Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis

Abstract

BackgroundAcute cholangitis (AC) requires the immediate initiation of antibiotic therapy in addition to treatment for biliary obstruction. Against a background of an increasing prevalence of multi-drug resistant (MDR) bacteria, the risk factors for the failure of empiric therapy must be defined.MethodsUsing a pathogen-based approach, 1764 isolates from positive bile duct cultures were retrospectively analyzed to characterize the respective pathogen spectra in two German tertiary centers. Using a patient-based approach, the clinical and laboratory data for 83 patients with AC were assessed to identify risk factors for AC with pathogens resistant to the applied empiric therapy.ResultsBile cultures were predominantly polymicrobial, and empiric antibiotic therapies did not cover the full biliary pathogen spectrum in 78% of cases. MDR bacteria were isolated from the bile of 24/83 (29%) patients. The univariate risk factors for biliary MDR bacteria were male sex, nosocomial AC, prior antibiotic exposure and prior biliary stenting, of which biliary stenting was the only independent risk factor according to multivariate analysis (OR = 3.8; 95% CI 1.3–11.0, P = 0.013). Although there were no significant differences in survival or hospital stay in AC patients with and without detected biliary MDR pathogens, the former more often had a concomitant bloodstream infection (58% vs. 24%; P = 0.019), including those involving MDR pathogens or fungi (21% vs. 2%; P = 0.007).ConclusionPatients with biliary stents who develop AC should receive empiric therapy covering enterococci and extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. These patients are at an increased risk for bloodstream infections by MDR pathogens or fungi.

Use of microbiological and patient data for choice of empirical antibiotic therapy in acute cholangitis

“…Anaerobes were detected in less than 10% of our patients. These results are consistent with other recent reports [7][8][9][10] and revise the classic view that both enterobacterales and anaerobes are the most important pathogens in biliary tract infections [11]. Bacteremia was detected in one third of cases with available blood culture results.…”

“…Epidemiological data from Germany suggest a frequency of 3GCRE of about 15% in hospitals [14]. In an analysis of cholangitis cases from two other German university hospitals, ESBL producing E.coli were detected at a rate of 31% [10]. In our cohort, the highest numbers of cholangitis associated with either 3GCRE or MRGN (See figure on previous page.)…”

Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis

“…There is a lack of clinical trials examining the benefit of blood cultures in patients with acute biliary tract infections. On the other hand, there is an argument that every opportunity should be used to identify microorganisms and susceptibility testing in the era of antimicrobial resistance .…”

“…A prospective cohort study in patients with acute cholecystitis involving 116 institutions worldwide showed that among 96 isolated E. coli , 16 (16.7%) were producing ESBL . However, the proportion of ESBL producing E. coli varies widely region to region: 31.2% in two German university hospitals , 70.0% in Korean university medical center and 66% in Indian medical college hospital . There are few reports about the prevalence of carbapenem resistant bacteria specifically among patients with acute cholangitis and cholecystitis.…”

Aktualisierte S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) zur Prävention, Diagnostik und Behandlung von Gallensteinen

“…Zwei Folgestudien konnten ebenfalls nicht eindeutig die Wirksamkeit dieser Maßnahmen nachweisen: Während eine Studie unter der Kombination von UDCA mit Levofloxacin eine niedrige Rate an Stentokklusionen und Cholangitiden fand [120], wurde in einer doppelblinden randomisierten Studie mit Ciprofloxacin bei 94 Patienten eine grenzwertig signifikante Abnahme der Cholangitishäufigkeit von 42 auf 21 % beobachtet [121]. Retrospektive infektiologische Untersuchungen weisen darauf hin, dass Patienten mit biliären Stents, die eine akute Cholangitis entwickeln, eine empirische Antibiotikatherapie, die Enterokokken und Extended spectrum β-Laktamasen (ESBL) -bildende Enterobakterien abdeckt, erhalten sollten [122].…”