Antimicrobial resistance in patients with decompensated liver cirrhosis and bacterial infections in a tertiary center in Northern Germany.

BACKGROUND AND AIMS: Bacterial infections are common in patients with decompensated liver cirrhosis and a leading cause of death. Reliable data on antibiotic resistance are required to initiate effective empiric therapy. We here aim to assess the antimicrobial resistance profile of bacteria among patients with liver cirrhosis and infection. METHODS: Overall, 666 cirrhotic patients admitted to Hannover Medical School between January 2012 and April 2018 with ascites were assessed for bacterial infection. In case of infection, bacteria cultured from microbiological specimens of ascites, blood or urine were identified and analyzed for resistances against common antibiotic agents. Furthermore, analyses compared two periods of time and community-acquired vs. nosocomial infections. RESULTS: In 281 patients with infection, microbiological sampling was performed and culture-positive results were obtained in 56.9%. Multidrug-resistant (MDR)-bacteria were found in 54 patients (19.2%). Gram-positive organisms were more common (n = 141/261, 54.0%) and detected in 116/192 culture-positive infections (60.4%). Comparing infections before and after 2015, a numerical decline for MDR-bacteria (23.8% vs. 15.6%, p = 0.08) was observed with a significant decline in meropenem resistance (34.9% vs. 19.5%, p = 0.03). MDR-bacteria were more frequent in the case of nosocomial infections. Of note, in ascites the majority of the tested bacteria were resistant against ceftriaxone (73.8%) whereas significantly less were resistant against meropenem (27.0%) and vancomycin (25.9%). CONCLUSIONS: In our tertiary center, distinct ratios of gram-positive infection with overall low ratios of MDR-bacteria were found. Adequate gram-positive coverage in the empiric therapy should be considered. Carbapenem treatment may be omitted even in nosocomial infection. In contrast, 3rd generation cephalosporins cannot be recommended even in community-acquired infection in our cirrhotic population.

Impact of the COVID-19 pandemic on patients with liver cirrhosis-the experience of a tertiary center in Germany.

BACKGROUND: The COVID-19 pandemic has caused a significant impact on the medical care of many diseases and has led to reduced presentations to the emergency department. Reduced presentations may be due to overwhelmed capacities of hospitals or collateral damage from fear of infection, lockdown regulations, or other reasons. The effect on patients with liver cirrhosis is not established. OBJECTIVE: We aim to assess the impact on the care of patients with liver cirrhosis in a tertiary center in Northern Germany. METHODS: All patients presenting to the emergency department with a diagnosis of cirrhosis between March 1 and May 31 from 2015-2020 were included. Reasons for presentation, duration of symptoms, the severity of liver disease, and 30-day mortality were assessed and compared between patients presenting during the COVID-19 pandemic and pre-COVID-19. RESULTS: Overall, 235 patients were included. Despite an overall decline in presentations to the emergency department by 11.7%, the frequency of patients presenting with liver cirrhosis has remained stable (non-significant increase by 19.5%). No significant difference could be detected for the MELD score, the CLIF-organ failure subscores, and the 30-day mortality before and during the COVID-19 pandemic. Up to 75% of patients with liver cirrhosis had symptoms >24 h before presenting to the emergency department. CONCLUSION: Despite the overall trend of reduced emergency presentations during the COVID-19 pandemic, the frequency of presentations of patients with liver cirrhosis did not decline. Morbidity and mortality were not affected in a setting of disposable healthcare resources. The late presentation to the emergency department in many cirrhotic patients may open opportunities for interventions (i.e., with early telemedicine intervention).

[Influence of a spontaneous bacterial peritonitis, nosocomial infections and acute-on-chronic liver failure on treatment revenues in patients with decompensated cirrhosis in Germany]. / Einfluss einer spontan bakteriellen Peritonitis, nosokomialer Infektionen und eines akut auf chronischen Leberversagens auf die Behandlungserlöse bei Patienten mit dekompensierter Leberzirrhose in Deutschland.

BACKGROUND: The economic effects of spontaneous bacterial peritonitis (SBP), nosocomial infections (nosInf) and acute-on-chronic liver failure (ACLF) have so far been poorly studied. We analyzed the impact of these complications on treatment revenues in hospitalized patients with decompensated cirrhosis. METHODS: 371 consecutive patients with decompensated liver cirrhosis, who received a paracentesis between 2012 and 2016, were included retrospectively. DRG (diagnosis-related group), "ZE/NUB" (additional charges/new examination/treatment methods), medication costs, length of hospital stay as well as different kinds of specific treatments (e. g., dialysis) were considered. Exclusion criteria included any kind of malignancy, a history of organ transplantation and/or missing accounting data. RESULTS: Total treatment costs (DRG + ZE/NUB) were higher in those with nosInf (€â€Š10,653 vs. €â€Š5,611, p < 0.0001) driven by a longer hospital stay (23 d vs. 12 d, p < 0.0001). Of note, revenues per day were not different (€â€Š473 vs. €â€Š488, p = 0.98) despite a far more complicated treatment with a more frequent need for dialysis (p < 0.0001) and high-complex care (p = 0.0002). Similarly, SBP was associated with higher total revenues (€â€Š10,307 vs. €â€Š6,659, p < 0.0001). However, the far higher effort for the care of SBP patients resulted in lower daily revenues compared to patients without SBP (€â€Š443 vs. €â€Š499, p = 0.18). ACLF increased treatment revenues to €â€Š10,593 vs. €6,369 without ACLF (p < 0.0001). While treatment of ACLF was more complicated, revenue per day was not different to no-ACLF patients (€â€Š483 vs. €â€Š480, p = 0.29). CONCLUSION: SBP, nosInf and/or ACLF lead to a significant increase in the effort, revenue and duration in the treatment of patients with cirrhosis. The lower daily revenue, despite a much more complex therapy, might indicate that these complications are not yet sufficiently considered in the German DRG system.

Low Serum Cholinesterase Identifies Patients With Worse Outcome and Increased Mortality After TIPS.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective treatment for portal hypertension-related complications. However, careful selection of patients is crucial. The aim of this study was to evaluate the prognostic value of serum cholinesterase (CHE) for outcomes and mortality after TIPS insertion. In this multicenter study, 389 consecutive patients with cirrhosis receiving a TIPS at Hannover Medical School, University Hospital Essen, or Medical University of Vienna were included. The Hannover cohort (n = 200) was used to initially explore the role of CHE, whereas patients from Essen and Vienna served as a validation cohort (n = 189). Median age of the patients was 58 years and median Model for End-Stage Liver Disease (MELD) score was 12. Multivariable analysis identified MELD score (hazard ratio [HR]: 1.16; P < 0.001) and CHE (HR: 0.61; P = 0.008) as independent predictors for 1-year survival. Using the Youden Index, a CHE of 2.5 kU/L was identified as optimal threshold to predict post-TIPS survival in the Hannover cohort (P < 0.001), which was confirmed in the validation cohort (P = 0.010). CHE < 2.5 kU/L was significantly associated with development of acute-on-chronic liver failure (P < 0.001) and hepatic encephalopathy (P = 0.006). Of note, CHE was also significantly linked to mortality in the subgroup of patients with refractory ascites (P = 0.001) as well as in patients with high MELD scores (P = 0.012) and with high-risk FIPS scores (P = 0.004). After propensity score matching, mortality was similar in patients with ascites and CHE < 2.5 kU/L if treated by TIPS or by paracentesis. Contrarily, in patients with CHE ≥ 2.5 kU/L survival was significantly improved by TIPS as compared to treatment with paracentesis (P < 0.001). Conclusion: CHE is significantly associated with mortality and complications after TIPS insertion. Therefore, we suggest that CHE should be evaluated as an additional parameter for selecting patients for TIPS implantation.

Frequency, characteristics and impact of multiple consecutive nosocomial infections in patients with decompensated liver cirrhosis and ascites.

BACKGROUND: Nosocomial infections are a particular threat for patients with liver cirrhosis. It is not uncommon that individuals develop even several consecutive infections during a single hospital stay. We aimed to investigate the impact and characteristics of multiple, consecutive nosocomial infections. METHODS: A total of 514 consecutive patients with liver cirrhosis and ascites were included and followed up for 28 days for nosocomial infection, death or liver transplantation (LTx). Laboratory values were assessed at the time of hospitalization as well as at the onset of each new infectious episode. RESULTS: 58% (n = 298) of the patients developed at least one nosocomial infection and in 23% (n = 119) even multiple infections were documented during a single hospital stay. Consecutive infections usually occurred shortly after the previous episode. Spontaneous bacterial peritonitis (SBP) was the most common infection. However, the proportion of SBP declined from 43% at the first to only 31% at the third nosocomial infection (p = 0.096). In contrast, the likelihood for other, less common types of infection such as blood stream infections increased. Third nosocomial infections were also more likely to be linked to the detection of fungal pathogens (21% vs. 52%; p = 0.001). Each additional infectious episode had a dramatic detrimental impact on LTx-free survival that was independent from the stage of liver disease (adjusted-HR: 6.76, p = 0.002 for first nosocomial infection; adjusted-HR: 14.69, p<0.001 for second nosocomial infection; adjusted-HR: 24.95, p<0.001 for third nosocomial infection). CONCLUSION: In patients with decompensated liver cirrhosis LTx-free survival significantly decreases with every consecutive infectious episode. Development of prevention strategies is urgently required.

Safety and feasibility of transjugular intrahepatic portosystemic shunt in elderly patients with liver cirrhosis and refractory ascites.

BACKGROUND & AIMS: The management of patients with refractory ascites (RA) is challenging, particularly at higher age. Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for RA, but safety data in elderly patients are rare. Our aim was to evaluate the safety and feasibility of TIPS in elderly patients with RA. METHODS: Overall, 160 consecutive cirrhotic patients receiving a TIPS for RA at Hannover Medical School between 2012 and 2018 were considered for this retrospective analysis. Periinterventional complications such as acute-on-chronic liver failure (ACLF) as well as survival were compared between patients <65 and ≥65 years. Propensity score matching was conducted to match elderly TIPS patients and patients treated with paracentesis. RESULTS: A number of 53 out of the 160 patients were ≥65 years (33%). Periinterventional course in those ≥65 years appeared to be slightly more complicated than in <65 years as reflected by a significantly longer hospital stay (p = 0.030) and more ACLF-episodes (21% vs. 9%; p = 0.044). 28-day mortality was similar between both groups (p = 0.350), whereas survival of the younger patients was significantly higher at 90 days (p = 0.029) and numerically higher at 1 year (p = 0.171). In the multivariate analysis age ≥65 years remained an independent predictor for 90-day mortality (HR: 2.58; p = 0.028), while it was not associated with 28-day and 1-year survival. Importantly, after matching for potential confounders 1-year survival was similar in elderly patients if treated with TIPS or paracentesis (p = 0.419). CONCLUSIONS: TIPS placement in elderly patients with RA appears to be slightly more complicated compared to younger individuals, but overall feasible and at least not inferior to paracentesis.

Sustained impact of nosocomial-acquired spontaneous bacterial peritonitis in different stages of decompensated liver cirrhosis.

BACKGROUND & AIMS: Bacterial infections, in particular a spontaneous bacterial peritonitis (SBP), are a major threat in patients with liver cirrhosis. Recently, it has been shown that the impact on mortality might be underestimated by established risk-scores. Onset of infection was suggested to define a distinct stage of cirrhosis. However, it remains unclear whether all stages of decompensated cirrhosis are equally affected. Moreover, if there is such a distinct stage, it must be determined whether it is reversible after the infection has resolved. In this study we aimed to further analyze the impact of a current as well as a resolved SBP in different stages of decompensated liver cirrhosis. METHODS: A number of 579 patients with liver cirrhosis and ascites were included. MELD-score was used to determine the stage of liver disease. Low (<15), intermediate (15-25) and high (>25) MELD-groups were compared. Patients were followed up for 90 days. Primary endpoint was overall mortality. Statistical analyses were performed using the log-rank test, Cox regression and competing risk analysis. RESULTS: Mortality was significantly higher in patients with nosocomial-acquired SBP (nSBP) compared to patients without SBP (p<0.001;HR = 2.05). However, the most prominent difference in mortality was documented in the intermediate MELD-group (nSBP: p = 0.02;HR = 2.10). Importantly, mortality in nSBP patients remained increased even after the initial nSBP episode had resolved (p<0.01;HR = 1.90). Again, this was only significant in those with intermediate MELD-scores (p = 0.02;HR = 2.28). While a current as well as a resolved nSBP were significantly linked to a higher mortality, neither of them did increase the likelihood for liver transplantation. CONCLUSIONS: Development of nSBP is independently associated with increased mortality supporting the concept of a distinct status of cirrhosis. Importantly, the prognosis remains unfavorable even after resolution of nSBP. This could be particularly relevant for patients with intermediate MELD-scores, who have limited chances for a donor liver.