Influence of Klebsiella pneumoniae and quinolone treatment on prognosis in patients with pancreatic cancer

Abstract

Background An increasing body of evidence suggests that microbiota may promote progression of pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that gammaproteobacteria (such as Klebsiella pneumoniae) influence survival in PDAC, and that quinolone treatment may attenuate this effect. Methods This was a retrospective study of patients from the Massachusetts General Hospital (USA) and Ludwig-Maximilians-University (Germany) who underwent preoperative treatment and pancreatoduodenectomy for locally advanced or borderline resectable PDAC between January 2007 and December 2017, and for whom a bile culture was available. Associations between tumour characteristics, survival data, antibiotic use and results of intraoperative bile cultures were investigated. Survival was analysed using Kaplan–Meier curves and Cox regression analysis. Results Analysis of a total of 211 patients revealed that an increasing number of pathogen species found in intraoperative bile cultures was associated with a decrease in progression-free survival (PFS) (–1·9 (95 per cent c.i. –3·3 to –0·5) months per species; P = 0·009). Adjuvant treatment with gemcitabine improved PFS in patients who were negative for K. pneumoniae (26·2 versus 15·3 months; P = 0·039), but not in those who tested positive (19·5 versus 13·2 months; P = 0·137). Quinolone treatment was associated with improved median overall survival (OS) independent of K. pneumoniae status (48·8 versus 26·2 months; P = 0·006) and among those who tested positive for K. pneumoniae (median not reached versus 18·8 months; P = 0·028). Patients with quinolone-resistant K. pneumoniae had shorter PFS than those with quinolone-sensitive K. pneumoniae (9·1 versus 18·8 months; P = 0·001). Conclusion K. pneumoniae may promote chemoresistance to adjuvant gemcitabine, and quinolone treatment is associated with improved survival.

Characterization of Gut Microbiota and Exploration of Potential Predictive Model for Hepatocellular Carcinoma Microvascular Invasion

“…It was also related to the lymphatic metastasis and prognosis of pancreatic cancer (38). Klebsiella pneumoniae may promote chemoresistance to adjuvant gemcitabine treatment while following intervention with antibiotic quinolone can improve survival (40). Interestingly, our results indicated that Monoglobales, a member of microbiota which has not been reported in liver disease or cancer study, shows gradually decreased abundancy in the four subgroups according to differential vascular invasion status (highest in NC, then in HCC-NVI, HCC-MVI, and lowest in HCC-MaVI).…”

Association of Antibiotic Receipt With Survival Among Patients With Metastatic Pancreatic Ductal Adenocarcinoma Receiving Chemotherapy

“…In a mouse model colonized with CDD L -expressing Escherichia coli , cotreatment with ciprofloxacin and gemcitabine induced a significant antitumor response while gemcitabine alone resulted in rapid tumor progression . Furthermore, in a multicenter retrospective study of 211 patients with PDAC undergoing pancreatoduodenectomy, adjuvant gemcitabine therapy was associated with an improvement in progression-free survival only among patients whose bile was not colonized with Klebsiella pneumoniae , a subspecies of Gammoproteobacteria . Preclinical studies have also identified bacteria-mediated molecular mechanisms of fluorouracil chemoresistance through autophagy activation and fluorouracil metabolization by bacterial thymidine phosphorylases .…”

“…Some preclinical studies have similarly discovered bacteria-mediated mechanisms of fluorouracil resistance while others have identified bacteria-mediated mechanisms of fluorouracil activation . Small retrospective studies of patients with PDAC have found associations between antibiotic exposure and improved treatment outcomes, particularly among patients receiving gemcitabine …”

The Interaction between Intratumoral Microbiome and Immunity Is Related to the Prognosis of Ovarian Cancer

“…Previous studies support the contribution of the intratumoral microbiota to cancer progression and treatment prognosis ( 29 , 33 , 48 , 49 , 57 – 59 ). Riquelme et al demonstrated that the composition of the pancreatic adenocarcinoma microbiome could influence the host immune response and natural history of the disease ( 33 ).…”