTERVENTIONS: Low tidal volume (VT) of 6 ml kg predicted body weight (pbw) during two-lung ventilation and 3 ml kgpbw during one-lung ventilation with 5 cmH2O positive end expired pressure versus intermediate VT of 10 ml kgpbw during two-lung ventilation and 5 ml kgpbw body weight during one-lung ventilation with no positive end-expiratory pressure. OUTCOME MEASURES: The primary outcome was the change in bronchoalveolar lavage (BAL) levels of preselected biomarkers for inflammation (TNF-α, IL-6 and IL-8) and lung injury (soluble Receptor for Advanced Glycation End-products, surfactant protein-D, Clara Cell protein 16 and Krebs von den Lungen 6), from start to end of ventilation. RESULTS: Median [IQR] VT in the protective ventilation group (n = 13) was 6.0 [5.7 to 7.8] and 3.1 [3.0 to 3.6] ml kgpbw during two and one-lung ventilation; VT in the conventional ventilation group (n = 16) was 9.8 [7.0 to 10.1] and 5.2 [5.0 to 5.5] ml kgpbw during two and one-lung ventilation. BAL levels of biomarkers for inflammation increased from start to end of ventilation in both groups; levels of soluble Receptor for Advanced Glycation End-products, Clara Cell protein 16 and Krebs von den Lungen 6 did not change, while levels of surfactant protein-D decreased. Changes in BAL biomarkers levels were not significantly different between the two ventilation strategies. CONCLUSION: Intra-operative protective ventilation compared with conventional ventilation does not affect changes in pulmonary levels of biomarkers for inflammation and lung injury in patients undergoing one-lung ventilation for oesophagectomy. TRIAL REGISTRATION: The 'Low versus Conventional tidal volumes during one-lung ventilation for minimally invasive oesophagectomy trial' (LoCo) was registered at the Netherlands Trial Register (study identifier NTR 4391).